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1.  Cost-Effectiveness Comparison of Response Strategies to a Large-Scale Anthrax Attack on the Chicago Metropolitan Area: Impact of Timing and Surge Capacity 
Rapid public health response to a large-scale anthrax attack would reduce overall morbidity and mortality. However, there is uncertainty about the optimal cost-effective response strategy based on timing of intervention, public health resources, and critical care facilities. We conducted a decision analytic study to compare response strategies to a theoretical large-scale anthrax attack on the Chicago metropolitan area beginning either Day 2 or Day 5 after the attack. These strategies correspond to the policy options set forth by the Anthrax Modeling Working Group for population-wide responses to a large-scale anthrax attack: (1) postattack antibiotic prophylaxis, (2) postattack antibiotic prophylaxis and vaccination, (3) preattack vaccination with postattack antibiotic prophylaxis, and (4) preattack vaccination with postattack antibiotic prophylaxis and vaccination. Outcomes were measured in costs, lives saved, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). We estimated that postattack antibiotic prophylaxis of all 1,390,000 anthrax-exposed people beginning on Day 2 after attack would result in 205,835 infected victims, 35,049 fulminant victims, and 28,612 deaths. Only 6,437 (18.5%) of the fulminant victims could be saved with the existing critical care facilities in the Chicago metropolitan area. Mortality would increase to 69,136 if the response strategy began on Day 5. Including postattack vaccination with antibiotic prophylaxis of all exposed people reduces mortality and is cost-effective for both Day 2 (ICER=$182/QALY) and Day 5 (ICER=$1,088/QALY) response strategies. Increasing ICU bed availability significantly reduces mortality for all response strategies. We conclude that postattack antibiotic prophylaxis and vaccination of all exposed people is the optimal cost-effective response strategy for a large-scale anthrax attack. Our findings support the US government's plan to provide antibiotic prophylaxis and vaccination for all exposed people within 48 hours of the recognition of a large-scale anthrax attack. Future policies should consider expanding critical care capacity to allow for the rescue of more victims.
Rapid public health response to a large-scale anthrax attack would reduce overall morbidity and mortality, but what is the optimal cost-effective response strategy for timing of intervention, public health resources, and critical care facilities? Using a hypothetical large-scale anthrax attack on the Chicago metropolitan area, this study compared response strategies that would begin either 2 days or 5 days after the attack and would consist of administering prophylaxis and vaccine in various combinations. The findings support the government's plan to provide antibiotic prophylaxis and vaccination for all exposed people within 48 hours of the recognition of a large-scale anthrax attack.
doi:10.1089/bsp.2011.0105
PMCID: PMC3440066  PMID: 22845046
2.  Optimizing the Dose of Pre-Pandemic Influenza Vaccines to Reduce the Infection Attack Rate 
PLoS Medicine  2007;4(6):e218.
Background
The recent spread of avian influenza in wild birds and poultry may be a precursor to the emergence of a 1918-like human pandemic. Therefore, stockpiles of human pre-pandemic vaccine (targeted at avian strains) are being considered. For many countries, the principal constraint for these vaccine stockpiles will be the total mass of antigen maintained. We tested the hypothesis that lower individual doses (i.e., less than the recommended dose for maximum protection) may provide substantial extra community-level benefits because they would permit wider vaccine coverage for a given total size of antigen stockpile.
Methods and Findings
We used a mathematical model to predict infection attack rates under different policies. The model incorporated both an individual's response to vaccination at different doses and the process of person-to-person transmission of pandemic influenza. We found that substantial reductions in the attack rate are likely if vaccines are given to more people at lower doses. These results are applicable to all three vaccine candidates for which data are available. As a guide to the magnitude of the effect, we simulated epidemics based on historical studies of immunogenicity. For example, for one of the vaccines for which data are available, the attack rate would drop from 67.6% to 58.7% if 160 out of the total US population of 300 million were given an optimal dose rather than 20 out of 300 million given the maximally protective dose (as promulgated in the US National Pandemic Preparedness Plan). Our results are conservative with respect to a number of alternative assumptions about the precise nature of vaccine protection. We also considered a model variant that includes a single high-risk subgroup representing children. For smaller stockpile sizes that allow vaccine to be offered only to the high-risk group at the optimal dose, the predicted benefits of using the homogenous model formed a lower bound in the presence of a risk group, even when the high-risk group was twice as infective and twice as susceptible.
Conclusions
In addition to individual-level protection (i.e., vaccine efficacy), the population-level implications of pre-pandemic vaccine programs should be considered when deciding on stockpile size and dose. Our results suggest that a lower vaccine dose may be justified in order to increase population coverage, thereby reducing the infection attack rate overall.
Steven Riley and colleagues examine the potential benefits of "stretching" a limited supply of vaccine and suggest that substantial reductions in the attack rate are possible if vaccines are given to more people at lower doses.
Editors' Summary
Background.
Every winter, millions of people catch influenza, a viral infection of the nose, throat, and airways. Most recover quickly, but the disease can be deadly. In the US, seasonal influenza outbreaks (epidemics) cause 36,000 excess deaths annually. And now there are fears that an avian (bird) influenza virus might trigger a human influenza pandemic—a global epidemic that could kill millions. Seasonal epidemics occur because flu viruses continually make small changes to their hemagglutinin and neuraminidase molecules, the viral proteins (antigens) that the immune system recognizes. Because of this “antigenic drift,” an immune system response (which can be induced by catching flu or by vaccination with disabled circulating influenza strains) that combats flu one year may provide only partial protection the next year. “Antigenic shift” (large changes in flu antigens) can cause pandemics because communities have no immunity to the changed virus.
Why Was This Study Done?
Although avian influenza virus, which contains a hemagglutinin type that differs from currently circulating human flu viruses, has caused a few cases of human influenza, it has not started a human pandemic yet because it cannot move easily between people. If it acquires this property, which will probably involve further small antigenic changes, it could kill millions of people before scientists can develop an effective vaccine against it. To provide some interim protection, many countries are preparing stockpiles of “pre-pandemic” vaccines targeted against the avian virus. The US, for example, plans to store enough pre-pandemic vaccine to provide maximum protection to 20 million people (including key health workers) out of its population of 300 million. But, given a limited stockpile of pre-pandemic vaccine, might giving more people a lower dose of vaccine, which might reduce the number of people susceptible to infection and induce herd immunity by preventing efficient transmission of the flu virus, be a better way to limit the spread of pandemic influenza? In this study, the researchers have used mathematical modeling to investigate this question.
What Did the Researchers Do and Find?
To predict the infection rates associated with different vaccination policies, the researchers developed a mathematical model that incorporates data on human immune responses induced with three experimental vaccines against the avian virus and historical data on the person–person transmission of previous pandemic influenza viruses. For all the vaccines, the model predicts that giving more people a low dose of the vaccine would limit the spread of influenza better than giving fewer people the high dose needed for full individual protection. For example, the researchers estimate that dividing the planned US stockpile of one experimental vaccine equally between 160 million people instead of giving it at the fully protective dose to 20 million people might avert about 27 million influenza cases in less than year. However, giving the maximally protective dose to the 9 million US health-care workers and using the remaining vaccine at a lower dose to optimize protection within the general population might avert only 14 million infections.
What Do These Findings Mean?
These findings suggest that, given a limited stockpile of pre-pandemic vaccine, increasing the population coverage of vaccination by using low doses of vaccine might reduce the overall influenza infection rate more effectively than vaccinating fewer people with fully protective doses of vaccine. However, because the researchers' model includes many assumptions, it can only give an indication of how different strategies might perform, not firm numbers for how many influenza cases each strategy is likely to avert. Before public-health officials use this or a similar model to help them decide the best way to use pre-pandemic vaccines to control a human influenza pandemic, they will need more information about the efficacy of these vaccines and about transmission rates of currently circulating viruses. They will also need to know whether pre-pandemic vaccines actually provide good protection against the pandemic virus, as assumed in this study, before they can recommend mass immunization with low doses of pre-pandemic vaccine, selective vaccination with high doses, or a mixed strategy.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040218.
US Centers for Disease Control and Prevention provide information on influenza and influenza vaccination for patients and health professionals (in English, Spanish, Filipino, Chinese, and Vietnamese)
The World Health Organization has a fact sheet on influenza and on the global response to avian influenza (in English, Spanish, French, Russian, Arabic, and Chinese)
The MedlinePlus online encyclopedia devotes a page to flu (in English and Spanish)
The UK Health Protection Agency information on avian, pandemic, and seasonal influenza
The US National Institute of Allergy and Infectious Diseases has a comprehensive feature called “focus on the flu”
doi:10.1371/journal.pmed.0040218
PMCID: PMC1892041  PMID: 17579511
3.  Misinformation and misbeliefs in the Tuskegee Study of Untreated Syphilis fuel mistrust in the healthcare system. 
The Tuskegee Study of Untreated Syphilis (TSUS) is an important issue in research, healthcare, ethics and race relations. The assumed consequences of knowledge of this study on the African-American community include mistrust of the healthcare system. In the July 2005 issue of the Journal of the National Medical Association, Brandon, Isaac and LaVeist (the authors), who were at the Center for Health Disparities Solutions, Johns Hopkins Bloomberg School of Public Health, reported the results of black-white differences in awareness of and knowledge about the TSUS and the effect of that awareness and knowledge on medical mistrust. The study surveyed blacks, whites and others in the Baltimore, MD community about their knowledge of and attitudes about the TSUS. The respondents who were aware of the TSUS were asked survey items to assess specific factual information about the TSUS. The respondents who were not aware of the TSUS were read a brief description of the TSUS taken from the CDC website. Both groups were asked if a similar study was possible today. The authors performed a regression analysis of mistrust of medical care based on race, knowledge of the TSUS and demographic variables. The editorial identified and explained challenges in the article, i.e., challenges in calculations, demographic analysis by race, knowledge of TSUS, cultural sensitivity and methodology. The authors miscalculated the "similar proportions" of blacks and whites who were aware of the TSUS; the recalculated proportions, favoring whites, were different than reported by others. There was no demographic analysis by race in their article--also different than other published reports. Most respondents--blacks and whites--who were aware of the TSUS at baseline answered incorrectly the author-selected questions about the TSUS, particularly the fact-based question of whether the TSUS researchers gave syphilis to the men-not dissimilar to one other report. The source for TSUS information (the CDC website) that was used to educate respondents who were not aware of the TSUS at baseline had contradictions, errors and challenges in black history, medical and public health history, and women's studies. The content of what was actually read to respondents was unknown. Proportionally more whites who were not aware of the TSUS but who were read author-selected information about the TSUS believed that a similar study could happen today-a belief and possibly mistrust of medical care that appeared to be induced-compared to whites with prestudy awareness of the TSUS but not read information from the CDC website. Both black groups were not dissimilar from each other. The authors used a survey that measured a race difference in response to a medical event (TSUS) specific to only one racial group (blacks) when there were inclusive examples specific to other groups available. The authors used "Tuskegee" as a single-word sound bite for the TSUS--a misuse that was inappropriate in scientific and research discourse and that may fuel mistrust of medical care. Whether knowledge of the TSUS was a predictor of mistrust of the healthcare system was inconclusive based on the results in the authors' article. The core findings of the article made believing their case difficult. The editorial suggested that bias and misinformation in undertaking, analysis and reporting the study may in itself fuel mistrust in medical care in the community. Because of these challenges, the editorial urged caution with regard to any change in research direction or policy debate based on the results reported in the article.
PMCID: PMC2594917  PMID: 16334509
4.  The Effects of Influenza Vaccination of Health Care Workers in Nursing Homes: Insights from a Mathematical Model 
PLoS Medicine  2008;5(10):e200.
Background
Annual influenza vaccination of institutional health care workers (HCWs) is advised in most Western countries, but adherence to this recommendation is generally low. Although protective effects of this intervention for nursing home patients have been demonstrated in some clinical trials, the exact relationship between increased vaccine uptake among HCWs and protection of patients remains unknown owing to variations between study designs, settings, intensity of influenza seasons, and failure to control all effect modifiers. Therefore, we use a mathematical model to estimate the effects of HCW vaccination in different scenarios and to identify a herd immunity threshold in a nursing home department.
Methods and Findings
We use a stochastic individual-based model with discrete time intervals to simulate influenza virus transmission in a 30-bed long-term care nursing home department. We simulate different levels of HCW vaccine uptake and study the effect on influenza virus attack rates among patients for different institutional and seasonal scenarios. Our model reveals a robust linear relationship between the number of HCWs vaccinated and the expected number of influenza virus infections among patients. In a realistic scenario, approximately 60% of influenza virus infections among patients can be prevented when the HCW vaccination rate increases from 0 to 1. A threshold for herd immunity is not detected. Due to stochastic variations, the differences in patient attack rates between departments are high and large outbreaks can occur for every level of HCW vaccine uptake.
Conclusions
The absence of herd immunity in nursing homes implies that vaccination of every additional HCW protects an additional fraction of patients. Because of large stochastic variations, results of small-sized clinical trials on the effects of HCW vaccination should be interpreted with great care. Moreover, the large variations in attack rates should be taken into account when designing future studies.
Using a mathematical model to simulate influenza transmission in nursing homes, Carline van den Dool and colleagues find that each additional staff member vaccinated further reduces the risk to patients.
Editors' Summary
Background.
Every winter, millions of people catch influenza, a contagious viral disease of the nose, throat, and airways. Most people recover completely from influenza within a week or two but some develop life-threatening complications such as bacterial pneumonia. As a result, influenza outbreaks kill about half a million people—mainly infants, elderly people, and chronically ill individuals—each year. To minimize influenza-related deaths, the World Health Organization recommends that vulnerable people be vaccinated against influenza every autumn. Annual vaccination is necessary because flu viruses continually make small changes to the viral proteins (antigens) that the immune system recognizes. This means that an immune response produced one year provides only partial protection against influenza the next year. To provide maximum protection against influenza, each year's vaccine contains disabled versions of the major circulating strains of influenza viruses.
Why Was This Study Done?
Most Western countries also recommend annual flu vaccination for health care workers (HCWs) in hospitals and other institutions to reduce the transmission of influenza to vulnerable patients. However, many HCWs don't get a regular flu shot, so should efforts be made to increase their rate of vaccine uptake? To answer this question, public-health experts need to know more about the relationship between vaccine uptake among HCWs and patient protection. In particular, they need to know whether a high rate of vaccine uptake by HCWs will provide “herd immunity.” Herd immunity occurs because, when a sufficient fraction of a population is immune to a disease that passes from person to person, infected people rarely come into contact with susceptible people, which means that both vaccinated and unvaccinated people are protected from the disease. In this study, the researchers develop a mathematical model to investigate the relationship between vaccine uptake among HCWs and patient protection in a nursing home department.
What Did the Researchers Do and Find?
To predict influenza virus attack rates (the number of patient infections divided by the number of patients in a nursing home department during an influenza season) at different levels of HCW vaccine uptake, the researchers develop a stochastic transmission model to simulate epidemics on a computer. This model predicts that as the HCW vaccination rate increases from 0 (no HCWs vaccinated) to 1 (all the HCWs vaccinated), the expected average influenza virus attack rate decreases at a constant rate. In the researchers' baseline scenario—a nursing home department with 30 beds where patients come into contact with other patients, HCWs, and visitors—the model predicts that about 60% of the patients who would have been infected if no HCWs had been vaccinated are protected when all the HCWs are vaccinated, and that seven HCWs would have to be vaccinated to protect one patient. This last figure does not change with increasing vaccine uptake, which indicates that there is no level of HCW vaccination that completely stops the spread of influenza among the patients; that is, there is no herd immunity. Finally, the researchers show that large influenza outbreaks can happen by chance at every level of HCW vaccine uptake.
What Do These Findings Mean?
As with all mathematical models, the accuracy of these predictions may depend on the specific assumptions built into the model. Therefore the researchers verified that their findings hold for a wide range of plausible assumptions. These findings have two important practical implications. First, the direct relationship between HCW vaccination and patient protection and the lack of any herd immunity suggest that any increase in HCW vaccine uptake will be beneficial to patients in nursing homes. That is, increasing the HCW vaccination rate from 80% to 90% is likely to be as important as increasing it from 10% to 20%. Second, even 100% HCW vaccination cannot guarantee that influenza outbreaks will not occasionally occur in nursing homes. Because of the large variation in attack rates, the results of small clinical trials on the effects of HCW vaccination may be inaccurate and future studies will need to be very large if they are to provide reliable estimates of the amount of protection that HCW vaccination provides to vulnerable patients.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050200.
Read the related PLoSMedicine Perspective by Cécile Viboud and Mark Miller
A related PLoSMedicine Research Article by Jeffrey Kwong and colleagues is also available
The World Health Organization provides information on influenza and on influenza vaccines (in several languages)
The US Centers for Disease Control and Prevention provide information for patients and professionals on all aspects of influenza (in English and Spanish)
The UK Health Protection Agency also provides information on influenza
MedlinePlus provides a list of links to other information about influenza (in English and Spanish)
The UK National Health Service provides information about herd immunity, including a simple explanatory animation
The European Centre for Disease Prevention and Control provides an overview on the types of influenza
doi:10.1371/journal.pmed.0050200
PMCID: PMC2573905  PMID: 18959470
5.  Frequency of Adverse Events after Vaccination with Different Vaccinia Strains 
PLoS Medicine  2006;3(8):e272.
Background
Large quantities of smallpox vaccine have been stockpiled to protect entire nations against a possible reintroduction of smallpox. Planning for an appropriate use of these stockpiled vaccines in response to a smallpox outbreak requires a rational assessment of the risks of vaccination-related adverse events, compared to the risk of contracting an infection. Although considerable effort has been made to understand the dynamics of smallpox transmission in modern societies, little attention has been paid to estimating the frequency of adverse events due to smallpox vaccination. Studies exploring the consequences of smallpox vaccination strategies have commonly used a frequency of approximately one death per million vaccinations, which is based on a study of vaccination with the New York City Board of Health (NYCBH) strain of vaccinia virus. However, a multitude of historical studies of smallpox vaccination with other vaccinia strains suggest that there are strain-related differences in the frequency of adverse events after vaccination. Because many countries have stockpiled vaccine based on the Lister strain of vaccinia virus, a quantitative evaluation of the adverse effects of such vaccines is essential for emergency response planning. We conducted a systematic review and statistical analysis of historical data concerning vaccination against smallpox with different strains of vaccinia virus.
Methods and Findings
We analyzed historical vaccination data extracted from the literature. We extracted data on the frequency of postvaccinal encephalitis and death with respect to vaccinia strain and age of vaccinees. Using a hierarchical Bayesian approach for meta-analysis, we estimated the expected frequencies of postvaccinal encephalitis and death with respect to age at vaccination for smallpox vaccines based on the NYCBH and Lister vaccinia strains. We found large heterogeneity between findings from different studies and a time-period effect that showed decreasing incidences of adverse events over several decades. To estimate death rates, we then restricted our analysis to more-recent studies. We estimated that vaccination with the NYCBH strain leads to an average of 1.4 deaths per million vaccinations (95% credible interval, 0–6) and that vaccination with Lister vaccine leads to an average of 8.4 deaths per million vaccinations (95% credible interval, 0–31). We combined age-dependent estimates of the frequency of death after vaccination and revaccination with demographic data to obtain estimates of the expected number of deaths in present societies due to vaccination with the NYCBH and Lister vaccinia strains.
Conclusions
Previous analyses of smallpox vaccination policies, which rely on the commonly assumed value of one death per million vaccinations, may give serious underestimates of the number of deaths resulting from vaccination. Moreover, because there are large, strain-dependent differences in the frequency of adverse events due to smallpox vaccination, it is difficult to extrapolate from predictions for the NYCBH-derived vaccines (stockpiled in countries such as the US) to predictions for the Lister-derived vaccines (stockpiled in countries such as Germany). In planning for an effective response to a possible smallpox outbreak, public-health decision makers should reconsider their strategies of when to opt for ring vaccination and when to opt for mass vaccination.
Analysis of historical data for adverse events suggests that the commonly assumed number of one death per million vaccinations is inaccurate. Large differences between different vaccinia strains used should be taken into account when mass vaccinations are considered.
Editors' Summary
Background.
For thousands of years, smallpox was one of the world's most-feared diseases. This contagious disease, caused by the variola virus, historically killed about 30 percent of the people it infected. Over the centuries, it probably killed more people than all other infectious diseases combined, but it was also the first disease to be prevented by vaccination. In 1796, the English physician Edward Jenner rubbed pus from the spots of a milkmaid with cowpox into scratches on a young boy's arm; according to folklore, people who caught cowpox, a related but mild disease of cows, were protected against smallpox. Six weeks later, after a mild bout of cowpox, when the boy was challenged with pus from a smallpox patient, he did not develop smallpox. This vaccination procedure was later refined so that people were inoculated with pure preparations of live vaccinia virus, which is closely related to the smallpox and cowpox viruses, and by 1979 a global vaccination campaign had totally eradicated the disease.
Why Was This Study Done?
Smallpox vaccination has some adverse effects. In particular, vaccinia virus occasionally infects the brain. This so-called post-vaccination encephalitis can cause permanent brain damage and, it has been estimated, kills one vaccinee in every million. Consequently, as smallpox became rarer, the dangers of vaccination began to outweigh its benefits. Routine smallpox vaccination stopped in the US in 1972, and in 1980 the World Health Organization recommended that all countries stop vaccination. Now, however, there are fears that smallpox may be used for bioterrorism. If this did happen, exposed individuals and their contacts, possibly even whole populations, would have to be vaccinated as quickly as possible (very few people now have strong immunity to smallpox). Many countries have stockpiles of smallpox vaccines for this eventuality, but these contain different vaccinia virus strains. In this study, the researchers examined historical data to discover whether these strains differ in their potential to cause encephalitis and death. This information should help public-health officials plan their vaccination strategies in response to a bioterrorism attack with smallpox.
What Did the Researchers Do and Find?
The researchers collected data from published studies on smallpox vaccination and adverse events from several countries from the late 1950s onwards. They then used these data to extrapolate how often the different vaccinia strains might cause encephalitis and death if they were used today in vaccination programs. They estimate that vaccinating with the New York City Board of Health (NYCBH) strain, which is stockpiled in the US, might cause 2.9 cases of post-vaccination encephalitis and 1.4 deaths per million vaccinated individuals. In contrast, the Lister strain, which is stockpiled in many European countries, might cause 26.2 cases of post-vaccination encephalitis and 2.5 deaths per million vaccinees. For both strains, vaccination of children younger than 1 year old would cause the highest death rate, and individuals being re-vaccinated would be less likely to die than those being vaccinated for the first time. Finally, the researchers use their figures to estimate that about ten people would die if mass vaccination with the NYCBH strain were used in the Netherlands (population 16 million), whereas 55 people would die if the Lister strain were used.
What Do These Findings Mean?
The data used in this study are of variable quality, so the figures calculated by the researchers are only estimates. For instance, given the scatter of the original data, mass vaccination in the Netherlands with the Lister strain might cause anywhere between seven and nearly 200 deaths. However, the study clearly suggests that more serious adverse events would occur after vaccination with the Lister strain than after vaccination with the NYCBH strain. It also indicates that even in the US, where the NYCBH vaccine strain is stockpiled, previous analyses of the effects of vaccination in response to a bioterrorist attack have probably underestimated how many people might die from post-vaccination encephalitis. Public-health decision makers should incorporate these new estimates into their planning for a smallpox outbreak. These increased estimates of adverse events after vaccination might, for example, make mass vaccination with the Lister strain of vaccinia virus less acceptable. Instead, public-health officials might decide to rely on vaccination of only the people directly exposed to released smallpox virus and their close contacts (ring vaccination) to contain a smallpox outbreak.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030272.
World Health Organization, information on smallpox and preparedness in the event of a smallpox outbreak
MedlinePlus encyclopedia entry on smallpox
US National Institute of Allergy and Infectious Diseases, patient fact sheet on smallpox
US Centers for Disease Control and Prevention, information for patients and professionals on smallpox
Wikipedia page on smallpox (note that Wikipedia is a free online encyclopedia that anyone can edit)
Wellcome Library MedHist, links to information on the history of smallpox vaccination
doi:10.1371/journal.pmed.0030272
PMCID: PMC1551910  PMID: 16933957
6.  Rates of Latent Tuberculosis in Health Care Staff in Russia 
PLoS Medicine  2007;4(2):e55.
Background
Russia is one of 22 high burden tuberculosis (TB) countries. Identifying individuals, particularly health care workers (HCWs) with latent tuberculosis infection (LTBI), and determining the rate of infection, can assist TB control through chemoprophylaxis and improving institutional cross-infection strategies. The objective of the study was to estimate the prevalence and determine the relative risks and risk factors for infection, within a vertically organised TB service in a country with universal bacille Calmette-Guérin (BCG) vaccination.
Methods and Findings
We conducted a cross-sectional study to assess the prevalence of and risk factors for LTBI among unexposed students, minimally exposed medical students, primary care health providers, and TB hospital health providers in Samara, Russian Federation. We used a novel in vitro assay (for gamma-interferon [IFN-γ]) release to establish LTBI and a questionnaire to address risk factors. LTBI was seen in 40.8% (107/262) of staff and was significantly higher in doctors and nurses (39.1% [90/230]) than in students (8.7% [32/368]) (relative risk [RR] 4.5; 95% confidence interval [CI] 3.1–6.5) and in TB service versus primary health doctors and nurses: respectively 46.9% (45/96) versus 29.3% (34/116) (RR 1.6; 95% CI 1.1–2.3). There was a gradient of LTBI, proportional to exposure, in medical students, primary health care providers, and TB doctors: respectively, 10.1% (24/238), 25.5% (14/55), and 55% (22/40). LTBI was also high in TB laboratory workers: 11/18 (61.1%).
Conclusions
IFN-γ assays have a useful role in screening HCWs with a high risk of LTBI and who are BCG vaccinated. TB HCWs were at significantly higher risk of having LTBI. Larger cohort studies are needed to evaluate the individual risks of active TB development in positive individuals and the effectiveness of preventive therapy based on IFN-γ test results.
Gamma-interferon assays were used in a cross-sectional study of Russian health care workers and found high rates of latent tuberculosis infection.
Editors' Summary
Background.
Tuberculosis (TB) is a very common and life-threatening infection caused by a bacterium, Mycobacterium tuberculosis, which is carried by about a third of the world's population. Many people who are infected do not develop the symptoms of disease; this is called “latent infection.” However, it is important to detect latent infection among people in high-risk communities, in order to prevent infected people from developing active disease, and therefore also reduce the spread of TB within the community. 22 countries account for 80% of the world's active TB, and Russia is one of these. Health care workers are particularly at risk for developing active TB disease in Russia, but the extent of latent infection is not known. In order to design appropriate measures for controlling TB in Russia, it is important to know how common latent infection is among health care workers, as well as other members of the community.
Why Was This Study Done?
The researchers here had been studying the spread of tuberculosis in Samara City in southeastern Russia, where the rate of TB disease among health care workers was very high; in 2004 the number of TB cases among health care workers on TB wards was over ten times that in the general population. There was also no information available on the rates of latent TB infection among health care workers in Samara City. The researchers therefore wanted to work out what proportion of health care workers in Samara City had latent TB infection, and particularly to compare groups whom they thought would be at different levels of risk (students, clinicians outside of TB wards, clinicians on TB wards, etc.). Finally, the researchers also wanted to use a new test for detecting latent TB infection. The traditional test for detecting TB infection (tuberculin skin test) is not very reliable among people who have received the Bacillus Calmette-Guérin (BCG) vaccination against TB earlier in life, as is the case in Russia. In this study a new test was therefore used, based on measuring the immune response to two proteins produced by M. tuberculosis, which are not present in the BCG vaccine strain.
What Did the Researchers Do and Find?
In this study the researchers tested health care workers from all the TB clinics in Samara City, as well as other clinical staff and students, for latent tuberculosis. In total, 630 people had blood samples taken for testing. A questionnaire was also used to collect information on possible risk factors for TB. As expected, the rate of latent TB infection was highest among clinical staff working in the TB clinics, 47% of whom were infected with M. tuberculosis. This compared to a 10% infection rate among medical students and 29% infection rate among primary care health workers. The differences in infection rate between medical students, primary care health workers, and TB clinic staff were statistically significant and reflected progressively increasing exposure to TB. Among primary care health workers, past exposure to TB was a risk factor for having latent TB infection.
What Do These Findings Mean?
This study showed that there was a high rate of latent TB infection among health care workers in Samara City and that infection is increasingly likely among people with either past or present exposure to TB. The results suggest that further research should be carried out to test whether mass screening for latent infection, followed by treatment, will reduce the rate of active TB disease among health care workers and also prevent further spread of TB. There are concerns that widespread treatment of latent infection may not be completely effective due to the relatively high prevalence of drug-resistant TB strains and any new initiatives would therefore need to be carefully evaluated.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040055.
The Stop TB Partnership has been set up to eliminate TB as a public health problem; its site provides data and resources about TB in each of the 22 most-affected countries, including Russia
Tuberculosis minisite from the World Health Organization, providing data on tuberculosis worldwide, details of the Stop TB strategy, as well as fact sheets and current guidelines
The US Centers for Disease Control has a tuberculosis minisite, including a fact sheet on latent TB
Information from the US Centers for Disease Control about the QuantiFERON-TB Gold test, used to test for latent TB infection in this study
doi:10.1371/journal.pmed.0040055
PMCID: PMC1796908  PMID: 17298167
7.  Exposure to Bioterrorism and Mental Health Response among Staff on Capitol Hill 
The October 2001 anthrax attacks heralded a new era of bioterrorism threat in the U.S. At the time, little systematic data on mental health effects were available to guide authorities' response. For this study, which was conducted 7 months after the anthrax attacks, structured diagnostic interviews were conducted with 137 Capitol Hill staff workers, including 56 who had been directly exposed to areas independently determined to have been contaminated. Postdisaster psychopathology was associated with exposure; of those with positive nasal swab tests, PTSD was diagnosed in 27% and any post-anthrax psychiatric disorder in 55%. Fewer than half of those who were prescribed antibiotics completed the entire course, and only one-fourth had flawless antibiotic adherence. Thirty percent of those not exposed believed they had been exposed; 18% of all study participants had symptoms they suspected were symptoms of anthrax infection, and most of them sought medical care. Extrapolation of raw numbers to large future disasters from proportions with incorrect belief in exposure in this limited study indicates a potential for important public health consequences, to the degree that people alter their healthcare behavior based on incorrect exposure beliefs. Incorrect belief in exposure was associated with being very upset, losing trust in health authorities, having concerns about mortality, taking antibiotics, and being male. Those who incorrectly believe they were exposed may warrant concern and potential interventions as well as those exposed. Treatment adherence and maintenance of trust for public health authorities may be areas of special concern, warranting further study to inform authorities in future disasters involving biological, chemical, and radiological agents.
doi:10.1089/bsp.2009.0031
PMCID: PMC2956562  PMID: 20028246
8.  A Comparative Analysis of Influenza Vaccination Programs 
PLoS Medicine  2006;3(10):e387.
Background
The threat of avian influenza and the 2004–2005 influenza vaccine supply shortage in the United States have sparked a debate about optimal vaccination strategies to reduce the burden of morbidity and mortality caused by the influenza virus.
Methods and Findings
We present a comparative analysis of two classes of suggested vaccination strategies: mortality-based strategies that target high-risk populations and morbidity-based strategies that target high-prevalence populations. Applying the methods of contact network epidemiology to a model of disease transmission in a large urban population, we assume that vaccine supplies are limited and then evaluate the efficacy of these strategies across a wide range of viral transmission rates and for two different age-specific mortality distributions.
We find that the optimal strategy depends critically on the viral transmission level (reproductive rate) of the virus: morbidity-based strategies outperform mortality-based strategies for moderately transmissible strains, while the reverse is true for highly transmissible strains. These results hold for a range of mortality rates reported for prior influenza epidemics and pandemics. Furthermore, we show that vaccination delays and multiple introductions of disease into the community have a more detrimental impact on morbidity-based strategies than mortality-based strategies.
Conclusions
If public health officials have reasonable estimates of the viral transmission rate and the frequency of new introductions into the community prior to an outbreak, then these methods can guide the design of optimal vaccination priorities. When such information is unreliable or not available, as is often the case, this study recommends mortality-based vaccination priorities.
A comparative analysis of two classes of suggested vaccination strategies, mortality-based strategies that target high-risk populations and morbidity-based strategies that target high-prevalence populations.
Editors' Summary
Background.
Influenza—a viral infection of the nose, throat, and airways that is transmitted in airborne droplets released by coughing or sneezing—is a serious public health threat. Most people recover quickly from influenza, but some individuals, especially infants, old people, and individuals with chronic health problems, can develop pneumonia and die. In the US, seasonal outbreaks (epidemics) of flu cause an estimated 36,000 excess deaths annually. And now there are fears that avian influenza might start a human pandemic—a global epidemic that could kill millions. Seasonal outbreaks of influenza occur because flu viruses continually change the viral proteins (antigens) to which the immune system responds. “Antigenic drift”—small changes in these proteins—means that an immune system response that combats flu one year may not provide complete protection the next winter. “Antigenic shift”—large antigen changes—can cause pandemics because communities have no immunity to the changed virus. Annual vaccination with vaccines based on the currently circulating viruses controls seasonal flu epidemics; to control a pandemic, vaccines based on the antigenically altered virus would have to be quickly developed.
Why Was This Study Done?
Most countries target vaccination efforts towards the people most at risk of dying from influenza, and to health-care workers who are likely come into contact with flu patients. But is this the best way to reduce the burden of illness (morbidity) and death (mortality) caused by influenza, particularly at the start of a pandemic, when vaccine would be limited? Old people and infants are much less likely to catch and spread influenza than school children, students, and employed adults, so could vaccination of these sections of the population—instead of those most at risk of death—be the best way to contain influenza outbreaks? In this study, the researchers used an analytical method called “contact network epidemiology” to compare two types of vaccination strategies: the currently favored mortality-based strategy, which targets high-risk individuals, and a morbidity-based strategy, which targets those segments of the community in which most influenza cases occur.
What Did the Researchers Do and Find?
Most models of disease transmission assume that each member of a community is equally likely to infect every other member. But a baby is unlikely to transmit flu to, for example, an unrelated, housebound elderly person. Contact network epidemiology takes the likely relationships between people into account when modeling disease transmission. Using information from Vancouver, British Columbia, Canada, on household size, age distribution, and occupations, and other factors such as school sizes, the researchers built a model population of a quarter of a million interconnected people. They then investigated how different vaccination strategies controlled the spread of influenza in this population. The optimal strategy depended on the level of viral transmissibility—the likelihood that an infectious person transmits influenza to a susceptible individual with whom he or she has contact. For moderately transmissible flu viruses, a morbidity-based vaccination strategy, in which the people most likely to catch the flu are vaccinated, was more effective at containing seasonal and pandemic outbreaks than a mortality-based strategy, in which the people most likely to die if they caught the flu are vaccinated. For highly transmissible strains, this situation was reversed. The level of transmissibility at which this reversal occurred depended on several factors, including whether vaccination was delayed and how many times influenza was introduced into the community.
What Do These Findings Mean?
The researchers tested their models by checking that they could replicate real influenza epidemics and pandemics, but, as with all mathematical models, they included many assumptions about influenza in their calculations, which may affect their results. Also, because the contact network used data from Vancouver, their results might not be applicable to other cities, or to nonurban areas. Nevertheless, their findings have important public health implications. When there are reasonable estimates of the viral transmission rate, and it is known how often influenza is being introduced into a community, contact network models could help public health officials choose between morbidity- and mortality-based vaccination strategies. When the viral transmission rate is unreliable or unavailable (for example, at the start of a pandemic), the best policy would be the currently preferred strategy of mortality-based vaccination. More generally, the use of contact network models should improve estimates of how infectious diseases spread through populations and indicate the best ways to control human epidemics and pandemics.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030387.
US Centers for Disease Control and Prevention information about influenza for patients and professionals, including key facts on vaccination
US National Institute of Allergy and Infectious Diseases feature on seasonal, avian, and pandemic influenza
World Health Organization fact sheet on influenza, with links to information on vaccination
UK Health Protection Agency information on seasonal, avian, and pandemic influenza
MedlinePlus entry on influenza
doi:10.1371/journal.pmed.0030387
PMCID: PMC1584413  PMID: 17020406
9.  Misrepresentations of the Tuskegee Study of Untreated Syphilis. 
The Tuskegee Study of Untreated Syphilis (TSUS) is the subject of medical research, healthcare, ethics, race relations and fictitious media portrayals (e.g., movie, play). Unraveling misrepresentations about the TSUS is important because prevailing views continue to contribute to alleged mistrust of the medical system by the black community and compromised doctor-patient and researcher-participant relationships. A comparative analysis of standard TSUS information was conducted and included evidenced-based alternative information in an effort to: (a) contextualize the TSUS with accurate medical, public health and historical information and (b) balance claims of racism, nontreatment and denial of treatment. An article in the Winter 2003 Radcliffe Quarterly misrepresented the images of two historical African-American health institutions, the John A. Andrew Memorial Hospital and the Tuskegee Veterans Administration Hospital. A critical analysis challenges these pictorial misrepresentations and documents, in part, a continuing and prevailing pattern of biased misrepresentations in discussions about the TSUS. The National Medical Association (NMA) and the Journal of the National Medical Association have a history of advocacy for African-American health, a record of combating racial discrimination and a quest for truth about the status of the black community. As past NMA historical notables have performed through their advancement, service and leadership, health professionals now have the opportunity, obligation and information to educate the American community about the TSUS with evidenced-based information.
Images
PMCID: PMC2568733  PMID: 15868777
10.  Efficacy of Pneumococcal Nontypable Haemophilus influenzae Protein D Conjugate Vaccine (PHiD-CV) in Young Latin American Children: A Double-Blind Randomized Controlled Trial 
PLoS Medicine  2014;11(6):e1001657.
In a double-blind randomized controlled trial, Xavier Saez-Llorens and colleagues examine the vaccine efficacy of PHiD-CV against community-acquired pneumonia in young children in Panama, Argentina, and Columbia.
Please see later in the article for the Editors' Summary
Background
The relationship between pneumococcal conjugate vaccine–induced antibody responses and protection against community-acquired pneumonia (CAP) and acute otitis media (AOM) is unclear. This study assessed the impact of the ten-valent pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) on these end points. The primary objective was to demonstrate vaccine efficacy (VE) in a per-protocol analysis against likely bacterial CAP (B-CAP: radiologically confirmed CAP with alveolar consolidation/pleural effusion on chest X-ray, or non-alveolar infiltrates and C-reactive protein ≥ 40 µg/ml); other protocol-specified outcomes were also assessed.
Methods and Findings
This phase III double-blind randomized controlled study was conducted between 28 June 2007 and 28 July 2011 in Argentine, Panamanian, and Colombian populations with good access to health care. Approximately 24,000 infants received PHiD-CV or hepatitis control vaccine (hepatitis B for primary vaccination, hepatitis A at booster) at 2, 4, 6, and 15–18 mo of age. Interim analysis of the primary end point was planned when 535 first B-CAP episodes, occurring ≥2 wk after dose 3, were identified in the per-protocol cohort. After a mean follow-up of 23 mo (PHiD-CV, n = 10,295; control, n = 10,201), per-protocol VE was 22.0% (95% CI: 7.7, 34.2; one-sided p = 0.002) against B-CAP (conclusive for primary objective) and 25.7% (95% CI: 8.4%, 39.6%) against World Health Organization–defined consolidated CAP. Intent-to-treat VE was 18.2% (95% CI: 5.5%, 29.1%) against B-CAP and 23.4% (95% CI: 8.8%, 35.7%) against consolidated CAP. End-of-study per-protocol analyses were performed after a mean follow-up of 28–30 mo for CAP and invasive pneumococcal disease (IPD) (PHiD-CV, n = 10,211; control, n = 10,140) and AOM (n = 3,010 and 2,979, respectively). Per-protocol VE was 16.1% (95% CI: −1.1%, 30.4%; one-sided p = 0.032) against clinically confirmed AOM, 67.1% (95% CI: 17.0%, 86.9%) against vaccine serotype clinically confirmed AOM, 100% (95% CI: 74.3%, 100%) against vaccine serotype IPD, and 65.0% (95% CI: 11.1%, 86.2%) against any IPD. Results were consistent between intent-to-treat and per-protocol analyses. Serious adverse events were reported for 21.5% (95% CI: 20.7%, 22.2%) and 22.6% (95% CI: 21.9%, 23.4%) of PHiD-CV and control recipients, respectively. There were 19 deaths (n = 11,798; 0.16%) in the PHiD-CV group and 26 deaths (n = 11,799; 0.22%) in the control group. A significant study limitation was the lower than expected number of captured AOM cases.
Conclusions
Efficacy was demonstrated against a broad range of pneumococcal diseases commonly encountered in young children in clinical practice.
Trial registration
www.ClinicalTrials.gov NCT00466947
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Pneumococcal diseases are illnesses caused by Streptococcus pneumoniae bacteria, pathogens (disease-causing organisms) that are transmitted through contact with infected respiratory secretions. S. pneumoniae causes mucosal diseases–infections of the lining of the body cavities that are connected to the outside world–such as community-acquired pneumonia (CAP; lung infection) and acute otitis media (AOM; middle-ear infection). It also causes invasive pneumococcal diseases (IPDs) such as septicemia and meningitis (infections of the bloodstream and the covering of the brain, respectively). Although pneumococcal diseases can sometimes be treated with antibiotics, CAP and IPDs are leading global causes of childhood deaths, particularly in developing countries. It is best therefore to avoid S. pneumoniae infections through vaccination. Vaccination primes the immune system to recognize and attack pathogens rapidly and effectively by exposing it to weakened or dead pathogens or to pathogen molecules that it recognizes as foreign (antigens). Because there are more than 90 S. pneumoniae variants (“serotypes”), each characterized by a different antigenic polysaccharide (complex sugar) coat, S. pneumoniae vaccines have to include antigens from multiple serotypes. For example, the PHiD-CV vaccine contains polysaccharides from ten S. pneumoniae serotypes.
Why Was This Study Done?
Although in most countries PHiD-CV has been licensed for protection against IPD and pneumococcal AOM, at the time of study, it was not known how well it protected against CAP and overall AOM, which are important public health problems. In this double-blind randomized controlled trial (the Clinical Otitis Media and Pneumonia Study; COMPAS), the researchers investigate the efficacy of PHiD-CV against CAP and AOM and assess other clinical end points, such as IPD, in Latin American infants. Double-blind randomized controlled trials compare the effects of interventions by assigning study participants to different interventions randomly and measuring predefined outcomes without the study participants or researchers knowing who has received which intervention until the trial is completed. Vaccine efficacy is the reduction in the incidence of a disease (the number of new cases that occur in a population in a given time) among trial participants who receive the vaccine compared to the incidence among participants who do not receive the vaccine.
What Did the Researchers Do and Find?
The researchers enrolled around 24,000 infants living in urban areas of Argentina, Panama, and Colombia. Half the infants were given PHiD-CV at 2, 4, and 6 months of age and a booster dose at age 15–18 months. The remaining infants were given a hepatitis control vaccine at the same intervals. The trial's primary end point was likely bacterial CAP (B-CAP) –radiologically confirmed CAP, with the airspaces (alveoli) in the lungs filled with liquid instead of gas (alveolar consolidation) or with non-alveolar infiltrates and raised blood levels of C-reactive protein (a marker of inflammation). In a planned interim analysis, which was undertaken after an average follow-up of 23 months, the vaccine efficacy in the per-protocol cohort (the group of participants who actually received their assigned intervention) was 22% against B-CAP. Intent-to-treat vaccine efficacy in the interim analysis (which considered all the trial participants regardless of whether they received their assigned intervention) was 18.2%. At the end of the study (average follow up 30 months), the vaccine efficacy against B-CAP was 18.2% and 16.7% in the per-protocol and intent-to-treat cohorts, respectively. Per-protocol vaccine efficacies against clinically confirmed AOM and vaccine serotype AOM were 16.1% and 67.1%, respectively. Against any IPD and against vaccine serotype IPD, the respective vaccine efficacies were 65% and 100%. Finally, about one-fifth of children who received PHiD-CV and a similar proportion who received the control vaccine experienced a serious adverse event (for example, gastroenteritis); 19 children who received PHiD-CV died compared to 26 children who received the control vaccine.
What Do These Findings Mean?
These findings indicate that in Latin America, a region with an intermediate burden of pneumococcal disease, PHiD-CV is efficacious against a broad range of pneumococcal diseases that often affect young children. The accuracy of these findings may be limited by the withdrawal of 14% of participants from the trial because of adverse media coverage and by the low number of reported cases of AOM. Moreover, because most study participants lived in urban areas, these findings may not be generalizable to rural settings. Despite these and other study limitations, these findings provide new information about the magnitude of the effect of PHiD-CV vaccination against CAP and AOM, two mucosal pneumococcal diseases of global public health importance.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001657.
The US Centers for Disease Control and Prevention provides information for patients and health professionals on all aspects of pneumococcal disease and pneumococcal vaccination, including personal stories
Public Health England provides information on pneumococcal disease and on pneumococcal vaccines
The not-for-profit Immunization Action Coalition has information on pneumococcal disease, including personal stories
The GAVI Alliance provides information about pneumococcal disease and the importance of vaccination
MedlinePlus has links to further information about pneumococcal infections, including pneumonia and otitis media (in English and Spanish)
More information about COMPAS is available
The European Medicines Agency provides information about PHiD-CV (Synflorix)
doi:10.1371/journal.pmed.1001657
PMCID: PMC4043495  PMID: 24892763
11.  Reinterpreting Ethnic Patterns among White and African American Men Who Inject Heroin: A Social Science of Medicine Approach 
PLoS Medicine  2006;3(10):e452.
Background
Street-based heroin injectors represent an especially vulnerable population group subject to negative health outcomes and social stigma. Effective clinical treatment and public health intervention for this population requires an understanding of their cultural environment and experiences. Social science theory and methods offer tools to understand the reasons for economic and ethnic disparities that cause individual suffering and stress at the institutional level.
Methods and Findings
We used a cross-methodological approach that incorporated quantitative, clinical, and ethnographic data collected by two contemporaneous long-term San Francisco studies, one epidemiological and one ethnographic, to explore the impact of ethnicity on street-based heroin-injecting men 45 years of age or older who were self-identified as either African American or white. We triangulated our ethnographic findings by statistically examining 14 relevant epidemiological variables stratified by median age and ethnicity. We observed significant differences in social practices between self-identified African Americans and whites in our ethnographic social network sample with respect to patterns of (1) drug consumption; (2) income generation; (3) social and institutional relationships; and (4) personal health and hygiene. African Americans and whites tended to experience different structural relationships to their shared condition of addiction and poverty. Specifically, this generation of San Francisco injectors grew up as the children of poor rural to urban immigrants in an era (the late 1960s through 1970s) when industrial jobs disappeared and heroin became fashionable. This was also when violent segregated inner city youth gangs proliferated and the federal government initiated its “War on Drugs.” African Americans had earlier and more negative contact with law enforcement but maintained long-term ties with their extended families. Most of the whites were expelled from their families when they began engaging in drug-related crime. These historical-structural conditions generated distinct presentations of self. Whites styled themselves as outcasts, defeated by addiction. They professed to be injecting heroin to stave off “dopesickness” rather than to seek pleasure. African Americans, in contrast, cast their physical addiction as an oppositional pursuit of autonomy and pleasure. They considered themselves to be professional outlaws and rejected any appearance of abjection. Many, but not all, of these ethnographic findings were corroborated by our epidemiological data, highlighting the variability of behaviors within ethnic categories.
Conclusions
Bringing quantitative and qualitative methodologies and perspectives into a collaborative dialog among cross-disciplinary researchers highlights the fact that clinical practice must go beyond simple racial or cultural categories. A clinical social science approach provides insights into how sociocultural processes are mediated by historically rooted and institutionally enforced power relations. Recognizing the logical underpinnings of ethnically specific behavioral patterns of street-based injectors is the foundation for cultural competence and for successful clinical relationships. It reduces the risk of suboptimal medical care for an exceptionally vulnerable and challenging patient population. Social science approaches can also help explain larger-scale patterns of health disparities; inform new approaches to structural and institutional-level public health initiatives; and enable clinicians to take more leadership in changing public policies that have negative health consequences.
Bourgois and colleagues found that the African American and white men in their study had a different pattern of drug use and risk behaviors, adopted different strategies for survival, and had different personal histories.
Editors' Summary
Background.
There are stark differences in the health of different ethnic groups in America. For example, the life expectancy for white men is 75.4 years, but it is only 69.2 years for African-American men. The reasons behind these disparities are unclear, though there are several possible explanations. Perhaps, for example, different ethnic groups are treated differently by health professionals (with some groups receiving poorer quality health care). Or maybe the health disparities are due to differences across ethnic groups in income level (we know that richer people are healthier). These disparities are likely to persist unless we gain a better understanding of how they arise.
Why Was This Study Done?
The researchers wanted to study the health of a very vulnerable community of people: heroin users living on the streets in the San Francisco Bay Area. The health status of this community is extremely poor, and its members are highly stigmatized—including by health professionals themselves. The researchers wanted to know whether African American men and white men who live on the streets have a different pattern of drug use, whether they adopt varying strategies for survival, and whether they have different personal histories. Knowledge of such differences would help the health community to provide more tailored and culturally appropriate interventions. Physicians, nurses, and social workers often treat street-based drug users, especially in emergency rooms and free clinics. These health professionals regularly report that their interactions with street-based drug users are frustrating and confrontational. The researchers hoped that their study would help these professionals to have a better understanding of the cultural backgrounds and motivations of their drug-using patients.
What Did the Researchers Do and Find?
Over the course of six years, the researchers directly observed about 70 men living on the streets who injected heroin as they went about their usual lives (this type of research is called “participant observation”). The researchers specifically looked to see whether there were differences between the white and African American men. All the men gave their consent to be studied in this way and to be photographed. The researchers also studied a database of interviews with almost 7,000 injection drug users conducted over five years, drawing out the data on differences between white and African men. The researchers found that the white men were more likely to supplement their heroin use with inexpensive fortified wine, while African American men were more likely to supplement heroin with crack. Most of the white men were expelled from their families when they began engaging in drug-related crime, and these men tended to consider themselves as destitute outcasts. African American men had earlier and more negative contact with law enforcement but maintained long-term ties with their extended families, and these men tended to consider themselves as professional outlaws. The white men persevered less in attempting to find a vein in which to inject heroin, and so were more likely to inject the drug directly under the skin—this meant that they were more likely to suffer from skin abscesses. The white men generated most of their income from panhandling (begging for money), while the African American men generated most of their income through petty crime and/or through offering services such as washing car windows at gas stations.
What Do These Findings Mean?
Among street-based heroin users, there are important differences between white men and African American men in the type of drugs used, the method of drug use, their social backgrounds, the way in which they identify themselves, and the health risks that they take. By understanding these differences, health professionals should be better placed to provide tailored and appropriate care when these men present to clinics and emergency rooms. As the researchers say, “understanding of different ethnic populations of drug injectors may reduce difficult clinical interactions and resultant physician frustration while improving patient access and adherence to care.” One limitation of this study is that the researchers studied one specific community in one particular area of the US—so we should not assume that their findings would apply to street-based heroin users elsewhere.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030452.
The US Centers for Disease Control (CDC) has a web page on HIV prevention among injection drug users
The World Health Organization has collected documents on reducing the risk of HIV in injection drug users and on harm reduction approaches
The International Harm Reduction Association has information relevant to a global audience on reducing drug-related harm among individuals and communities
US-focused information on harm reduction is available via the websites of the Harm Reduction Coalition and the Chicago Recovery Alliance
Canada-focused information can be found at the Street Works Web site
The Harm Reduction Journal publishes open-access articles
The CDC has a web page on eliminating racial and ethnic health disparities
The Drug Policy Alliance has a web page on drug policy in the United States
doi:10.1371/journal.pmed.0030452
PMCID: PMC1621100  PMID: 17076569
12.  Anthrax Postexposure Prophylaxis in Postal Workers, Connecticut, 2001 
Emerging Infectious Diseases  2002;8(10):1133-1137.
After inhalational anthrax was diagnosed in a Connecticut woman on November 20, 2001, postexposure prophylaxis was recommended for postal workers at the regional mail facility serving the patient’s area. Although environmental testing at the facility yielded negative results, subsequent testing confirmed the presence of Bacillus anthracis. We distributed questionnaires to 100 randomly selected postal workers within 20 days of initial prophylaxis. Ninety-four workers obtained antibiotics, 68 of whom started postexposure prophylaxis and 21 discontinued. Postal workers who stopped or never started taking prophylaxis cited as reasons disbelief regarding anthrax exposure, problems with adverse events, and initial reports of negative cultures. Postal workers with adverse events reported predominant symptoms of gastrointestinal distress and headache. The influence of these concerns on adherence suggests that communication about risks of acquiring anthrax, education about adverse events, and careful management of adverse events are essential elements in increasing adherence.
doi:10.3201/eid0810.020346
PMCID: PMC2730305  PMID: 12396928
Anthrax; Bacillus anthracis; prophylaxis; adverse effects; ciprofloxacin; doxycycline; patient noncompliance; Connecticut
13.  Significant Reduction of Antibiotic Use in the Community after a Nationwide Campaign in France, 2002–2007 
PLoS Medicine  2009;6(6):e1000084.
Didier Guillemot and colleagues describe the evaluation of a nationwide programme in France aimed at decreasing unnecessary outpatient prescriptions for antibiotics. The campaign was successful, particularly in reducing prescriptions for children.
Background
Overuse of antibiotics is the main force driving the emergence and dissemination of bacterial resistance in the community. France consumes more antibiotics and has the highest rate of beta-lactam resistance in Streptococcus pneumoniae than any other European country. In 2001, the government initiated “Keep Antibiotics Working”; the program's main component was a campaign entitled “Les antibiotiques c'est pas automatique” (“Antibiotics are not automatic”) launched in 2002. We report the evaluation of this campaign by analyzing the evolution of outpatient antibiotic use in France 2000–2007, according to therapeutic class and geographic and age-group patterns.
Methods and Findings
This evaluation is based on 2000–2007 data, including 453,407,458 individual reimbursement data records and incidence of flu-like syndromes (FLSs). Data were obtained from the computerized French National Health Insurance database and provided by the French Sentinel Network. As compared to the preintervention period (2000–2002), the total number of antibiotic prescriptions per 100 inhabitants, adjusted for FLS frequency during the winter season, changed by −26.5% (95% confidence interval [CI] −33.5% to −19.6%) over 5 years. The decline occurred in all 22 regions of France and affected all antibiotic therapeutic classes except quinolones. The greatest decrease, −35.8% (95% CI −48.3% to −23.2%), was observed among young children aged 6–15 years. A significant change of −45% in the relationship between the incidence of flu-like syndromes and antibiotic prescriptions was observed.
Conclusions
The French national campaign was associated with a marked reduction of unnecessary antibiotic prescriptions, particularly in children. This study provides a useful method for assessing public-health strategies designed to reduce antibiotic use.
Editors' Summary
Background
In 1928, Alexander Fleming discovered penicillin, the first antibiotic (a drug that kills bacteria). By the early 1940s, large amounts of penicillin could be made and, in the following decades, several other classes of powerful antibiotics were discovered. For a time, it looked like bacteria and the diseases that they cause had been defeated. But bacteria rapidly became resistant to these wonder drugs and nowadays, antibiotic resistance is a pressing public-health concern. Almost every type of disease-causing bacteria has developed resistance to one or more antibiotic in clinical use, and multidrug-resistant bacteria are causing outbreaks of potentially fatal diseases in hospitals and in the community. For example, multidrug-resistant Streptococcus pneumoniae (multidrug-resistant pneumococci or MRP) is now very common. S. pneumoniae colonize the nose and throat (the upper respiratory tract) and can cause diseases that range from mild ear infections to life-threatening pneumonia, particularly in young children and elderly people.
Why Was This Study Done?
For years, doctors have been prescribing (and patients have been demanding) antibiotics for viral respiratory infections (VRIs) such as colds and flu even though antibiotics do not cure viral infections. This overuse of antibiotics has been the main driving force in the spread of MRP. Thus, the highest rate of S. pneumoniae antibiotic resistance in Europe occurs in France, which has one of the highest rates of antibiotic consumption in the world. In 2001 France initiated “le plan national pour préserver l'efficacité des antibiotiques” to reduce the inappropriate use of antibiotics, particularly for the treatment of VRIs among children. The main component of the program was the “Antibiotiques c'est pas automatique” (“Antibiotics are not automatic”) campaign, which ran from 2002 to 2007 during the winter months when VRIs mainly occur. The campaign included an educational campaign for health care workers, the promotion of rapid tests for diagnosis of streptococcal infections, and a public information campaign about VRIs and about antibiotic resistance. In this study, the researchers evaluate the campaign by analyzing outpatient antibiotic use throughout France from 2000 to 2007.
What Did the Researchers Do and Find?
The researchers obtained information about antibiotic prescriptions and about the occurrence of flu-like illnesses during the study period from the French National Health Insurance database and national disease surveillance system, respectively. After adjusting for variations in the frequency of flu-like illnesses, compared to the preintervention period (2000–2002), the number of antibiotic prescriptions per 100 inhabitants decreased by a quarter over the five winters of the “Antibiotics are not automatic” campaign. The use of all major antibiotic classes except quinolones decreased in all 22 regions of France. Thus, whereas in 2000, more than 70 prescriptions per 100 inhabitants were issued during the winter in 15 regions, by 2006/7, no regions exceeded this prescription rate. The greatest decrease in prescription rate (a decrease of more than a third by 2006/7) was among children aged 6–15 years. Finally, although the rates of antibiotic prescriptions reflected the rates of flu-like illness throughout the campaign, by 2006/7 this relationship was much weaker, which suggests that fewer antibiotics were being prescribed for VRIs.
What Do These Findings Mean?
These findings indicate that the “Antibiotics are not automatic” campaign was associated with a reduction in antibiotic prescriptions, particularly in children. Because the whole French population was exposed to the campaign, these findings do not prove that the campaign actually caused the reduction in antibiotic prescriptions. The observed decrease might have been caused by other initiatives in France or elsewhere or by the introduction of a S. pneumoniae vaccine during the study period, for example. However, an independent survey indicated that fewer members of the public expected an antibiotic prescription for a VRI at the end of the campaign than at the start, that more people knew that antibiotics only kill bacteria, and that doctors were more confident about not prescribing antibiotics for VRIs. Thus, campaigns like “Antibiotics are not automatic” may be a promising way to reduce the overuse of antibiotics and to slow the spread of antibiotic resistance until new classes of effective antibiotics are developed.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000084.
This study is further discussed in a PLoS Medicine Perspective by Stephen Harbarth and Benedikt Huttner
The Bugs and Drugs Web site from the UK National electronic Library of Infection provides information about antibiotic resistance and links to other resources
The US National Institute of Allergy and Infectious Diseases provides information on antimicrobial drug resistance and on pneumococcal pneumonia
The US Centers for Disease Control and Prevention also have information on antibiotic resistance (in English and Spanish)
The European Surveillance of Antimicrobial Consumption Web site provides information on antibiotic consumption in European countries
Les antibiotiques c'est pas automatique provides information about the “Antibiotics are not automatic” campaign (in French)
Information on the Plan National pour Pérserver l'efficacité des antibiotiques is also available (in French)
doi:10.1371/journal.pmed.1000084
PMCID: PMC2683932  PMID: 19492093
14.  Anthrax vaccination strategies 
Molecular aspects of medicine  2009;30(6):490-502.
The biological attack conducted through the U.S. postal system in 2001 broadened the threat posed by anthrax from one pertinent mainly to soldiers on the battlefield to one understood to exist throughout our society. The expansion of the threatened population placed greater emphasis on the reexamination of how we vaccinate against Bacillus anthracis. The currently-licensed Anthrax Vaccine, Adsorbed (AVA) and Anthrax Vaccine, Precipitated (AVP) are capable of generating a protective immune response but are hampered by shortcomings that make their widespread use undesirable or infeasible. Efforts to gain U.S. Food and Drug Administration (FDA) approval for licensure of a second generation recombinant protective antigen (rPA)-based anthrax vaccine are ongoing. However, this vaccine's reliance on the generation of a humoral immune response against a single virulence factor has led a number of scientists to conclude that the vaccine is likely not the final solution to optimal anthrax vaccine design. Other vaccine approaches, which seek a more comprehensive immune response targeted at multiple components of the B. anthracis organism, are under active investigation. This review seeks to summarize work that has been done to build on the current PA-based vaccine methodology and to evaluate the search for future anthrax prophylaxis strategies.
doi:10.1016/j.mam.2009.08.006
PMCID: PMC2783700  PMID: 19729034
Bacillus anthracis; anthrax; vaccine
15.  Mass Vaccination with a New, Less Expensive Oral Cholera Vaccine Using Public Health Infrastructure in India: The Odisha Model 
Introduction
The substantial morbidity and mortality associated with recent cholera outbreaks in Haiti and Zimbabwe, as well as with cholera endemicity in countries throughout Asia and Africa, make a compelling case for supplementary cholera control measures in addition to existing interventions. Clinical trials conducted in Kolkata, India, have led to World Health Organization (WHO)-prequalification of Shanchol, an oral cholera vaccine (OCV) with a demonstrated 65% efficacy at 5 years post-vaccination. However, before this vaccine is widely used in endemic areas or in areas at risk of outbreaks, as recommended by the WHO, policymakers will require empirical evidence on its implementation and delivery costs in public health programs. The objective of the present report is to describe the organization, vaccine coverage, and delivery costs of mass vaccination with a new, less expensive OCV (Shanchol) using existing public health infrastructure in Odisha, India, as a model.
Methods
All healthy, non-pregnant residents aged 1 year and above residing in selected villages of the Satyabadi block (Puri district, Odisha, India) were invited to participate in a mass vaccination campaign using two doses of OCV. Prior to the campaign, a de jure census, micro-planning for vaccination and social mobilization activities were implemented. Vaccine coverage for each dose was ascertained as a percentage of the censused population. The direct vaccine delivery costs were estimated by reviewing project expenditure records and by interviewing key personnel.
Results
The mass vaccination was conducted during May and June, 2011, in two phases. In each phase, two vaccine doses were given 14 days apart. Sixty-two vaccination booths, staffed by 395 health workers/volunteers, were established in the community. For the censused population, 31,552 persons (61% of the target population) received the first dose and 23,751 (46%) of these completed their second dose, with a drop-out rate of 25% between the two doses. Higher coverage was observed among females and among 6–17 year-olds. Vaccine cost at market price (about US$1.85/dose) was the costliest item. The vaccine delivery cost was $0.49 per dose or $1.13 per fully vaccinated person.
Discussion
This is the first undertaken project to collect empirical evidence on the use of Shanchol within a mass vaccination campaign using existing public health program resources. Our findings suggest that mass vaccination is feasible but requires detailed micro-planning. The vaccine and delivery cost is affordable for resource poor countries. Given that the vaccine is now WHO pre-qualified, evidence from this study should encourage oral cholera vaccine use in countries where cholera remains a public health problem.
Author Summary
Cholera – an acute life-threatening diarrheal illness – continues to disrupt public health in resource poor countries. The devastating outbreaks in Haiti and Zimbabwe – to name just two of many occurrences – calls for the use of available oral cholera vaccines as an additional tool in the arsenal of cholera control measures. An oral cholera vaccine (Shanchol) has been licensed in India since 2009; however, there has only been limited use of this vaccine in government public health programs. A vaccination campaign using 2 doses of Shanchol was conducted in Odisha, India, during May and June, 2011, where 31,552 persons (61% of the target population) received the first dose and 23,751 of them completed their second dose. The vaccine delivery cost was $0.49 per dose. Through our findings and experience, we discuss the organization of the cholera vaccination campaign in Odisha, the challenges met for conducting the campaign and the strategies designed to overcome those challenges, and the delivery costs incurred in the use of this vaccine, the first of its kind, in a public health setting. We believe that evidence from this study is of significant interest and use to policymakers from countries where cholera remains a public health problem.
doi:10.1371/journal.pntd.0002629
PMCID: PMC3916257  PMID: 24516675
16.  Conjunctival FOXP3 Expression in Trachoma: Do Regulatory T Cells Have a Role in Human Ocular Chlamydia trachomatis Infection? 
PLoS Medicine  2006;3(8):e266.
Background
Trachoma, caused by ocular infection with Chlamydia trachomatis, remains the leading infectious cause of blindness and in 2002 was responsible for 3.6% of total global blindness. Although transmission can be successfully interrupted using antibiotics and improvements in public and personal hygiene, the long-term success of the control programmes advocated by the World Health Organization are still uncertain. For the complete control and prevention of trachoma, a vaccine would be highly desirable. Currently there are no licensed vaccines for trachoma, and no human vaccine trials have been conducted since the 1960s. A barrier to new attempts to design and introduce a vaccine is the identification of immunologic correlates of protective immunity or immunopathology. We studied important correlates of the immune response in a trachoma-endemic population in order to improve our knowledge of this disease. This is essential for the successful development of a vaccine against both ocular and genital C. trachomatis infection.
Methods and Findings
We used quantitative real-time PCR for C. trachomatis 16S rRNA to identify conjunctival infection. The expression of IFN-γ, IDO, IL-10, and FOXP3 mRNA transcripts was measured. We evaluated the role of immune effector and regulatory responses in the control of chlamydial infection and in the resolution of clinical signs of trachoma in endemic communities in Gambia. All host transcripts examined were detectable even in normal conjunctiva. The levels of these transcripts were increased, compared to normal uninfected conjunctiva, when infection was detected, with or without clinical disease signs. Interestingly, when clinical disease signs were present in the absence of infection, the expression of a regulatory T cell transcription factor, FOXP3, remained elevated.
Conclusions
There is evidence of an increase in the magnitude of the local anti-chlamydial cytokine immune responses with age. This increase is coupled to a decline in the prevalence of infection and active trachoma, suggesting that effective adaptive immunity is acquired over a number of years. The anti-chlamydial and inflammatory immune response at the conjunctival surface, which may control chlamydial replication, is closely matched by counter inflammatory or regulatory IL-10 expression. Differences in the level of FOXP3 expression in the conjunctiva may indicate a role for regulatory T cells in the resolution of the conjunctival immune response, which is important in protection from immunopathology. However, the expression of cytokines that control chlamydial replication and those that regulate the conjunctival immune response is not simply juxtaposed; the interaction between the infection and the clinical disease process is therefore more complex.
The immune response in a trachoma-endemic population showed an increase in local anti-chlamydial cytokine responses with age, associated with a decline in the prevalence of infection and active trachoma.
Editors' Summary
Background.
Trachoma is the leading infectious cause of blindness worldwide. Six million people—most of whom live in crowded, unhygienic conditions with limited water supplies—are blind because of repeated eye infections with Chlamydia trachomatis. This bacterium passes easily from person to person on hands or clothing and is also spread by flies. Successive infections starting in childhood cause progressive scarring of the inside of the eyelid. Eventually, the eyelashes turn inwards and rub painfully over the front of the eye (the cornea). This causes corneal scarring, loss of corneal transparency, and, finally, irreversible loss of sight, usually in adulthood. C. trachomatis infections can be prevented by improving personal hygiene and by reducing fly breeding sites, and they can be treated with antibiotics. In addition, early scarring of the eyelid and turned-in eyelashes can be treated surgically.
Why Was This Study Done?
Through the above interventions, the World Health Organization hopes to eliminate trachoma by 2020, but a vaccine might also be necessary. To develop a vaccine, the human immune response to C. trachomatis needs to be better understood. As with other diseases, the immune response to C. trachomatis includes a pro-inflammatory side, which activates immune cells to attack the bacteria, and a regulatory side, which keeps the pro-inflammatory responses in check. The balance between these two sides is not perfect, however. Although the immune response deals with C. trachomatis infections efficiently, it also causes some of the tissue damage that leads to scarring and loss of sight. In this study, the researchers have investigated the human immune response to C. trachomatis to provide immunological information that might help vaccine development.
What Did the Researchers Do and Find?
The researchers examined school children living in Gambia, where trachoma is very common, for clinical signs of active trachoma (for example, red or swollen eyelids). To find out which children were infected with C. trachomatis, the researchers collected a few cells from the surface of their eyes and looked for a ribonucleic acid (RNA) molecule that is only made by C. trachomatis. The researchers also looked in these samples for human messenger RNA (mRNA) molecules that are made during pro-inflammatory and regulatory immune responses.
The children formed four groups based on infection with C. trachomatis and clinical signs. Some children—particularly the older ones—were uninfected and had no clinical signs. Others were infected but showed no clinical signs—these children were incubating the bacteria. Some were infected and had clinical disease; these children had the highest bacterial loads. Finally, children recovering from an infection carried no bacteria but still had some clinical signs.
The researchers detected different types of immune response in each of these groups. Children incubating the bacteria had a strong pro-inflammatory response—their immune systems were trying to fight off infection. The pro-inflammatory response was even stronger in the infected children with clinical signs, but now the regulatory response had also increased, presumably to limit inflammation. In children in the recovery phase, only regulatory immune cells, which were making an mRNA from a gene called FOXP3, remained active.
What Do These Findings Mean?
The relative rarity of infections and active disease in older children together with indications of a more active immune response to infection indicates that protective immunity to C. trachomatis is acquired through repeated exposure to it. This bodes well for the development of a vaccine, which would speed up the acquisition of this natural immunity. Furthermore, the new information about immune responses at different stages of infection with C. trachomatis should help in vaccine design. The findings need to be confirmed by tracking immune responses in individual children during episodes of infection, but could then be used to help design vaccines that produce good protective immunity against C. trachomatis without causing too much collateral tissue damage. The current results suggest, for example, that regulatory immune cells are important in limiting the inflammatory response, so vaccine developers may need to ensure that their vaccines stimulate the production of this sort of cell as well as of the pro-inflammatory cells needed to clear the infection.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030266.
• NHS Direct Online patient information on trachoma
• World Health Organization information on trachoma and its elimination
• US Centers for Disease Control and Prevention general information on trachoma
• MedlinePlus encyclopedia entry on trachoma
doi:10.1371/journal.pmed.0030266
PMCID: PMC1526769  PMID: 16881731
17.  Call-Tracking Data and the Public Health Response to Bioterrorism-Related Anthrax 
Emerging Infectious Diseases  2002;8(10):1088-1092.
After public notification of confirmed cases of bioterrorism-related anthrax, the Centers for Disease Control and Prevention’s Emergency Operations Center responded to 11,063 bioterrorism-related telephone calls from October 8 to November 11, 2001. Most calls were inquiries from the public about anthrax vaccines (58.4%), requests for general information on bioterrorism prevention (14.8%), and use of personal protective equipment (12.0%); 882 telephone calls (8.0%) were referred to the state liaison team for follow-up investigation. Of these, 226 (25.6%) included reports of either illness clinically confirmed to be compatible with anthrax or direct exposure to an environment known to be contaminated with Bacillus anthracis. The remaining 656 (74.4%) included no confirmed illness but reported exposures to “suspicious” packages or substances or the receipt of mail through a contaminated facility. Emergency response staff must handle high call volumes following suspected or actual bioterrorist attacks. Standardized health communication protocols that address contact with unknown substances, handling of suspicious mail, and clinical evaluation of suspected cases would allow more efficient follow-up investigations of clinically compatible cases in high-risk groups.
doi:10.3201/eid0810.020355
PMCID: PMC2730299  PMID: 12396921
anthrax; bioterrorism; triage; Centers for Disease Control and Prevention
18.  Association between the 2008–09 Seasonal Influenza Vaccine and Pandemic H1N1 Illness during Spring–Summer 2009: Four Observational Studies from Canada 
PLoS Medicine  2010;7(4):e1000258.
In three case-control studies and a household transmission cohort, Danuta Skowronski and colleagues find an association between prior seasonal flu vaccination and increased risk of 2009 pandemic H1N1 flu.
Background
In late spring 2009, concern was raised in Canada that prior vaccination with the 2008–09 trivalent inactivated influenza vaccine (TIV) was associated with increased risk of pandemic influenza A (H1N1) (pH1N1) illness. Several epidemiologic investigations were conducted through the summer to assess this putative association.
Methods and Findings
Studies included: (1) test-negative case-control design based on Canada's sentinel vaccine effectiveness monitoring system in British Columbia, Alberta, Ontario, and Quebec; (2) conventional case-control design using population controls in Quebec; (3) test-negative case-control design in Ontario; and (4) prospective household transmission (cohort) study in Quebec. Logistic regression was used to estimate odds ratios for TIV effect on community- or hospital-based laboratory-confirmed seasonal or pH1N1 influenza cases compared to controls with restriction, stratification, and adjustment for covariates including combinations of age, sex, comorbidity, timeliness of medical visit, prior physician visits, and/or health care worker (HCW) status. For the prospective study risk ratios were computed. Based on the sentinel study of 672 cases and 857 controls, 2008–09 TIV was associated with statistically significant protection against seasonal influenza (odds ratio 0.44, 95% CI 0.33–0.59). In contrast, estimates from the sentinel and three other observational studies, involving a total of 1,226 laboratory-confirmed pH1N1 cases and 1,505 controls, indicated that prior receipt of 2008–09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring–summer 2009, with estimated risk or odds ratios ranging from 1.4 to 2.5. Risk of pH1N1 hospitalization was not further increased among vaccinated people when comparing hospitalized to community cases.
Conclusions
Prior receipt of 2008–09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring–summer 2009 in Canada. The occurrence of bias (selection, information) or confounding cannot be ruled out. Further experimental and epidemiological assessment is warranted. Possible biological mechanisms and immunoepidemiologic implications are considered.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every winter, millions of people catch influenza—a viral infection of the airways—and hundreds of thousands of people die as a result. These seasonal epidemics occur because small but frequent changes in the influenza virus mean that an immune response produced one year through infection or vaccination provides only partial protection against influenza the next year. Annual vaccination with killed influenza viruses of the major circulating strains can greatly reduce a person's risk of catching influenza. Consequently, many countries run seasonal influenza vaccination programs. In most of Canada, vaccination with a mixture of three inactivated viruses (a trivalent inactivated vaccine or TIV) is provided free to children aged 6–23 months, to elderly people, to people with long-term conditions that increase their risk of influenza-related complications, and those who provide care for them; in Ontario, free vaccination is offered to everyone older than 6 months.
In addition, influenza viruses occasionally emerge that are very different and to which human populations have virtually no immunity. These viruses can start global epidemics (pandemics) that can kill millions of people. Experts have been warning for some time that an influenza pandemic is long overdue and, in March 2009, the first cases of influenza caused by a new virus called pandemic A/H1N1 2009 (pH1N1; swine flu) occurred in Mexico. The virus spread rapidly and on 11 June 2009, the World Health Organization declared that a global pandemic of pH1N1 influenza was underway. By the end of February 2010, more than 16,000 people around the world had died from pH1N1.
Why Was This Study Done?
During an investigation of a school outbreak of pH1N1 in the late spring 2009 in Canada, investigators noted that people with illness characterized by fever and coughing had been vaccinated against seasonal influenza more often than individuals without such illness. To assess whether this association between prior vaccination with seasonal 2008–09 TIV and subsequent pH1N1 illness was evident in other settings, researchers in Canada therefore conducted additional studies using different methods. In this paper, the researchers report the results of four additional studies conducted in Canada during the summer of 2009 to assess this possible association.
What Did the Researchers Do and Find?
The researchers conducted four epidemiologic studies. Epidemiology is the study of the causes, distribution, and control of diseases in populations.
Three of the four studies were case-control studies in which the researchers assessed the frequency of prior vaccination with the 2008–09 TIV in people with pH1N1 influenza compared to the frequency among healthy members of the general population or among individuals who had an influenza-like illness but no sign of infection with an influenza virus. The researchers also did a household transmission study in which they collected information about vaccination with TIV among the additional cases of influenza that were identified in 47 households in which a case of laboratory-confirmed pH1N1 influenza had occurred. The first of the case-control studies, which was based on Canada's vaccine effectiveness monitoring system, showed that, as expected, the 2008–09 TIV provided protection against seasonal influenza. However, estimates from all four studies (which included about 1,200 laboratory-confirmed pH1N1 cases and 1,500 controls) showed that prior recipients of the 2008–09 TIV had approximately 1.4–2.5 times increased chances of developing pH1N1 illness that needed medical attention during the spring–summer of 2009 compared to people who had not received the TIV. Prior seasonal vaccination was not associated with an increase in the severity of pH1N1 illness, however. That is, it did not increase the risk of being hospitalized among those with pH1N1 illness.
What Do These Findings Mean?
Because all the investigations in this study are “observational,” the people who had been vaccinated might share another unknown characteristic that is actually responsible for increasing their risk of developing pH1N1 illness (“confounding”). Furthermore, the results reported in this study might have arisen by chance, although the consistency of results across the studies makes this unlikely. Thus, the finding of an association between prior receipt of 2008–09 TIV and an increased risk of pH1N1 illness is not conclusive and needs to be investigated further, particularly since some other observational studies conducted in other countries have reported that seasonal vaccination had no influence or may have been associated with reduced chances of pH1N1 illness. If the findings in the current study are real, however, they raise important questions about the biological interactions between seasonal and pandemic influenza strains and vaccines, and about the best way to prevent and control both types of influenza in future.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/ 10.1371/journal.pmed.1000258.
This article is further discussed in a PLoS Medicine Perspective by Cécile Viboud and Lone Simonsen
FightFlu.ca, a Canadian government Web site, provides access to information on pH1N1 influenza
The US Centers for Disease Control and Prevention provides information about influenza for patients and professionals, including specific information on H1N1 influenza
Flu.gov, a US government website, provides access to information on H1N1, avian and pandemic influenza
The World Health Organization provides information on seasonal influenza and has detailed information on pH1N1 influenza (in several languages)
The UK Health Protection Agency provides information on pandemic influenza and on pH1N1 influenza
doi:10.1371/journal.pmed.1000258
PMCID: PMC2850386  PMID: 20386731
19.  Serotype-Specific Changes in Invasive Pneumococcal Disease after Pneumococcal Conjugate Vaccine Introduction: A Pooled Analysis of Multiple Surveillance Sites 
PLoS Medicine  2013;10(9):e1001517.
In a pooled analysis of data collected from invasive pneumococcal disease surveillance databases, Daniel Feikin and colleagues examine serotype replacement after the introduction of 7-valent pneumococcal conjugate vaccine (PCV7) into national immunization programs.
Please see later in the article for the Editors' Summary
Background
Vaccine-serotype (VT) invasive pneumococcal disease (IPD) rates declined substantially following introduction of 7-valent pneumococcal conjugate vaccine (PCV7) into national immunization programs. Increases in non-vaccine-serotype (NVT) IPD rates occurred in some sites, presumably representing serotype replacement. We used a standardized approach to describe serotype-specific IPD changes among multiple sites after PCV7 introduction.
Methods and Findings
Of 32 IPD surveillance datasets received, we identified 21 eligible databases with rate data ≥2 years before and ≥1 year after PCV7 introduction. Expected annual rates of IPD absent PCV7 introduction were estimated by extrapolation using either Poisson regression modeling of pre-PCV7 rates or averaging pre-PCV7 rates. To estimate whether changes in rates had occurred following PCV7 introduction, we calculated site specific rate ratios by dividing observed by expected IPD rates for each post-PCV7 year. We calculated summary rate ratios (RRs) using random effects meta-analysis. For children <5 years old, overall IPD decreased by year 1 post-PCV7 (RR 0·55, 95% CI 0·46–0·65) and remained relatively stable through year 7 (RR 0·49, 95% CI 0·35–0·68). Point estimates for VT IPD decreased annually through year 7 (RR 0·03, 95% CI 0·01–0·10), while NVT IPD increased (year 7 RR 2·81, 95% CI 2·12–3·71). Among adults, decreases in overall IPD also occurred but were smaller and more variable by site than among children. At year 7 after introduction, significant reductions were observed (18–49 year-olds [RR 0·52, 95% CI 0·29–0·91], 50–64 year-olds [RR 0·84, 95% CI 0·77–0·93], and ≥65 year-olds [RR 0·74, 95% CI 0·58–0·95]).
Conclusions
Consistent and significant decreases in both overall and VT IPD in children occurred quickly and were sustained for 7 years after PCV7 introduction, supporting use of PCVs. Increases in NVT IPD occurred in most sites, with variable magnitude. These findings may not represent the experience in low-income countries or the effects after introduction of higher valency PCVs. High-quality, population-based surveillance of serotype-specific IPD rates is needed to monitor vaccine impact as more countries, including low-income countries, introduce PCVs and as higher valency PCVs are used.
Please see later in the article for the Editors' Summary
Editors’ Summary
Background
Pneumococcal disease–a major cause of illness and death in children and adults worldwide–is caused by Streptococcus pneumoniae, a bacterium that often colonizes the nose and throat harmlessly. Unfortunately, S. pneumoniae occasionally spreads into the lungs, bloodstream, or covering of the brain, where it causes pneumonia, septicemia, and meningitis, respectively. These invasive pneumococcal diseases (IPDs) can usually be successfully treated with antibiotics but can be fatal. Consequently, it is better to avoid infection through vaccination. Vaccination primes the immune system to recognize and attack disease-causing organisms (pathogens) rapidly and effectively by exposing it to weakened or dead pathogens or to pathogen molecules that it recognizes as foreign (antigens). Because there are more than 90 S. pneumoniae variants or “serotypes,” each characterized by a different antigenic polysaccharide (complex sugar) coat, vaccines that protect against S. pneumoniae have to include multiple serotypes. Thus, the pneumococcal conjugate vaccine PCV7, which was introduced into the US infant immunization regimen in 2000, contains polysaccharides from the seven S. pneumoniae serotypes mainly responsible for IPD in the US at that time.
Why Was This Study Done?
Vaccination with PCV7 was subsequently introduced in several other high- and middle-income countries, and IPD caused by the serotypes included in the vaccine declined substantially in children and in adults (because of reduced bacterial transmission and herd protection) in the US and virtually all these countries. However, increases in IPD caused by non-vaccine serotypes occurred in some settings, presumably because of “serotype replacement.” PCV7 prevents both IPD caused by the serotypes it contains and carriage of these serotypes. Consequently, after vaccination, previously less common, non-vaccine serotypes can colonize the nose and throat, some of which can cause IPD. In July 2010, a World Health Organization expert consultation on serotype replacement called for a comprehensive analysis of the magnitude and variability of pneumococcal serotype replacement following PCV7 use to help guide the introduction of PCVs in low-income countries, where most pneumococcal deaths occur. In this pooled analysis of data from multiple surveillance sites, the researchers investigate serotype-specific changes in IPD after PCV7 introduction using a standardized approach.
What Did the Researchers Do and Find?
The researchers identified 21 databases that had data about the rate of IPD for at least 2 years before and 1 year after PCV7 introduction. They estimated whether changes in IPD rates had occurred after PCV7 introduction by calculating site-specific rate ratios–the observed IPD rate for each post-PCV7 year divided by the expected IPD rate in the absence of PCV7 extrapolated from the pre-PCV7 rate. Finally, they used a statistical approach (random effects meta-analysis) to estimate summary (pooled) rate ratios. For children under 5 years old, the overall number of observed cases of IPD in the first year after the introduction of PCV7 was about half the expected number; this reduction in IPD continued through year 7 after PCV7 introduction. Notably, the rate of IPD caused by the S. pneumonia serotypes in PCV7 decreased every year, but the rate of IPD caused by non-vaccine serotypes increased annually. By year 7, the number of cases of IPD caused by non-vaccine serotypes was 3-fold higher than expected, but was still smaller than the decrease in vaccine serotypes, thereby leading to the decrease in overall IPD. Finally, smaller decreases in overall IPD also occurred among adults but occurred later than in children 2 years or more after PCV7 introduction.
What Do These Findings Mean?
These findings show that consistent, rapid, and sustained decreases in overall IPD and in IPD caused by serotypes included in PCV7 occurred in children and thus support the use of PCVs. The small increases in IPD caused by non-vaccine serotypes that these findings reveal are likely to be the result of serotype replacement, but changes in antibiotic use and other factors may also be involved. These findings have several important limitations, however. For example, PCV7 is no longer made and extrapolation of these results to newer PCV10 and PCV13 formulations should be done cautiously. On the other hand, many of the serotypes causing serotype replacement after PCV7 are included in these higher valency vaccines. Moreover, because the data analyzed in this study mainly came from high-income countries, these findings may not be generalizable to low-income countries. Nevertheless, based on their analysis, the researchers make recommendations for the collection and analysis of IPD surveillance data that should allow valid interpretations of the effect of PCVs on IPD to be made, an important requisite for making sound policy decisions about vaccination against pneumococcal disease.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001517.
The US Centers for Disease Control and Prevention provides information for patients and health professionals on all aspects of pneumococcal disease and pneumococcal vaccination, including personal stories
Public Health England provides information on pneumococcal disease and on pneumococcal vaccines
The World Health Organization also provides information on pneumococcal vaccines
The not-for-profit Immunization Action Coalition has information on pneumococcal disease, including personal stories
MedlinePlus has links to further information about pneumococcal infections (in English and Spanish)
The International Vaccine Access Center at Johns Hopkins Bloomberg School of Public Health has more information on introduction of pneumococcal conjugate vaccines in low-income countries
doi:10.1371/journal.pmed.1001517
PMCID: PMC3782411  PMID: 24086113
20.  Adherence to Antimicrobial Inhalational Anthrax Prophylaxis among Postal Workers, Washington, D.C., 2001 
Emerging Infectious Diseases  2002;8(10):1138-1144.
In October 2001, two envelopes containing Bacillus anthracis spores were processed at the Washington, D.C., Processing and Distribution Center of the U.S. Postal Service; inhalational anthrax developed in four workers at this facility. More than 2,000 workers were advised to complete 60 days of postexposure prophylaxis to prevent inhalational anthrax. Interventions to promote adherence were carried out to support workers, and qualitative information was collected to evaluate our interventions. A quantitative survey was administered to a convenience sample of workers to assess factors influencing adherence. No anthrax infections developed in any workers involved in the interventions or interviews. Of 245 workers, 98 (40%) reported full adherence to prophylaxis, and 45 (18%) had completely discontinued it. Experiencing adverse effects to prophylaxis, anxiety, and being <45 years old were risk factors for discontinuing prophylaxis. Interventions, especially frequent visits by public health staff, proved effective in supporting adherence.
doi:10.3201/eid0810.020331
PMCID: PMC2730315  PMID: 12396929
adherence; Bacillus anthracis; bioterrorism; antimicrobial prophylaxis; compliance
21.  The Legacy of the U. S. Public Health Services Study of Untreated Syphilis in African American Men at Tuskegee on the Affordable Care Act and Health Care Reform Fifteen Years After President Clinton’s Apology 
Ethics & behavior  2012;22(6):411-418.
This special issue addresses the legacy of the United States Public Health Service Syphilis Study on health reform, particularly the Affordable Care Act (ACA). The 12 manuscripts cover the history and current practices of ethical abuses affecting American Indians, Latinos, Asian Americans and African Americans in the United States and in one case, internationally. Commentaries and essays include the voice of a daughter of one of the study participants in which we learn of the stigma and maltreatment some of the families experienced and how the study has impacted generations within the families. Consideration is given in one essay to utilizing narrative storytelling with the families to help promote healing.
This article provides the reader a roadmap to the themes that emerged from the collection of articles. These themes include population versus individual consent issues, need for better government oversight in research and health care, the need for overhauling our bioethics training to develop a population level, culturally driven approach to research bioethics. The articles challenge and inform us that some of our assumptions about how the consent process best works to protect racial/ethnic minorities may be merely assumptions and not proven facts. Articles challenge the belief that low participation rates seen in biomedical studies have resulted from the legacy of the USPHS Syphilis Study rather than a confluence of factors rooted in racism, bias and negative treatment. Articles in this special issue challenge the “cultural paranoia” of mistrust and provide insights into how the distrust may serve to lengthen rather than shorten the lives of racial/ethnic minorities who have been used as guinea pigs on more than one occasion. We hope that the guidance offered on the importance of developing a new framework to bioethics can be integrated into the foundation of health care reform.
doi:10.1080/10508422.2012.730808
PMCID: PMC3636721  PMID: 23630410
Tuskegee; research bioethics; survivors
22.  Professional Uncertainty and Disempowerment Responding to Ethnic Diversity in Health Care: A Qualitative Study 
PLoS Medicine  2007;4(11):e323.
Background
While ethnic disparities in health and health care are increasing, evidence on how to enhance quality of care and reduce inequalities remains limited. Despite growth in the scope and application of guidelines on “cultural competence,” remarkably little is known about how practising health professionals experience and perceive their work with patients from diverse ethnic communities. Using cancer care as a clinical context, we aimed to explore this with a range of health professionals to inform interventions to enhance quality of care.
Methods and Findings
We conducted a qualitative study involving 18 focus groups with a purposeful sample of 106 health professionals of differing disciplines, in primary and secondary care settings, working with patient populations of varying ethnic diversity in the Midlands of the UK. Data were analysed by constant comparison and we undertook processes for validation of analysis. We found that, as they sought to offer appropriate care, health professionals wrestled with considerable uncertainty and apprehension in responding to the needs of patients of ethnicities different from their own. They emphasised their perceived ignorance about cultural difference and were anxious about being culturally inappropriate, causing affront, or appearing discriminatory or racist. Professionals' ability to think and act flexibly or creatively faltered. Although trying to do their best, professionals' uncertainty was disempowering, creating a disabling hesitancy and inertia in their practice. Most professionals sought and applied a knowledge-based cultural expertise approach to patients, though some identified the risk of engendering stereotypical expectations of patients. Professionals' uncertainty and disempowerment had the potential to perpetuate each other, to the detriment of patient care.
Conclusions
This study suggests potential mechanisms by which health professionals may inadvertently contribute to ethnic disparities in health care. It identifies critical opportunities to empower health professionals to respond more effectively. Interventions should help professionals acknowledge their uncertainty and its potential to create inertia in their practice. A shift away from a cultural expertise model toward a greater focus on each patient as an individual may help.
From a qualitative study, Joe Kai and colleagues have identified opportunities to empower health professionals to respond more effectively to challenges in their work with patients from diverse ethnic communities.
Editors' Summary
Background.
Communities are increasingly diverse in terms of ethnicity (belonging to a group of people defined by social characteristics such as cultural tradition or national origin) and race (belonging to a group identified by inherited physical characteristics). Although health professionals and governments are striving to ensure that everybody has the same access to health care, there is increasing evidence of ethnic inequalities in health-care outcomes. Some of these inequalities reflect intrinsic differences between groups of people—Ashkenazi Jews, for example, often carry an altered gene that increases their chance of developing aggressive breast cancer. Often, however, these differences reflect inequalities in the health care received by different ethnic groups. To improve this situation, “cultural competence” has been promoted over recent years. Cultural competence is the development of skills by individuals and organizations that allow them to work effectively with people from different cultures. Health professionals are now taught about ethnic differences in health beliefs and practices, religion, and communication styles to help them provide the best service to all their patients.
Why Was This Study Done?
Numerous guidelines aim to improve cultural competency but little is known about how health professionals experience and perceive their work with patients from diverse ethnic groups. Is their behavior influenced by ethnicity in ways that might contribute to health care disparities? For example, do doctors sometimes avoid medical examinations for fear of causing offence because of cultural differences? If more were known about how health professionals handle ethnic diversity (a term used here to include both ethnicity and race) it might be possible to reduce ethnic inequalities in health care. In this qualitative study, the researchers have explored how health professionals involved in cancer care are affected by working with ethnically diverse patients. A qualitative study is one that collects nonquantitative data such as how doctors “feel” about treating people of different ethnic backgrounds; a quantitative study might compare clinical outcomes in different ethnic groups.
What Did the Researchers Do and Find?
The researchers enrolled 106 doctors, nurses, and other health-related professionals from different health-service settings in the Midlands, an ethnically diverse region of the UK. They organized 18 focus groups in which the health professionals described their experiences of caring for people from ethnic minority backgrounds. The participants were encouraged to recall actual cases and to identify what they saw as problems and strengths in their interactions with these patients. The researchers found that the health professionals wrestled with many challenges when providing health care for patients from diverse ethnic backgrounds. These challenges included problems with language and with general communication (for example, deciding when it was acceptable to touch a patient to show empathy). Health professionals also worried they did not know enough about cultural differences. As a result, they said they often felt uncertain of their ability to avoid causing affront or appearing racist. This uncertainty, the researchers report, disempowered the health professionals, sometimes making them hesitate or fail to do what was best for their patient.
What Do These Findings Mean?
These findings reveal that health professionals often experience considerable uncertainty when caring for ethnically diverse patients, even after training in cultural competency. They also show that this uncertainty can lead to hesitancy and inertia, which might contribute to ethnic health care inequalities. Because the study participants were probably already interested in ethnic diversity and health care, interviews with other health professionals (and investigations of patient experiences) are needed to confirm these findings. Nevertheless, the researchers suggest several interventions that might reduce health care inequalities caused by ethnic diversity. For example, health professionals should be encouraged to recognize their uncertainty and should have access to more information and training about ethnic differences. In addition, there should be a shift in emphasis away from relying on knowledge-based cultural information towards taking an “ethnographic” approach. In other words, health professionals should be helped to feel able to ask their patients about what matters most to them as individuals about their illness and treatment.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040323.
Information on cultural competence and health care is available from the US National Center for Cultural Competence (in English and Spanish) and DiversityRx
PROCEED (Professionals Responding to Cancer in Ethnic Diversity) is a multimedia training tool for educators within the health and allied professions developed from the results of this study; a press release on PROCEED is available from the University of Nottingham
Transcultural Health Care Practice: An educational resource for nurses and health care practitioners is available on the web site of the UK Royal College of Nursing
doi:10.1371/journal.pmed.0040323
PMCID: PMC2071935  PMID: 18001148
23.  Evidence of Local Persistence of Human Anthrax in the Country of Georgia Associated with Environmental and Anthropogenic Factors 
Background
Anthrax is a soil-borne disease caused by the bacterium Bacillus anthracis and is considered a neglected zoonosis. In the country of Georgia, recent reports have indicated an increase in the incidence of human anthrax. Identifying sub-national areas of increased risk may help direct appropriate public health control measures. The purpose of this study was to evaluate the spatial distribution of human anthrax and identify environmental/anthropogenic factors associated with persistent clusters.
Methods/Findings
A database of human cutaneous anthrax in Georgia during the period 2000–2009 was constructed using a geographic information system (GIS) with case data recorded to the community location. The spatial scan statistic was used to identify persistence of human cutaneous anthrax. Risk factors related to clusters of persistence were modeled using a multivariate logistic regression. Areas of persistence were identified in the southeastern part of the country. Results indicated that the persistence of human cutaneous anthrax showed a strong positive association with soil pH and urban areas.
Conclusions/Significance
Anthrax represents a persistent threat to public and veterinary health in Georgia. The findings here showed that the local level heterogeneity in the persistence of human cutaneous anthrax necessitates directed interventions to mitigate the disease. High risk areas identified in this study can be targeted for public health control measures such as farmer education and livestock vaccination campaigns.
Author Summary
Anthrax is a zoonotic bacterial disease that occurs nearly worldwide. Despite a large number of countries reporting endemic anthrax, persistence of the disease appears to be associated with specific ecological factors related to soil composition and climatic conditions. Human cases are most often associated with handling infected livestock or contaminated meat and most cases are in cutaneous form (skin infections). Following the collapse of the Soviet Union, the country of Georgia has undergone major restructuring in land management and livestock handling and anthrax remains a serious public health risk. Few studies have evaluated the local spatial patterns of human anthrax. Here we identify areas on the landscape where human cutaneous anthrax persisted over the last decade. Persistence was found to be associated with both anthropogenic and environmental factors including soil pH and livestock density. These findings aid in the establishment of spatial baseline estimates of the disease and allow public health officials to adopt targeted anthrax control strategies, such as livestock vaccination campaigns and farmer education.
doi:10.1371/journal.pntd.0002388
PMCID: PMC3764226  PMID: 24040426
24.  Comparison of response rates and cost-effectiveness for a community-based survey: postal, internet and telephone modes with generic or personalised recruitment approaches 
Background
Epidemiological research often requires collection of data from a representative sample of the community or recruitment of specific groups through broad community approaches. The population coverage of traditional survey methods such as mail-outs to residential addresses, and telephone contact via public directories or random-digit-dialing is declining and survey response rates are falling. There is a need to explore new sampling frames and consider multiple response modes including those offered by changes in telecommunications and internet technology.
Methods
We evaluated response rates and cost-effectiveness for three modes of survey administration (postal invitation/postal survey, postal invitation/internet survey and postal invitation/telephone survey) and two styles of contact approach (personalised and generic) in a community survey of greywater use. Potential respondents were contacted only once, with no follow up of non-responders.
Results
The telephone survey produced the highest adjusted response rate (30.2%), followed by the personalised postal survey (10.5%), generic postal survey (7.5%) and then the internet survey (4.7% for the personalised approach and 2.2% for the generic approach). There were some differences in household characteristics and greywater use rates between respondents to different survey modes, and between respondents to personalised and generic approaches. These may be attributable to the differing levels of motivations needed for a response, and varying levels of interest in the survey topic among greywater users and non-users. The generic postal survey had the lowest costs per valid survey received (Australian $22.93), followed by the personalised postal survey ($24.75).
Conclusions
Our findings suggest that postal surveys currently remain the most economic option for population-based studies, with similar costs for personalised and generic approaches. Internet surveys may be effective for specialised groups where email lists are available for initial contact, but barriers other than household internet access still exist for community-based surveys. Given the increasing recruitment challenges facing community-based studies, there is an imperative to gather contemporary comparative data on different survey modes and recruitment approaches in order to determine their strengths, limitations and costs. Researchers also need to document and report on the potential biases in the target and respondent populations and how this may affect the data collected.
doi:10.1186/1471-2288-12-132
PMCID: PMC3502082  PMID: 22938205
Survey methods; Postal survey; Telephone survey; Internet survey; Cost-effectiveness
25.  Overcoming language barriers in community-based research with refugee and migrant populations: options for using bilingual workers 
Background
Although the challenges of working with culturally and linguistically diverse groups can lead to the exclusion of some communities from research studies, cost effective strategies to encourage access and promote cross-cultural linkages between researchers and ethnic minority participants are essential to ensure their views are heard and their health needs identified. Using bilingual research assistants is one means to achieve this. In a study exploring alcohol and other drug service use by migrant women in Western Australia, bilingual workers were used to assist with participant recruitment and administration of a survey to 268 women who spoke more than 40 different languages.
Discussion
Professional interpreters, bilingual students, bilingual overseas-trained health professionals and community sector bilingual workers were used throughout the research project. For the initial qualitative phase, professional interpreters were used to conduct interviews and focus group sessions, however scheduling conflicts, inflexibility, their inability to help with recruitment and the expense prompted exploration of alternative options for interview interpreting in the quantitative component of the study. Bilingual mature-age students on work placement and overseas-trained health professionals provided good entry into their different community networks and successfully recruited and interviewed participants, often in languages with limited interpreter access. Although both groups required training and supervision, overseas-trained health professionals often had existing research skills, as well as understanding of key issues such as confidentiality and referral processes. Strategies to minimise social desirability bias and the need to set boundaries were discussed during regular debriefing sessions. Having a number of workers recruiting participants also helped minimise the potential for selection bias. The practical and educational experience gained by the bilingual workers was regarded as capacity building and a potentially valuable community resource for future health research projects.
Summary
The use of bilingual workers was key to the feasibility and success of the project. The most successful outcomes occurred with students and overseas-trained health professionals who had good community networks for recruitment and the required linguistic skills. By describing the advantages and disadvantages encountered when working with bilingual workers, we offer practical insights to assist other researchers working with linguistically diverse groups.
doi:10.1186/1472-698X-14-11
PMCID: PMC4016643  PMID: 24725431
Bilingual workers; Cross cultural research; Migrants; Refugees; Communication; Interpreting

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