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1.  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
2.  Anthrax Outbreaks in Bangladesh, 2009–2010 
During August 2009–October 2010, a multidisciplinary team investigated 14 outbreaks of animal and human anthrax in Bangladesh to identify the etiology, pathway of transmission, and social, behavioral, and cultural factors that led to these outbreaks. The team identified 140 animal cases of anthrax and 273 human cases of cutaneous anthrax. Ninety one percent of persons in whom cutaneous anthrax developed had history of butchering sick animals, handling raw meat, contact with animal skin, or were present at slaughtering sites. Each year, Bacillus anthracis of identical genotypes were isolated from animal and human cases. Inadequate livestock vaccination coverage, lack of awareness of the risk of anthrax transmission from animal to humans, social norms and poverty contributed to these outbreaks. Addressing these challenges and adopting a joint animal and human health approach could contribute to detecting and preventing such outbreaks in the future.
doi:10.4269/ajtmh.2012.11-0234
PMCID: PMC3403762  PMID: 22492157
3.  Molecular Characterization and Drug Resistance Patterns of Strains of Mycobacterium tuberculosis Isolated from Patients in an AIDS Counseling Center in Port-au-Prince, Haiti: a 1-Year Study 
Journal of Clinical Microbiology  2003;41(2):694-702.
Tuberculosis (TB) is one of the most common opportunistic diseases that appear among human immunodeficiency virus (HIV)-positive patients in Haiti. In this context the probable emergence of multidrug-resistant (MDR) strains of Mycobacterium tuberculosis is of great epidemiological concern. However, as routine culture of M. tuberculosis and drug susceptibility testing are not performed in Haiti, it has not been possible so far to evaluate the rate of drug resistance among M. tuberculosis isolates from circulating TB cases. This report describes the first study on the molecular typing and drug resistance of M. tuberculosis isolates from patients with culture-positive pulmonary tuberculosis monitored at the GHESKIO Centers in Haiti during the year 2000. Clinical, epidemiological, and drug susceptibility testing results were available for 157 patients with confirmed cases of TB, with a total of 8.9% of patients harboring MDR M. tuberculosis. A significant association between the occurrence of resistance and previous TB treatment was observed (P < 0.001), suggesting that a previous history of TB treatment was a risk factor associated with MDR TB in Haiti. The DNAs of individual isolates from 106 samples were available and were typed by spoligotyping and determination of the variable number of tandem DNA repeats. Both typing methods provided interpretable results for 96 isolates, and the clusters observed were further confirmed by ligation-mediated PCR to define potential cases of active transmission. Thirty-three (34%) of the isolates were found to be grouped into 11 clusters with two or more identical patterns. However, an assessment of risk factors (sex, HIV positivity, previous treatment, drug resistance) showed that none was significantly associated with the active transmission of TB. These observations suggest that acquired MDR TB is prevalent in Haiti and may be associated with compliance issues during TB treatment since prior TB therapy is the strongest risk factor associated with MDR TB. Prevention of TB transmission in Haiti should target active case investigation, routine detection of drug resistance, and adequate treatment of patients. The use of directly observed short-course therapy should be enforced throughout the country; and relapses, reactivations, or newly acquired infections should be discriminated by genotyping methods.
doi:10.1128/JCM.41.2.694-702.2003
PMCID: PMC149692  PMID: 12574269
4.  Anthrax Lethal Factor as an Immune Target in Humans and Transgenic Mice and the Impact of HLA Polymorphism on CD4+ T Cell Immunity 
PLoS Pathogens  2014;10(5):e1004085.
Bacillus anthracis produces a binary toxin composed of protective antigen (PA) and one of two subunits, lethal factor (LF) or edema factor (EF). Most studies have concentrated on induction of toxin-specific antibodies as the correlate of protective immunity, in contrast to which understanding of cellular immunity to these toxins and its impact on infection is limited. We characterized CD4+ T cell immunity to LF in a panel of humanized HLA-DR and DQ transgenic mice and in naturally exposed patients. As the variation in antigen presentation governed by HLA polymorphism has a major impact on protective immunity to specific epitopes, we examined relative binding affinities of LF peptides to purified HLA class II molecules, identifying those regions likely to be of broad applicability to human immune studies through their ability to bind multiple alleles. Transgenics differing only in their expression of human HLA class II alleles showed a marked hierarchy of immunity to LF. Immunogenicity in HLA transgenics was primarily restricted to epitopes from domains II and IV of LF and promiscuous, dominant epitopes, common to all HLA types, were identified in domain II. The relevance of this model was further demonstrated by the fact that a number of the immunodominant epitopes identified in mice were recognized by T cells from humans previously infected with cutaneous anthrax and from vaccinated individuals. The ability of the identified epitopes to confer protective immunity was demonstrated by lethal anthrax challenge of HLA transgenic mice immunized with a peptide subunit vaccine comprising the immunodominant epitopes that we identified.
Author Summary
Anthrax is of concern with respect to human exposure in endemic regions, concerns about bioterrorism and the considerable global burden of livestock infections. The immunology of this disease remains poorly understood. Vaccination has been based on B. anthracis filtrates or attenuated spore-based vaccines, with more recent trials of next-generation recombinant vaccines. Approaches generally require extensive vaccination regimens and there have been concerns about immunogenicity and adverse reactions. An ongoing need remains for rationally designed, effective and safe anthrax vaccines. The importance of T cell stimulating vaccines is inceasingly recognized. An essential step is an understanding of immunodominant epitopes and their relevance across the diverse HLA immune response genes of human populations. We characterized CD4 T cell immunity to anthrax Lethal Factor (LF), using HLA transgenic mice, as well as testing candidate peptide epitopes for binding to a wide range of HLA alleles. We identified anthrax epitopes, noteworthy in that they elicit exceptionally strong immunity with promiscuous binding across multiple HLA alleles and isotypes. T cell responses in humans exposed to LF through either natural anthrax infection or vaccination were also examined. Epitopes identified as candidates were used to protect HLA transgenic mice from anthrax challenge.
doi:10.1371/journal.ppat.1004085
PMCID: PMC4006929  PMID: 24788397
5.  Strategies to Prevent Cholera Introduction during International Personnel Deployments: A Computational Modeling Analysis Based on the 2010 Haiti Outbreak 
PLoS Medicine  2016;13(1):e1001947.
Background
Introduction of Vibrio cholerae to Haiti during the deployment of United Nations (UN) peacekeepers in 2010 resulted in one of the largest cholera epidemics of the modern era. Following the outbreak, a UN-commissioned independent panel recommended three pre-deployment intervention strategies to minimize the risk of cholera introduction in future peacekeeping operations: screening for V. cholerae carriage, administering prophylactic antimicrobial chemotherapies, or immunizing with oral cholera vaccines. However, uncertainty regarding the effectiveness of these approaches has forestalled their implementation by the UN. We assessed how the interventions would have impacted the likelihood of the Haiti cholera epidemic.
Methods and Findings
We developed a stochastic model for cholera importation and transmission, fitted to reported cases during the first weeks of the 2010 outbreak in Haiti. Using this model, we estimated that diagnostic screening reduces the probability of cases occurring by 82% (95% credible interval: 75%, 85%); however, false-positive test outcomes may hamper this approach. Antimicrobial chemoprophylaxis at time of departure and oral cholera vaccination reduce the probability of cases by 50% (41%, 57%) and by up to 61% (58%, 63%), respectively. Chemoprophylaxis beginning 1 wk before departure confers a 91% (78%, 96%) reduction independently, and up to a 98% reduction (94%, 99%) if coupled with vaccination. These results are not sensitive to assumptions about the background cholera incidence rate in the endemic troop-sending country. Further research is needed to (1) validate the sensitivity and specificity of rapid test approaches for detecting asymptomatic carriage, (2) compare prophylactic efficacy across antimicrobial regimens, and (3) quantify the impact of oral cholera vaccine on transmission from asymptomatic carriers.
Conclusions
Screening, chemoprophylaxis, and vaccination are all effective strategies to prevent cholera introduction during large-scale personnel deployments such as that precipitating the 2010 Haiti outbreak. Antimicrobial chemoprophylaxis was estimated to provide the greatest protection at the lowest cost among the approaches recently evaluated by the UN.
A cholera outbreak modeling study reveals that chemprophylaxis treatment for deployed peacekeepers in Haiti would have reduced the risk of disease introduction by 90%.
Editors' Summary
Background
Cholera—a bacterial gut infection caused by Vibrio cholerae—is a global killer. Epidemics (outbreaks) of cholera in countries across Africa, Asia, and South and Central America where cholera is endemic (always present) affect 1–4 million people and kill up to 142,000 people every year. People get cholera by eating food or drinking water contaminated with feces from an infected person, so cholera epidemics occur in places with poor sanitation such as refugee camps and in regions where an earthquake or another natural disaster has disrupted water and sanitation systems. Most people who become infected with V. cholerae have no or mild symptoms, but these asymptomatically infected individuals can shed bacteria in their feces for up to 2 wk. Other infected people develop severe diarrhea, producing profuse watery feces. The standard treatment for cholera is replacement of fluids and salts lost through diarrhea with oral rehydration fluid or, in the worst cases, by fluid replacement directly into a vein. If left untreated, patients with severe cholera can die from dehydration within hours of developing symptoms.
Why Was This Study Done?
In 2010, a large cholera epidemic affected Haiti, which had been free of cholera for more than a century. This epidemic, which has resulted in nearly 9,000 deaths to date, was probably caused by contamination of water by infected sewage from the MINUSTAH (Mission des Nations Unies pour la stabilisation en Haïti) base, a UN peacekeeping mission established in Haiti in 2004. In January 2010, a massive earthquake hit Haiti, and in October that year, 454 troops from Nepal (a cholera-endemic country) were deployed to a MINUSTAH base in central Haiti as part of an ongoing peacekeeping operation to maintain political stability. Following the Haiti cholera outbreak, a panel of experts recommended that peacekeeping troops coming from countries where cholera is endemic should be screened for V. cholerae carriage, treated prophylactically with antimicrobial drugs (prophylactic treatments prevent a disease occurring), and/or immunized with oral cholera vaccines before deployment. However, because of uncertainty about the effectiveness of these pre-deployment intervention strategies, the UN has not implemented any of them. Here, the researchers use computational modeling to investigate whether these interventions would have prevented the Haiti cholera outbreak.
What Did the Researchers Do and Find?
The researchers developed a mathematical model to simulate the arrival of asymptomatically infected peacekeepers (or those with mild illness that would not have prevented their deployment) and the dynamics of cholera transmission from the MINUSTAH base to the community. They used this model to investigate the effect of the three proposed pre-deployment intervention strategies on (1) the probability of undetected importation of V. cholerae from an endemic source country by an asymptomatically infected peacekeeper, and (2) the subsequent probability of transmission of V. cholerae from peacekeepers to the general public, two events needed to establish an epidemic. According to the model, diagnostic screening reduced the probability of cases occurring by 82%, whereas antimicrobial chemoprophylaxis at the time of departure and oral cholera vaccination reduced the probability of cases by 50% and 61%, respectively. Chemoprophylaxis beginning a week before deployment reduced the probability of cases by 91% when used alone and by 98% when coupled with vaccination. Finally, the researchers estimated that antimicrobial chemoprophylaxis with conventional therapies would cost under US$1 per peacekeeper, whereas the other two pre-deployment intervention strategies would be considerably more expensive.
What Do These Findings Mean?
The accuracy of these findings is likely to be affected by the many assumptions made by the researchers in constructing their mathematical model. In addition, further research is needed to validate the use of rapid tests for detecting asymptomatic V. cholerae carriage, to compare the prophylactic efficacy of different antimicrobial regimens, and to quantify the impact of oral cholera vaccination on disease transmission from asymptomatic carriers. Nevertheless, these findings, which are likely to be generalizable to other settings, suggest that screening, chemoprophylaxis, and vaccination would all effectively prevent cholera introduction during large-scale personnel deployments like the one that precipitated the cholera outbreak in Haiti. However, although antimicrobial chemoprophylaxis is likely to provide the greatest protection at the lowest cost, this strategy is controversial because of increasing levels of drug resistance. Moreover, the researchers stress that proper sewage disposal must be implemented in tandem with any biomedical intervention designed to limit the risk of cholera introduction into disease-free areas by peacekeepers or other troops.
Additional Information
This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001947.
The World Health Organization provides information about cholera in several languages
The US Centers for Disease Control and Prevention also provides information about cholera for the public, medical professionals and travelers, specific information about the cholera epidemic in Haiti published a year into the outbreak, and CDC videos about defeating cholera and managing dehydration (in English, French and Spanish) are available
The UK National Health Service (NHS) Choices website provides information about cholera
Information about the UN in Haiti is available, including information on fighting cholera in the country, a recent fact sheet about the ongoing cholera epidemic, and a warning that cholera eradication in Haiti will take many years
The United Nations has published the report of the Independent Panel of Experts on the Cholera Outbreak in Haiti and its own follow-up to the panel’s policy recommendations
The not-for-profit organization Médecins Sans Frontières (MSF) is tackling several cholera outbreaks around the world; its website includes a 2014 report about the cholera epidemic in Haiti
MedlinePlus provides links to further resources about cholera
doi:10.1371/journal.pmed.1001947
PMCID: PMC4727895  PMID: 26812236
6.  Changing Patterns of Human Anthrax in Azerbaijan during the Post-Soviet and Preemptive Livestock Vaccination Eras 
We assessed spatial and temporal changes in the occurrence of human anthrax in Azerbaijan during 1984 through 2010. Data on livestock outbreaks, vaccination efforts, and human anthrax incidence during Soviet governance, post-Soviet governance, preemptive livestock vaccination were analyzed. To evaluate changes in the spatio-temporal distribution of anthrax, we used a combination of spatial analysis, cluster detection, and weighted least squares segmented regression. Results indicated an annual percent change in incidence of +11.95% from 1984 to 1995 followed by declining rate of −35.24% after the initiation of livestock vaccination in 1996. Our findings also revealed geographic variation in the spatial distribution of reporting; cases were primarily concentrated in the west early in the study period and shifted eastward as time progressed. Over twenty years after the dissolution of the Soviet Union, the distribution of human anthrax in Azerbaijan has undergone marked changes. Despite decreases in the incidence of human anthrax, continued control measures in livestock are needed to mitigate its occurrence. The shifting patterns of human anthrax highlight the need for an integrated “One Health” approach that takes into account the changing geographic distribution of the disease.
Author Summary
Zoonotic diseases, such as anthrax, represent a threat to public and veterinary health in many developing parts of the world. Control of anthrax is dependent upon several factors, including proper management of outbreaks and livestock vaccination. Following the dissolution of the Soviet Union, resources for disease management in Azerbaijan were dramatically diminished leading to increases in zoonotic diseases. In this study, our objective was to analyze human anthrax incidence during Soviet governance, post-Soviet governance, and after the implementation of a preemptive livestock vaccination campaign to identify potential changes in the occurrence of the disease. We applied spatial and temporal statistical approaches in a geographic information system to describe changes. Our findings provide evidence of a changing incidence and a shift in the geographic patterns of human anthrax. These findings highlight the importance of proper livestock disease management to mitigate human disease and the need for dynamic surveillance that takes into account changes in the distribution of disease.
doi:10.1371/journal.pntd.0002985
PMCID: PMC4102439  PMID: 25032701
7.  Improved Response to Disasters and Outbreaks by Tracking Population Movements with Mobile Phone Network Data: A Post-Earthquake Geospatial Study in Haiti 
PLoS Medicine  2011;8(8):e1001083.
Linus Bengtsson and colleagues examine the use of mobile phone positioning data to monitor population movements during disasters and outbreaks, finding that reports on population movements can be generated within twelve hours of receiving data.
Background
Population movements following disasters can cause important increases in morbidity and mortality. Without knowledge of the locations of affected people, relief assistance is compromised. No rapid and accurate method exists to track population movements after disasters. We used position data of subscriber identity module (SIM) cards from the largest mobile phone company in Haiti (Digicel) to estimate the magnitude and trends of population movements following the Haiti 2010 earthquake and cholera outbreak.
Methods and Findings
Geographic positions of SIM cards were determined by the location of the mobile phone tower through which each SIM card connects when calling. We followed daily positions of SIM cards 42 days before the earthquake and 158 days after. To exclude inactivated SIM cards, we included only the 1.9 million SIM cards that made at least one call both pre-earthquake and during the last month of study. In Port-au-Prince there were 3.2 persons per included SIM card. We used this ratio to extrapolate from the number of moving SIM cards to the number of moving persons. Cholera outbreak analyses covered 8 days and tracked 138,560 SIM cards.
An estimated 630,000 persons (197,484 Digicel SIM cards), present in Port-au-Prince on the day of the earthquake, had left 19 days post-earthquake. Estimated net outflow of people (outflow minus inflow) corresponded to 20% of the Port-au-Prince pre-earthquake population. Geographic distribution of population movements from Port-au-Prince corresponded well with results from a large retrospective, population-based UN survey. To demonstrate feasibility of rapid estimates and to identify areas at potentially increased risk of outbreaks, we produced reports on SIM card movements from a cholera outbreak area at its immediate onset and within 12 hours of receiving data.
Conclusions
Results suggest that estimates of population movements during disasters and outbreaks can be delivered rapidly and with potentially high validity in areas with high mobile phone use.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, millions of people are affected by disasters—sudden calamitous events that disrupt communities and cause major human, material, economic, and environmental losses. Disasters can be natural (for example, earthquakes and infectious disease outbreaks) or man-made (for example, terrorist attacks and industrial accidents). Whenever a disaster strikes, governments, international bodies, and humanitarian agencies swing into action to help the affected population by providing food, water, shelter, and medical assistance. Within days of the earthquake that struck Haiti on January 12, 2010, for instance, many governments pledged large sums of money to help the Haitians, and humanitarian agencies such as Oxfam and the International Federation of Red Cross and Red Crescent Societies sent tons of food and hundreds of personnel into the country. And when a cholera outbreak began in Haiti in October 2010, the world responded by sending further assistance.
Why Was This Study Done?
An instinctive response to any disaster is to flee the affected area, but such population movements after a disaster can increase the loss of human life by complicating the provision of relief assistance, the assessment of needs, and infectious disease surveillance. Unfortunately, there are no rapid or accurate methods available to track population movements after disasters. Relief coordinators currently rely on slow, potentially biased methods such as eye witness accounts and aerial images of shelters to track population movements. In this geospatial analysis, the researchers investigate whether position data from mobile phone SIMs (subscriber identity modules) can be used to estimate the magnitude and trends of population movements by retrospectively following the positions of SIMs in Haiti before and after the earthquake and tracking SIMs during the first few days of the cholera outbreak. Every time a SIM makes a call, the mobile phone network database records which mobile phone tower connected the call. Thus, the database can provide a geographic position for each mobile phone caller.
What Did the Researchers Do and Find?
The researchers obtained anonymized data on the position of 1.9 million SIMs in Haiti from 42 days before the earthquake to 158 days afterwards. Nearly 200,000 SIMs that were present in Haiti's capital Port-au-Prince when the earthquake struck had left 19 days post-earthquake. Just under a third of Port-au-Prince's inhabitants were mobile phone subscribers at the time of the earthquake, so this movement of SIMs equates to the movement of about 630,000 people. Notably, although the SIM-based estimates of numbers leaving Port-au-Prince matched the estimates reported by the Haitian National Civil Protection Agency (NPCA), which were largely based on counting ship and bus movements and which were used during the relief operation, the estimated geographical distribution of displaced people reported by the NPCA was very different to that obtained by analyzing SIM movements. By contrast, the geographical distribution of the population obtained from SIM movements closely matched that reported by a retrospective United Nations Population Fund household survey. Finally, to demonstrate the feasibility of producing rapid estimates of population movements during disasters, the researchers tracked nearly 140,000 SIMs during the first 8 days of the Haitian cholera outbreak and showed that they could distribute analyses of SIM movements within 12 hours of receiving data from the mobile phone company.
What Do These Findings Mean?
These findings suggest that estimates of population movements during disasters and infectious disease outbreaks can be delivered rapidly and accurately in areas of high mobile use by analyzing mobile phone data. 86% of the world's population now has mobile phone network coverage and, in 2009, there were already 3.2 billion mobile phone subscriptions in the developing world, which has a population of 5.5 billion people. Thus, this tracking method could be useful in many parts of the world, including those particularly vulnerable to disasters. However, because mobile phone use varies between sections of society, because some areas have a low density of mobile phone towers, and because disasters can destroy these towers, this approach may not be effective in all disasters. The researchers recommend, therefore, that the use of mobile phone data for tracking population movements is evaluated further and that relationships are built up with mobile phone companies to ensure rapid implementation of the approach after future disasters.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001083.
Internal Displacement Monitoring Centre provides information on population displacement during natural disasters
The International Federation of Red Cross and Red Crescent Societies provides information in several languages about disaster management and about the 2010 earthquake in Haiti
Oxfam also has information on conflicts and natural disasters and the Haiti earthquake and cholera outbreak (in several languages)
EM-DAT, the International Disaster Database contains essential core information on 18,000 mass disasters in the world from 1990 until the present
doi:10.1371/journal.pmed.1001083
PMCID: PMC3168873  PMID: 21918643
8.  Serodiagnosis of Human Cutaneous Anthrax in India Using an Indirect Anti-Lethal Factor IgG Enzyme-Linked Immunosorbent Assay 
Anthrax, caused by Bacillus anthracis, is primarily a zoonotic disease. Being a public health problem also in several developing countries, its early diagnosis is very important in human cases. In this study, we describe the use of an indirect enzyme-linked immunosorbent assay (ELISA) for detection of anti-lethal factor (anti-LF) IgG in human serum samples. A panel of 203 human serum samples consisting of 50 samples from patients with confirmed cutaneous anthrax, 93 samples from healthy controls from areas of India where anthrax is nonendemic, 44 samples from controls from an area of India where anthrax is endemic, and 16 patients with a disease confirmed not to be anthrax were evaluated with an anti-LF ELISA. The combined mean anti-LF ELISA titer for the three control groups was 0.136 ELISA unit (EU), with a 95% confidence interval (CI) of 0.120 to 0.151 EU. The observed sensitivity and specificity of the ELISA were 100% (95% CI, 92.89 to 100%) and 97.39% (95% CI, 93.44 to 99.28%), respectively, at a cutoff value of 0.375 EU, as decided by receiver operating characteristic (ROC) curve analysis. The likelihood ratio was found to be 49.98. The positive predictive value (PPV), negative predictive value (NPV), efficiency, and Youden's index (J) for reliability of the assay were 92.5%, 100%, 98.02%, and 0.97, respectively. The false-positive predictive rate and false-negative predictive rate of the assay were 2.61% and 0%. The assay could be a very useful tool for early diagnosis of cutaneous anthrax cases, as antibodies against LF appear much earlier than those against other anthrax toxins in human serum samples.
doi:10.1128/CVI.00598-12
PMCID: PMC3571271  PMID: 23269414
9.  A Community-Based Study of Factors Associated with Continuing Transmission of Lymphatic Filariasis in Leogane, Haiti 
Seven rounds of mass drug administration (MDA) have been administered in Leogane, Haiti, an area hyperendemic for lymphatic filariasis (LF). Sentinel site surveys showed that the prevalence of microfilaremia was reduced to <1% from levels as high as 15.5%, suggesting that transmission had been reduced. A separate 30-cluster survey of 2- to 4-year-old children was conducted to determine if MDA interrupted transmission. Antigen and antifilarial antibody prevalence were 14.3% and 19.7%, respectively. Follow-up surveys were done in 6 villages, including those selected for the cluster survey, to assess risk factors related to continued LF transmission and to pinpoint hotspots of transmission. One hundred houses were mapped in each village using GPS-enabled PDAs, and then 30 houses and 10 alternates were chosen for testing. All individuals in selected houses were asked to participate in a short survey about participation in MDA, history of residence in Leogane and general knowledge of LF. Survey teams returned to the houses at night to collect blood for antigen testing, microfilaremia and Bm14 antibody testing and collected mosquitoes from these communities in parallel. Antigen prevalence was highly variable among the 6 villages, with the highest being 38.2% (Dampus) and the lowest being 2.9% (Corail Lemaire); overall antigen prevalence was 18.5%. Initial cluster surveys of 2- to 4-year-old children were not related to community antigen prevalence. Nearest neighbor analysis found evidence of clustering of infection suggesting that LF infection was focal in distribution. Antigen prevalence among individuals who were systematically noncompliant with the MDAs, i.e. they had never participated, was significantly higher than among compliant individuals (p<0.05). A logistic regression model found that of the factors examined for association with infection, only noncompliance was significantly associated with infection. Thus, continuing transmission of LF seems to be linked to rates of systematic noncompliance.
Author Summary
Lymphatic filariasis (LF) is a mosquito-borne parasitic disease that affects an estimated 120 million people worldwide with over 1 billion at risk for infection. LF is considered to be a leading cause of permanent disability worldwide due to the clinical manifestations of the disease. A global effort was established to eliminate LF by 2020 through interruption of transmission by annual mass administrations of anti-parasitic drugs. In Leogane, Haiti, seven rounds of drug administration have been administered and, though infection levels have dropped, transmission has not been interrupted. In this study the authors examined factors that could contribute to continuing transmission of LF in Haiti. Ongoing transmission was confirmed by high infection rates among young children. Infection was found to cluster at the household level within communities. The factor most associated with this transmission was systematic noncompliance with drug administration (i.e. never taking the medication). While increased health education and awareness campaigns may improve noncompliance, new tools and approaches may be needed to stop transmission of LF in Haiti. Understanding obstacles and solutions from the Haiti program could aid elimination programs in other countries.
doi:10.1371/journal.pntd.0000640
PMCID: PMC2843627  PMID: 20351776
10.  Human anti-anthrax protective antigen neutralizing monoclonal antibodies derived from donors vaccinated with anthrax vaccine adsorbed 
Background
Potent anthrax toxin neutralizing human monoclonal antibodies were generated from peripheral blood lymphocytes obtained from Anthrax Vaccine Adsorbed (AVA) immune donors. The anti-anthrax toxin human monoclonal antibodies were evaluated for neutralization of anthrax lethal toxin in vivo in the Fisher 344 rat bolus toxin challenge model.
Methods
Human peripheral blood lymphocytes from AVA immunized donors were engrafted into severe combined immunodeficient (SCID) mice. Vaccination with anthrax protective antigen and lethal factor produced a significant increase in antigen specific human IgG in the mouse serum. The antibody producing lymphocytes were immortalized by hybridoma formation. The genes encoding the protective antibodies were rescued and stable cell lines expressing full-length human immunoglobulin were established. The antibodies were characterized by; (1) surface plasmon resonance; (2) inhibition of toxin in an in vitro mouse macrophage cell line protection assay and (3) in vivo in a Fischer 344 bolus lethal toxin challenge model.
Results
The range of antibodies generated were diverse with evidence of extensive hyper mutation, and all were of very high affinity for PA83~1 × 10-10-11M. Moreover all the antibodies were potent inhibitors of anthrax lethal toxin in vitro. A single IV dose of AVP-21D9 or AVP-22G12 was found to confer full protection with as little as 0.5× (AVP-21D9) and 1× (AVP-22G12) molar equivalence relative to the anthrax toxin in the rat challenge prophylaxis model.
Conclusion
Here we describe a powerful technology to capture the recall antibody response to AVA vaccination and provide detailed molecular characterization of the protective human monoclonal antibodies. AVP-21D9, AVP-22G12 and AVP-1C6 protect rats from anthrax lethal toxin at low dose. Aglycosylated versions of the most potent antibodies are also protective in vivo, suggesting that lethal toxin neutralization is not Fc effector mediated. The protective effect of AVP-21D9 persists for at least one week in rats. These potent fully human anti-PA toxin-neutralizing antibodies are attractive candidates for prophylaxis and/or treatment against Anthrax Class A bioterrorism toxins.
doi:10.1186/1476-8518-2-5
PMCID: PMC420254  PMID: 15140257
11.  Dengue Virus Infections among Haitian and Expatriate Non-governmental Organization Workers — Léogane and Port-au-Prince, Haiti, 2012 
In October 2012, the Haitian Ministry of Health and the US CDC were notified of 25 recent dengue cases, confirmed by rapid diagnostic tests (RDTs), among non-governmental organization (NGO) workers. We conducted a serosurvey among NGO workers in Léogane and Port-au-Prince to determine the extent of and risk factors for dengue virus infection. Of the total 776 staff from targeted NGOs in Léogane and Port-au-Prince, 173 (22%; 52 expatriates and 121 Haitians) participated. Anti-dengue virus (DENV) IgM antibody was detected in 8 (15%) expatriates and 9 (7%) Haitians, and DENV non-structural protein 1 in one expatriate. Anti-DENV IgG antibody was detected in 162 (94%) participants (79% of expatriates; 100% of Haitians), and confirmed by microneutralization testing as DENV-specific in 17/34 (50%) expatriates and 42/42 (100%) Haitians. Of 254 pupae collected from 68 containers, 65% were Aedes aegypti; 27% were Ae. albopictus. Few NGO workers reported undertaking mosquito-avoidance action. Our findings underscore the risk of dengue in expatriate workers in Haiti and Haitians themselves.
Author Summary
Dengue is the most common mosquito-borne viral disease in the world, and caused an estimated 390 million infections and 96 million cases in the tropics and subtropics in 2010. Over the last decade, the number of cases of dengue and the severity of dengue virus infections have increased in the Americas, including the Caribbean, yet little is still known about dengue in Haiti. Following an outbreak of dengue in mostly expatriate NGO workers, the investigators of this study took blood samples from expatriate and Haitian NGO workers living in two cities in Haiti and tested them for evidence of current, recent, and past dengue virus infection. They also investigated the amount and kinds of mosquitoes at homes and work sites. The study found recent infections among some Haitians and expatriates and widespread past infections among all Haitians and most expatriates. It also found that many people were not doing basic things to avoid mosquito bites, like applying mosquito repellent multiple times a day and wearing long sleeves or pants. These findings highlight the likely endemicity of dengue virus in Haiti, and the need to improve knowledge and awareness of dengue prevention among expatriates visiting Haiti and local Haitians.
doi:10.1371/journal.pntd.0003269
PMCID: PMC4214624  PMID: 25356592
12.  Influence on clinical practice of routine intra-partum fetal monitoring. 
British Medical Journal  1975;3(5979):341-343.
An attempt has been made to monitor by continuous fetal heart rate according all women admitted in labour. Altogether 85% of the 1070 patients delivered at one hospital were monitored in 1973 and 92% in 1974. Perinatal mortality fell significantly from levels in preceding years to 15-8 and 11-7 per 1000 births, respectively, in 1973 and 1974. The fall was primarily due to the elimination of intra-partum stillbirths and a significant reduction in neonatal mortality. The incidence of caesarean sections also fell from 9-7% in 1973 to 5-8% in 1974. All patients should be monitored because it is impossible to predict reliably intra-partum fetal distress from maternal "high-risk" factors present before the onset of labour.
PMCID: PMC1673830  PMID: 239781
13.  Genetic Diversity of Plasmodium falciparum in Haiti: Insights from Microsatellite Markers 
PLoS ONE  2015;10(10):e0140416.
Hispaniola, comprising Haiti and the Dominican Republic, has been identified as a candidate for malaria elimination. However, incomplete surveillance data in Haiti hamper efforts to assess the impact of ongoing malaria control interventions. Characteristics of the genetic diversity of Plasmodium falciparum populations can be used to assess parasite transmission, which is information vital to evaluating malaria elimination efforts. Here we characterize the genetic diversity of P. falciparum samples collected from patients at seven sites in Haiti using 12 microsatellite markers previously employed in population genetic analyses of global P. falciparum populations. We measured multiplicity of infections, level of genetic diversity, degree of population geographic substructure, and linkage disequilibrium (defined as non-random association of alleles from different loci). For low transmission populations like Haiti, we expect to see few multiple infections, low levels of genetic diversity, high degree of population structure, and high linkage disequilibrium. In Haiti, we found low levels of multiple infections (12.9%), moderate to high levels of genetic diversity (mean number of alleles per locus = 4.9, heterozygosity = 0.61), low levels of population structure (highest pairwise Fst = 0.09 and no clustering in principal components analysis), and moderate linkage disequilibrium (ISA = 0.05, P<0.0001). In addition, population bottleneck analysis revealed no evidence for a reduction in the P. falciparum population size in Haiti. We conclude that the high level of genetic diversity and lack of evidence for a population bottleneck may suggest that Haiti’s P. falciparum population has been stable and discuss the implications of our results for understanding the impact of malaria control interventions. We also discuss the relevance of parasite population history and other host and vector factors when assessing transmission intensity from genetic diversity data.
doi:10.1371/journal.pone.0140416
PMCID: PMC4604141  PMID: 26462203
14.  Reliability and Validity of the Haitian Creole PHQ-9 
Journal of General Internal Medicine  2014;29(12):1679-1686.
ABSTRACT
BACKGROUND
There is limited information on depression in Haitians and this is partly attributable to the absence of culturally and linguistically adapted measures for depression.
OBJECTIVE
To perform a psychometric evaluation of the Haitian-Creole version of the PHQ-9 administered to men who have sex with men (MSM) in the Republic of Haiti.
DESIGN
This study uses a cross-sectional design and data are from the Integrated Behavioral and Biological HIV Survey (IBBS) for MSM in Haiti.
PARTICIPANTS
Inclusion criteria required that participants be male, ≥ 18 years, report sexual relations with a male partner in the last 12 months, and lived in Haiti during the past 3 months. Respondent Driven Sampling was used for participant recruitment.
MAIN MEASURES
A structured questionnaire was verbally administered in Haitian-Creole capturing information on sociodemographics, sexual behaviors, human immunodeficiency virus (HIV) status and depressive symptomatology using the PHQ-9. Psychometric analyses of the translated PHQ-9 assessed unidimensionality, factor structure, reliability, construct validity, and differential item functioning (DIF) across subgroups (age, educational level, sexual orientation and HIV status).
KEY RESULTS
In a study population of 1,028 MSM, the Haitian-Creole version of the PHQ-9 is unidimensional, has moderately high internal consistency reliability (α = 0.78), and shows evidence of construct validity where HIV-positive subjects have greater depression (p = 0.002). There is no evidence of DIF across age, education, sexual orientation or HIV status. HIV-positive MSM are twice as likely to screen positive for moderately severe and severe depressive symptoms compared to their HIV-negative counterparts.
CONCLUSIONS
There is strong evidence for the psychometric adequacy of the translated PHQ-9 screening tool as a measure of depression with MSM in Haiti. Future research is necessary to examine the predictive validity of depression for subsequent health behaviors or clinical outcomes among Haitian MSM.
doi:10.1007/s11606-014-2951-5
PMCID: PMC4242883  PMID: 25092004
Depression; Haiti; HIV/AIDS; International health; men who have sex with men
15.  Recent outbreak of cutaneous anthrax in Bangladesh: clinico-demographic profile and treatment outcome of cases attended at Rajshahi Medical College Hospital 
BMC Research Notes  2012;5:464.
Background
Human cutaneous anthrax results from skin exposure to B. anthracis, primarily due to occupational exposure. Bangladesh has experienced a number of outbreaks of cutaneous anthrax in recent years. The last episode occurred from April to August, 2011 and created mass havoc due to its dreadful clinical outcome and socio-cultural consequences. We report here the clinico-demographic profile and treatment outcome of 15 cutaneous anthrax cases attended at the Dermatology Outpatient Department of Rajshahi Medical College Hospital, Bangladesh between April and August, 2011 with an aim to create awareness for early case detection and management.
Findings
Anthrax was suspected primarily based on cutaneous manifestations of typical non-tender ulcer with black eschar, with or without oedema, and a history of butchering, or dressing/washing of cattle/goat or their meat. Diagnosis was established by demonstration of large gram-positive rods, typically resembling B. anthracis under light microscope where possible and also by ascertaining therapeutic success. The mean age of cases was 21.4 years (ranging from 3 to 46 years), 7 (46.7%) being males and 8 (53.3%) females. The majority of cases were from lower middle socioeconomic status. Types of exposures included butchering (20%), contact with raw meat (46.7%), and live animals (33.3%). Malignant pustule was present in upper extremity, both extremities, face, and trunk at frequencies of 11 (73.3%), 2 (13.3%), 1 (6.7%) and 1 (6.7%) respectively. Eight (53.3%) patients presented with fever, 7 (46.7%) had localized oedema and 5 (33.3%) had regional lymphadenopathy. Anthrax was confirmed in 13 (86.7%) cases by demonstration of gram-positive rods. All cases were cured with 2 months oral ciprofloxacin combined with flucoxacillin for 2 weeks.
Conclusions
We present the findings from this series of cases to reinforce the criteria for clinical diagnosis and to urge prompt therapeutic measures to treat cutaneous anthrax successfully to eliminate the unnecessary panic of anthrax.
doi:10.1186/1756-0500-5-464
PMCID: PMC3493280  PMID: 22929128
Cutaneous anthrax; Clinico-demographic profile; Therapeutic response; Bangladesh
16.  Predictability of anthrax infection in the Serengeti, Tanzania 
The Journal of applied ecology  2011;48(6):1333-1344.
Summary
Anthrax is endemic throughout Africa, causing considerable livestock and wildlife losses and severe, sometimes fatal, infection in humans. Predicting the risk of infection is therefore important for public health, wildlife conservation and livestock economies. However, because of the intermittent and variable nature of anthrax outbreaks, associated environmental and climatic conditions, and diversity of species affected, the ecology of this multihost pathogen is poorly understood.We explored records of anthrax from the Serengeti ecosystem in north-west Tanzania where the disease has been documented in humans, domestic animals and a range of wildlife. Using spatial and temporal case-detection and seroprevalence data from wild and domestic animals, we investigated spatial, environmental, climatic and species-specific associations in exposure and disease.Anthrax was detected annually in numerous species, but large outbreaks were spatially localized, mostly affecting a few focal herbivores.Soil alkalinity and cumulative weather extremes were identified as useful spatial and temporal predictors of exposure and infection risk, and for triggering the onset of large outbreaks.Interacting ecological and behavioural factors, specifically functional groups and spatiotemporal overlap, helped to explain the variable patterns of infection and exposure among species.Synthesis and applications. Our results shed light on ecological drivers of anthrax infection and suggest that soil alkalinity and prolonged droughts or rains are useful predictors of disease occurrence that could guide risk-based surveillance. These insights should inform strategies for managing anthrax including prophylactic livestock vaccination, timing of public health warnings and antibiotic provision in high-risk areas. However, this research highlights the need for greater surveillance (environmental, serological and case-detection-orientated) to determine the mechanisms underlying anthrax dynamics.
doi:10.1111/j.1365-2664.2011.02030.x
PMCID: PMC3272456  PMID: 22318563
Bacillus anthracis; disease ecology; exposure; infectious disease; multihost; serology; surveillance; susceptibility; zoonosis
17.  Whole genome protein microarrays for serum profiling of immunodominant antigens of Bacillus anthracis 
A commercial Bacillus anthracis (Anthrax) whole genome protein microarray has been used to identify immunogenic Anthrax proteins (IAP) using sera from groups of donors with (a) confirmed B. anthracis naturally acquired cutaneous infection, (b) confirmed B. anthracis intravenous drug use-acquired infection, (c) occupational exposure in a wool-sorters factory, (d) humans and rabbits vaccinated with the UK Anthrax protein vaccine and compared to naïve unexposed controls. Anti-IAP responses were observed for both IgG and IgA in the challenged groups; however the anti-IAP IgG response was more evident in the vaccinated group and the anti-IAP IgA response more evident in the B. anthracis-infected groups. Infected individuals appeared somewhat suppressed for their general IgG response, compared with other challenged groups. Immunogenic protein antigens were identified in all groups, some of which were shared between groups whilst others were specific for individual groups. The toxin proteins were immunodominant in all vaccinated, infected or other challenged groups. However, a number of other chromosomally-located and plasmid encoded open reading frame proteins were also recognized by infected or exposed groups in comparison to controls. Some of these antigens e.g., BA4182 are not recognized by vaccinated individuals, suggesting that there are proteins more specifically expressed by live Anthrax spores in vivo that are not currently found in the UK licensed Anthrax Vaccine (AVP). These may perhaps be preferentially expressed during infection and represent expression of alternative pathways in the B. anthracis “infectome.” These may make highly attractive candidates for diagnostic and vaccine biomarker development as they may be more specifically associated with the infectious phase of the pathogen. A number of B. anthracis small hypothetical protein targets have been synthesized, tested in mouse immunogenicity studies and validated in parallel using human sera from the same study.
doi:10.3389/fmicb.2015.00747
PMCID: PMC4534840  PMID: 26322022
anthrax; microarray; immunology; protein; antibody; infection
18.  Natural cutaneous anthrax infection, but not vaccination, induces a CD4+ T cell response involving diverse cytokines 
Cell & Bioscience  2015;5:20.
Background
Whilst there have been a number of insights into the subsets of CD4+ T cells induced by pathogenic Bacillus anthracis infections in animal models, how these findings relate to responses generated in naturally infected and vaccinated humans has yet to be fully established. We describe the cytokine profile produced in response to T cell stimulation with a previously defined immunodominant antigen of anthrax, lethal factor (LF), domain IV, in cohorts of individuals with a history of cutaneous anthrax, compared with vaccinees receiving the U.K. licenced Anthrax Vaccine Precipitated (AVP) vaccine.
Findings
We found that immunity following natural cutaneous infection was significantly different from that seen after vaccination. AVP vaccination was found to result in a polarized IFNγ CD4+ T cell response, while the individuals exposed to B. anthracis by natural infection mounted a broader cytokine response encompassing IFNγ, IL-5, −9, −10, −13, −17, and −22.
Conclusions
Vaccines seeking to incorporate the robust, long-lasting, CD4 T cell immune responses observed in naturally acquired cutaneous anthrax cases may need to elicit a similarly broad spectrum cellular immune response.
doi:10.1186/s13578-015-0011-4
PMCID: PMC4464127  PMID: 26075052
Anthrax; Cytokine; Lethal factor; T cell; Bacillus anthracis; Vaccination; Infection
19.  Urban air pollution and mortality in a cohort of Norwegian men. 
Environmental Health Perspectives  2004;112(5):610-615.
We investigated the association between total and cause-specific mortality and individual measures of long-term air pollution exposure in a cohort of Norwegian men followed from 1972-1973 through 1998. Data from a follow-up study on cardiovascular risk factors among 16,209 men 40-49 years of age living in Oslo, Norway, in 1972-1973 were linked with data from the Norwegian Death Register and with estimates of average yearly air pollution levels at the participants' home addresses from 1974 to 1998. Cox proportional-hazards regression was used to estimate associations between exposure and total and cause-specific mortality. During the follow-up time 4,227 men died from a disease corresponding to an ICD-9 (International Classification of Diseases, Revision 9) code < 800. Controlling for a number of potential confounders, the adjusted risk ratio for dying was 1.08 [95% confidence interval (CI), 1.06-1.11] for a 10- microg/m3 increase in average exposure to nitrogen oxides (NOx) at the home address from 1974 through 1978. Corresponding adjusted risk ratios for dying from a respiratory disease other than lung cancer were 1.16 (95% CI, 1.06-1.26); from lung cancer, 1.11 (95% CI, 1.03-1.19); from ischemic heart diseases, 1.08 (95% CI, 1.03-1.12); and from cerebrovascular diseases, 1.04 (95% CI, 0.94-1.15). The findings indicate that urban air pollution may increase the risk of dying. The effect seemed to be strongest for deaths from respiratory diseases other than lung cancer.
PMCID: PMC1241929  PMID: 15064169
20.  The dissemination of anthrax from imported wool: Kidderminster 1900–14 
Background: A century ago anthrax was a continuing health risk in the town of Kidderminster. The distribution of cases in people and in animals provides an indication of the routes by which spores were disseminated. The response to these cases provides an insight into attitudes to an occupational and environmental risk at the time and can be compared with responses in more recent times.
Aims: To assess the distribution of anthrax cases associated with the use of contaminated wool and to review the response to them.
Methods: The area studied was Kidderminster, Worcestershire, England, from 1900 to 1914. Data sources were national records of the Factory Inspectorate and local records from the infirmary, Medical Officer of Health and inquest reports, and county agricultural records, supplemented by contemporary and later review articles. Case reports and summary data were analysed, and discussions and actions taken to improve precautions reviewed.
Results: There were 36 cases of anthrax, with five deaths, one of which was the sole case of the internal form of the disease. Cases of cutaneous anthrax were most frequently found in those handling raw wool, but they also occurred in workers at later stages of the spinning process and in people with little or no recorded exposure to contaminated wool. Limited precautionary measures were in place at the start of the study period. Some improvements were made, especially in the treatment of infections, but wool with a high risk of anthrax contamination continued to be used and cases continued to arise. Major changes were made to the disposal of waste and to agricultural practice in contaminated areas to curtail outbreaks in farm animals.
Conclusions: The introduction of anthrax as a contaminant of imported wool led not only to cases in the highly exposed groups of workers but also to cases in other members of the population and in farm animals. The measures taken during the study period reduced fatalities from cutaneous anthrax but did not eliminate the disease. Public concern about the cases was muted.
doi:10.1136/oem.2002.001131
PMCID: PMC1740714  PMID: 14739375
21.  Lethal Factor Toxemia and Anti-Protective Antigen Antibody Activity in Naturally Acquired Cutaneous Anthrax 
The Journal of Infectious Diseases  2011;204(9):1321-1327.
Cutaneous anthrax outbreaks occurred in Bangladesh from August to October 2009. As part of the epidemiological response and to confirm anthrax diagnoses, serum samples were collected from suspected case patients with observed cutaneous lesions. Anthrax lethal factor (LF), anti-protective antigen (anti-PA) immunoglobulin G (IgG), and anthrax lethal toxin neutralization activity (TNA) levels were determined in acute and convalescent serum of 26 case patients with suspected cutaneous anthrax from the first and largest of these outbreaks. LF (0.005–1.264 ng/mL) was detected in acute serum from 18 of 26 individuals. Anti-PA IgG and TNA were detected in sera from the same 18 individuals and ranged from 10.0 to 679.5 μg/mL and 27 to 593 units, respectively. Seroconversion to serum anti-PA and TNA was found only in case patients with measurable toxemia. This is the first report of quantitative analysis of serum LF in cutaneous anthrax and the first to associate acute stage toxemia with subsequent antitoxin antibody responses.
doi:10.1093/infdis/jir543
PMCID: PMC3182309  PMID: 21908727
22.  Establishment of a Canine Rabies Burden in Haiti through the Implementation of a Novel Surveillance Program 
PLoS Neglected Tropical Diseases  2015;9(11):e0004245.
The Republic of Haiti is one of only several countries in the Western Hemisphere in which canine rabies is still endemic. Estimation methods have predicted that 130 human deaths occur per year, yet existing surveillance mechanisms have detected few of these rabies cases. Likewise, canine rabies surveillance capacity has had only limited capacity, detecting only two rabid dogs per year, on average. In 2013, Haiti initiated a community-based animal rabies surveillance program comprised of two components: active community bite investigation and passive animal rabies investigation. From January 2013 –December 2014, 778 rabies suspect animals were reported for investigation. Rabies was laboratory-confirmed in 70 animals (9%) and an additional 36 cases were identified based on clinical diagnosis (5%), representing an 18-fold increase in reporting of rabid animals compared to the three years before the program was implemented. Dogs were the most frequent rabid animal (90%). Testing and observation ruled out rabies in 61% of animals investigated. A total of 639 bite victims were reported to the program and an additional 364 bite victims who had not sought medical care were identified during the course of investigations. Only 31% of people with likely rabies exposures had initiated rabies post-exposure prophylaxis prior to the investigation. Rabies is a neglected disease in-part due to a lack of surveillance and understanding about the burden. The surveillance methods employed by this program established a much higher burden of canine rabies in Haiti than previously recognized. The active, community-based bite investigations identified numerous additional rabies exposures and bite victims were referred for appropriate medical care, averting potential human rabies deaths. The use of community-based rabies surveillance programs such as HARSP should be considered in canine rabies endemic countries.
Author Summary
The Republic of Haiti has highest estimated burden of human rabies in the Western Hemisphere, at 130 estimated human deaths annually. Rabies surveillance systems in the majority of the developing world, including Haiti, are ineffective, resulting in underreporting of cases and contributing to the further neglect of this disease. In 2013 a passive rabies surveillance program was implemented in three of Haiti’s 140 communes near the nation’s capital city. Four animal rabies surveillance officers conducted 778 suspect animal rabies investigations in a two-year period and on average found a rabid animal for every 7.4 investigations. Prior to the implementation of this surveillance program Haiti reported an average of two canine and seven human rabies cases each year, for the entire country. This program identified 70 rabid animals and an additional 36 probable rabid animals in only a selected area of the country. These 106 cases represent an 18-fold increase in animal rabies reporting in Haiti. These findings support that canine rabies is a significant burden in Haiti and present data that can be used to improve human rabies burden estimations and enhance canine rabies control efforts.
doi:10.1371/journal.pntd.0004245
PMCID: PMC4657989  PMID: 26600437
23.  The Effect of Anthrax Bioterrorism on Emergency Department Presentation 
Study Objective:
From September through December 2001, 22 Americans were diagnosed with anthrax, prompting widespread national media attention and public concern over bioterrorism. The purpose of this study was to determine the effect of the threat of anthrax bioterrorism on patient presentation to a West Coast emergency department (ED).
Methods:
This survey was conducted at an urban county ED in Oakland, CA between December 15, 2001 and February 15, 2002. During random 8-hour blocks, all adult patients presenting for flu or upper respiratory infection (URI) symptoms were surveyed using a structured survey instrument that included standard visual numerical and Likert scales.
Results:
Eighty-nine patients were interviewed. Eleven patients (12%) reported potential exposure risk factors. Eighty percent of patients watched television, read the newspaper, or listened to the radio daily, and 83% of patients had heard about anthrax bioterrorism. Fifty-five percent received a chest x-ray, 10% received either throat or blood cultures, and 28% received antibiotics. Twenty-one percent of patients surveyed were admitted to the hospital. Most patients were minimally concerned that they may have contracted anthrax (mean=3.3±3.3 where 0=no concern and 10=extremely concerned). Patient concern about anthrax had little influence on their decision to visit the ED (mean=2.8±3.0 where 0=no influence and 10=greatly influenced). Had they experienced their same flu or URI symptoms one year prior to the anthrax outbreak, 91% of patients stated they would have sought medical attention.
Conclusions:
After considerable exposure to media reports about anthrax, most patients in this urban West Coast ED population were not concerned about anthrax infection. Fear of anthrax had little effect on decisions to come to the ED, and most would have sought medical help prior to the anthrax outbreak.
PMCID: PMC2906971  PMID: 20847852
24.  Factors associated with forced sex among women accessing health services in rural Haiti: implications for the prevention of HIV infection and other sexually transmitted diseases☆ 
Social science & medicine (1982)  2005;60(4):679-689.
The goals of the current study were to: (1) estimate the prevalence of forced sex among women accessing services at a women’s health clinic in rural Haiti; and (2) examine factors associated with forced sex in this population. Based on data from a case-control study of risk factors for sexually transmitted diseases (STDs), a cross-sectional analysis to examine factors associated with forced sex was performed. A number of factors related to gender inequality/socioeconomic vulnerability placed women in rural Haiti at higher risk of forced sex. The strongest factors associated with forced sex in multivariate analyses were: age, length of time in a relationship, occupation of the woman’s partner, STD-related symptoms, and factors demonstrating economic vulnerability. The findings suggest that prevention efforts must go beyond provision of information and education to the pursuit of broader initiatives at both local and national levels. At the community level, policy-makers should consider advancing economic opportunities for women who are vulnerable to forced sex. Improving access to community-based income-generating activities may begin to address this problem. However, the viability of these local projects depends largely upon Haiti’s ‘macro-economic’ situation. In order to ensure the success of local initiatives, external humanitarian and development assistance to Haiti should be supported. By broadening the definition of “prevention” interventions, we may begin to address the systemic problems that contribute to the occurrence of forced sex and the increasing incidence of HIV infection throughout the world, such as gender inequality and economic vulnerability. Taking into account factors influencing risk at the local level as well as the macro-level will potentially improve our capacity to reduce the risk of forced sex and the spread of STDs, including HIV infection, for millions of women living in poverty worldwide.
doi:10.1016/j.socscimed.2004.06.010
PMCID: PMC3407680  PMID: 15571887
Forced sex; STD transmission; HIV prevention; Haiti; Biosocial research
25.  Cholera Transmission in Ouest Department of Haiti: Dynamic Modeling and the Future of the Epidemic 
PLoS Neglected Tropical Diseases  2015;9(10):e0004153.
In the current study, a comprehensive, data driven, mathematical model for cholera transmission in Haiti is presented. Along with the inclusion of short cycle human-to-human transmission and long cycle human-to-environment and environment-to-human transmission, this novel dynamic model incorporates both the reported cholera incidence and remote sensing data from the Ouest Department of Haiti between 2010 to 2014. The model has separate compartments for infectious individuals that include different levels of infectivity to reflect the distribution of symptomatic and asymptomatic cases in the population. The environmental compartment, which serves as a source of exposure to toxigenic V. cholerae, is also modeled separately based on the biology of causative bacterium, the shedding of V. cholerae O1 by humans into the environment, as well as the effects of precipitation and water temperature on the concentration and survival of V. cholerae in aquatic reservoirs. Although the number of reported cholera cases has declined compared to the initial outbreak in 2010, the increase in the number of susceptible population members and the presence of toxigenic V. cholerae in the environment estimated by the model indicate that without further improvements to drinking water and sanitation infrastructures, intermittent cholera outbreaks are likely to continue in Haiti.
Author Summary
Based on the model-fitted trend and the observed incidence, there is evidence that after an initial period of intense transmission, the cholera epidemic in Haiti stabilized during the third year of the outbreak and became endemic. The model estimates indicate that the proportion of the population susceptible to infection is increasing and that the presence of toxigenic V. cholerae in the environment remains a potential source of new infections. Given the lack of adequate improvements to drinking water and sanitation infrastructure, these conditions could facilitate ongoing, seasonal cholera epidemics in Haiti.
doi:10.1371/journal.pntd.0004153
PMCID: PMC4619523  PMID: 26488620

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