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1.  Evidence of Local Persistence of Human Anthrax in the Country of Georgia Associated with Environmental and Anthropogenic Factors 
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.
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.
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.
PMCID: PMC3764226  PMID: 24040426
2.  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.
PMCID: PMC149692  PMID: 12574269
3.  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.
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.
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
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
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
PMCID: PMC3168873  PMID: 21918643
4.  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.
PMCID: PMC3403762  PMID: 22492157
5.  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.
PMCID: PMC2843627  PMID: 20351776
6.  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.
PMCID: PMC4214624  PMID: 25356592
7.  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.
PMCID: PMC4006929  PMID: 24788397
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.
PMCID: PMC3571271  PMID: 23269414
9.  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.
PMCID: PMC4102439  PMID: 25032701
10.  Human anti-anthrax protective antigen neutralizing monoclonal antibodies derived from donors vaccinated with anthrax vaccine adsorbed 
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.
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.
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.
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.
PMCID: PMC420254  PMID: 15140257
11.  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
12.  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.
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.
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.
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.
PMCID: PMC3493280  PMID: 22929128
Cutaneous anthrax; Clinico-demographic profile; Therapeutic response; Bangladesh
13.  Predictability of anthrax infection in the Serengeti, Tanzania 
The Journal of applied ecology  2011;48(6):1333-1344.
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.
PMCID: PMC3272456  PMID: 22318563
Bacillus anthracis; disease ecology; exposure; infectious disease; multihost; serology; surveillance; susceptibility; zoonosis
14.  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.
PMCID: PMC3407680  PMID: 15571887
Forced sex; STD transmission; HIV prevention; Haiti; Biosocial research
15.  The Increase of Imported Malaria Acquired in Haiti among US Travelers in 2010 
From 2004 to 2009, the number of malaria cases reported in Haiti increased nearly fivefold. The effect of the 2010 earthquake and its aftermath on malaria transmission in Haiti is not known. Imported malaria cases in the United States acquired in Haiti tripled from 2009 to 2010, likely reflecting both the increased number of travelers arriving from Haiti and the increased risk of acquiring malaria infection in Haiti. The demographics of travelers and the proportion of severe cases are similar to those statistics reported in previous years. Non-adherence to malaria chemoprophylaxis remains a nearly universal modifiable risk factor among these cases.
PMCID: PMC3247100  PMID: 22232442
16.  Optimizing the Use of Chief Complaint & Diagnosis for Operational Decision Making: An EMR Case Study of the 2010 Haiti Earthquake 
PLoS Currents  2014;6:ecurrents.dis.2c6c4d44dc0260af0867e0bc30b85aa7.
Introduction: Data from an electronic medical record (EMR) system can provide valuable insight regarding health consequences in the aftermath of a disaster. In January of 2010, the U.S. Department of Health and Human Services (HHS) deployed medical personnel to Haiti in response to a crippling earthquake. An EMR system was used to record patient encounters in real-time and to provide data for decision support during response activities. Problem: During the Haiti response, HHS monitored the EMR system by recoding diagnoses into seven broad categories. At the conclusion of the response, it was evident that a new diagnosis categorization process was needed to provide a better description of the patient encounters that were seen in the field. After examining the EMRs, researchers determined nearly half of the medical records were missing diagnosis data. The objective of this study was to develop and test a new method of categorization for patient encounters to provide more detailed data for decision making. Methods: A single researcher verified or assigned a new diagnosis for 8,787 EMRs created during the Haiti response. This created a new variable, the Operational Code, which was based on available diagnosis data and chief complaint. Retrospectively, diagnoses recorded in the field and Operational Codes were categorized into eighteen categories based on the ICD-9-CM diagnostic system. Results: Creating an Operational Code variable led to a more robust data set and a clearer depiction emerged of the clinical presentations seen at six HHS clinics set up in the aftermath of Haiti’s earthquake. The number of records with an associated ICD-9 code increased 106% from 4,261 to 8,787. The most frequent Operational Code categories during the response were: General Symptoms, Signs, and Ill-Defined Conditions (34.2%), Injury and Poisoning (18.9%), Other (14.7%), Respiratory (4.8%), and Musculoskeletal and Connective Tissue (4.8%). Conclusion: The Operational Code methodology provided more detailed data about patient encounters. This methodology could be used in future deployments to improve situational awareness and decision-making capabilities during emergency response operations.
PMCID: PMC4172476  PMID: 25642366
17.  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
18.  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.
PMCID: PMC1740714  PMID: 14739375
19.  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.
PMCID: PMC3182309  PMID: 21908727
20.  Evolutionary Dynamics of Vibrio cholerae O1 following a Single-Source Introduction to Haiti 
mBio  2013;4(4):e00398-13.
Prior to the epidemic that emerged in Haiti in October of 2010, cholera had not been documented in this country. After its introduction, a strain of Vibrio cholerae O1 spread rapidly throughout Haiti, where it caused over 600,000 cases of disease and >7,500 deaths in the first two years of the epidemic. We applied whole-genome sequencing to a temporal series of V. cholerae isolates from Haiti to gain insight into the mode and tempo of evolution in this isolated population of V. cholerae O1. Phylogenetic and Bayesian analyses supported the hypothesis that all isolates in the sample set diverged from a common ancestor within a time frame that is consistent with epidemiological observations. A pangenome analysis showed nearly homogeneous genomic content, with no evidence of gene acquisition among Haiti isolates. Nine nearly closed genomes assembled from continuous-long-read data showed evidence of genome rearrangements and supported the observation of no gene acquisition among isolates. Thus, intrinsic mutational processes can account for virtually all of the observed genetic polymorphism, with no demonstrable contribution from horizontal gene transfer (HGT). Consistent with this, the 12 Haiti isolates tested by laboratory HGT assays were severely impaired for transformation, although unlike previously characterized noncompetent V. cholerae isolates, each expressed hapR and possessed a functional quorum-sensing system. Continued monitoring of V. cholerae in Haiti will illuminate the processes influencing the origin and fate of genome variants, which will facilitate interpretation of genetic variation in future epidemics.
Vibrio cholerae is the cause of substantial morbidity and mortality worldwide, with over three million cases of disease each year. An understanding of the mode and rate of evolutionary change is critical for proper interpretation of genome sequence data and attribution of outbreak sources. The Haiti epidemic provides an unprecedented opportunity to study an isolated, single-source outbreak of Vibrio cholerae O1 over an established time frame. By using multiple approaches to assay genetic variation, we found no evidence that the Haiti strain has acquired any genes by horizontal gene transfer, an observation that led us to discover that it is also poorly transformable. We have found no evidence that environmental strains have played a role in the evolution of the outbreak strain.
PMCID: PMC3705451  PMID: 23820394
21.  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).
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.
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.
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
22.  Identification of chlamydia and gonorrhoea among women in rural Haiti: maximising access to treatment in a resource poor setting 
Sexually Transmitted Infections  2006;82(2):175-181.
To develop a risk assessment algorithm that will increase the identification and treatment of women with cervical infection in rural Haiti.
Study participants were randomly selected from new patients who accessed services at a women's health clinic in rural Haiti between June 1999 and December 2002. This case‐control study included women who tested positive for chlamydia and/or gonorrhoea based on the Gen‐Probe PACE 2 laboratory test as cases. Controls were women who tested negative for both of these infections.
Women from this area of rural Haiti had a limited level of education and lived in impoverished housing conditions. The sensitivity estimates of Haitian Ministry of Health and WHO algorithms for detecting chlamydia and/or gonorrhoea were generally low (ranging from 16.1% to 68.1%) in this population. Risk scores based on logistic regression models of local risk factors for chlamydia and gonorrhoea were developed and sensitivity estimates were higher for algorithms based on these risk scores (up to 98.8%); however, specificity was compromised.
A risk assessment algorithm to identify women with chlamydia and/or gonorrhoea is more sensitive and less specific than the syndromic management approach advocated by WHO and adapted by the Haitian Ministry of Health. Using a risk assessment tool with high sensitivity based on local risk factors of cervical infection will maximise access to care, improve outcomes, and decrease morbidity in women who have cervical infection in rural Haiti.
PMCID: PMC2564696  PMID: 16581750
chlamydia; gonorrhoea; Haiti
23.  Population Genetics of Vibrio cholerae from Nepal in 2010: Evidence on the Origin of the Haitian Outbreak 
mBio  2011;2(4):e00157-11.
Cholera continues to be an important cause of human infections, and outbreaks are often observed after natural disasters, such as the one following the 2010 earthquake in Haiti. Once the cholera outbreak was confirmed, rumors spread that the disease was brought to Haiti by a battalion of Nepalese soldiers serving as United Nations peacekeepers. This possible connection has never been confirmed. We used whole-genome sequence typing (WGST), pulsed-field gel electrophoresis (PFGE), and antimicrobial susceptibility testing to characterize 24 recent Vibrio cholerae isolates from Nepal and evaluate the suggested epidemiological link with the Haitian outbreak. The isolates were obtained from 30 July to 1 November 2010 from five different districts in Nepal. We compared the 24 genomes to 10 previously sequenced V. cholerae isolates, including 3 from the Haitian outbreak (began July 2010). Antimicrobial susceptibility and PFGE patterns were consistent with an epidemiological link between the isolates from Nepal and Haiti. WGST showed that all 24 V. cholerae isolates from Nepal belonged to a single monophyletic group that also contained isolates from Bangladesh and Haiti. The Nepalese isolates were divided into four closely related clusters. One cluster contained three Nepalese isolates and three Haitian isolates that were almost identical, with only 1- or 2-bp differences. Results in this study are consistent with Nepal as the origin of the Haitian outbreak. This highlights how rapidly infectious diseases might be transmitted globally through international travel and how public health officials need advanced molecular tools along with standard epidemiological analyses to quickly determine the sources of outbreaks.
Cholera is one of the ancient classical diseases and particularly prone to cause major outbreaks following major natural disasters, such as earthquakes and hurricanes, where the normal separation between sewage and drinking water is destroyed. This was the case following the 2010 earthquake in Haiti. Rumors spread that the disease was brought to Haiti by a battalion of Nepalese soldiers serving as United Nations peacekeepers. This possible connection has never been confirmed. Sequencing the genomes of bacteria can give detailed information on whether isolates from different sites share a common origin. We used this technology to sequence isolates of Vibrio cholerae from Nepal, identify single-nucleotide polymorphisms (SNPs), and compare these high-resolution genotypes to the complete genome sequences of isolates from the Haiti outbreak. We provide support for the hypothesis that the isolates were brought to Haiti from Nepal.
PMCID: PMC3163938  PMID: 21862630
24.  Increased standardized incidence ratio of breast cancer in female electronics workers 
BMC Public Health  2007;7:102.
In 1994, a hazardous waste site, polluted by the dumping of solvents from a former electronics factory, was discovered in Taoyuan, Taiwan. This subsequently emerged as a serious case of contamination through chlorinated hydrocarbons with suspected occupational cancer. The objective of this study was to determine if there was any increased risk of breast cancer among female workers in a 23-year follow-up period.
A total of 63,982 female workers were retrospectively recruited from the database of the Bureau of Labor Insurance (BLI) covering the period 1973–1997; the data were then linked with data, up to 2001, from the National Cancer Registry at the Taiwanese Department of Health, from which standardized incidence ratios (SIRs) for different types of cancer were calculated as compared to the general population.
There were a total of 286 cases of breast cancer, and after adjustment for calendar year and age, the SIR was close to 1. When stratified by the year 1974 (the year in which the regulations on solvent use were promulgated), the SIR of the cohort of workers who were first employed prior to 1974 increased to 1.38 (95% confidence interval, 1.11–1.70). No such trend was discernible for workers employed after 1974. When 10 years of employment was considered, there was a further increase in the SIR for breast cancer, to 1.62. Those workers with breast cancer who were first employed prior to 1974 were employed at a younger age and for a longer period. Previous qualitative studies of interviews with the workers, corroborated by inspection records, showed a short-term high exposure to chlorinated alkanes and alkenes, particularly trichloroethylene before 1974. There were no similar findings on other types of cancer.
Female workers with exposure to trichloroethylene and/or mixture of solvents, first employed prior to 1974, may have an excess risk of breast cancer.
PMCID: PMC1906757  PMID: 17559641
25.  Economic Risk Factors for HIV Infection Among Women in Rural Haiti: Implications for HIV Prevention Policies and Programs in Resource-Poor Settings 
Journal of Women's Health  2010;19(5):885-892.
The goals of this study were to (1) estimate the prevalence of HIV infection among women accessing services at a women's health center in rural Haiti and (2) to identify economic risk factors for HIV infection in this population.
Women who accessed healthcare services at this center between June 1999 and December 2002 were recruited to participate. The analysis was based on data from a case-control study of sexually transmitted diseases (STDs) in rural Haiti. HIV prevalence in the study population was 4%.
In multivariate analyses, partner occupation was associated with HIV infection in women, with mechanic (OR 9.0, 95% CI 1.8-45) and market vendor (OR 4.2, 95% CI 1.6-11) reflecting the strongest partner occupational risk factors. Partner's occupation as a farmer reduced the risk of infection in women by 60% (95% CI 0.14-1.1). Factors indicating low socioeconomic status (SES), such as food insecurity (OR 2.0, 95% CI 0.75-5.6) and using charcoal for cooking (OR 1.7, 95% CI 0.72-3.8) suggested an association with HIV infection.
Given pervasive gender inequality in Haiti, women's economic security often relies on their partners' income earning activities. Our findings show that although factors reflecting poverty are associated with HIV-positive status, stronger associations are observed for women whose partners indicated a more secure occupation (e.g., mechanic or market vendor). Policies and programs that expand access to education and economic opportunities for women and girls may have long-term implications for HIV prevention in Haiti and other resource-poor settings.
PMCID: PMC2875958  PMID: 20380576

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