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.
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.
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.
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.
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.
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.
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.
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.
Cutaneous anthrax; Clinico-demographic profile; Therapeutic response; Bangladesh
Haiti has an HIV/AIDS epidemic of the highest magnitude outside of sub-Saharan Africa. Factors such as relationship power imbalances, traditional gender role acceptance, and patriarchal belief systems that devalue women's sexuality have increased Haitian women's vulnerability to HIV infection. Because of these influences and since the HIV epidemic is largely heterosexually transmitted, it is important to understand the role that men's beliefs and behaviors play in the continuing risk of young men and women in Haiti. The purpose of this study was to gather information from male community members through semi-structured interviews in order to describe the prevalence of HIV/AIDS risk behaviors (e.g., condom use, number of sexual partners) among expectant fathers in Haiti and identify predictive psychosocial variables of HIV/AIDS risk behaviors. Results from this study showed that men who were not married (OR = 0.22, p = 0.05) and men who had medium (OR = 22.50, p < 0.001) and high sexual communication (OR = 36.51, p < 0.001) were more likely to use condoms. This study also showed that high stigma associated with HIV (OR = 16.07, p < 0.05), low HIV knowledge (OR = 0.10, p < 0.01), and high decision making power (OR = 62.52, p < 0.001) were predictors of multiple sex partners for the expectant fathers in the sample. HIV prevention programs should be designed to increase knowledge about HIV transmission, treatment, prevention and personal risk of contraction as well as correct misconceptions about individuals with HIV or AIDS and promote sex communication among partners.
Haiti; HIV risk behaviors; HIV/AIDS Knowledge; Men; Power; Sex communication; Stigma
Haiti is among the countries facing serious human resource shortages for healthcare. In rural Haiti, Partners In Health works with the Ministry of Health at public clinics to provide HIV and primary healthcare services. The needs of daily, long term adherence to medication for the treatment of HIV and TB drove recruitment of community health workers (CHW) who ultimately play a key role in the delivery of care. This qualitative study evaluated CHW role in the health system in the context of both HIV and non-HIV related services, as well as challenges and facilitating factors they faced in this role.
We used qualitative methods including focus group discussions and group interviews in four sites in rural Haiti. Data from 462 CHW were analyzed for themes and content according to standard ethnographic methods.
CHW contributed to a wide range of primary health services and non-HIV related activities. Recognition from the community, status, satisfaction of contributing to the well-being of their people and remuneration were facilitating factors to performing their work. Among the challenges, insufficient materials to cope with the obstacles on the ground, lack of diagnostic and treatment roles in their activities, high work load, and desire for ongoing training and a higher salary were described.
CHW initially hired to assist with HIV prevention and treatment represent an important part of the health system in rural Haiti in both HIV-related and primary healthcare services. CHW programs have important potential for building capacity in the health workforce and thereby contributing to strengthening of the health system as a whole. Attention must be paid to adequate remuneration, training and provision of materials.
Community health worker; health system strengthening
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.
Results are presented from a number of epidemiological studies using enzyme immunoassays (EIA) based on the purified anthrax toxin antigens, protective antigen, lethal factor and oedema factor. Studies on sera from a group of 62 human anthrax patients in Turkey and from cattle in Britain following two unrelated outbreaks of anthrax show that EIA using protective antigen can be a useful diagnostic aid and will detect subclinical infections in appropriate circumstances. A serological survey on wildlife in the Etosha National Park, Namibia, where anthrax is endemic, showed that naturally acquired anthrax-specific antibodies are rare in herbivores but common in carnivores; in carnivores, titres appear to reflect the prevalence of anthrax in their ranges. Problems, as yet unresolved, were encountered in studies on sera from pigs following an outbreak of anthrax on a farm in Wales. Clinical details, including treatment, of the human and one of the bovine outbreaks are summarized and discussed in relation to the serological findings.
Anthrax is a zoonotic disease caused by Bacillus anthracis. It is potentially fatal and highly contagious disease. Herbivores are the natural host. Human acquire the disease incidentally by contact with infected animal or animal products. In the 18th century an epidemic destroyed approximately half of the sheep in Europe. In 1900 human inhalational anthrax occured sporadically in the United States. In 1979 an outbreak of human anthrax occured in Sverdlovsk of Soviet Union. Anthrax continued to represent a world wide presence. The incidence of the disease has decreased in developed countries as a result of vaccination and improved industrial hygiene. Human anthrax clinically presents in three forms, i.e. cutaneous, gastrointestinal and inhalational. About 95% of human anthrax is cutaneous and 5% is inhalational. Gastrointestinal anthrax is very rare (less than 1%). Inhalational form is used as a biological warefare agent. Penicillin, ciprofloxacin (and other quinolones), doxicyclin, ampicillin, imipenem, clindamycin, clarithromycin, vancomycin, chloramphenicol, rifampicin are effective antimicrobials. Antimicrobial therapy for 60 days is recommended. Human anthrax vaccine is available. Administration of anti-protective antigen (PA) antibody in combination with ciprofloxacin produced 90%-100% survival. The combination of CPG-adjuvanted anthrax vaccine adsorbed (AVA) plus dalbavancin significantly improved survival.
Anthrax; Bacillus anthracis; Zoonotic disease; Contagious disease; Cutaneous anthrax; Inhalational anthrax; Gastrointestinal anthrax; Human anthrax
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.
Forced sex; STD transmission; HIV prevention; Haiti; Biosocial research
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.
When swallowed, anthrax spores may cause lesions from the oral cavity to the cecum. Gastrointestinal anthrax is greatly underreported in rural disease-endemic areas of the world. The apparent paucity of this form of anthrax reflects the lack of facilities able to make the diagnosis in these areas. The spectrum of disease, ranging from subclinical infection to death, has not been fully recognized. In some community-based studies, cases of gastrointestinal anthrax outnumbered those of cutaneous anthrax. The oropharyngeal variant, in particular, is unfamiliar to most physicians. The clinical features of oropharyngeal anthrax include fever and toxemia, inflammatory lesion(s) in the oral cavity or oropharynx, enlargement of cervical lymph nodes associated with edema of the soft tissue of the cervical area, and a high case-fatality rate. Awareness of gastrointestinal anthrax in a differential diagnosis remains important in anthrax-endemic areas but now also in settings of possible bioterrorism.
anthrax; anthrax classification; anthrax epidemiology; anthrax diagnosis; bioterrorism
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.
Background. Haitian immigrant women residing in Little Haiti, a large ethnic enclave in Miami-Dade County, experience the highest cervical cancer incidence rates in South Florida. While this disparity primarily reflects lack of access to screening with cervical cytology, the burden of human papillomavirus (HPV) which causes virtually all cases of cervical cancer worldwide, varies by population and may contribute to excess rate of disease. Our study examined the prevalence of oncogenic and nononcogenic HPV types and risk factors for HPV infection in Little Haiti. Methods. As part of an ongoing community-based participatory research initiative, community health workers recruited study participants between 2007 and 2008, instructed women on self-collecting cervicovaginal specimens, and collected sociodemographic and healthcare access data. Results. Of the 242 women who contributed adequate specimens, the overall prevalence of HPV was 20.7%, with oncogenic HPV infections (13.2% of women) outnumbering nononcogenic infections (7.4%). Age-specific prevalence of oncogenic HPV was highest in women 18–30 years (38.9%) although the prevalence of oncogenic HPV does not appear to be elevated relative to the general U.S. population. The high prevalence of oncogenic types in women over 60 years may indicate a substantial number of persistent infections at high risk of progression to precancer.
Restaveks, or indentured foster children, are a poorly understood, vulnerable subclass of Haitian society. From 2001 to the present, a partnership between multiple US academic medical centers and Project Medishare for Haiti has held an ongoing series of mobile clinics in rural Haiti. Multiple cases of restavek-related illness were identified. At a recent pair of mobile clinics, the authors identified two restavek cases that were significantly worse off than their communal peer groups and required immediate care. Given the lack of a robust legal support to protect orphaned children in Haiti, clinicians have an important role in advocating for restaveks at the bedside. The plight of Haiti's restaveks is widely reported in the human rights literature but is not publicly recognized as an issue for community health and wellbeing among physicians. To address these health disparities, the health consequences of an entire class of neglected children must be further explored.
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.
To provide family physicians with an overview of the evidence for managing superficial cutaneous abscesses.
SOURCES OF INFORMATION
PubMed (from 1950), EMBASE (from 1974), The Cochrane Library (from 1966), and Google (from 1998) were searched as were reference lists of identified articles. Summary sites, such as ACP Journal Club and InfoPOEMs, and background resources were also reviewed.
There are many areas of debate regarding abscess management, including pain control, necessity of culture and sensitivity testing, empiric treatment with antibiotics, and open versus primary closure of wounds. Usefulness of cultures and empiric antibiotic treatment has risen to the forefront with the increasing incidence of community-acquired, methicillin-resistant Staphylococcus aureus.
In immunocompetent patients with no confounding risk factors, incision and drainage under local anesthetic is generally sufficient for abscess management. There is no compelling evidence for routine cultures or empiric treatment with antibiotics. Further research is required.
Bacillus anthracis is the causative agent of anthrax, and its spores have been developed into lethal bioweapons. To mitigate an onslaught from airborne anthrax spores that are maliciously disseminated, it is of paramount importance to develop a rapid-response anthrax vaccine that can be mass administered by nonmedical personnel during a crisis. We report here that intranasal instillation of a nonreplicating adenovirus vector encoding B. anthracis protective antigen could confer rapid and sustained protection against inhalation anthrax in mice in a single-dose regimen in the presence of preexisting adenovirus immunity. The potency of the vaccine was greatly enhanced when codons of the antigen gene were optimized to match the tRNA pool found in human cells. In addition, an adenovirus vector encoding lethal factor can confer partial protection against inhalation anthrax and might be coadministered with a protective antigen-based vaccine.
Protective antigen (PA)-based anthrax vaccines acting on toxins are less effective than live attenuated vaccines, suggesting that additional antigens may contribute to protective immunity. Several reports indicate that capsule or spore-associated antigens may enhance the protection afforded by PA. Addition of formaldehyde-inactivated spores (FIS) to PA (PA-FIS) elicits total protection against cutaneous anthrax. Nevertheless, vaccines that are effective against cutaneous anthrax may not be so against inhalational anthrax. The aim of this work was to optimize immunization with PA-FIS and to assess vaccine efficacy against inhalational anthrax. We assessed the immune response to recombinant anthrax PA from Bacillus anthracis (rPA)-FIS administered by various immunization protocols and the protection provided to mice and guinea pigs infected through the respiratory route with spores of a virulent strain of B. anthracis. Combined subcutaneous plus intranasal immunization of mice yielded a mucosal immunoglobulin G response to rPA that was more than 20 times higher than that in lung mucosal secretions after subcutaneous vaccination. The titers of toxin-neutralizing antibody and antispore antibody were also significantly higher: nine and eight times higher, respectively. The optimized immunization elicited total protection of mice intranasally infected with the virulent B. anthracis strain 17JB. Guinea pigs were fully protected, both against an intranasal challenge with 100 50% lethal doses (LD50) and against an aerosol with 75 LD50 of spores of the highly virulent strain 9602. Conversely, immunization with PA alone did not elicit protection. These results demonstrate that the association of PA and spores is very much more effective than PA alone against experimental inhalational anthrax.
Epidemiological data on 448 cases of human cutaneous anthrax from the Gambia showed that this particular strain of anthrax bacillus causes widespread morbidity and some mortality with, at the same time, subclinical infection. Analysis also showed that anthrax is not an occupationally related disease in the Gambia.
The possibility of human-to-human spread, affecting all age groups and both sexes, by means of a communal toilet article was also shown. The fact that the strain is a good toxin producer but contains a weak antigen may have accounted for the repeated clinical infection and the fact that antibody titres were generally transient. Subclinical infection in animals was also found, particularly in sheep and goats, and also, with an unusually low mortality, in cows. Insect vectors were not excluded, but were unlikely. Vultures may spread the disease from village to village. Some possible public health and immunization procedures are discussed, with a view to containing this difficult problem in this part of west Africa.
Anthrax caused by Bacillus anthracis is a public health problem in several developing countries whose main source of income is farming. Anthrax is a disease of herbivorous animals, and humans can be infected by handling infected animals or contaminated animal products. Specific diagnostic tests are unavailable in India for the detection and confirmation of cutaneous anthrax in humans. Here, we describe the development of an enzyme-linked immunosorbent assay (ELISA) for detection of serum antibodies against Bacillus anthracis protective antigen in the Indian population. A total of 405 serum samples collected from different groups were tested by the developed ELISA. The assay provided a specificity of 99.41% (95% confidence interval [CI], 97.89 to 99.93) and a sensitivity of 100% (CI, 94.4 to 100) using a cutoff value of 0.29 ELISA unit (EU). The positive predictive value (PPV) and negative predictive value (NPV) of the assay were 97% and 100%, respectively. The efficiency and J index for the reliability of the assay were 99.5% and 0.994, respectively. The assay can be a very useful tool for surveillance as well as for diagnosis of cutaneous anthrax cases in India.
Bacillus anthracis spores cause natural infections and are used as biological weapons. Inhalation infection with B. anthracis, the etiological agent of anthrax, is almost always lethal, yet cutaneous infections usually remain localized and resolve spontaneously. Neutrophils are typically recruited to cutaneous but seldom to other forms of anthrax infections, raising the possibility that neutrophils kill B. anthracis. In this study we infected human neutrophils with either spores or vegetative bacteria of a wild-type strain, or strains, expressing only one of the two major virulence factors. The human neutrophils engulfed B. anthracis spores, which germinated intracellularly and were then efficiently killed. Interestingly, neutrophil killing was independent of reactive oxygen species production. We fractionated a human neutrophil granule extract by high-performance liquid chromatography and identified α-defensins as the component responsible for B. anthracis killing. These data suggest that the timely recruitment of neutrophils can control cutaneous infections and possibly other forms of B. anthracis infections, and that α-defensins play an important role in the potent anti-B. anthracis activity of neutrophils.
Bacillus anthracis is the bacterium that causes anthrax, a disease that can occur through natural infections and also through intentional release. B. anthracis makes spores, which are in a dormant state, similar to seeds of a plant, and are extremely resistant to the environment. B. anthracis spores can infect through the skin or the lung. Lung infections disseminate through the body and are lethal. In contrast, skin infections often remain localized, and patients survive even without treatment. It is not well understood why these bacteria cause a localized infection through the skin and a lethal disease through the lung.
Little is known about how B. anthracis is controlled. Neutrophils are the first white blood cells recruited to a site of infection and are specialized in killing microbes. Previous studies show that neutrophils are abundant in the skin form, but not in the lung form of anthrax. The researchers report that human neutrophils can take up B. anthracis spores. Once inside, the spores germinate to form vegetative bacteria. The vegetative bacteria are extremely susceptible to neutrophil-killing mechanisms. The B. anthracis virulence factors (molecules that make bacteria cause diseases) manipulate other human cells but do not deter neutrophils. B. anthracis is indeed exquisitely sensitive to the neutrophil protein α-defensin. These data support a new model where B. anthracis skin, but not lung, infections are controlled by the antimicrobial activity of neutrophils.