clove and Plague

Yersinia pestis, the bacterial causative agent of plague, remains an important threat to human health. Plague is a rodent-borne disease that has historically shown an outstanding ability to colonize and persist across different species, habitats, and environments while provoking sporadic cases, outbreaks, and deadly global epidemics among humans. Between September and November 2017, an outbreak of urban pneumonic plague was declared in Madagascar, which refocused the attention of the scientific community on this ancient human scourge. Given recent trends and plague's resilience to control in the wild, its high fatality rate in humans without early treatment, and its capacity to disrupt social and healthcare systems, human plague should be considered as a neglected threat. A workshop was held in Paris in July 2018 to review current knowledge about plague and to identify the scientific research priorities to eradicate plague as a human threat. It was concluded that an urgent commitment is needed to develop and fund a strong research agenda aiming to fill the current knowledge gaps structured around 4 main axes: (i) an improved understanding of the ecological interactions among the reservoir, vector, pathogen, and environment; (ii) human and societal responses; (iii) improved diagnostic tools and case management; and (iv) vaccine development. These axes should be cross-cutting, translational, and focused on delivering context-specific strategies. Results of this research should feed a global control and prevention strategy within a "One Health" approach.

Topics: Animals; Disease Outbreaks; Disease Reservoirs; Humans; Insect Vectors; Madagascar; Neglected Diseases; Plague; Rodentia; Siphonaptera; Yersinia pestis

Plague is an infectious disease found worldwide and has been responsible for pandemics throughout history. Yersinia pestis, the causative bacterium, survives in rodent hosts with flea vectors that also transmit it to humans. It has been endemic in Madagascar for a century but the 1990s saw major outbreaks and in 2006 the WHO described the plague as re-emerging in Madagascar and the world. This review highlights the variety of factors leading to plague re-emergence in Madagascar, including climate events, insecticide resistance, and host and human behaviour. It also addresses areas of concern for future epidemics and ways to mitigate these. Pinpointing and addressing current and future drivers of plague re-emergence in Madagascar will be essential to controlling future outbreaks both in Madagascar and worldwide.

Topics: Animals; Madagascar; Plague; Rodentia; Siphonaptera; Yersinia pestis

Madagascar has just emerged from the grip of an acute urban pneumonic plague outbreak, which began in August 2017, before the usual plague season of October-April and outside the traditional plague foci in the northern and central highlands. The World Health Organization reported a total of 2417 confirmed, probable and suspected cases, including 209 deaths between 1 August and 26 November 2017. The severity and scope of this outbreak, which has affected those in higher socioeconomic groups as well as those living in poverty, along with factors including the potential for use of multi-drug-resistant strains of plague in bioterrorism, highlights the ongoing threat posed by this ancient disease. Factors likely to have contributed to transmission include human behaviour, including burial practices and movement of people, poor urban planning leading to overcrowding and ready transmission by airborne droplets, climatic factors and genomic subtypes. The outbreak demonstrates the importance of identifying targeted pneumonic plague therapies and of developing vaccines that can be administered in planned programmes in developing countries such as Madagascar where plague is endemic. The dominance of pneumonic plague in this outbreak suggests that we need to focus more urgently on the danger of person-to-person transmission, as well as the problem of transmission of plague from zoonotic sources.

Topics: Animals; Disease Outbreaks; Disease Reservoirs; Endemic Diseases; Humans; Lung; Madagascar; Plague; Rats; Yersinia pestis; Zoonoses

After centuries of epidemics and more than a hundred years since the identification of the causative bacterium, very little is known about the plague dynamics in animal reservoirs, vectors and the changing vulnerabilities for humans. The recent plague epidemic in Madagascar in 2017 highlights these gaps existing within the knowledge of the disease dynamics, the factors influencing it, the performance of diagnostic tests and the best recommended treatment. As the eradication of plague will not be possible due to the widespread existence of the bacterium in wildlife, a One Health approach, drawing on animal, human and environmental health disciplines is needed to better control this poverty-related disease. This article focused on the various aspects of the disease for which more tools and better understanding are required to better control the disease in endemic countries.

Topics: Africa; Animals; Anti-Bacterial Agents; Asia; Bacterial Vaccines; Disease Outbreaks; Disease Reservoirs; Humans; Insect Bites and Stings; Insect Vectors; Madagascar; Molecular Diagnostic Techniques; North America; Plague; Poverty; Rodentia; Siphonaptera; Social Determinants of Health; Yersinia pestis

Plague, in the Middle Ages known as Black Death, continues to occur at permanent foci in many countries, in Africa, Asia, South America, and even the USA. During the last years outbreaks were reported from at least 3 geographical areas, in all cases after tens of years without reported cases. The recent human plague outbreaks in Libya and Algeria suggest that climatic and other environmental changes in Northern Africa may be favourable for

Topics: Africa; Africa, Northern; Algeria; Asia; Disease Outbreaks; Humans; Libya; Madagascar; Plague; South America; Yersinia pestis

Plague, a zoonosis caused by Yersinia pestis, is still found in Africa, Asia, and the Americas. Madagascar reports almost one third of the cases worldwide. Y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. Flea vector and wild rodent host population dynamics are tightly correlated with modulation of climatic conditions, an association that could be crucial for both the maintenance of foci and human plague epidemics. The black rat Rattus rattus, the main host of Y. pestis in Madagascar, is found to exhibit high resistance to plague in endemic areas, opposing the concept of high mortality rates among rats exposed to the infection. Also, endemic fleas could play an essential role in maintenance of the foci. This review discusses recent advances in the understanding of the role of these factors as well as human behavior in the persistence of plague in Madagascar.

Topics: Animals; Madagascar; Plague; Rats; Siphonaptera; Yersinia pestis

Plague remains a public health concern worldwide, but particularly in Africa. Despite the long-standing history of human plague, it is difficult to get a historical and recent overview of the general situation. We searched and screened available information sources on human plague occurrences in African countries and compiled information on when, where and how many cases occurred in a centralised database. We found records that plague was probably already present before the third pandemic and that hundreds of thousands of human infections have been reported in 26 countries since 1877. In the first 30 years of the 20th century, the number of human cases steadily increased to reach a maximum in 1929. From then on the number decreased and fell below 250 after 1945. Since the 1980s, again increasingly more human infections have been reported with the vast majority of cases notified in East Africa and Madagascar. We show that public health concerns regarding the current plague situation are justified and that the disease should not be neglected, despite the sometimes questionability of the numbers of cases. We conclude that improving plague surveillance strategies is absolutely necessary to obtain a clear picture of the plague situation in endemic regions.

Topics: Africa; Disease Outbreaks; Humans; Incidence; Madagascar; Plague; Population Surveillance

Bubonic plague is the primary manifestation of infection with Yersinia pestis, accounting for 90% of all plague cases and with 75% of global cases reported in Madagascar. All drugs in use for treating plague are registered based on experimental data and anecdotal evidence, and no regimen currently recommended is supported by a randomized clinical trial. The IMASOY trial intends to fill this knowledge gap by comparing two 10-day regimens included in the national guidelines in Madagascar. The primary objective of the trial is to test the hypothesis that ciprofloxacin monotherapy is non-inferior to streptomycin followed by ciprofloxacin for the treatment of bubonic plague, thus avoiding the need for injectable, potentially toxic, aminoglycosides.. A two-arm parallel-group randomized control trial will be conducted across peripheral health centres in Madagascar in five districts. Males and non-pregnant females of all ages with suspected bubonic or pneumonic plague will be recruited over the course of three plague 'seasons'. The primary endpoint of the trial is to assess the proportion of patients with bubonic plague who have a therapeutic response to treatment (defined as alive, resolution of fever, 25% reduction in the size of measurable buboes, has not received an alternative treatment and no clinical decision to continue antibiotics) as assessed on day 11.. If successful, the trial has the potential to inform the standard of care guidelines not just in Madagascar but in other countries afflicted by plague. The trial is currently ongoing and expected to complete recruitment in 2022.. ClinicalTrials.gov NCT04110340 . Registered on 1 October 2019.

Topics: Ciprofloxacin; Equivalence Trials as Topic; Female; Humans; Madagascar; Male; Plague; Streptomycin; Yersinia pestis

The effect of two different insecticides on flea control was tested from January to March 2000 in the Ivory village and the Ambatolahy village: Knox-Out, a microcapsulated formulation of diazinon, organophosphorous compound (240 gr/L) and the deltamethrin powder (2 g/kg ai), respectively. The villages are located 2.5 km apart in the Betafo region in Madagascar. Deltamethrin is a pyrethroid and is still used in the National Plague Control Program, whereas diazinon has not previously been applied in plague control in Madagascar. The flea index and the prevalence of rats carrying fleas in the two villages before and after (at one and two months follow-up, respectively) were measured to evaluate the effect of each insecticide. Flea index decreased significantly in both villages by at the first month follow-up. However, at the second month follow-up no significant differences in comparison to pre-treatment index values were observed in any of the villages. This study has demonstrated a similar immediate effect of deltamethrin and of diazinon, and confirmed the absence of remanent action of the two insecticides.

Topics: Animals; Chemistry, Pharmaceutical; Diazinon; Disease Reservoirs; Drug Compounding; Follow-Up Studies; Insect Control; Insect Vectors; Insecticides; Madagascar; Nitriles; Pesticide Residues; Plague; Powders; Prevalence; Pyrethrins; Rats; Rural Health; Siphonaptera; Yersinia pestis

Plague is still prevalent in more than 20 countries. Two F1 antigen diagnostic assays (an immunocapture ELISA and an immunogold chromatography dipstick) were evaluated using bubo aspirates, serum and urine specimens from patients suspected with plague. The specificity of the two F1 assays was found 100%. Using bacteriology as a gold reference diagnostic assay, 52 patients were Yersinia pestis culture positive and 141 negative. The sensitivity of the F1 ELISA test was 100% in bubo, 52% in serum and 58% in urine specimens. In culture negative patients, the F1 antigen could be found in 10% bubo aspirates, 5% serum and 7% urine specimens of culture negative patients for whom a seroconversion for anti-F1 antibodies was also observed. The sensitivity of the dipstick assay was 98% on bubo aspirates specimens. Compared to the ELISA test, the agreement rate was 97.5% and the correlation coefficient tau = 0.90 (p < 10(-3)). In conclusion, the diagnosis of bubonic plague has to be performed on bubo fluid rather than on serum or urine specimens. Both the F1 ELISA and the dipstick assays are valuable tools for an early diagnosis and for the surveillance of plague.

Topics: Antibodies, Monoclonal; Antigens, Bacterial; Bacterial Proteins; Disease Outbreaks; Enzyme-Linked Immunosorbent Assay; Humans; Immunohistochemistry; Madagascar; Plague; Sensitivity and Specificity; Yersinia pestis

Topics: Humans; Madagascar; Plague

Africa sees the surge of plague cases in recent decades, with hotspots in the Democratic Republic of Congo, Madagascar, and Peru. A rodent-borne scourge, the bacterial infection known as plague is transmitted to humans via the sneaky bites of fleas, caused by Yersinia pestis. Bubonic plague has a case fatality rate of 20.8% with treatment, but in places such as Madagascar the mortality rate can increase to 40-70% without treatment.. Tragedy strikes in the Ambohidratrimo district as three lives are claimed by the plague outbreak and three more fight for survival in the hospitals, including one man in critical condition, from the Ambohimiadana, Antsaharasty, and Ampanotokana communes, bringing the total plague victims in the area to a grim to five. Presently, the biggest concern is the potential plague spread among humans during the ongoing COVID-19 pandemic. Effective disease control can be achieved through training and empowering local leaders and healthcare providers in rural areas, implementing strategies to reduce human-rodent interactions, promoting water, sanitation and hygiene practices (WASH) practices, and carrying out robust vector, reservoir and pest control, diversified animal surveillance along with human surveillance should be done to more extensively to fill the lacunae of knowledge regarding the animal to human transmission. The lack of diagnostic laboratories equipped represents a major hurdle in the early detection of plague in rural areas. To effectively combat plague, these tests must be made more widely available. Additionally, raising awareness among the general population through various means such as campaigns, posters and social media about the signs, symptoms, prevention, and infection control during funerals would greatly decrease the number of cases. Furthermore, healthcare professionals should be trained on the latest methods of identifying cases, controlling infections and protecting themselves from the disease.. Despite being endemic to Madagascar, the outbreak's pace is unparalleled, and it may spread to non-endemic areas. The utilization of a One Health strategy that encompasses various disciplines is crucial for minimizing catastrophe risk, antibiotic resistance, and outbreak readiness. Collaboration across sectors and proper planning ensures efficient and consistent communication, risk management, and credibility during disease outbreaks.

Topics: Animals; COVID-19; Disease Outbreaks; Humans; Madagascar; Male; One Health; Pandemics; Plague

Madagascar is among the 10 highest burden countries for malnutrition. Protein-energy malnutrition, anemia, and vitamin deficiencies are major public health problems. Hunger is exacerbated by an annual locust invasion. The current policy of large-scale government spraying of pesticides from planes is logistically complex, costly, and damaging to the environment.. Our research aimed to study the feasibility of turning the locust invasion into a protein-rich food supply for families and an economic opportunity for youth.. We conducted 20 focus group discussions (FGDs) with females and males aged 18-24 and 25 years or older and with female artisans in 6 swarm communes in Madagascar's south to understand enablers and barriers to collection, preparation, and consumption of locusts.. Enablers include consumption by all ages in Antandroy culture and perception of locusts as a delicacy, tasty, and free. Family members have different roles in the collection and preparation of locusts. Local technologies for mass collection include digging trenches in fields and entrapment via sisal netting. Common preparations include boiling in salted water, drying, skewering, frying, and grinding locusts into flour. Disablers include pesticide contamination of locusts and the view that locusts are a famine food.. Our research provided a first step in demonstrating the feasibility of transforming locust infestations into economic and nutritional opportunities in a fragile environment with high levels of poverty and malnutrition. It contributes to advocacy in Madagascar to end the use of pesticides. It responds to the government desire to address the protein-energy malnutrition burden and youth poverty in an integrated way.

Topics: Adolescent; Adult; Female; Humans; Madagascar; Male; Malnutrition; Pesticides; Plague; Protein-Energy Malnutrition; Qualitative Research; Sustainable Development; Young Adult

Plague, caused by the bacterium Yersinia pestis, remains an important disease in Madagascar, where the oriental rat flea, Xenopsylla cheopis, is a primary vector. To control fleas, synthetic pyrethroids (SPs) have been used for >20 years, resulting in resistance in many X. cheopis populations. The most common mechanisms of SP resistance are target site mutations in the voltage-gated sodium channel (VGSC) gene.. We obtained 25 collections of X. cheopis from 22 locations across Madagascar and performed phenotypic tests to determine resistance to deltamethrin, permethrin, and/or dichlorodiphenyltrichloroethane (DDT). Most populations were resistant to all these insecticides. We sequenced a 535 bp segment of the VGSC gene and identified two different mutations encoding distinct substitutions at amino acid position 1014, which is associated with knockdown resistance (kdr) to SPs in insects. Kdr mutation L1014F occurred in all 25 collections; a rarer mutation, L1014H, was found in 12 collections. There was a significant positive relationship between the frequency of kdr alleles and the proportion of individuals surviving exposure to deltamethrin. Phylogenetic comparisons of 12 VGSC alleles in Madagascar suggested resistant alleles arose from susceptible lineages at least three times. Because genotype can reasonably predict resistance phenotype, we developed a TaqMan PCR assay for the rapid detection of kdr resistance alleles.. Our study provides new insights into VGSC mutations in Malagasy populations of X. cheopis and is the first to report a positive correlation between VGSC genotypes and SP resistance phenotypes in fleas. Widespread occurrence of these two SP resistance mutations in X. cheopis populations in Madagascar reduces the viability of these insecticides for flea control. However, the TaqMan assay described here facilitates rapid detection of kdr mutations to inform when use of these insecticides is still warranted to reduce transmission of plague.

Topics: Animals; Flea Infestations; Humans; Insecticides; Madagascar; Mutation; Phylogeny; Plague; Rats; Siphonaptera; Xenopsylla; Yersinia pestis

Human plague cases are reported annually in the central highland regions of Madagascar, where the disease is endemic. The socioenvironmental characteristics and lifestyles of the populations of the central highland localities could be linked to this endemicity. The aim of this study was to determine socioenvironmental determinants that may be associated with plague risk and explain this variation in epidemiological contexts.. The current study was based on the distribution of plague cases between 2006 and 2015 that occurred in localities of districts positioned in the central highlands. Household surveys were performed from June to August 2017 using a questionnaire and direct observations on the socioenvironmental aspects of households in selected localities. Bivariate and multivariate analyses were performed to highlight the socioenvironmental parameters associated with plague risk in both districts.. A total of 503 households were surveyed, of which 54.9% (276/503) were in Ambositra and 45.1% (227/503) were in Tsiroanomandidy. Multivariate analyses showed that thatched roofs [adjusted odds ratio (AOR): 2.63; 95% confidence interval (95% CI): 1.78-3.88] and ground floor houses [AOR: 2.11; 95% CI: 1.3-3.45-] were significantly associated with the vulnerability of a household to plague risk (p value<0.05).. Plague risk in two districts of the Malagasy central highlands is associated with human socioenvironmental characteristics. Socioenvironmental characteristics are parameters expressing spatial heterogeneity through the difference in epidemiological expression of the plague in Ambositra and Tsiroanomandidy. These characteristics could be used as indicators of vulnerability to plague risk in plague-endemic areas.

Topics: Black People; Humans; Madagascar; Multivariate Analysis; Plague; Risk; Social Determinants of Health; Social Environment

Plague is a re-emerging zoonotic disease and a major public health concern in several portions of the world, especially in Madagascar. We report on the presence of different subtypes of Yersinia pestis co-occurring in the same locality. After confirmation of a human plague case in Ambohitromby Commune (Ankazobe District) via isolation of Y. pestis, we undertook small mammal trapping to identify the circulation of Y. pestis amongst rodents in this locality; blood samples were collected from rodents for seroprevalence analysis. Of the 60 individuals of Rattus rattus captured, one yielded an isolate of Y. pestis, 13 others were positive for F1 antigen of Y. pestis using a rapid diagnostic test, and 4 were PCR positive targeting the caf1 and pla genes; 28/60 (46.7%) of the captured R. rattus were seropositive for Y. pestis. Whole-genome SNP analyses revealed that the two isolates obtained from the human case, and the R. rattus belonged to two different subtypes of Y. pestis (s05 and s13, respectively) that were circulating concurrently in Ambohitromby in 2016. Three Y. pestis subtypes (s03, s05 and s13) have now been isolated from Ambohitromby. Subtype s05 had been persisting there for >10 years but one or both of the other subtypes may have been introduced from the Central Highlands region as they were not observed in previous years (s13) or only observed once previously (s03). High seroprevalence against Y. pestis in R. rattus suggests that a portion of the local murine population may have acquired resistance to Y. pestis. Future research should focus on genomically characterizing Y. pestis strains circulating in Ankazobe District and other plague-endemic regions of Madagascar to better understand the overall phylogeography of Y. pestis.

Topics: Animals; Madagascar; Mammals; Mice; Plague; Rats; Rodent Diseases; Seroepidemiologic Studies; Yersinia pestis; Zoonoses

Klebsiella pneumoniae can lead to a wide range of diseases including pneumonia, bloodstream and urinary tract infections. During a short period of a pulmonary plague epidemic in October 2017 in Madagascar, 12 K. pneumoniae isolates were identified in ten sputum and two buboes aspirate samples. These isolates were from 12 patients suspected of plague, without epidemiological relationships, but were negative for Yersinia pestis in culture. Data were collected from the plague national surveillance system. The isolates were characterized by antimicrobial susceptibility testing and whole-genome sequencing. Real-time PCR was performed to confirm the presence of K. pneumoniae DNA in buboes. All isolates were identified as K. pneumoniae sensu stricto. Five isolates were extended-spectrum β-lactamases producers; eleven different sequence types were identified. Five isolates belonged to known hypervirulent sequence types. Our results demonstrate community-acquired pneumonia caused by K. pneumoniae isolates in patients suspected of plague stressing the importance of bed-side differential diagnosis.

Topics: beta-Lactamases; Humans; Klebsiella Infections; Klebsiella pneumoniae; Madagascar; Plague

During outbreaks, the lack of diagnostic "gold standard" can mask the true burden of infection in the population and hamper the allocation of resources required for control. Here, we present an analytical framework to evaluate and optimize the use of diagnostics when multiple yet imperfect diagnostic tests are available. We apply it to laboratory results of 2,136 samples, analyzed with 3 diagnostic tests (based on up to 7 diagnostic outcomes), collected during the 2017 pneumonic (PP) and bubonic plague (BP) outbreak in Madagascar, which was unprecedented both in the number of notified cases, clinical presentation, and spatial distribution. The extent of these outbreaks has however remained unclear due to nonoptimal assays. Using latent class methods, we estimate that 7% to 15% of notified cases were Yersinia pestis-infected. Overreporting was highest during the peak of the outbreak and lowest in the rural settings endemic to Y. pestis. Molecular biology methods offered the best compromise between sensitivity and specificity. The specificity of the rapid diagnostic test was relatively low (PP: 82%, BP: 85%), particularly for use in contexts with large quantities of misclassified cases. Comparison with data from a subsequent seasonal Y. pestis outbreak in 2018 reveal better test performance (BP: specificity 99%, sensitivity: 91%), indicating that factors related to the response to a large, explosive outbreak may well have affected test performance. We used our framework to optimize the case classification and derive consolidated epidemic trends. Our approach may help reduce uncertainties in other outbreaks where diagnostics are imperfect.

Topics: Disease Outbreaks; Epidemics; Humans; Madagascar; Plague; Yersinia pestis

Among the many collaterals of the COVID-19 pandemic is the disruption of health services and vital clinical research. COVID-19 has magnified the challenges faced in research and threatens to slow research for urgently needed therapeutics for Neglected Tropical Diseases (NTDs) and diseases affecting the most vulnerable populations. Here we explore the impact of the pandemic on a clinical trial for plague therapeutics and strategies that have been considered to ensure research efforts continue.. To understand the impact of the COVID-19 pandemic on the trial accrual rate, we documented changes in patterns of all-cause consultations that took place before and during the pandemic at health centres in two districts of the Amoron'I Mania region of Madagascar where the trial is underway. We also considered trends in plague reporting and other external factors that may have contributed to slow recruitment.. During the pandemic, we found a 27% decrease in consultations at the referral hospital, compared to an 11% increase at peripheral health centres, as well as an overall drop during the months of lockdown. We also found a nation-wide trend towards reduced number of reported plague cases.. COVID-19 outbreaks are unlikely to dissipate in the near future. Declining NTD case numbers recorded during the pandemic period should not be viewed in isolation or taken as a marker of things to come. It is vitally important that researchers are prepared for a rebound in cases and, most importantly, that research continues to avoid NTDs becoming even more neglected.

Topics: COVID-19; Disease Notification; Epidemiological Monitoring; Health Impact Assessment; Humans; Madagascar; Neglected Diseases; Pandemics; Patient Acceptance of Health Care; Patient Selection; Plague; Randomized Controlled Trials as Topic; Referral and Consultation; Research; Tropical Medicine

Rodents represent a serious threat to food security and public health. The extent to which rodent control can mitigate the risk from rodent-borne disease depends on both the effectiveness of control in reducing rodent abundance and the impact on disease epidemiology. Focusing on a plague-endemic region of Madagascar, this study compared the effectiveness of 3 methods: live-traps, snap-traps, and rodenticides. Control interventions were implemented inside houses between May and October 2019. Tracking tiles monitored rodent abundance. Rodent fleas, the vector involved in plague transmission, were collected. Rodent populations consisted of Rattus rattus and Mus musculus. In terms of trap success, we found that our live-trap regime was more effective than snap-traps. While all 3 control strategies appeared to reduce in-house rodent activity in the short term, we found no evidence of a longer-term effect, with in-house rodent abundance in treated sites comparable to non-treatment sites by the following month. Endemic flea, Synopsyllus fonquerniei, is a key plague vector usually found on rats living outdoors. Although we found no evidence that its abundance inside houses increased following control, this may have been due to a lack of power caused by significant variation in S. fonquerniei abundance. The presence of S. fonquerniei in houses was more likely when S. fonquerniei abundance on outdoor rats was higher, which in turn correlated with high rat abundance. Our results emphasize that control strategies need to consider this connectivity between in-house rat-flea populations and the outdoor populations, and any potential consequences for plague transmission.

Topics: Animals; Bacterial Zoonoses; Insect Vectors; Madagascar; Plague; Population Density; Rats; Rodent Control; Siphonaptera

The epidemiology of Yersinia pestis, the causative agent of plague, involves vectors and reservoirs in its transmission cycle. The passive plague surveillance in Madagascar targets mainly rodent and fleas. However, carnivores are routinely surveyed as sentinels of local plague activity in some countries. The aim of this study is to assess the use of domestic dog (Canis familiaris) as sentinel animal for field surveillance of plague in a highly endemic area in Madagascar. Cross-sectional surveys of plague antibody prevalence in C. familiaris were conducted in endemic areas with contrasting histories of plague cases in humans, as well as a plague free area. Rodent capture was done in parallel to evaluate evidence for Y. pestis circulation in the primary reservoirs. In 2 sites, dogs were later re-sampled to examine evidence of seroconversion and antibody persistence. Biological samplings were performed between March 2008 and February 2009. Plague antibody detection was assessed using anti-F1 ELISA. Our study showed a significant difference in dog prevalence rates between plague-endemic and plague-free areas, with no seropositive dogs detected in the plague free area. No correlation was found between rodents and dog prevalence rates, with an absence of seropositive rodents in some area where plague circulation was indicated by seropositive dogs. This is consistent with high mortality rates in rodents following infection. Re-sampling dogs identified individuals seropositive on both occasions, indicating high rates of re-exposure and/or persistence of plague antibodies for at least 9 months. Seroconversion or seropositive juvenile dogs indicated recent local plague circulation. In Madagascar, dog surveillance for plague antibody could be useful to identify plague circulation in new areas or quiescent areas within endemic zones. Within active endemic areas, monitoring of dog populations for seroconversion (negative to positive) or seropositive juvenile dogs could be useful for identifying areas at greatest risk of human outbreaks.

Topics: Animals; Antibodies, Bacterial; Bacterial Zoonoses; Disease Outbreaks; Dog Diseases; Dogs; Endemic Diseases; Humans; Madagascar; Plague; Prevalence; Sentinel Species; Sentinel Surveillance

According to the WHO, 75% of the world's plague cases are found in Madagascar, with an average of 200 to 700 cases suspected annually (mainly bubonic plague). In 2017, a pneumonic plague epidemic of unusual proportions occurred, which raised several challenges for laboratory confirmation of cases, pointing to the need for the development of Yersinia pestis isolation procedures, especially those that can be performed in remote areas. As the WHO gold standard for plague diagnosis is bacterial culture, we sought to develop a simple method to prepare a highly selective medium, fit for use in remote areas where plague is endemic. The performance of the new medium, named improved BIN, was examined in terms of growth support and selectivity with spiked samples as well in isolating Y. pestis from clinical specimens, and it was compared to the results obtained with commercially available selective media. The preparation of the new medium is less complex and its performance was found to be superior to that of first-generation BIN medium. The growth support of the medium is higher, there is no batch diversity, and it maintains high selectivity properties. In 55 clinical specimens obtained from patients suspected to be infected with Y. pestis, approximately 20% more Y. pestis-positive isolates were identified by the improved BIN medium than were identified by commercially available selective media. The improved BIN medium is notably advantageous for the isolation of Y. pestis from clinical specimens obtained from plague patients, thus offering better surveillance tools and proper promotion of medical treatment to more patients suspected of being infected with Y. pestis.

Topics: Agar; Culture Media; Humans; Madagascar; Plague; Yersinia pestis

Plague is endemic to the central highlands of Madagascar. Sporadic human cases or outbreaks can occur annually in these areas. In Madagascar, the associations between endemicity and the knowledge, attitudes and practices (KAP) of the population with regard to this disease remain poorly documented. The aim of this study was to assess KAP related to plague among the population living in the central highlands.. A cross-sectional survey was conducted in the general population from June to August 2017. Based on the reported cases of plague between 2006 and 2015 in two central highland districts, a KAP questionnaire was administered in the population. Based on the proportion of correct answers provided by respondents, KAP scores were classified into three KAP categories: low (< Mean - SD), medium (Mean ± SD) and good (> Mean + SD). Multivariate analyses were performed to determine the associations between population KAP scores related to plague and sociodemographic and epidemiological factors. In addition, individual interviews and focus groups with health professionals were conducted to assess plague perception.. A total of 597 individuals participated in the survey; 20% (n = 119) had a good KAP score, 62% (n = 370) a medium KAP score and 18% (n = 108) a low KAP score. Among the 119 respondents with good KAP scores, 80% (n = 95) resided in Ambositra district, and 20% (n = 24) resided in Tsiroanomandidy district. According to the health professionals in the two districts, populations in endemic areas are well aware of the plague. There were significant associations (p <  0.05) of not owning a mobile phone, having no contact with a former plague case, and living in Tsiroanomandidy district with a lower KAP score.. The results of the study showed the need to adapt plague control interventions to the local context to allow a better allocation of human and financial resources. Doing so would minimize delays in patient management care and increase community resilience to plague epidemics.

Topics: Cross-Sectional Studies; Disease Outbreaks; Health Knowledge, Attitudes, Practice; Humans; Madagascar; Plague

Human plague cases, mainly in the bubonic form, occur annually in endemic regions of the central highlands of Madagascar. The aim of this study was to compare the dynamics of the epidemiological features of the human plague in two districts of the central highlands region.. In Madagascar, all clinically suspected plague cases that meet clinical and epidemiological criteria specified in the World Health Organization (WHO) standard case definition are reported to the national surveillance system. Data on plague cases reported between 2006 and 2015 in the districts of Ambositra and Tsiroanomandidy were analysed. Statistical comparisons between the epidemiological characteristics of the two districts were conducted.. A total of 840 cases of plague were reported over the studied period, including 563 (67%) probable and confirmed cases (P + C). Out of these P + C cases, nearly 86% (488/563) were cases of bubonic plague. Reported clinical forms of plague were significantly different between the districts from 2006 to 2015 (p = 0.001). Plague cases occurred annually in a period of 10 years in the Tsiroanomandidy district. During the same period, the Ambositra district was characterized by a one-year absence of cases.. The differences in the epidemiological situation with respect to the plague from 2006 to 2015 in the two central highlands districts may suggest that several factors other than biogeographical factors determine the representation of the plague and its dynamics in this region. Considering the epidemiological situations according to the specific contexts of the districts could improve the results in the fight against the plague in Madagascar.

Topics: Humans; Incidence; Madagascar; Plague; World Health Organization

Plague is a highly fatal disease caused by Yersinia pestis. Late diagnosis hampers disease outcome and effectiveness of control measures, induces death and disease spread. Advance on its diagnosis was the use of lateral flow rapid diagnostic test (RDT).. We assessed the performance of the plague RDT based on Y. pestis F1 antigen detection more than 15 years after its deployment in Madagascar. We compared the RDT with bacteriological culture results, using data from plague notified cases collected during the periods for which both tests were performed independently and systematically.. Used with bubonic plague (BP) patient samples, RDTs had a sensitivity of 100% (95% CI: 99.7-100%), a specificity of 67% (95% CI: 64-70%) with a good agreement between bacteriology and RDT results (86%; κ = 0.70, 95% CI 0.67-0.73). For pneumonic plague (PP), RDT had a sensitivity of 100% (95% CI: 91-100%) and a specificity of 59% (95% CI: 49-68%) and concordance between the bacteriological and plague RDT results was moderate (70%; κ = 0.43, 95% CI 0.32-0.55). Analysis focusing on the 2017-2018 plague season including the unprecedented epidemic of PP showed that RDT used on BP samples still had a sensitivity of 100% (95% CI: 85-100%) and a specificity of 82% (95% CI: 48-98%) with a very good agreement with bacteriology 94% (κ = 0.86, 95% CI 0.67-1); for PP samples, concordance between the bacteriological and plague RDT results was poor (61%; κ = - 0.03, 95% CI -0.17 - 0.10).. RDT performance appeared to be similar for the diagnosis of BP and PP except during the 2017 PP epidemic where RDT performance was low. This RDT, with its good sensitivity on both plague clinical forms during a normal plague season, remained a potential test for alert. Particularly for BP, it may be of great value in the decision process for the initiation of therapy. However, for PP, RDT may deliver false negative results due to inconsistent sample quality. Plague diagnosis could be improved through the development of next generation of RDTs.

Topics: Bacterial Proteins; Bacteriological Techniques; Diagnostic Tests, Routine; Epidemics; Humans; Madagascar; Plague; Retrospective Studies; Yersinia pestis

The Oriental rat flea, Xenopsylla cheopis (Rothschild 1903), is a cosmopolitan flea usually found infesting domestic rats. This flea is a well-known major human plague vector in Madagascar. As part of field sampling, fleas and small mammals were collected in the village of South Andranofeno and the natural reserve of Sohisika, two sites of the district of Ankazobe, located in the Central Highlands of Madagascar. Rats inside houses and forest small mammals were trapped using Besancon Technical Services and pitfall traps, respectively. Their fleas were collected and preserved for laboratory works. Collected fleas from the village and forest belonged to five species, which were X. cheopis, Synopsyllus fonquerniei (Wagner and Roubaud 1932) (Siphonaptera: Pulicidae), Echidnophaga gallinacea (Westwood 1875) (Siphonaptera: Pulicidae), Ctenocephalides felisstrongylus (Jordan 1925) (Siphonaptera: Pulicidae), Pulex irritans (Linnaeus 1758) (Siphonaptera: Pulicidae). After sampling in the forest zone, one specimen of X. cheopis was unexpectedly collected while infesting an endemic tenrec Setifer setosus (Schreber 1777) (Afrosoricida: Tenrecidae). Polymerase chain reaction (PCR) diagnosis on all collected fleas allowed detecting plague bacterium Yersinia pestis (Lehmann and Neumann 1896) (Enterobacterales: Yersiniaceae) on nine specimens of the endemic flea S. fonquerniei collected inside forest. The presence of the oriental rat flea in forest highlights the connection between human and wild environments due to animal movements and the fact that the rat flea can infest various hosts. As only one specimen of X. cheopis was collected on S. setosus, we hypothesize that flea was carried from the village to forest. Yersinia pestis infection of forest fleas outlines plague circulation in this sylvatic area.

Topics: Animal Distribution; Animals; Eulipotyphla; Flea Infestations; Forests; Madagascar; Plague; Rats; Xenopsylla; Yersinia pestis

In late 2017, Madagascar experienced a large urban outbreak of pneumonic plague, the largest outbreak to date this century. During the outbreak, there were widespread reports of plague patients presenting with atypical symptoms, such as prolonged duration of illness and upper respiratory tract symptoms. Reported mortality among plague cases was also substantially lower than that reported in the literature (25% versus 50% in treated patients). A prospective multicenter observational study was carried out to investigate potential reasons for these atypical presentations. Few subjects among our cohort had confirmed or probable plague, suggesting that, in part, there was overdiagnosis of plague cases by clinicians. However, 35% subjects reported using an antibiotic with anti-plague activity before hospital admission, whereas 55% had antibiotics with anti-plague activity detected in their serum at admission. Although there may have been overdiagnosis of plague by clinicians during the outbreak, the high frequency of community antibiotic may partly explain the relatively few culture-positive sputum samples during the outbreak. Community antibiotic use may have also altered the clinical presentation of plague patients. These issues make accurate detection of patients and the development of clinical case definitions and triage algorithms in urban pneumonic plague outbreaks difficult.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Cohort Studies; Female; Humans; Infant; Madagascar; Male; Middle Aged; Plague; Prospective Studies

Several tests are available for plague confirmation but bacteriological culture with Yersinia pestis strain isolation remains the gold standard according to the World Health Organization. However, this is a time consuming procedure; requiring specific devices and well-qualified staff. In addition, strain isolation is challenging if antibiotics have been administered prior to sampling. Here, we developed a loop-mediated isothermal amplification (LAMP) technique, a rapid, simple, sensitive and specific technique that would be able to detect Y. pestis in human biological samples.. LAMP primers were designed to target the caf1 gene which is specific to Y. pestis. The detection limit was determined by testing 10-fold serial dilution of Y. pestis DNA. Cross-reactivity was tested using DNA extracts from 14 pathogens and 47 residual samples from patients suffering from non-plague diseases. Specificity and sensitivity of the LAMP caf1 were assessed on DNA extracts of 160 human biological samples. Then, the performance of the LAMP caf1 assay was compared to conventional PCR and bacteriological culture.. The detection limit of the developed Y. pestis LAMP assay was 3.79 pg/μl, similar to conventional PCR. The result could be read out within 45 min and as early as 35 minutes in presence of loop primer, using a simple water bath at 63°C. This is superior to culture with respect to time (requires up to 10 days) and simplicity of equipment compared to PCR. Furthermore, no cross-reactivity was found when tested on DNA extracts from other pathogens and human biological samples from patients with non-plague diseases. Compared to the gold standard, LAMP sensitivity and specificity were 97.9% (95% CI: 89.1%-99.9%) and 94.6% (95% CI: 88.6%-97.9%), respectively.. LAMP detected Y. pestis effectively with high sensitivity and specificity in human plague biological samples. It can potentially be used in the field during outbreaks in resource limited countries such as Madagascar.

Topics: Bacteriological Techniques; DNA, Bacterial; Feasibility Studies; Humans; Limit of Detection; Madagascar; Nucleic Acid Amplification Techniques; Plague; Time Factors; Yersinia pestis

The rapid detection of ongoing outbreak - and the identification of causative pathogen - is pivotal for the early recognition of public health threats. The emergence and re-emergence of infectious diseases are linked to several determinants, both human factors - such as population density, travel, and trade - and ecological factors - like climate change and agricultural practices. Several technologies are available for the rapid molecular identification of pathogens [e.g. real-time polymerase chain reaction (PCR)], and together with on line monitoring tools of infectious disease activity and behaviour, they contribute to the surveillance system for infectious diseases. Web-based surveillance tools, infectious diseases modelling and epidemic intelligence methods represent crucial components for timely outbreak detection and rapid risk assessment. The study aims to integrate the current prevention and control system with a prediction tool for infectious diseases, based on regression analysis, to support decision makers, health care workers, and first responders to quickly and properly recognise an outbreak. This study has the intention to develop an infectious disease regressive prediction tool working with an off-line database built with specific epidemiological parameters of a set of infectious diseases of high consequences. The tool has been developed as a first prototype of a software solution called Infectious Diseases Seeker (IDS) and it had been established in two main steps, the database building stage and the software implementation stage (MATLAB

Topics: China; Communicable Diseases; Democratic Republic of the Congo; Disease Outbreaks; Female; Hemorrhagic Fever, Ebola; Humans; Madagascar; Male; Plague; Public Health Surveillance; Severe Acute Respiratory Syndrome; Software

Plague, a fatal disease caused by the bacillus, Yersinia pestis, still affects resources-limited countries. Information on antibody response to plague infection in human is scarce. Anti-F1 Ig G are among the known protective antibodies against Y. pestis infection. As a vaccine preventable disease, knowledge on antibody response is valuable for the development of an effective vaccine to reduce infection rate among exposed population in plague-endemic regions. In this study, we aim to describe short and long-term humoral immune responses against Y. pestis in plague-confirmed patients from Madagascar, the most affected country in the world.. Bubonic (BP) and pneumonic plague (PP) patients were recruited from plague- endemic foci in the central highlands of Madagascar between 2005 and 2017. For short-term follow-up, 6 suspected patients were enrolled and prospectively investigated for kinetics of the anti-F1 IgG response, whereas the persistence of antibodies was retrospectively studied in 71 confirmed convalescent patients, using an ELISA which was validated for the detection of plague in human blood samples in Madagascar.. Similarly to previous findings, anti-F1 IgG rose quickly during the first week after disease onset and increased up to day 30. In the long-term study, 56% of confirmed cases remained seropositive, amongst which 60 and 40% could be considered as high- and low-antibody responders, respectively. Antibodies persisted for several years and up to 14.8 years for one individual. Antibody titers decreased over time but there was no correlation between titer and time elapsed between the disease onset and serum sampling. In addition, the seroprevalence rate was not significantly different between gender (P = 0.65) nor age (P = 0.096).. Our study highlighted that the circulating antibody response to F1 antigen, which is specific to Y. pestis, may be attributable to individual immune responsiveness. The finding that a circulating anti-F1 antibody titer could persist for more than a decade in both BP and PP recovered patients, suggests its probable involvement in patients' protection. However, complementary studies including analyses of the cellular immune response to Y. pestis are required for the better understanding of long-lasting protection and development of a potential vaccine against plague.

Topics: Adolescent; Adult; Animals; Antibodies, Bacterial; Antigens, Bacterial; Bacterial Proteins; Child; Female; Follow-Up Studies; Humans; Immunity, Humoral; Immunoglobulin G; Madagascar; Male; Plague; Prospective Studies; Retrospective Studies; Seroepidemiologic Studies; Yersinia pestis; Young Adult

Madagascar is more seriously affected by plague, a zoonosis caused by Yersinia pestis, than any other country. The Plague National Control Program was established in 1993 and includes human surveillance. During 1998-2016, a total of 13,234 suspected cases were recorded, mainly from the central highlands; 27% were confirmed cases, and 17% were presumptive cases. Patients with bubonic plague (median age 13 years) represented 93% of confirmed and presumptive cases, and patients with pneumonic plague (median age 29 years) represented 7%. Deaths were associated with delay of consultation, pneumonic form, contact with other cases, occurrence after 2009, and not reporting dead rats. A seasonal pattern was observed with recrudescence during September-March. Annual cases peaked in 2004 and decreased to the lowest incidence in 2016. This overall reduction occurred primarily for suspected cases and might be caused by improved adherence to case criteria during widespread implementation of the F1 rapid diagnostic test in 2002.

Topics: Antigens, Bacterial; Case-Control Studies; Data Analysis; Disease Outbreaks; History, 20th Century; History, 21st Century; Humans; Immunoassay; Madagascar; Plague; Population Surveillance; Risk Factors; Seroepidemiologic Studies; Yersinia pestis

Zoonosis calls for a multispecies approach to medical semiotics, a method involving the decipherment of outward symptoms and the construction of narrative. In Madagascar, early detection of bubonic plague outbreaks relies on sightings of sick and dead rats. However, people most vulnerable to plague often do not perceive warning signs, and plague symptoms do not always present in rat and human bodies. In August 2015, a plague outbreak killed 10 residents of a rural hamlet in the central highlands. To reconstruct the transmission chain, scientists elicited survivors' memories of dead rats in the vicinity. Not only were these clues imperceptible to most, but residents had also constructed an alternative outbreak narrative based on different evidence. Stark health disparities, a lack of historical memory of the plague, and genetic adaptations of rats and plague bacteria have created a problem of "semiotic cluelessness" that complicates outbreak control measures and increases mortality.

Topics: Animals; Anthropology, Medical; Disease Outbreaks; Humans; Madagascar; Narration; Plague; Rats; Zoonoses

Topics: Disease Outbreaks; Epidemics; Forecasting; Humans; Madagascar; Plague

Madagascar accounts for 75% of global plague cases reported to WHO, with an annual incidence of 200-700 suspected cases (mainly bubonic plague). In 2017, a pneumonic plague epidemic of unusual size occurred. The extent of this epidemic provides a unique opportunity to better understand the epidemiology of pneumonic plagues, particularly in urban settings.. Clinically suspected plague cases were notified to the Central Laboratory for Plague at Institut Pasteur de Madagascar (Antananarivo, Madagascar), where biological samples were tested. Based on cases recorded between Aug 1, and Nov 26, 2017, we assessed the epidemiological characteristics of this epidemic. Cases were classified as suspected, probable, or confirmed based on the results of three types of diagnostic tests (rapid diagnostic test, molecular methods, and culture) according to 2006 WHO recommendations.. 2414 clinically suspected plague cases were reported, including 1878 (78%) pneumonic plague cases, 395 (16%) bubonic plague cases, one (<1%) septicaemic case, and 140 (6%) cases with unspecified clinical form. 386 (21%) of 1878 notified pneumonic plague cases were probable and 32 (2%) were confirmed. 73 (18%) of 395 notified bubonic plague cases were probable and 66 (17%) were confirmed. The case fatality ratio was higher among confirmed cases (eight [25%] of 32 cases) than probable (27 [8%] of 360 cases) or suspected pneumonic plague cases (74 [5%] of 1358 cases) and a similar trend was seen for bubonic plague cases (16 [24%] of 66 confirmed cases, four [6%] of 68 probable cases, and six [2%] of 243 suspected cases). 351 (84%) of 418 confirmed or probable pneumonic plague cases were concentrated in Antananarivo, the capital city, and Toamasina, the main seaport. All 50 isolated Yersinia pestis strains were susceptible to the tested antibiotics.. This predominantly urban plague epidemic was characterised by a large number of notifications in two major urban areas and an unusually high proportion of pneumonic forms, with only 23% having one or more positive laboratory tests. Lessons about clinical and biological diagnosis, case definition, surveillance, and the logistical management of the response identified in this epidemic are crucial to improve the response to future plague outbreaks.. US Agency for International Development, WHO, Institut Pasteur, US Department of Health and Human Services, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases, Models of Infectious Disease Agent Study of the National Institute of General Medical Sciences, AXA Research Fund, and the INCEPTION programme.

Topics: Adolescent; Adult; Child; Child, Preschool; Cities; Epidemics; Female; Humans; Incidence; Infant; Infant, Newborn; Madagascar; Male; Middle Aged; Plague; Yersinia pestis; Young Adult

Bubonic is the most prevalent plague form in Madagascar. Indoor ground application of insecticide dust is the conventional method used to control potentially infected rodent fleas that transmit the plague bacterium from rodents to humans. The use of bait stations is an alternative approach for vector control during plague epidemics, as well as a preventive control method during non-epidemic seasons. Bait stations have many advantages, principally by reducing the amount of insecticide used, lowering the cost of the treatment and minimizing insecticide exposure in the environment. A previous study reported promising results on controlling simultaneously the reservoir and vectors, when slow-acting rodenticide was incorporated in bait stations called "Boîtes de Kartman". However, little evidence of an effective control of the fleas prior to the elimination of rodents was found. In this study, we evaluated bait stations containing insecticide powder and non-toxic attractive rodent bait for their potential to control rat fleas. Its efficacy was compared to the standard method. The impact of both methods on indoor and outdoor rodent fleas, as well as the human household flea Pulex irritans were analyzed at different time points after treatments. Bait stations did not cause any significant immediate or delayed reduction of rat fleas and increasing the number of operational bait stations per household did not significantly improve their efficacy. Insecticide ground dusting appeared to be the most efficient method to control indoor rat fleas. Both methods appeared to have little impact on the density of outdoor rat fleas and human fleas. These results demonstrate limited effectiveness for bait stations and encourage the maintenance of insecticide dusting as a first-line control strategy in case of epidemic emergence of plague, when immediate effect on rodent fleas is needed. Recommendations are given to improve the efficacy of the bait station method.

Topics: Animals; Flea Infestations; Humans; Insect Vectors; Insecticides; Madagascar; Pest Control; Plague; Rats; Rodentia; Siphonaptera; Yersinia pestis

The emergence of antibiotic-resistant Yersinia pestis strains represents a public health concern. Two antibiotic-resistant Y. pestis strains isolated from Madagascar have been previously identified and characterised. Both strains carried conjugative plasmids that conferred resistance to streptomycin or to multiple antibacterial drugs, respectively. Here we characterised a novel Y. pestis strain (IP2180H) that exhibited resistance to doxycycline. This strain was isolated from a rat in Antananarivo (Madagascar) in 1998. Resistance was carried by a conjugative plasmid (pIP2180H) homologous to pB71 from Salmonella enterica. The plasmid of the previously identified streptomycin-resistant Y. pestis strain was also sequenced and it was found that the three antibiotic resistance Y. pestis plasmids sequenced until now are genetically unrelated and are also unrelated to multidrug resistance plasmids from the phylogenetically close bacterial species Yersinia pseudotuberculosis. The fact that the three antibiotic-resistant Malagasy Y. pestis strains were isolated from different hosts, at different times, from distant locations, and carried unrelated plasmids indicates independent horizontal acquisition of genetic material and further demonstrates the capacity of Y. pestis to acquire antibiotic resistance plasmids under natural conditions. Since these resistance plasmids can frequently carry or easily trap antibiotic resistance cassettes, the emergence of new multidrug-resistant Y. pestis strains may be expected and would represent a major health threat.

Topics: Animals; Anti-Bacterial Agents; Disk Diffusion Antimicrobial Tests; DNA, Bacterial; Doxycycline; Drug Resistance, Multiple, Bacterial; Madagascar; Plague; Plasmids; Rats; Streptomycin; Yersinia pestis

Topics: Disease Outbreaks; Humans; Madagascar; Plague; Public Health Surveillance; Yersinia pestis

Topics: Communicable Disease Control; Disease Outbreaks; Humans; Madagascar; Plague; Yersinia pestis

Topics: Epidemics; Government Programs; Humans; Madagascar; Plague; Public Health; Yersinia pestis

Topics: Aircraft; Humans; Internationality; Madagascar; Plague; Risk Factors; Travel

From August to November 2017, Madagascar endured an outbreak of plague. A total of 2417 cases of plague were confirmed, causing a death toll of 209. Public health intervention efforts were introduced and successfully stopped the epidemic at the end of November. The plague, however, is endemic in the region and occurs annually, posing the risk of future outbreaks. To understand the plague transmission, we collected real-time data from official reports, described the outbreak's characteristics, and estimated transmission parameters using statistical and mathematical models. The pneumonic plague epidemic curve exhibited multiple peaks, coinciding with sporadic introductions of new bubonic cases. Optimal climate conditions for rat flea to flourish were observed during the epidemic. Estimate of the plague basic reproduction number during the large wave of the epidemic was high, ranging from 5 to 7 depending on model assumptions. The incubation and infection periods for bubonic and pneumonic plague were 4.3 and 3.4 days and 3.8 and 2.9 days, respectively. Parameter estimation suggested that even with a small fraction of the population exposed to infected rat fleas (1/10,000) and a small probability of transition from a bubonic case to a secondary pneumonic case (3%), the high human-to-human transmission rate can still generate a large outbreak. Controlling rodent and fleas can prevent new index cases, but managing human-to-human transmission is key to prevent large-scale outbreaks.

Topics: Animals; Basic Reproduction Number; Epidemics; Humans; Madagascar; Models, Theoretical; Plague; Public Health; Rats; Risk; Siphonaptera; Yersinia pestis

Plague is a rodent-borne disease caused by Yersinia pestis. Most human infections are bubonic plague, as a result of being bitten by infected rodent fleas. Madagascar, Democratic Republic of Congo and Peru are the three most affected countries. Plague was introduced into eastern Madagascar in 1898 by boat from India. It is estimated that the risk of introduction of plague from Madagascar to neighboring islands is very high due to the maritime links. We conducted a study of plague reservoirs and vectors in Longoni Port in Mayotte and Mahajanga Port in Madagascar during two seasons to highlight a non-negligible risk of introduction of Y. pestis to Mayotte. The results showed that two main reservoirs of plague in Madagascar Suncus murinus and Rattus rattus and the main flea vector Xenopsylla cheopis exists in and surrounding the port of Longoni. Y. pestis was isolated from Rattus norvegicus captured close to the port of Mahajanga during this study. Plague bacteria circulate within populations of rodent without causing rodent die-off in Mahajanga. The risk of introduction of plague from Madagascar to Mayotte exists due to the regular exchanges. Continuous surveillance of rat, shrew and flea populations is therefore necessary in all the surrounding countries that have regular exchanges with Madagascar to prevent the spread of the plague.

Topics: Animals; Comoros; Disease Vectors; Humans; Insect Vectors; Madagascar; Plague; Rats; Rodent Diseases; Rodentia; Siphonaptera; Yersinia pestis

In Madagascar, plague (Yersinia pestis infection) is endemic in the central highlands, maintained by the couple Rattus rattus/flea. The rat is assumed to die shortly after infection inducing migration of the fleas. However we previously reported that black rats from endemic areas can survive the infection whereas those from non-endemic areas remained susceptible. We investigate the hypothesis that lineages of rats can acquire resistance to plague and that previous contacts with the bacteria will affect their survival, allowing maintenance of infected fleas. For this purpose, laboratory-born rats were obtained from wild black rats originating either from plague-endemic or plague-free zones, and were challenged with Y. pestis. Survival rate and antibody immune responses were analyzed.. Inoculation of low doses of Y. pestis greatly increase survival of rats to subsequent challenge with a lethal dose. During challenge, cytokine profiles support activation of specific immune response associated with the bacteria control. In addition, F1 rats from endemic areas exhibited higher survival rates than those from non-endemic ones, suggesting a selection of a resistant lineage. In Madagascar, these results support the role of black rat as long term reservoir of infected fleas supporting maintenance of plague transmission.

Topics: Animals; Animals, Wild; Bacterial Proteins; Disease Reservoirs; Insect Vectors; Madagascar; Plague; Rats; Siphonaptera; Yersinia pestis

The flea Xenopsylla cheopis (Siphonaptera: Pulicidae) is a vector of plague. Despite this insect's medical importance, especially in Madagascar where plague is endemic, little is known about the organization of its natural populations. We undertook population genetic analyses (i) to determine the spatial genetic structure of X. cheopis in Madagascar and (ii) to determine the potential risk of plague introduction in the neighboring island of Mayotte.. We genotyped 205 fleas from 12 sites using nine microsatellite markers. Madagascan populations of X. cheopis differed, with the mean number of alleles per locus per population ranging from 1.78 to 4.44 and with moderate to high levels of genetic differentiation between populations. Three distinct genetic clusters were identified, with different geographical distributions but with some apparent gene flow between both islands and within Malagasy regions. The approximate Bayesian computation (ABC) used to test the predominant direction of flea dispersal implied a recent population introduction from Mayotte to Madagascar, which was estimated to have occurred between 1993 and 2012. The impact of this flea introduction in terms of plague transmission in Madagascar is unclear, but the low level of flea exchange between the two islands seems to keep Mayotte free of plague for now.. This study highlights the occurrence of genetic structure among populations of the flea vector of plague, X. cheopis, in Madagascar and suggests that a flea population from Mayotte has been introduced to Madagascar recently. As plague has not been reported in Mayotte, this introduction is unlikely to present a major concern for plague transmission. Nonetheless, evidence of connectivity among flea populations in the two islands indicates a possibility for dispersal by fleas in the opposite direction and thus a risk of plague introduction to Mayotte.

Topics: Alleles; Animals; Bayes Theorem; Cluster Analysis; Comoros; Gene Flow; Genes, Insect; Genetic Variation; Genetics, Population; Genotype; Insect Vectors; Madagascar; Microsatellite Repeats; Plague; Xenopsylla; Yersinia pestis

Yersinia pestis appears to be maintained in multiple, geographically separate, and phylogenetically distinct subpopulations within the highlands of Madagascar. However, the dynamics of these locally differentiated subpopulations through time are mostly unknown. To address that gap and further inform our understanding of plague epidemiology, we investigated the phylogeography of Y. pestis in Madagascar over an 18 year period.. We generated whole genome sequences for 31 strains and discovered new SNPs that we used in conjunction with previously identified SNPs and variable-number tandem repeats (VNTRs) to genotype 773 Malagasy Y. pestis samples from 1995 to 2012. We mapped the locations where samples were obtained on a fine geographic scale to examine phylogeographic patterns through time. We identified 18 geographically separate and phylogenetically distinct subpopulations that display spatial and temporal stability, persisting in the same locations over a period of almost two decades. We found that geographic areas with higher levels of topographical relief are associated with greater levels of phylogenetic diversity and that sampling frequency can vary considerably among subpopulations and from year to year. We also found evidence of various Y. pestis dispersal events, including over long distances, but no evidence that any dispersal events resulted in successful establishment of a transferred genotype in a new location during the examined time period.. Our analysis suggests that persistent endemic cycles of Y. pestis transmission within local areas are responsible for the long term maintenance of plague in Madagascar, rather than repeated episodes of wide scale epidemic spread. Landscape likely plays a role in maintaining Y. pestis subpopulations in Madagascar, with increased topographical relief associated with increased levels of localized differentiation. Local ecological factors likely affect the dynamics of individual subpopulations and the associated likelihood of observing human plague cases in a given year in a particular location.

Topics: Endemic Diseases; Genome, Bacterial; Genotype; Humans; Madagascar; Phylogeography; Plague; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; Spatio-Temporal Analysis; Yersinia pestis

Topics: Cities; Disease Outbreaks; Humans; Madagascar; Plague

Topics: Anti-Bacterial Agents; Child; Disease Outbreaks; Global Health; Hemorrhagic Fever, Ebola; Humans; International Cooperation; Madagascar; Plague; World Health Organization

Prisons in Madagascar are at high risk of plague outbreak. Occurrence of plague epidemic in prisons can cause significant episode of urban plague through the movement of potentially infected humans, rodents and fleas. Rodent and flea controls are essential in plague prevention, by reducing human contact with plague reservoirs and vectors. Insecticide treatment is the key step available for the control of rat fleas which transmit the disease from infected rodents to human. The implementation of an adapted flea control strategy should rely on the insecticide susceptibility status of the targeted population. For the purpose of plague prevention campaign in prisons, we conducted insecticide resistance survey on Xenopsylla cheopis, the rat flea.. Fleas were collected on rats caught in six prisons of Madagascar. They were exposed to insecticide treated filter papers and mortality was recorded following World Health Organization protocol.. The fleas collected in the prisons had different resistance patterns, while a high level of resistance to insecticides tested was described in the Antanimora prison, located in the heart of Antananarivo, the capital of Madagascar.. This finding is alarming in the context of public health, knowing that the effectiveness of flea control could be jeopardized by insecticide resistance. In order to establish more accurate rat fleas control in prisons, the main recommendations are based on continuous monitoring insecticide susceptibility of flea, insecticide rotation, and the development of a new method for flea control.

Topics: Animals; Insect Vectors; Insecticide Resistance; Insecticides; Madagascar; Plague; Prisons; Risk; Xenopsylla

Identifying key reservoirs for zoonoses is crucial for understanding variation in incidence. Plague re-emerged in Mahajanga, Madagascar in the 1990s but there has been no confirmed case since 1999. Here we combine ecological and genetic data, from during and after the epidemics, with experimental infections to examine the role of the shrew Suncus murinus in the plague epidemiological cycle. The predominance of S. murinus captures during the epidemics, their carriage of the flea vector and their infection with Yersinia pestis suggest they played an important role in the maintenance and transmission of plague. S. murinus exhibit a high but variable resistance to experimental Y. pestis infections, providing evidence of its ability to act as a maintenance host. Genetic analyses of the strains isolated from various hosts were consistent with two partially-linked transmission cycles, with plague persisting within the S. murinus population, occasionally spilling over into the rat and human populations. The recent isolation from a rat in Mahajanga of a Y. pestis strain genetically close to shrew strains obtained during the epidemics reinforces this hypothesis and suggests circulation of plague continues. The observed decline in S. murinus and Xenopsylla cheopis since the epidemics appears to have decreased the frequency of spillover events to the more susceptible rats, which act as a source of infection for humans. Although this may explain the lack of confirmed human cases in recent years, the current circulation of plague within the city highlights the continuing health threat.

Topics: Animals; Disease Outbreaks; Disease Reservoirs; Humans; Insect Vectors; Madagascar; Plague; Rats; Shrews; Xenopsylla; Yersinia pestis; Zoonoses

Transmission potential and severity of pneumonic plague in Madagascar were assessed. Accounting for reporting delay, the reproduction number was estimated at 1.73. The case fatality risk was estimated as 5.5%. Expected numbers of exported cases from Madagascar were estimated across the world and all estimates were below 1 person from August to October, 2017.

Topics: Contact Tracing; Disease Outbreaks; Endemic Diseases; Epidemics; Female; Humans; Madagascar; Male; Plague; Population Surveillance; Yersinia pestis

Topics: Animals; Disease Outbreaks; Disease Vectors; Humans; Madagascar; Plague; Rats; Siphonaptera; Survival Analysis; Yersinia pestis

Topics: Epidemics; Forecasting; Hemorrhagic Fever, Ebola; Humans; Madagascar; Plague

Topics: Africa, Central; Algeria; Asia; Communicable Diseases, Emerging; Disease Outbreaks; Epidemics; Humans; Iran; Madagascar; Plague; United States

Genetic analysis of pathogenic organisms is a useful tool for linking human cases together and/or to potential environmental sources. The resulting data can also provide information on evolutionary patterns within a targeted species and phenotypic traits. However, the instruments often used to generate genotyping data, such as single nucleotide polymorphisms (SNPs), can be expensive and sometimes require advanced technologies to implement. This places many genotyping tools out of reach for laboratories that do not specialize in genetic studies and/or lack the requisite financial and technological resources. To address this issue, we developed a low cost and low tech genotyping system, termed agarose-MAMA, which combines traditional PCR and agarose gel electrophoresis to target phylogenetically informative SNPs.. To demonstrate the utility of this approach for generating genotype data in a resource-constrained area (Madagascar), we designed an agarose-MAMA system targeting previously characterized SNPs within Yersinia pestis, the causative agent of plague. We then used this system to genetically type pathogenic strains of Y. pestis in a Malagasy laboratory not specialized in genetic studies, the Institut Pasteur de Madagascar (IPM). We conducted rigorous assay performance validations to assess potential variation introduced by differing research facilities, reagents, and personnel and found no difference in SNP genotyping results. These agarose-MAMA PCR assays are currently employed as an investigative tool at IPM, providing Malagasy researchers a means to improve the value of their plague epidemiological investigations by linking outbreaks to potential sources through genetic characterization of isolates and to improve understanding of disease ecology that may contribute to a long-term control effort.. The success of our study demonstrates that the SNP-based genotyping capacity of laboratories in developing countries can be expanded with manageable financial cost for resource constraint laboratories. This is a practical formula that reduces resource-driven limitations to genetic research and promises to advance global collective knowledge of infectious diseases emanating from resource limited regions of the world.

Topics: Costs and Cost Analysis; Electrophoresis, Agar Gel; Genotyping Techniques; Health Resources; Humans; Madagascar; Plague; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Yersinia pestis

Fipronil was evaluated as a systemic control agent for the rat flea Xenopsylla cheopis (Rothschild), the main vector of Yersinia pestis (Yersin), the causative agent of plague, in Madagascar. The effectiveness of fipronil as a systemic control agent against X. cheopis was assessed by determining the toxicity values of the "Lethal Dose 50" (LD50). Two techniques were used to evaluate the systemic action of the insecticide on the vector: 1) an artificial feeding device filled with blood-fipronil mixture from which X. cheopis was fed and 2) rodent hosts, Rattus norvegicus (Berkenhout) and Rattus rattus (L.), which fed on fipronil-treated bait. As a standardized control method, the susceptibility of X. cheopis to fipronil was evaluated by exposure to impregnated paper within World Health Organization (WHO) insecticide test protocol to compare its effect to the systemic activity of the studied insecticide. Results showed that when administered in a systemic way, fipronil appears to be more effective: the toxicity level was evaluated to be ninefold higher compared with the WHO test. Compared with other methods, which require indiscriminate dusting of rodent burrows and human dwellings, fipronil applied in a systemic way enables the direct targeting of the plague vector. Thus, this method appears to be a superior alternative to fipronil-dusting for the control of the main plague vector in Madagascar. However, subsequent tests in the field are necessary to confirm the suitability of fipronil administration in a systemic way on large scales.

Topics: Animals; Humans; Insect Control; Insect Vectors; Insecticides; Madagascar; Plague; Pyrazoles; Rats; Xenopsylla; Yersinia pestis

During a pneumonic plague outbreak in Moramanga, Madagascar, we identified 4 confirmed, 1 presumptive, and 9 suspected plague case-patients. Human-to-human transmission among close contacts was high (reproductive number 1.44) and the case fatality rate was 71%. Phylogenetic analysis showed that the Yersinia pestis isolates belonged to group q3, different from the previous outbreak.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Contact Tracing; Female; Humans; Madagascar; Male; Middle Aged; Plague; Yersinia pestis; Young Adult

Plague is a rodent disease transmissible to humans by infected flea bites, and Madagascar is one of the countries with the highest plague incidence in the world. This study reports the susceptibility of the main plague vector Xenopsylla cheopis to 12 different insecticides belonging to 4 insecticide families (carbamates, organophosphates, pyrethroids and organochlorines). Eight populations from different geographical regions of Madagascar previously resistant to deltamethrin were tested with a World Health Organization standard bioassay. Insecticide susceptibility varied amongst populations, but all of them were resistant to six insecticides belonging to pyrethroid and carbamate insecticides (alphacypermethrin, lambdacyhalothrin, etofenprox, deltamethrin, bendiocarb and propoxur). Only one insecticide (dieldrin) was an efficient pulicide for all flea populations. Cross resistances were suspected. This study proposes at least three alternative insecticides (malathion, fenitrothion and cyfluthrin) to replace deltamethrin during plague epidemic responses, but the most efficient insecticide may be different for each population studied. We highlight the importance of continuous insecticide susceptibility surveillance in the areas of high plague risk in Madagascar.

Topics: Animals; Female; Humans; Insect Vectors; Insecticides; Madagascar; Male; Parasitic Sensitivity Tests; Plague; Xenopsylla

Plague, a zoonosis caused by Yersinia pestis, is found in Asia, the Americas but mainly in Africa, with the island of Madagascar reporting almost one third of human cases worldwide. In the highlands of Madagascar, plague is transmitted predominantly by two flea species which coexist on the island, but differ in their distribution. The endemic flea, Synopsyllus fonquerniei, dominates flea communities on rats caught outdoors, while the cosmopolitan flea, Xenopsylla cheopis, is found mostly on rats caught in houses. Additionally S. fonquerniei seems restricted to areas above 800 m. Climatic constraints on the development of the two main vectors of plague could explain the differences in their distribution and the seasonal changes in their abundance. Here we present the first study on effects of temperature and relative humidity on the immature stages of both vector species.. We examined the two species' temperature and humidity requirements under experimental conditions at five different temperatures and two relative humidities. By employing multivariate and survival analysis we established the impact of temperature and relative humidity on development times and survival for both species. Using degree-day analysis we then predicted the average developmental threshold for larvae to reach pupation and for pupae to complete development under each treatment. This analysis was undertaken separately for the two relative humidities and for the two species.. Development times and time to death differed significantly, with the endemic S. fonquerniei taking on average 1.79 times longer to complete development and having a shorter time to death than X. cheopis under adverse conditions with high temperature and low humidity. Temperature had a significant effect on the development times of flea larvae and pupae. While humidity did not affect the development times of either species, it did influence the time of death of S. fonquerniei. Using degree-day analysis we estimated an average developmental threshold of 9 °C for S. fonquerniei, and 12.5 °C for X. cheopis.. While many vector-borne diseases are limited to warm, low-lying regions, plague in Madagascar is unusual in being most prevalent in the cool, highland regions of the country. Our results point towards the possibility that this is because the endemic flea vector, S. fonquerniei, is better adapted to cool temperatures than the exotic flea vector, X. cheopis. Future warming caused by climate change might reduce the area suitable for S. fonquerniei and may thus reduce the incidence of plague in Madagascar.

Topics: Animals; Environmental Exposure; Humans; Insect Vectors; Madagascar; Plague; Rats; Siphonaptera; Survival Analysis

Topics: Adult; Americas; Disease Outbreaks; Female; Humans; Influenza A virus; Influenza, Human; Lassa Fever; Madagascar; Male; Nigeria; Plague; Zika Virus Infection

Plague has been responsible for two major historic pandemics (6th-8th century CE; 14th-19th century CE) and a modern one. The recent Malagasy plague outbreaks raised new concerns on the deadly potential of the plague-causing bacteria Yersinia pestis. Between September 2014 and April 2015, outbreaks of bubonic and pneumonic plague hit the Malagasy population. Two hundred and sixty-three cases, including 71 deaths, have been reported in 16 different districts with a case fatality rate of 27%. The scope of our study was to ascertain whether the risk factors for health in modern-day populations exposed to plague and in ancient populations that faced the two historic pandemics varied or remained substantially unaltered.. The risk of mortality of the Malagasy population with those obtained from the reconstruction of three samples of European populations exposed to the historic pandemics was contrasted.. The evidence shows that the risks of death are not uniform across age neither in modern nor in historic populations exposed to plague and shows precise concentrations in specific age groups (children between five and nine years of age and young adults).. Although in the post-antibiotic era, the fatality rates have drastically reduced, both modern and historic populations were exposed to the same risk factors that are essentially represented by a low standard of environmental hygiene, poor nutrition, and weak health systems.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Europe; Female; History, 15th Century; History, 16th Century; History, 17th Century; History, 18th Century; History, 19th Century; History, Medieval; Humans; Infant; Infant, Newborn; Madagascar; Male; Middle Aged; Mortality; Plague; Risk Factors; Survival Analysis; Yersinia pestis; Young Adult

Topics: Animals; Humans; Insect Vectors; Madagascar; Plague; Rodentia; Xenopsylla; Yersinia pestis

Plague is an infectious disease caused by the bacterium Yersinia pestis, which, during the fourteenth century, caused the deaths of an estimated 75-200 million people in Europe. Plague epidemics still occur in Africa, Asia and South America. Madagascar is today one of the most endemic countries, reporting nearly one third of the human cases worldwide from 2004 to 2009. The persistence of plague in Madagascar is associated with environmental and climatic conditions. In this paper we present a case study of the spatio-temporal analysis of plague incidence in Madagascar from 1980 to 2007. We study the relationship of plague with temperature and precipitation anomalies, and with elevation. A joint spatio-temporal analysis of the data proves to be computationally intractable. We therefore develop a spatio-temporal log-Gaussian Cox process model, but then carry out marginal temporal and spatial analyses. We also introduce a spatially discrete approximation for Gaussian processes, whose parameters retain a spatially continuous interpretation. We find evidence of a cumulative effect, over time, of temperature anomalies on plague incidence, and of a very high relative risk of plague occurrence for locations above 800 m in elevation. Our approach provides a useful modeling framework to assess the relationship between exposures and plague risk, irrespective of the spatial resolution at which the latter has been recorded.

Topics: Humans; Incidence; Madagascar; Plague; Spatio-Temporal Analysis

Yersinia pestis, the causative agent of plague, is endemic to Madagascar, particularly to the central highlands. Although plague has not been previously reported in northern Madagascar, an outbreak of pneumonic plague occurred in this remote area in 2011. Over a 27-day period, 17 suspected, 2 presumptive, and 3 confirmed human cases were identified, and all 15 untreated 20 patients died. Molecular typing of Y. pestis isolated from 2 survivors and 5 Rattus rattus rat samples identified the Madagascar-specific 1.ORI3-k single-nucleotide polymorphism genotype and 4 clustered regularly interspaced short palindromic repeat patterns. This outbreak had a case-fatality rate of 100% for nontreated patients. The Y. pestis 1.ORI3-k single-nucleotide polymorphism genotype might cause larger epidemics. Multidrug-resistant strains and persistence of the pathogen in natural foci near human settlements pose severe risks to populations in plague-endemic regions and require outbreak response strategies.

Topics: Adolescent; Animals; Base Sequence; Contact Tracing; Disease Outbreaks; Endemic Diseases; Female; Genes, Bacterial; Humans; Madagascar; Male; Molecular Typing; Plague; Polymorphism, Single Nucleotide; Rats; Yersinia pestis

Topics: Epidemics; Geography, Medical; Humans; Madagascar; Plague; Socioeconomic Factors; Yersinia pestis

Yersinia pestis is the causative agent of human plague and is endemic in various African, Asian and American countries. In Madagascar, the disease represents a significant public health problem with hundreds of human cases a year. Unfortunately, poor infrastructure makes outbreak investigations challenging.. DNA was extracted directly from 93 clinical samples from patients with a clinical diagnosis of plague in Madagascar in 2007. The extracted DNAs were then genotyped using three molecular genotyping methods, including, single nucleotide polymorphism (SNP) typing, multi-locus variable-number tandem repeat analysis (MLVA), and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) analysis. These methods provided increasing resolution, respectively. The results of these analyses revealed that, in 2007, ten molecular groups, two newly described here and eight previously identified, were responsible for causing human plague in geographically distinct areas of Madagascar.. Plague in Madagascar is caused by numerous distinct types of Y. pestis. Genotyping method choice should be based upon the discriminatory power needed, expense, and available data for any desired comparisons. We conclude that genotyping should be a standard tool used in epidemiological investigations of plague outbreaks.

Topics: Clustered Regularly Interspaced Short Palindromic Repeats; Genotype; Humans; Madagascar; Multilocus Sequence Typing; Phylogeny; Plague; Polymorphism, Single Nucleotide; Yersinia pestis

Topics: Budgets; Female; Health Expenditures; Health Services; Health Services Accessibility; HIV Infections; Humans; Madagascar; Malaria; Male; Plague; Poliomyelitis; Politics

Topics: Animals; Disease Outbreaks; Female; Humans; Madagascar; Male; Molecular Sequence Data; Plague; Siphonaptera; Yersinia pestis

Plague, a zoonosis caused by Yersinia pestis, is found in Asia and the Americas, but predominantly in Africa, with the island of Madagascar reporting almost one third of human cases worldwide. Plague's occurrence is affected by local climate factors which in turn are influenced by large-scale climate phenomena such as the El Niño Southern Oscillation (ENSO). The effects of ENSO on regional climate are often enhanced or reduced by a second large-scale climate phenomenon, the Indian Ocean Dipole (IOD). It is known that ENSO and the IOD interact as drivers of disease. Yet the impacts of these phenomena in driving plague dynamics via their effect on regional climate, and specifically contributing to the foci of transmission on Madagascar, are unknown. Here we present the first analysis of the effects of ENSO and IOD on plague in Madagascar.. We use a forty-eight year monthly time-series of reported human plague cases from 1960 to 2008. Using wavelet analysis, we show that over the last fifty years there have been complex non-stationary associations between ENSO/IOD and the dynamics of plague in Madagascar. We demonstrate that ENSO and IOD influence temperature in Madagascar and that temperature and plague cycles are associated. The effects on plague appear to be mediated more by temperature, but precipitation also undoubtedly influences plague in Madagascar. Our results confirm a relationship between plague anomalies and an increase in the intensity of ENSO events and precipitation.. This work widens the understanding of how climate factors acting over different temporal scales can combine to drive local disease dynamics. Given the association of increasing ENSO strength and plague anomalies in Madagascar it may in future be possible to forecast plague outbreaks in Madagascar. The study gives insight into the complex and changing relationship between climate factors and plague in Madagascar.

Topics: Climate; El Nino-Southern Oscillation; Humans; Incidence; Madagascar; Plague; Seasons

The incidence of bubonic plague in Madagascar is high. This study reports the susceptibility of 32 different populations of a vector, the flea Xenopsylla cheopis (Siphonaptera: Pulicidae), to the insecticide Deltamethrin. Despite the use of Deltamethrin against fleas, plague epidemics have re-emerged in Madagascar. The majority of the study sites were located in the Malagasy highlands where most plague cases have occurred over the last 10 years. X. cheopis fleas were tested for susceptibility to Deltamethrin (0.05%): only two populations were susceptible to Deltamethrin, four populations were tolerant and 26 populations were resistant. KD50 (50% Knock-Down) and KD90 (90% Knock-Down) times were determined, and differed substantially from 9.4 to 592.4 minutes for KD50 and 10.4 min to 854.3 minutes for KD90. Susceptibility was correlated with latitude, but not with longitude, history of insecticide use nor date of sampling. Combined with the number of bubonic plague cases, our results suggest that an immediate switch to an insecticide other than Deltamethrin is required for plague vector control in Madagascar.

Topics: Animals; Flea Infestations; Insecticide Resistance; Insecticides; Lethal Dose 50; Madagascar; Nitriles; Plague; Pyrethrins; Rats; Rodent Diseases; Xenopsylla

A cluster of human plague cases occurred in the seaport city of Mahajanga, Madagascar, from 1991 to 1999 following 62 years with no evidence of plague, which offered insights into plague pathogen dynamics in an urban environment. We analyzed a set of 44 Mahajanga isolates from this 9-year outbreak, as well as an additional 218 Malagasy isolates from the highland foci. We sequenced the genomes of four Mahajanga strains, performed whole-genome sequence single-nucleotide polymorphism (SNP) discovery on those strains, screened the discovered SNPs, and performed a high-resolution 43-locus multilocus variable-number tandem-repeat analysis of the isolate panel. Twenty-two new SNPs were identified and defined a new phylogenetic lineage among the Malagasy isolates. Phylogeographic analysis suggests that the Mahajanga lineage likely originated in the Ambositra district in the highlands, spread throughout the northern central highlands, and was then introduced into and became transiently established in Mahajanga. Although multiple transfers between the central highlands and Mahajanga occurred, there was a locally differentiating and dominant subpopulation that was primarily responsible for the 1991-to-1999 Mahajanga outbreaks. Phylotemporal analysis of this Mahajanga subpopulation revealed a cycling pattern of diversity generation and loss that occurred during and after each outbreak. This pattern is consistent with severe interseasonal genetic bottlenecks along with large seasonal population expansions. The ultimate extinction of plague pathogens in Mahajanga suggests that, in this environment, the plague pathogen niche is tenuous at best. However, the temporary large pathogen population expansion provides the means for plague pathogens to disperse and become ecologically established in more suitable nonurban environments.. Maritime spread of plague led to the global dissemination of this disease and affected the course of human history. Multiple historical plague waves resulted in massive human mortalities in three classical plague pandemics: Justinian (6th and 7th centuries), Middle Ages (14th to 17th centuries), and third (mid-1800s to the present). Key to these events was the pathogen's entry into new lands by "plague ships" via seaport cities. Although initial disease outbreaks in ports were common, they were almost never sustained for long and plague pathogens survived only if they could become established in ecologically suitable habitats. Although plague pathogens' ability to invade port cities has been essential for intercontinental spread, these regions have not proven to be a suitable long-term niche. The disease dynamics in port cities such as Mahajanga are thus critical to plague pathogen amplification and dispersal into new suitable ecological niches for the observed global long-term maintenance of plague pathogens.

Topics: Animals; Cluster Analysis; DNA, Bacterial; Genome, Bacterial; Genotype; Humans; Madagascar; Minisatellite Repeats; Molecular Epidemiology; Molecular Sequence Data; Molecular Typing; Pandemics; Phylogeny; Plague; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; Yersinia pestis

Although bubonic plague is an endemic zoonosis in many countries around the world, the factors responsible for the persistence of this highly virulent disease remain poorly known. Classically, the endemic persistence of plague is suspected to be due to the coexistence of plague resistant and plague susceptible rodents in natural foci, and/or to a metapopulation structure of reservoirs. Here, we test separately the effect of each of these factors on the long-term persistence of plague. We analyse the dynamics and equilibria of a model of plague propagation, consistent with plague ecology in Madagascar, a major focus where this disease is endemic since the 1920s in central highlands. By combining deterministic and stochastic analyses of this model, and including sensitivity analyses, we show that (i) endemicity is favoured by intermediate host population sizes, (ii) in large host populations, the presence of resistant rats is sufficient to explain long-term persistence of plague, and (iii) the metapopulation structure of susceptible host populations alone can also account for plague endemicity, thanks to both subdivision and the subsequent reduction in the size of subpopulations, and extinction-recolonization dynamics of the disease. In the light of these results, we suggest scenarios to explain the localized presence of plague in Madagascar.

Topics: Animals; Computer Simulation; Disease Resistance; Ecology; Endemic Diseases; Fertility; Madagascar; Markov Chains; Models, Biological; Plague; Rats; Siphonaptera

Landscape may affect the distribution of infectious diseases by influencing the population density and dispersal of hosts and vectors. Plague (Yersinia pestis infection) is a highly virulent, re-emerging disease, the ecology of which has been scarcely studied in Africa. Human seroprevalence data for the major plague focus of Madagascar suggest that plague spreads heterogeneously across the landscape as a function of the relief. Plague is primarily a disease of rodents. We therefore investigated the relationship between disease distribution and the population genetic structure of the black rat, Rattus rattus, the main reservoir of plague in Madagascar.. We conducted a comparative study of plague seroprevalence and genetic structure (15 microsatellite markers) in rat populations from four geographic areas differing in topology, each covering about 150-200 km(2) within the Madagascan plague focus. The seroprevalence levels in the rat populations mimicked those previously reported for humans. As expected, rat populations clearly displayed a more marked genetic structure with increasing relief. However, the relationship between seroprevalence data and genetic structure differs between areas, suggesting that plague distribution is not related everywhere to the effective dispersal of rats.. Genetic diversity estimates suggested that plague epizootics had only a weak impact on rat population sizes. In the highlands of Madagascar, plague dissemination cannot be accounted for solely by the effective dispersal of the reservoir. Human social activities may also be involved in spreading the disease in rat and human populations.

Topics: Animals; Genetic Variation; Genetics, Population; Madagascar; Plague; Population Density; Rats; Rodent Diseases; Seroepidemiologic Studies; Topography, Medical; Yersinia pestis

Genome scans using amplified fragment length polymorphism (AFLP) markers became popular in nonmodel species within the last 10 years, but few studies have tried to characterize the anonymous outliers identified. This study follows on from an AFLP genome scan in the black rat (Rattus rattus), the reservoir of plague (Yersinia pestis infection) in Madagascar. We successfully sequenced 17 of the 22 markers previously shown to be potentially affected by plague-mediated selection and associated with a plague resistance phenotype. Searching these sequences in the genome of the closely related species Rattus norvegicus assigned them to 14 genomic regions, revealing a random distribution of outliers in the genome (no clustering). We compared these results with those of an in silico AFLP study of the R. norvegicus genome, which showed that outlier sequences could not have been inferred by this method in R. rattus (only four of the 15 sequences were predicted). However, in silico analysis allowed the prediction of AFLP markers distribution and the estimation of homoplasy rates, confirming its potential utility for designing AFLP studies in nonmodel species. The 14 genomic regions surrounding AFLP outliers (less than 300 kb from the marker) contained 75 genes encoding proteins of known function, including nine involved in immune function and pathogen defence. We identified the two interleukin 1 genes (Il1a and Il1b) that share homology with an antigen of Y. pestis, as the best candidates for genes subject to plague-mediated natural selection. At least six other genes known to be involved in proinflammatory pathways may also be affected by plague-mediated selection.

Topics: Amplified Fragment Length Polymorphism Analysis; Animals; Disease Resistance; Genetic Loci; Genomics; Madagascar; Plague; Rats; Selection, Genetic; Yersinia pestis

Yersinia pestis is the causative agent of plague, a fulminant disease that is often fatal without antimicrobial treatment. Plasmid (IncA/C)-mediated multidrug resistance in Y. pestis was reported in 1995 in Madagascar and has generated considerable public health concern, most recently because of the identification of IncA/C multidrug-resistant plasmids in other zoonotic pathogens. Here, we demonstrate no resistance in 392 Y. pestis isolates from 17 countries to eight antimicrobials used for treatment or prophylaxis of plague.

Topics: Africa; Americas; Animals; Anti-Bacterial Agents; Asia; Drug Resistance, Bacterial; Humans; Madagascar; Microbial Sensitivity Tests; Phylogeography; Plague; Plasmids; Public Health; Siphonaptera; Yersinia pestis

Plague (Yersinia pestis infection) is a highly virulent rodent disease that persists in many natural ecosystems. The black rat (Rattus rattus) is the main host involved in the plague focus of the central highlands of Madagascar. Black rat populations from this area are highly resistant to plague, whereas those from areas in which the disease is absent (low altitude zones of Madagascar) are susceptible. Various lines of evidence suggest a role for the Major Histocompatibility Complex (MHC) in plague resistance. We therefore used the MHC region as a candidate for detecting signatures of plague-mediated selection in Malagasy black rats, by comparing population genetic structures for five MHC-linked microsatellites and neutral markers in two sampling designs. We first compared four pairs of populations, each pair including one population from the plague focus and one from the disease-free zone. Plague-mediated selection was expected to result in greater genetic differentiation between the two zones than expected under neutrality and this was observed for one MHC-class I-linked locus (D20Img2). For this marker as well as for four other MHC-linked loci, a geographic pattern of genetic structure was found at local scale within the plague focus. This pattern would be expected if plague selection pressures were spatially variable. Finally, another MHC-class I-linked locus (D20Rat21) showed evidences of balancing selection, but it seems more likely that this selection would be related to unknown pathogens more widely distributed in Madagascar than plague.

Topics: Animals; Disease Resistance; Evolution, Molecular; Genetic Loci; Genetic Markers; Histocompatibility Antigens; Madagascar; Microsatellite Repeats; Plague; Rats; Selection, Genetic

Plague is endemic within the central highlands of Madagascar, where its main reservoir is the black rat, Rattus rattus. Typically this species is considered susceptible to plague, rapidly dying after infection inducing the spread of infected fleas and, therefore, dissemination of the disease to humans. However, persistence of transmission foci in the same area from year to year, supposes mechanisms of maintenance among which rat immune responses could play a major role. Immunity against plague and subsequent rat survival could play an important role in the stabilization of the foci. In this study, we aimed to investigate serological responses to plague in wild black rats from endemic areas of Madagascar. In addition, we evaluate the use of a recently developed rapid serological diagnostic test to investigate the immune response of potential reservoir hosts in plague foci.. We experimentally infected wild rats with Yersinia pestis to investigate short and long-term antibody responses. Anti-F1 IgM and IgG were detected to evaluate this antibody response. High levels of anti-F1 IgM and IgG were found in rats one and three weeks respectively after challenge, with responses greatly differing between villages. Plateau in anti-F1 IgM and IgG responses were reached for as few as 500 and 1500 colony forming units (cfu) inoculated respectively. More than 10% of rats were able to maintain anti-F1 responses for more than one year. This anti-F1 response was conveniently followed using dipsticks.. Inoculation of very few bacteria is sufficient to induce high immune response in wild rats, allowing their survival after infection. A great heterogeneity of rat immune responses was found within and between villages which could heavily impact on plague epidemiology. In addition, results indicate that, in the field, anti-F1 dipsticks are efficient to investigate plague outbreaks several months after transmission.

Topics: Animals; Animals, Wild; Autoantibodies; Disease Reservoirs; Enzyme-Linked Immunosorbent Assay; Female; Immunoglobulin G; Immunoglobulin M; Madagascar; Male; Plague; Rats; Yersinia pestis

Plague was introduced to Madagascar in 1898 and continues to be a significant human health problem. It exists mainly in the central highlands, but in the 1990s was reintroduced to the port city of Mahajanga, where it caused extensive human outbreaks. Despite its prevalence, the phylogeography and molecular epidemiology of Y. pestis in Madagascar has been difficult to study due to the great genetic similarity among isolates. We examine island-wide geographic-genetic patterns based upon whole-genome discovery of SNPs, SNP genotyping and hypervariable variable-number tandem repeat (VNTR) loci to gain insight into the maintenance and spread of Y. pestis in Madagascar.. We analyzed a set of 262 Malagasy isolates using a set of 56 SNPs and a 43-locus multi-locus VNTR analysis (MLVA) system. We then analyzed the geographic distribution of the subclades and identified patterns related to the maintenance and spread of plague in Madagascar. We find relatively high levels of VNTR diversity in addition to several SNP differences. We identify two major groups, Groups I and II, which are subsequently divided into 11 and 4 subclades, respectively. Y. pestis appears to be maintained in several geographically separate subpopulations. There is also evidence for multiple long distance transfers of Y. pestis, likely human mediated. Such transfers have resulted in the reintroduction and establishment of plague in the port city of Mahajanga, where there is evidence for multiple transfers both from and to the central highlands.. The maintenance and spread of Y. pestis in Madagascar is a dynamic and highly active process that relies on the natural cycle between the primary host, the black rat, and its flea vectors as well as human activity.

Topics: Analysis of Variance; Cluster Analysis; DNA, Bacterial; Humans; Madagascar; Minisatellite Repeats; Molecular Epidemiology; Molecular Typing; Phylogeography; Plague; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Yersinia pestis

In Madagascar, the black rat, Rattus rattus, is the main reservoir of plague (Yersinia pestis infection), a disease still responsible for hundreds of cases each year in this country. This study used experimental plague challenge to assess susceptibility in wild-caught rats to better understand how R. rattus can act as a plague reservoir. An important difference in plague resistance between rat populations from the plague focus (central highlands) and those from the plague-free zone (low altitude area) was confirmed to be a widespread phenomenon. In rats from the plague focus, we observed that sex influenced plague susceptibility, with males slightly more resistant than females. Other individual factors investigated (weight and habitat of sampling) did not affect plague resistance. When infected at high bacterial dose (more than 10⁵ bacteria injected), rats from the plague focus died mainly within 3-5 days and produced specific antibodies, whereas after low-dose infection (< 5,000 bacteria), delayed mortality was observed and surviving seronegative rats were not uncommon. These results concerning plague resistance level and the course of infection in the black rat would contribute to a better understanding of plague circulation in Madagascar.

Topics: Animals; Antibodies, Bacterial; Disease Models, Animal; Disease Reservoirs; Enzyme-Linked Immunosorbent Assay; Female; Madagascar; Male; Plague; Rats; Sex Factors; Survival Analysis; Yersinia pestis

Madagascar remains one of the world's largest plague foci. The black rat, Rattus rattus, is the main reservoir of plague in rural areas. This species is highly susceptible to plague in plague-free areas (low-altitude regions), whereas rats from the plague focus areas (central highlands) have evolved a disease-resistance polymorphism. We used the candidate gene CCR5 to investigate the genetic basis of plague resistance in R. rattus. We found a unique non-synonymous substitution (H184R) in a functionally important region of the gene. We then compared (i) CCR5 genotypes of dying and surviving plague-challenged rats and (ii) CCR5 allelic frequencies in plague focus and plague-free populations. Our results suggested a higher prevalence of the substitution in resistant animals compared to susceptible individuals, and a tendency for higher frequencies in plague focus areas compared to plague-free areas. Therefore, the CCR5 polymorphism may be involved in Malagasy black rat plague resistance. CCR5 and other undetermined plague resistance markers may provide useful biological information about host evolution and disease dynamics.

Topics: Analysis of Variance; Animals; Disease Reservoirs; Immunity, Innate; Madagascar; Plague; Polymorphism, Genetic; Rats; Receptors, CCR5; Rodent Diseases; Yersinia pestis

The transmission potential of primary pneumonic plague, caused by Yersinia pestis, is one of the key epidemiological determinants of a potential biological weapon, and requires clarification and time dependent interpretation.. This study estimated the reproduction number and its time dependent change through investigations of outbreaks in Mukden, China (1946), and Madagascar (1957). Reconstruction of an epidemic tree, which shows who infected whom, from the observed dates of onset was performed using the serial interval. Furthermore, a likelihood based approach was used for the time inhomogeneous evaluation of the outbreaks for which there was scarcity of cases.. According to the estimates, the basic reproduction number, R(0), was on the order of 2.8 to 3.5, which is higher than previous estimates. The lower 95% confidence intervals of R(0) exceeded unity. The effective reproduction number declined below unity after control measures were introduced in Mukden, and before the official implementation in Madagascar.. While the time course of the latter outbreak could be explained by intrinsic factors and stochasticity in this remote and scarcely populated area, the former in Mukden suggests the possible continued chains of transmission in highly populated areas. Using the proposed methods, the who infected whom information permitted the evaluation of the time inhomogeneous transmission potential in relation to public health measures. The study also tackles the problem of statistical estimation of R(0) based on similar information, which was previously performed simply by counting the number of secondary transmissions regardless of time.

Topics: China; Disease Outbreaks; Epidemiologic Methods; Humans; Madagascar; Plague; Time Factors

To describe the principal characteristics and epidemiological trends for human plague in modern times based on the largest reported series of cases from the highly active Malagasy focus.. We used a file of 20,900 notified cases of suspected plague, 4,473 of which were confirmed or probable, to carry out a statistical analysis of incidence and mortality rates and associated factors for 5-year periods from 1957 to 2001.. Our analysis of trends showed (1) an increase in the incidence rate and the number of districts affected, (2) an increase in the proportion of bubonic forms (64.8-96.8%) at the expense of the pneumonic forms (35.2-3.2%) more frequent in elderly subjects and (3) a decrease in case fatality rate (CFR, 55.7-20.9%) associated with five factors: clinical form, season, province, urban/rural and period considered. The median age of patients was 14 years and more men than women were affected.. Since the end of the 1980s, the incidence of plague in Madagascar has increased in both rural and urban areas, because of multiple socioeconomic and environmental factors. However, the plague mortality rate has tended to decrease, together with the frequency of pneumonic forms, because of the strengthening of control measures. Making dipstick tests for the rapid diagnosis of human cases and epizootics in rats available for health structures should make it possible to raise the alarm and to react rapidly, thereby further decreasing morbidity and CFR.

Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Health Surveys; Humans; Incidence; Infant; Madagascar; Male; Middle Aged; Plague; Risk Factors; Seasons; Sex Distribution

Topics: Humans; Madagascar; Plague; Reagent Kits, Diagnostic

Plague is often fatal without prompt and appropriate treatment. It affects mainly poor and remote populations. Late diagnosis is one of the major causes of human death and spread of the disease, since it limits the effectiveness of control measures. We aimed to develop and assess a rapid diagnostic test (RDT) for plague.. We developed a test that used monoclonal antibodies to the F1 antigen of Yersinia pestis. Sensitivity and specificity were assessed with a range of bacterial cultures and clinical samples, and compared with findings from available ELISA and bacteriological tests for plague. Samples from patients thought to have plague were tested with the RDT in the laboratory and by health workers in 26 pilot sites in Madagascar.. The RDT detected concentrations of F1 antigen as low as 0.5 ng/mL in up to 15 min, and had a shelf life of 21 days at 60 degrees C. Its sensitivity and specificity were both 100%. RDT detected 41.6% and 31% more positive clinical specimens than did bacteriological methods and ELISA, respectively. The agreement rate between tests done at remote centres and in the laboratory was 89.8%. With the combination of bacteriological methods and F1 ELISA as reference standard, the positive and negative predictive values of the RDT were 90.6% and 86.7%, respectively.. Our RDT is a specific, sensitive, and reliable test that can easily be done by health workers at the patient's bedside, for the rapid diagnosis of pneumonic and bubonic plague. This test will be of key importance for the control of plague in endemic countries.

Topics: Antibodies, Monoclonal; Enzyme-Linked Immunosorbent Assay; Humans; Madagascar; Plague; Reagent Kits, Diagnostic; Sensitivity and Specificity; Sputum; Time Factors; Yersinia pestis

Topics: Animals; Disease Outbreaks; Disease Susceptibility; Disease Vectors; Madagascar; Plague; Rats; Rodent Diseases; Siphonaptera; Urban Population

The foundations of local health services in Madagascar were laid when the island was taken over by the French in 1896. Medical care was a major priority for the first colonial governor named General Galliéni. Local health services expanded greatly from 1896 to 1950 thanks notably to institutions such as the Tananarive Medical School and Pasteur Institute. These services played a crucial role in the fight against smallpox and bubonic plague. However they were also used for political purposes by both colonial and independent governments. In sum the history of local health services in Madagascar can be described as a battle between political power and scientific knowledge. The overall result is positive for some and controversial for others.

Topics: France; Health Services, Indigenous; History, 19th Century; History, 20th Century; Humans; Madagascar; Plague; Politics; Smallpox

Topics: Chromatography; Diagnosis, Differential; Humans; Immunoassay; Madagascar; Plague; Time Factors

A method associating an anticoagulant rodenticide and an insecticide called Kartman bait-box aimed both at fighting reservoir and vectors of plague. It was evaluated in two neighbourhoods of Antananarivo (Madagascar) from October 2002 to May 2003. It involved the local community in the control. The study was carried out in Ambodirano-Ampefiloha refered as treated neighbourhood in which the Kartman bait box were laid out with an anticoagulant rodenticide and an insecticide with a rapid action versus a "pilot neighbourhood", Ankorondrano-Andranomahery in which the boxes were provided with non poisoning bait and non insecticidal white powder. The rodenticide used was Baraki (difethialone 25 ppm) and the insecticide was a powder of Propoxur 3%. The evaluation of effectiveness of this method was based on the four following parameters: (1) the number of dead rats collected daily inside and in the vicinity of the houses, (2) the daily number of baits non consumed in the Kartman bait box, (3) the cheopis index of the rats trapped using the BTS trap, and (4) the flea carrier index of the rats captured monthly with BTS trap. The cheopis index and the flea carrier index of the rats were calculated monthly. The number of rats that died in the treated neighbourhood was of 968 versus 3 in the pilot neighbourhood. The other parameters reached a stable level after 3 months. Between days 120 and 180, the mean number of unconsumed baits was 2.79 in the treated neighbourhood versus 0.14 in the pilot neighbourhood, the flea carriage (percentage of parasitized hosts) was 0% versus 61% in the pilot neighbourhood, and the cheopis index was 0.0 versus 5.0 in the pilot neighbourhood. This study demonstrates that Kartman bait-boxes reached the rat borne and the vectors of plague found in urban area. We propose to use this method extensively both during epidemic and inter-epidemic contexts.

Topics: 4-Hydroxycoumarins; Animals; Disease Reservoirs; Disease Vectors; Endemic Diseases; Equipment Design; Humans; Insect Control; Insect Vectors; Insecticides; Madagascar; Pilot Projects; Plague; Population Density; Poverty Areas; Propoxur; Rodent Control; Rodenticides; Siphonaptera; Time Factors; Urban Health

The first case of plague was introduced in Madagascar in 1898 in the east coast by way of boat from India. In 1921, plague reach the highlands and a large epidemic over the next twenty years. Until the beginning of the 80's, only of few case were identified, notified mostly in rural setting. However gradually it has re-emerged as a public health problem. Urban plague is located in the city of Antananarivo (resurgence in 1978 after 28 years of apparent silence) and in Mahajanga port (resurgence in 1991 after 63 years of silence). The reactivation of the Plague National Control Program from 1994 will allow better surveillance. The aim of this analysis is to update the epidemiological data on human plague in Madagascar based on reported cases obtained from the Central Lab of the Pasteur Institute of Madagascar from 1980 to 2001 (16,928 suspected cases of which 3,500 are likely positives or confirmed positives). The Plague season runs from October to March on the central highlands and July to November on the north-western coast. Sex-ratio male/female is 1.3/1, and the age-group of 5 to 25 years is more affected. The case fatality rate was 40% in the beginning of the 1980's, and decreased to 20% by the end of the 1990's. The percentage of case with pulmonary plague decrease from 15% to less than 5%. However, geographical extension is demonstrated: 4 districts in 1980, 30 districts in 1999 and 21 districts in 2001. In 2002, the diffusion of a new rapid test (reagent strip) in the primary health centres (CSB) in 42 endemic districts may help to decrease the morbidity and the letality due to plague and improve its control at the national level.

Topics: Adolescent; Adult; Age Distribution; Child; Child, Preschool; Disease Notification; Disease Outbreaks; Female; Humans; Incidence; Madagascar; Male; Middle Aged; Morbidity; Plague; Population Surveillance; Reagent Strips; Rural Health; Seasons; Sex Distribution; Urban Health

From 1995 to 1998, outbreaks of bubonic plague occurred annually in the coastal city of Mahajanga, Madagascar. A total of 1,702 clinically suspected cases of bubonic plague were reported, including 515 laboratory confirmed by Yersinia pestis isolation (297), enzyme-linked immunosorbent assay, or both. Incidence was higher in males and young persons. Most buboes were inguinal, but children had a higher frequency of cervical or axillary buboes. Among laboratory-confirmed hospitalized patients, the case-fatality rate was 7.9%, although all Y. pestis isolates were sensitive to streptomycin, the recommended antibiotic. In this tropical city, plague outbreaks occur during the dry and cool season. Most cases are concentrated in the same crowded and unsanitary districts, a result of close contact among humans, rats, and shrews. Plague remains an important public health problem in Madagascar, and the potential is substantial for spread to other coastal cities and abroad.

Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Child; Child, Preschool; Disease Outbreaks; Female; Humans; Incidence; Madagascar; Male; Middle Aged; Plague; Sex Distribution; Urban Population; Yersinia pestis

Plague was introduced to Madagascar in 1898, and it has been characterized by a predominant distribution to the central highlands in the following decades. An increase of plague cases has been observed in the past 20 years, in particular in the capital, Antananarivo, and in the coastal town, Mahajanga, after long periods of silence in 28 and 63 years, respectively. A total of 2,982 confirmed or presumptive cases were reviewed in order to describe the changes in the epidemiological pattern of the disease from 1980 through 1999. The mean annual number of plague cases has increased from 33 during the 1980-1984 period to 298 during the 1995-1999 period. A similar trend of distribution has been observed from the first period to the second by an increase of endemic districts above 800 m altitude from 17 to 37. However, the lethality rate has in the same 20 years observation period decreased from 41.6% to 20.7%, probably due to re-enforcing measures as part of the national control program.

Topics: Altitude; Cause of Death; Communicable Diseases, Emerging; Disease Outbreaks; Endemic Diseases; Humans; Incidence; Madagascar; Plague; Population Surveillance

The transmission of Yersinia pestis is intense among rats in the wholesale market Tsenabe Isotry in the capital Antananarivo (anti-F1 sero-prevalence 80%, flea index 8.4 for a cut-off risk index of > 1). However, the number of plague-suspected (not laboratory confirmed) human cases has only been 3 in this district during a four years period from 1995 to 1999. A seroepidemiological survey among the market vendors was undertaken in June 1999 to test the hypothesis that the low incidence of human plague is due to acquired immunity. In addition, surveillance of the rat and the flea populations in the market was carried out. Only 3 (3.2%) of 95 screened vendors were anti-F1 IgG positive, whereas the markers of plague transmission among rodents and fleas were still high. This result suggests that the low incidence of human plague was not due to acquired immunity but to other factors such as the limited contact between humans and the rat fleas because of the abundance of rats, the absence of epizootic due to the resistance of rats in the capital and a particular behaviour of the predominant rat Rattus norvegicus.

Topics: Adolescent; Adult; Aged; Animals; Antibodies, Bacterial; Bacterial Proteins; Commerce; Disease Outbreaks; Disease Vectors; Female; Humans; Immunity, Active; Incidence; Madagascar; Male; Middle Aged; Plague; Population Density; Population Surveillance; Rats; Risk Factors; Seroepidemiologic Studies; Siphonaptera; Surveys and Questionnaires; Urban Health

Between the 20th October and the 18th November 1998, an outbreak of bubonic plague was declared in a hamlet in the Ikongo district of Madagascar. We conducted an epidemiological survey because of the re-emergence of the disease in this area (the last cases had been notified in 1965) and because of the low altitude compared to the classical Malagasy foci. The outbreak had been preceded by an important rat epizootics during September. A total of 21 cases were registered with an attack rate of 16.7% (21/126) and a lethality rate of 33% (7/21). The disease was more prevalent in males (66% of cases) and children aged < 15 years, as observed in general throughout the country. The anti-F1 seroprevalence among the contact population was 13.5% (13/96), probably attributable to subclinical infection by Yersinia pestis. No rodent was trapped during the survey, but an endemic hedgehog (Tenrec ecaudatus) was highly seropositive, suggesting a recent transmission of the plague bacillus among this species. The small mammals and vectors possibly involved in these new foci were investigated in May 1999.

Topics: Adolescent; Animals; Antibodies, Bacterial; Child; Child, Preschool; Disease Outbreaks; Female; Hedgehogs; Humans; Madagascar; Male; Plague; Yersinia pestis

Our survey of mammals and fleas arose as a result of an outbreak of bubonic plague at an usually low altitude in the Ikongo district (Madagascar), while a previous study had found anti-F1 antibodies in an endemic hedgehog. Animals were sampled with live traps in two hamlets (Antanambao-Vohidrotra, 540 m alt. and Ambalagoavy, 265 m alt.) and with pitfall traps in a neighbouring forest (750 m alt.). Rat fleas were collected by brushing the fur and free-living fleas by use of light traps. The introduced shrew Suncus murinus was found only in the village of Ambalagoavy while the black rat (Rattus rattus) was found in all three sites and the only seropositive rat was caught at Antanambao-Vohidrotra. In contrast, among the Tenrecidae (endemic shrews and hedgehogs) found in the forest near the first village, four animals were found seropositive for anti-F1 antibodies. One of them was carrying the endemic flea Paractenopsyllus pauliani, not yet reported as a vector of plague. The endemic vector of plague, Synopsyllus fonquerniei, was found only in the first village of Antanambao-Vohidrotra, and the cosmopolite flea Xenopsylla cheopis only in Ambalagoavy. Although no Yersinia pestis could be isolated and no F1-antigen could be detected in these animals, we found evidence of the recent transmission of plague in Antanambao-Vohidrotra and the nearby forest, but not in Ambalagoavy. These data corroborate with the sylvatic plague cycle hypothesis in Madagascar and its involvement in the outcome of the bubonic plague outbreak in this district.

Topics: Animals; Antibodies, Bacterial; Disease Outbreaks; Disease Reservoirs; Disease Vectors; Hedgehogs; Humans; Madagascar; Muridae; Plague; Rats; Shrews; Siphonaptera; Yersinia pestis

The authors report the results of a randomized epidemiological survey aiming to assess the sero-prevalence of plague in the general population > or = 2-year-old in Mahajanga. In 656 sera tested (by ELISA), the prevalence of anti-F1 antibodies was found to be 6.1%@1000 inhabitants, close to the expected prevalence in the area, where plague reappeared in 1991 after 62 years of absence. The study also demonstrated that the shrew, Suncus murinus, is an important reservoir in the plague transmission in Mahajanga.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Antibodies, Bacterial; Bacterial Proteins; Carrier State; Child; Child, Preschool; Disease Outbreaks; Disease Vectors; Female; Humans; Madagascar; Male; Middle Aged; Plague; Population Surveillance; Seroepidemiologic Studies; Shrews; Urban Health

The resistance of Xenopsylla cheopis from urban area to pyrethroids, to DDT, and their susceptibility to carbamate are known. We have evaluated the susceptibility of X. cheopis collected from three rural localities: Ambodisiarivo (district of Antananarivo Avaradrano), Mandoto (district of Betafo), Analaroa (district of Anjozorobe) in the province of Antananarivo and in Besoa (district of Ambalavao) in the province of Fianarantsoa. The standard WHO protocol was used and four insecticides were tested: deltamethrin 0.025%, cyfluthrin 0.15% (pyrethroids), DDT 4% (organochlorine), propoxur 1% and bendiocarb 0.1% (carbamate). X. cheopis has been shown resistance to DDT 4%, to deltamethrin 0.025% but was susceptible in the rural area around Antananarivo City. They were tolerant to deltamethrin 0.025% and cyfluthrin 0.15% but susceptible to propoxur 0.1% and bendiocarbe 1% in the districts of Betafo and Anjozorobe. In Besoa, X. cheopis was resistant to DDT 4%, tolerant to deltamethrin 0.025% and cyfluthrin 0.15% but susceptible to propoxur 0.1% and bendiocarbe 1%. These results indicate that DDT and pyrethroids can not be recommended any more for the vector control in the rural area around the capital. The use of pyrethroids in the other districts of the central highland must be joined with a X. cheopis susceptibility control. In case of resistance to pyrethroids, carbamates would be proposed to control plague vector in the rural area. The high level of resistance to DDT and pyrethroid in the rural area around the capital confirms the importance of studying the flea population in different area of Madagascar and the possibility of the gene resistance propagation.

Topics: Altitude; Animals; Carbamates; DDT; Humans; Insect Control; Insect Vectors; Insecticide Resistance; Insecticides; Lethal Dose 50; Madagascar; Plague; Pyrethrins; Rural Health; Siphonaptera

Topics: Animal Husbandry; Animal Nutritional Physiological Phenomena; Animals; Endemic Diseases; Humans; Insect Vectors; Madagascar; Plague; Reproduction; Siphonaptera; Temperature; Time Factors

The diagnostic value of a PCR assay that amplifies a 501-bp fragment of the Yersinia pestis caf1 gene has been determined in a reference laboratory with 218 bubo aspirates collected from patients with clinically suspected plague managed in a regional hospital in Madagascar. The culture of Y. pestis and the detection of the F1 antigen (Ag) by enzyme-linked immunosorbent assay (ELISA) were used as reference diagnostic methods. The sensitivity of PCR was 89% (57 of 64) for the Y. pestis-positive patients, and 80.7% (63 of 78) for the F1 Ag-positive patients. The specificity of PCR for the culture-, F1 Ag-, and antibody-negative patients (n = 105) was 100%. Because in Madagascar most patients with plague are managed and their clinical samples are collected in remote villages, the usefulness of PCR was evaluated for routine diagnostic use in the operational conditions of the control program. The sensitivity of PCR was 50% (25 of 50) relative to the results of culture and 35.2% (19 of 54) relative to the results of the F1 Ag immunocapture ELISA. The specificity of PCR under these conditions was 96%. In conclusion, the PCR method was found to be very specific but not as sensitive as culture or the F1 Ag detection method. The limitation in sensitivity may have been due to suboptimal field conditions and the small volumes of samples used for DNA extraction. This technique is not recommended as a routine diagnostic test for plague in Madagascar.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ambulatory Care Facilities; Antigens, Bacterial; Bacterial Proteins; Child; Child, Preschool; Disease Outbreaks; Enzyme-Linked Immunosorbent Assay; Female; Hospitals; Humans; Infant; Madagascar; Male; Middle Aged; Plague; Polymerase Chain Reaction; Yersinia pestis

Plague is a re-emerging disease and pneumonic plague is the most feared clinical form. We describe a well-documented outbreak of pneumonic plague in Madagascar.. Field epidemiological data were collected. Biological tests (microscopy, culture of Yersinia pestis, F1 antigen ELISA and dipstick assays, IgG anti-F1 ELISA) were done on sputum, serum, or necropsy samples. The infection rate among 154 contacts was assessed by anti-F1 serological techniques.. The index case was a bubonic patient with a secondary lung infection, who contaminated a traditional healer and his family. Funeral ceremonies and attendance on patients contaminated other villagers. In total 18 cases were recorded, and eight died. F1 antigen could be detected in sputum by ELISA and dipstick tests as early as the second day after the onset of the symptoms and also 48 h after treatment. Among the contact population 13 of 154 (8.4%) have been exposed to the plague bacillus (symptomless or latent infections).. The F1 dipstick assay on sputum is an invaluable diagnostic tool for pneumonic plague. Treatment of patients and chemoprophylaxis of contacts were efficient in stopping the epidemic.

Topics: Adolescent; Adult; Child; Child, Preschool; Disease Outbreaks; Female; Humans; Madagascar; Male; Plague; Sputum

From 1996 to 1998, 5,965 patients with suspected plague were identified in 38 districts of Madagascar (40% of the total population are exposed). Using standard bacteriology, 917 of them were confirmed or presumptive (C + P) cases. However, more than 2,000 plague cases could be estimated using F1 antigen assay. Two out of the 711 Yersinia pestis isolates tested were resistant to chloramphenicol and to ampicillin (both isolates found in the harbour of Mahajanga). Urban plague (Mahajanga harbour and Antananarivo city) accounted for 37.4% of the C + P cases. Bubonic plague represented 97.2% of the cases, and the lethality rate was still high (20%). In comparing the exposed population, plague was more prevalent in males (M:F sex ratio 1.3:1) and patients under 20 years (2.7% babies under two years). Buboes were mainly localised in the inguinal/femoral regions (55.8%). The epidemiological risk factors are discussed.

Topics: Adolescent; Adult; Age Distribution; Aged; Anti-Bacterial Agents; Bacterial Proteins; Child; Child, Preschool; Female; Geography; Humans; Infant; Infant, Newborn; Madagascar; Male; Microbial Sensitivity Tests; Middle Aged; Plague; Seasons; Sex Distribution; Sex Factors; Survival Rate; Yersinia pestis

We conducted a seroepidemiological survey of human plague in the general population using random sampling in the area of Ambositra, the main focus of plague in the central highlands of Madagascar (520 confirmed and presumptive cases notified during the past 10 years). Sera were tested using an ELISA IgG F1 assay. Considering the internal validity of the assay and the sampling method, the overall corrected prevalence of F1 antibodies was 0.6% (95% CI: 0.2%-1.8%). Being nearly 0 up to the age of 40, the corrected prevalence increased markedly after 45 years to 6.2%. Six of 20 individuals who declared to have been treated for clinical suspicion of bubonic plague in the past had F1 antibodies. The seroprevalence did not differ according to gender except in individuals > 60, where antibodies were significantly more frequent in males. This study suggests that the number of clinically suspected cases of plague provided by the surveillance network was plausible, despite some true cases being missed and a significant number of false positives. We also confirm that Yersinia pestis infections may occur without marked clinical manifestations and patients may recover without treatment, in accordance with old observations of pestis minor.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Bacterial; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Humans; Incidence; Madagascar; Male; Middle Aged; Plague; Prevalence; Sensitivity and Specificity; Seroepidemiologic Studies; Yersinia pestis

Plague is a re-emerging disease endemic in at least 24 countries. Non-endemic countries should be able to confirm plague to prevent outbreaks due to imported cases. We established a combination of a IgG/IgM screening ELISA and a confirmation immunoblot employing F1 capsular antigen (CA) for the serodiagnosis of plague in countries where yersiniosis is present. The ELISA and the immunoblot assay showed a specificity of 96.1% and 100% among sera from healthy German blood donors. This group had a seroprevalence of 39% of anti-yersinia outer protein (YOP) antibodies obviously caused by previous Y. enterocolitica infection. The ELISA detected anti-F1 CA antibodies in 22 and the immunoblot in 20 out of 26 sera of plague vaccinees. Five control sera from bacteriologically confirmed plague cases from Madagascar reacted positively. It can be concluded that anti-YOP antibodies do not affect assays based on purified F1 CA.

Topics: Antibodies, Bacterial; Disease Outbreaks; Enzyme-Linked Immunosorbent Assay; Germany; Humans; Immunoblotting; Immunoglobulin G; Immunoglobulin M; Madagascar; Mass Screening; Plague; Seroepidemiologic Studies; Serologic Tests

Several pathogenicity islands have recently been identified in different bacterial species, including a high-pathogenicity island (HPI) in Yersinia enterocolitica 1B. In Y. pestis, a 102-kb chromosomal fragment (pgm locus) that carries genes involved in iron acquisition and colony pigmentation can be deleted en bloc. In this study, characterization and mapping of the 102-kb region of Y. pestis 6/69 were performed to determine if this unstable region is a pathogenicity island. We found that the 102-kb region of Y. pestis is composed of two clearly distinct regions: an approximately 35-kb iron acquisition segment, which is an HPI per se, linked to an approximately 68-kb pigmentation segment. This linkage was preserved in all of the Y. pestis strains studied. However, several nonpigmented Y. pestis strains harboring an irp2 gene have been previously identified, suggesting that the pigmentation segment is independently mobile. Comparison of the physical map of the 102-kb region of these strains with that of strain 6/69 and complementation experiments were carried out to determine the genetic basis of this phenomenon. We demonstrate that several different mechanisms involving mutations and various-size deletions are responsible for the nonpigmented phenotype in the nine strains studied. However, no deletion corresponded exactly to the pigmentation segment. The 102-kb region of Y. pestis is an evolutionarily stable linkage of an HPI with a pigmentation segment in a region of the chromosome prone to rearrangement in vitro.

Topics: Bacterial Outer Membrane Proteins; Bacterial Proteins; Chromosome Walking; Chromosomes, Bacterial; Cosmids; Democratic Republic of the Congo; Genetic Linkage; Germany; Humans; Iron; Iron-Binding Proteins; Kenya; Madagascar; Molecular Epidemiology; Periplasmic Binding Proteins; Pigments, Biological; Plague; Polymerase Chain Reaction; Recombination, Genetic; Repetitive Sequences, Nucleic Acid; Restriction Mapping; Vietnam; Yersinia pestis

After a thirty year period of successful control, bubonic plague showed the first signs of return in Madagascar where a fatal outbreak occurred in Antananarivo in 1978. A second outbreak was observed in Mahajanga in 1991 after more than a half century. In 1997, 459 confirmed or presumptive cases were reported, as compared to 150 to 250 cases during the last years. However the actual extent of this recrudescence must be placed in the perspective of a more efficient control program that has led to better reporting of suspected cases and availability of more accurate diagnostic techniques. Recent research has led to the development of highly effective immunological diagnostic tools (detection of antibodies and F1 antigen) allowing not only better surveillance of the disease in man and animals but also renewed study of the epidemiological cycle in the current environment. In this regard the capacity of several endemic fleas as vectors and the role of the rat Rattus norvegicus and the musk shrew Suncus murinus are currently under investigation. Genetic study of strains collected from 1936 to 1996 has demonstrated the appearance of 3 new ribotypes of Yersinia pestis since 1982 in the zones of strongest plague activity in Madagascar. A strain showing multiresistance to standard therapeutic antibiotic agents was isolated in 1995. Bubonic plaque is a priority health problem in Madagascar but remains a major concern for the rest of the world.

Topics: Animals; Anti-Bacterial Agents; Disease Outbreaks; Disease Reservoirs; Humans; Madagascar; Male; Microbial Sensitivity Tests; Plague; Rats; Recurrence; Shrews; Yersinia pestis

After an absence of 62 years, an epidemic of plague occurred in the harbour city of Majunga (Madagascar) from July 1995 to March 1996, following sporadic cases in March and May 1995. By 15 March 1996, 617 clinically suspected cases of bubonic plague had been notified. Laboratory testing was carried out for 394 individuals: 60 (15.2%) were confirmed to have bubonic plague and 48 (12.2%) were considered as presumptive cases. The incidence was significantly higher in males in all age groups and in both sexes in the 5-19 age group. Twenty-four deaths were related to plague, but early treatment with streptomycin has confirmed its effectiveness insofar as the case-farality ratio was only 8.7% among confirmed and presumptive cases admitted to hospital. The difficulty of clinically diagnosing bubonic plague was affirmed. The disease met favourable conditions through the poverty and low level of hygiene prevalent in most parts of Majunga.

Topics: Adolescent; Adult; Age Factors; Aged; Anti-Bacterial Agents; Child; Child, Preschool; Disease Outbreaks; Female; Humans; Incidence; Infant; Infant, Newborn; Madagascar; Male; Middle Aged; Plague; Sex Factors; Streptomycin; Urban Population

Yersinia pestis, the causative agent of plague, has been responsible for at least three pandemics. During the last pandemic, which started in Hong Kong in 1894, the microorganism colonized new, previously unscathed geographical areas where it has become well established. The aim of this longitudinal study was to investigate the genetic stability of Y. pestis strains introduced into a new environment just under a century ago and to follow the epidemiology of any new genetic variant detected. In the present study, 187 strains of Y. pestis isolated between 1939 and 1996 from different regions of Madagascar and responsible mainly for human cases of bubonic and pneumonic plague were studied. Our principal genotyping method was rRNA gene profiling (ribotyping), which has previously been shown to be an effective scheme for typing Y. pestis strains of different geographical origins. We report that all studied Y. pestis strains isolated in Madagascar before 1982 were of classical ribotype B, the ribotype attributed to the Y. pestis clone that spread around the world during the third pandemic. In 1982, 1983, and 1994, strains with new ribotypes, designated R, Q, and T, respectively, were isolated on the high-plateau region of the island. Analysis of other genotypic traits such as the NotI genomic restriction profiles and the EcoRV plasmid restriction profiles revealed that the new variants could also be distinguished by specific genomic and/or plasmid profiles. A follow-up of these new variants indicated that strains of ribotypes Q and R have become well established in their ecosystem and have a tendency to spread to new geographical areas and supplant the original classical strain.

Topics: Animals; Anti-Bacterial Agents; Biological Evolution; DNA, Bacterial; Electrophoresis, Gel, Pulsed-Field; Genetic Variation; Geography; Guinea Pigs; Humans; Madagascar; Microbial Sensitivity Tests; Plague; Rats; Restriction Mapping; RNA Probes; Yersinia pestis

Topics: Disease Outbreaks; Humans; Madagascar; Plague; Yersinia pestis

Plague appeared in Madagascar in 1898, the pandemic coinciding with the French conquest. Until 1921, harbor epidemics occurred in Tamatave, Majunga, Diégo-Suarez, Fort-Dauphin, Vatomandry. In 1921, probably favored by the building of roads and railways, plague takes root on the High Lands where it becomes endemic above 800 meters. The vaccine achievement by Girard and Robic with the EV strain, and its mass application from 1935 by Estrade, Milliau, Brault, Seyberlich and Jan Keguistel, allowed to control the disease. The D.D.T. and sulfamids discovery makes the urban epidemics almost disappear, allowing it to subsist as only rural sporadic or familial cases with a low mortality. The mass vaccination can be stopped in 1959. Since 1988 the diseases incidence has been increasing, probably in relation with the quasi disappearance of deinsectisation and antibiotics. Nevertheless, urban epidemics are still rare and limited in a parallel direction to the substitution, in the city, of Rattus rattus, main reservoir and victim of the disease, by Rattus norvegicus, less sensitive to the infection.

Topics: Animals; Colonialism; Disease Outbreaks; Epidemiology; France; History, 19th Century; History, 20th Century; Humans; Madagascar; Plague; Rats

After a recall of the epidemiological cycle of plague, the authors describe the course of this disease from 1989 to 1992. Out of 2676 pathological samples suspected of plague, 2105 biological examinations were carried out. 312 cases were confirmed and 335 considered as probable. 93% of those positive cases come from the plague triangle located in the Central Highlands and delimited by Ambatondrazaka, Miarinarivo and Fianarantsoa and they occur during the rainy season (November to March). However, an outbreak of urban epidemics is possible on the coast during the cold season. The most frequent clinical form had been bubonic plague (90%). Plague did not much concern young children and men are affected more often than women. Clinically, toxi-infectious syndrome, lymph node reaction and hemoptoïc spits can be noted. The 1989-1992 results are compared with those of the two previous studies.

Topics: Adolescent; Adult; Age Factors; Child; Child, Preschool; Diagnosis, Differential; Female; Humans; Incidence; Infant; Madagascar; Male; Morbidity; Plague; Population Surveillance; Residence Characteristics; Seasons; Sex Ratio

Plague has existed in Madagascar since 1896, with epidemic control achieved by GIRARD with an EV vaccine in 1937. Plague persists in Madagascar, however, due to the large animal reservoir. With a predilection for nodal tissues, Yersinia pestis is a virulent bacteria that is potent inducer of antibody synthesis. Immunity mechanisms stimulated by infection were studied: 1. In human by immunoenzymatic methods 2. In mice by seroprotection and vaccinating tests. Induced immunity for people in endemic and endemic-epidemic areas, is significant, affecting approximately 70% of these populations. In non endemic areas, immunity is found in only 33% of the population, perhaps this explains the persistence of epidemic? In all cases, this immunity is a quick onset (6 days), is persistent (> 2 years), and has demonstrable serious recognition of YOP (Yersinia Outer Proteins) by Western Blot method. Human antibodies were shown to be protective for mice. Animals vaccinated by YOP were protected equally well, when compared to animals infected with Yersinia pestis and subsequently treated with antibiotics. Finally, YOP aerosols were also shown to induce antibodies. In conclusion, plague is a vaccinatable bacterial disease and YOP can be used as an animal vaccine to permit plague control in the rat reservoir.

Topics: Aerosols; Animals; Bacterial Outer Membrane Proteins; Disease Reservoirs; Humans; Madagascar; Plague; Plague Vaccine; Rats; Yersinia pestis

Plague is a bacterial disease, induced by Yersinia pestis growth in rodents, with human transmission by fleas. In numerous cases, lymph node reaction is important. This survey (329 patients and contacts) is the most extensive ever realised, associating plasmidic virulence and immunity studies. From the results, we can retain that: All the strains were 47 Plasmid+. The immunity was precocious, specific, of high titer and persistent. In conclusion, in plaque endemic zone, high bacillus circulation induced a high and perhaps (to prove) protective immunity.

Topics: Antibodies, Bacterial; Enzyme-Linked Immunosorbent Assay; Humans; Madagascar; Plague; Plasmids; Seroepidemiologic Studies; Yersinia pestis

Topics: Animals; Disease Outbreaks; Disease Vectors; Humans; Madagascar; Plague; Rats; Siphonaptera

Topics: History, 20th Century; Humans; Madagascar; Plague; Recurrence

Topics: Animals; France; Guinea Pigs; History, 19th Century; History, 20th Century; Humans; Madagascar; Plague; Plague Vaccine; Rabbits; Rats

Topics: History, Modern 1601-; Madagascar; Plague

Topics: Communicable Disease Control; History, Modern 1601-; Madagascar; Plague; Politics

Topics: Adolescent; Adult; Age Factors; Child; Child, Preschool; Female; Humans; Infant; Madagascar; Male; Pest Control; Plague; Sex Factors; Vaccination

Topics: Africa; Animals; Asia; Disease Reservoirs; Humans; India; Madagascar; North America; Plague; Rats; Rodentia; South America

Topics: Animals; Antibody Formation; Disease Reservoirs; Eulipotyphla; Immunodiffusion; Madagascar; Plague

Topics: Animals; Insect Vectors; Madagascar; Mice; Plague; Rodent Diseases; Siphonaptera

Topics: Adolescent; Adult; Aged; Animals; Child; Child, Preschool; Disease Reservoirs; Disease Vectors; Female; Humans; Infant; Infant, Newborn; Madagascar; Male; Middle Aged; Plague

Topics: Asian People; Autopsy; Black People; Humans; Madagascar; Plague; Punctures

The history of plague in Africa during the period 1935-49 is reviewed. Much of the information derives from a questionnaire sent to all African territories in 1950. The annual incidence of plague in Africa declined, particularly from 1946 onwards. In 1949, under 400 cases were reported, as compared with over 6,000 in 1935. By the end of 1949, plague was still active in the Belgian Congo, Kenya and Tanganyika, Madagascar, and southern Africa. No cases were reported from Egypt, Tunisia, Algeria, Morocco, Senegal, or Uganda during 1949. A comparison of the seasonal incidence of plague with prevailing atmospheric conditions (temperature and rainfall) in African territories shows that human plague is more frequent in warm moist weather-60 degrees -80 degrees F (15 degrees -27 degrees C)-than in hot dry, or cold, weather-over 80 degrees F (27 degrees C) or under 60 degrees F (15 degrees C). The highlands of equatorial Africa and of Madagascar appear to provide the optimum environment for the persistence of plague on the domestic (murine) plane and the high-veld and Kalahari of southern Africa on the sylvatic plane. The rat (Rattus rattus) and the multimammate mouse (R. (Mastomys) natalensis) and their fleas Xenopsylla brasiliensis and X. cheopis appear to be mainly responsible for the persistence of the reservoir in the East African highlands; R. rattus and X. cheopis play this role in Madagascar. The gerbils (Tatera and Desmodillus) and their burrow fleas X. philoxera and X. piriei are the main reservoirs of plague in southern Africa. Within these areas, Pasteurella pestis finds an environment suitable for its continued survival; the conditions seem to be comparable to those defined as obtaining in endemic centres in India. Elsewhere in Africa such endemic centres do not appear to exist.

Topics: Africa; Africa, Southern; Animals; Data Collection; Democratic Republic of the Congo; Egypt; Humans; India; Kenya; Madagascar; Mice; Plague; Rats; Rodentia; Senegal; Siphonaptera; Tanzania; Uganda; Yersinia pestis

Topics: Autopsy; Humans; Madagascar; Plague; Punctures

Topics: Asian People; Black People; Humans; Madagascar; Plague