Minoarisoa Rajerison

Institut Pasteur International Network · Plague Unit

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 r...

Objectives: Plague has been a threat to human health in Tanzania since 1886. This zoonotic disease has established several endemic foci in the country, posing a risk of outbreaks. This study was conducted to investigate the presence of Yersinia pestis in small mammals in five districts. These districts were selected because of recent (Mbulu), past...

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 plagu...

Plague, a zoonotic disease caused by the bacterium Yersinia pestis , remains a major public health threat in Madagascar. To better understand the risk of transmission to humans and to guide targeted plague prevention and control measures, a survey of Y. pestis infection and exposure in mammals and their fleas was implemented. Small mammals were cap...

Background Plague is a zoonotic disease caused by the bacterium Yersinia pestis , highly prevalent in the Central Highlands, a mountainous region in the center of Madagascar. After a plague-free period of over 60 years in the northwestern coast city of Mahajanga, the disease reappeared in 1991 and caused several outbreaks until 1999. Previous resea...

Antimicrobial resistance (AMR) is a well-recognized, widespread, and growing issue of concern. With increasing incidence of AMR, the ability to respond quickly to infection with or exposure to an AMR pathogen is critical. Approaches that could accurately and more quickly identify whether a pathogen is AMR also are needed to more rapidly respond to...

Rickettsioses are among emerging infectious diseases around the world. In Madagascar, little information is available regarding Rickettsia (Rickettsiales: Rickettsiaceae) diversity and their potential impacts on public health. In fact, molecular screening of ectoparasites of mammals reported the presence of three species, Rickettsia africae, Ricket...

Background 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 w...

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 r...

Two monoclonal antibodies directed to the V antigen of Yersinia pestis have been tested for protective efficacy in a murine model of bubonic plague. Mice were infected with a current clinical isolate from Madagascar, designated Y.pestis 10-21/S. Mab7.3, delivered to mice intra-periteoneally at either 24h prior to, or 24h post- infection, was fully...

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,...

Background: Pneumonic plague (PP), caused by Yersinia pestis, is the most feared clinical form of plague due to its rapid lethality and potential to cause outbreaks. PP outbreaks are now rare due to antimicrobial therapy. Methods: A PP outbreak in Madagascar involving transmission of a Y. pestis strain resistant to streptomycin, the current reco...

Background 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. Methods In Madagascar, all clinically suspected plague cases tha...

Background 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...

According to the WHO, 75% of the world’s plague cases are found in Madagascar, with an average of 200–700 suspected cases 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 p...

Klebsiella pneumoniae can lead to a wide range of diseases including pneumonia, bloodstream, and urinary tract infections. During a short period of a 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, withou...

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 effecti...

Background 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. Purpose The aim of this study is...

Background Human plague cases, mainly the bubonic form, occur annually in the endemic regions of the central highlands of Madagascar. The aim of the study is to compare the evolution of the epidemiological features of human plague in two districts of the central highlands. Methods In Madagascar, all clinically suspected plague cases that meet clini...

Background: Plague is endemic to the central highlands of Madagascar. Sporadic human cases or outbreaks can occur annually in these areas. In Madagascar, the association between endemicity and the knowledge, attitudes and practices (KAP) of populations with regard to this disease remain poorly documented. The aim of this study was to assess KAP rel...

Background 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 valuab...

Background Plague is still a major public health concern in Madagascar despite the effort to reduce human cases and understand its epidemiology. In several localities known as plague foci, human cases are reported but the origin of the infection is most on the time unknown. In the present study, we report the presence of different genotypes of Yers...

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. B...

Background 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 antib...

Background: 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 randomiz...

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 als...

We conducted a national human serologic study of a hantavirus detected in Madagascar rodents using a commercial kit and a new ELISA targeting the virus. Our results suggest a conservative estimate of 2.7% (46/1,680) IgG seroprevalence. A second single-district study using the new ELISA revealed a higher prevalence (7.2%; 10/139).

Background: 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). Methods: We assessed the performance of the plague RDT based on Y. pestis F1 anti...

In developing countries, estimates of the prevalence and diversity of Leptospira infections in livestock, an important but neglected zoonotic pathogen and cause of livestock productivity loss, are lacking. In Madagascar, abattoir sampling of cattle and pigs demonstrated a prevalence of infection of 20% in cattle and 5% in pigs by real-time PCR. In...

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 pr...

Leptospirosis is a neglected zoonotic bacterial disease caused by pathogenic Leptospira spp. Only limited studies have been conducted on the presence of Leptospira spp. in rats in Antananarivo, the capital city of Madagascar. We assessed Leptospira prevalence in small mammals in urban areas of Antananarivo where sanitation is inadequate and there i...

Background: 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, particularl...

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 presu...

Objectives 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 a...

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 o...

We identified mixed infections of pathogenic Leptospira in small mammals across a landscape-scale study area in Madagascar by using primers targeting different Leptospira spp. Using targeted primers increased prevalence estimates and evidence for transmission between endemic and invasive hosts. Future studies should assess rodentborne transmission...

Background: Plague is a life-threatening disease caused by the bacterium, Yersinia pestis. Madagascar is the leading country for human plague cases worldwide. Human plague is a serious disease, particularly in its septicaemic and pneumonic forms. We report a case of pneumonic plague co-infected by a MDR-Stenotrophomonas maltophilia. Case presenta...

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...

Background 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 nuc...

PCR master mix calculation sheet indicating final concentration and volume addition of each reagent. (DOCX)

Agarose gel pictures for each assays generated at both NAU and IPM or NAU only. (DOCX)

Y. pestis 3a TaqMan assay design. (DOCX)

Side by side comparison of 2% agarose gel electrophoresis in a 1x Lithium Borate and 1x TAE matrix. Electrophoresis was conducted with identical PCR products, equipment and agarose gel conditions. The two runs differ only in buffer solution used. (DOCX)

SNP allele state for the 16 isolates shown in Table 1. (DOCX)

Agarose gel pictures of negative controls (human background DNA and Bacillus anthracis–A0635 and A0643) on a subset of MAMA tools. (DOCX)

Background 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...

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 m...

Final generalized linear models (GLM) models for analyses of small mammal and flea abundances. (PDF)

Coefficients from final GLM models for small mammal and flea abundance. (PDF)

Plague indicators during epidemics, post epidemics periods, and 15 years after the last human outbreak. (PDF)

Emergence of antibiotic-resistant Y. pestis strains represents a public health concern. Two antibiotic-resistant Y. pestis strains isolated from Madagascar were previously identified and characterized. Both strains carried conjugative plasmids that conferred resistance to streptomycin or to multiple antibacterial drugs. Here we characterized a nove...

Background: 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 epidemio...

Sample selection for whole genome sequencing. MLVA phylogenies of 458 and 315 Group I (A) and Group II (B), respectively, Malagasy Y. pestis samples used to select candidates for whole genome sequencing. The MLVA phylogenies consist of neighbor-joining dendrograms constructed in MEGA6 [35] using mean character based distance matrices. Each MLVA cla...

Primers used in SNP amplicon sequencing. (XLSX)

Map of Madagascar. The 32 districts (shaded and numbered 1–32) where Yersinia pestis samples analyzed in this study were collected are indicated. The core districts included in the heavily sampled Betafo and Moramanga regions are shaded yellow and purple, respectively. The neighboring districts where additional samples belonging to the subgroups do...

SNPs analyzed in this study. (XLSX)

Detection of a temporal signal. (A) Table showing each taxon name (tip), the date of isolation, and distance of each tip from the root (CO92). (B) Linear regression to determine how correlated root to tip distance is with date of isolation. (C) Random distribution of 10,000 permutations, where root to tip distances were shuffled each time, and corr...

Samples in this study. (XLSX)

Background: 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...

Background Rickettsiae are obligate intracellular bacteria responsible for many febrile syndromes around the world, including in sub-Saharan Africa. Vectors of these pathogens include ticks, lice, mites and fleas. In order to assess exposure to flea-associated Rickettsia species in Madagascar, human and small mammal samples from an urban and a rura...