Plague, a reemerging disease in Madagascar.

Human cases of plague, which had virtually disappeared in Madagascar after the 1930s, reappeared in 1990 with more than 200 confirmed or presumptive cases reported each year since. In the port of Mahajanga, plague has been reintroduced, and epidemics occur every year. In Antananarivo, the capital, the number of new cases has increased, and many rodents are infected with Yersinia pestis. Despite surveillance for the sensitivity of Y. pestis and fleas to drugs and insecticides and control measures to prevent the spread of sporadic cases, the elimination of plague has been difficult because the host and reservoir of the bacillus, Rattus rattus, is both a domestic and a sylvatic rat

Genetic structure of black rat populations in a rural plague focus in Madagascar

Correspondance: [email protected] genetic structure of reservoir populations is a key characteristic in understanding the persistence of infectious diseases in natural systems. In the Highlands of Madagascar, where plague has persisted since 1920, the black rat, Rattus rattus (L., 1758), is the sole species acting as a reservoir of the disease. Ecological surveys have shown a clear correlation between the locations of the plague-persistence area in Madagascar (above 800 m elevation) and the distribution area of one endemic plague vector, the flea Synopsyllus fonquerniei, which is found exclusively on rats living outdoors. This clear habitat segregation has led to the suggestion that R. rattus populations in the central highlands are divided into indoor- and outdoor-dwelling populations. Using eight microsatellite markers, we analysed the genetic structure of R. rattus populations living within a human plague focus in relation to habitat and geographic distance. We found that habitat by itself was not a structuring factor, unlike geographic distance. Nevertheless, the significant genotypic differentiation of R. rattus populations that was found at a fine spatial scale might relate to differences in population dynamics between rats in indoor and outdoor habitats

Plant-derived recombinant F1, V, and F1-V fusion antigens of Yersinia pestis activate human cells of the innate and adaptive immune system

Plague is still endemic in different regions of the world. Current vaccines raise concern for their side effects and limited protection, highlighting the need for an efficacious and rapidly producible vaccine. F1 and V antigens of Yersinia pestis, and F1-V fusion protein produced in Nicotiana benthamiana administered to guinea pigs resulted in immunity and protection against an aerosol challenge of virulent h pestis. We examined the effects of plant-derived F1, V, and F1-V on human cells of the innate immunity. F1, V, and F1-V proteins engaged TLR2 signalling and activated IL-6 and CXCL-8 production by monocytes, without affecting the expression of TNF-alpha, IL-12, IL-10, IL-1 beta, and CXCL10. Native F1 antigen and recombinant plant-derived F1 (rF1) and rF1-V all induced similar specific T-cell responses, as shown by their recognition by T-cells from subjects who recovered from E pestis infection. Native F1 and rF1 were equally well recognized by serum antibodies of Y. pestis-primed donors, whereas serological reactivity to rF1-V hybrid was lower, and that to rV was virtually absent. In conclusion, plant-derived F1, V, and F1-V antigens are weakly reactogenic for human monocytes and elicit cell-mediated and humoral responses similar to those raised by Y pestis infection

Термодинамический расчет диаграммы плавкости системы Mg—MgO—B при давлении 2 ГПа

В рамках модельных представлений феноменологической термодинамики выполнен расчет фазовых равновесий с участием жидкой фазы в тройной системе Mg—MgO—B при давлении 2 ГПа. Диаграмма плавкости системы характеризуется наличием пяти нонвариантных четырехфазных равновесий, три из которых перитектические, а два — эвтектические. Область первичной кристаллизации диборида магния MgB₂ расположена вблизи двойной системы Mg—B и выклинивается по мере увеличения концентрации кислорода, уступая в точке перитектического равновесия L + MgB₂ ↔ MgO + MgB₄ (1345 K, 68 % (ат.) В, 10 % (ат.) О) областям кристаллизации MgO и MgB₄

Immune Responses to Plague Infection in Wild Rattus rattus, in Madagascar: A Role in Foci Persistence?

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

Contrasted Patterns of Selection on MHC-Linked Microsatellites in Natural Populations of the Malagasy Plague Reservoir

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

Plague: past, present and future

[Introduction] Recent experience with SARS (severe acute respiratory syndrome) [1] and avian flu shows that the public and political response to threats from new anthropozoonoses can be near-hysteria. This can readily make us forget more classical animal-borne diseases, such as plague (Box 1). Three recent international meetings on plague (Box 2) concluded that: (1) it should be re-emphasised that the plague bacillus (Yersinia pestis) still causes several thousand human cases per year [2,3] (Figure 1); (2) locally perceived risks far outstrip the objective risk based purely on the number of cases [2]; (3) climate change might increase the risk of plague outbreaks where plague is currently endemic and new plague areas might arise [2,4]; (4) remarkably little is known about the dynamics of plague in its natural reservoirs and hence about changing risks for humans [5]; and, therefore, (5) plague should be taken much more seriously by the international community than appears to be the case

Screening of Tanzanian medicinal plants for anti-Candida activity

BACKGROUND: Candida albicans has become resistant to the already limited, toxic and expensive anti-Candida agents available in the market. These factors necessitate the search for new anti-fungal agents. METHODS: Sixty-three plant extracts, from 56 Tanzanian plant species obtained through the literature and interviews with traditional healers, were evaluated for anti-Candida activity. Aqueous methanolic extracts were screened for anti-Candida activity by bioautography agar overlay method, using a standard strain of Candida albicans (ATCC 90028). RESULTS: Twenty- seven (48%) out of the 56 plants were found to be active. Extracts of the root barks of Albizia anthelmintica and Balanites aegyptiaca, and roots of Plectranthus barbatus showed strong activity. CONCLUSION: The extracts that showed strong anti-Candida activity are worth of further investigation in order to isolate and identify the active compounds

Plague Circulation and Population Genetics of the Reservoir Rattus rattus: The Influence of Topographic Relief on the Distribution of the Disease within the Madagascan Focus.

International audienceBACKGROUND: 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. METHODOLOGYPRINCIPAL FINDINGS: 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. CONCLUSIONSSIGNIFICANCE: 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