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The presence of the filarial genus Litomosa in Malagasy bats is demonstrated by the finding of L. goodmani n. sp. from Miniopterus gleni and Litomosa sp. (male unknown) from M. manavi, both in the Special Reserve of Ankarana. These materials are compared to the 22 Litomosa species, including two Indian species originally placed in the genus Litomosoides, L. fotedari (Gupta & Trivedi, 1989) n. comb. and L. tewarii (Gupta & Trivedi, 1989) n. comb., and the new taxon L. seurati n. sp. (= L. beaucournui Bain, 1966 pro parte), type-host Rhinolophus ferrum-equinum, Algeria, distinguished by the narrow area rugosa and the female caudal extremity with two conspicuous points, instead of several small ones. The Malagasy material belongs to a group of species close to the type, L. filaria, which have a male area rugosa composed of cuticular bosses and microfilariae folded within the sheath, and which are parasitic in Vespertilionidae, Hipposideridae and Rhinolophidae from Africa and Europe. The two Malagasy species resemble L. seurati n. sp., L. beshkovi Jancev, 1971, L. chiropterum Ortlepp, 1932, L. adami Petit, 1980 and L. ottavianii Lagrange et Bettini, 1948, with the enlarged third segment of the buccal capsule. L. goodmani n. sp. is distinct with its small size and female caudal extremity with a single point, which is suppressed in old mature worms; the females of Litomosa sp. have two conical points. Relationships among Litomosa species appear to be dependent upon both the chiropteran host groups and the geographical region.

Background: Hepatitis A virus (HAV) is an enteric, viral, infectious disease endemic in many developing countries such as Madagascar. Infection is often subclinical or asymptomatic in children; however, symptomatic acute infections become more common with increasing age. In some developing countries, improvements in living conditions have led to changes in the epidemiological pattern of HAV infection. There are very few reports on the prevalence of HAV in Madagascar. This study was to determine the seroprevalence of hepatitis A virus antibodies in relation to age in the city of Antananarivo, Madagascar.Methods: Serum samples collected in 2004 during a cross-sectional survey of individuals aged between two and 24 years from Antananarivo were tested for anti-HAV antibody using a commercial enzyme immunoassay kit. Subjects were investigated using a standardized social and medical history questionnaire.Results: 926 subjects were enrolled including 406 males and 520 females. There were 251 children under 10 years old and 675 subjects between 10 and 24 years old. Of the 926 serum samples tested, 854 (92.2%) were positive for anti-HAV antibodies. The number of seropositive samples was similar for males and females. The overall seroprevalence was 83.7% (210/251) for children under 10 years old and 95.5% (644/675) for subjects aged between 10 and 24 years (p < 0.001).Conclusion: Despite improvements in sanitary conditions and hygiene over the last few years, the prevalence of HAV in Antananarivo is high. Only children under five years old remain susceptible to HAV infection. Immunization against HAV is not needed at the present time in the Madagascan population, but should be recommended for travellers. [ABSTRACT FROM AUTHOR]

As the national reference laboratory for febrile illness in Madagascar, we processed samples from the first epidemic wave of COVID-19, between March and September 2020. We fit generalized additive models to cycle threshold (C t ) value data from our RT-qPCR platform, demonstrating a peak in high viral load, low-C t value infections temporally coincident with peak epidemic growth rates estimated in real time from publicly-reported incidence data and retrospectively from our own laboratory testing data across three administrative regions. We additionally demonstrate a statistically significant effect of duration of time since infection onset on C t value, suggesting that C t value can be used as a biomarker of the stage at which an individual is sampled in the course of an infection trajectory. As an extension, the population-level C t distribution at a given timepoint can be used to estimate population-level epidemiological dynamics. We illustrate this concept by adopting a recently-developed, nested modeling approach, embedding a within-host viral kinetics model within a population-level Susceptible-Exposed-Infectious-Recovered (SEIR) framework, to mechanistically estimate epidemic growth rates from cross-sectional C t distributions across three regions in Madagascar. We find that C t -derived epidemic growth estimates slightly precede those derived from incidence data across the first epidemic wave, suggesting delays in surveillance and case reporting. Our findings indicate that public reporting of C t values could offer an important resource for epidemiological inference in low surveillance settings, enabling forecasts of impending incidence peaks in regions with limited case reporting., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Following the first detection of SARS-CoV-2 in passengers arriving from Europe on 19 March 2020, Madagascar took several mitigation measures to limit the spread of the virus in the country., Methods: Nasopharyngeal and/or oropharyngeal swabs were collected from travellers to Madagascar, suspected SARS-CoV-2 cases and contact of confirmed cases. Swabs were tested at the national reference laboratory using real-time RT-PCR. Data collected from patients were entered in an electronic database for subsequent statistical analysis. All distribution of laboratory-confirmed cases were mapped, and six genomes of viruses were fully sequenced., Results: Overall, 26,415 individuals were tested for SARS-CoV-2 between 18 March and 18 September 2020, of whom 21.0% (5,553/26,145) returned positive. Among laboratory-confirmed SARS-CoV-2-positive patients, the median age was 39 years (IQR: 28-52), and 56.6% (3,311/5,553) were asymptomatic at the time of sampling. The probability of testing positive increased with age with the highest adjusted odds ratio of 2.2 [95% CI: 1.9-2.5] for individuals aged 49 years and more. Viral strains sequenced belong to clades 19A, 20A and 20B indicative of several independent introduction of viruses., Conclusions: Our study describes the first wave of the COVID-19 in Madagascar. Despite early strategies in place Madagascar could not avoid the introduction and spread of the virus. More studies are needed to estimate the true burden of disease and make public health recommendations for a better preparation to another wave., (© 2021 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

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 related to plague among the population living in the central highlands., Methods: 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., Results: 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., Conclusion: 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.

Background: Tuberculosis rapid molecular assays, including GeneXpert MTB/RIF® and Loopamp MTBC Detection Kit®, are highly sensitive and specific. Such performance does not automatically translate in improved disease control and highly depends on their use, local epidemiology and the diagnostic algorithms they're implemented within. We evaluate the performance of both assays and assess their impact on additional cases notification when implemented within WHO recommended tuberculosis diagnostic algorithms in Madagascar., Methods: Five hundred forty eight presumptive pulmonary tuberculosis patients were prospectively recruited between November 2013 and December 2014 in Antananarivo, Madagascar, a high TB incidence sub-Saharan African urban setting. Both molecular assays were evaluated as first line or add-on testing following negative smear microscopy. Based on locally defined assay performance characteristics we measure the impact of both assays and WHO-recommended diagnostic algorithms on additional tuberculosis case notifications., Results: High sensitivity and specificity was confirmed for both GeneXpert MTB/RIF® (86.6% (95% CI 81.1-90.7%) and 97.4% (95% CI 94.9-98.8%)) and Loopamp MTBC Detection Kit® (84.6% (95% CI 78.9-89.0%) and 98.4% (95% CI 96.2-99.4%)). Implementation of GeneXpert MTB/RIF® and Loopamp MTBC Detection Kit® increased tuberculosis diagnostic algorithms sensitivity from 73.6% (95% CI 67.1-79.3%) up to 88.1% (95% CI 82.8-91.9%). This increase was highest when molecular assays were used as add-on testing following negative smear microscopy. As add-on testing, GeneXpert MTB/RIF® and Loopamp MTBC Detection Kit® respectively improved case detection by 23.8 and 21.2% (p < 0.05)., Conclusion: Including GeneXpert MTB/RIF® or Loopamp MTBC Detection Kit® molecular assays for TB detection on sputum samples from presumptive TB cases can significantly increase case notification in TB diagnostic centers. The TB case detection rate is further increased when those tests are use as second-line follow-on testing following negative smear microscopy results. A country wide scale-up and digital integration of molecular-based TB diagnosis assays shows promises for TB control in Madagascar.

Background: Tungiasis is highly prevalent in low- and middle-income countries but remains often under diagnosed and untreated eventually leading to chronic sequels. The objective of the study was to assess whether tungiasis-associated inflammation can be detected and quantified by high-resolution infrared thermography (HRIT) and whether after removal of the parasite inflammation resolves rapidly., Methods: Patients with tungiasis were identified through active case finding. Clinical examination, staging, and thermal imaging as well as conventional photography were performed. In exemplary cases, the embedded sandfly was extracted and regression of inflammation was assessed by thermal imaging 4 days after extraction., Results: The median perilesional temperature was significantly higher than the median temperature of the affected foot (rho = 0.480, p  = 0.003). Median perilesional temperature measured by high-resolution infrared thermography was positively associated with the degree of pain (rho = 0.395, p  < 0.017) and semi-quantitative scores for acute (rho = 0.380, p  < 0.022) and chronic (rho = 0.337, p  < 0.044) clinical pathology. Four days after surgical extraction, inflammation and hyperthermia of the affected area regressed significantly (rho = 0.457, p  = 0.005). In single cases, when clinical examination was difficult, lesions were identified through HRIT., Conclusion: We proved that HRIT is a useful tool to assess tungiasis-associated morbidity as well as regression of clinical pathology after treatment. Additionally, HRIT might help to diagnose hidden and atypical manifestations of tungiasis. Our findings, although still preliminary, suggest that HRIT could be used for a range of infectious skin diseases prevalent in the tropics., Trial Registration: ISRCTN11415557, Registration date: 13 July 2011.

The mechanisms by which the airborne pathogen Mycobacterium tuberculosis spreads within the lung and leaves its primary niche to colonize other organs, thus inducing extrapulmonary forms of tuberculosis (TB) in humans, remains poorly understood. Herein, we used a transcriptomic approach to investigate the host cell gene expression profile in M. tuberculosis-infected human macrophages (ΜΦ). We identified 33 genes, encoding proteins involved in angiogenesis, for which the expression was significantly modified during infection, and we show that the potent angiogenic factor VEGF is secreted by M. tuberculosis-infected ΜΦ, in an RD1-dependent manner. In vivo these factors promote the formation of blood vessels in murine models of the disease. Inhibiting angiogenesis, via VEGF inactivation, abolished mycobacterial spread from the infection site. In accordance with our in vitro and in vivo results, we show that the level of VEGF in TB patients is elevated and that endothelial progenitor cells are mobilized from the bone marrow. These results strongly strengthen the most recent data suggesting that mycobacteria take advantage of the formation of new blood vessels to disseminate.

Background: Madagascar, as other malaria endemic countries, depends mainly on international funding for the implementation of malaria control interventions (MCI). As these funds no longer increase, policy makers need to know whether these MCI actually provide the expected protection. This study aimed at measuring the effectiveness of MCI deployed in all transmission patterns of Madagascar in 2012-2013 against the occurrence of clinical malaria cases., Methods: From September 2012 to August 2013, patients consulting for non-complicated malaria in 31 sentinel health centres (SHC) were asked to answer a short questionnaire about long-lasting insecticidal nets (LLIN) use, indoor residual spraying (IRS) in the household and intermittent preventive treatment of pregnant women (IPTp) intake. Controls were healthy all-ages individuals sampled from a concurrent cross-sectional survey conducted in areas surrounding the SHC. Cases and controls were retained in the database if they were resident of the same communes. The association between Plasmodium infection and exposure to MCI was calculated by multivariate multilevel models, and the protective effectiveness (PE) of an intervention was defined as 1 minus the odds ratio of this association., Results: Data about 841 cases (out of 6760 cases observed in SHC) and 8284 controls was collected. The regular use of LLIN provided a significant 51 % PE (95 % CI [16-71]) in multivariate analysis, excluding in one transmission pattern where PE was -11 % (95 % CI [-251 to 65]) in univariate analysis. The PE of IRS was 51 % (95 % CI [31-65]), and the PE of exposure to both regular use of LLIN and IRS was 72 % (95 % CI [28-89]) in multivariate analyses. Vector control interventions avoided yearly over 100,000 clinical cases of malaria in Madagascar. The maternal PE of IPTp was 73 %., Conclusions: In Madagascar, LLIN and IRS had good PE against clinical malaria. These results may apply to other countries with similar transmission profiles, but such case-control surveys could be recommended to identify local failures in the effectiveness of MCI.

Background: The malaria burden in Madagascar dropped down last decade, largely due to scale-up of control measures. Nevertheless, a significant rise of malaria cases occurred in 2011-2012 in two regions of the rainy South-Eastern Madagascar, where malaria is considered as mesoendemic and the population is supposed to be protected by its acquired immunity against Plasmodium. A multidisciplinary investigation was conducted in order to identify the causes of the outbreak., Methods: In March 2012, a cross-sectional study was conducted in 20 randomly selected clusters, involving the rapid diagnostic testing of all ≥6 month-old members of households and a questionnaire about socio-demographic data and exposure to malaria control interventions. Changes in environmental conditions were evaluated by qualitative interview of local authorities, climatic conditions were evaluated by remote-sensing, and stock outs of malaria supplies in health facilities were evaluated by quantitative means. Two long-lasting insecticidal nets (LLINs) were sampled in each cluster in order to evaluate their condition and the remanence of their insecticidal activity. The entomological investigation also encompassed the collection Anopheles vectors in two sites, and the measure of their sensitivity to deltamethrin., Results: The cross-sectional survey included 1615 members of 440 households. The mean Plasmodium infection rate was 25.6 % and the mean bed net use on the day before survey was 71.1 %. The prevalence of Plasmodium infections was higher in 6-14 year-old children (odds ratio (OR) 7.73 [95 % CI 3.58-16.68]), in rural areas (OR 6.25 [4.46-8.76]), in poorest socio-economic tercile (OR 1.54 [1.13-2.08]), and it was lower in individuals sleeping regularly under the bed net (OR 0.51 [0.32-0.82]). Stock outs of anti-malarial drugs in the last 6 months have been reported in two third of health facilities. Rainfalls were increased as compared with the three previous rainy seasons. Vectors collected were sensitive to pyrethroids. Two years after distribution, nearly all LLINs collected showed a loss of physical integrity and insecticide activity,, Conclusions: Increased rainfall, decreasing use and reduced insecticide activity of long-lasting insecticide-treated nets, and drug shortages may have been responsible for, or contributed to, the outbreak observed in South-Eastern Madagascar in 2011-2012. Control interventions for malaria elimination must be sustained at the risk of triggering harmful epidemics, even in zones of high transmission.

Identifying those Mycobacterium tuberculosis latent-infected individuals most at risk of developing active tuberculosis (TB) using routine clinical and laboratory tests remains a huge challenge in TB control efforts. We conducted a prospective longitudinal study of clinical and laboratory markers associated with the risk of developing active TB in contacts with latent M. tuberculosis infection.HIV-negative household contacts (n=296) of pulmonary TB patients underwent monitoring of clinical features, full blood cell counts, tuberculin skin text (TST) and chest radiography performed regularly during 18 months of follow-up. Paired statistical tests, a Kaplan-Meier analysis and Cox proportional hazard modelling were performed on variables between contacts progressing or not progressing to active TB.The appearance of TB disease symptoms in contacts was significantly associated with an elevated peripheral percentage of blood monocytes (adjusted hazard ratio (aHR) 6.25, 95% CI 1.63-23.95; p<0.01), a ≥14 mm TST response (aHR 5.72, 95% CI 1.22-26.80; p=0.03) and an increased monocyte:lymphocyte ratio (aHR 4.97, 95% CI 1.3-18.99; p=0.03). Among contacts having TST ≥14 mm, a strong association with risk of progression to TB was found with an elevated blood monocyte percentage (aHR 8.46, 95% CI 1.74-41.22; p<0.01).Elevated percentage of peripheral blood monocytes plus an elevated TST response are potential biomarkers for identifying contacts of TB patients at highest risk of developing active TB., (Copyright ©ERS 2015.)

Objective: Although the Bacillus Calmette-Guérin vaccine (BCG) protects young children against serious forms of TB, protection against pulmonary TB is variable. We assessed BCG vaccine-induced cellular immune responses and determined for how long they could be detected during childhood in Antananarivo, Madagascar., Methods: We assessed BCG vaccine-induced cellular immune responses by TST and IGRA (in-house ELISPOT assay) using BCG and PPD as stimulation antigen, and compared results between vaccinated and non-vaccinated schoolchildren of two age groups, 6-7 and 13-14 years old., Results: Three hundred and sixty-three healthy schoolchildren were enrolled. TST was performed on 351 children and IGRA on 142. A high proportion (66%; 229/343) of the children had no TST reactivity (induration size 0 mm). TST-positive responses (≥15 mm) were more prevalent among 13-14 year-old (31.7%) than 6-7 year old (16.5%) children, both in the non-vaccinated (43% vs. 9%, p<0.001) and vaccinated (29% vs. 13%, p=0.002) subgroups. There were no significant differences in TST responses between vaccinated and non-vaccinated children in either of the age groups. The IGRA response to BCG and to PPD stimulation was not significantly different according to BCG vaccination record or to age group. A high rate (15.5%; 22/142) of indeterminate IGRA responses was observed. There was very poor agreement between TST and IGRA-PPD findings (k= 0.08) and between TST and IGRA-BCG findings (k= 0.02)., Conclusion: Analysis of TST and IGRA response to stimulation with BCG and PPD revealed no difference in immune response between BCG-vaccinated and non-vaccinated children; also no decrease of the BCG vaccine-induced cellular immune response over time was observed. We conclude that TST and IGRA have limitations in assessing a role of BCG or tuberculosis-related immunity.

Background: In the last decade, an important scale-up was observed in malaria control interventions. Madagascar entered the process for pre-elimination in 2007. Policy making needs operational indicators, but also indicators about effectiveness and impact of malaria control interventions (MCI). This study is aimed at providing data about malaria infection, morbidity, and mortality, and MCI in Madagascar., Methods: Two nationwide surveys were simultaneously conducted in 2012-2013 in Madagascar: a study about non-complicated clinical malaria cases in 31 sentinel health facilities, and a cross-sectional survey (CSS) in 62 sites. The CSS encompassed interviews, collection of biological samples and verbal autopsies (VA). Data from CSS were weighted for age, sex, malaria transmission pattern, and population density. VA data were processed with InterVA-4 software., Results: CSS included 15,746 individuals of all ages. Parasite rate (PR) as measured by rapid diagnostic tests was 3.1%, and was significantly higher in five to 19 year olds, in males, poorer socio-economic status (SES) quintiles and rural areas. Long-lasting insecticidal nets (LLIN) use was 41.7% and was significantly lower in five to 19 year olds, males and wealthier SES quintiles. Proportion of persons covered by indoor residual spraying (IRS) was 66.8% in targeted zones. Proportion of persons using other insecticides than IRS was 22.8%. Coverage of intermittent preventive treatment during pregnancy was 21.5%. Exposure to information, education and communication messages about malaria was significantly higher in wealthier SES for all media but information meetings. The proportion of fever case managements considered as appropriate with regard to malaria was 15.8%. Malaria was attributed as the cause of death in 14.0% of 86 VA, and 50% of these deaths involved persons above the age of five years. The clinical case study included 818 cases of which people above the age of five accounted for 79.7%. In targeted zones, coverage of LLIN and IRS were lower in clinical cases than in general population., Conclusions: This study provides valuable data for the evaluation of effectiveness and factors affecting MCI. MCI and evaluation surveys should consider the whole population and not only focus on under-fives and pregnant women in pre-elimination or elimination strategies.

Melioidosis is an often fatal infectious disease affecting humans and animals in the tropics. Only sporadic cases have been reported from Africa and the Indian Ocean region. We describe 2 confirmed autochthonous cases of human melioidosis in Madagascar, both from novel genotypes of Burkholderia pseudomallei.

Background: Tuberculosis continues to cause unacceptably high levels of disease and death worldwide. Active preventive strategies are required to improve tuberculosis control and to increase the number of cases treated in developing countries. The aim of this study was to evaluate the utility of the tuberculin skin test (TST) in first-year schoolchildren as a means of increasing the number of tuberculosis cases detected through the screening of close contacts., Methods: All members of the households of 90 schoolchildren assigned to three groups on the basis of TST category (≤ 5 mm, [5-15)mm, ≥ 15 mm) were screened for sputum smear-positive pulmonary tuberculosis. The percentage detection of tuberculosis in close contacts was compared between TST categories., Results: We identified 433 close contacts of the 90 schoolchildren, who were then evaluated for tuberculosis. We identified 11 cases of pulmonary tuberculosis among the close contacts (7 already on treatment and 4 previously undiagnosed): 0 in TST category ≤ 5 mm, 3 in TST category [5-15) mm and 8 in TST category ≥ 15 mm). This approach increased the detection of tuberculosis cases by a factor of 1.6 in first-year schoolchildren of the TST ≥ 5 mm group., Conclusion: TST in first-year schoolchildren is a potentially effective method for improving the detection of tuberculosis in close contacts.

Background: In Madagascar, indoor residual spraying (IRS) with insecticide was part of the national malaria control programme since the middle of the twentieth century. It was mainly employed in the highlands and the foothill areas, which are prone to malaria epidemics. Prior to a policy change foreseeing a shift from DDT to pyrethroids, a study was carried out to assess the entomological and parasitological impacts of IRS in areas with DDT or pyrethroids and in areas without IRS., Methods: The study was carried out from October 2002 to February 2005 in three communes of the western foothill area of Madagascar. Two communes received IRS with DDT in February 2003, then IRS with pyrethroids (alphacypermethrin or deltamethrin) in February 2004. The third commune remained untreated. Mosquitoes were collected at night using human landing catches and early in the morning in resting places. Blood smears were obtained from schoolchildren and microscopically examined for Plasmodium presence., Results: In total, 18,168 human landing mosquitoes and 12,932 resting anophelines were collected. The Anopheles species caught comprised 10 species. The main and most abundant malaria vector was Anopheles funestus (72.3% of human-seeking malaria vectors caught indoors). After IRS had taken place, this species exhibited a lower human biting rate and a lower sporozoite index. Overall, 5,174 blood smears were examined with a mean plasmodic index of 19.9%. A total of four Plasmodium species were detected. Amongst tested school children the highest plasmodial index was 54.6% in the untreated commune, compared to 19.9% in the commune sprayed with DDT and 11.9% in the commune sprayed with pyrethroid. The highest prevalence of clinical malaria attacks in children present at school the day of the survey was 33% in the untreated commune compared to 8% in the areas which received IRS., Conclusion: In terms of public health, the present study shows (1) a high efficacy of IRS with insecticide, (2) a similar efficacy of DDT and pyrethroid and (3) a similar efficacy of alphacypermethrin and deltamethrin. The use of IRS with DDT and pyrethroid greatly decreased the vector-human contact, with an associated decrease of the plasmodial index. However malaria transmission did not reach zero, probably due to the exophilic host-seeking and resting behaviours of the malaria vectors, thus avoiding contact with insecticide-treated surfaces indoors. The study highlights the strengths and weaknesses of the IRS implementation and the need for complementary tools for an optimal vector control in Madagascar.

Tungiasis (sand flea disease) is a neglected tropical disease. Heavy infestation results in mutilation of the feet and difficulty in walking. We identified eight individuals with extremely severe tungiasis in rural Madagascar. To prevent reinfestation, four individuals received solid shoes and four received a daily application of an herbal repellent effective against Tunga penetrans. Over a period of 10 weeks the feet were examined and the severity of tungiasis-associated morbidity was measured. Within this period, the severity score for acute tungiasis decreased 41% in the shoe group and 89% in the repellent group. The four major inflammation-related symptoms disappeared in the four patients of the repellent group, but only in two patients of the shoe group. Those observations indicate that cases with extremely severe tungiasis, associated morbidity almost totally disappears within 10 weeks if the feet are protected by a repellent. Wearing shoes reduced acute morbidity only marginally.

Background: Tungiasis, a parasitic skin disease caused by the female sand flea Tunga penetrans, is a prevalent condition in impoverished communities in the tropics. In this setting, the ectoparasitosis is associated with important morbidity. It causes disfigurement and mutilation of the feet. Feasible and effective treatment is not available. So far prevention is the only means to control tungiasis-associated morbidity., Methodology: In two villages in Central Madagascar, we assessed the efficacy of the availability of closed shoes and the twice-daily application of a plant-based repellent active against sand fleas (Zanzarin) in comparison to a control group without intervention. The study population was randomized into three groups: shoe group, repellent group and control group and monitored for ten weeks. The intensity of infestation, the attack rate and the severity of tungiasis-associated morbidity were assessed every two weeks., Findings: In the repellent group, the median attack rate became zero already after two weeks. The intensity of the infestation decreased constantly during the observation period and tungiasis-associated morbidity was lowered to an insignificant level. In the shoe group, only a marginal decrease in the intensity of infestation and in the attack rate was observed. At week 10, the intensity of infestation, the attack rate and the severity score for acute tungiasis remained significantly higher in the shoe group than in the repellent group. Per protocol analysis showed that the protective effect of shoes was closely related to the regularity with which shoes were worn., Conclusions: Although shoes were requested by the villagers and wearing shoes was encouraged by the investigators at the beginning of the study, the availability of shoes only marginally influenced the attack rate of female sand fleas. The twice-daily application of a plant-based repellent active against sand fleas reduced the attack to zero and lowered tungiasis-associated morbidity to an insignificant level.

Only a small fraction of individuals infected with Mycobacterium tuberculosis develop clinical tuberculosis (TB) in their lifetime. Genetic epidemiological evidence suggests a genetic determinism of pulmonary TB (PTB), but the molecular basis of genetic predisposition to PTB remains largely unknown. We used a positional-cloning approach to carry out ultrafine linkage-disequilibrium mapping of a previously identified susceptibility locus in chromosomal region 8q12-13 by genotyping 3,216 SNPs in a family-based Moroccan sample including 286 offspring with PTB. We observed 44 PTB-associated SNPs (p < 0.01), which were genotyped in an independent set of 317 cases and 650 controls from Morocco. A single signal, consisting of two correlated SNPs close to TOX, rs1568952 and rs2726600 (combined p = 1.1 × 10(-5) and 9.2 × 10(-5), respectively), was replicated. Stronger evidence of association was found in individuals who developed PTB before the age of 25 years (combined p for rs1568952 = 4.4 × 10(-8); odds ratio of PTB for AA versus AG/GG = 3.09 [1.99-4.78]). The association with rs2726600 (p = 0.04) was subsequently replicated in PTB-affected subjects under 25 years in a study of 243 nuclear families from Madagascar. Stronger evidence of replication in Madagascar was obtained for additional SNPs in strong linkage disequilibrium with the two initial SNPs (p = 0.003 for rs2726597), further confirming the signal. We thus identified around rs1568952 and rs2726600 a cluster of SNPs strongly associated with early-onset PTB in Morocco and Madagascar. SNP rs2726600 is located in a transcription-factor binding site in the 3' region of TOX, and further functional explorations will focus on CD4 T lymphocytes., (Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Objective: The tuberculin skin test (TST) is an important tool in the diagnosis of tuberculosis infection in children. However, the interpretation of TST may be complicated by prior Bacillus Calmette-Guerin (BCG) vaccination. We evaluated the effect of vaccination with BCG on TST reactivity in first-year pupils attending state schools in Antananarivo., Methods: STs were performed on 376 first-year schoolchildren, aged 6 and 7, attending two state primary schools. The relationships between epidemiological information, BCG status (vaccination, BCG scars) and TST reactivity were assessed to compare TST sensitivity between children with and without BCG vaccination and between those with and without a BCG scar., Result: The prevalence of positive TST results of ≥5, ≥10 and ≥ 15 mm was 20.2% (76/376), 18.3% (69/376) and 11.4% (43/376), respectively. BCG vaccination was not associated with TST reactivity, whatever the threshold used: ≥5 mm (odds ratio (OR, 1.2; 95% confidence interval (CI), 0.7-2.0); ≥10 mm (OR, 0.9; 95% CI, 0.6-1.7); ≥15 mm (OR, 0.6; 95% CI, 0.3-1.2)., Conclusion: These results suggest that in Madagascar, a positive TST result indicates TB infection (active or latent) rather than past BCG vaccination. Therefore, high BCG vaccination coverage does not appear to impair the usefulness of the TST as a tool for diagnosing tuberculosis., (© 2012 Blackwell Publishing Ltd.)

Background: To improve the diagnosis of tuberculosis (TB), more rapid diagnostic techniques such as antibody detection based on immunochromatographic methods were developed. The objective of this study was to evaluate the performance of the SD Rapid TB kit for the diagnosis of active TB with serums from patients and close contact controls in Antananarivo, Madagascar., Findings: We conducted a population-based case-control study. The sera of 60 confirmed TB patients and 60 healthy contacts paired for sex and age were tested. The controls were healthy contacts who were exposed to TB but had no clinical or radiological evidence of TB. The SD Rapid TB kit was used with serum samples according to the instructions of the manufacturer. Sensitivity, specificity, accuracy and predictive values were calculated using culture on Lövenstein-Jensen media as "gold standard".In this study, the sensitivity of the test was 55% and the specificity 90%. The positive predictive value and the negative predictive value were 84.61% and 66.66%, respectively, for diagnosis of pulmonary TB., Conclusions: This study shows that the SD Rapid TB test is a simple and fast method. This test has a good specificity and could therefore help rule in TB if positive, but lacks adequate sensitivity.

The majority of healthy individuals exposed to Mycobacterium tuberculosis will not develop tuberculosis (TB), though many may become latently infected. More precise measurement of the human immune response to M. tuberculosis infection may help us understand this difference and potentially identify those subjects most at risk of developing active disease. Gamma interferon (IFN-gamma) production has been widely used as a proxy marker to study infection and to examine the human immune response to specific M. tuberculosis antigens. It has been suggested that genetically distinct M. tuberculosis strains may invoke different immune responses, although how these differences influence the immune responses and clinical outcome in human tuberculosis is still poorly understood. We therefore evaluated the antigen-specific IFN-gamma production responses in peripheral blood mononuclear cells from two cohorts of subjects recruited in Antananarivo, Madagascar, from 2004 to 2006 and examined the influence of the infecting M. tuberculosis strains on this response. The cohorts were sputum-positive index cases and their household contacts. Clinical strains isolated from the TB patients were typed by spoligotyping. Comparison of the IFN-gamma responses with the spoligotype of the infecting clinical strains showed that "modern" M. tuberculosis strains, like Beijing and Central Asian (CAS) strains, tended to induce lower IFN-gamma responses than "ancient" strains, like East African-Indian (EAI) strains, in index cases and their household contacts. These results suggest that new strains may have evolved to induce a host response different from that of ancient strains. These findings could have important implications in the development of therapeutic and diagnostic strategies.

Madagascar has long been recognized for its unique and diverse biota. In particular, significant effort has been made to establish baseline population data to better conserve the endemic avifauna. During field expeditions between 1993 and 2004, birds were mist-netted at 11 different sites, at elevations from 60 m to 2,050 m above sea level. Data on endemic status, forest type, and habitat preference were recorded. Thin blood films from 947 birds, belonging to 26 families and 64 species, were examined by light microscopy to determine the prevalence of blood parasites. Of these 947 birds, 30.7% were infected by at least one species of blood parasite, 26.8% of which were infected by more than one species. Species of Haemoproteus were the most prevalent (17.4%), followed by microfilariae (11.0%), Leucocytozoon spp. (9.4%), Plasmodium spp. (1.9%), Trypanosoma spp. (0.9%), and Babesia spp. (0.2%). Species level identifications confirmed the presence of 47 species of hemosporidians and trypanosomes, which is notably high and mirrors the diversity of their avian hosts. Eleven (23.4%) of these parasite species were new to science and thought to be endemic to the island. Significant differences in prevalence were observed by sample site, forest type (humid vs. dry), and habitat preference. Birds from all elevational zones sampled were infected, although not all parasite genera were present in each zone. Four of the six endemic avian families or subfamilies (Bernieridae, Brachypteraciidae, Philepittinae [Eurylaimidae], and Vangidae) were sampled and found to be parasitized. Of the families with the largest sample sizes, the Zosteropidae and Ploceidae had the highest prevalence of infection (65.6% and 49.3%, respectively). The vectors of hematozoan parasites in Madagascar are currently unknown. These results add to the current knowledge of avian parasitism in Madagascar and are of particular interest for the conservation of endemic species, as well as threatened or endangered populations.

Background: The risk factors for the transmission of HCV vary substantially between countries and geographic regions. The overall prevalence in south and east Africa region has been estimated to be 1.6% but limited information about the epidemiology of HCV infection in Madagascar is available, Methods: A cross-sectional survey for hepatitis C antibodies was conducted in 2,169 subjects of the general population of Antananarivo to determine seroprevalence of hepatitis C and associated risk factors., Results: The overall seroprevalence was 1.2% (25/2,169). The prevalence did not differ significantly according to gender but it increased with age (Chi2 tendency test, p < 10-5). The variable history of hospitalization, previous therapeutic injections, dental treatment, intravenous drug use, and abnormal ALT and AST were statistically significantly related with the presence of HCV antibodies. No relationship with past history of blood transfusion was observed., Conclusion: HCV prevalence in Madagascar seems to be similar to that in most other east African countries. Age appears to be an important risk factor. Iatrogenic causes of HCV transmission need to be further evaluated because all HCV cases had a history of receiving therapeutic injections and data suggested a cumulative effect in relation with therapeutic injections.

Malaria transmission remains poorly documented in areas of low transmission. A study has been carried out over two consecutive years in Analamiranga, a village located at an altitude of 885m on the western edge of the Malagasy highlands, with the aim of generating and updating malariometric indexes for both mosquitoes and schoolchildren. In this village, no vector control measures were performed during the study period nor during previous decades. Mosquitoes were collected monthly when landing on human volunteers and in various resting-places. Blood samples were taken every 3 months from schoolchildren aged 6-12 years and microscopically examined. Of 7,480 mosquitoes collected on human subjects, 5,790 were anophelines. Ten anopheline species were represented and three of these, Anopheles funestus, Anopheles arabiensis and Anopheles mascarensis, accounted for 59.2% of the collection. Of these three species 4,640 were also collected in resting places. The proportion of mosquitoes fed on bovids was high; conversely, the anthropophilic rate (mosquitoes fed on human beings) was especially low: 31%, 7% and 1%, respectively, for A. funestus, A. arabiensis and A. mascarensis. The only confirmed malaria vector was A. funestus with a low sporozoite index (of 6,830 A. funestus, five were positive for Plasmodium falciparum and four for Plasmodium vivax). The annual entomological inoculation rate (number of bites of infected anophelines per adult person) was estimated at 2.49 with low variation over the 2 years. Overall, 909 thick blood smears were tested from blood samples taken from schoolchildren with 30.3% being malaria-positive. The four Plasmodium species infecting human subjects were detected in the following proportions: P. falciparum 78.9%, P. vivax 19.4%, Plasmodium malariae 1.0% and Plasmodium ovale 0.7%. The proportions of children who were infected with any Plasmodium ranged from 10.7% in February to 51.0% in September. Parasitemic children with fever (axillary temperature >37.5 degrees C) accounted for 16.4% of the children sampled. This study demonstrates that there are substantial parasitological consequences of even a relatively low entomological transmission and also recommends including exterior resting-places of mosquitoes in future spraying campaigns in the highlands of Madagascar.

This study aims to evaluate the prevalence and density of haemoparasites in wild malagasy bats. Among the 440 bats, belonging to 14 species sampled in 5 localities in different bio-climatic zones of the island, 93 (21%) showed at least 1 haemoparasite with, by order of frequency, Haemoproteidae (15.7% of 440 bats), microfilariae (7.0%) and Trypanosoma (0.7%). Among these 93 bats, 92 (99%) belonged to the family Vespertilionidae. Four bat species, all endemic to the Madagascar region (Madagascar and Comoros), were found to harbour parasites: Miniopterus manavi with Haemoproteidae (38% of 129 individuals), microfilariae (23%) and Trypanosoma (2%); Myotis goudoti with Haemoproteidae (24% of 68 individuals) and microfilariae (1%); Miniopterus gleni with Haemoproteidae (23% of 13 individuals); and Triaenops furculus with Haemoproteidae (4% of 28 individuals). The sex of bats was not linked to parasite prevalence. Within Miniopterus manavi, those individuals with greater weight also had a higher prevalence of microfilariae; and within the individuals harbouring microfilariae the greatest weights corresponded to the highest density of microfilariae. Ten bat species (with 202 individuals examined) were negative for any haemoparasite. This study is the first to provide evidence of haemoparasites in Malagasy bats; it provides interesting insights, especially concerning the parasite distribution per bat species and families, the pathogenicity of this type of parasitism and the parasite transmission by arthropod vectors.

This study aims to evaluate the prevalence and density of haemoparasites in native Malagasy birds. Among the 387 birds, belonging to 43 species sampled at six localities in different bio-climatic zones of the island, 139 (35.9%) showed at least 1 hemoparasite with, by order of frequency, Plasmodium and/or Haemoproteus (19.9%), microfilariae (13.7% of 387 birds), Leucocytozoon (11.1%) and Trypanosoma (1.0%). An analysis to further elucidate these observations took into account the interaction of different environmental variables (altitude, season, site of collection) or aspects of the birds (age, weight, sex). There is evidence that some parasites preferentially infect some bird species or families. The largest male birds harboured the highest prevalences and densities of haemoparasite, regardless of species. These findings extend knowledge of bird/blood parasite relationships of Malagasy birds and provide interesting insights, especially concerning the pathogenicity of this type of parasitism and the parasite transmission by insect vectors.

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.