Rindra Vatosoa Randremanana

Viral Etiology of Influenza-Like Illnesses in Antananarivo, Madagascar, July 2008 to June 2009

Background In Madagascar, despite an influenza surveillance established since 1978, little is known about the etiology and prevalence of viruses other than influenza causing influenza-like illnesses (ILIs). Methodology/Principal Findings From July 2008 to June 2009, we collected respiratory specimens from patients who presented ILIs symptoms in public and private clinics in Antananarivo (the capital city of Madagascar). ILIs were defined as body temperature ≥38°C and cough and at least two of the following symptoms: sore throat, rhinorrhea, headache and muscular pain, for a maximum duration of 3 days. We screened these specimens using five multiplex real time Reverse Transcription and/or Polymerase Chain Reaction assays for detection of 14 respiratory viruses. We detected respiratory viruses in 235/313 (75.1%) samples. Overall influenza virus A (27.3%) was the most common virus followed by rhinovirus (24.8%), RSV (21.2%), adenovirus (6.1%), coronavirus OC43 (6.1%), influenza virus B (3.9%), parainfluenza virus-3 (2.9%), and parainfluenza virus-1 (2.3%). Co-infections occurred in 29.4% (69/235) of infected patients and rhinovirus was the most detected virus (27.5%). Children under 5 years were more likely to have one or more detectable virus associated with their ILI. In this age group, compared to those ≥5 years, the risk of detecting more than one virus was higher (OR = 1.9), as was the risk of detecting of RSV (OR = 10.1) and adenovirus (OR = 4.7). While rhinovirus and adenovirus infections occurred year round, RSV, influenza virus A and coronavirus OC43 had defined period of circulation. Conclusions In our study, we found that respiratory viruses play an important role in ILIs in the Malagasy community, particularly in children under 5 years old. These data provide a better understanding of the viral etiology of outpatients with ILI and describe for the first time importance of these viruses in different age group and their period of circulation.

Case-control study of the etiology of infant diarrheal disease in 14 districts in Madagascar.

Background Acute diarrhea is a major cause of childhood morbidity and mortality worldwide. Its microbiological causes and clinico-epidemiological aspects were examined during the rainy seasons from 2008 to 2009 in 14 districts in Madagascar. Methods Stool specimens of 2196 children with acute diarrhea and 496 healthy children were collected in a community setting. Intestinal parasites were diagnosed by microscopy and bacteria by culturing methods. Rota-, astro and adenoviruses were identified using commercially available ELISA kits and rotaviruses were confirmed using reverse transcriptase polymerase chain reaction (RT-PCR). Results Intestinal microorganisms were isolated from 54.6% of diarrheal patients and 45.9% of healthy subjects (p = <0.01). The most common pathogens in diarrheic patients were intestinal parasites (36.5%). Campylobacter spp. and Rotavirus were detected in 9.7% and 6.7% of diarrheic patients. The detection rates of Entamoeba histolytica, Trichomonas intestinalis and Giardia lamblia were much greater in diarrheal patients than in non diarrheal subjects (odds ratios of 5.1, 3.2, 1.7 respectively). The abundance of other enteropathogens among the non diarrheal group may indicate prolonged excretion or limited pathogenicity. Conclusion In developing countries, where the lack of laboratory capacities is great, cross sectional studies of enteropathogens and their spatial distribution, including diarrheal and non diarrheal subjects, are interesting tools in order to advise regional policies on treatment and diarrheic patient management.

Spatial clustering of pulmonary tuberculosis and impact of the care factors in Antananarivo City

Objective  To analyse the spatial distribution of TB in Antananarivo and investigate risk factors.

Determining areas that require indoor insecticide spraying using Multi Criteria Evaluation, a decision-support tool for malaria vector control programmes in the Central Highlands of Madagascar

BackgroundThe highlands of Madagascar present an unstable transmission pattern of malaria. The population has no immunity, and the central highlands have been the sites of epidemics with particularly high fatality. The most recent epidemic occurred in the 1980s, and caused about 30,000 deaths. The fight against malaria epidemics in the highlands has been based on indoor insecticide spraying to control malaria vectors. Any preventive programme involving generalised cover in the highlands will require very substantial logistical support. We used multicriteria evaluation, by the method of weighted linear combination, as basis for improved targeting of actions by determining priority zones for intervention.ResultsImage analysis and field validation showed the accuracy of mapping rice fields to be between 82.3% and 100%, and the Kappa coefficient was 0.86 to 0.99.A significant positive correlation was observed between the abundance of the vector Anopheles funestus and temperature; the correlation coefficient was 0.599 (p < 0.001). A significant negative correlation was observed between vector abundance and human population density: the correlation coefficient was -0.551 (p < 0.003). Factor weights were determined by pair-wise comparison and the consistency ratio was 0.04. Risk maps of the six study zones were obtained according to a gradient of risk. Nine of thirteen results of alert confirmed by the Epidemiological Surveillance Post were in concordance with the risk map.ConclusionThis study is particularly valuable for the management of vector control programmes, and particularly the reduction of the vector population with a view to preventing disease. The risk map obtained can be used to identify priority zones for the management of resources, and also help avoid systematic and generalised spraying throughout the highlands: such spraying is particularly difficult and expensive.The accuracy of the mapping, both as concerns time and space, is dependent on the availability of data. Continuous monitoring of malaria transmission factors must be undertaken to detect any changes. A regular case notification allows risk map to be verified. These actions should therefore be implemented so that risk maps can be satisfactorily assessed.

Bayesian mapping of pulmonary tuberculosis in Antananarivo, Madagascar

BackgroundTuberculosis (TB), an infectious disease caused by the Mycobacterium tuberculosis is endemic in Madagascar. The capital, Antananarivo is the most seriously affected area. TB had a non-random spatial distribution in this setting, with clustering in the poorer areas. The aim of this study was to explore this pattern further by a Bayesian approach, and to measure the associations between the spatial variation of TB risk and national control program indicators for all neighbourhoods.MethodsCombination of a Bayesian approach and a generalized linear mixed model (GLMM) was developed to produce smooth risk maps of TB and to model relationships between TB new cases and national TB control program indicators. The TB new cases were collected from records of the 16 Tuberculosis Diagnostic and Treatment Centres (DTC) of the city from 2004 to 2006. And five TB indicators were considered in the analysis: number of cases undergoing retreatment, number of patients with treatment failure and those suffering relapse after the completion of treatment, number of households with more than one case, number of patients lost to follow-up, and proximity to a DTC.ResultsIn Antananarivo, 43.23% of the neighbourhoods had a standardized incidence ratio (SIR) above 1, of which 19.28% with a TB risk significantly higher than the average. Identified high TB risk areas were clustered and the distribution of TB was found to be associated mainly with the number of patients lost to follow-up (SIR: 1.10, CI 95%: 1.02-1.19) and the number of households with more than one case (SIR: 1.13, CI 95%: 1.03-1.24).ConclusionThe spatial pattern of TB in Antananarivo and the contribution of national control program indicators to this pattern highlight the importance of the data recorded in the TB registry and the use of spatial approaches for assessing the epidemiological situation for TB. Including these variables into the model increases the reproducibility, as these data are already available for individual DTCs. These findings may also be useful for guiding decisions related to disease control strategies.

Seroprevalence of hepatitis C and associated risk factors in urban areas of Antananarivo, Madagascar

BackgroundThe 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 availableMethodsA 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.ResultsThe 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.ConclusionHCV 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.

Geographical and environmental approaches to urban malaria in Antananarivo (Madagascar)

BackgroundPrevious studies, conducted in the urban of Antananarivo, showed low rate of confirmed malaria cases. We used a geographical and environmental approach to investigate the contribution of environmental factors to urban malaria in Antananarivo.MethodsRemote sensing data were used to locate rice fields, which were considered to be the principal mosquito breeding sites. We carried out supervised classification by the maximum likelihood method. Entomological study allowed vector species determination from collected larval and adult mosquitoes. Mosquito infectivity was studied, to assess the risk of transmission, and the type of mosquito breeding site was determined. Epidemiological data were collected from November 2006 to December 2007, from public health centres, to determine malaria incidence. Polymerase chain reaction was carried out on dried blood spots from patients, to detect cases of malaria. Rapid diagnostic tests were used to confirm malaria cases among febrile school children in a school survey.A geographical information system was constructed for data integration. Altitude, temperature, rainfall, population density and rice field surface area were analysed and the effects of these factors on the occurrence of confirmed malaria cases were studied.ResultsPolymerase chain reaction confirmed malaria in 5.1% of the presumed cases. Entomological studies showed An. arabiensis as potential vector. Rice fields remained to be the principal breeding sites. Travel report was considered as related to the occurrence of P. falciparum malaria cases.ConclusionGeographical and environmental factors did not show direct relationship with malaria incidence but they seem ensuring suitability of vector development. Absence of relationship may be due to a lack of statistical power. Despite the presence of An. arabiensis, scarce parasitic reservoir and rapid access to health care do not constitute optimal conditions to a threatening malaria transmission. However, imported malaria case is suggestive to sustain the pocket transmission in Antananarivo.

Longitudinal survey of malaria morbidity over 10 years in Saharevo (Madagascar): further lessons for strengthening malaria control

BackgroundMadagascar has been known for having bio-geo-ecological diversity which is reflected by a complex malaria epidemiology ranging from hyperendemic to malaria-free areas. Malaria-related attacks and infection are frequently recorded both in children and adults living in areas of low malaria transmission. To integrate this variability in the national malaria control policy, extensive epidemiological studies are required to up-date previous records and adjust strategies.MethodsA longitudinal malaria survey was conducted from July 1996 to June 2005 among an average cohort of 214 villagers in Saharevo, located at 900 m above the sea. Saharevo is a typical eastern foothill site at the junction between a costal wet tropical area (equatorial malaria pattern) and a drier high-altitude area (low malaria transmission).ResultsPassive and active malaria detection revealed that malaria transmission in Saharevo follows an abrupt seasonal variation. Interestingly, malaria was confirmed in 45% (1,271/2,794) of malaria-presumed fevers seen at the health centre. All four Plasmodia that infect humans were also found: Plasmodium falciparum; Plasmodium vivax, Plasmodium malariae and Plasmodium ovale. Half of the malaria-presumed fevers could be confirmed over the season with the highest malaria transmission level, although less than a quarter in lower transmission time, highlighting the importance of diagnosis prior to treatment intake. P. falciparum malaria has been predominant (98%). The high prevalence of P. falciparum malaria affects more particularly under 10 years old children in both symptomatic and asymptomatic contexts. Children between two and four years of age experienced an average of 2.6 malaria attacks with P. falciparum per annum. Moreover, estimated incidence of P. falciparum malaria tends to show that half of the attacks (15 attacks) risk to occur during the first 10 years of life for a 60-year-old adult who would have experienced 32 malaria attacks.ConclusionThe incidence of malaria decreased slightly with age but remained important among children and adults in Saharevo. These results support that a premunition against malaria is slowly acquired until adolescence. However, this claims for a weak premunition among villagers in Saharevo and by extension in the whole eastern foothill area of Madagascar. While the Malagasy government turns towards malaria elimination plans nowadays, choices and expectations to up-date and adapt malaria control strategies in the foothill areas are discussed in this paper.

Susceptibility of Plasmodium falciparum to the drugs used to treat severe malaria (quinine) and to prevent malaria (mefloquine, cycloguanil) in Comoros Union and Madagascar

OBJECTIVES To monitor the sensitivity of Plasmodium falciparum to the drugs used to treat severe malaria and to prevent malaria in Comoros and Madagascar. DESIGN We used the in vitro isotopic method to test the sensitivity of P. falciparum to quinine, mefloquine and cycloguanil. RESULTS We tested fresh isolates of P. falciparum, collected from patients living in urban, suburban and rural areas and suffering from uncomplicated malaria in 2001, against at least one of the antimalarials cited above. In both countries all of the successfully tested isolates were sensitive to quinine (N = 243) and to cycloguanil (N = 67). The mean IC50 ranged from 85.7 to 133.7 nM for quinine. For cycloguanil, the mean IC50 ranged from 1.4 to 20.2 nM and the highest IC50 value (102.5 nM) was recorded in Comoros. Only 0.9% (1/110) of the informative isolates from Madagascar were mefloquine-resistant (0/18 in Comoros). The mefloquine mean IC50s were 8.2 nM, 14.1 nM and 11.6 nM respectively in the rural, suburban and urban areas of Madagascar, and 5.9 nM in Comoros. A positive correlation was found between quinine and mefloquine IC50s (N = 127, r = 0.48, p < 10(-6)), but in vitro mefloquine was 6-16 times more potent than quinine. No correlation was noticed between the activities of quinine and cycloguanil or between the activities of mefloquine and cycloguanil. CONCLUSION We therefore advocate the use of a full-course regimen of quinine, as recommended by the World Health Organisation (WHO), to treat above all severe malaria in Madagascar and Comoros. Our results also demonstrate that the use of mefloquine- and cycloguanil-based antimalarials is still justified to prevent malaria in both countries, mainly in the case of travellers.

Rotavirus genotypes in children in the community with diarrhea in Madagascar.

In the context of the possible introduction of a preventive vaccine against rotaviruses in Madagascar, the G and P genotypes distribution of the rotaviruses circulating in the children in Madagascar was studied, and the presence of emerging genotypes and unusual strains were assessed. From February 2008 to May 2009, 1,679 stools specimens were collected from children ≤5 years old with diarrhea. ELISA was used for antigen detection, and molecular amplification of VP7 and VP4 gene fragments was used for genotyping. Rotavirus antigen was detected in 104 samples (6.2%). Partial sequences of VP7 and VP4 genes were obtained from 81 and 80 antigen‐positive stools, respectively. The most frequent G and P types combinations detected were G9P[8] (n = 51; 64.6%), followed by G1P[8] (n = 15; 18.9%), and G1P[6] (n = 8; 10.1%). A few unusual G‐P combinations, such as G4P[6] (n = 3; 3.8%), G9P[6] (n = 1; 1.3%), and G3P[9] reassortant feline human virus (n = 1; 1.3%) were identified. Both VP4 and VP7 sequences in one of the three G4P[6] isolates were closely related to those in porcine strains, and one was a reassortant human porcine virus. These findings give an overview of the strains circulating in Madagascar and should help public health authorities to define a vaccine strategy. J. Med. Virol. 85:1652–1660, 2013.