Milijaona Randrianarivelojosia - Academia.edu (original) (raw)
Papers by Milijaona Randrianarivelojosia
PLOS Neglected Tropical Diseases, 2018
Background The increasing use of malaria diagnostic tests reveals a growing proportion of patient... more Background The increasing use of malaria diagnostic tests reveals a growing proportion of patients with fever but no malaria. Clinicians and health care workers in low-income countries have few tests to diagnose causes of fever other than malaria although several diseases share common symptoms. We propose here to assess etiologies of fever in Madagascar to ultimately improve management of febrile cases. Methodology Consenting febrile outpatients aged 6 months and older were recruited in 21 selected sentinel sites throughout Madagascar from April 2014 to September 2015. Standard clinical examinations were performed, and blood and upper respiratory specimens were taken for rapid diagnostic tests and molecular assays for 36 pathogens of interest for Madagascar in terms of public health, regardless of clinical status. Principal findings A total of 682 febrile patients were enrolled. We detected at least one pathogen in 40.5% (276/682) of patients and 6.2% (42/682) with co-infections. Among all tested patients, 26.5% (181/682) had at least one viral infection, 17.0% (116/682) had malaria and 1.0% (7/682) presented a bacterial or a mycobacterial infection. None or very few of the highly prevalent infectious agents in Eastern Africa and Asia were detected in this study, such as zoonotic bacteria or arboviral infections.
The American Journal of Tropical Medicine and Hygiene, 2007
We assessed the status of point mutations associated with chloroquine resistance in pfcrt codon 7... more We assessed the status of point mutations associated with chloroquine resistance in pfcrt codon 76 and in pfmdr1 codon 86 among Plasmodium falciparum isolates from symptomatic patients in 3 sites in Madagascar. The in vitro susceptibility of P. falciparum isolates to quinoline-containing drugs was also determined. All isolates (N ס 117) successfully typed were pfcrt wild-type, except one from Tsiroanomandidy (1 of 27). However, 67.5% (95% CI: 58.2-75.9%) of these isolates contained mutant pfmdr1 86Y. The pfmdr1 N86Y mutation is associated with higher mefloquine susceptibility, but it did not affect the sensitivity of parasites to chloroquine or quinine. Our findings demonstrate that pfmdr1 mutant P. falciparum are prevalent in Madagascar and confirm the low prevalence of pfcrt mutant P. falciparum after 60 years of chloroquine use. They provide additional field-based evidence for increased mefloquine susceptibility in pfmdr1 mutant P. falciparum and are suggestive of the intrahost selection of pfmdr1 mutant parasites.
Parassitologia, 2002
Chloroquine has been used in Madagascar since 1945 and remains the first-line treatment for uncom... more Chloroquine has been used in Madagascar since 1945 and remains the first-line treatment for uncomplicated cases of malaria. Low-grades of resistance type R1 and R2 have been reported. Thus, in vitro tests were performed in order to monitor the drug sensitivity of Plasmodium falciparum from different study sites, with the aim of identifying alternatives to chloroquine. Chloroquine IC50 values ranged from 0.2 nM to 283.4 nM (n = 190, mean IC50 = 52.6 nM; 95% CI = 46.1-59.1 nM). Fifteen isolates (7.9%) were chloroquine-resistant. One mefloquine-resistant isolate was detected (1/139). The test isolates were sensitive to amodiaquine (n = 118), quinine (n = 212), pyrimethamine (n = 86) and cycloguanil (n = 79). The median IC50 for amodiaquine was 12.3 nM (mean IC50 = 15.3 nM, 95% CI = 13.3-17.3 nM). Amodiaquine was 3.4 times as active as chloroquine in vitro and 7 times as active as quinine against P. falciparum. These results indicate that amodiaquine may be a potent alternative to chlor...
BioMed Research International, 2018
Introduction. In Madagascar, malaria control relies on the countrywide use of long lasting insect... more Introduction. In Madagascar, malaria control relies on the countrywide use of long lasting insecticide treated bed nets (LLINs) and on indoor residual spraying (IRS) in the central highland area as well as a small area on the eastern coast. We tested insecticide resistance mechanisms of Anopheles funestus from Tsararano, a malaria endemic village in the coastal health district of Marovoay. Methods. Insecticide susceptibility bioassays were done in July 2017 on first-generation Anopheles funestus (F1) to assess (i) the susceptibility to permethrin (0.05%), deltamethrin (0.05%), DDT (4%), malathion (5%), fenitrothion (1%), and bendiocarb (0.1%); (ii) the effect of preexposure to the piperonyl butoxide (PBO) synergist; and (iii) the enzymatic activities of cytochrome P450, esterases, and glutathione S-transferases (GST). Results. Our results demonstrated that An. funestus was phenotypically resistant to pyrethroids and bendiocarb, with a mortality rate (MR) of 33.6% (95%CI: 24.5-43.7%)...
Médecine tropicale : revue du Corps de santé colonial, 2000
Chloroquine is still the drug of choice for first-line treatment of uncomplicated malaria in Mada... more Chloroquine is still the drug of choice for first-line treatment of uncomplicated malaria in Madagascar. However development and spread of chloroquine-resistance could compromise this therapeutic strategy in the future. The purpose of this 1997 study was to compare the efficacy of combined treatment using sulfadoxine and pyrimethamine and single-agent treatment using chloroquine for management of uncomplicated malaria. Study data were collected at four sites in coastal areas of Madagascar where transmission of malaria is perennial. Prevalence of malaria ranged from 15 p. 100 to 22 p. 100 in school children and from 24 p. 100 to 72 p. 100 in outpatient consulting spontaneously at community health centers. All four Plasmodium species affecting man were identified. Plasmodium falciparum was involved in 83 p. 100 of cases. In vivo testing of the susceptibility of Plasmodium falciparum to chloroquine was performed in 149 patients according to the standard simplified 7-day protocol of the...
MalariaGEN is a data-sharing network that enables groups around the world to work together on the... more MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research ...
Malaria Journal, 2016
Background: The malaria burden in Madagascar dropped down last decade, largely due to scale-up of... more 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 SouthEastern 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 socioeconomic 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 SouthEastern 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.
Do ethnobotanical and laboratory data predict clinical safety and efficacy of anti-malarial plants?
Madagascar joined “Roll Back Malaria” in 2002. During the last 15 years, the Malagasy government ... more Madagascar joined “Roll Back Malaria” in 2002. During the last 15 years, the Malagasy government has received significant external funds to implement malaria operational strategies. Madagascar recorded progress due to scale-up interventions. Nevertheless, the number of malaria cases has increased significantly since 2012. This paper aims to estimate the cost of the national malaria program corresponding to the national strategic plan from 2009 to 2013 and the cost-effectiveness of two malaria control strategies (indoor spraying insecticide -IRSand insecticide treated nets -ITN), using household survey data from 2014 in two districts in Madagascar. The cost-effectiveness of IRS and ITN was estimated at the district level. For this purpose, the total cost of the national malaria control program (NMCP) and the cost of cases averted were calculated. The NMCP has cost USD 46,588,677 or USD 2.1 per capita per year from 2009 to 2013. The implementation of IRS costs about 4 times more than ...
BMC medicine, May 23, 2018
Reliable measures of disease burden over time are necessary to evaluate the impact of interventio... more Reliable measures of disease burden over time are necessary to evaluate the impact of interventions and assess sub-national trends in the distribution of infection. Three Malaria Indicator Surveys (MISs) have been conducted in Madagascar since 2011. They provide a valuable resource to assess changes in burden that is complementary to the country's routine case reporting system. A Bayesian geostatistical spatio-temporal model was developed in an integrated nested Laplace approximation framework to map the prevalence of Plasmodium falciparum malaria infection among children from 6 to 59 months in age across Madagascar for 2011, 2013 and 2016 based on the MIS datasets. The model was informed by a suite of environmental and socio-demographic covariates known to influence infection prevalence. Spatio-temporal trends were quantified across the country. Despite a relatively small decrease between 2013 and 2016, the prevalence of malaria infection has increased substantially in all area...
Revue d'Épidémiologie et de Santé Publique, 2017
Malaria journal, Jan 11, 2016
Madagascar, as other malaria endemic countries, depends mainly on international funding for the i... more 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. 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...
Effect of the supernatant from mice liver cells primary culture on in vitro growth of Plasmodium ... more Effect of the supernatant from mice liver cells primary culture on in vitro growth of Plasmodium falciparum isolates" : Cultivation of Plasmodium falciparum has been a major research success, leading to a greater understanding of the parasite. Despite the fact that several P. falciparum clones have been maintained in continuous culture in different laboratories, research in genomics and proteomics would require parasitic material produced from fresh wild isolates. We have tested the effect of the supernatant from primary culture of mice hepatocytes on in vitro growth of P. falciparum isolates. Parasitized blood samples were collected from Madagascan malarious patients naturally infected. Isolates proliferation was assessed by use of isotopic method. The asexual erythrocytic stages of P. falciparum were grown for 42 hours in RPMI 1640-based medium plus L15 medium- based supernatant from mice liver cells culture, and in standard RPMI 1640-based medium alone. The mean of parasite ...
Archives de l'Institut Pasteur de Madagascar, 2002
This study aims to evaluate the prevalence and density of haemoparasites in native Malagasy birds... more 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 ...
La culture in vitro des stades sanguins de Plasmodium falciparum a de nombreuses applications. De... more La culture in vitro des stades sanguins de Plasmodium falciparum a de nombreuses applications. Des clones de P falciparum sont maintenus en culture continue dans differents laboratoires travaillant sur le paludisme. Cependant, la recherche en genomique necessite davantage l'obtention de molecules parasitaires a partir des isolats sauvages. Nous avons teste l'effet du surnageant de culture primaire d'hepatocytes sur la croissance in vitro de P. falciparum preleve dans le sang de porteurs de parasites naturellement infectes a Madagascar. La proliferation des parasites a ete evaluee par la methode isotopique basee sur l'incorporation de l'hypoxanthine tritiee. On a compare la culture pendant 42 heures soit dans le milieu standard a base de RPMI 1640 additionne de surnageant de culture d'hepatocytes a base de L15, soit dans le milieu standard seul. La moyenne des facteurs de proliferation des parasites etait 1,5 fois plus elevee en presence de surnageant de cultu...
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 2004
OBJECTIVES To monitor the sensitivity of Plasmodium falciparum to the drugs used to treat severe ... more 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, su...
Malaria Journal, 2021
Background Numerous studies have been undertaken to advance knowledge of apicomplexan parasites i... more Background Numerous studies have been undertaken to advance knowledge of apicomplexan parasites infecting vertebrates, including humans. Of these parasites, the genus Plasmodium has been most extensively studied because of the socio-economic and public health impacts of malaria. In non-human vertebrates, studies on malaria or malaria-like parasite groups have been conducted but information is far from complete. In Madagascar, recent studies on bat blood parasites indicate that three chiropteran families (Miniopteridae, Rhinonycteridae, and Vespertilionidae) are infected by the genus Polychromophilus with pronounced host specificity: Miniopterus spp. (Miniopteridae) harbour Polychromophilus melanipherus and Myotis goudoti (Vespertilionidae) is infected by Polychromophilus murinus. However, most of the individuals analysed in previous studies were sampled on the western and central portions of the island. The aims of this study are (1) to add new information on bat blood parasites in ...
PLOS ONE, 2018
Introduction Intestinal parasitic infections are a major public health problem in inter-tropical ... more Introduction Intestinal parasitic infections are a major public health problem in inter-tropical areas. The aim of our study was to describe the situation in Mahajanga, Madagascar with a particular focus on two protozoa, Dientamoeba fragilis and Blastocystis sp. Methods This was a prospective study from February to June 2015. Stool samples from symptomatic hospitalized patients and asymptomatic volunteers were submitted to microscopy and molecular assays in order to detect parasites. Results A wide panel of intestinal parasites were identified among the 265 included subjects, protozoa being the most prevalent with 72.8% whereas the prevalence of helminths and microsporidia was of 7.9% and 4.5%, respectively. Blastocystis sp. was the most prevalent protozoa (64.5% of the entire cohort) followed by various amoebas (35.5%) and flagellates (27,5%). We only detected subtypes 1, 2 and 3 of Blastocystis sp. Among the patients positive for D. fragilis (9.4%), 23 carried genotype 1 and 1 genotype 2. For the first time, we detected in 4 human stools the DNA of a recently described protozoon, Simplicimonas similis. Interestingly, subjects living in urban areas harbored significantly more different parasitic species than subjects living in rural areas with a correlation between sanitary level of neighborhood and protozoan infection. However, there was no difference in prevalence of digestive symptoms between parasite-free and parasite-infected subjects, except for Giardia intestinalis which had more symptomatic carriers.
PLOS Neglected Tropical Diseases, 2018
Background The increasing use of malaria diagnostic tests reveals a growing proportion of patient... more Background The increasing use of malaria diagnostic tests reveals a growing proportion of patients with fever but no malaria. Clinicians and health care workers in low-income countries have few tests to diagnose causes of fever other than malaria although several diseases share common symptoms. We propose here to assess etiologies of fever in Madagascar to ultimately improve management of febrile cases. Methodology Consenting febrile outpatients aged 6 months and older were recruited in 21 selected sentinel sites throughout Madagascar from April 2014 to September 2015. Standard clinical examinations were performed, and blood and upper respiratory specimens were taken for rapid diagnostic tests and molecular assays for 36 pathogens of interest for Madagascar in terms of public health, regardless of clinical status. Principal findings A total of 682 febrile patients were enrolled. We detected at least one pathogen in 40.5% (276/682) of patients and 6.2% (42/682) with co-infections. Among all tested patients, 26.5% (181/682) had at least one viral infection, 17.0% (116/682) had malaria and 1.0% (7/682) presented a bacterial or a mycobacterial infection. None or very few of the highly prevalent infectious agents in Eastern Africa and Asia were detected in this study, such as zoonotic bacteria or arboviral infections.
The American Journal of Tropical Medicine and Hygiene, 2007
We assessed the status of point mutations associated with chloroquine resistance in pfcrt codon 7... more We assessed the status of point mutations associated with chloroquine resistance in pfcrt codon 76 and in pfmdr1 codon 86 among Plasmodium falciparum isolates from symptomatic patients in 3 sites in Madagascar. The in vitro susceptibility of P. falciparum isolates to quinoline-containing drugs was also determined. All isolates (N ס 117) successfully typed were pfcrt wild-type, except one from Tsiroanomandidy (1 of 27). However, 67.5% (95% CI: 58.2-75.9%) of these isolates contained mutant pfmdr1 86Y. The pfmdr1 N86Y mutation is associated with higher mefloquine susceptibility, but it did not affect the sensitivity of parasites to chloroquine or quinine. Our findings demonstrate that pfmdr1 mutant P. falciparum are prevalent in Madagascar and confirm the low prevalence of pfcrt mutant P. falciparum after 60 years of chloroquine use. They provide additional field-based evidence for increased mefloquine susceptibility in pfmdr1 mutant P. falciparum and are suggestive of the intrahost selection of pfmdr1 mutant parasites.
Parassitologia, 2002
Chloroquine has been used in Madagascar since 1945 and remains the first-line treatment for uncom... more Chloroquine has been used in Madagascar since 1945 and remains the first-line treatment for uncomplicated cases of malaria. Low-grades of resistance type R1 and R2 have been reported. Thus, in vitro tests were performed in order to monitor the drug sensitivity of Plasmodium falciparum from different study sites, with the aim of identifying alternatives to chloroquine. Chloroquine IC50 values ranged from 0.2 nM to 283.4 nM (n = 190, mean IC50 = 52.6 nM; 95% CI = 46.1-59.1 nM). Fifteen isolates (7.9%) were chloroquine-resistant. One mefloquine-resistant isolate was detected (1/139). The test isolates were sensitive to amodiaquine (n = 118), quinine (n = 212), pyrimethamine (n = 86) and cycloguanil (n = 79). The median IC50 for amodiaquine was 12.3 nM (mean IC50 = 15.3 nM, 95% CI = 13.3-17.3 nM). Amodiaquine was 3.4 times as active as chloroquine in vitro and 7 times as active as quinine against P. falciparum. These results indicate that amodiaquine may be a potent alternative to chlor...
BioMed Research International, 2018
Introduction. In Madagascar, malaria control relies on the countrywide use of long lasting insect... more Introduction. In Madagascar, malaria control relies on the countrywide use of long lasting insecticide treated bed nets (LLINs) and on indoor residual spraying (IRS) in the central highland area as well as a small area on the eastern coast. We tested insecticide resistance mechanisms of Anopheles funestus from Tsararano, a malaria endemic village in the coastal health district of Marovoay. Methods. Insecticide susceptibility bioassays were done in July 2017 on first-generation Anopheles funestus (F1) to assess (i) the susceptibility to permethrin (0.05%), deltamethrin (0.05%), DDT (4%), malathion (5%), fenitrothion (1%), and bendiocarb (0.1%); (ii) the effect of preexposure to the piperonyl butoxide (PBO) synergist; and (iii) the enzymatic activities of cytochrome P450, esterases, and glutathione S-transferases (GST). Results. Our results demonstrated that An. funestus was phenotypically resistant to pyrethroids and bendiocarb, with a mortality rate (MR) of 33.6% (95%CI: 24.5-43.7%)...
Médecine tropicale : revue du Corps de santé colonial, 2000
Chloroquine is still the drug of choice for first-line treatment of uncomplicated malaria in Mada... more Chloroquine is still the drug of choice for first-line treatment of uncomplicated malaria in Madagascar. However development and spread of chloroquine-resistance could compromise this therapeutic strategy in the future. The purpose of this 1997 study was to compare the efficacy of combined treatment using sulfadoxine and pyrimethamine and single-agent treatment using chloroquine for management of uncomplicated malaria. Study data were collected at four sites in coastal areas of Madagascar where transmission of malaria is perennial. Prevalence of malaria ranged from 15 p. 100 to 22 p. 100 in school children and from 24 p. 100 to 72 p. 100 in outpatient consulting spontaneously at community health centers. All four Plasmodium species affecting man were identified. Plasmodium falciparum was involved in 83 p. 100 of cases. In vivo testing of the susceptibility of Plasmodium falciparum to chloroquine was performed in 149 patients according to the standard simplified 7-day protocol of the...
MalariaGEN is a data-sharing network that enables groups around the world to work together on the... more MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research ...
Malaria Journal, 2016
Background: The malaria burden in Madagascar dropped down last decade, largely due to scale-up of... more 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 SouthEastern 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 socioeconomic 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 SouthEastern 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.
Do ethnobotanical and laboratory data predict clinical safety and efficacy of anti-malarial plants?
Madagascar joined “Roll Back Malaria” in 2002. During the last 15 years, the Malagasy government ... more Madagascar joined “Roll Back Malaria” in 2002. During the last 15 years, the Malagasy government has received significant external funds to implement malaria operational strategies. Madagascar recorded progress due to scale-up interventions. Nevertheless, the number of malaria cases has increased significantly since 2012. This paper aims to estimate the cost of the national malaria program corresponding to the national strategic plan from 2009 to 2013 and the cost-effectiveness of two malaria control strategies (indoor spraying insecticide -IRSand insecticide treated nets -ITN), using household survey data from 2014 in two districts in Madagascar. The cost-effectiveness of IRS and ITN was estimated at the district level. For this purpose, the total cost of the national malaria control program (NMCP) and the cost of cases averted were calculated. The NMCP has cost USD 46,588,677 or USD 2.1 per capita per year from 2009 to 2013. The implementation of IRS costs about 4 times more than ...
BMC medicine, May 23, 2018
Reliable measures of disease burden over time are necessary to evaluate the impact of interventio... more Reliable measures of disease burden over time are necessary to evaluate the impact of interventions and assess sub-national trends in the distribution of infection. Three Malaria Indicator Surveys (MISs) have been conducted in Madagascar since 2011. They provide a valuable resource to assess changes in burden that is complementary to the country's routine case reporting system. A Bayesian geostatistical spatio-temporal model was developed in an integrated nested Laplace approximation framework to map the prevalence of Plasmodium falciparum malaria infection among children from 6 to 59 months in age across Madagascar for 2011, 2013 and 2016 based on the MIS datasets. The model was informed by a suite of environmental and socio-demographic covariates known to influence infection prevalence. Spatio-temporal trends were quantified across the country. Despite a relatively small decrease between 2013 and 2016, the prevalence of malaria infection has increased substantially in all area...
Revue d'Épidémiologie et de Santé Publique, 2017
Malaria journal, Jan 11, 2016
Madagascar, as other malaria endemic countries, depends mainly on international funding for the i... more 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. 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...
Effect of the supernatant from mice liver cells primary culture on in vitro growth of Plasmodium ... more Effect of the supernatant from mice liver cells primary culture on in vitro growth of Plasmodium falciparum isolates" : Cultivation of Plasmodium falciparum has been a major research success, leading to a greater understanding of the parasite. Despite the fact that several P. falciparum clones have been maintained in continuous culture in different laboratories, research in genomics and proteomics would require parasitic material produced from fresh wild isolates. We have tested the effect of the supernatant from primary culture of mice hepatocytes on in vitro growth of P. falciparum isolates. Parasitized blood samples were collected from Madagascan malarious patients naturally infected. Isolates proliferation was assessed by use of isotopic method. The asexual erythrocytic stages of P. falciparum were grown for 42 hours in RPMI 1640-based medium plus L15 medium- based supernatant from mice liver cells culture, and in standard RPMI 1640-based medium alone. The mean of parasite ...
Archives de l'Institut Pasteur de Madagascar, 2002
This study aims to evaluate the prevalence and density of haemoparasites in native Malagasy birds... more 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 ...
La culture in vitro des stades sanguins de Plasmodium falciparum a de nombreuses applications. De... more La culture in vitro des stades sanguins de Plasmodium falciparum a de nombreuses applications. Des clones de P falciparum sont maintenus en culture continue dans differents laboratoires travaillant sur le paludisme. Cependant, la recherche en genomique necessite davantage l'obtention de molecules parasitaires a partir des isolats sauvages. Nous avons teste l'effet du surnageant de culture primaire d'hepatocytes sur la croissance in vitro de P. falciparum preleve dans le sang de porteurs de parasites naturellement infectes a Madagascar. La proliferation des parasites a ete evaluee par la methode isotopique basee sur l'incorporation de l'hypoxanthine tritiee. On a compare la culture pendant 42 heures soit dans le milieu standard a base de RPMI 1640 additionne de surnageant de culture d'hepatocytes a base de L15, soit dans le milieu standard seul. La moyenne des facteurs de proliferation des parasites etait 1,5 fois plus elevee en presence de surnageant de cultu...
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 2004
OBJECTIVES To monitor the sensitivity of Plasmodium falciparum to the drugs used to treat severe ... more 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, su...
Malaria Journal, 2021
Background Numerous studies have been undertaken to advance knowledge of apicomplexan parasites i... more Background Numerous studies have been undertaken to advance knowledge of apicomplexan parasites infecting vertebrates, including humans. Of these parasites, the genus Plasmodium has been most extensively studied because of the socio-economic and public health impacts of malaria. In non-human vertebrates, studies on malaria or malaria-like parasite groups have been conducted but information is far from complete. In Madagascar, recent studies on bat blood parasites indicate that three chiropteran families (Miniopteridae, Rhinonycteridae, and Vespertilionidae) are infected by the genus Polychromophilus with pronounced host specificity: Miniopterus spp. (Miniopteridae) harbour Polychromophilus melanipherus and Myotis goudoti (Vespertilionidae) is infected by Polychromophilus murinus. However, most of the individuals analysed in previous studies were sampled on the western and central portions of the island. The aims of this study are (1) to add new information on bat blood parasites in ...
PLOS ONE, 2018
Introduction Intestinal parasitic infections are a major public health problem in inter-tropical ... more Introduction Intestinal parasitic infections are a major public health problem in inter-tropical areas. The aim of our study was to describe the situation in Mahajanga, Madagascar with a particular focus on two protozoa, Dientamoeba fragilis and Blastocystis sp. Methods This was a prospective study from February to June 2015. Stool samples from symptomatic hospitalized patients and asymptomatic volunteers were submitted to microscopy and molecular assays in order to detect parasites. Results A wide panel of intestinal parasites were identified among the 265 included subjects, protozoa being the most prevalent with 72.8% whereas the prevalence of helminths and microsporidia was of 7.9% and 4.5%, respectively. Blastocystis sp. was the most prevalent protozoa (64.5% of the entire cohort) followed by various amoebas (35.5%) and flagellates (27,5%). We only detected subtypes 1, 2 and 3 of Blastocystis sp. Among the patients positive for D. fragilis (9.4%), 23 carried genotype 1 and 1 genotype 2. For the first time, we detected in 4 human stools the DNA of a recently described protozoon, Simplicimonas similis. Interestingly, subjects living in urban areas harbored significantly more different parasitic species than subjects living in rural areas with a correlation between sanitary level of neighborhood and protozoan infection. However, there was no difference in prevalence of digestive symptoms between parasite-free and parasite-infected subjects, except for Giardia intestinalis which had more symptomatic carriers.