Resistance-mediating Polymorphisms in Plasmodium falciparum Infections in Kinshasa, Democratic Republic of the Congo

2009 ◽  
Vol 80 (4) ◽  
pp. 555-558 ◽  
Author(s):  
Linda Mobula ◽  
Philip J. Rosenthal ◽  
Bruce Lilley ◽  
Antoinette K. Tshefu
2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Jeanine A. C. M. Loonen ◽  
Dominic B. Dery ◽  
Bertin Z. Musaka ◽  
Janvier B. Bandibabone ◽  
Teun Bousema ◽  
...  

Abstract Background Malaria remains a major public health concern in the Democratic Republic of the Congo (DRC) and its control is affected by recurrent conflicts. Médecins Sans Frontières (MSF) initiated several studies to better understand the unprecedented incidence of malaria to effectively target and implement interventions in emergency settings. The current study evaluated the main vector species involved in malaria transmission and their resistance to insecticides, with the aim to propose the most effective tools and strategies for control of local malaria vectors. Methods This study was performed in 52 households in Shamwana (Katanga, 2014), 168 households in Baraka (South Kivu, 2015) and 269 households in Kashuga (North Kivu, 2017). Anopheles vectors were collected and subjected to standardized Word Health Organization (WHO) and Center for Disease Control (CDC) insecticide susceptibility bioassays. Mosquito species determination was done using PCR and Plasmodium falciparum infection in mosquitoes was assessed by ELISA targeting circumsporozoite protein. Results Of 3517 Anopheles spp. mosquitoes collected, Anopheles gambiae sensu lato (s.l.) (29.6%) and Anopheles funestus (69.1%) were the main malaria vectors. Plasmodium falciparum infection rates for An. gambiae s.l. were 1.0, 2.1 and 13.9% for Shamwana, Baraka and Kashuga, respectively. Anopheles funestus showed positivity rates of 1.6% in Shamwana and 4.4% in Baraka. No An. funestus were collected in Kashuga. Insecticide susceptibility tests showed resistance development towards pyrethroids in all locations. Exposure to bendiocarb, malathion and pirimiphos-methyl still resulted in high mosquito mortality. Conclusions This is one of only few studies from these conflict areas in DRC to report insecticide resistance in local malaria vectors. The data suggest that current malaria prevention methods in these populations are only partially effective, and require additional tools and strategies. Importantly, the results triggered MSF to consider the selection of a new insecticide for indoor residual spraying (IRS) and a new long-lasting insecticide-treated net (LLIN). The reinforcement of correct usage of LLINs and the introduction of targeted larviciding were also included as additional vector control tools as a result of the studies.


2019 ◽  
Author(s):  
Molly N/A Deutsch-Feldman ◽  
Ozkan Aydemir ◽  
Margaret Carrel ◽  
Nicholas F. Brazeau ◽  
Samir Bhatt ◽  
...  

Abstract Background: Drug resistant malaria is a growing concern in the Democratic Republic of the Congo (DRC), where previous studies indicate that parasites resistant to sulfadoxine/pyrimethamine or chloroquine are spatially clustered. This study explores longitudinal changes in spatial patterns to understand how resistant malaria may be spreading within the DRC, using samples from nation-wide population-representative surveys. Methods: We selected 552 children with PCR-detectable Plasmodium falciparum infection and identified known variants in the pfdhps and pfcrt genes associated with resistance. We compared the proportion of mutant parasites in 2013 to those previously reported from adults in 2007, and identified risk factors for carrying a resistant allele using multivariate mixed-effects modeling. Finally, we fit a spatial-temporal model to the observed data, providing smooth allele frequency estimates over space and time. Results: The proportion of co-occurring pfdhps K540E/A581G mutations increased by 16% between 2007 and 2013. The spatial-temporal model suggests that the spatial range of the pfdhps double mutants expanded over time, while the prevalence and range of pfcrt mutations remained steady. Conclusions: This study uses population-representative samples to describe the changing landscape of SP resistance within the DRC, and the persistence of chloroquine resistance. Vigilant molecular surveillance is critical for controlling the spread of resistance.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Molly Deutsch-Feldman ◽  
Ozkan Aydemir ◽  
Margaret Carrel ◽  
Nicholas F. Brazeau ◽  
Samir Bhatt ◽  
...  

Abstract Background Drug resistant malaria is a growing concern in the Democratic Republic of the Congo (DRC), where previous studies indicate that parasites resistant to sulfadoxine/pyrimethamine or chloroquine are spatially clustered. This study explores longitudinal changes in spatial patterns to understand how resistant malaria may be spreading within the DRC, using samples from nation-wide population-representative surveys. Methods We selected 552 children with PCR-detectable Plasmodium falciparum infection and identified known variants in the pfdhps and pfcrt genes associated with resistance. We compared the proportion of mutant parasites in 2013 to those previously reported from adults in 2007, and identified risk factors for carrying a resistant allele using multivariate mixed-effects modeling. Finally, we fit a spatial-temporal model to the observed data, providing smooth allele frequency estimates over space and time. Results The proportion of co-occurring pfdhps K540E/A581G mutations increased by 16% between 2007 and 2013. The spatial-temporal model suggests that the spatial range of the pfdhps double mutants expanded over time, while the prevalence and range of pfcrt mutations remained steady. Conclusions This study uses population-representative samples to describe the changing landscape of SP resistance within the DRC, and the persistence of chloroquine resistance. Vigilant molecular surveillance is critical for controlling the spread of resistance.


2018 ◽  
Vol 73 (10) ◽  
pp. 2704-2715 ◽  
Author(s):  
Papy Nkoli Mandoko ◽  
Florent Rouvier ◽  
Lebon Matendo Kakina ◽  
Destin Moke Mbongi ◽  
Christine Latour ◽  
...  

2019 ◽  
Author(s):  
Molly N/A Deutsch-Feldman ◽  
Ozkan Aydemir ◽  
Margaret Carrel ◽  
Nicholas F. Brazeau ◽  
Samir Bhatt ◽  
...  

Abstract Background: Drug resistant malaria is a growing concern in the Democratic Republic of the Congo (DRC), where previous studies indicate that parasites resistant to sulfadoxine/pyrimethamine or chloroquine are spatially clustered. This study explores longitudinal changes in spatial patterns to understand how resistant malaria may be spreading within the DRC, using samples from nation-wide population-representative surveys. Methods: We selected 552 children with PCR-detectable Plasmodium falciparum infection and identified known variants in the pfdhps and pfcrt genes associated with resistance. We compared the proportion of mutant parasites in 2013 to those previously reported from adults in 2007, and identified risk factors for carrying a resistant allele using multivariate mixed-effects modeling. Finally, we fit a spatial-temporal model to the observed data, providing smooth allele frequency estimates over space and time. Results: The proportion of co-occurring pfdhps K540E/A581G mutations increased by 16% between 2007 and 2013. The spatial-temporal model suggests that the spatial range of the pfdhps double mutants expanded over time, while the prevalence and range of pfcrt mutations remained steady. Conclusions: This study uses population-representative samples to describe the changing landscape of SP resistance within the DRC, and the persistence of chloroquine resistance. Vigilant molecular surveillance is critical for controlling the spread of resistance.


2014 ◽  
Vol 58 (9) ◽  
pp. 5528-5536 ◽  
Author(s):  
M. A. Onyamboko ◽  
C. I. Fanello ◽  
K. Wongsaen ◽  
J. Tarning ◽  
P. Y. Cheah ◽  
...  

ABSTRACTAn open-label, randomized controlled trial was carried out in 2011–2012 in the Democratic Republic of the Congo to test the efficacy, safety, and tolerability of the artemisinin-based combination treatments dihydroartemisinin-piperaquine, amodiaquine-artesunate, and artemether-lumefantrine. Six hundred eighty-four children aged 3 to 59 months with uncomplicatedPlasmodium falciparummalaria were randomly allocated to each study arm. Children were hospitalized for 3 days, given supervised treatment, and followed up weekly for 42 days. All regimens were well tolerated and rapidly effective. The median parasitemia clearance half-life was 2.2 h, and half-lives were similar between arms (P= 0.19). The PCR-uncorrected cure rates by day 42 were 73.0% for amodiaquine-artesunate, 70.2% for artemether-lumefantrine, and 86.3% for dihydroartemisinin-piperaquine (P= 0.001). Early treatment failure occurred in three patients (0.5%), one in each arm. The PCR-corrected cure rates were 93.4% for amodiaquine-artesunate, 92.7% for artemether-lumefantrine, and 94.3% for dihydroartemisinin-piperaquine (P= 0.78). The last provided a longer posttreatment prophylactic effect than did the other two treatments. The day 7 plasma concentration of piperaquine was below 30 ng/ml in 47% of the children treated with dihydroartemisinin-piperaquine, and the day 7 lumefantrine concentration was below 280 ng/ml in 37.0% of children who received artemether-lumefantrine. Thus, although cure rates were all satisfactory, they could be improved by increasing the dose. (This study has been registered with the International Standard Randomized Controlled Trial Number Register [www.isrctn.org] under registration no. ISRCTN20984426.)


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