Dieudonné M Mvumbi | Université de Liège (original) (raw)

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Papers by Dieudonné M Mvumbi

Acta Tropica, 2016

Faced with intense levels of chloroquine (CQ) resistance in Plasmodium falciparum malaria, Rwanda... more Faced with intense levels of chloroquine (CQ) resistance in Plasmodium falciparum malaria, Rwanda replaced CQ with amodiaquine (AQ)+sulfadoxine-pyrimethamine (SP) in 2001, and subsequently with artemether-lumefantrine (AL) in 2006, as first-line treatments for uncomplicated malaria. Following years of discontinuation of CQ use, re-emergence of CQ-susceptible parasites has been reported in countries including Malawi, Kenya and Tanzania. In contrast, high levels of SP resistant mutant parasites continue to be reported even in countries of presumed reduced SP drug selection pressure. The prevalence and distributions of genetic polymorphisms linked with CQ and SP resistance at two sites of different malaria transmission intensities are described here to better understand drug-related genomic adaptations over time and exposure to varying drug pressures in Rwanda. Using filter paper blood isolates collected from P. falciparum infected patients, DNA was extracted and a nested PCR performed to identify resistance-mediating polymorphisms in the pfcrt, pfmdr1, pfdhps and pfdhfr genes. Amplicons from a total of 399 genotyped samples were analysed by ligase detection reaction fluorescent microsphere assay. CQ susceptible pfcrt 76K and pfmdr1 86N wild-type parasites were found in about 50% and 81% of isolates, respectively. Concurrently, SP susceptible pfdhps double (437G-540E), pfdhfr triple (108N-51I-59R), quintuple pfdhps 437G-540E/pfdhfr 51I-59R-108N and sextuple haplotypes were found in about 84%, 85%, 74% and 18% of isolates, respectively. High-level SP resistance associated pfdhfr 164L and pfdhps 581G mutant prevalences were noted to decline. Mutations pfcrt 76T, pfdhfr 59R and pfdhfr 164L were found differentially distributed between the two study sites with the pfdhfr 164L mutants found only at Ruhuha site, eastern Rwanda. Overall, sustained intense levels of SP resistance mutations and a recovery of CQ susceptible parasites were found in this study following 7 years and 14 years of drug withdrawal from use, respectively. Most likely, the sustained high prevalence of resistant parasites is due to the use of DHFR/DHPS inhibitors like trimethoprim-sulfamethoxazole (TS) for the treatment of and prophylaxis against bacterial infections among HIV infected individuals as well as the continued use of IPTp-SP within the East and Central African regions for malaria prevention among pregnant women. With regard to CQ, the slow recovery of CQ susceptible parasites may have been caused partly by the continued use of CQ and/or CQ mimicking antimalarial drugs like AQ in spite of policies to withdraw it from Rwanda and the neighbouring countries of Uganda and Tanzania. Continued surveillance of P. falciparum CQ and SP associated polymorphisms is recommended for guiding future rational drug policy-making and mitigation of future risk of anti-malaria drug resistance development.

Research Square (Research Square), Dec 3, 2019

Research Square (Research Square), Feb 4, 2020

Research Square (Research Square), Feb 28, 2020

Malaria Journal, Mar 20, 2020

Infection, Genetics and Evolution, 2021

International Journal of Infectious Diseases, Apr 1, 2014

Background. Getting DNA became capital since the emergence of molecular assays. Plasmodium DNA is... more Background. Getting DNA became capital since the emergence of molecular assays. Plasmodium DNA is used for malaria diagnosis by PCR, monitoring of molecular resistance or for clinical vaccine trial. DNA is commonly extracted from liquid whole blood or fixed on filter paper. In our study, we investigated two different extraction methods: with the Maxwell® 16 LEV (Promega Corporation, Wisconsin, USA) and with the QiAamp® (Qiagen GmbH, Hilden, Germany) from blood dried and stained on slides known as thick blood films (TBF). Methods. We made a series of TBFs from a blood sample containing Plasmodium ovale (parasitaemia: 1240 parasites/µl), using among 15µl of blood per TBF. We scratched out the TBF and transferred the material to a microcentrifuge tube containing 100 µl of PBS. We used that mixture as sample for our extraction by Maxwell®16 (with LEV blood DNA kit and LEV simply RNA cells kit) and by QiAamp. We quantified the extracted DNA with a spectrophotometer (Nanodrop®) and amplified it by Real-time PCR (RT-PCR). We compared quantity and Ct values for both methods. Results. Plasmodium DNA has been correctly extracted and quantified as well as by Maxwell® than by Qiagen. Extraction with the Maxwell® gave more DNA than Qiagen (12.56 ng VS 3.74 ng) if using LEV blood DNA kit but lower DNA amounts (a less quantity) when using LEV simply RNA cells kit (1,99ng VS 3,74ng). The lowest Ct value has been obtained when using LEV simply RNA cells kit of Maxwell®. Only LEV blood DNA has not given any signal in RT-PCR. Conclusion. Both methods described in our study achieve the extraction of DNA. However, extraction from TBFs uses lower amounts of blood (50µl) than the extraction from whole blood (200µl). Maxwell seems to be better than Qiagen because extraction is automated and faster with a higher yield. We conclude that TBFs are a reliable source for Plasmodium DNA in low income countries where sample transport and preservation are difficult.

Malaria Journal, 2021

Background This study aimed to estimate the socio-economic costs of uncomplicated malaria and to ... more Background This study aimed to estimate the socio-economic costs of uncomplicated malaria and to explore health care-seeking behaviours that are likely to influence these costs in the Democratic Republic of Congo (DRC), a country ranked worldwide as the second most affected by malaria. Methods In 2017, a cross-sectional survey included patients with uncomplicated malaria in 64 healthcare facilities from 10 sentinel sites of the National Malaria Control Programme (NMCP) in the DRC. A standard questionnaire was used to assess health care-seeking behaviours of patients. Health-related quality of life (HRQL) and disutility weights (DW) of illness were evaluated by using the EuroQol Group’s descriptive system (EQ-5D-3L) and its visual analogue scale (EQ VAS). Malaria costs were estimated from a patient’s perspective. Probabilistic sensitivity analyses (PSA) evaluated the uncertainty around the cost estimates. Generalized regression models were fitted to assess the effect of potential pre...

BACKGROUND: The national policy for malaria treatment of the Democratic Republic of Congo recomme... more BACKGROUND: The national policy for malaria treatment of the Democratic Republic of Congo recommends two first-line artemisinin-based combinations for the treatment of uncomplicated malaria: artesunate-amodiaquine and artemether-lumefantrine. This study investigated the presence of markers associated with resistance to the current first-line artemisinin-based combination therapy (ACT) in isolates of Plasmodium falciparum from treatment failure patients in the Democratic Republic of Congo. METHODS: From November 2018 to November 2019, dried blood spots were taken from patients returning to health centres for fever within 28 days after an initial malaria treatment in six sentinel sites of the National Malaria Control Programme across Democratic Republic of Congo. The new episode of malaria was first detected by a rapid diagnostic test and then confirmed by a real-time PCR assay to define treatment failure. Fragments of interest in pfk13 and pfcrt genes were amplified by conventional P...

Additional file 1: Table S1. Plasmodium falciparum K13 nucleotide sequences from 2019-study.

BMC Infectious Diseases, 2022

Background Because of the loss of chloroquine (CQ) effectiveness, the Democratic Republic of Cong... more Background Because of the loss of chloroquine (CQ) effectiveness, the Democratic Republic of Congo (DRC)’s malaria treatment policy replaced CQ by sulfadoxine–pyrimethamine (SP) as first-line treatment of uncomplicated malaria in 2003, which in turn was replaced by artemisinin-based combination therapies (ACT) in 2005. The World Health Organization (WHO) recommends monitoring of anti-malarial drug resistance every 2 years. The study aimed to provide baseline data for biennial molecular surveillance of anti-malarial drug resistance by comparing data from a study conducted in 2019 to previously published data from a similar study conducted in 2017 in the DRC. Methods From July to November 2019, a cross-sectional study was conducted in ten sites which were previously selected for a similar study conducted in 2017 across the DRC. P. falciparum malaria was diagnosed by a rapid diagnostic test (RDT) or by microscopy and dried blood samples (DBS) were taken from patients who had a positive...

Additional file 1: Pfk13 and pfcrt sequences for wild and mutant isolates.

Additional file 2:: Minimal data set containing raw data.

The Lancet Infectious Diseases, 2020

Malaria Research and Treatment, 2016

Malaria remains a major public health problem in the Democratic Republic of Congo (DRC) with 14 m... more Malaria remains a major public health problem in the Democratic Republic of Congo (DRC) with 14 million cases reported by the WHO Malaria Report in 2014. Asymptomatic malaria cases are known to be prevalent in endemic areas and are generally untreated, resulting in a significant source of gametocytes that may serve as reservoir of disease transmission. Considering that microscopy certainly underestimates the prevalence of Plasmodium infections within asymptomatic carriers and that PCR assays are currently recognized as the most sensitive methods for Plasmodium identification, this study was conducted to weigh the asymptomatic carriage in DRC by a molecular method. Six provinces were randomly selected for blood collection in which 80 to 100 individuals were included in the study. Five hundred and eighty blood samples were collected and molecular diagnosis was performed. Globally, almost half of the samples collected from asymptomatic individuals (280/580; 48.2%) had Plasmodium infect...