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result(s) for
"Mutsaers, Mathijs"
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Genetic diversity, population structure, and drug resistance of Plasmodium falciparum in Kenya: a systematic review and meta-analysis
by
Masakhwe, Clement Asabo
,
Mutsaers, Mathijs
,
Rosanas-Urgell, Anna
in
Antimalarials - pharmacology
,
Antiparasitic agents
,
Biological diversity
2025
A systematic review and meta-analysis of studies carried out in Kenya to assess
Plasmodium falciparum
genetic diversity and drug resistance was conducted with the aim of tracking parasite dynamics over time and space. In Kenya, malaria has declined in certain regions making it an ideal setting to investigate the impact of control interventions on the parasite population. A systematic electronic search yielded a total of 737 articles from PUBMED (392), google scholar (105) science direct (16) and Web of Science (224). Of these, 58 articles published in Kenya between 2002 and 2023 were eligible and included 21 articles on
P. falciparum
genetic diversity and 37 articles on drug resistance. Two independent reviewers performed screening, quality and risk of bias assessment and data extraction. Non-parametric tests were used to assess temporal trends. Heterogeneity across studies was assessed using I
2
statistic and visualized using forest and funnel plots. p-values less than 0.05 were considered significant. To determine parasite diversity, MOI and drug resistance, microsatellites, antigenic targets (
Pfmsp1
,
Pfmsp2
,
Pfcsp
,
Pfglurp
,
Pfs47
), SNPs,
Pfdhfr/Pfdhps
,
Pfcrt
, and
Pfmdr1
genes were genotyped using PCR, sequencing, restriction fragment length polymorphism and Mass array.Expected heterozygosity (
He
) was high: 0.79 (95% CI 0.77–0.81), 0.80 (95%CI 0.78–0.81) and 0.96 (95% CI 0.96–0.97) in the Lake Basin, Highlands and Coastal region respectively. Heterogeneity was low in the Lake Basin (I
2
= 32.9%), moderate in the Highlands (I
2
= 57.6%), and high at the Coast (I
2
= 92%). Infections were multiclonal (34% to 80%) with a high mean MOI (2–4.8) and lacked spatial or temporal trends. Genetic differentiation varied over time and between regions.
Pfcrt
haplotype CVIET reduced from 96% in 1999 to 1% in 2017, whereas the CVMNK haplotype increased from 6.8% in 1998 to 98.8% in 2017. A temporal increase in frequency of
Pfdhfr-51I
,
Pfdhfr-59R, Pfdhps-437G
and
Pfdhps-540E
(Mann–Kendall test p < 0.05) was reported.
Pfk13
mutations (R539T, N458Y, R561H, A675V and V568G) were reported in the Lake Basin and Highland regions (2018–2024).
Pfmdr1
NFD and NYD haplotypes, increased between 2012 and 2017. This review highlights
P. falciparum
diversity, multiclonal infections, temporal shifts in drug resistance mutations and low to moderate genetic differentiation in parasites from different regions suggesting ongoing transmission and potential connectivity between parasite populations.
Journal Article
Half-decade of scaling up malaria control: malaria trends and impact of interventions from 2018 to 2023 in Rwanda
by
Kubahoniyesu, Theogene
,
Ngabonziza, Jean Claude Semuto
,
Rukundo, Gilbert
in
Analysis
,
Annual reports
,
Anopheles
2025
Background
Rwanda has made significant strides in malaria control. This study reviews malaria epidemiology and control strategies in Rwanda from 2018 to 2023, documenting their impact, persistent gaps and emerging challenges.
Methods
Data on Rwanda’s malaria context from 2018 to 2023 were obtained through a literature review of peer-reviewed articles and grey literature, including annual reports from the malaria programmes, partners, the African Union, and the World Health Organization (WHO). Specific keywords used for the search included “malaria”, “Rwanda”, “case management”, “control”, “treatment”, and “prevention”. Moreover, epidemiological data for this period was extracted from the Health Management Information System (HMIS). Data analysis was done using R & R-Studio, ANOVA to assess the statistical significance (P < 0.05) of observed trends and T-test to compare the focal and blanket IRS techniques.
Results/Discussion
Between 2018 and 2023, all malaria indicators showed improvement. Malaria incidence dropped from 345 to 40 cases per 1000 persons (P = 0.00292), the severe malaria rate decreased from 112 to 10/100,000 persons (P = 0.018), and the mortality rate fell from 2.72 to 0.258 deaths /100,000 persons (P = 0.00617). Among children under 5 years of age, incidence decreased significantly from 331 to 52/1,000 persons (P = 0.00123), the severe malaria rate dropped from 214 to 29/100,000 persons (P = 0.00399), and mortality declined from 5 to 0.453/100,000 persons (P = 0.00504). Over the same period, key malaria interventions expanded. The proportion of cases treated by CHWs increased significantly, improving access to early diagnosis and treatment (from 13 to 59%), and the new generations of ITNs (PBO and dual-active ingredient nets) were deployed in 9 districts. Since 2019, a blanket spraying technique has been adopted in 12 IRS districts replacing the focal spraying technique contributing to the significant decrease of malaria incidence from 2019 to 2023 (P = 0.0025). However, new challenges have emerged, including the rise of the
K13
R561H mutation associated with artemisinin resistance, the spread of insecticide resistance, and limited intervention coverage due to resource constraints.
Conclusion
To sustain the progress achieved, it is essential to intensify malaria control efforts, foster compliance with intervention strategies, enhance surveillance systems for timely and effective responses, and secure long-term funding to sustain these measures.
Journal Article
Plasmodium vivax genomic surveillance in the Peruvian Amazon with Pv AmpliSeq assay
by
Guetens, Pieter
,
Figueroa-Ildefonso, Erick
,
Delgado-Ratto, Christopher
in
Analysis
,
Assaying
,
Asymptomatic
2024
Plasmodium vivax is the most predominant malaria species in Latin America, constituting 71.5% of malaria cases in 2021. With several countries aiming for malaria elimination, it is crucial to prioritize effectiveness of national control programs by optimizing the utilization of available resources and strategically implementing necessary changes. To support this, there is a need for innovative approaches such as genomic surveillance tools that can investigate changes in transmission intensity, imported cases and sources of reintroduction, and can detect molecular markers associated with drug resistance.
Here, we apply a modified highly-multiplexed deep sequencing assay: Pv AmpliSeq v2 Peru. The tool targets a newly developed 41-SNP Peru barcode for parasite population analysis within Peru, the 33-SNP vivaxGEN-geo panel for country-level classification, and 11 putative drug resistance genes. It was applied to 230 samples from the Peruvian Amazon (2007-2020), generating baseline surveillance data. We observed a heterogenous P. vivax population with high diversity and gene flow in peri-urban areas of Maynas province (Loreto region) with a temporal drift using all SNPs detected by the assay (nSNP = 2909). In comparison, in an indigenous isolated area, the parasite population was genetically differentiated (FST = 0.07-0.09) with moderate diversity and high relatedness between isolates in the community. In a remote border community, a clonal P. vivax cluster was identified, with distinct haplotypes in drug resistant genes and ama1, more similar to Brazilian isolates, likely representing an introduction of P. vivax from Brazil at that time. To test its applicability for Latin America, we evaluated the SNP Peru barcode in P. vivax genomes from the region and demonstrated the capacity to capture local population clustering at within-country level.
Together this data shows that P. vivax transmission is heterogeneous in different settings within the Peruvian Amazon. Genetic analysis is a key component for regional malaria control, offering valuable insights that should be incorporated into routine surveillance.
Journal Article
High throughput estimates of Wolbachia, Zika and chikungunya infection in Aedes aegypti by near-infrared spectroscopy to improve arbovirus surveillance
by
Garcia, Gabriela A
,
Sikulu-Lord Maggy
,
Mutsaers Mathijs
in
Aedes aegypti
,
Biology
,
Chikungunya virus
2021
Deployment of Wolbachia to mitigate dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) transmission is ongoing in 12 countries. One way to assess the efficacy of Wolbachia releases is to determine invasion rates within the wild population of Aedes aegypti following their release. Herein we evaluated the accuracy, sensitivity and specificity of the Near Infrared Spectroscopy (NIRS) in estimating the time post death, ZIKV-, CHIKV-, and Wolbachia-infection in trapped dead female Ae. aegypti mosquitoes over a period of 7 days. Regardless of the infection type, time post-death of mosquitoes was accurately predicted into four categories (fresh, 1 day old, 2–4 days old and 5–7 days old). Overall accuracies of 93.2, 97 and 90.3% were observed when NIRS was used to detect ZIKV, CHIKV and Wolbachia in dead Ae. aegypti female mosquitoes indicating NIRS could be potentially applied as a rapid and cost-effective arbovirus surveillance tool. However, field data is required to demonstrate the full capacity of NIRS for detecting these infections under field conditions.Santos et al. demonstrate that the Near Infrared Spectroscopy (NIRS) can accurately estimate the death time of trapped female Aedes aegypti and vector infection with Zika virus, Chikungunya virus, or Wolbachia in a 7-day trapping period. This study suggests that NIRS may provide an accurate and inexpensive tool that improves arbovirus surveillance systems.
Journal Article
Failure of artemether-lumefantrine therapy in travellers returning to Belgium with Plasmodium falciparum malaria: an observational case series with genomic analysis
by
Bruggemans, Anne
,
Malotaux, Jiska
,
Florence, Eric
in
Antimalarials - pharmacology
,
Antiparasitic agents
,
Artemether
2024
Background
Failure of artemisinin-based combination therapy is increasingly reported in patients with Plasmodium falciparum malaria in sub-Saharan Africa. We aimed to describe the clinical and genomic characteristics of recent cases of P. falciparum malaria failing artemether-lumefantrine in Belgium.
Methods
Travel-related cases of malaria confirmed at the national reference laboratory of the Institute of Tropical Medicine, Antwerp, Belgium, were reviewed. All cases for which attending clinicians reported persistence (beyond Day 3 post-treatment initiation, i.e. early failure) or recrudescence (from Day 7 to 42, i.e. late failure) of P. falciparum parasites despite adequate drug intake were analysed. Both initial and persistent/recurrent samples were submitted to next generation sequencing to investigate resistance-conferring mutations.
Results
From July 2022 to June 2023, eight P. falciparum cases of failure with artemether-lumefantrine therapy were reported (early failure = 1; late failure = 7). All travellers were returning from sub-Saharan Africa, most (6/8) after a trip to visit friends and relatives. PfKelch13 (PF3D7_1343700) mutations associated with resistance to artemisinin were found in two travellers returning from East Africa, including the validated marker R561H in the patient with early failure and the candidate marker A675V in a patient with late failure. Additional mutations were detected that could contribute to decreased susceptibility to artemisinin in another three cases, lumefantrine in six cases and proguanil in all eight participants. Various regimens were used to treat the persistent/recrudescent cases, with favourable outcome.
Conclusion
Within a 12-month period, we investigated eight travellers returning from sub-Saharan Africa with P. falciparum malaria and in whom artemether-lumefantrine failure was documented. Mutations conferring resistance to antimalarials were found in all analysed blood samples, especially against lumefantrine and proguanil, but also artemisinin. There is a pressing need for systematic genomic surveillance of resistance to antimalarials in international travellers with P. falciparum malaria, especially those experiencing treatment failure.
Journal Article