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The Journal of Infectious Diseases Feb 2021Our current knowledge of the clinical burden, biology, and transmission of Plasmodium malariae is extremely scarce. To start addressing some of those questions, we...
Our current knowledge of the clinical burden, biology, and transmission of Plasmodium malariae is extremely scarce. To start addressing some of those questions, we experimentally infected Anopheles gambiae mosquitoes with fresh P. malariae isolates obtained from asymptomatic individuals in Lambaréné, Gabon. The proportion of mosquitoes infected via direct membrane feeding assay with either P. malariae monoinfections (16% [19 of 121]) or coinfections (28% [31 of 112]) was higher after serum replacement than in parallel groups without serum replacement (4% [4 of 102] and 4% [2 of 45], respectively; P < .01). Our results show that isolates from asymptomatic carriers can be used for experimental studies of P. malariae transmission.
Topics: Animals; Anopheles; Female; Gabon; Humans; Malaria; Malaria, Falciparum; Mosquito Vectors; Plasmodium falciparum; Plasmodium malariae
PubMed: 32621750
DOI: 10.1093/infdis/jiaa382 -
Journal of Hepatology Mar 2022
Topics: Animals; Humans; Liver; Malaria; Parasites; Plasmodium malariae
PubMed: 34711453
DOI: 10.1016/j.jhep.2021.05.034 -
Emerging Infectious Diseases Jun 2023Achieving malaria elimination requires considering both Plasmodium falciparum and non-P. falciparum infections. We determined prevalence and geographic distribution of 4...
Achieving malaria elimination requires considering both Plasmodium falciparum and non-P. falciparum infections. We determined prevalence and geographic distribution of 4 Plasmodium spp. by performing PCR on dried blood spots collected within 8 regions of Tanzania during 2017. Among 3,456 schoolchildren, 22% had P. falciparum, 24% had P. ovale spp., 4% had P. malariae, and 0.3% had P. vivax infections. Most (91%) schoolchildren with P. ovale infections had low parasite densities; 64% of P. ovale infections were single-species infections, and 35% of those were detected in low malaria endemic regions. P. malariae infections were predominantly (73%) co-infections with P. falciparum. P. vivax was detected mostly in northern and eastern regions. Co-infections with >1 non-P. falciparum species occurred in 43% of P. falciparum infections. A high prevalence of P. ovale infections exists among schoolchildren in Tanzania, underscoring the need for detection and treatment strategies that target non-P. falciparum species.
Topics: Humans; Child; Plasmodium falciparum; Prevalence; Tanzania; Coinfection; Plasmodium malariae; Malaria; Malaria, Falciparum; Malaria, Vivax
PubMed: 37209670
DOI: 10.3201/eid2906.221016 -
The Lancet. Microbe Aug 2022High-quality evidence for the therapeutic efficacy and effectiveness of antimalarials for infections caused by Plasmodium malariae, Plasmodium ovale spp, and...
Effectiveness of pyronaridine-artesunate against Plasmodium malariae, Plasmodium ovale spp, and mixed-Plasmodium infections: a post-hoc analysis of the CANTAM-Pyramax trial.
BACKGROUND
High-quality evidence for the therapeutic efficacy and effectiveness of antimalarials for infections caused by Plasmodium malariae, Plasmodium ovale spp, and mixed-Plasmodium infections is scarce. In this study, we aimed to analyse the efficacy of pyronaridine-artesunate for the treatment of non-falciparum and mixed-species Plasmodium infections from a large phase 3b/4 clinical trial in central Africa.
METHODS
This post-hoc analysis was done in a random subset of samples from two sites (in the Democratic Republic of the Congo and in Gabon) of the CANTAM-Pyramax trial assessing pyronaridine-artesunate therapy. We randomly selected paired dried blood spot samples from day 0 and day 28 (or unforeseen visit) and analysed them by quantitative PCR for mixed Plasmodium infections or non-falciparum mono-infections. Day 28 (or unforeseen visit) samples positive for non-falciparum malaria were re-assessed by microscopy to identify microscopic versus submicroscopic infections. Analyses were done on two sample sets: a per-protocol set and an intention-to-treat set.
FINDINGS
Among 1502 randomly selected samples, 192 (12·8%) showed mixed-Plasmodium infections or non-falciparum mono-infections. We did not detect P vivax in the samples. For both the per-protocol and intention-to-treat sets, the overall day 28 cure rates for P malariae, P ovale curtisi, and P ovale wallikeri were 96·3% or higher (95% CIs from 81·0-99·9 to 95·7-100). Cure rates were consistently high in P malariae (99·2%, 95·7-100) and P ovale spp (97·9%, 88·7-99·9, for P ovale curtisi and 96·3%, 81·0-99·9, for P ovale wallikeri) infections.
INTERPRETATION
This post-hoc analysis provides important evidence supporting the high efficacy of pyronaridine-artesunate against mono-infections with P malariae, P ovale curtisi, or P ovale wallikeri and mixed-Plasmodium infections in a real-world setting.
FUNDING
Medicines for Malaria Venture.
Topics: Artesunate; Drug Combinations; Humans; Malaria; Naphthyridines; Plasmodium malariae; Plasmodium ovale
PubMed: 35654079
DOI: 10.1016/S2666-5247(22)00092-1 -
Scientific Reports Dec 2022Plasmodium malariae, a neglected human malaria parasite, contributes up to 10% of malaria infections in sub-Saharan Africa (sSA). Though P. malariae infection is...
Plasmodium malariae structure and genetic diversity in sub-Saharan Africa determined from microsatellite variants and linked SNPs in orthologues of antimalarial resistance genes.
Plasmodium malariae, a neglected human malaria parasite, contributes up to 10% of malaria infections in sub-Saharan Africa (sSA). Though P. malariae infection is considered clinically benign, it presents mostly as coinfections with the dominant P. falciparum. Completion of its reference genome has paved the way to further understand its biology and interactions with the human host, including responses to antimalarial interventions. We characterized 75 P. malariae isolates from seven endemic countries in sSA using highly divergent microsatellites. The P. malariae infections were highly diverse and five subpopulations from three ancestries (independent of origin of isolates) were determined. Sequences of 11 orthologous antimalarial resistance genes, identified low frequency single nucleotide polymorphisms (SNPs), strong linkage disequilibrium between loci that may be due to antimalarial drug selection. At least three sub-populations were detectable from a subset of denoised SNP data from mostly the mitochondrial cytochrome b coding region. This evidence of diversity and selection calls for including P. malariae in malaria genomic surveillance towards improved tools and strategies for malaria elimination.
Topics: Humans; Africa South of the Sahara; Antimalarials; Malaria; Microsatellite Repeats; Plasmodium malariae; Polymorphism, Single Nucleotide; Drug Resistance
PubMed: 36536036
DOI: 10.1038/s41598-022-26625-w -
Parasites & Vectors Jun 2022Although Plasmodium falciparum infection is largely documented and this parasite is the main target for malaria eradication, other Plasmodium species persist, and these...
BACKGROUND
Although Plasmodium falciparum infection is largely documented and this parasite is the main target for malaria eradication, other Plasmodium species persist, and these require more attention in Africa. Information on the epidemiological situation of non-P. falciparum species infections is scarce in many countries, including in the Democratic Republic of the Congo (hereafter Republic of the Congo) where malaria is highly endemic. The aim of this study was to determine the prevalence and distribution of non-P. falciparum species infections in the region south of Brazzaville.
METHODS
A cross-sectional survey was conducted in volunteers living in rural and urban settings during the dry and rainy seasons in 2021. Socio-demographic and clinical parameters were recorded. Plasmodium infection in blood samples was detected by microscopic analysis and nested PCR (sub-microscopic analysis).
RESULTS
Of the 773 participants enrolled in the study, 93.7% were from the rural area, of whom 97% were afebrile. The prevalence of microscopic and sub-microscopic Plasmodium spp. infection was 31.2% and 63.7%, respectively. Microscopic Plasmodium malariae infection was found in 1.3% of participants, while sub-microscopic studies detected a prevalence of 14.9% for P. malariae and 5.3% for Plasmodium ovale. The rate of co-infection of P. malariae or P. ovale with P. falciparum was 8.3% and 2.6%, respectively. Higher rates of sub-microscopic infection were reported for the urban area without seasonal fluctuation. In contrast, non-P. falciparum species infection was more pronounced in the rural area, with the associated risk of the prevalence of sub-microscopic P. malariae infection increasing during the dry season.
CONCLUSION
There is a need to include non-P. falciparum species in malaria control programs, surveillance measures and eradication strategies in the Republic of the Congo.
Topics: Congo; Cross-Sectional Studies; Humans; Malaria; Malaria, Falciparum; Plasmodium falciparum; Prevalence
PubMed: 35706053
DOI: 10.1186/s13071-022-05312-9 -
Computational and Structural... 2022Malaria is a tropical disease caused by spp. and transmitted by the bite of infected mosquitoes. Protein kinases (PKs) play key roles in the life cycle of the...
Malaria is a tropical disease caused by spp. and transmitted by the bite of infected mosquitoes. Protein kinases (PKs) play key roles in the life cycle of the etiological agent of malaria, turning these proteins attractive targets for antimalarial drug discovery campaigns. As part of an effort to understand parasite signaling functions, we report the results of a bioinformatics pipeline analysis of PKs of eight species. To date, no and kinome assemble has been conducted. We classified, curated and annotated predicted kinases to update kinomes published to date, as well as report for the first time the kinomes of and . Overall, from 76 to 97 PKs were identified among all spp. kinomes. Most of the kinases were assigned to seven of nine major kinase groups: AGC, CAMK, CMGC, CK1, STE, TKL, OTHER; and the group FIKK. About 30% of kinases have been deeply classified into group, family and subfamily levels and only about 10% remained unclassified. Furthermore, updating and comparing the kinomes of and allowed for the prioritization and selection of kinases as potential drug targets that could be explored for discovering new drugs against malaria. This integrated approach resulted in the selection of 37 protein kinases as potential targets and the identification of investigational compounds with moderate activity against asexual (3D7 and Dd2 strains) stages that could serve as starting points for the search of potent antimalarial leads in the future.
PubMed: 35891792
DOI: 10.1016/j.csbj.2022.07.003 -
The Journal of Molecular Diagnostics :... Oct 2021Plasmodium malariae and Plasmodium ovale are increasingly gaining public health attention as the global transmission of falciparum malaria is decreasing. However, the...
Plasmodium malariae and Plasmodium ovale are increasingly gaining public health attention as the global transmission of falciparum malaria is decreasing. However, the absence of reliable Plasmodium species-specific detection tools has hampered accurate diagnosis of these minor Plasmodium species. In this study, SYBR Green-based real-time PCR assays were developed for the detection of P. malariae and P. ovale using cooperative primers that significantly limit the formation and propagation of primers-dimers. Both the P. malariae and P. ovale cooperative primer-based assays had at least 10-fold lower detection limit compared with the corresponding conventional primer-based assays. More important, the cooperative primer-based assays were evaluated in a cross-sectional study using 560 samples obtained from two health facilities in Ghana. The prevalence rates of P. malariae and P. ovale among the combined study population were 18.6% (104/560) and 5.5% (31/560), respectively. Among the Plasmodium-positive cases, P. malariae and P. ovale mono-infections were 3.6% (18/499) and 1.0% (5/499), respectively, with the remaining being co-infections with Plasmodium falciparum. The study demonstrates the public health importance of including detection tools with lower detection limits in routine diagnosis and surveillance of nonfalciparum species. This will be necessary for comprehensively assessing the effectiveness of malaria interventions and control measures aimed toward global malaria elimination.
Topics: Adolescent; Adult; Child; Child, Preschool; Coinfection; Cross-Sectional Studies; DNA Primers; Female; Ghana; Humans; Limit of Detection; Malaria, Falciparum; Male; Plasmodium falciparum; Plasmodium malariae; Plasmodium ovale; Prevalence; RNA, Ribosomal, 18S; Real-Time Polymerase Chain Reaction; Young Adult
PubMed: 34425259
DOI: 10.1016/j.jmoldx.2021.07.022 -
Malaria Journal May 2021Malaria control and elimination strategies are based on levels of transmission that are usually determined by data collected from health facilities. In endemic areas,...
BACKGROUND
Malaria control and elimination strategies are based on levels of transmission that are usually determined by data collected from health facilities. In endemic areas, asymptomatic Plasmodium infection is thought to represent the majority of infections, though they are not diagnosed nor treated. Therefore, there might be an underestimation of the malaria reservoir, resulting in inadequate control strategies. In addition, these untreated asymptomatic Plasmodium infections maintain transmission, making it difficult or impossible to reach malaria elimination goals. Thus, the aim of this study was to determine the prevalence of asymptomatic Plasmodium infections in southeastern Senegal.
METHODS
A cross sectional study was conducted among asymptomatic individuals (N = 122) living in the village of Andiel located in Bandafassi, Kédougou, which consisted of about 200 inhabitants during the malaria transmission season in late October 2019. For each individual without malaria-related symptoms and who consented to participate, a rapid diagnostic test (RDT) was performed in the field. Results were confirmed in the laboratory with photo-induced electron transfer (PET-PCR).
RESULTS
Malaria prevalence was 70.3% by PET-PCR and 41.8% by RDT. During the same period, the health post of the area reported 49. 1% test positivity rate by RDT. The majority of the infected study population, 92.9%, was infected with a single species and 7.1% had two or three species of Plasmodium. Plasmodium falciparum was predominant and represented 90.2% of the infections, while 6.5% were due to Plasmodium ovale and 3.3% to Plasmodium malariae. 59.4% of children targeted for SMC (zero to ten years old) were infected.
CONCLUSION
In southeastern Senegal, where the transmission is the highest, malaria control strategies should address asymptomatic Plasmodium infections at the community level. The results suggest that this area could be eligible for mass drug administration. Moreover, non-falciparum species could be more common and its prevalence should be determined countrywide.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asymptomatic Infections; Child; Child, Preschool; Female; Humans; Infant; Malaria; Malaria, Falciparum; Malaria, Vivax; Male; Middle Aged; Plasmodium falciparum; Plasmodium malariae; Plasmodium ovale; Plasmodium vivax; Prevalence; Senegal; Young Adult
PubMed: 33980241
DOI: 10.1186/s12936-021-03746-7 -
The Korean Journal of Parasitology Feb 2021As malaria remains a major health problem worldwide, various diagnostic tests have been developed, including microscopy-based and rapid diagnostic tests. LabChip...
As malaria remains a major health problem worldwide, various diagnostic tests have been developed, including microscopy-based and rapid diagnostic tests. LabChip real-time PCR (LRP) is a small and portable device used to diagnose malaria using lab-on-a-chip technology. This study aimed to evaluate the diagnostic performance of LRP for detecting malaria parasites. Two hundred thirteen patients and 150 healthy individuals were enrolled from May 2009 to October 2015. A diagnostic detectability of LRP for malaria parasites was compared to that of conventional RT-PCR. Sensitivity of LRP for Plasmodium vivax, P. falciparum, P. malariae, and P. ovale was 95.5%, 96.0%, 100%, and 100%, respectively. Specificity of LRP for P. vivax, P. falciparum, P. malariae, and P. ovale was 100%, 99.3%, 100%, and 100%, respectively. Cohen's Kappa coefficients between LRP and CFX96 for detecting P. vivax, P. falciparum, P. malariae, and P. ovale were 0.96, 0.98, 1.00, and 1.00, respectively. Significant difference was not observed between the results of LRP and conventional RT-PCR and microscopic examination. A time required to amplify DNAs using LRP and conventional RT-PCR was 27 min and 86 min, respectively. LRP amplified DNAs 2 times more fast than conventional RT-PCR due to the faster heat transfer. Therefore, LRP could be employed as a useful tool for detecting malaria parasites in clinical laboratories.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; DNA, Protozoan; Diagnostic Tests, Routine; Female; Humans; Infant; Lab-On-A-Chip Devices; Malaria; Male; Middle Aged; Plasmodium falciparum; Plasmodium ovale; Plasmodium vivax; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity; Young Adult
PubMed: 33684990
DOI: 10.3347/kjp.2021.59.1.77