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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 -
Microbiology Spectrum Jun 2023Human malaria is a life-threatening parasitic disease with high impact in the sub-Saharan Africa region, where 95% of global cases occurred in 2021. While most malaria...
Human malaria is a life-threatening parasitic disease with high impact in the sub-Saharan Africa region, where 95% of global cases occurred in 2021. While most malaria diagnostic tools are focused on Plasmodium falciparum, there is a current lack of testing non-P. falciparum cases, which may be underreported and, if undiagnosed or untreated, may lead to severe consequences. In this work, seven species-specific loop-mediated isothermal amplification (LAMP) assays were designed and evaluated against TaqMan quantitative PCR (qPCR), microscopy, and enzyme-linked immunosorbent assays (ELISAs). Their clinical performance was assessed with a cohort of 164 samples of symptomatic and asymptomatic patients from Ghana. All asymptomatic samples with a parasite load above 80 genomic DNA (gDNA) copies per μL of extracted sample were detected with the Plasmodium falciparum LAMP assay, reporting 95.6% (95% confidence interval [95% CI] of 89.9 to 98.5) sensitivity and 100% (95% CI of 87.2 to 100) specificity. This assay showed higher sensitivity than microscopy and ELISA, which were 52.7% (95% CI of 39.7 to 67%) and 67.3% (95% CI of 53.3 to 79.3%), respectively. Nine samples were positive for , indicating coinfections with P. falciparum, which represented 5.5% of the tested population. No samples were detected as positive for P. vivax, , P. knowlesi, or P. cynomolgi by any method. Furthermore, translation to the point-of-care was demonstrated with a subcohort of 18 samples tested locally in Ghana using our handheld lab-on-chip platform, Lacewing, showing comparable results to a conventional fluorescence-based instrument. The developed molecular diagnostic test could detect asymptomatic malaria cases, including submicroscopic parasitemia, and it has the potential to be used for point-of-care applications. The spread of Plasmodium falciparum parasites with / gene deletions presents a major threat to reliable point-of-care diagnosis with current rapid diagnostic tests (RDTs). Novel molecular diagnostics based on nucleic acid amplification are needed to address this liability. In this work, we overcome this challenge by developing sensitive tools for the detection of Plasmodium falciparum and non-P. falciparum species. Furthermore, we evaluate these tools with a cohort of symptomatic and asymptomatic malaria patients and test a subcohort locally in Ghana. The findings of this work could lead to the implementation of DNA-based diagnostics to fight against the spread of malaria and provide reliable, sensitive, and specific diagnostics at the point of care.
Topics: Humans; Animals; Parasites; Point-of-Care Systems; Sensitivity and Specificity; Malaria; Malaria, Vivax; Malaria, Falciparum; Plasmodium falciparum
PubMed: 37158750
DOI: 10.1128/spectrum.05222-22 -
Tropical Medicine and Infectious Disease Mar 2023We propose a protocol suitable for point-of-care diagnosis of malaria utilizing a simple and purification-free DNA extraction method with the combination of...
We propose a protocol suitable for point-of-care diagnosis of malaria utilizing a simple and purification-free DNA extraction method with the combination of loop-mediated isothermal amplification assay and lateral flow (LAMP-LF). The multiplex LAMP-LF platform developed here can simultaneously detect and genus (for and ). Through the capillary effect, the results can be observed by the red band signal on the test and control lines within 5 min. The developed multiplex LAMP-LF was tested with 86 clinical blood samples on-site at Hospital Kapit, Sarawak, Malaysia. By using microscopy as the reference method, the multiplex LAMP-LF showed 100% sensitivity (95% confidence interval (CI): 91.4 to 100.00%) and 97.8% specificity (95% CI: 88.2% to 99.9%). The high sensitivity and specificity of multiplex LAMP-LF make it ideal for use as a point-of-care diagnostic tool. The simple and purification-free DNA extraction protocol can be employed as an alternative DNA extraction method for malaria diagnosis in resource-limited settings. By combining the simple DNA extraction protocol and multiplex LAMP-LF approach, we aim to develop a simple-to-handle and easy-to-read molecular diagnostic tool for malaria in both laboratory and on-site settings.
PubMed: 37104326
DOI: 10.3390/tropicalmed8040199 -
Microbiology Spectrum Jun 2023Malaria treatments resulted in the decline of the deadliest Plasmodium falciparum globally while species, such as , infections have been increasingly detected across...
Malaria treatments resulted in the decline of the deadliest Plasmodium falciparum globally while species, such as , infections have been increasingly detected across sub-Saharan Africa. Currently, no experimental drug sensitivity data are available to guide effective treatment and management of infections, which is necessary for effective malaria elimination. We conducted a prospective study to evaluate epidemiology over 1 year and determined susceptibility of the field isolates to existing and lead advanced discovery antimalarial drugs. We report that while P. falciparum dominated both symptomatic and asymptomatic malaria cases, in mono or co-infections caused 7.16% of symptomatic malaria. Frontline antimalarials artesunate and lumefantrine inhibited as potently as P. falciparum. Chloroquine, which has been withdrawn in Ghana, was also highly inhibitory against both and P. falciparum. In addition, and P. falciparum displayed high susceptibility to quinine, comparable to levels observed with chloroquine. Pyrimethamine, which is a major drug for disease massive prevention, also showed great inhibition of , comparable to effects on P. falciparum. Furthermore, we identified strong inhibition of using GNF179, a close analogue of KAF156 imidazolopiperazines, which is a novel class of antimalarial drugs currently in clinical phase II testing. We further demonstrated that the phosphatidylinositol-4-OH kinase (PI4K)-specific inhibitor, KDU691, is highly inhibitory against and P. falciparum field isolates. Our data indicated that existing and lead advanced discovery antimalarial drugs are suitable for the treatment of infections in Ghana. Current malaria control and elimination tools such as drug treatments are not specifically targeting . can form hypnozoite and cause relapsing malaria. is the third most dominant species in Africa and requires radical cure treatment given that it can form liver dormant forms called hypnozoites that escape all safe treatments. The inappropriate treatment of would sustain its transmission in Africa where the medical need is the greatest. This is a hurdle for successful malaria control and elimination. Here, we provided experiment data that were lacking to guide treatment and disease control policy makers using reference antimalarial drugs. We also provided key experimental data for 2 clinical candidate drugs that can be used for prioritization selection of lead candidate's identification for clinical development.
Topics: Humans; Antimalarials; Plasmodium falciparum; Plasmodium ovale; Ghana; Prospective Studies; Malaria; Malaria, Falciparum; Chloroquine
PubMed: 37093000
DOI: 10.1128/spectrum.04916-22 -
BioRxiv : the Preprint Server For... Mar 2023and represent distinct non-recombining malaria species that are increasing in prevalence in sub-Saharan Africa. Though they circulate sympatrically, co-infection...
and represent distinct non-recombining malaria species that are increasing in prevalence in sub-Saharan Africa. Though they circulate sympatrically, co-infection within human and mosquito hosts has rarely been described. Separate 18S rRNA real-time PCR assays that detect and were modified to allow species determination in parallel under identical cycling conditions. The lower limit of detection was 0.6 plasmid copies/μL (95% CI 0.4-1.6) for and 4.5 plasmid copies/μL (95% CI( 2.7- 18) for , or 0.1 and 0.8 parasites/μL, respectively, assuming 6 copies of 18s rRNA per genome. However, the assays showed cross-reactivity at concentrations greater than 10 plasmid copies/μL (roughly 200 parasites/μL). Mock mixtures were used to establish criteria for classifying mixed infections that prevented false-positive detection while maintaining sensitive detection of the minority ovale species down to 10° copies/μL (<1 parasite/μL). When the modified real-time PCR assays were applied to field-collected blood samples from Tanzania and Cameroon, species identification by real-time PCR was concordant with nested PCR, but additionally detected two mixed infections where nested PCR detected a single species. When real-time PCR was applied to 14 oocyst-positive midguts saved from mosquitoes fed on -infected persons, mixed infections were detected in 11 (79%). Based on these results, 8/9 carriers transmitted both species to mosquitoes, though both species could only be detected in the blood of two carriers. The described real-time PCR approach can be used to identify the natural occurrence of mixed infections in human and mosquito hosts and reveals that such co-infections and co-transmission are likely more common than appreciated.
PubMed: 37034766
DOI: 10.1101/2023.03.31.535020 -
Acta Medica Indonesiana Jan 2023Plasmodium ovale consists of two subspecies - P. ovale wallikeri and P. ovale curtisi. Increased reports of imported malaria ovale in non-endemic regions and mixed...
Plasmodium ovale consists of two subspecies - P. ovale wallikeri and P. ovale curtisi. Increased reports of imported malaria ovale in non-endemic regions and mixed infection of P. ovale with other Plasmodium species suggest that P. ovale might be under-detected during routine surveillance. Areas endemic with P. ovale have mostly been reported in African and Western Pacific countries. A recent case report in Indonesia indicated that regions with P. ovale endemicity are not only distributed in Lesser Sunda and Papua, but also in North Sumatra.
Topics: Humans; Plasmodium ovale; Indonesia; Malaria; Coinfection
PubMed: 36999258
DOI: No ID Found -
Research Square Mar 2023Water resource development projects such as dams and irrigation schemes have a positive impact on food security and poverty reduction but might result in increased...
BACKGROUND
Water resource development projects such as dams and irrigation schemes have a positive impact on food security and poverty reduction but might result in increased prevalence of malaria.
METHODS
Two cross-sectional surveys were conducted in the dry and wet seasons in irrigated and non-irrigated clusters of Arjo sugarcane and Gambella rice development areas of Ethiopia in 2019. A total of 4464 and 2176 blood samples were collected from Arjo and Gambella. A subset of 2244 microscopy negative blood samples were analyzed by PCR.
RESULTS
Prevalence by microscopy was 2.0% (88/4464) in Arjo and 6.1% (133/2176) in Gambella. In Gambella, prevalence was significantly higher in irrigated clusters (10.4% vs 3.6%) than in non-irrigated clusters ( < 0.001), but no difference was found in Arjo (2.0% vs 2.0%; p = 0.993). Level of education was an individual risk factors associated with infection in Arjo [AOR: 3.2; 95%CI (1.27-8.16)] and in Gambella [AOR: 1.7; 95%CI (1.06-2.82)]. While duration of stay in the area for < 6 months [AOR: 4.7; 95%CI (1.84-12.15)] and being a migrant worker [AOR: 4.7; 95%CI (3.01-7.17)] were risk factors in Gambella. Season [AOR: 15.9; 95%CI (6.01-42.04)], no ITN utilization [AOR: 22.3; 95%CI (7.74-64.34)] were risk factors in Arjo, and irrigation [AOR: 2.4; 95%CI (1.45-4.07)] and family size [AOR: 2.3; 95%CI (1.30-4.09)] risk factors in Gambella. Of the 1713 and 531 randomly selected smear negative samples from Arjo and Gambella and analyzed by PCR the presence of Plasmodium infection was 1.2% and 12.8%, respectively. and were identified by PCR in both sites.
CONCLUSION
Strengthening malaria surveillance and control in project development areas and proper health education for at-risk groups residing or working in such development corridors is needed.
PubMed: 36993196
DOI: 10.21203/rs.3.rs-2692688/v1 -
Nature Communications Mar 2023Plasmodium falciparum (Pf) is the dominant malaria parasite in Nigeria though P. vivax (Pv), P. ovale (Po), and P. malariae (Pm) are also endemic. Blood samples...
Plasmodium falciparum (Pf) is the dominant malaria parasite in Nigeria though P. vivax (Pv), P. ovale (Po), and P. malariae (Pm) are also endemic. Blood samples (n = 31,234) were collected from children aged 0-14 years during a 2018 nationwide HIV survey and assayed for Plasmodium antigenemia, Plasmodium DNA, and IgG against Plasmodium MSP1-19 antigens. Of all children, 6.6% were estimated to have Pm infection and 1.4% Po infection with no Pv infections detected. The highest household wealth quintile was strongly protective against infection with Pm (aOR: 0.11, 95% CI: 0.05-0.22) or Po (aOR= 0.01, 0.00-0.10). Overall Pm seroprevalence was 34.2% (95% CI: 33.3-35.2) with lower estimates for Po (12.1%, 11.6-12.5) and Pv (6.3%, 6.0-6.7). Pm seropositivity was detected throughout the country with several local government areas showing >50% seroprevalence. Serological and DNA indicators show widespread exposure of Nigerian children to Pm with lower rates to Po and Pv.
Topics: Humans; Child; Seroepidemiologic Studies; Nigeria; Plasmodium; Malaria; Malaria, Vivax; Plasmodium falciparum; Antigens, Protozoan; Immunoglobulin G; Malaria, Falciparum; Plasmodium vivax
PubMed: 36914649
DOI: 10.1038/s41467-023-37010-0