Plasmodium Infection Research Articles

Micronutrient status, food security, anaemia, Plasmodium infection, and physical activity as predictors of primary schoolchildren's body composition in Côte d'Ivoire

BackgroundStunting and overt malnutrition remain prevalent among school age children in rural areas of Côte d'Ivoire while obesity is increasing in urban areas. Associations of children's nutritional status, Plasmodium infection, physical activity and household characteristics with body composition were analyzed to identify what factors might be contributing to this dual burden of disease.MethodsLongitudinal growth curve models (LGCM) evaluated associations of micronutrient status, household food security, Plasmodium falciparum prevalence and physical activity assessed at three time points with fat free mass and fat mass.ResultsMore severe anaemia was inversely associated with FFM and TrFFM trajectories overall and among girls. P. falciparum infection had an indirect inverse association with FFM trajectories through anaemia among girls and through reductions of vitamin A directly associated with FFM. Changes in zinc concentrations were positively associated with FM trajectories overall and among boys. Food insecurity was inversely associated with FFM among boys from lower socio-economic status (SES) households while increased MVPA was associated with reduced fat mass among girls.ConclusionsThe integration of Malaria control programs with efforts to improve household healthy diet and promote physical activity can lead to improvements in body composition and overall child health and wellbeing.

Signature cytokine-associated transcriptome analysis of effector γδ T cells identifies subset-specific regulators of peripheral activation.

γδ T cells producing either interleukin-17A (γδ17 cells) or interferon-γ (γδIFN cells) are generated in the mouse thymus, but the molecular regulators of their peripheral functions are not fully characterized. Here we established an Il17a-GFP:Ifng-YFP double-reporter mouse strain to analyze at unprecedented depth the transcriptomes of pure γδ17 cell versus γδIFN cell populations from peripheral lymph nodes. Within a very high fraction of differentially expressed genes, we identify a panel of 20 new signature genes in steady-state γδ17 cells versus γδIFN cells, which we further validate in models of experimental autoimmune encephalomyelitis and cerebral malaria, respectively. Among the signature genes, we show that the co-receptor CD6 and the signaling protein Themis promote the activation and proliferation of peripheral γδIFN cells in response to T cell antigen receptor stimulation in vitro and to Plasmodium infection in vivo. This resource can help to understand the distinct activities of effector γδ T cell subsets in pathophysiology.

Differential B cell mediated immune response during Plasmodium yoelii infection in mice.

B lymphocytes are essential components of the humoral immune response and categorized into various subsets according to specific surface markers, functions, and developmental stages. Each subset of B cells plays a distinct role in the immune response, contributing to the overall effectiveness of the immune system. In this study, we investigated the modulation of different splenic subsets of B cells during Plasmodium yoelii infection. Balb/c mice infected with each Plasmodium yoelii XL and Plasmodium yoelii XNL parasite were used for phenotypic characterization of splenic B cell subsets through flow-cytometry. Our findings indicate that both lethal and non-lethal infections of Plasmodium yoelii result in significant alterations within the B cell compartment of the spleen in Balb/c mice during malaria infection. Notably, a differential expansion of immature B cell subsets T1 and T2 was noticed. A continuous reduction in frequency of both subsets (T1 and T2) during infection with lethal parasite while an increase in these subsets during the recovery from infection with non-lethal parasite was observed. Further, the frequencies of mature B cell subsets, follicular B cells and marginal zone B cells, were reduced during lethal infection which may be leading to susceptibility. Whereas non-lethal parasite infection resulted in increased frequency of follicular B cells in spleen which indicates towards establishment of germinal centre for generation of long-term immunity/resistance to infection. This differential expansion of splenic B cell subsets reflects the distinct characteristics of lethal and non-lethal parasite. Overall, these findings illustrate the potential role of B cells in resistance/susceptibility during malaria infection and further enhance our understanding of the B cell mediated immunological aspects of Plasmodium infection.

Association Between Plasmodium Infection and Blood Count Values: Implications for Malaria Diagnosis in Resource-Limited Settings

PurposeMalaria remains a major global health challenge, particularly in sub-Saharan Africa and low- and middle-income countries (LMICs), contributing substantially to mortality and morbidity rates. In resource-limited settings, access to specialized diagnostic tests is often restricted, making basic blood analysis a valuable diagnostic tool. This study investigated the correlation between malaria infection and full blood count values in a rural region of Ghana during the 2022 rainy season, aiming to highlight diagnostic insights available from routine blood analyses.MethodsA retrospective case-control analysis was conducted on 544 confirmed malaria cases, comparing their blood values with those of matched malaria-negative controls.ResultsParasitaemia levels peaked during the rainy season, with July showing the highest values. Malaria-positive patients exhibited lower levels of haemoglobin, white blood cells, lymphocytes, and platelets, but higher neutrophil counts compared to controls. Middle-aged women had significantly lower haemoglobin levels than men, and younger individuals showed higher parasitaemia levels. A negative correlation was found between Plasmodium density and haemoglobin and platelet counts, while positive correlations were observed with white blood cell and neutrophil counts.ConclusionThis study highlights the significant burden of malaria in rural Ghana during the rainy season and underscores the impact of infection on blood values. Routine full blood count analysis provides a practical and accessible diagnostic tool in resource-limited settings. The findings emphasise the importance of targeted interventions for high-risk groups, particularly children and women, to improve patient management and reduce malaria-related morbidity.Graphical

Comparative performance of microscopy, rapid diagnostic tests, and multiplex real-time PCR for detection of malaria parasites among pregnant women in northwest Ethiopia

BackgroundLow malaria parasitaemia is a diagnostic challenge in pregnancy, leading to false negative microscopy and rapid diagnostic test (RDT) results. However, these submicroscopic or subpatent infections could cause adverse pregnancy outcomes. Thus, evaluating the diagnostic performance of microscopy, RDT, and multiplex qPCR in pregnancy is vital for informed decisions.MethodsA total of 835 peripheral blood and 372 placental blood samples were collected from 835 pregnant women attending first antenatal care or admitted for delivery at selected health facilities in northwest Ethiopia between November 2021 and July 2022. In multiplex qPCR, all microscopy and/or RDT positive samples were extracted and amplified individually, whereas all samples negative by both RDT and microscopy were extracted after pooling ten samples together and tested for Plasmodium genus. The diagnostic performance of microscopy, RDT, and multiplex qPCR in pregnancy was compared and evaluated against each other.ResultsUsing multiplex qPCR as a reference test, microscopy had a sensitivity of 73.8% (95% confidence interval (CI): 65.9–80.7) and 62.2% (95% CI: 46.5–76.2) to detect Plasmodium parasites in peripheral and placental blood samples, respectively, with a 100% (95% CI: 98.9–100) specificity in both samples. Similarly, the RDT had a sensitivity of 67.6% (95% CI: 59.3–75.1) and a specificity of 96.5% (95% CI: 94.9–97.8) for Plasmodium infection diagnosis in peripheral blood and a sensitivity of 62.2% (95% CI: 46.5–76.2) and a specificity of 98.8% (95% CI: 96.9–99.7) in placental blood samples. Considering microscopy as a reference test, multiplex qPCR showed a sensitivity of 100% (95% CI: 96.6–100) and a specificity of 94.8% (95% CI: 93.0–96.3) to diagnose Plasmodium infections in both peripheral and placental blood samples. Pooled multiplex qPCR detected 34 peripheral and 12 placental blood Plasmodium infections from microscopy and RDT negative samples. The pooled assay obviated about half of the reactions and its testing costs. Microscopy showed almost perfect agreement (κ = 0.823) with multiplex qPCR for detecting malaria parasites in pregnancy, whereas the RDT showed a substantial agreement (κ = 0.684).ConclusionMultiplex qPCR had a better performance for Plasmodium infection diagnosis in pregnancy compared to microscopy and RDT. Pooled multiplex qPCR could be a sensitive and resource-efficient strategy for epidemiological surveillance of Plasmodium infections in pregnancy.

Targeting anemia-induced CD71 + reticulocytes protects mice from Plasmodium infection.

This work was supported by grants from the Crohn's and Colitis Foundation (CCF) and American Heart Association (AHA) Career Development Award (854385 and 855256 respectively) to Piu Saha; grant from the National Institutes of Health (NIH) to Matam Vijay-Kumar (DK134053) and Liver Scholar Award from American liver Foundation to Beng San Yeoh.

The malaria parasite PP1 phosphatase controls the initiation of the egress pathway of asexual blood-stages by regulating the rounding-up of the vacuole.

A sustained blood-stage infection of the human malaria parasite P. falciparum relies on the active exit of merozoites from their host erythrocytes. During this process, named egress, the infected red blood cell undergoes sequential morphological events: the rounding-up of the surrounding parasitophorous vacuole, the disruption of the vacuole membrane and finally the rupture of the red blood cell membrane. These events are coordinated by two intracellular second messengers, cGMP and calcium ions (Ca2+), that control the activation of their dedicated kinases, PKG and CDPKs respectively, and thus the secretion of parasitic factors that assist membranes rupture. We had previously identified the serine-threonine phosphatase PP1 as an essential enzyme required for the rupture of the surrounding vacuole. Here, we address its precise positioning and function within the egress signaling pathway by combining chemical genetics and live-microscopy. Fluorescent reporters of the parasitophorous vacuole morphology were expressed in the conditional PfPP1-iKO line which allowed to monitor the kinetics of natural and induced egress, as well as the rescue capacity of known egress inducers. Our results underscore a dual function for PP1 in the egress cascade. First, we provide further evidence that PP1 controls the homeostasis of the second messenger cGMP by modulating the basal activity of guanylyl cyclase alpha and consequently the PKG-dependent downstream Ca2+ signaling. Second, we demonstrate that PP1 also regulates the rounding-up of the parasitophorous vacuole, as this step is almost completely abolished in PfPP1-null schizonts. Strikingly, our data show that rounding-up is the step triggered by egress inducers, and support its reliance on Ca2+, as the calcium ionophore A23187 bypasses the egress defect of PfPP1-null schizonts, restores proper egress kinetics and promotes the initiation of the rounding-up step. Therefore, this study places the phosphatase PP1 upstream of the cGMP-PKG signaling pathway, and sheds new light on the regulation of rounding-up, the first step in P. falciparum blood stage egress cascade.

Diversity, abundance of anopheline species, and malaria transmission dynamics in high-altitude areas of western Cameroon.

Background : Assessing vector bionomics is crucial to improving vector control strategies. Several entomological studies have been conducted to describe malaria transmission in different eco-epidemiological settings in Cameroon; knowledge gaps persist, particularly in highland areas. This study aimed to characterize malaria vectors in three localities along an altitudinal gradient in the western region: Santchou (700 m), Dschang (1400 m), and Penka Michel (1500 m). Methods : Human landing catches were conducted from May to June 2023 from 6:00 pm to 9:00 am. Mosquitoes were sorted into genera, and all Anopheles species were identified using morphological taxonomic keys and species-specific Polymerase Chain reaction (PCR). Entomological indicators were assessed including species composition and abundance, biting behavior, infection rate, and entomological inoculation rate (EIR). Genomic DNA from the head and thoraces were tested for Plasmodium infection by real-time PCR. Results : 2,835 Anopheles mosquitoes were identified, including An. gambiae, An. coluzzii, An. funestus, An. leesoni, An. nili, and An. ziemanni , with An. gambiae being the most prevalent at all sites. The human-biting rate of An. gambiae s.l. was significantly higher (p-value < 0.001) in Penka Michel compared to Santchou and Dschang (45.25 b/h/n vs 3.1 b/h/n and 0.41 b/h/n), and appears to be the most infected vector, and infectious vector distribution is highly focal, with entomological inoculation rates 13-fold higher in Penka Michel compared to Santchou (1.11 vs 0.08ibites/human/night). P. falciparum was the dominant malaria parasite (67% at Santchou, 62% at Penka Michel), but P. malariae (30%) and P. ovale (1.21%) infections were also detected. Conclusion : The study highlights a difference in mosquito composition and host-seeking behavior with altitude and the need for continued surveillance to monitor vector populations and prevent potential malaria outbreaks in these highland areas.

Malaria prevalence, transmission potential and efficacy of artemisinin-based combination therapy in the Kenyan Central highlands: a zone previously characterized as malaria-free

BackgroundThe current study sought to re-evaluate malaria prevalence, susceptibility to artemisinin-based combination therapy (ACT), transmission patterns and the presence of malaria vectors in the Kikuyu area of the Kenyan Central highlands, a non-traditional/low risk malaria transmission zone where there have been anecdotal reports of emerging malaria infections.MethodsSampling of adult mosquitoes was done indoors, while larvae were sampled outdoors in June 2019. The malaria clinical study was an open label non-randomized clinical trial where the efficacy of one ACT drug, was evaluated in two health facilities. Microscopy was used at the facility while nested 18 s rRNA subunit gene PCR amplification and MSP-1 and MSP-2 family alleles genotyping was done in the laboratory. Anti-malarial resistance gene markers Pfk13 and Pfmdr1 were profiled.ResultsAnopheles funestus mosquitoes were the predominant vectors at 76.35% of all larvae collections (N = 148). Only two non-blood fed, parasites negative adult mosquitoes were collected from houses sampled. Parasitological analysis of the 838 patients screened resulted in 41 positives whose treatment outcome was 100% Adequate Clinical and Parasitological Response (ACPR). From the 35 positive samples genotyped, 29 (82.9%) were polyclonal. The overall mean MOI was 2.8 (95% CI 2.36–3.35). The MOI for msp-1 and msp-2 genes, was 2.02 (95% CI 0.72–2.27) and 2.9 (95% CI 2.22–3.55), and parasite strains range of 1–3 and 1–7, respectively. Polyclonal variation in the two genes was at 76.4% and 70.3%, respectively. The Pfk13 gene revealed no single nucleotide polymorphisms (SNP) associated with suspected artemisinin resistance nor was there any pfmdr1 N86 mutant allele detected.ConclusionThe Plasmodium infections positivity rate observed in the study site was very low but significant. A proportion of participants who tested positive did not report recent history of travel. This observation together with the finding of competent known vectors can probably suggest that several of the cases could have been acquired and transmitted locally. The observed genetic diversity and polyclonal variations was on the contrary and suggest that these are imported cases. This however does not rule out a likely changing malaria transmission scenario in this zone, thus the need for further investigations.

Delayed post-juvenile moult in malaria-infected Eurasian blackcaps.

Parasites have their strongest impact on fitness when host defences deplete resources needed for other critical life-history stages, such as development, breeding or migration. Among birds, one greatly neglected stage that could be altered by parasites is post-juvenile moult (PJM), through which yearling juvenile birds replace their fast-generated, low-quality juvenile feathers with adult-like feathers after leaving the nest. The earlier the birds complete PJM, the earlier they will be prepared to withstand forthcoming challenges, such as adverse winter conditions or migration. We used data from 435 juvenile Eurasian blackcaps (Sylvia atricapilla) sampled during three years in 26 localities spanning the wide range of environmental conditions across Iberian Spain to test whether haemosporidian infections (presence and abundance in blood of parasites of the genera Haemoproteus, Plasmodium and Leucocytozoon) were related to the progress of PJM. Controlling for body condition, sex, year and date of capture, infected blackcaps (single-infected or co-infected) had lower moult scores indicative of delayed moult, especially when birds had Plasmodium infections or high intensities of Haemoproteus parasites. Our results broaden the range of fitness costs that haemosporidian parasites may have on birds, as delayed post-juvenile plumage acquisition can impact subsequent key life-history stages.

Automated total nucleic acid extraction with magnetic beads for the detection of Plasmodium falciparum in large study cohorts

Abstract Background Molecular methods play an important role in clinical trials assessing anti-malarial drugs and vaccines, as well as in epidemiological studies aimed at detecting Plasmodium species, especially when dealing with large sample sizes. Molecular techniques are more sensitive and generally have a higher throughput compared to the gold standard microscopy. Further optimization can be achieved with automation of nucleic acid isolation, allowing for rapid and precise extraction. This study evaluated the isolation of total nucleic acids from Plasmodium falciparum mocked samples using an automated extraction method with a magnetic bead-based kit compared to a manual silica column-based kit. Additionally, two different RNA preservation solutions were compared. Methods Plasmodium falciparum Dd2 parasites were serially diluted and spiked into whole blood. The dilutions were stored in two different RNA preservation solutions and total nucleic acids extracted with an automated magnetic bead-based kit and a manual silica column-based kit. Subsequently, a reverse transcription (RT) qPCR for Plasmodium detection targeting Plasmodium 18S rRNA and DNA in a single reaction was performed and the quantification cycle (Cq) values across the different sample groups were compared. Results Comparable Cq values across the various sample preparations were obtained, suggesting minimal influence from RNA preservation solutions (p = 0.686) or extraction methods (p = 0.119) on RT-qPCR outcomes. Automated nucleic acids extraction allowed processing numerous samples in a shorter timeframe and showed similar efficiency in detecting Plasmodium in blood samples by RT-qPCR as manual extraction. Conclusions The automated method for nucleic acid isolation is a valuable tool for the detection of Plasmodium infections in large-scale studies. It is efficient, reliable, and cost-effective. Its potential applications extend to other molecular surveillance studies to support malaria control measures.

Asymptomatic Malaria Cases and Plasmodium Species in Mainland Tanzania and Zanzibar Archipelago (Pemba).

Malaria remains a major public health threat in Sub-Saharan Africa. According to the World Health Organization (WHO) estimates, Plasmodium falciparum species account for nearly 100% of the malaria cases occurring on the African continent. According to the Centers for Disease Control and Prevention (CDC), falciparum malaria predominates, but non-falciparum species are also present in Africa. The aim of the study was to assess the occurrence of asymptomatic malaria cases, as well as to identify Plasmodium species at two different settings with the lowest index of infections in Tanzania (according to the Tanzanian Ministry of Health < 1%), i.e., on the mainland (Arusha Region) and on the Pemba Island (Zanzibar Archipelago). The study was conducted in June 2023 and involved 722 individuals, including 449 residents of mainland Tanzania and 273 residents of the Zanzibar Archipelago. The screening consisted of two phases. In the first one, which was carried out at two different settings, i.e., in the Karatu Lutheran Hospital (Arusha Region, mainland Tanzania) and the Amal Hospital (Pemba, Zanzibar Archipelago), mRDTs (malaria rapid diagnostic tests) were performed, haemoglobin concentrations were measured, and blood samples for further molecular tests were collected onto Whatman micro cards from each of the individuals involved. In the second phase (conducted in Poland, Europe), RT-PCR tests for malaria were performed. The screening found asymptomatic Plasmodium infections in 4.2% of the study subjects from mainland Tanzania and in 4.8% from the Archipelago. The research confirmed cases of P. falciparum malaria but also found single cases of mixed infections with P. falciparum + P. malariae or P. ovale. The results demonstrated that the occurrence of malaria in northern mainland and Zanzibar Archipelago is higher than the official MoH reports present. The study findings are consistent with the reports by CDC, which suggest that non-falciparum species are also present in Sub-Saharan Africa.

Spatiotemporal dynamics of malaria and climate influence on its incidence in Condorcanqui Province, 2005–2022

BackgroundAmazonas is a region in northern Peru with the second-highest incidence of malaria. Approximately 95% of the cases are reported in the Condorcanqui province, where native communities living along the banks of Santiago River lack access to potable water, sewage, and electricity. This study aimed to analyse malaria’s spatial, temporal, and climatic characteristics in Condorcanqui to guide future studies and prevention strategies.MethodsA database provided by DIRESA-Amazonas was evaluated. Database included cases from 44 health facilities serving 112 native communities. According to the malaria control programs implemented in Peru, the study was divided into three periods: 2005–2010, 2011–2016, and 2017–2022. A Spearman correlation analysis was also conducted to assess the relationship between malaria incidence and climate variables.ResultsDuring the study periods, 10,632 cases were reported, including Plasmodium vivax (84.87%), Plasmodium falciparum (14.91%) and Plasmodium malariae (0.23%) infections. Annual incidence rates (AIRs) significantly varied across the study periods (p < 0.001). A significant reduction in malaria incidence occurred during the first period, largely attributed to PAMAFRO programme interventions. Subsequent periods, showed a gradual increase in cases, with a peak of P. vivax in 2019 and the reintroduction of P. falciparum. Males and individuals aged 0–11 years presented the greatest number of cases. Significant correlations were found between malaria incidence and the Oceanic Niño Index (ONI) at lag0 (ρ = 0.14, p = 0.037), corrected precipitation at lag1 (ρ = 0.16, p = 0.020), and minimum wind speed at lag1 (ρ = 0.15, p = 0.024).ConclusionsMalaria incidence in Condorcanqui has increased over the last 5 years, driven by climatic influences such as the ONI, precipitation, and low wind speeds. Without immediate preventive efforts, cases are expected to continue rising. Effective control strategies must tackle the social, economic, and political issues that heighten vulnerability, such as poverty and limited healthcare access. Maintaining control initiatives and tailoring them to local needs will be essential for achieving long-term reductions of malaria in Peru.

Asymptomatic Plasmodium falciparum infections and determinants of carriage in a seasonal malaria chemoprevention setting in Northern Cameroon and south Senegal (Kedougou)

BackgroundAmong the several strategies recommended for the fight against malaria, seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine combination (SPAQ) targets children 3 months to 5 years in Sahel regions of Africa to reduce mortality and mortality. Since SMC with SPAQ is administered to symptoms-free children for prevention of malaria, it is anticipated that a proportion of asymptomatic parasitaemic children will also be treated and may result in a drop in both the overall population prevalence of asymptomatic malaria infections, subsequent risk of symptomatic malaria infections and transmission. Age-specific carriage of asymptomatic Plasmodium spp. infections (API) was evaluated in target children and adults in Cameroon and Senegal, prior to the 2018 SMC campaign in both countries.MethodsA baseline household survey was carried out in August 2018 in two areas in Cameroon and one in Senegal just before the beginning of distribution of SPAQ for SMC. The survey included collection of fingerpick blood for malaria rapid diagnostic testing (RDT) and administration of a pre-tested questionnaire on demographics and malaria risk factors to participants. The age-specific prevalence of API in all study sites was analysed, first as a distribution of RDT-positives in 5-year age categories and secondly, with age as a continuous variable in the whole sample, using the Wilcoxon rank sum test. Risk factors for carriage of asymptomatic infections were examined using logistic regression analysis in STATA v.16 and Rv4.1.2.ResultsIn total, 6098 participants were surveyed. In Cameroon, overall prevalence of API was 34.0% (32.1–36.0%) in Adamaoua, and 43.5% (41.0–45.7%) in the North. The median age of RDT positivity was higher in Senegal: 11 years (IQR 7–16) than in Cameroon—Adamaoua: 8 years (4–17) and North: 8 years (4–12) and significantly different between the three study regions. In all three study sites, asymptomatic carriage was significantly higher in the older age group (5–10 in Cameroon, and 7–14 in Senegal), compared to the younger age group, although the median age of participants was lower among RDT-negatives in the North compared to RDT-positives. Health area, gender and last infection within past year significantly confounded the relationship between age and parasite carriage in Adamaoua and Senegal but not in North Cameroon. Absence of bed net and previous infection within one month of the survey all independently predicted carriage of asymptomatic parasites in multivariate regression analysis.ConclusionUnder five years asymptomatic Plasmodium infection in northern Cameroon prior to SMC season remained high in 2018, irrespective of history of SMC implementation in the study areas in Cameroon. Compared to Adamaoua, peak asymptomatic malaria parasite rate was observed in children 5–10 years, which is out of the SMC target age-range. Health area, last infection within the past month and to a lesser extent gender affected the association between age and asymptomatic carriage in all sites except the North region of Cameroon, indicating wide heterogeneity in risk of malaria among the general population in that geography. Follow-up studies designed to measure SMC effects in Cameroon are warranted as it may become necessary to extend age of SMC eligibility to 10 years, as is practiced in Senegal.

Microscopic prevalence and risk factors of asymptomatic malaria in Gorgora, western Dembia, Northwest Ethiopia: exploring hidden threats during minor transmission season

BackgroundMalaria poses a significant public health threat globally, particularly in African regions, where asymptomatic malaria is a considerable logistic problem. Individuals with asymptomatic malaria do not seek treatment, and thus they are invisible to health facilities and represent a substantial hidden reservoir of Plasmodium species. This study aimed to determine the prevalence of asymptomatic malaria and its associated factors in Gorgora, western Dembia district, Northwest Ethiopia.MethodsA community-based cross-sectional study was conducted from May to June 2023 in the Gorgora area, Western Dembia district, Northwest Ethiopia. Data were collected using a semi-structured questionnaire. Giemsa-stained blood smear microscopy was employed for the diagnosis of Plasmodium species. The data were entered into Epi Data version 4.6 and exported to SPSS version 25 for analysis. Bivariate and multivariable binary logistic regression analyses were conducted to identify associated factors.ResultsAmong the 357 individuals who participated in this study, 9.2% (33/357) [95% CI 6.40–12.70: p = 0.000] were confirmed to be infected with Plasmodium species. Plasmodium falciparum and Plasmodium vivax accounted for 66.7% and 33.3%, respectively. Not using bed nets [AOR = 7.3, 95% CI 2.08–23.46, p = 0.006)], previous malaria history [AOR = 2.6, 95% CI 1.01–6.45, p = 0.041], outdoor activities at night [AOR = 8.3, 95% CI 3.21–21.30, p = 0.000], and family size [AOR = 3.3, 95% CI 1.18–9.22, p = 0.023] were significantly associated with asymptomatic malaria (p < 0.05).ConclusionsA considerable proportion of asymptomatic Plasmodium infections was found which likely act as a reservoir of transmission. This has implications for ongoing malaria control programmes that are based on the treatment of symptomatic patients and highlight the need for intervention strategies targeting asymptomatic carriers. Not using bed nets, engaging in outdoor activities at night, and having a family size of more than five increased the odds of developing asymptomatic malaria. The district health office and health extension workers should collaborate to promote the regular use of mosquito bed nets among community residents.

Performance of the Bioline™ Malaria Ag Pf/Pan and Bioline™ Malaria Ag Pf/Pv for Malaria Diagnostics: Madagascar In-Country Evaluation.

Malaria remains a significant public health concern in Madagascar. The WHO recommends using parasitological methods to confirm Plasmodium infection before treatment. This study evaluated the performance of two rapid diagnostic tests (RDTs), Bioline™ Malaria Ag Pf/Pan (Abbott Point of Care, Princeton, NJ) and Bioline™ Malaria Ag Pf/Pv (Abbott Point of Care, Princeton, NJ), compared with microscopy and polymerase chain reaction (PCR) as reference methods. A prospective, diagnostic performance study was conducted in two malaria-endemic districts with different epidemiological contexts: Ifanadiana (Plasmodium falciparum [P. falciparum] transmission) and Mandoto (Plasmodium vivax transmission). Symptomatic patients and asymptomatic individuals aged 3-81 years were enrolled between April and July 2023. Finger prick blood samples were used for RDTs, Giemsa-stained blood films, and molecular analysis. Among 675 participants (401 symptomatic, 274 asymptomatic), the performance for detecting P. falciparum and non-falciparum/vivax malaria in symptomatic patients for Bioline™ Malaria Ag Pf/Pan was 96.5% (95% CI: 93.4-98.4%) and 91.5% (95% CI: 82.5-96.8%) sensitivity and 76.0% (95% CI: 64.7-85.1%) specificity, and the performance for Bioline™ Malaria Ag Pf/Pv was 95.0% and 91.5% sensitivity and 76.0% specificity. In asymptomatic individuals, the performance was 90.3% (95% CI: 83.4-95.0%) and 33.3% (95% CI: 4.3-77.7%) sensitivity and 85.4% (95% CI: 78.9-90.6%) specificity for Bioline™ Malaria Ag Pf/Pan and 80.6% (95% CI: 80.1-93.1%) and 0% (95% CI: 0-84.2%) sensitivity and 86.0% (95% CI: 79.7-91.0%) and 86.1% (95% CI: 79.7-91.0%) specificity for Bioline™ Malaria Ag Pf/Pv. Rapid diagnostic test performance varies with local epidemiology in symptomatic patients. The results emphasize the need for careful consideration of RDT use based on local epidemiology and clinical context. Both RDTs could be used when microscopy and PCR are unavailable.

Burden and clinical characteristics of recurrent Plasmodium vivax infections, and impact of primaquine for radical cure: a systematic scoping review in India

Burden and clinical characteristics of recurrent Plasmodium vivax infections, and impact of primaquine for radical cure: a systematic scoping review in India

Drug Interaction Studies of Cabamiquine:Ganaplacide Combination against Hepatic Plasmodium berghei.

New antimalarial combination therapies with novel modes of action are required to counter the emergence and spread of Plasmodium drug resistance against existing therapeutics. Here, we present a study to evaluate the preventive activity of a combination of clinical antimalarial drug candidates, cabamiquine and ganaplacide, that have multistage activity against the liver and blood stages of Plasmodium infection. Cabamiquine (DDD107498, M5717) inhibits parasite protein synthesis, and ganaplacide (KAF156) inhibits protein trafficking, blocks the establishment of new permeation pathways, and causes endoplasmic reticulum expansion. The pharmacodynamic parameters of a combination of the two compounds were assessed employing a pharmacometrics approach in conjunction with in vitro-in silico checkerboard analysis. The in vitro study was performed on a previously established 3D infection platform based on human hepatic cell lines that sustain infection by rodent P. berghei parasites. The in vivo efficacy of this drug combination was assessed against the liver stage of the P. berghei. Our results show that the combination of both drugs at the tested concentrations does not interfere with the drugs respective mode of action or affect hepatocyte cell viability. The drug combination was fully effective in preventing the appearance of blood stage parasites when a systemic plasma Cav0-24/EC50 ratio >2 for ganaplacide and >5 for cabamiquine was achieved. These findings demonstrate that chemoprevention using a combination of cabamiquine and ganaplacide has the potential to target the asymptomatic liver stage of Plasmodium infection and prevent the development of parasitemia.

Diagnosis of Plasmodium infections using artificial intelligence techniques versus standard microscopy in a reference laboratory.

Diagnosing malaria using standard techniques is time-consuming. With limited staffing in many laboratories, this may lead to delays in reporting. Innovative technologies are changing the diagnostic landscape and may help alleviate staffing shortages. The miLab MAL, an automated artificial intelligence-driven instrument was compared with standard microscopy at LabCorp reference laboratories. Four hundred eight samples submitted for parasitic examination were prepared with thick and thin smears and Noul's malaria platform miLab MAL, and evaluated for positivity, negativity, percent positivity, and species identification. Of 408 samples, 399 samples were manually negative, while 397 were negative by miLab MAL. Two samples initially classified as negative manually were found positive by miLab MAL. In all nine cases, Plasmodium falciparum was identified by both methods. Percentage parasitemia was higher in the manually calculated method, especially when >1%. miLab MAL was accurate in identifying the absence of Plasmodium falciparum and exhibited higher sensitivity than the manual method. All positive samples detected by microscopy were also identified with miLab MAL. All positive Plasmodium cases were correctly identified by miLab MAL. However, the number of positive samples was limited to only Plasmodium falciparum. Although parasitemia by the manual method was on average six times higher than with miLab MAL, this may be due to sampling variability. The findings show that miLab MAL can be used to screen out negative Plasmodium falciparum samples. Further studies assessing parasitemia between methods and identification of non-falciparum samples are necessary to assess the reliability of this new technology.

Chromobacterium biopesticide overcomes insecticide resistance in malaria vector mosquitoes.

Vector mosquito control is an integral part of malaria control. The global emergence of insecticide resistance in malaria-transmitting Anophelines has become an impediment and has created an urgent need for novel mosquito control approaches. Here, we show that a biopesticide derived from the soil-dwelling bacterium Chromobacterium sp. Panama (Csp_P) kills insecticide-resistant Anopheles mosquitoes, regardless of their resistance mechanisms. In addition, sublethal dose of Csp_P acts as a synergist to now used chemical insecticides across multiple classes. Moreover, Csp_P reduces host-seeking behavior and malaria parasite infection in vector mosquitoes in ways that further decrease transmission. Mosquito glutathione S-transferases are essential for Csp_P's mosquito-killing mechanism. Enclosed field trials in Burkina Faso, conducted in diverse ecological settings and supported by a mathematical model, have now demonstrated its potential for malaria control in settings with widespread insecticide resistance.