Malaria Journal最新文献

Background: Almost 500,000 children under 5 years die annually from severe malaria in Africa. Prompt access to effective antimalarial treatment is crucial to reduce mortality. Current clinical guidelines recommend pre-referral rectal artesunate (RAS) followed by injectable artesunate and a 3-day course of artemisinin-based combination therapy (ACT). However, adherence to this treatment algorithm is not always feasible due to many reasons. Integrated community case management (iCCM) presents a promising strategy to improve timely access to care through community health workers (CHWs). This study aims to: (i) assess the feasibility of providing rapid treatment of severe malaria with RAS to children aged 6 months-5 years by CHWs or in health facilities (HFs) without injectable artesunate; (ii) evaluate recrudescence rates in children under 5 following RAS by either ACT for whom referral was not feasible or those after referral completion; and (iii) assess the impact of upgrading iCCM services on access to the formal healthcare system, including severe malaria care.

Methods: This is an effectiveness-implementation hybrid Type 3 study. The study is being conducted in Nchelenge, Zambia and Kapolowe, Democratic Republic of Congo using phased rollout of upgraded iCCM according to national guidelines. CHWs will diagnose, treat and monitor study participants, while research assistants will visit each participant on day 14 to complete a questionnaire, conduct in-depth interviews (IDIs) as well as focus group discussions (FGDs) with caregivers of sampled study participants. Primary outcomes include: (i) time from symptom onset to treatment initiation in the participants who seek care via CHWs or HFs; (ii) 28-day PCR-corrected cure rates following RAS + ACT or RAS + injectable artesunate + ACT treatment; and (iii) the proportion of study population utilizing formal healthcare services within the preceding 6 months, including suspected severe malaria cases.

Discussion: This study will provide essential evidence on the feasibility and effectiveness of community-based pre-referral treatment for severe malaria in resource-limited settings, address access barriers to injectable artesunate and facility-based care, inform policy and programmatic adaptations and guide scalable strategies to enhance timely treatment, reduce mortality and mitigate drug resistance in high-burden malaria regions.

Introduction: Malaria is the leading cause of morbidity and mortality in the Democratic Republic of the Congo (DRC), posing a significant public health challenge, especially among children aged 6-59 months. This study aims to determine the prevalence and factors associated with malaria in this age group.

Methods: The study analyzed secondary data from a weighted sample of 10,013 children aged 6-59 months who underwent a malaria rapid diagnostic test, drawn from the 2023/24 DRC Demographic and Health Survey. Descriptive, bivariate, and multivariable modified Poisson regression analyses were conducted. A factor was considered significant if the p-value was less than 0.05, with a 95% confidence interval (CI).

Results: The overall prevalence of malaria among children aged 6-59 months in the DRC was 33% (95% CI = 30.2, 35.6), varying significantly between provinces, from 5% in Kinshasa to 61% in Bas-Uele province. Factors associated with malaria in this age group included children aged 24-59 months (APR = 1.25, 95% CI = 1.15, 1.36), children of mothers with no education (APR = 1.15, 95% CI = 1.03, 1.29) and those with primary education (APR = 1.13, 95% CI = 1.02, 1.30), children from the poor wealth quintile (APR = 1.52, 95% CI = 1.08, 2.13) and the middle wealth quintile (APR = 1.42, 95% CI = 1.03, 1.95), children who never slept under an insecticide-treated net (ITN) (APR = 1.18, 95% CI = 1.06, 1.30), children from households without a television (APR = 1.73, 95% CI = 1.22, 2.45), and those living in houses with unimproved floor material (APR = 1.54, 95% CI = 1.10, 2.08) or unimproved roof material (APR = 1.27, 95% CI = 1.04, 1.54).

Conclusion: The prevalence of malaria remains high among children aged 6-59 months. The study highlights the need for strategies that include scaling up the distribution of insecticide-treated nets (ITNs) and educating caregivers on their proper use, improving access to timely diagnosis and treatment, and integrating multisectoral approaches that address socioeconomic vulnerabilities.

Background: Identity-by-descent (IBD), which describes recent genetic co-ancestry between pairs of genomes, is a fundamental concept in population genomics. It has been used to estimate genetic relatedness, detect selection signals, and understand population demography. The IBD detection method hmmIBD demonstrates high accuracy in inferring IBD segments between haploid genomes, including Plasmodium falciparum, and is widely used in malaria genomic surveillance. However, the current single-threaded implementation of hmmIBD does not utilize the full capacity of multi-processor computers, making it difficult to apply to large data sets, and does not accommodate non-uniform recombination rates across the genome.

Methods: We developed an enhanced implementation of hmmIBD, named hmmibd-rs, which leverages multi-threaded computing to parallelize IBD inference over genome pairs and which supports optional, user-defined recombination rate maps for more accurate IBD detection and filtration from genomes with non-uniform recombination. We further streamlined large-scale IBD detection by incorporating auxiliary built-in functionalities to preprocess input directly from the standard binary variant call format (BCF) and filter IBD output to reduce disk usage.

Results: Our new implementation significantly reduces IBD detection computation time nearly linearly with the increased number of CPU threads used; using 128 threads shortens IBD detection time from 5.2 days to 1.3 h for 220 million pairs of simulated Plasmodium falciparum-like chromosomes, increasing computational speed by approximately 100 × over the single-threaded hmmIBD algorithm. Incorporating non-uniform recombination rates in hmmibd-rs enhances the accuracy of IBD inference by mitigating the overestimation of IBD breakpoints in recombination cold spots and their underestimation in hot spots. Non-uniform rates also improve length filtration of IBD segments, dramatically reducing the rate of false positive in recombination cold spots. When applied to empirical data sets, hmmibd-rs completes the detection of IBD from MalariaGEN Pf7 (n ≈ 10,000 monoclonal samples) within hours, enabling a single-day IBD analysis pipeline for large genomic data sets.

Conclusion: hmmibd-rs builds upon, accelerates, and enhances hmmIBD for efficient and accurate IBD detection, serving as a crucial tool for advancing large-scale malaria genomic surveillance.

Background: Malaria remains a major global public health concern with the greatest burden in tropical and subtropical regions, particularly sub-Saharan Africa. Uganda ranks among the world's highest burden countries, with its warm temperatures, abundant rainfall and diverse mosquito breeding habitats sustaining year-round malaria transmission in malaria endemic areas. This study assessed malaria incidence trends and their association with climate variables in Yumbe district, Uganda.

Methods: A retrospective ecological time-series study analysed malaria incidence (2017-2021) in Yumbe district, Uganda, using District Health Information System reports and Uganda National Meteorological Authority climate data (daily temperature and rainfall). Data were cleaned in Excel and analysed in R software V4.5.1. Monthly/annual summaries, seasonal pattern graphs, Kendall's tau correlations for non-linear associations, and Multiple Linear and Poisson regressions with lag effects were done. Time series analysis involved seasonal decomposition, cross-correlation, and ARIMAX modelling. A multivariable OLS regression on log(1 + cases) with best-lagged rainfall and minimum temperature further assessed climate influence.

Results: Between 2017 and 2021, a total of 2,066,711 malaria cases were reported in Yumbe district. Malaria trends closely followed rainfall patterns, peaking during the period of high precipitation. Time-series analysis showed that rainfall was positively associated with malaria incidence at one-month lag (β = 0.38, p < 0.05), while minimum temperature was inversely associated (β = - 0.29, p < 0.05). Statistical analysis revealed rainfall (mm) strongly led malaria cases by 1 month (r = 0.759, p < 0.001). Maximum temperature showed no significant effect on malaria incidence.

Conclusion: Malaria incidence in Yumbe district is strongly influenced by rainfall and minimum temperature. This study highlights the role of climate variability in malaria transmission in malaria endemic areas. Integrating climate data into surveillance and early warning systems could enhance timely interventions in malaria endemic areas like Yumbe district.

Background: Compliance with evidence-based treatment guidelines, supported by quality-assured parasitological diagnosis, is the mainstay of malaria case-management in Nigeria. However, despite increased attention, the quality of inpatient paediatric and adult, test-and-treat malaria case-management, and routine accuracy of malaria microscopy, has rarely been examined in public and private hospitals.

Methods: A cross-sectional assessment was undertaken at 18 public and private hospitals in September 2024 in Kano State, Nigeria. Data collection included hospital assessments, interviews with inpatient health workers, review of all paediatric and medical ward admission files for August 2024, and re-checking of routine malaria slides archived during the 3-month post-assessment period. Descriptive analyses included 18 hospitals, 72 health workers, 2,814 suspected malaria admissions, and 211 malaria slides.

Results: Nearly all hospitals (94.4%) provided parasitological diagnostic services (microscopy or RDT) and stocked recommended antimalarials (injectable artesunate and ACT). Most health workers had received training on severe malaria (73.6%), but only 16.7% received supportive supervision. The composite test-and-treat performance was 39.3%, higher for children than adults (45.7% vs 26.5%) and in public compared to private hospitals (39.8% vs 30.8%). Among suspected malaria patients, 73.7% were tested on admissions and 90.2% of those with severe malaria were treated with artesunate. Children, compared to adults, were more commonly tested (79.8% vs 61.7%) and treated with artesunate (93.5% vs 80.1%). Patients in private hospitals, compared to public, were more often tested (84.3% vs 73.0%) but less frequently treated with artesunate (73.1% vs 91.2%). Only 30.0% of artesunate-treated patients were prescribed ACT-more commonly among adults than children (48.3% vs 23.0%) and in private than in public hospitals (89.2% vs 26.9%). ACT use for admitted non-severe cases was rare (2.4%), whereas non-compliance with test negative results was high (75.8%). The sensitivity, specificity, positive and negative predictive values of routine microscopy compared to expert readings were 93.2%, 42.5%, 29.9% and 95.9%, respectively.

Conclusions: Inpatient compliance with malaria test-and-treat guidelines varied between performance tasks, age groups, and hospital sectors. Clinicians can be confident in negative slides but should be cautious with positive results. Quality assurance of malaria diagnosis and continuous clinical and laboratory quality improvement interventions, with enhanced linkages, are needed.

Background: Malaria remains a leading cause of morbidity and mortality, particularly among children under five years of age in sub-Saharan Africa. Nigeria has the highest burden of malaria cases worldwide, accounting for 26% of all cases. The introduction of the R21/Matrix malaria vaccine is promising for reducing the malaria burden. However, vaccine awareness, perceptions, and willingness to pay among caregivers are key to ensuring successful rollout. This study assessed caregivers' awareness, perceptions, acceptability, and willingness to pay for the R21/MATRIX malaria vaccine in endemic communities in Lagos, Nigeria.

Methods: A community-based cross-sectional survey was conducted among 372 caregivers of children under five years of age. A multistage sampling technique was employed to select respondents from five malaria-endemic communities in Lagos. Data were collected via a semi-structured, interviewer-administered questionnaire. Descriptive statistics were computed, and binary logistic regression was used to identify predictors of vaccine awareness, perception, and willingness to pay.

Results: Awareness of the R21/MATRIX vaccine was low (9.7%), with the internet as the primary source of information. Positive perceptions of the vaccine were high, with 98.1% of caregivers believing it to be safe and effective. Acceptability was also high, as 76.6% of the caregivers indicated that they would "definitely" vaccinate their child. Willingness to pay was reported by 71.2% of the respondents, with 51.9% willing to pay between ₦1,001-₦5,000 per dose. The factors significantly associated with awareness included gender, marital status, and relationship with the child (p < 0.05). Higher household income and guardianship status increased the likelihood of willingness to pay (p < 0.05).

Conclusions: Despite the low awareness of the R21/MATRIX malaria vaccine, caregivers demonstrated a strong positive perception, high acceptability, and moderate willingness to pay. Targeted community awareness campaigns focused on the benefits and safety of the vaccine are essential to improve knowledge of the vaccine in endemic communities.

Background: New malaria control tools are urgently needed. Transmission-blocking vaccines (TBVs) target sexual parasite stages in mosquitoes to prevent disease spread. TBV testing requires specialised mosquito transmission assays, such as the Direct Skin Feeding (DSF) bioassay. DSF is a xenodiagnostic tool that mimics parasite transmission to mosquitoes as it naturally occurs but has not previously been scaled up nor standardised for use in clinical trials.

Methods: DSF bioassays were performed on large cohorts of participants, including children five years and older, during observational and interventional studies conducted over a 15-year period at sites around Bamako, Mali. Human, mosquito and parasite parameters were monitored to assess DSF safety and acceptability, vector performance, and individual- and population-level transmission dynamics. Standardised procedures developed for DSF included mosquito colony maintenance, mosquito preparation for DSF, feeding procedures, quality control metrics, ethical approaches and volunteer follow-up.

Results: From 2011 through 2025, 37,984 DSF bioassays were performed on 2,796 rural study participants aged 5 years and older, at two Mali study sites. DSFs were well-accepted and safe, with a low refusal rate (0.8% of subjects in vaccine studies) and rare adverse events (AE) that met grading criteria (11 subjects; 0.032%). The few immediate and short-term skin reactions that met AE grading criteria were mild or moderate in severity, all resolving within 48 h. DSF infrastructure was progressively scaled up to a capacity of 120 assays per day requiring 36,000 female mosquitoes per week. Rates of DSF positivity were highest in studies where feeds were conducted on individuals with known Plasmodium falciparum parasitaemia (average 18.4%) vs studies where feeds were conducted on all participants irrespective of blood smear status (average 1.6%).

Conclusions: The DSF bioassay is a xenodiagnostic tool to detect transmissible malaria parasites, and a scalable and safe method for evaluating TBV efficacy. DSF offers several advantages including close mimicry of naturally occurring transmission, simplicity of performance and standardisation, and scalable throughput to support late-stage vaccine trials. While parasite transmission rates measured by DSF were low overall at study sites in Mali, sufficient transmission endpoints are generated to assess efficacy of interventions that interrupt transmission, supporting the DSF bioassay as a surrogate efficacy endpoint for TBV studies.

Malaria remains a global health concern, with Africa bearing the highest global burden of malaria, as Plasmodium falciparum malaria remains the leading cause of malaria-related mortality on the continent. The transmission dynamics of malaria are shaped by a combination of factors, including climate conditions, economic constraints, geographic variability, human activities, and security instability. Owing to repeated infections and widespread implementation of early interventions, there has been a notable rise in cases of clinically atypical malaria and asymptomatic Plasmodium carriers, which increases the risk of misdiagnosis and underdiagnosis. Despite these challenges, African nations have made substantial progress in malaria control and elimination. Key advancements include, increased distribution of insecticide-treated nets use, increased indoor residual spraying, widespread rapid diagnostic tests, intermittent preventive treatment in vulnerable populations, deployment of artemisinin-based combination therapies (ACTs), and of late, the deployment of malaria vaccines to children under 5 years. Between 2000 and 2022, the WHO African Region reported a 40% reduction in malaria incidence and a 60% decline in mortality. Nonetheless, the continent faces emerging threats that could hinder further progress. These include persistent poverty, the effects of climate change, inadequate healthcare infrastructure and coverage, increased outdoor transmission linked to changing mosquito behavior, the appearance of new vector species, and rising resistance to both antimalarial drugs and insecticides. To address these challenges, a multi-faceted strategy is essential. This includes cross-border prevention and control efforts, expansion of seasonal malaria chemoprevention programmes, identification of molecular markers of resistance, development of novel antimalarial agents, and scaled-up implementation of vaccines such as RTS,S/AS01 and R21/Matrix-M. Implementation of approaches employed by countries such as China in malaria elimination and strengthening global-Africa cooperation in the fight against malaria could further accelerate progress. This review aims to provide a comprehensive overview of global malaria with a focus on Africa and global efforts toward the continent's malaria elimination goals.

Background: Serine/arginine-rich splicing factor 1 (SR1), an orthologue of hypothetical RNA-binding protein (HRB1) in yeast, is essential to the asexual development of Plasmodium falciparum and P. berghei. However, their interacting proteins in malaria parasites remain unclear.

Methods: To identify SR1-interacting proteins in malaria parasites, transgenic Pb ANKA expressing green fluorescent protein-fused PbSR1 (PBANKA_1232100) was generated and performed immunoprecipitation coupled to mass spectrometry (IP-MS) using the transgenic parasites. To investigate the developmental stage at which PbSR1 and RhopH2 are expressed, transgenic parasites co-expressing the fusion proteins PbSR1::GFP and RhopH2::mCherry were generated and western blot analysis and live-cell fluorescence imaging were performed.

Results: The fluorescence signal of PbSR1::GFP was stronger in nuclei than the cytoplasm of malaria parasites. IP-MS of the transgenic parasites indicated that PbSR1 interacts with nuclear proteins, including RNA-binding protein and small nuclear ribonucleoprotein, and cytoplasmic proteins, such as RhopH1 (or Clag3), RhopH2, and RhopH3. Live-cell fluorescence imaging showed that co-localization of PbSR1 and RhopH2 in the cytoplasm was observed in trophozoites and gametocytes but not mature schizonts and merozoites. From these results, trophozoites, immature schizonts and gametocytes are candidate stages at which cytoplasmic PbSR1 interacts with RhopH2.

Conclusions: PbSR1 interacts with nuclear proteins and rhoptry proteins.

Background: Pathogen genotyping via polymerase chain reaction (PCR) amplicon sequencing (AmpSeq) is an informative disease surveillance tool. Several large AmpSeq panels containing > 100 multiplexed PCR amplicons have been developed as alternatives to whole-genome sequencing (WGS) methods for the Plasmodium spp. parasites that cause malaria, especially for parasite drug resistance tracking and relatedness analysis. However, these large multiplexes typically yield sparse data for samples with parasitemia below 10 parasites/μl. Smaller multiplexes optimized for low-parasitemia genotyping have received insufficient methodological work but have the potential to serve multiple important use cases. Managing contamination risk during PCR steps represents another key methodological gap that requires attention in the AmpSeq field.

Methods: Here we describe a new 6-locus Plasmodium falciparum AmpSeq 'miniplex' (SIMPLseq) optimized for high-sensitivity analyses that also integrates a contamination detection system based on well-specific inline barcodes applied during first-round PCR (PCR1; in addition to conventional indexing steps during second-round PCR). We assess panel diversity using publicly available WGS and use mock samples to estimate sensitivity and precision relative to 4CAST, a previously described miniplex. We also create deliberate contamination events to assess contamination detection rigor and estimate unintentional contamination rates during assay application to malaria-infected dried blood spots collected in Mali.

Results: SIMPLseq shows high haplotypic diversity in silico, distinguishing 96.0% of sample pairs drawn randomly from 12 subnational sample sets. SIMPLseq outperforms 4CAST in sensitivity analyses, achieving 100% average locus detection at ≥ 0.5 parasites/μl and ≥ 50% average locus detection at 0.25 and 0.125 parasites/μl, with zero false-positive haplotypes at a 1% detection limit across 25 replicates. Inline barcoding does not significantly affect yield when using a 'sentinel' design, whereby one of the six multiplexed PCR1 primer pairs contains the well-specific sequence pair. Sentinel barcoding correctly identified all 24 contaminations introduced deliberately during PCR1 product handling and identified 39 unintentional contaminations in the 1420-sample Malian run.

Conclusions: SIMPLseq significantly extends the malaria genomic epidemiology toolkit, coupling high-sensitivity P. falciparum genotyping with PCR contamination detection in a simple laboratory protocol that uses only open-source reagents and does not require a costly pre-amplification step. Key prospective use cases for SIMPLseq include recurrent infection classification, polyclonality estimation, and genotypic infection endpoint application to intervention efficacy trials.