Malaria Journal最新文献

Background: In conflict-affected regions of Cameroon, access to malaria care is severely hindered by displacement, insecurity, and disrupted health systems. In response, we conducted an operational research aimed at breaking barriers to malaria services in conflict-affected communities of Cameroon.

Methods: In 2021, a participatory co-creation workshop was held on the 21st and 22nd of October 2021, bringing together stakeholders from government health services, community leaders, internally displaced persons (IDPs), and community health workers (CHWs)to collaboratively design interventions aimed at addressing barriers to accessing malaria treatment. The workshop built on prior formative research conducted in 80 conflict-affected communities across the South West and Littoral regions of Cameroon, which identified context-specific challenges to malaria care. The design process included plenary sessions, group discussions, and facilitated brainstorming, and employed participatory methods to ensure that community voices shaped the development of the interventions.

Lessons learned: Three community-based innovations were co-created through this process. Community Health Participatory Approach (CoHPA) was designed to replace the traditional top-down community dialogue structure with a participatory, inclusive model. The Health Voucher System was designed to address financial and geographical barriers, a voucher-based system was introduced to enable access to subsidized malaria services. Vouchers covered malaria testing, treatment, and transport to health facilities. The Supportive Supervision Model was developed to enhance the capacity and motivation of CHWs, who play a crucial role in delivering malaria services in hard-to-reach areas.

Discussion: The co-creation process was key to developing contextually relevant and community-owned malaria interventions. It led to three innovations: the CoHPA model, which introduced internal community-led accountability mechanisms; a Health Voucher System that addressed both financial and transport barriers to care; and a supportive supervision model that aimed to improve CHW performance through bi-directional feedback and recognition. While each intervention introduced novel, context-sensitive elements, concerns remain about their scalability, sustainability, and integration into existing health systems without continued support and investment.

Conclusion: The co-creation process produced three community-driven interventions with potential to break key barriers in access to malaria case management in conflict-affected communities of Cameroon. Pilot implementation and community buy-in for integration into national health systems are essential next steps.

Background: Seasonal Malaria Chemoprevention, which involves giving sulphadoxine-pyrimethamine and amodiaquine (SPAQ) to children aged 3-59 months, is a key strategy for preventing malaria in Ghana. Although SPAQ has been used since 2015, systematic evidence on adverse drug reactions remains limited. This study assessed the patterns and incidence of ADRs associated with SMC to guide safety practices, strengthen public trust, and inform policy.

Materials and methods: We analyzed SPAQ-related ADRs reported to the Ghana Food and Drugs Authority (FDA) database between 2015 and 2023 using STATA IC 16. Incomplete records were excluded. ADRs were classified by age, sex, seriousness, and reporter category, with serious cases further categorized by outcomes such as hospitalization and death. Consistent classification was ensured with standardized MedDRA coding. Annual incidence per 100,000 SPAQ doses was calculated using ADR reports and dispensing data from the National Malaria Elimination Programme.

Results: A total of 2,097 ADRs were analyzed. Slightly more than half (51.2%) involved male children, and 60.3% occurred among those aged 13-59 months. The most frequently reported ADRs were fever (22.7%), vomiting (21.5%), and diarrhoea (16.9%). Serious reactions accounted for 8.6% of cases, most often leading to prolonged hospitalization. The incidence of ADRs declined from 220.63 per 100,000 doses in 2015 to 0.34 in 2023. Caregivers/non-healthcare professionals submitted two-thirds of reports.

Conclusion: SMC with SPAQ is generally safe in Ghana, though serious ADRs continue to occur. The low reporting rate by healthcare professionals, contrasted with high reporting by caregivers, underscores the need to enhance professional engagement, ensure accurate community reporting, and expand active surveillance during SMC campaigns.

Introduction: Malaria poses considerable risk to pregnant women and their unborn babies. Despite the known effectiveness of intermittent preventive treatment in pregnancy using sulfadoxine pyrimethamine(IPTp-SP) and long-lasting insecticide nets (LLINs), their use is hindered by several challenges. This study, therefore, assessed factors associated with utilisation of malaria preventive services (MPS) among pregnant women attending primary healthcare centres in Ile-Ife, Nigeria, using a mixed-method approach.

Methods: This was a mixed-method cross-sectional study design conducted among 200 pregnant women in ten selected healthcare facilities across two Local Government Areas (LGAs) of Ile Ife, Nigeria. While the quantitative data was collected from pregnant women using a semi-structured adapted questionnaire, qualitative data was collected from health workers and pregnant women using key informant interviews (KIIs) and focused group discussions (FGDs), respectively. Quantitative data was analysed using SPSS version 25.0, with logistic regression used to determine the factors influencing utilisation of LLINs and IPTp-SP. Thematic analysis of qualitative data was conducted using ATLAS.ti.

Results: Less than half (34%) of the respondents had good knowledge of malaria preventive services (MPS). While 62.5% of the respondents owned LLINs, only 47.5% reported current utilisation. Utilisation of at least one dose of IPTp-SP was at 50.8% and 7% for three or more doses. The multivariable analysis showed a statistically significant association between IPTp-SP uptake and occupation, good knowledge of malaria preventive services and gravidity. Factors that influenced utilisation of MPS include out-of-stock commodities, lack of money, late and irregular ANC attendance due to insufficient funds for transportation, the distance to healthcare facilities, and pregnant women's preference for visiting mission houses (faith-based homes where spiritual and maternity services are provided) over attending antenatal care (ANC), and insufficient training of healthcare providers.

Conclusions: Modalities to maintain constant availability of malaria preventive commodities at ANC clinics should be put in place. In addition to the conventional awareness programmes, optimal utilisation of MPS can be achieved through the integration of unconventional healthcare providers such as faith-based and traditional birth attendants into malaria in pregnancy preventive initiatives. Also, educational interventions and continuous health workers training are crucial.

Background: Pyrimethamine resistance in Plasmodium falciparum is driven by mutations at dihydrofolate reductase (DHFR) residues N51I, C59R, S108N/T, and I164L, with parallel substitutions in P. vivax (N50I, S58R, S117N/T, S173L). To evaluate the influence of drug pressure on parasite evolution, we compared the dihydrofolate reductase-thymidylate synthase (dhfr-ts) genes of human and zoonotic malaria parasites exposed to different drug environments.

Methods: Blood samples were collected from patients with symptomatic malaria in Thailand (P. falciparum, n = 241; P. vivax, n = 115) and from sympatric zoonotic infections, mainly in naturally infected macaques (P. knowlesi, n = 18; P. inui, n = 64). Complete dhfr-ts sequences were determined and validated.

Results: Among 356 human and 145 zoonotic dhfr-ts sequences, zoonotic parasites exhibited markedly higher mutation counts, haplotype diversity, and nucleotide diversity. In P. falciparum, the high prevalence of the quadruple IRNL mutant indicated strong directional selection. In P. vivax, the coexistence of wild-type alleles and mutations outside resistance-associated residues suggests incomplete fixation. In zoonotic parasites, elevated rates of synonymous versus nonsynonymous substitutions, along with an excess of rare variants, indicate that purifying selection and genetic drift act against slightly deleterious mutations, likely due to protein functional or structural constraints.

Conclusions: Antifolate drug pressure has driven human malaria dhfr-ts genes toward fixation, whereas zoonotic orthologues evolve under a mutation-selection-drift balance. These findings highlight both the potential utility of antifolates against zoonotic malaria and the evolutionary consequences of sustained drug pressure.

Background: 3-Hydroxypropanamidines represent a promising novel, highly lipophilic class of oral antimalarial drugs developed in response to the urgent need for new antimalarials due to the increasing resistance of Plasmodia. A preclinically guided selection approach was conducted, combining optimized in silico, in vitro/ex vivo, and in vivo assays to guide pharmacokinetic-driven compound selection.

Methods: Preliminary sorting was enabled by several in vitro/ex vivo assays (intestinal permeability, plasma protein binding, blood-to-plasma ratio, and microsomal stability), adapted for high lipophilicity. To challenge this sorting, the most promising and the least promising 3-HPAs were selected for further in vivo studies in Plasmodium berghei-infected mice (concentration-time profiles and racemate separation). Finally, a physiologically based pharmacokinetic model was built for the overall most promising 3-HPA to gain initial insights into its pharmacokinetic behavior in humans.

Results: The most hydrophilic compounds, TKK130 (a low-extraction drug) and SAKK381 (a high-extraction drug), presented the most promising in vitro/ex vivo pharmacokinetic profiles (i.e., the highest intestinal permeability and unbound plasma fraction). In particular, TKK130 was favorable because the blood-to-plasma ratio indicated a slight preference for distribution into red blood cells. One of the most lipophilic 3-HPAs, SAKK394 (a low-extraction drug), exhibited the poorest in vitro/ex vivo profile. In vivo, TKK130 demonstrated a sustained pharmacokinetic profile with the highest dose-adjusted total exposure over time, the lowest enantioselective clearance, and a 100% cure rate without signs of toxicity. The physiologically based pharmacokinetic model for the most promising TKK130 demonstrated a good fit to the in vivo data. Extrapolation to humans enabled the first human pharmacokinetic prediction, which was compared to the profile of lumefantrine. Profiles in adults were characterized by high interindividual variability (e.g., total exposure of 814-3856 ng/mL h) and food effects (e.g., total exposure (fasted 1846 ng/mL h vs. fed 3407 ng/mL h)).

Conclusions: TKK130 was identified as the most favorable compound of the novel antimalarial 3-hydroxypropanamidines because of its encouraging pharmacokinetic profile, combined with its excellent in vivo efficacy and lack of observed toxicity in mice. TKK130 is a promising candidate for further preclinical and clinical development.

Background: For thousands of years, humans have been plagued by the deadly disease malaria, affecting millions of people and harming their physical, social, and economic well-being. Despite significant progress over the past two decades in reducing malaria-related morbidity and mortality, malaria remains a major public health threat, particularly in Ethiopia. It is important to assess the treatment outcome of severe malaria and the factors influencing them due to the high prevalence and epidemic nature of the disease in the Gambella region of Ethiopia.

Methods: An institution-based retrospective study was conducted at Gambella General Hospital among 417 children aged from one month to fourteen years who were admitted with severe malaria between May 2022 to May 2024. Data were collected using pre-tested data collection forms. The collected data were cleaned and entered into EPIData, which was again exported into statistical software for analysis. Bivariate and multivariable logistic regression analyses were used to determine associations between determinants and the outcome variable. A significance level was set at p < 0.25 and p < 0.05 for bivariate and multivariable logistic regression, respectively.

Results: Of 417 children enrolled in the study, the mean age was 4.03 years (SD of ± 2.11 years). The overall case fatality rate for severe malaria was 9.11%. High case fatality rates were also observed among children presenting with severe anemia 31.8%, convulsions 27%, pulmonary edema 19.7%, Coma 18.5%, acute kidney injury 18.4%, and comorbid illnesses 16.9%. The majority of the children (91.7%) admitted to the hospital had Plasmodium falciparum, which accounted for 34 (89.5%) of the deaths. Among the predictor variables assessed, convulsion, severe anemia, and comorbid illnesses were significantly associated with the outcome.

Conclusion: In this study, the overall case fatality rate of severe malaria in children was notably high. This underscores the pressing necessity of prioritizing intervention packages that include preventive strategies, early detection, and the prompt identification of features that indicate severity.

Background: Indoor residual spraying (IRS) of insecticides is widely used as an effective method to control malaria vector mosquitoes in sub-Saharan Africa. In 2023, a new IRS product, VECTRON™ T500 (Mitsui Chemicals Crop & Life Solutions, Inc.), was launched. This product contains broflanilide, a novel active ingredient for IRS, and has been confirmed to exhibit long-lasting insecticidal efficacy against malaria vector mosquitoes. However, the discriminating concentration to assess the susceptibility of wild Anopheles populations to broflanilide has not yet been determined.

Methods: In this study, WHO bottle bioassays were conducted in nine research facilities to collect dose response data on broflanilide against adult female mosquitoes of the insecticide susceptible Anopheles gambiae s.s. Kisumu strain. These data were statistically analysed and validated following WHO guidelines.

Results: It was determined that the preliminary discriminating concentration of broflanilide for An. gambiae mosquitoes should be 18 μg/bottle.

Conclusions: In this study, the preliminary discriminating concentration of broflanilide for An. gambiae mosquitoes was determined. The results of this study will provide a useful benchmark for susceptibility monitoring of wild mosquito populations in regions of sub-Saharan Africa into which VECTRON™ T500 is being introduced for malaria vector control.

Background: Malaria remains a leading cause of febrile illness in Senegal, disproportionately affecting young populations. Test-and-treat remains a key strategy for malaria control but relies on accurate diagnosis and effective treatment. This study evaluated and compared the diagnostic accuracy of malaria among febrile patients in three regions in Senegal with high incidence of malaria.

Methods: Data from 948 febrile patients were included to compare the diagnosis of malaria between standard of care malaria diagnostics (RDT and Microscopy) and references quantitative and qualitative PCR methods, which discriminates the four major human malaria species.

Results: The analysis showed that PCR detected malaria infection in 75.29% (716/948) of patients, of which 70.25% involved non-falciparum species, including P. ovale, P. vivax, and P. malariae. Microscopy and RDT missed 31.5% and 18.92% of PCR-positive infections, respectively. In addition, half of mono-infections with non-falciparum species were misdiagnosed as P. falciparum by both microscopy and RDT. Furthermore, microscopy failed to detect a high proportion of P. falciparum infections confirmed by PCR, including those with higher parasitemia than the microscopy theoretical limit of detection.

Conclusions: The study highlights notable limitations and concerns for malaria diagnostic in Senegal, especially for microscopy-detectable P. falciparum parasitemia and non-falciparum infections. As malaria epidemiology trends shift toward mixed-species infections, the solely reliance on microscopy and RDT for the diagnosis of malaria may be critical since missed infections can lead to untreated cases and sustained transmission and impede elimination efforts.

Background: Effective malaria vector control in endemic areas requires understanding the distribution and composition of Anopheles species, as shifts in malaria vector species and composition can influence the efficacy of control interventions and transmission patterns. The current study explored the temporal and spatial distribution of Anopheles species and their infection with Plasmodium in different transmission settings in Tanga region and Unguja, Zanzibar, United Republic of Tanzania.

Methods: From September 2021 to December 2023, monthly entomological surveys were conducted in 11 villages in Tanga and four Shehias in Unguja. Anopheles mosquitoes were sampled every month in each of 11 villages in Tanga and four Shehias in Unguja, 10 households were consented to participate in each village or Shehia. Mosquitoes were collected indoors and outdoors using CDC light traps, Furvela tent traps, Indoor and Outdoor prokopack. Species identification was performed using PCR, and Plasmodium infections were detected using TaqMan real-time PCR assay.

Results: A total of 4771 Anopheles mosquitoes collected (3,766 and 905 in Tanga and Unguja respectively), PCR amplification failed in 100 samples. Among successfully identified specimens, An. gambiae s.s. (43.8%) and An. merus (37.1%) were predominant. In Unguja, An. arabiensis (55.7%) and An. merus (41.9%) were most common. Seasonal variations were observed, with An. gambiae s.s. and An. funestus s.s. peaking in the short rainy season, An. arabiensis peaking in both dry and long rainy seasons, and An. merus peaked during both the wet and dry seasons, suggesting relatively stable occurrence throughout the year. Plasmodium infection rates for An. gambiae s.s., An. funestus s.s., An. arabiensis, and An. merus were 3.0% in Tanga and 1.2% in Unguja but only found in An. arabiensis. In Tanga, An. gambiae s.s., An. merus, and An. funestus s.s. were more abundant in upland and lowland areas than in the highlands, with urbanization limiting An. merus occurrence. In Unguja, An. arabiensis and An. merus were less common in semi-urban areas but showed a sharp increase during the wet season.

Conclusions: The study indicates a shift in An. gambiae s.l. sibling species composition has taken place in the study areas compared to previous reports. In the past, An. merus was not considered an important vector in Tanzania. However, in this study An. merus was observed as the second most abundant species across coastal and inland areas of Tanga and Unguja during both wet and dry season. Combined with its observed infection with P. falciparum, the findings suggest An. merus may contribute to perennial transmission of malaria in the region. This presents a new challenge to malaria vector surveillance and control including the need for a year-round multi-strategic approach.