Malaria Journal最新文献

Background: Malaria is a significant public health concern, particularly in sub-Saharan Africa, where it causes considerable morbidity and mortality. Severe malaria is a major cause of mortality among children under five, contributing to Uganda's high malaria mortality burden. Effective case management of severe malaria is crucial which should be guided by the Uganda clinical guidelines adopted from the World Health Organization. This study explored the barriers and facilitators to healthcare providers' adherence to severe malaria treatment guidelines in children at Mbale Regional Referral hospital, Uganda.

Materials and methods: A qualitative descriptive approach was carried out at Mbale Regional Referral Hospital, eastern Uganda. A total of 21 healthcare providers (doctors, nurses, pharmacists; Laboratory technicians; Blood Bank health workers; and clinical officers) were purposively recruited during the study period. Data was collected through key informant interviews, audio recorded, and analyzed using thematic analysis using Braun and Clark's approach. Adherence to the Lincoln and Gubba principles of credibility, conformability, transferability, and dependability was ensured. Data was presented in tables and narratives. Avis Donabedian model was employed to explore the facilitators and barriers to adherence to the severe malaria management guideline.

Results: The study identified key facilitators under three themes: Structure (availability of resources, drugs, and training); Process (optimal working conditions, manageable workloads, and use of monitoring tools like yellow stickers); and Patient-related factors (caretaker cooperation, effective communication, and trust-building). Barriers included structure resource constraints, staffing and work load issues; process, delayed referrals, delays in the lab, limited working hours in the lab and pharmacy, low CMEs attendance among nurses; patient related factors like patient financial limitations and poor patient cooperation.

Conclusion: This study identified facilitators and barriers to adherence to severe malaria management guidelines in children under five. The barriers and facilitators emerged in terms of structural, processes, patient characteristics and outcome. Addressing resource shortages and improving staffing and workload conditions are crucial for better adherence. Enhancing patient education and strengthening health system infrastructure are also essential for ensuring timely and effective care.

Background: Genetic metrics derived from Plasmodium falciparum infections offer a potential complement to conventional malaria surveillance by utilizing features of parasite diversity and relatedness to estimate transmission intensity. However, the performance of genetic metrics to predict epidemiologic metrics across a wide range of transmission settings remains understudied.

Methods: Dried blood spots from 3563 symptomatic malaria cases were collected from 26 sentinel health facilities across Uganda during two collections in 2023. Amplicon deep sequencing of 165 polyallelic microhaplotypes was performed using MAD⁴HatTeR. Within-host diversity metrics (complexity of infection (COI), effective complexity of infection (eCOI), percent polyclonality, within-host relatedness) and between-host relatedness metrics were calculated. Associations with prevalence and recent incidence were evaluated using correlation and regression analyses, and estimation accuracy was examined using nested grouped cross-validation.

Results: Marked geographic heterogeneity in malaria burden was evident across sites; parasite prevalence ranged from 5.0 to 49.23% in Round 1, while incidence ranged from 91 to 1062 cases per 1000 person-years (PY) in Round 1 and 33 to 1667 cases per 1000 PY in Round 2. COI and eCOI had a strong positive association with parasite prevalence. The proportion of highly related infection pairs was negatively associated with both prevalence and incidence and was the genetic metric most consistently associated with incidence. Nested grouped cross-validation identified single-predictor models using COI or eCOI as optimal for estimating prevalence, yielding a pooled cross-validated correlation of r = 0.79. Models estimating incidence showed weaker performance, with models incorporating both diversity and relatedness metrics achieving a pooled correlation of r = 0.37.

Conclusions: Microhaplotype-based metrics of within-host diversity, particularly COI and eCOI, reliably reflected spatial variation in malaria prevalence across Uganda, while between-host relatedness provided complementary information and was the strongest predictor of incidence. These findings indicate that parasite genomic metrics derived from polyallelic microhaplotypes can capture broad differences in transmission intensity reflected by parasite prevalence, but may have more limited ability to predict incidence. Integration of genomic metrics with harmonized epidemiologic data and expanded sampling of asymptomatic infections will be important next steps to understand the potential utility of parasite genetic metrics for malaria surveillance and subnational stratification.

Background: Anopheles mosquitoes, vectors of human malaria, are highly sensitive to environmental change. As climate alters temperature and precipitation patterns, mosquito populations may shift in sibling species composition, location and timing, altering transmission dynamics. Understanding these patterns is key for malaria control. This study explores links between meteorological factors and Anopheles abundance across a diversity of sites in Tanga and Unguja, Tanzania, to predict mosquito peaks and support the development of early warning systems for malaria outbreaks.

Methods: Adult Anopheles mosquitoes were sampled monthly from September/October 2021 to December/September 2023 across 11 sites in Tanga and 4 shehias in Unguja. Spatio-temporal Generalized Additive Mixed Effects Models (GAMMs) were employed to assess the influence of meteorological factors on Anopheles abundance. Models were built and validated using mosquito counts alongside climate covariates obtained from Copernicus ERA5-Land and NASA's POWER platforms.

Results: A total of 4312 adult Anopheles mosquitoes were sampled in Tanga and 1450 in Unguja. The GAMM revealed region-specific climatic drivers. In Tanga, Anopheles abundance increased with higher maximum temperatures but declined with higher minimum temperatures. In Unguja, abundance exhibited a non-linear relationship with mean temperature, peaking below 27.5 °C and decreasing thereafter. Precipitation in Tanga positively influenced Anopheles abundance both concurrently and with a two-month lag, whereas in Unguja only the two-month lag effect was significant. Relative humidity exhibited a non-linear effect in both regions, with higher humidity associated with increased abundance. The GAMMs demonstrated strong predictive performance as evidenced by low MAE and RMSE, Theil's U < 1, and correlation exceeding 0.8 between observed and predicted values. Importantly, the models accurately forecasted Anopheles abundance peaks in Unguja in November 2023, preceding the reported malaria surge in Zanzibar in late 2023 and early 2024, highlighting its potential as a proxy for malaria risk and a scalable early warning system to support proactive targeted vector control.

Conclusion: The study highlights the importance of integrating meteorological variability into mosquito surveillance and control. The spatio-temporal GAMM captured weather-driven mosquito dynamics and predicted surges in Anopheles abundance prior to the Zanzibar malaria outbreak in late 2023. These insights can guide targeted interventions across diverse eco-climatic regions, enhancing malaria vector control.

Background: Argentina was certified malaria-free by the WHO in 2019 after eight years with no instances of local transmission. Epidemiological surveillance was focused on detecting Plasmodium vivax in areas where the last cases had been reported.

Methods: During the national malaria surveillance program (2013-2018), several human blood samples were collected across neighborhoods using traditional microscopy and molecular techniques (2013-2017) to detect any silent circulation of P. vivax. In 2022, post-certification, 92 blood samples preserved in Whatman FTA paper were analyzed for the first time to detect the presence of Plasmodium parasites by amplifying and sequencing a fragment of the Plasmodium cytochrome b gene.

Results: A submicroscopic, asymptomatic P. vivax infection was identified in a 66-year-old individual from La Bendición neighborhood, Salvador Mazza, Salta province (northwestern Argentina). The individual had no history of travel to any P. vivax-endemic region. This case was the first detected infection among the samples collected from various localities along Argentina's borders with Bolivia (northwest) and Brazil (northeast).

Discussion: This finding highlights the risk of silent circulation of P. vivax in areas previously assumed to be malaria-free and raises concerns regarding the timing of the certification. This is the first molecularly confirmed submicroscopic infection of P. vivax reported prior to malaria-free certification in Argentina and the Southern Cone region.

Conclusions: Currently, there is no active epidemiological or entomological surveillance in the area where the case was recorded. It is imperative to strengthen the surveillance system to maintain the country's malaria-free status within the national health system agenda and address the risks of silent malaria circulation and re-emergence. Furthermore, to comply with the national malaria program guidelines and WHO requirements to maintain malaria-free certification, the development and implementation of highly sensitive diagnostic tools to detect asymptomatic cases is crucial.

Background: Malaria remains the leading cause of under-five mortality in Burkina Faso, one of the ten most affected countries globally. Despite substantial control efforts, persistent inequalities continue to limit progress. Addressing the complex and interrelated determinants of malaria is crucial to achieving national elimination targets. This study examined the prevalence of malaria and its associated individual and contextual factors using nationally representative data.

Methods: We analyzed data from 5674 children aged 6-59 months included in the 2021 Burkina Faso Demographic and Health Survey (DHS), which used a two-stage stratified cluster sampling design. Malaria infection was defined by positive microscopy results. Modified Poisson regression models were applied to estimate adjusted prevalence ratios (aPR).

Results: The overall malaria prevalence among children under five was 14.1% (95% CI: 13-15). Substantial regional disparities were observed, ranging from 5.1% in the Centre region to 29.3% in the Sahel. Compared with children aged 6-12 months, the risk of malaria increased with age, with aPR of 1.46 (13-23 months), 2.07 (24-35 months), 1.93 (36-47 months), and 1.93 (48-59 months). Higher malaria prevalence was also observed among children living in rural areas (aPR = 2.21), in households without electricity (aPR = 2.01), and in poor households (aPR = 1.60).

Conclusion: Malaria disparities in Burkina Faso reflect both individual and contextual vulnerabilities. Children aged 24-59 months and those living in rural, poor, or electricity-deprived households were at higher risk. Achieving malaria elimination requires policies that promote equitable access to electricity, poverty reduction, and targeted interventions for vulnerable groups in rural areas.

Background: Malaria remains a major public health concern in low- and middle-income countries (LMICs), particularly in urban settings experiencing rapid vector adaptation. India, contributing significantly to South-East Asia's malaria burden, faces persistent urban transmission. While previous studies have explored local determinants of vector-borne diseases, large-scale analyses examining the interplay of socioeconomic factors, water availability, storage practices, and disease prevention behaviors remain limited.

Methods: We conducted a socioeconomic and health survey in the cities of Ahmedabad and Surat, India, between September and November 2023. Data were collected from 4,074 households, comprising 15,484 individuals, and we examined associations between socioeconomic indicators, water availability, storage practices, and mosquito-borne disease incidence and prevention behaviors. Logistic regressions were used to identify significant predictors.

Results: We find that self-reported disease prevalence was low, with 77 cases of malaria, dengue, and chikungunya, equivalent to 18.90 cases per 1,000 households. Socioeconomic factors such as wealth, caste, and family size were significantly associated with disease reporting and prevention practices. Households in the richest wealth quintile were more likely to adopt prevention measures, but less likely to perceive mosquito-related risks. Water management practices, particularly storage in clean large containers, were associated with increased disease symptoms and prevention measures, highlighting the complexity of vector control. Households with impermeable storage containers reported reduced use of active prevention measures.

Conclusion: Socioeconomic disparities and water management practices significantly influence malaria incidence and prevention behaviors. Targeted interventions prioritizing disadvantaged households, improved water storage practices, and enhanced investments in preventive care are essential to reduce vector-borne disease vulnerability and accelerate India's malaria elimination goals.

Background: The growing resistance to current antimalarial drugs has stalled the eradication of malaria in endemic countries. DSM265 has recently been studied in phase I and II clinical trials.

Aim: This meta-analysis aims to evaluate the safety, pharmacokinetics (PK), and antiparasitic activity of DSM265 based on available early-phase clinical trials.

Methods: This systematic review (PROSPERO: CRD42024499167) was conducted to identify any relevant clinical trials reporting DSM265 safety and PK data. Five databases were searched, i.e., PubMed, Cochrane CENTRAL, EBSCOhost, Clinicaltrials.gov, and ScienceDirect. Eligible clinical trials on DSM265 that reported safety outcomes and PK parameters were included. The risk of bias was assessed by Cochrane's Collaboration tool. Meta-analysis was conducted to present the pooled adverse events (AEs) and summary estimates for PK parameters, including maximum drug concentration (C_max [μg/mL]), time to maximum drug concentration (T_max [hours (h)]), elimination half-lives (T_1/2 [h]), and area under the concentration-time curves (AUCs [h·μg/mL]). Subgroup analysis and meta-regression analyses were conducted among various doses and drug formulations.

Results: Seven trials were eligible for systematic review. Overall, DSM265 was associated with increased risks of AEs (relative risk [RR] [95% CI] = 1.46 [1.15, 1.84]); subgroup analysis showed significant risks only among the low-dose (25-250 mg) (RR [95% CI] = 1.86 CI [1.36, 2.54]) and high-dose (600-1200 mg) (RR [95% CI] = 1.67 CI [1.03, 2.72]) subgroups. When given as oral suspension at 400 mg dose, DSM265 achieved C_max: 9.3 μg/mL (95% CI = 7.5, 11.2), T_max: 5.4 h (95% CI = 2.7, 8.2), T_1/2: 112.1 h (95% CI = 91.3, 132.9), and AUC_0-∞h: 1,601.9 h·μg/mL (95% CI = 1,233.5, 1970.3). A substantial heterogeneity in PK parameters was evident and justified in meta-regression, which showed linear dose-PK parameter relationships. DSM265 has been shown to target Plasmodium falciparum DHODH with greater selectivity compared to Plasmodium vivax. Furthermore, the drug did not exhibit anti-gametocyte activity which was consistent with preclinical studies.

Conclusion: In this meta-analysis, DSM265 demonstrated a favorable safety profile after a single 400 mg dose. While preclinical signals of teratogenicity and testicular toxicity have halted further development, these effects were not reported in the included clinical trials. Substantial variability in PK parameters was noted, driven primarily by administered doses.

Background: The distribution of insecticide-treated nets (ITNs) through mass campaigns remains a cornerstone of malaria vector control. As new ITN products are introduced to address rising insecticide resistance, understanding the cost of such campaigns is essential for informed policy decisions. This study aimed to estimate the programmatic and annualized economic costs of campaigns that distributed pyrethroid-PBO ITNs in Ondo and Anambra States, Nigeria, using a single-phase, door-to-door strategy.

Methods: A micro-costing approach was used to estimate campaign economic costs from the provider perspective. Financial costs were obtained retrospectively from campaign financial records, while opportunity costs were assessed through key informant interviews and focus group discussions. Shadow pricing was employed to value resources without market prices. We estimated the programmatic economic costs of delivering ITNs to households, and annualized costs, accounting for ITN lifespan beyond one year.

Results: A total of 2,965,125 pyrethroid-PBO nets were distributed in Ondo State and 3,850,316 in Anambra State. The programmatic economic cost of delivering an ITN to a household was estimated at $3.22 in Ondo and $3.19 in Anambra. Net procurement was the primary cost driver, accounting for 77% of the total costs of delivery to households in Ondo and 82% in Anambra. Unit distribution costs were $0.74 per net in Ondo and $0.57 in Anambra. Financial costs comprised 98% of total economic costs in Ondo and 97% in Anambra. Assuming an ITN lifespan of 2.5 years and a 3% annual discount rate, the annual economic cost was $1.36 per ITN distributed and $0.72 per person potentially protected in Ondo, and $1.34 and $0.69 respectively in Anambra. Sensitivity analysis indicated that ITN durability was the dominant factor influencing annual cost per person protected, while variations in discount rate (3-5%) had only modest effects.

Conclusion: ITN campaign economic costs in this study were lower than most estimates from other African countries. While net procurement was the primary cost driver, the cost per year of effective protection was strongly influenced by ITN durability, highlighting the need for strategies that extend functional net lifespan. The findings provide essential inputs for cost-effectiveness analyses of campaign deployment of new generation nets when combined with epidemiological impact data.

Background: The effect of seasonal malaria chemoprevention (SMC) strategy on malaria transmission using a single low dose of primaquine (SLDPQ) added to artemisinin-based combination therapy has not been established in Africa. An agent-based model and simulation (ABMS) was used to assess SMC effectiveness using dihydroartemisinin-piperaquine (DP) with and without SLDPQ in Masasi and Nanyumbu Districts, Tanzania.

Methods: ABMS was developed in AnyLogic platform using secondary data from a cluster-randomized DP-based SMC study conducted in the districts, to assess the effectiveness of DP with and without SLDPQ for control of malaria in under-five children. The model incorporated human, mosquito, transmission, intervention, and environment sub-models, and simulated three monthly rounds of SMC over a 180-day period. Environment temperature, an important factor in mosquito breeding was simulated in three scenarios, first using average field temperature, and then when it was increased or decreased by 1⁰C from the average. Model outputs were compared with field results to evaluate external validity.

Results: Overall, 2275 participants, 1135 in the intervention and 1140 in the control arm were involved in the model. At baseline, malaria prevalence was 11.5% (130/1135) and 16.3% (186/1140) in the intervention and control arm, respectively. At the end of 125-day simulation period malaria prevalence declined to 4.1% (47/1135), and it rebounded to 7.1% (80/1135) at the end of 180-day simulation period after three rounds of DP alone administration. Addition of SLDPQ to DP led to a further declined of the prevalence to 1.4% (16/1135) and 3.9% (44/1135) at the end of 125-day and 180-day, respectively. In the DP alone, the increase in average temperature by 1˚C further decreased malaria prevalence to 2.6% (30/1135) and 5.0% (57/1135) at the end of 125-day and 180-day, respectively, whereas the decrease of temperature by 1 ˚C decreased the malaria prevalence to 3.2% (36/1135) and 4.2% (48/1135) at the end of 125-day and 180-day, respectively.

Conclusions: The ABMS has demonstrated that addition of SLDPQ to DP reduced malaria transmission significantly regardless of the increase or decrease of the average temperature by 1 ˚C. SLDPQ can be added to DP-SMC and scaled-out for the control of malaria in Tanzania.

Context: In the remote areas of the Democratic Republic of Congo, particularly in the Kapolowe health zone, the healthcare-seeking behaviour of mothers with children suffering from severe malaria remains a major challenge. This is often a key factor in the deaths of many children because they do not receive effective treatment in a timely manner due to various factors, including socio-economic, geographical, cultural, and structural factors. At the community level, where the administration of medications via injection is not possible, a pre-referral community intervention has the potential to reduce morbidity and mortality. To successfully implement this in a community, it is essential to understand the healthcare-seeking behaviour of parents with severely ill children under five and the challenges they face.

Methods: Using a qualitative approach, 30 focus groups discussions were conducted in 30 villages within the Kapolowe health zone. Of these, 9 groups were selected based on pre-established criteria and were manually analysed in depth using the inductive method. The three delays model was adapted to guide the analysis. Data which were collected focused on participants' understanding of suspected malaria symptoms, actions taken when illness began, reasons behind these actions, and the difficulties encountered when seeking care.

Results: The findings indicate that mothers in Kapolowe often delay seeking care when their children become ill. When they do seek care, they frequently resort to self-medication with both modern medicines and traditional remedies. Barriers to access included geographical distance, impassable roads, lack of transportation and healthcare facilities, as well as financial difficulties related to both direct and indirect costs of care. Cultural factors also played a significant role in decision making, with mothers preferring to wait, rely on traditional practices, or turn to prayers.

Conclusion: Healthcare-seeking behaviour in Kapolowe is shaped by structural, financial, and cultural barriers. This findings underscore the need to strengthen the health system in Kapolowe by developing strategies that account for lived realities of the community.