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Abstract Background Plasmodium vivax and Plasmodium falciparum cause a significant illness burden in Peru. Anopheline indices for populated communities in the peri-Iquitos region of Loreto have been reported to be remarkably low, with entomological inoculation rates (EIR) estimated at one to 30 infective bites per year based on a few studies in close proximity to the urban centre of Iquitos and surrounding deforested areas. Local reports suggest that a large number of the reported cases are contracted outside of populated communities in undeveloped riverine areas frequented by loggers and fishermen. Methods To better understand vectorial capacity in suspected high malaria transmission zones in a rural district near Iquitos, Peru, mosquito collections were conducted at different points in the seasonality of malaria transmission in 21 sites frequented by occupational labourers. Prevalence of Plasmodium spp in vectors was determined by circumsporozoite protein ELISA on individual mosquitoes. Slide surveillance was performed for humans encountered in the zone. Results In total, of 8,365 adult female mosquitoes examined, 98.5% were identified as Anopheles darlingi and 117 (1.4%) tested positive for sporozoites (P. falciparum, P. vivax VK210 or P. vivax VK247). Measured human biting rates at these sites ranged from 0.102 to 41.13 bites per person per hour, with EIR values as high as 5.3 infective bites per person per night. Six percent of the 284 blood films were positive for P. vivax or P. falciparum; however, 88% of the individuals found to be positive were asymptomatic at the time of sampling. Conclusions The results of this study provide key missing indices of prominent spatial and temporal heterogeneity of vectorial capacity in the Amazon Basin of Peru. The identification of a target human subpopulation as a principal reservoir and dispersion source of Plasmodium species has important implications for vaccine development and the delivery of effective targeted malaria control strategies.

Abstract Background In 2020, Malawi had 6.9 million malaria cases and 2551 deaths, mainly in children under five years of age. The 2017–2022 Malawi malaria control strategic plan promoted the consistent use of insecticide-treated nets through free distribution and mass campaigns. Despite widespread availability of the control strategy plan, Chikwawa District continues to suffer from high malaria burden especially among under five children, due to inconsistent insecticide-treated (ITN) net usage. For this reason, this study aimed at exploring caregivers’ perceptions on insecticide-treated net utilisation and also find out about its effectiveness among those who consistently use them. Methods This study used a sequential exploratory mixed methods design. The data used for quantitative analysis was drawn from the population of under-five children’s caregivers within the catchment area of Chikwawa district hospital. The sample size was 96 participants, as determined by Cochran’s formula. The data collection lasted from December 2023 to April 2024 and included four in-depth interviews and three focus group discussions to address the objectives qualitatively. Results The study revealed that 91.67% of households used ITNs, with 87.50% using them daily. The significant factors influencing ITN utilisation included the number of nets, user satisfaction, perceived impact, user habits, acquisition method, and usage frequency (all p values

Abstract Background Attractive targeted sugar bait (ATSB) stations containing bait (to attract) and ingestion toxicant (to kill) sugar-foraging mosquitoes are hypothesized to reduce malaria transmission by shortening the lifespan of Anopheles vectors. Methods A two-arm cluster-randomized controlled trial (cRCT) was conducted in Western Province Zambia. Seventy clusters of 250–350 households were assigned (1:1) by restricted randomization to an intervention arm (ATSB) or control arm (no ATSB) in the context of standard of care vector control (insecticide-treated nets and/or indoor residual spraying). Two ATSB stations (Westham Sarabi, 0.11% dinotefuran w/w) were maintained on exterior walls of eligible household structures for a 7-month deployment period (December-June) during the high malaria transmission season. The primary outcome was clinical malaria incidence among two consecutive seasonal cohorts of children aged 1–14 years, followed-up monthly from January-June in 2022 and 2023. Secondary outcome was Plasmodium falciparum prevalence among individuals aged over six months. Analysis compared clinical malaria incidence and prevalence between arms among the intention-to-treat population. Results ATSB coverage, assessed by cross-sectional survey, was 98.3% in March–April 2022 and 89.5% in March–April 2023. 4494 children contributed any follow-up time to the cohort, with 2313 incident malaria cases in the intervention arm (1.28 per child per six-month transmission season), and 2449 in the control arm (1.38 per child-season). The incidence rate ratio between the two arms was 0.91 (95% CI 0.72–1.15, p = 0.42). 2536 individuals participated in cross-sectional surveys, with prevalence of P. falciparum 50.7% in the intervention arm and 53.5% in the control arm. The odds ratio between the two arms was 0.89 (95% CI 0.66–1.18, p = 0.42). Secondary covariable-adjusted and subgroup analyses did not substantially alter the findings. No serious adverse events associated with the intervention were reported. Conclusions Two ATSB stations deployed per eligible structure for two consecutive transmission seasons did not result in a statistically significant reduction in clinical malaria incidence among children aged 1–14 years or in P. falciparum prevalence in rural western Zambia. Further studies are needed to assess the efficacy of ATSB stations in different settings and with different deployment strategies. Trial registration The trial is registered with Clinicaltrials.gov (NCT04800055).

Abstract Background Modern housing has been shown to reduce the risk of malaria infections compared to traditional houses; however, it is unclear if the effects differ in different malaria transmission settings. This study evaluated the effects of modern housing on malaria among different endemic areas. Methods Electronic databases, clinical trial registries and grey literature were searched for randomized controlled trials, cohort studies, case–control studies, and cross-sectional surveys on housing done between 1987 and 2022. Forest plots were done, and the quality of evidence was assessed using the Grading of Recommendations, Assessments, Development and Evaluation Framework. Results Twenty-one studies were included; thirteen were cross-sectional, four were case–control and four were cohort studies. Cohort studies showed an adjusted risk ratio of 0.68 (95% CI 0.48–0.96), and cross-sectional studies indicated an adjusted odds ratio (aOR) of 0.79 (95%CI 0.75–0.83). By endemic transmission regions, the adjusted odds ratio in the high endemic settings was 0.80 (95%CI 0.76–085); in the moderate transmission regions, aOR = 0.76 (95%CI 0.67–0.85) and in the low transmission settings, aOR = 0.67 (95%CI 0.48–0.85). Conclusions The evidence from observational studies suggests that there are no differences in the protective effects of modern houses compared to traditional houses on malaria by endemicity level. This implies that good quality modern housing protects against malaria regardless of the malaria transmission settings.

Abstract Background The complex interaction between malaria and undernutrition leads to increased mortality and morbidity rate among young children in malaria-endemic regions. Results from previous interventions suggest that improving nutritional status of young children may reduce the burden of malaria. This study tested a hypothesis that provision of lipid-based nutrient supplements (LNS) or corn-soy blend (CSB) supplementation to 6–18-month-old children in Malawi would reduce the prevalence of asymptomatic malaria among them. Methods A total of 840 6-month-old children were enrolled in a randomized trial. The participants received 12-month supplementation with three different daily dietary supplementations: CSB, soy-LNS, or milk-LNS, and one control group without supplementation. The prevalence rate of asymptomatic Plasmodium falciparum was determined by real-time PCR from the participant’s dried blood spots (DBS) collected at the baseline and every 3 months. The global null hypothesis was tested using modified Poisson regression to estimate the prevalence ratio (PR) between the control group and three intervention groups at all ages combined. All the models were adjusted for malaria at baseline, season of DBS sample collection, site of enrolment, and household asset Z-score. Results All children combined, the prevalence of P. falciparum was 14.1% at enrollment, 8.7% at 9 months, 11.2% at 12 months, 13.0% at 15 months and 22.4% at 18 months of age. Among all samples that were taken after enrolment, the prevalence was 12.1% in control group, 12.2% in milk-LNS, 14.0% in soy-LNS, and 17.2% in CSB group. Compared to children in the control group the prevalence ratio of positive malaria tests was 1.19 (95% CI 0.81–1.74; P = 0.372) in the milk-LNS group, 1.32 (95% CI 0.88–1.96; P = 0.177) in the soy-LNS group and 1.72 (95% CI 1.19–2.49; P = 0.004) in the CSB group. Conclusion The study findings do not support a hypothesis that LNS or CSB supplementation would reduce the prevalence of asymptomatic malaria among Malawian children. In contrast, there was a signal of a possible increase in malaria prevalence among children supplemented with CSB.

Abstract Background The World Health Organization recommends the provision of intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) at 4-week intervals from gestational week 13 to delivery in areas of moderate to high malaria transmission intensity. However, the effect of IPTp-SP has been compromised in some areas due to parasite resistance, raising the importance of parasitological and chemoprophylactic surveillance, and monitoring SP-resistance markers in the Plasmodium falciparum population. Methods Between November 2013 and April 2014 in Nchelenge, Zambia, 1086 pregnant women received IPTp-SP at antenatal-care bookings. Blood samples were collected on day 0, and on day 28 post-treatment to test for malaria parasites and to estimate SP parasitological efficacy in the treatment and prevention of parasitaemia. A random sample of 96, day 0 malaria-positive samples were analysed to estimate the prevalence of SP-resistance markers in the P. falciparum population. Results The overall parasitological and prophylactic failure among women who had paired day 0 and day 28 blood slides was 18.6% (95% CI 15.5, 21.8; 109 of 590). Among pregnant women who had asymptomatic parasitaemia on day 0, the day 28 PCR-uncorrected parasitological failure was 30.0% (95% CI 23.7, 36.2; 62 of 207) and the day 28 PCR-corrected parasitological failure was 15.6% (95% CI: 10.6, 20.6; 32 of 205). Among women who tested negative at day 0, 12.3% (95% CI: 9.0, 15.6; 47 of 383) developed parasitaemia at day 28. Among the 96 malaria-positive samples assayed from day 0, 70.8% (95% CI: 60.8, 79.2) contained the DHPS double (Gly-437 + Glu-540) mutation and 92.7% (95% CI: 85.3, 96.5) had the DHFR triple (Asn-108 + Ile-51 + Arg-59) mutation. The quintuple mutation (DHFR triple + DHPS double) and the sextuple mutant (DHFR triple + DHPS double + Arg-581) were found among 68.8% (95% CI: 58.6, 77.3) and 9.4% (95% CI: 4.2, 16.0) of samples, respectively. Conclusion The parasitological and chemoprophylactic failure of SP, and the prevalence of resistance markers in Nchelenge is alarmingly high. Alternative therapies are urgently needed to safeguard pregnant women against malarial infection.

Abstract Malawi is midway through its current Malaria Strategic Plan 2017–2022, which aims to reduce malaria incidence and deaths by at least 50% by 2022. Malariometric data are available with health surveillance data housed in District Health Information Software 2 (DHIS2) and household survey data from two recent Malaria Indicator Surveys (MIS) and a Demographic and Health Survey (DHS). Strengths and weaknesses of the data were discussed during a consultative meeting in Lilongwe, Malawi in July 2019. The first 3 days included in-depth exploration and analysis of surveillance and survey data by 13 participants from the National Malaria Control Programme, district health offices, and partner organizations. Key indicators derived from both DHIS2 and MIS/DHS sources were analysed with three case studies, and presented to stakeholders on the fourth day of the meeting. Applications of the findings to programmatic decision-making and strategic plan evaluation were critiqued and discussed.

Abstract Background HIV-infected individuals on antiretroviral therapy (ART) require treatment with artemisinin-based combination therapy (ACT) when infected with malaria. Dihydroartemisinin–piperaquine (DPQ) is recommended for treatment of Plasmodium falciparum malaria, but its efficacy and safety has not been evaluated in HIV-infected individuals on ART, among whom drug–drug interactions are expected. Day-42 adequate clinical and parasitological response (ACPR) and incidence of adverse events were assessed in HIV-infected individuals on non-nucleoside reverse transcriptase inhibitor-based ART (efavirenz and nevirapine) with uncomplicated P. falciparum malaria treated with dihydroartemisinin–piperaquine. Methods An open label single arm clinical trial was conducted in Malawi (Blantyre and Chikhwawa districts) and Mozambique (Manhiça district) involving patients aged 15–65 years with uncomplicated P. falciparum malaria who were on efavirenz-based or nevirapine-based ART. They received a directly-observed 3-day standard treatment of DPQ and were followed up until day 63 for malaria infection and adverse events. Day-42 PCR-corrected-ACPRs (95% confidence interval [CI]) were calculated for the intention-to-treat (ITT) population. Results The study enrolled 160 and 61 patients on efavirenz and nevirapine-based ART, with a baseline geometric mean (95% CI) parasite density of 2681 (1964–3661) and 9819 (6606–14,593) parasites/µL, respectively. The day-42 PCR-corrected ACPR (95% CI) was 99.4% (95.6–99.9%) in the efavirenz group and 100% in the nevirapine group. Serious adverse events occurred in 5.0% (8/160) and 3.3% (2/61) of the participants in the efavirenz and nevirapine group, respectively, but none were definitively attributable to DPQ. Cases of prolonged QT interval (> 60 ms from baseline) occurred in 31.2% (48/154) and 13.3% (8/60) of the patients on the efavirenz and nevirapine ART groups, respectively. These were not clinically significant and resolved spontaneously over time. As this study was not designed to compare the efficacy and safety of DPQ in the two ART groups, no formal statistical comparisons were made between the two ART groups. Conclusions DPQ was highly efficacious and safe for the treatment of malaria in HIV-infected patients concurrently taking efavirenz- or nevirapine-based ART, despite known pharmacokinetic interactions between dihydroartemisinin–piperaquine and efavirenz- or nevirapine-based ART regimens. Trial registration Pan African Clinical Trials Registry (PACTR): PACTR201311000659400. Registered on 4 October 2013, https://pactr.samrc.ac.za/Search.aspx

Abstract Background HIV-infected individuals on antiretroviral therapy (ART) require treatment with artemisinin-based combination therapy (ACT) when infected with malaria. Artemether–lumefantrine (AL) is the most commonly used ACT for treatment of falciparum malaria in Africa but there is limited evidence on the safety and efficacy of AL in HIV-infected individuals on ART, among whom drug–drug interactions are expected. Day-42 adequate clinical and parasitological response (ACPR) and incidence of adverse events was assessed in HIV-infected individuals on efavirenz-based ART with uncomplicated falciparum malaria treated with AL. Methods A prospective, open label, non-randomized, interventional clinical trial was conducted at St Paul’s Hospital in northern Zambia, involving 152 patients aged 15–65 years with uncomplicated falciparum malaria, who were on efavirenz-based ART. They received a 3-day directly observed standard treatment of AL and were followed up until day 63. Day-42 polymerase chain reaction (PCR)-corrected ACPRs (95% confidence interval [CI]) were calculated for the intention-to-treat population. Results Enrolled patients had a baseline geometric mean (95% CI) parasite density of 1108 (841–1463) parasites/µL; 16.4% (25/152) of the participants had a recurrent malaria episode by day 42. However, PCR data was available for 17 out of the 25 patients who had malaria recurrence. Among all the 17 patients, PCR findings demonstrated malaria re-infection, making the PCR-adjusted day-42 ACPR 100% in the 144 patients who could be evaluated. Even when eight patients with missing PCR data were considered very conservatively as failures, the day-42 ACPR was over 94%. None of the participants, disease or treatment characteristics, including day-7 lumefantrine concentrations, predicted the risk of malaria recurrence by day 42. AL was well tolerated following administration. There were only two cases of grade 3 neutropaenia and one serious adverse event of lobar pneumonia, none of which was judged as probably related to intake of AL. Conclusions AL was well tolerated and efficacious in treating uncomplicated falciparum malaria in HIV co-infected adults on efavirenz-based ART. However, a higher than anticipated proportion of participants experienced malaria re-infection, which highlights the need for additional malaria prevention measures in this sub-population after treatment with AL. Trial registration Pan African Clinical Trials Registry (PACTR): PACTR201311000659400. Registered on 4 October 2013. https://pactr.samrc.ac.za/Search.aspx

Abstract Background Entomological monitoring is important for public health because it provides data on the distribution, abundance and host-seeking behaviour of disease vectors. Various methods for sampling mosquitoes exist, most of which are biased towards, or specifically target, certain portions of a mosquito population. This study assessed the Suna trap, an odour-baited trap for sampling host-seeking mosquitoes both indoors and outdoors. Methods Two separate field experiments were conducted in villages in southern Malawi. The efficiency of the Suna trap in sampling mosquitoes was compared to that of the human landing catch (HLC) indoors and outdoors and the Centers for Disease, Control and Prevention Light Trap (CDC-LT) indoors. Potential competition between two Suna traps during simultaneous use of the traps indoors and outdoors was assessed by comparing mosquito catch sizes across three treatments: one trap indoors only; one trap outdoors only; and one trap indoors and one trap outdoors used simultaneously at the same house. Results The efficiency of the Suna trap in sampling female anophelines was similar to that of HLC indoors (P = 0.271) and HLC outdoors (P = 0.125), but lower than that of CDC-LT indoors (P = 0.001). Anopheline catch sizes in the Suna trap used alone indoors were similar to indoor Suna trap catch sizes when another Suna trap was simultaneously present outdoors (P = 0.891). Similarly, catch sizes of female anophelines with the Suna trap outdoors were similar to those that were caught outdoors when another Suna trap was simultaneously present indoors (P = 0.731). Conclusions The efficiency of the Suna trap in sampling mosquitoes was equivalent to that of the HLC. Whereas the CDC-LT was more efficient in collecting female anophelines indoors, the use of this trap outdoors is limited given the requirement of setting it next to an occupied bed net. As demonstrated in this research, outdoor collections are also essential because they provide data on the relative contribution of outdoor biting to malaria transmission. Therefore, the Suna trap could serve as an alternative to the HLC and the CDC-LT, because it does not require the use of humans as natural baits, allows standardised sampling conditions across sampling points, and can be used outdoors. Furthermore, using two Suna traps simultaneously indoors and outdoors does not interfere with the sampling efficiency of either trap, which would save a considerable amount of time, energy, and resources compared to setting the traps indoors and then outdoors in two consecutive nights.

Abstract Background Increased engagement of communities has been emphasized in global plans for malaria control and elimination. Three interventions to reinforce and complement national malaria control recommendations were developed and applied within the context of a broad-based development initiative, targeting a rural population surrounding a wildlife reserve. The interventions, which were part of a 2-year research trial, and assigned to the village level, were implemented through trained local volunteers, or ‘health animators’, who educated the community and facilitated collective action. Results Community workshops on malaria were designed to increase uptake of national recommendations; a manual was developed, and training of health animators conducted, with educational content and analytical tools for a series of fortnightly community workshops in annual cycles at village level. The roll-back malaria principle of diagnosis, treatment and use of long-lasting insecticidal nets was a central component of the workshops. Structural house improvement to reduce entry of malaria vectors consisted of targeted activities in selected villages to mobilize the community into voluntarily closing the eaves and screening the windows of their houses; the project provided wire mesh for screening. Corrective measures were introduced to respond to field challenges. Committees were established at village level to coordinate the house improvement activities. Larval source management (LSM) in selected villages consisted of two parts: one on removal of standing water bodies by the community at large; and one on larviciding with bacterial insecticide Bacillus thuringiensis israelensis by trained village committees. Community workshops on malaria were implemented as ‘core intervention’ in all villages. House improvement and LSM were implemented in addition to community workshops on malaria in selected villages. Conclusions Three novel interventions for community mobilization on malaria prevention and control were described. The interventions comprised local organizational structure, education and collective action, and incorporated elements of problem identification, planning and evaluation. These methods could be applicable to other countries and settings.

Abstract Background Zambia was an early adopter of insecticide-treated nets strategy in 2001, and policy for mass distribution with long-lasting insecticidal nets (LLINs) in 2005. Since then, the country has implemented mass distribution supplemented with routine delivery through antenatal care and under five clinics in health facilities. The national targets of universal (100%) coverage and 80% utilization of LLINs have not been attained. Free mass LLIN distribution campaign in Zambia offers important lessons to inform future campaigns in the African region. Methods This study reviewed LLIN free mass distribution campaign information derived from Zambia’s national and World Health Organization Global Malaria Programme annual reports and strategic plans published between 2001 and 2016. Results In 2014, a nationwide mass distribution campaign in Zambia delivered all the 6.0 million LLINs in 6 out of 10 provinces in 4 months between June and September before the onset of the rainy season. Compared with 235,800 LLINs and 2.9 million LLINs distributed on a rolling basis in 2008 and 2013, respectively, the 2014 mass campaign, which distributed 6 million LLINs represented the largest one-time-nationwide LLIN distribution in Zambia. The province (Luapula) with highest malaria transmission, mostly with rural settings recorded 98–100% sleeping spaces in homes covered with LLINs. The percentage of households owning at least 1 LLIN increased from 50.9% in 2006 to 77.7% in 2015. The 2014 mass campaign involved a coordinated response with substantial investments into macro (central) and micro (district) level planning, capacity building, tracking and logistics management supported by a new non-health sector partnership landscape. Coordination of LLIN distribution and logistics benefited from the mobile phone technology to transmit “real time” data on commodity tracking that facilitated timely delivery to districts. Conclusion Free mass distribution of LLINs policy was adopted in 2005 in Zambia. Consistently implemented, has not only contributed to increased coverage of LLINs, but has also produced the added value and lessons of strengthening joint planning, strategic coordination, partnerships with non-health sector institutions and community engagement with traditional leaders at community. Furthermore, the mass distribution, through improving coverage has indirect added (spin-off) value or impact on other arthropod-borne diseases, in addition to malaria.

Abstract Background Malaria case management is one of the key strategies to control malaria. Various studies have demonstrated the feasibility of home management of malaria (HMM). However, data on the costs and effectiveness of artemisinin-based combination therapy (ACT) and rapid diagnostic tests via HMM is limited. Method Cost-effectiveness of home management versus health facility-based management of uncomplicated malaria in two rural districts in Zambia was analysed from a providers' perspective. The sample included 16 community health workers (CHWs) and 15 health facilities. The outcome measure was the cost per case appropriately diagnosed and treated. Costs of scaling-up HMM nationwide were estimated based on the CHW utilisation rates observed in the study. Results HMM was more cost effective than facility-based management of uncomplicated malaria. The cost per case correctly diagnosed and treated was USD 4.22 for HMM and USD 6.12 for facility level. Utilization and adherence to diagnostic and treatment guidelines was higher in HMM than at a health facility. Conclusion HMM using ACT and RDTs was more efficient at appropriately diagnosing and treating malaria than the health facility level. Scaling up this intervention requires significant investments.

Abstract Background Malaria remains a leading cause of morbidity, mortality and non-fatal disability in Zambia, especially among children, pregnant women and the poor. Data gathered by the National Malaria Control Centre has shown that recently observed widespread treatment failure of SP and chloroquine precipitated a surge in malaria-related morbidity and mortality. As a result, the Government has recently replaced chloroquine and SP with combination therapy as first-line treatment for malaria. Despite the acclaimed therapeutic advantages of ACTs over monotherapies with SP and CQ, the cost of ACTs is much greater, raising concerns about affordability in many poor countries such as Zambia. This study evaluates the cost-effectiveness analysis of artemether-lumefantrine, a version of ACTs adopted in Zambia in mid 2004. Methods Using data gathered from patients presenting at public health facilities with suspected malaria, the costs and effects of using ACTs versus SP as first-line treatment for malaria were estimated. The study was conducted in six district sites. Treatment success and reduction in demand for second line treatment constituted the main effectiveness outcomes. The study gathered data on the efficacy of, and compliance to, AL and SP treatment from a random sample of patients. Costs are based on estimated drug, labour, operational and capital inputs. Drug costs were based on dosages and unit prices provided by the Ministry of Health and the manufacturer (Norvatis). Findings The results suggest that AL produces successful treatment at less cost than SP, implying that AL is more cost-effective. While it is acknowledged that implementing national ACT program will require considerable resources, the study demonstrates that the health gains (treatment success) from every dollar spent are significantly greater if AL is used rather than SP. The incremental cost-effectiveness ratio is estimated to be US$4.10. When the costs of second line treatment are considered the ICER of AL becomes negative, indicating that there are greater resource savings associated with AL in terms of reduction of costs of complicated malaria treatment. Conclusion This study suggests the decision to adopt AL is justifiable on both economic and public health grounds.