Community acceptance of a novel malaria intervention, Attractive Targeted Sugar Baits, in the Zambia phase III trial.

BACKGROUND: Community acceptance is an important criterion to assess in community trials, particularly for new tools that require high coverage and use by a target population. Installed on exterior walls of household structures, the attractive targeted sugar bait (ATSB) is a new vector control tool designed to attract and kill mosquitoes. ATSBs were evaluated in Western Zambia during a two-year cluster randomized controlled trial to assess the efficacy of ATSBs in reducing malaria transmission. Community acceptance of ATSBs was critical for successful trial implementation. METHODS: A community engagement strategy outlined activities and key messages to promote acceptance. Annual cross-sectional surveys, conducted during the peak transmission period, assessed households for presence of ATSBs as well as perceived benefits, concerns, and willingness to use ATSBs. Sixteen focus group discussions and 16 in-depth interviews, conducted at the end of each ATSB station deployment period, obtained a range of perceptions and household experiences with ATSB stations, as well as ITN use in the context of ATSB deployment. RESULTS: Methods used during the study to promote acceptance and continued use of ATSBs were effective in achieving greater than 90% coverage, a high (greater than 70%) level of perceived benefits, and fewer than 10% of households reporting safety concerns. Common facilitators of acceptance included the desire for protection against malaria and reduction of mosquitoes, trust in health initiatives, and understanding of the product. Common barriers to acceptance included misconceptions of product impact on mosquitoes, continued cases of malaria, association with satanism, and damage to household structures. DISCUSSION: Future use of the ATSB intervention will likely require activities that foster community acceptance before, during, and after the intervention is introduced. Additional research may be needed to understand the impact of different levels of community engagement on ATSB station coverage, ATSB station perception, and ITN use. CONCLUSION: There was high acceptance of ATSB stations during the trial in Western Zambia. Continuous and intense community engagement efforts contributed to sustained ATSB coverage and trust in the product. Acceptance of ATSBs during programmatic delivery requires further research.

Deployment of attractive targeted sugar baits in western Zambia: installation, monitoring, removal, and disposal procedures during a Phase III cluster randomized controlled trial.

BACKGROUND: Attractive Targeted Sugar Baits (ATSBs) offer a complementary vector control strategy to interventions targeting blood feeding or larval control by attacking the sugar feeding behaviour of adult mosquitoes using an attract-and-kill approach. Western Zambia was the first location to receive and deploy ATSB Sarabi version 1.2 stations in a Phase III cluster randomized controlled trial. This paper describes ATSB station installation, monitoring, removal, and disposal, quantifies ATSB station coverage, and reports major reasons for ATSB station replacement. METHODS: ATSB stations were deployed during two annual transmission seasons, through scheduled installation and removal campaigns. During deployment, monitoring was conducted per protocol to maintain high coverage of the ATSB stations in good condition. Routine monitoring visits during the trial captured details on ATSB station damage necessitating replacement following pre-defined replacement criteria. Annual cross-sectional household surveys measured ATSB station coverage during peak malaria transmission. RESULTS: A total of 67,945 ATSB stations were installed in Year 1 (41,695 initially installed+ 26,250 installed during monitoring) and 69,494 ATSB stations were installed in Year 2 (41,982 initially installed+ 27,512 installed during monitoring) across 35 intervention clusters to maintain high coverage of two ATSB stations in good condition per eligible household structure. The primary reasons for ATSB station replacement due to damage were holes/tears and presence of mold. Cross-sectional household surveys documented high coverage of ATSB stations across Year 1 and Year 2 with 93.1% of eligible structures having ≥ 2 ATSB stations in any condition. DISCUSSION: ATSB station deployment and monitoring efforts were conducted in the context of a controlled cRCT to assess potential product efficacy. Damage to ATSB stations during deployment required replacement of a subset of stations. High coverage of eligible structures was maintained over the two-year study despite replacement requirements. Additional research is needed to better understand the impact of damage on ATSB station effectiveness under programmatic conditions, including thresholds of threats to physical integrity and biological deterioration on product efficacy. CONCLUSIONS: Optimizing ATSB stations to address causes of damage and conducting implementation research to inform optimal delivery and cost-effective deployment will be important to facilitate scale-up of ATSB interventions.

Characteristics of the Western Province, Zambia, trial site for evaluation of attractive targeted sugar baits for malaria vector control.

BACKGROUND: The attractive targeted sugar bait (ATSB) is a novel malaria vector control tool designed to attract and kill mosquitoes using a sugar-based bait, laced with oral toxicant. Western Province, Zambia, was one of three countries selected for a series of phase III cluster randomized controlled trials of the Westham ATSB Sarabi version 1.2. The trial sites in Kenya, Mali, and Zambia were selected to represent a range of different ecologies and malaria transmission settings across sub-Saharan Africa. This case study describes the key characteristics of the ATSB Zambia trial site to allow for interpretation of the results relative to the Kenya and Mali sites. METHODS: This study site characterization incorporates data from the trial baseline epidemiological and mosquito sugar feeding surveys conducted in 2021, as well as relevant literature on the study area. RESULTS: CHARACTERIZATION OF THE TRIAL SITE: The trial site in Zambia was comprised of 70 trial-designed clusters in Kaoma, Nkeyema, and Luampa districts. Population settlements in the trial site were dispersed across a large geographic area with sparsely populated villages. The overall population density in the 70 study clusters was 65.7 people per square kilometre with a total site population of 122,023 people living in a geographic area that covered 1858 square kilometres. However, the study clusters were distributed over a total area of approximately 11,728 square kilometres. The region was tropical with intense and seasonal malaria transmission. An abundance of trees and other plants in the trial site were potential sources of sugar meals for malaria vectors. Fourteen Anopheles species were endemic in the site and Anopheles funestus was the dominant vector, likely accounting for around 95% of all Plasmodium falciparum malaria infections. Despite high coverage of indoor residual spraying and insecticide-treated nets, the baseline malaria prevalence during the peak malaria transmission season was 50% among people ages six months and older. CONCLUSION: Malaria transmission remains high in Western Province, Zambia, despite coverage with vector control tools. New strategies are needed to address the drivers of malaria transmission in this region and other malaria-endemic areas in sub-Saharan Africa.

Entomological effects of attractive targeted sugar bait station deployment in Western Zambia: vector surveillance findings from a two-arm cluster randomized phase III trial.

BACKGROUND: Attractive targeted sugar bait (ATSB) stations are a novel tool with potential to complement current approaches to malaria vector control. To assess the public health value of ATSB station deployment in areas of high coverage with standard vector control, a two-arm cluster-randomized controlled trial (cRCT) of Sarabi ATSB® stations (Westham Ltd., Hod-Hasharon, Israel) was conducted in Western Province, Zambia, a high-burden location were Anopheles funestus is the dominant vector. The trial included 70 clusters and was designed to measure the effect of ATSBs on case incidence and infection prevalence over two 7-month deployments. Reported here are results of the vector surveillance component of the study, conducted in a subset of 20 clusters and designed to provide entomological context to guide overall interpretation of trial findings. METHODS: Each month, 200 paired indoor-outdoor human landing catch (HLC) and 200 paired light trap (LT) collections were conducted to monitor An. funestus parity, abundance, biting rates, sporozoite prevalence, and entomological inoculation rates (EIR). RESULTS: During the study 20,337 female An. funestus were collected, 11,229 from control and 9,108 from intervention clusters. A subset of 3,131 HLC specimens were assessed for parity: The mean non-parous proportion was 23.0% (95% CI 18.2-28.7%, total n = 1477) in the control and 21.2% (95% CI 18.8-23.9%, total n = 1654) in the intervention arm, an OR = 1.05 (95% CI 0.82-1.34; p = 0.688). A non-significant reduction in LT abundance (RR = 0.65 [95% CI 0.30-1.40, p = 0.267]) was associated with ATSB deployment. HLC rates were highly variable, but model results indicate a similar non-significant trend with a RR = 0.68 (95%CI 0.22-2.00; p = 0.479). There were no effects on sporozoite prevalence or EIR. CONCLUSIONS: Anopheles funestus parity did not differ across study arms, but ATSB deployment was associated with a non-significant 35% reduction in vector LT density, results that are consistent with the epidemiological impact reported elsewhere. Additional research is needed to better understand how to maximize the potential impact of ATSB approaches in Zambia and other contexts. TRIAL REGISTRATION NUMBER: This trial was registered with Clinicaltrials.gov (NCT04800055, 16 March 2021).

Burden of malaria in pregnancy among adolescent girls compared to adult women in 5 sub-Saharan African countries: A secondary individual participant data meta-analysis of 2 clinical trials

Malaria is among the top causes of death in adolescent girls (10 to 19 years) globally. Adolescent motherhood is associated with increased risk of adverse maternal and neonatal outcomes. The interaction of malaria, adolescence, and pregnancy is especially relevant in malaria endemic areas, where rates of adolescent pregnancy are high. However, data on burden of malaria among adolescent girls are limited. This study aimed at investigating whether adolescent girls were at a greater risk of experiencing malaria-related outcomes in pregnancy-parasitaemia and clinical disease-than adult women. An individual secondary participant-level meta-analysis was conducted using data from 5,804 pregnant women participating in 2 malaria prevention clinical trials in Benin, Gabon, Kenya, Mozambique, and Tanzania between 2009 and 2014. Of the sample, 1,201 participants were adolescent girls with a mean age of 17.5 years (standard deviation (SD) 1.3) and 886 (73.8%) of them primigravidae. Among the 4,603 adult women with mean age of 27.0 years (SD 5.4), 595 (12.9%) were primigravidae. Mean gestational age at enrolment was 20.2 weeks (SD 5.2) and 1,069 (18.4%) participants were HIV-infected. Women were followed monthly until the postpartum visit (1 month to 6 weeks after delivery). This study considered outcomes including clinical episodes during pregnancy, peripheral parasitaemia at delivery, and placental malaria. A 2-stage meta-analysis approach was followed by pooling single multivariable regression results into standard DerSimonian-Laird random-effects models. Adolescent girls were more likely than adult women to present with clinical malaria during pregnancy (incidence risk ratio (IRR) 1.70, 95% confidence interval (CI) 1.20; 2.39, p-value = 0.003, I2 = 0.0%, N = 4,092), peripheral parasitaemia at delivery (odds ratio (OR) 2.28, 95% CI 1.46; 3.55, p-value < 0.001, I2 = 0.0%, N = 3,977), and placental infection (OR 1.97, 95% CI 1.31; 2.98, p-value = 0.001, I2 = 1.4%, N = 4,797). Similar associations were observed among the subgroup of HIV-uninfected participants: IRR 1.72 (95% CI 1.22; 2.45, p-value = 0.002, I2 = 0.0%, N = 3,531) for clinical malaria episodes, OR 2.39 (95% CI 1.49; 3.86, p-value < 0.001, I2 = 0.0%, N = 3,053) for peripheral parasitaemia, and OR 1.88 (95% CI 1.06 to 3.33, p-value = 0.03, I2 = 34.9%, N = 3,847) for placental malaria. Among HIV-infected subgroups statistically significant associations were not observed. Similar associations were found in the subgroup analysis by gravidity. The small sample size and outcome prevalence in specific countries limited the inclusion of some countries in the meta-analysis. Furthermore, peripheral parasitaemia and placental malaria presented a considerable level of missing data-12.6% and 18.2% of participants had missing data on those outcomes, respectively. Given the original scope of the clinical trials, asymptomatic malaria infection was only assessed at the end of pregnancy through peripheral and placental parasitaemia.

Reduced exposure to malaria vectors following indoor residual spraying of pirimiphos-methyl in a high-burden district of rural Mozambique with high ownership of long-lasting insecticidal nets: entomological surveillance results from a cluster-randomized trial

Background: The need to develop new products and novel approaches for malaria vector control is recognized as a global health priority. One approach to meeting this need has been the development of new products for indoor residual spraying (IRS) with novel active ingredients for public health. While initial results showing the impact of several of these next-generation IRS products have been encouraging, questions remain about how to best deploy them for maximum impact. To help address these questions, a 2-year cluster-randomized controlled trial to measure the impact of IRS with a microencapsulated formulation of pirimiphos-methyl (PM) in an area with high ownership of long-lasting insecticidal nets (LLINs) was conducted in a high-transmission district of central Mozambique with pyrethroid resistant vectors. Presented here are the results of the vector surveillance component of the trial. Methods: The 2 year, two-armed trial was conducted in Mopeia District, Zambezia Province, Mozambique. In ten sentinel villages, five that received IRS with PM in October-November 2016 and again in October-November 2017 and five that received no IRS, indoor light trap collections and paired indoor-outdoor human landing collections catches (HLCs) were conducted monthly from September 2016 through October 2018. A universal coverage campaign in June 2017, just prior to the second spray round, distributed 131,540 standard alpha-cypermethrin LLINs across all study villages and increased overall net usage rates in children under 5 years old to over 90%. Results: The primary malaria vector during the trial was Anopheles funestus sensu lato (s.l.), and standard World Health Organization (WHO) tube tests with this population indicated variable but increasing resistance to pyrethroids (including alpha-cypermethrin, from > 85% mortality in 2017 to 7% mortality in 2018) and uniform susceptibility to PM (100% mortality in both years). Over the entire duration of the study, IRS reduced An. funestus s.l. densities by 48% (CI95 33-59%; p < 0.001) in indoor light traps and by 74% (CI95 38-90%; p = 0.010) during indoor and outdoor HLC, though in each study year reductions in vector density were consistently greatest in those months immediately following the IRS campaigns and waned over time. Overall there was no strong preference for An. funestus to feed indoors or outdoors, and these biting behaviours did not differ significantly across study arms: observed indoor-outdoor biting ratios were 1.10 (CI95 1.00-1.21) in no-IRS villages and 0.88 (CI95 0.67-1.15) in IRS villages. The impact of IRS was consistent in reducing HLC exposures both indoors (75% reduction: CI95 47-88%; p = 0. < 0.001) and outdoors (68% reduction: CI95 22-87%; p = 0.012). While substantially fewer Anopheles gambiae s.l. were collected during the study, trends show a similar impact of IRS on this key vector group as well, with a 33% (CI95 7-53%; p = 0.019) reduction in mosquitoes collected in light traps and a non-statistically significant 39% reduction (p = 0.249) in HLC landing rates. Conclusion: IRS with PM used in addition to pyrethroid-only LLINs substantially reduced human exposures to malaria vectors during both years of the cluster-randomized controlled trial in Mopeia-a high-burden district where the primary vector, An. funestus s.l., was equally likely to feed indoors or outdoors and demonstrated increasing resistance to pyrethroids. Findings suggest that IRS with PM can provide effective vector control, including in some settings where pyrethroid-only ITNs are widely used. Trial registration clinicaltrials.gov , NCT02910934. Registered 22 September 2016, https://www.clinicaltrials.gov/ct2/show/NCT02910934.

A public health paradox: the women most vulnerable to malaria are the least protected

Raquel Gonzalez and colleagues highlight an urgent need to evaluate antimalarials that can be safely administered to HIV-infected pregnant women on antiretroviral treatment and cotrimoxazole prophylaxis. African HIV-infected pregnant women are the most vulnerable population group to malaria infection. • Paradoxically, these women are also the least protected against malaria due to fear of potential interactions between antiretroviral and antimalarial drugs. • Action is urgently needed to evaluate antimalarials that can be safely administered to HIV-infected pregnant women on antiretroviral treatment and cotrimoxazole prophylaxis.

Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Infected Women Receiving Cotrimoxazole Prophylaxis: A Multicenter Randomized Placebo-Controlled Trial

Background: Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in HIV-negative pregnant women, but it is contraindicated in HIV-infected women taking daily cotrimoxazole prophylaxis (CTXp) because of potential added risk of adverse effects associated with taking two antifolate drugs simultaneously. We studied the safety and efficacy of mefloquine (MQ) in women receiving CTXp and long-lasting insecticide treated nets (LLITNs). Methods and findings: A total of 1,071 HIV-infected women from Kenya, Mozambique, and Tanzania were randomized to receive either three doses of IPTp-MQ (15 mg/kg) or placebo given at least one month apart; all received CTXp and a LLITN. IPTp-MQ was associated with reduced rates of maternal parasitemia (risk ratio [RR], 0.47 [95% CI 0.27-0.82]; p=0.008), placental malaria (RR, 0.52 [95% CI 0.29-0.90]; p=0.021), and reduced incidence of non-obstetric hospital admissions (RR, 0.59 [95% CI 0.37-0.95]; p=0.031) in the intention to treat (ITT) analysis. There were no differences in the prevalence of adverse pregnancy outcomes between groups. Drug tolerability was poorer in the MQ group compared to the control group (29.6% referred dizziness and 23.9% vomiting after the first IPTp-MQ administration). HIV viral load at delivery was higher in the MQ group compared to the control group (p=0.048) in the ATP analysis. The frequency of perinatal mother to child transmission of HIV was increased in women who received MQ (RR, 1.95 [95% CI 1.14-3.33]; p=0.015). The main limitation of the latter finding relates to the exploratory nature of this part of the analysis. Conclusions: An effective antimalarial added to CTXp and LLITNs in HIV-infected pregnant women can improve malaria prevention, as well as maternal health through reduction in hospital admissions. However, MQ was not well tolerated, limiting its potential for IPTp and indicating the need to find alternatives with better tolerability to reduce malaria in this particularly vulnerable group. MQ was associated with an increased risk of mother to child transmission of HIV, which warrants a better understanding of the pharmacological interactions between antimalarials and antiretroviral drugs.

Malaria control in the municipality of San Esteban, Honduras / Control de la malaria en el municipio de San Esteban, Honduras

OBJECTIVES: To assess the burden of malaria in San Esteban, Department of Olancho, Honduras, and provide recommendations for control. METHODS: Malaria causes appreciable morbidity in San Esteban. In 2006, health workers reported an increase in malaria cases and requested recommendations for control. In 2005, 385 cases (Plasmodium vivax, 316; P. falciparum, 69) were detected from 4 007 blood smears in the San Esteban laboratory (slide positivity rate = 9.6 percent). During May-July 2006, we assessed the burden of malaria and made recommendations. We reviewed epidemiologic data from slide-confirmed malaria cases in 2005 and 2006 and conducted a knowledge, attitudes, and practices survey in households to assess malaria diagnostic, treatment, and prevention practices. RESULTS: During May-July 2006, 143 laboratory-confirmed malaria cases were detected (P. vivax, 134; P. falciparum, 9) in San Esteban, compared with 104 (P. vivax, 79; P. falciparum, 25) in May-July 2005. From January 2005 to July 2006, 538 cases were detected in San Esteban, with increased frequency in May-October and the highest incidence in children 0-14 years old. We administered 112 surveys in 19 communities. Seventy percent of respondents reported a history of malaria in a household member, with the highest frequency reported in mothers (45 percent) and children under 14 years old (37 percent). Most households did not have mosquito protection such as bed nets, screens, or indoor residual insecticide. CONCLUSIONS: Malaria is ongoing in San Esteban, with increased incidence in children. We recommend increased availability and promotion of insecticide-treated bed nets, improved timing and coverage of indoor residual spraying, and improved community malaria practices through education sessions.

OBJETIVOS: Evaluar la carga de malaria en San Esteban, departamento de Olancho, Honduras, y ofrecer recomendaciones para su control. MÉTODOS: La malaria es causa de una considerable morbilidad en San Esteban. En 2006, los trabajadores sanitarios informaron un aumento de casos de malaria y solicitaron recomendaciones para su control. En 2005, en el laboratorio de San Esteban se detectaron 385 casos (316 por Plasmodium vivax y 69 por P. falciparum) en 4 007 frotis sanguíneos (tasa de positividad: 9,6 por ciento). Entre mayo y julio de 2006 se evaluó la carga de malaria y se hicieron las recomendaciones. Se revisaron los datos epidemiológicos de los casos confirmados de 2005 y 2006 y se aplicó una encuesta sobre conocimientos, actitudes y hábitos en los hogares para evaluar las prácticas relacionadas con el diagnóstico, el tratamiento y la prevención de la malaria. RESULTADOS: Entre mayo y julio de 2006 en San Esteban se detectaron 143 casos de malaria confirmados por el laboratorio (134 por P. vivax y 9 por P. falciparum), en comparación con 104 (79 por P. vivax y 25 por P. falciparum) entre mayo y julio de 2005. Entre enero de 2005 y julio de 2006 se detectaron 538 casos en San Esteban, con un aumento en la frecuencia entre mayo y octubre y la mayor incidencia en niños de 0 a 14 años. Se aplicaron 112 encuestas en 19 comunidades. De los que respondieron, 70 por ciento había tenido algún miembro del hogar con malaria, con una mayor frecuencia en las madres (45 por ciento) y los menores de 14 años (37 por ciento). La mayoría de los hogares carecían de protección contra los mosquitos, como mosquiteros para las camas y ventanas o fumigación de interiores. CONCLUSIONES: La malaria se mantiene en aumento en San Esteban, con una mayor incidencia en los niños. Se recomienda incrementar la disponibilidad y la promoción de mosquiteros tratados con insecticidas, mejorar la periodicidad y la cobertura de la fumigación de interiores y mejorar los hábitos...

A rapid assessment approach for public health decision-making related to the prevention of malaria during pregnancy

Objective: To develop a rapid field assessment methodology to address the burden of malaria during pregnancy and the options for intervening within the existing antenatal care system in Kenya. Methods: Surveys consisting of questionnaires, sampling of blood for parasitaemia and anaemia, and birth outcome assessment were conducted in antenatal clinics, delivery units, and in the community in Ksumu and Mombasa, Kenya. Findings: T he ratges of maternal anaemia and severe anaemia, were, resctively, 79 cent and 8 cent in Kisumu, and 95 cent and 24 cent in Mombasa. The rates of placental parasitaemia were 27 cent and 24 cent and the ratges of low birth weight were 18 cent and 24 cent in Kisumu and Mombasa, respectively. Women with placental parasitaemia had a higher incidence of low birth wight compared with women without placental parasitaemai in both Kisumu (28 cent vs 16 cent,P=0.0004) and Mombasa (42 cent vs 20 cent, P=0.004). A total of 95 cent and 98 cent for women in Kisumu and Mombasa, respectively, reported attending an antenatal clinic during their previous pregnancy. Conclusion: This metodology can be used by ministries of health to collect data for decision-making regarding malaria control during pregnancy: it can also privide a baseline measurement on which to evaluate subsequent interventions