A cluster randomized trial of delivery of intermittent preventive treatment of malaria in pregnancy at the community level in Malawi.

BACKGROUND: Malaria in pregnancy doubles the risk of low birthweight; up to 11% of all neonatal deaths in sub-Saharan Africa are associated with malaria in pregnancy. To prevent these and other adverse health consequences, the World Health Organization recommends administering intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine for all pregnant women at each antenatal care (ANC) visit, starting as early as possible in the second trimester. The target is for countries to administer a minimum of three doses (IPTp3+) to at least 85% of pregnant women. METHODS: A cluster randomized, controlled trial was conducted to assess the effect of delivery of IPTp by community health workers on the coverage of IPTp3 + and ANC visits in Malawi. Community delivery of IPTp was implemented within two districts in Malawi over a 21-month period, from November 2018 to July 2020. In control sites, IPTp was delivered at health facilities. Representative samples of women who delivered in the prior 12 months were surveyed at baseline (n = 370, December 2017) and endline (n = 687, August 2020). A difference in differences analysis was conducted to assess the change in coverage of IPTp and ANC over time, accounting for clustering at the health facility level. RESULTS: Overall IPTp coverage increased over the study period. At baseline, women received a mean of 2.3 IPTp doses (range 0-5 doses) across both arms, and at endline, women received a mean of 2.8 doses (range 0-9 doses). Despite overall increases, the change in IPTp3 + coverage was not significantly different between intervention and control groups (6.9%, 95% CI: -5.9%, 19.6%). ANC4 + coverage increased significantly in the intervention group compared with the control group, with a difference-in-differences of 25.3% points (95% CI: 1.3%, 49.3%). CONCLUSIONS: In order to reduce the burden of malaria in pregnancy, new strategies are needed to improve uptake of effective interventions such as IPTp. While community health workers' delivery of IPTp did not increase uptake in this study, they may be effective in other settings or circumstances. Further research can help identify the health systems characteristics that are conducive to community delivery of IPTp and the operational requirements for effective implementation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03376217. Registered December 6, 2017, https://clinicaltrials.gov/ct2/show/NCT03376217 .

Malaria knowledge and experiences with community health workers among recently pregnant women in Malawi.

BACKGROUND: The World Health Organization recommends three or more doses of intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) to mitigate the negative effects of malaria in pregnancy (MIP). Many pregnant women in Malawi are not receiving the recommended number of doses. Community delivery of IPTp (cIPTp) is being piloted as a new approach to increase coverage. This survey assessed recently pregnant women's knowledge of MIP and their experiences with community health workers (CHWs) prior to implementing cIPTp. METHODS: Data were collected via a household survey in Ntcheu and Nkhata Bay Districts, Malawi, from women aged 16-49 years who had a pregnancy resulting in a live birth in the previous 12 months. Survey questions were primarily open response and utilized review of the woman's health passport whenever possible. Analyses accounted for selection weighting and clustering at the health facility level and explored heterogeneity between districts. RESULTS: A total of 370 women were interviewed. Women in both districts found their community health workers (CHWs) to be helpful (77.9%), but only 35.7% spoke with a CHW about antenatal care and 25.8% received assistance for malaria during their most recent pregnancy. A greater proportion of women in Nkhata Bay than Ntcheu reported receiving assistance with malaria from a CHW (42.7% vs 21.9%, p = 0.01); women in Nkhata Bay were more likely to cite IPTp-SP as a way to prevent MIP (41.0% vs 24.8%, p = 0.02) and were more likely to cite mosquito bites as the only way to spread malaria (70.6% vs 62.0% p = 0.03). Women in Nkhata Bay were more likely to receive 3 + doses of IPTp-SP (IPTp3) (59.2% vs 41.8%, p = 0.0002). Adequate knowledge was associated with increased odds of receiving IPTp3, although not statistically significantly so (adjusted odds ratio = 1.50, 95% confidence interval 0.97-2.32, p-value 0.066). CONCLUSIONS: Women reported positive experiences with CHWs, but there was not a focus on MIP. Women in Nkhata Bay were more likely to be assisted by a CHW, had better knowledge, and were more likely to receive IPTp3+ . Increasing CHW focus on the dangers of MIP and implementing cIPTp has the potential to increase IPTp coverage.

The effect of mobile phone text message reminders on health workers' adherence to case management guidelines for malaria and other diseases in Malawi: lessons from qualitative data from a cluster-randomized trial.

BACKGROUND: Mobile health (mHealth), which uses technology such as mobile phones to improve patient health and health care delivery, is increasingly being tested as an intervention to promote health worker (HW) performance. This study assessed the effect of short messaging services (SMS) reminders in a study setting. Following a trial of text-message reminders to HWs to improve case management of malaria and other childhood diseases in southern Malawi that showed little effect, qualitative data was collected to explore the reasons why the intervention was ineffective and describe lessons learned. METHODS: Qualitative data collection was undertaken to lend insight into quantitative results from a trial in which 105 health facilities were randomized to three arms: (1) twice-daily text-message reminders to HWs, including clinicians and drug dispensers, on case management of malaria; (2) twice-daily text-message reminders to HWs on case management of malaria, pneumonia and diarrhoea; and, (3) a control arm. In-depth interviews were conducted with 50 HWs in the intervention arms across seven districts. HWs were asked about acceptability and feasibility of the text-messaging intervention and its perceived impact on recommended case management. The interviews were recorded, transcribed and translated into English for a thematic and framework analysis. Nvivo 11 software was used for data management and analysis. RESULTS: A total of 50 HWs were interviewed at 22 facilities. HWs expressed high acceptance of text-message reminders and appreciated messages as job aids and practical reference material for their day-to-day work. However, HWs said that health systems barriers, including very high outpatient workload, commodity stock-outs, and lack of supportive supervision and financial incentives demotivated them, limited their ability to act on messages and therefore adherence to case management guidelines. Drug dispensers were more likely than clinicians to report usage of text-message reminders. Despite these challenges, nearly all HWs expressed a desire for a longer duration of the SMS intervention. CONCLUSIONS: Text-message reminders to HWs can provide a platform to improve understanding of treatment guidelines and case management decision-making skills, but might not improve actual adherence to guidelines. More interaction, for example through targeted supervision or two-way technology communication, might be an essential intervention component to help address structural barriers and facilitate improved clinical practice.

Health worker adherence to malaria treatment guidelines at outpatient health facilities in southern Malawi following implementation of universal access to diagnostic testing.

BACKGROUND: Appropriate diagnosis and treatment are essential for reducing malaria mortality. A cross-sectional outpatient health facility (HF) survey was conducted in southern Malawi from January to March 2015 to determine appropriate malaria testing and treatment practices four years after implementation of a policy requiring diagnostic confirmation before treatment. METHODS: Enrolled patients were interviewed, examined and had their health booklet reviewed. Health workers (HWs) were asked about training, supervision and access to the 2013 national malaria treatment guidelines. HFs were assessed for malaria diagnostic and treatment capacity. Weighted descriptive analyses and logistic regression of patient, HW and HF characteristics related to testing and treatment were performed. RESULTS: An evaluation of 105 HFs, and interviews of 150 HWs and 2342 patients was completed. Of 1427 suspect uncomplicated malaria patients seen at HFs with testing available, 1072 (75.7%) were tested, and 547 (53.2%) tested positive. Testing was more likely if patients spontaneously reported fever (odds ratio (OR) 2.6; 95% confidence interval (CI) 1.7-4.0), headache (OR 1.5; 95% CI 1.1-2.1) or vomiting (OR 2.0; 95% CI 1.0-4.0) to HWs and less likely if they reported skin problems (OR 0.4; 95% CI 0.2-0.6). Altogether, 511 (92.7%) confirmed cases and 98 (60.3%) of 178 presumed uncomplicated malaria patients (at HFs without testing) were appropriately treated, while 500 (96.6%) of 525 patients with negative tests did not receive anti-malarials. Only eight (5.7%) suspect severe malaria patients received appropriate pre-referral treatment. Appropriate treatment was more likely for presumed uncomplicated malaria patients (at HFs without testing) with elevated temperature (OR 1.5/1 °C increase; 95% CI 1.1-1.9), who reported fever to HWs (OR 5.7; 95% CI 1.9-17.6), were seen by HWs with additional supervision visits in the previous 6 months (OR 1.2/additional visit; 95% CI 1.0-1.4), or were seen by older HWs (OR 1.1/year of age; 95% CI 1.0-1.1). CONCLUSIONS: Correct testing and treatment practices were reasonably good for uncomplicated malaria when testing was available. Pre-referral treatment for suspect severe malaria was unacceptably rare. Encouraging HWs to elicit and appropriately respond to patient symptoms may improve practices.

Scale-up of integrated malaria vector control: lessons from Malawi.

PROBLEM: Indoor residual spraying and long-lasting insecticidal nets (LLINs) are key tools for malaria vector control. Malawi has struggled to scale up indoor residual spraying and to improve LLIN coverage and usage. APPROACH: In 2002, the Malawian National Malaria Control Programme developed guidelines for insecticide treated net distribution to reach the strategic target of at least 60% coverage of households with an LLIN. By 2005, the target coverage was 80% of households and the Global Fund financed the scale-up. The US President's Malaria Initiative funded the indoor residual spraying intervention. LOCAL SETTING: Malawi's entire population is considered to be at risk of malaria. Poor vector control, insecticide resistance in malaria vectors and insufficient technical and financial support have exacerbated the malaria burden. RELEVANT CHANGES: Between 2002 and 2012, 18 248 206 LLINs had been distributed. The coverage of at least one LLIN per household increased from 27% (3689/13 664) to 58% (1974/3404). Indoor residual spraying coverage increased from 28 227 to 653 592 structures between 2007 and 2011. However, vector resistance prompted a switch from pyrethroids to organophosphates for indoor residual spraying, which increased the cost and operations needed to be cut back from seven to one district. Malaria cases increased from 2 853 315 in 2002 to 6 748 535 in 2010, and thereafter dropped to 4 922 596 in 2012. LESSONS LEARNT: A single intervention-based approach for vector control may have suboptimal impact. Well-coordinated integrated vector management may offer greater benefits. A resistance management plan is essential for effective and sustainable vector control.

In vivo efficacy of artemether-lumefantrine and artesunate-amodiaquine for uncomplicated Plasmodium falciparum malaria in Malawi, 2014.

BACKGROUND: Malaria causes significant morbidity in Malawi, with an estimated 5 million cases in 2014. Artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) are the first- and second-line treatments for uncomplicated malaria, respectively, but emerging resistance threatens their efficacy. In order to understand whether AL and ASAQ remain efficacious for the treatment of uncomplicated Plasmodium falciparum malaria in Malawi, a therapeutic efficacy trial was conducted. METHODS: During March-July 2014, febrile children aged 6-59 months with microscopy-confirmed uncomplicated P. falciparum malaria (1000-200,000 parasites/µL) were enrolled in a 28-day randomized in vivo efficacy trial at three sites: one each in northern (Karonga), central (Nkhotakota) and southern (Machinga) Malawi. The study was powered to estimate site-specific efficacy for AL and overall efficacy for ASAQ, with 3:1 randomization to AL or ASAQ. Blood was collected for malaria microscopy and molecular testing on days 0-3, 7, 14, 21, and 28. Recrudescence and reinfection were differentiated using polymerase chain reaction (PCR) genotyping of merozoite surface protein. The primary outcome was the PCR-corrected day 28 Kaplan-Meier cumulative success rate. RESULTS: A total of 452 children were enrolled; 303/338 (89 %) and 98/114 (86 %) reached a study endpoint in AL and ASAQ arms, respectively. All treatment failures occurred after day 3. The day 28 uncorrected cumulative success rate was 97.1 % (95 % confidence interval [CI]: 93.9-100 %) for ASAQ and 76.8 % (95 % CI 72.1-81.5 %) for AL, with 82.5 % (95 % CI 75.4-89.7 %), 69 % (95 % CI 59.9-78.1 %), and 78.2 % (95 % CI 70.2-86.3 %) success in the northern, central, and southern regions, respectively. The day 28 PCR-corrected cumulative success rate was 99 % (95 % CI 97.2-100 %) in the ASAQ arm and 99.3 % (95 % CI 98.3-100 %) in the AL arm, with 98-100 % efficacy in each site. CONCLUSIONS: As evidenced by the day 28 PCR-corrected cumulative success rates, both AL and ASAQ remain efficacious treatments for uncomplicated malaria in Malawi. The lower uncorrected efficacy in the AL arm compared to ASAQ may be explained by the shorter half-life of lumefantrine (3-6 days) compared to amodiaquine (9-18 days). The high reinfection rate suggests that there is a continued need to scale-up effective malaria prevention interventions.

Increasing insecticide resistance in Anopheles funestus and Anopheles arabiensis in Malawi, 2011-2015.

BACKGROUND: Susceptibility of principal Anopheles malaria vectors to common insecticides was monitored over a 5-year period across Malawi to inform and guide the national malaria control programme. METHODS: Adult blood-fed Anopheles spp. and larvae were collected from multiple sites in sixteen districts across the country between 2011 and 2015. First generation (F1) progeny aged 2-5 days old were tested for susceptibility, using standard WHO procedures, against pyrethroids (permethrin and deltamethrin), carbamates (bendiocarb and propoxur), organophosphates (malathion and pirimiphos-methyl) and an organochlorine (DDT). RESULTS: Mortality of Anopheles funestus to deltamethrin, permethrin, bendiocarb and propoxur declined significantly over the 5-year (2011-2015) monitoring period. There was wide variation in susceptibility to DDT but it was not associated with time. In contrast, An. funestus exhibited 100% mortality to the organophosphates (malathion and pirimiphos-methyl) at all sites tested. There was reduced mortality of Anopheles arabiensis to deltamethrin over time though this was not statistically significant. However, mortality of An. arabiensis exposed to permethrin declined significantly over time. Anopheles arabiensis exposed to DDT were more likely to be killed if there was high ITN coverage in the mosquito collection area the previous year. There were no other associations between mosquito mortality in a bioassay and ITN coverage or IRS implementation. Mortality of An. funestus from four sites exposed to deltamethrin alone ranged from 2 to 31% and from 41 to 94% when pre-exposed to the synergist piperonyl butoxide followed by deltamethrin. For permethrin alone, mortality ranged from 2 to 13% while mortality ranged from 63 to 100% when pre-exposed to PBO. CONCLUSION: Pyrethroid resistance was detected in An. funestus and An. arabiensis populations across Malawi and has worsened over the last 5 years. New insecticides and control strategies are urgently needed to reduce the burden of malaria in Malawi.

Preventing malaria transmission by indoor residual spraying in Malawi: grappling with the challenge of uncertain sustainability.

BACKGROUND: In the past decade, there has been rapid scale-up of insecticide-based malaria vector control in the context of integrated vector management (IVM) according to World Health Organization recommendations. Endemic countries have deployed indoor residual spraying (IRS) and long-lasting insecticidal nets as hallmark vector control interventions. This paper discusses the successes and continued challenges and the way forward for the IRS programme in Malawi. CASE DESCRIPTION: The National Malaria Control Programme in Malawi, with its efforts to implement an integrated approach to malaria vector control, was the 'case' for this study. Information sources included all available data and accessible archived documentary records on IRS in Malawi. A methodical assessment of published and unpublished documents was conducted via a literature search of online electronic databases. DISCUSSION: Malawi has implemented IRS as the main malaria transmission-reducing intervention. However, pyrethroid and carbamate resistance in malaria vectors has been detected extensively across the country and has adversely affected the IRS programme. Additionally, IRS activities have been characterized by substantial inherent logistical and technical challenges culminating into missed targets. As a consequence, programmatic IRS operations have been scaled down from seven districts in 2010 to only one district in 2014. The future of the IRS programme in Malawi is uncertain due to limited funding, high cost of alternative insecticides and technical resource challenges being experienced in the country. CONCLUSIONS: The availability of a long-lasting formulation of the organophosphate pirimiphos-methyl makes the re-introduction of IRS a possibility and may be a useful approach for the management of pyrethroid resistance. Implementing the IVM strategy, advocating for sustainable domestic funding, including developing an insecticide resistance monitoring and management plan and vector surveillance guidelines will be pivotal in steering entomologic monitoring and future vector control activities in Malawi.

The Effect of Text Message Reminders to Health Workers on Quality of Care for Malaria, Pneumonia, and Diarrhea in Malawi: A Cluster-Randomized, Controlled Trial.

The use of mobile technologies in medicine, or mHealth, holds promise to improve health worker (HW) performance, but evidence is mixed. We conducted a cluster-randomized controlled trial to evaluate the effect of text message reminders to HWs in outpatient health facilities (HFs) on quality of care for malaria, pneumonia, and diarrhea in Malawi. After a baseline HF survey (2,360 patients) in January 2015, 105 HFs were randomized to three arms: 1) text messages to HWs on malaria case management; 2) text messages to HWs on malaria, pneumonia, and diarrhea case management (latter two for children < 5 years); and 3) control arm (no messages). Messages were sent beginning April 2015 twice daily for 6 months, followed by an endline HF survey (2,536 patients) in November 2015. An intention-to-treat analysis with difference-in-differences binomial regression modeling was performed. The proportion of patients with uncomplicated malaria managed correctly increased from 42.8% to 59.6% in the control arm, from 43.7% to 55.8% in arm 1 (effect size -4.7%-points, 95% confidence interval (CI): -18.2, 8.9, P = 0.50) and from 30.2% to 50.9% in arm 2 (effect size 3.9%-points, 95% CI: -14.1, 22.0, P = 0.67). Prescription of first-line antibiotics to children < 5 years with clinically defined pneumonia increased in all arms, but decreased in arm 2 (effect size -4.1%-points, 95% CI: -42.0, 33.8, P = 0.83). Prescription of oral rehydration solution to children with diarrhea declined slightly in all arms. We found no significant improvements in malaria, pneumonia, or diarrhea treatment after HW reminders, illustrating the importance of rigorously testing new interventions before adoption.

Malaria Control Interventions Contributed to Declines in Malaria Parasitemia, Severe Anemia, and All-Cause Mortality in Children Less Than 5 Years of Age in Malawi, 2000-2010.

Malaria control intervention coverage increased nationwide in Malawi during 2000-2010. Trends in intervention coverage were assessed against trends in malaria parasite prevalence, severe anemia (hemoglobin < 8 g/dL), and all-cause mortality in children under 5 years of age (ACCM) using nationally representative household surveys. Associations between insecticide-treated net (ITN) ownership, malaria morbidity, and ACCM were also assessed. Household ITN ownership increased from 27.4% (95% confidence interval [CI] = 25.9-29.0) in 2004 to 56.8% (95% CI = 55.6-58.1) in 2010. Similarly intermittent preventive treatment during pregnancy coverage increased from 28.2% (95% CI = 26.7-29.8) in 2000 to 55.0% (95% CI = 53.4-56.6) in 2010. Malaria parasite prevalence decreased significantly from 60.5% (95% CI = 53.0-68.0) in 2001 to 20.4% (95% CI = 15.7-25.1) in 2009 in children aged 6-35 months. Severe anemia prevalence decreased from 20.4% (95% CI: 17.3-24.0) in 2004 to 13.1% (95% CI = 11.0-15.4) in 2010 in children aged 6-23 months. ACCM decreased 41%, from 188.6 deaths per 1,000 live births (95% CI = 179.1-198.0) during 1996-2000, to 112.1 deaths per 1,000 live births (95% CI = 105.8-118.5) during 2006-2010. When controlling for other covariates in random effects logistic regression models, household ITN ownership was protective against malaria parasitemia in children (odds ratio [OR] = 0.81, 95% CI = 0.72-0.92) and severe anemia (OR = 0.82, 95% CI = 0.72-0.94). After considering the magnitude of changes in malaria intervention coverage and nonmalaria factors, and given the contribution of malaria to all-cause mortality in malaria-endemic countries, the substantial increase in malaria control interventions likely improved child survival in Malawi during 2000-2010.