Post-discharge malaria chemoprevention (PMC) in Malawi: caregivers` acceptance and preferences with regard to delivery methods.

BACKGROUND: In malaria endemic countries of sub-Saharan Africa, many children develop severe anaemia due to previous and current malaria infections. After blood transfusions and antimalarial treatment at the hospital they are usually discharged without any follow-up. In the post-discharge period, these children may contract new malaria infections and develop rebound severe anaemia. A randomised placebo-controlled trial in Malawi showed 31% reduction in malaria- and anaemia-related deaths or hospital readmissions among children under 5 years of age given antimalarial drugs for 3 months post-discharge. Thus, post-discharge malaria chemoprevention (PMC) may provide substantial protection against malaria and anaemia in young children living in areas of high malaria transmission. A delivery implementation trial is currently being conducted in Malawi to determine the optimal strategy for PMC delivery. In the trial, PMC is delivered through community- or facility-based methods with or without the use of reminders via phone text message or visit from a Health Surveillance Assistant. This paper describes the acceptance of PMC among caregivers. METHODS: From October to December 2016, 30 in-depth interviews and 5 focus group discussions were conducted with caregivers of children who recently completed the last treatment course in the trial. Views on the feasibility of various delivery methods and reminder strategies were collected. The interviews were transcribed verbatim, translated to English, and coded using the software programme NVivo. RESULTS: Community-based delivery was perceived as more favourable than facility-based delivery due to easy home access to drugs and fewer financial concerns. Many caregivers reported lack of visits from Health Surveillance Assistants and preferred text message reminders sent directly to their phones rather than waiting on these visits. Positive attitudes towards active use of health cards for remembering treatment dates were especially evident. Additionally, caregivers shared positive experiences from participation in the programme and described dihydroartemisinin-piperaquine as a safe and effective antimalarial drug that improved the health and well-being of their children. CONCLUSIONS: Post-discharge malaria chemoprevention given to children under the age of 5 previously treated for severe anaemia is highly accepted among caregivers. Caregivers prefer community-based delivery with use of health cards as their primary tool of reference. TRIAL REGISTRATION: NCT02721420 (February 13, 2016).

Introducing post-discharge malaria chemoprevention (PMC) for management of severe anemia in Malawian children: a qualitative study of community health workers' perceptions and motivation.

BACKGROUND: Severe malarial anaemia is one of the leading causes of paediatric hospital admissions in Malawi. Post-discharge malaria chemoprevention (PMC) is the intermittent administration of full treatment courses of antimalarial to children recovering from severe anaemia and findings suggest that this intervention significantly reduces readmissions and deaths in these children. Community delivery of health interventions utilizing community health workers (CHWs) has been successful in some programmes and not very positive in others. In Malawi, there is an on-going cluster randomised trial that aims to find the optimum strategy for delivery of dihydroartemesinin-piperaquine (DHP) for PMC in children with severe anaemia. Our qualitative study aimed to explore the feasibility of utilizing CHWs also known as health surveillance assistants (HSAs) to remind caregivers to administer PMC medication in the existing Malawian health system. METHODS: Between December 2016 and March 2018, 20 individual in-depth-interviews (IDIs) and 2 focus group discussions (FGDs) were conducted with 39 HSAs who had the responsibility of conducting home visits to remind caregivers of children who were prescribed PMC medication in the trial. All interviews were conducted in the local language, transcribed verbatim, and translated into English. The transcripts were uploaded to NVIVO 11 and analysed using the thematic framework analysis method. RESULTS: Although intrinsic motivation was reportedly high, adherence to the required number of home visits was very poor with only 10 HSAs reporting full adherence. Positive factors for adherence were the knowledge and perception of the effectiveness of PMC and the recognition from the community as well as health system. Poor training, lack of supervision, high workload, as well as technical and structural difficulties; were reported barriers to adherence by the HSAs. CONCLUSIONS: Post-discharge malaria chemoprevention with DHP is perceived as a positive approach to manage children recovering from severe anaemia by HSAs in Malawi. However, adherence to home visit reminders was very poor and the involvement of HSAs in a scale up of this intervention may pose a challenge in the existing Malawian health system. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02721420 . The trial was registered on 26 March 2016.

Predicting adherence to postdischarge malaria chemoprevention in Malawian pre-school children: A prognostic multivariable analysis.

Chemoprevention with antimalarials is a key strategy for malaria control in sub-Saharan Africa. Three months of postdischarge malaria chemoprevention (PDMC) reduces malaria-related mortality and morbidity in pre-school children recently discharged from hospital following recovery from severe anemia. Research on adherence to preventive antimalarials in children is scarce. We aimed to investigate the predictors for caregivers' adherence to three courses of monthly PDMC in Malawi. We used data from a cluster randomized implementation trial of PDMC in Malawi (n = 357). Modified Poisson regression for clustered data was used to obtain relative risks of predictors for full adherence to PDMC. We did not find a conclusive set of predictors for PDMC adherence. The distribution of households across a socio-economic index and caregivers' education showed mixed associations with poor adherence. Caregivers of children with four or more malaria infections in the past year were associated with reduced adherence. With these results, we cannot confirm the associations established in the literature for caregiver adherence to artemisinin-based combination therapies (ACTs). PDMC combines multiple factors that complicate adherence. Our results may indicate that prevention interventions introduce a distinct complexity to ACT adherence behavior. Until we better understand this relationship, PDMC programs should ensure high program fidelity to sustain adherence by caregivers during implementation.

Dihydroartemisinin-piperaquine or sulphadoxine-pyrimethamine for the chemoprevention of malaria in children with sickle cell anaemia in eastern and southern Africa (CHEMCHA): a protocol for a multi-centre, two-arm, double-blind, randomised, placebo-controlled superiority trial.

BACKGROUND: An estimated 300,000 babies are born with sickle cell anaemia (SCA) annually. Affected children have chronic ill health and suffer premature death. Febrile illnesses such as malaria commonly precipitate acute crises in children with SCA. Thus, chemoprophylaxis for malaria is an important preventive strategy, but current regimes are either sub-optimally effective (e.g. monthly sulphadoxine-pyrimethamine, SP) or difficult to adhere to (e.g. daily proguanil). We propose dihydroartemisinin-piperaquine (DP) as the agent with the most potential to be used across Africa. METHODS: This will be a randomised, double-blind, parallel-group superiority trial of weekly single-day courses of DP compared to monthly single-day courses of SP in children with SCA. The study will be conducted in eastern (Uganda) and southern (Malawi) Africa using randomisation stratified by body weight and study centre. Participants will be randomised using an allocation of 1:1 to DP or SP. We will investigate the efficacy, safety, acceptability and uptake and cost-effectiveness of malaria chemoprevention with weekly courses of DP vs monthly SP in 548 to 824 children with SCA followed up for 12-18 months. We will also assess toxicity from cumulative DP dosing and the development of resistance. Participant recruitment commenced on 30 April 2021; follow-up is ongoing. DISCUSSION: At the end of this study, findings will be used to inform regional health policy. This manuscript is prepared from protocol version 2.1 dated 1 January 2022. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov, NCT04844099 . Registered on 08 April 2021.

Projected health impact of post-discharge malaria chemoprevention among children with severe malarial anaemia in Africa.

Children recovering from severe malarial anaemia (SMA) remain at high risk of readmission and death after discharge from hospital. However, a recent trial found that post-discharge malaria chemoprevention (PDMC) with dihydroartemisinin-piperaquine reduces this risk. We developed a mathematical model describing the daily incidence of uncomplicated and severe malaria requiring readmission among 0-5-year old children after hospitalised SMA. We fitted the model to a multicentre clinical PDMC trial using Bayesian methods and modelled the potential impact of PDMC across malaria-endemic African countries. In the 20 highest-burden countries, we estimate that only 2-5 children need to be given PDMC to prevent one hospitalised malaria episode, and less than 100 to prevent one death. If all hospitalised SMA cases access PDMC in moderate-to-high transmission areas, 38,600 (range 16,900-88,400) malaria-associated readmissions could be prevented annually, depending on access to hospital care. We estimate that recurrent SMA post-discharge constitutes 19% of all SMA episodes in moderate-to-high transmission settings.

"Satanism is witchcraft's younger sibling": Changing perceptions of natural and supernatural anaemia causality in Malawian children.

In countries of sub-Saharan Africa, many children are admitted to hospital with severe forms of anaemia. The late hospital admissions of anaemic children contribute significantly to child morbidity and mortality in these countries. This qualitative study explores local health beliefs and traditional treatment practices that may hinder timely seeking of hospital care for anaemic children. In January of 2019, nine focus group discussions were conducted with 90 participants in rural communities of Malawi. The participants represented four groups of caregivers; mothers, fathers, grandmothers and grandfathers of children under the age of five. The Malawian medical landscape is comprised of formal and informal therapeutic alternatives-and this myriad of modalities is likely to complicate the healthcare choices of caregivers. When dealing with child illness, many participants reported how they would follow a step-by-step, 'multi-try' therapeutic pathway where a combination of biomedical and traditional treatment options were sought at varying time points depending on the perceived cause and severity of symptoms. The participants linked anaemia to naturalistic (malaria, poor nutrition and the local illnesses kakozi and kapamba), societal (the local illness msempho) and supernatural or personalistic (witchcraft and Satanism) causes. Most participants agreed that anaemia due to malaria and poor nutrition should be treated at hospital. As for local illnesses, many grandparents suggested herbal treatment offered by traditional healers, while the majority of parents would opt for hospital care. However, participants across all age groups claimed that anaemia caused by witchcraft and Satanism could only be dealt with by traditional healers or prayer, respectively. The multiple theories of anaemia causality combined with extensive use of and trust in traditional and complementary medicine may explain the frequent delay in admittance of anaemic children to hospital.

Isotopic measurement of iron requirements in sub-Saharan African children.

BACKGROUND: Prevention of iron deficiency in African children is a public health priority. Current WHO/FAO estimations of iron requirements are derived from factorial estimates based on healthy, iron-sufficient "model" children using data derived mainly from adults. OBJECTIVES: In this study, we aimed to quantify iron absorption, loss, and balance in apparently healthy 5- to 7-y-old children living in rural Africa. METHODS: We directly measured long-term iron absorption and iron loss in a 2-y observational study in Malawian children (n = 48) using a novel stable iron isotope method. RESULTS: Of the 36 children with height-for-age and weight-for-age z scores ≥-2, 13 (36%) were iron deficient (soluble transferrin receptor >8.3 mg/L) and 23 were iron sufficient. Iron-deficient children weighed more than iron-sufficient children [mean difference (95% CI): +2.1 (1.4, 2.7) kg; P = 0.01]. Mean iron losses did not differ significantly between iron-deficient and iron-sufficient children and were comparable to WHO/FAO median estimates of 19 µg/(d × kg). In iron-sufficient children, median (95% CI) dietary iron absorption was 32 (28, 34) µg/(d × kg), comparable to WHO/FAO-estimated median requirements of 32 µg/(d × kg). In iron-deficient children, absorption of 28 (25, 30) µg/(d × kg) was not increased to correct their iron deficit, likely because of a lack of bioavailable dietary iron. Twelve children (25%) were undernourished (underweight, stunted, or both). CONCLUSIONS: Our results suggest that WHO/FAO iron requirements are adequate for healthy iron-sufficient children in this rural area of Malawi, but iron-deficient children require additional bioavailable iron to correct their iron deficit.

A cohort analysis of survival and outcomes in severely anaemic children with moderate to severe acute malnutrition in Malawi.

INTRODUCTION: Moderate to severe acute malnutrition (SAM/MAM) and severe anaemia are important and associated co-morbidities in children aged less than five years. Independently, these two morbidities are responsible for high risk of in-hospital and post-discharge deaths and hospital readmissions. The primary objective of this study is to investigate the risk of death among severely anaemic children with moderate to severe acute malnutrition compared to children with severe anaemia alone. METHODS: This was a retrospective analysis of data collected from a large prospective study that was investigating severe anaemia in children aged less than 5 years old. The study was conducted at Queen Elizabeth Central Hospital in Blantyre and Chikhwawa district hospital in southern Malawi. Children aged less than five years old; with severe anaemia were screened and enrolled. Each child was followed up for eighteen months at one, three, six, twelve and eighteen months after enrolment. Data were analysed using STATA 15. RESULTS: Between July 2002 and July 2004, 382 severely anaemic children were enrolled in the main study. A total of 52 children were excluded due to missing anthropometric data. Out of the 330 included, 53 children were moderately to severely malnourished and 277 were not. At the end of the 18-month follow period, 28.3% of children with MAM/SAM died compared to 13% of children without MAM/SAM (RR 2.1, CI 0.9-4.2, p = 0.03). Similarly, children with moderate to severe malnutrition reported a significantly higher number of malaria infection cases (33.9%) compared to children with severe anaemia alone (27.9%, p = 0.02). However, the number of hospitalizations and recurrence of severe anaemia was similar and not statistically significant between the two groups (RR 0.8 (0.4-1.4), p = 0.6 and RR 1.1 (0.3-2.8), p = 0.8). CONCLUSION: Among children with severe anaemia, those who also had moderate to severe malnutrition had a twofold higher risk of dying compared to those who did not. It is therefore crucial to investigate acute malnutrition among severely anaemic children, as this might be treatable factor associated with high mortality.

Adherence to community versus facility-based delivery of monthly malaria chemoprevention with dihydroartemisinin-piperaquine for the post-discharge management of severe anemia in Malawian children: A cluster randomized trial.

BACKGROUND: The provision of post-discharge malaria chemoprevention (PMC) in children recently admitted with severe anemia reduces the risk of death and re-admissions in malaria endemic countries. The main objective of this trial was to identify the most effective method of delivering dihydroartemesinin-piperaquine to children recovering from severe anemia. METHODS: This was a 5-arm, cluster-randomized trial among under-5 children hospitalized with severe anemia at Zomba Central Hospital in Southern Malawi. Children were randomized to receive three day treatment doses of dihydroartemesinin-piperaquine monthly either; 1) in the community without a short text reminder; 2) in the community with a short message reminder; 3) in the community with a community health worker reminder; 4) at the facility without a short text reminder; or 5) at the facility with a short message reminder. The primary outcome measure was adherence to all treatment doses of dihydroartemesinin-piperaquine and this was assessed by pill-counts done by field workers during home visits. Poisson regression was utilized for analysis. RESULTS: Between March 2016 and October 2018, 1460 clusters were randomized. A total of 667 children were screened and 375 from 329 clusters were eligible and enrolled from the hospital. Adherence was higher in all three community-based compared to the two facility-based delivery (156/221 [70·6%] vs. 78/150 [52·0%], IRR = 1·24,95%CI 1·06-1·44, p = 0·006). This was observed in both the SMS group (IRR = 1·41,1·21-1·64, p<0·001) and in the non-SMS group (IRR = 1·37,1·18-1·61, p<0·001). Although adherence was higher among SMS recipients (98/148 66·2%] vs. non-SMS 82/144 (56·9%), there was no statistical evidence that SMS reminders resulted in greater adherence ([IRR = 1·03,0·88-1·21, p = 0·68). When compared to the facility-based non-SMS arm (control arm), community-based delivery utilizing CHWs resulted in higher adherence [39/76 (51·3%) vs. 54/79 (68·4%), IRR = 1·32, 1·14-1·54, p<0·001]. INTERPRETATION: Community-based delivery of dihydroartemesinin-piperaquine for post-discharge malaria chemoprevention in children recovering from severe anemia resulted in higher adherence compared to facility-based methods. TRIAL REGISTRATION: NCT02721420; ClinicalTrials.gov.