Hepatic mitochondrial and peroxisomal alterations in acutely ill malnourished Malawian children: A postmortem cohort study.

Objectives: To describe and compare liver mitochondrial and peroxisomal histopathology by nutritional status in children who died following hospitalization for acute illness in Malawi. Methods: Liver tissue was collected using Minimally Invasive Tissue Sampling from eleven children under-five years old who died during hospitalization and were either non-wasted (n = 4), severely wasted (n = 4) or had edematous malnutrition (n = 3). Histology was assessed on hematoxylin and eosin stained slides. Mitochondrial and peroxisomal ultrastructural features were characterized using electron microscopy (EM) and immunofluorescence (IF). Results: Hepatic steatosis was present in 50 % of non-wasted and severely wasted children and all children with edematous malnutrition. Edematous malnutrition was associated with 56 % and 45 % fewer mitochondria than severe wasting (p < 0.001) and no wasting (p = 0.006), respectively, and abnormal mitochondrial morphology compared to severe wasting (p = 0.002) and no wasting (p = 0.035). Peroxisomal abundance was reduced in edematous malnutrition compared to severe wasting (p = 0.005), but did not differ from no-wasting. Conclusion: Edematous malnutrition is associated with reduced abundance and altered morphology of hepatic mitochondria and peroxisomes. Interventions targeting improvements in hepatic metabolic function may be beneficial in improving metabolism and reducing mortality in children with severe malnutrition, particularly in those with nutritional edema.

Psychosis Recovery Orientation in Malawi by Improving Services and Engagement (PROMISE) protocol.

Malawi has a population of around 20 million people and is one of the world's most economically deprived nations. Severe mental illness (largely comprising psychoses and severe mood disorders) is managed by a very small number of staff in four tertiary facilities, aided by clinical officers and nurses in general hospitals and clinics. Given these constraints, psychosis is largely undetected and untreated, with a median duration of untreated psychosis (DUP) of around six years. Our aim is to work with people with lived experience (PWLE), caregivers, local communities and health leaders to develop acceptable and sustainable psychosis detection and management systems to increase psychosis awareness, reduce DUP, and to improve the health and lives of people with psychosis in Malawi. We will use the UK Medical Research Council guidance for developing and evaluating complex interventions, including qualitative work to explore diverse perspectives around psychosis detection, management, and outcomes, augmented by co-design with PWLE, and underpinned by a Theory of Change. Planned deliverables include a readily usable management blueprint encompassing education and community supports, with an integrated care pathway that includes Primary Health Centre clinics and District Mental Health Teams. PWLE and caregivers will be closely involved throughout to ensure that the interventions are shaped by the communities concerned. The effect of the interventions will be assessed with a quasi-experimental sequential implementation in three regions, in terms of DUP reduction, symptom remission, functional recovery and PWLE / caregiver impact, with quality of life as the primary outcome. As the study team is focused on long-term impact, we recognise the importance of having embedded, robust evaluation of the programme as a whole. We will therefore evaluate implementation processes and outcomes, and cost-effectiveness, to demonstrate the value of this approach to the Ministry of Health, and to encourage longer-term adoption across Malawi.

Primary motivations for and experiences with paediatric minimally invasive tissue sampling (MITS) participation in Malawi: a qualitative study.

OBJECTIVE: To understand family member consent decision-making influences and experiences in Malawi in order to inform future minimally invasive tissue sampling (MITS) studies. DESIGN: Qualitative study. SETTING: Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi, which serves as the central referral hospital for southern Malawi and where MITS participants were recruited from. PARTICIPANTS: Families of paediatric MITS participants. METHODS: We conducted in-depth interviews with 16 families 6 weeks after the death of paediatric MITS participants. Data were analysed using a combination of thematic content and theoretical framework approaches to explain the findings. RESULTS: Improved cause of death (CoD) ascertainment was the principal motivator for participation to protect remaining or future children. Community burial norms, religious doctrine and relationships with healthcare workers (HCWs) were not reported influencers among family members who consented to the procedure. Primary consenters varied, with single mothers more likely to consent independently or with only female family members present. Clear understanding of MITS procedures appeared limited 6 weeks postprocedure, but research was described as voluntary and preconsent information satisfactory for decision-making. Most families intended to share about MITS only with those involved in the consent process, for fear of rumours or judgement by extended family members and the wider community. CONCLUSION: Among those who consented to MITS, decision-making was informed by individual and household experiences and beliefs, but not by religious affiliation or experiences with HCWs. While understanding of the MITS procedure was limited at the time of interview, families found informed consent information sufficient for decision-making. Future MITS studies should continue to explore information presentation best practices to facilitate informed consent during the immediate grieving period.

Hypothetical acceptability of hospital-based post-mortem pediatric minimally invasive tissue sampling in Malawi: The role of complex social relationships.

BACKGROUND: Child mortality rates remain unacceptably high in low-resource settings. Cause of death (CoD) is often unknown. Minimally invasive tissue sampling (MITS)-using biopsy needles to obtain post-mortem samples-for histopathological and microbiologic investigation is increasingly being promoted to improve child and adult CoD attribution. "MITS in Malawi" is a sub-study of the Childhood Acute Illness & Nutrition (CHAIN) Network, which aims to identify biological and socioeconomic mortality risk factors among young children hospitalized for acute illness or undernutrition. MITS in Malawi employs standard MITS and a novel post-mortem endoscopic intestinal sampling approach to better understand CoD among children with acute illness and/or malnutrition who die during hospitalization. AIM: To understand factors that may impact MITS acceptability and inform introduction of the procedure to ascertain CoD among children with acute illness or malnutrition who die during hospitalization in Malawi. METHODS: We conducted eight focus group discussions with key hospital staff and community members (religious leaders and parents of children under 5) to explore attitudes towards MITS and inform consent processes prior to commencing the MITS in Malawi study. We used thematic content analysis drawing on a conceptual framework developed from emergent themes and MITS acceptability literature. RESULTS: Feelings of power over decision-making within the hospital and household, trust in health systems, and open and respectful health worker communication with parents were important dimensions of MITS acceptability. Other facilitating factors included the potential for MITS to add CoD information to aid sense-making of death and contribute to medical knowledge and new interventions. Potential barriers to acceptability included fears of organ and blood harvesting, disfigurement to the body, and disruption to transportation and burial plans. CONCLUSION: Social relationships and power dynamics within healthcare systems and households are a critical component of MITS acceptability, especially given the sensitivity of death and autopsy.

Implementing an mhGAP-based training and supervision package to improve healthcare workers' competencies and access to mental health care in Malawi.

BACKGROUND: It is now well established that the integration of mental health care into primary care is one of the most effective ways of reducing the substantial treatment gap for mental disorders which exists in most low- and middle-income countries. This study set out to determine whether a Mental Health Gap Action Programme (mhGAP) training and supervision package could be contextualised and implemented within the existing health care system in five districts in Southern Malawi. In addition, the study assessed the feasibility of holding community awareness events and establishing peer support groups in each district to further improve the access of the population to evidence-based mental health care. METHODS: A lead training team of experienced Malawian mental health professionals was appointed and mhGAP training materials were contextualised for use in Malawi. The lead team delivered a 4-day training package to district mental health teams in five districts covering three core conditions: psychosis, moderate-severe depression, and alcohol and substance use disorders. District mental health teams then delivered a 2-day training package and provided monthly supervision for 3 months to 500 non-specialist healthcare workers. Paired sample t-tests were used to compare knowledge, confidence and attitude scores before and immediately after training, and after 6 months in two districts. Case detection rates measured pre- and post-training in the pilot district were compared using Wilcoxon Rank Sum Test. Community awareness events were held and peer support groups were established in each of the five districts. The acceptability of the package was assessed through focus group discussions involving specialist and non-specialist healthcare workers, users and carers. RESULTS: Non-specialist healthcare workers' knowledge and confidence scores significantly increased immediately after training in comparison to pre-training. These scores were maintained at 6 months. However, no statistically significant change in attitude scores was detected. Case detection rates increased immediately after the training in comparison to pre-training. Responses from focus group discussion participants illustrated the programme's acceptability. CONCLUSIONS: This study demonstrated that, with minimal additional funding and working within existing structures, an mhGAP based training at primary and secondary health care levels is feasible in Southern Malawi.

Simple Screening Tool to Help Identify High-Risk Children for Targeted HIV Testing in Malawian Inpatient Wards.

BACKGROUND: To meet global AIDS goals, pediatric HIV diagnosis must be strengthened. Provider-initiated testing and counseling, which is recommended by the WHO, faces persistent implementation challenges in low-resource settings. Alternative approaches are needed. SETTING: Malawi has achieved high coverage of HIV diagnosis and treatment, but there are gaps among pediatric populations. This study assessed the sensitivity and specificity of a brief screening tool to identify at-risk pediatric patients for targeted HIV testing in Malawi. METHODS: A tool containing 6 yes/no items was used for children (aged 1-15 years) in the inpatient pediatric wards at 12 hospitals in Malawi (July 2016-July 2017). Questions were based on an established tool, translated to Chichewa, and implemented by HIV diagnostic assistants. All participating children were provided HIV testing and counseling per Ministry of Health guidelines. Analysis estimated the tool's characteristics including sensitivity, specificity, negative, and positive predictive values. RESULTS: HIV prevalence among the 8602 participants was 1.1% (n = 90). Children with a screening tool score of 1 had double the odds of being HIV positive than those with a score of 0. Frequent sickness was the most sensitive predictor of HIV status (55.1%), and having a deceased parent was the most specific (96.7%). False classification of HIV-negative status was rare (n = 14) but occurred more often among boys and younger children. CONCLUSIONS: A brief screening tool for pediatric inpatients helped target HIV testing in those most at risk in a low-pediatric-prevalence, resource-constrained setting. Future research should include a direct, rigorous comparison with PITC including comparative effectiveness, efficiency, and cost effectiveness.