Prevention of treatment abandonment remains an important challenge to increase survival of Wilms tumor in sub-Saharan Africa: A report from Wilms Africa-CANCaRe Africa.

BACKGROUND: The Wilms Africa studies implemented an adapted Wilm's tumor (WT) treatment protocol in sub-Saharan Africa in two phases. Phase I began with four sites and provided out-of-pocket costs. Phase II expanded the number of sites, but lost funding provision. Objective is to describe the outcomes of Phase II and compare with Phase I. METHODS: Wilms Africa Phase I (n = 4 sites; 2014-2018) and Phase II (n = 8 sites; 2021-2022) used adapted treatment protocols. Funding for families' out-of-pocket costs was provided during Phase I but not Phase II. Eligibility criteria were age less than 16 years and newly diagnosed unilateral WT. We documented patients' outcome at the end of planned first-line treatment categorized as treatment abandonment, death during treatment, and disease-related events (death before treatment, persistent disease, relapse, or progressive disease). Sensitivity analysis compared outcomes in the same four sites. RESULTS: We included 431 patients in Phase I (n = 201) and Phase II (n = 230). The proportion alive without evidence of disease decreased from 69% in Phase I to 54% in Phase II at all sites (p = .002) and 58% at the original four sites (p = .04). Treatment abandonment increased overall from 12% to 26% (p < .001), and was 20% (p = .04) at the original four sites. Disease-related events (5% vs. 6% vs. 6%) and deaths during treatment (14% vs. 14% vs. 17%) were similar. CONCLUSION: Provision of out-of-pocket costs was important to improve patient outcomes at the end of planned first-line treatment in WT. Prevention of treatment abandonment remains an important challenge.

Prevalence, mortality, and aetiology of paediatric shock in a tertiary hospital in Malawi: A cohort study.

Shock is considered one of the most important mechanisms of critical illness in children. However, data on paediatric shock in sub-Saharan Africa is limited, which constrains development of effective treatment strategies. We aimed to describe the prevalence, mortality, and aetiology of paediatric shock in a tertiary hospital in Malawi. Children aged two months to 16 years presenting with shock (FEAST criteria; respiratory distress and/or impaired consciousness, and at least one sign of impaired circulation; capillary refill>3 seconds, cold extremities, weak pulse, or severe tachycardia) to the emergency department were included and followed-up prospectively using routinely collected data between February 2019 and January 2020. Prevalence, mortality and aetiology of shock were reported for both the FEAST criteria and World Health Organization (WHO) definition. The association between aetiology and mortality was assessed with univariable analysis. Of all screened admissions (N = 12,840), 679 (5.3%) children presented with shock using FEAST criteria and the mortality was 79/663 (11.9%). WHO-defined shock applied to 16/12,840 (0.1%) and the mortality was 9/15 (60.0%). Main diagnoses were viral/reactive airway diseases (40.4%), severe pneumonia (14.3%), gastroenteritis (11.3%) and presumed sepsis (5.7%). Children diagnosed with presumed sepsis and gastroenteritis had the highest odds of dying (OR 11.3; 95%-CI:4.9-25.8 and OR 4.4; 95%-CI:2.4-8.2). Considering the high mortality, prevalence of paediatric shock (FEAST and WHO definitions) in Malawi is high. Sepsis and gastroenteritis are diagnoses associated with poor outcome in these children. Consensus on a clinical meaningful definition for paediatric shock is essential to boost future studies.

Towards zero percent treatment abandonment of patients with common and curable childhood cancer types in Blantyre, Malawi.

BACKGROUND: Treatment abandonment is a common cause of treatment failure in low-income countries (LIC). We implemented a comprehensive package of interventions aiming to enable all families to complete the treatment of their child. The objective of this study was to evaluate the impact of those interventions. PROCEDURE: In this prospective and historically controlled study, we included all children younger than 16 years with a newly diagnosed common and curable cancer type (acute lymphoblastic leukaemia [ALL], Hodgkin disease, Wilms tumour, retinoblastoma and Burkitt lymphoma) admitted to the Queen Elizabeth Central Hospital in Blantyre, Malawi, between 1 June 1 2019 and 1 June 1 2020. Interventions to enable treatment completion included full funding of costs to the family (treatment, transport, accommodation and food in the hospital) and tracking of patients if they did not attend treatment appointments. The outcomes of patients were compared with those of a similar historical cohort. RESULTS: The intervention cohort of 150 patients were compared to 264 historical control patients. Treatment abandonment decreased significantly from 19% (49/264) to 7% (10/150) (p < .001). The proportion of patients with Wilms tumour, retinoblastoma or ALL alive without evidence of disease at the end of treatment increased from 38% (57/149) to 53% (44/83) (p = .03). CONCLUSION: A simple and relatively low-cost comprehensive intervention package with no costs for families, significantly decreased treatment abandonment. This strategy may increase survival of children with common and curable cancers in LIC, especially when coupled with improvements in access to treatment and quality of treatment, including supportive care.

The effects of malnutrition on cardiac function in African children.

OBJECTIVE: Cardiac dysfunction may contribute to high mortality in severely malnourished children. Our objective was to assess the effect of malnutrition on cardiac function in hospitalised African children. DESIGN: Prospective cross-sectional study. SETTING: Public referral hospital in Blantyre, Malawi. PATIENTS: We enrolled 272 stable, hospitalised children ages 6-59 months, with and without WHO-defined severe acute malnutrition. MAIN OUTCOME MEASURES: Cardiac index, heart rate, mean arterial pressure, stroke volume index and systemic vascular resistance index were measured by the ultrasound cardiac output monitor (USCOM, New South Wales, Australia). We used linear regression with generalised estimating equations controlling for age, sex and anaemia. RESULTS: Our primary outcome, cardiac index, was similar between those with and without severe malnutrition: difference=0.22 L/min/m(2) (95% CI -0.08 to 0.51). No difference was found in heart rate or stroke volume index. However, mean arterial pressure and systemic vascular resistance index were lower in children with severe malnutrition: difference=-8.6 mm Hg (95% CI -12.7 to -4.6) and difference=-200 dyne s/cm(5)/m(2) (95% CI -320 to -80), respectively. CONCLUSIONS: In this largest study to date, we found no significant difference in cardiac function between hospitalised children with and without severe acute malnutrition. Further study is needed to determine if cardiac function is diminished in unstable malnourished children.

Viral CNS infections in children from a malaria-endemic area of Malawi: a prospective cohort study.

BACKGROUND: Fever with reduced consciousness is an important cause of hospital admission of children in sub-Saharan Africa, with high mortality. Cerebral malaria, diagnosed when acute Plasmodium falciparum infection and coma are recorded with no other apparent reason, is one important cause. We investigated whether viruses could also be an important cause of CNS infection in such patients, and examined the relative contribution of viral pathogens and malaria parasitaemia. METHODS: We did a prospective cohort study in Blantyre, Malawi. From March 1, 2002, to Aug 31, 2004, we enrolled children aged between 2 months and 15 years who were admitted to hospital with suspected non-bacterial CNS infections. Children with a cerebrospinal fluid (CSF) white cell count of less than 1000 cells per µL and negative bacterial microscopy and culture were deemed to have suspected viral CNS infection. Blood was examined for asexual forms of P falciparum. PCR was done on CSF or on post-mortem brain biopsy specimens to detect 15 viruses known to cause CNS infection. FINDINGS: Full outcome data were available for 513 children with suspected viral CNS infection, of whom 94 (18%) died. 163 children (32%) had P falciparum parasitaemia, of whom 34 (21%) died. At least one virus was detected in the CNS in 133 children (26%), of whom 43 (33%) died. 12 different viruses were detected; adenovirus was the most common, affecting 42 children; mumps, human herpes virus 6, rabies, cytomegalovirus, herpes simplex virus 1, and enterovirus were also important. 45 (9%) of the 513 children had both parasitaemia and viral infection, including 27 (35%) of 78 diagnosed clinically with cerebral malaria. Children with dual infection were more likely to have seizures than were those with parasitaemia alone, viral infection only, or neither (p<0·0001). 17 (38%) of the 45 children with dual infection died, compared with 26 (30%) of 88 with viral infection only, 17 (14%) of 118 with parasitaemia only, and 34 (13%) of 262 with neither (p<0·0001). Logistic regression showed children with a viral CNS infection had a significantly higher mortality than did those who did not have a viral CNS infection (p=0·001). INTERPRETATION: Viral CNS infections are an important cause of hospital admission and death in children in Malawi, including in children whose coma might be attributed solely to cerebral malaria. Interaction between viral infection and parasitaemia could increase disease severity. FUNDING: Wellcome Trust, US National Institutes of Health, and UK Medical Research Council.