Despite improvements in the diagnosis and documentation of severe malaria cases, there remains uncertainty about the burden of severe malaria cases at the population level. Here we present a comprehensive estimate of severe malaria cases in children from 19 malaria-endemic countries in SSA. Our estimates are based on data from population-based household surveys that allow severe malaria cases outside of the formal healthcare system to be directly captured in estimates.
The prevalence estimate of severe malaria in this study (4.5% of malaria-infected children) is consistent with other estimates of severe malaria. This acknowledges that other estimates of severe malaria cases account only for children who access the formal healthcare system [1, 12]. Household surveys test all children age 6–59 months for malaria, and while some of the children who were showing signs of severe illness would have eventually accessed the formal healthcare system, some of these children would have died, recovered at home, or received care outside of the formal healthcare system [7, 9, 12–14]. Estimating severe malaria through household surveys provides countries with a standardized estimate of severe malaria that is comparable across time as well with other countries.
Findings from this study confirm previous observations that severe malaria is dependent on age and transmission intensity [5–8]. Younger children were significantly more likely to have severe malaria, and although not significant, the risk of severe malaria was greater in high malaria transmission zones. However, unlike previous research, we did not find an interaction between age and the intensity of malaria transmission in relation to having at least one symptom of severe malaria (data not shown) . One explanation is the limited age range of children (6–59 months) in this analysis. Past studies that have examined the association of variations in age and endemicity on the clinical manifestation of severe malaria included children up to age 10 [5, 6, 8].
Children surveyed between 2015–2018 were significantly less likely to have severe malaria symptoms as compared to children surveyed between 2011–2015. This is controlling for malaria transmission level and is irrespective of variations in malaria prevalence since all children included in the analysis were positive for malaria, according to RDT. This finding aligns with the 2019 World Malaria Report, which reported a decrease in malaria deaths since 2010 . While the role of malaria control interventions in this difference cannot be assumed, since 2015, there has been an increase in the number of malaria interventions in SSA, including the implementation of seasonal malaria chemoprevention and universal coverage of insecticide-treated nets . The impact of these interventions on severe malaria cases needs further exploration.
This analysis also indirectly highlights potential variation in care-seeking patterns for severe malaria cases across SSA. Urban children were significantly more likely to have at least one severe malaria symptom as compared to rural children despite a higher prevalence of severe malaria among the rural population. In addition, the country was highly significant in the model even when controlling for malaria endemicity. By examining severe malaria cases at the household level, this analysis is more likely to include children whose caregivers have taken them to a healthcare facility but whose illness did not resolve or have not sought care for the child’s illness. While the decision to seek care is ultimately decided by the caregiver, it is highly influenced by factors such as the availability of government-based facilities, country wealth, cost of care, and education[14, 20–23]. Further exploration is needed into country and urban-rural variations in care-seeking and its association with severe malaria burden estimates.
This study has a several limitations. Children with severe malaria frequently develop one or more complications, including severe anemia, respiratory distress, or cerebral malaria. This analysis examined children who had at least one symptomatic marker for severe malaria. We did not disaggregate this analysis by proxies for respiratory distress or cerebral malaria. Examining severe anemia is possible because this is a discrete diagnosis based on hemoglobin levels. However, to fully disaggregate by respiratory distress or cerebral malaria would require additional questions about symptoms such as prostration and the number and severity of convulsions .
The use of household-level data is a noteworthy advantage of this study, but it also introduces a principal limitation. There is a risk of including uncomplicated malaria cases or non-malaria cases in our proxy definition. Malaria positivity is based on RDT-detectable antigens that continue to circulate in the blood after the infection has cleared, and severe malaria symptoms are non-specific . Our definition of severe malaria relies on caregiver self-report rather than a diagnosis by a clinician at a health facility. Although the interviewer for the biomarker questionnaire is a trained biomarker health technician (usually a nurse), which may improve the questionnaire responses, the non-specific nature of severe malaria remains an issue. We have addressed this limitation by narrowing the proxy definition of severe malaria to only examine loss of consciousness, rapid breathing, seizures, or severe anemia (hemoglobin < 5 g/dL adjusted for altitude). These symptoms are more distinct than some other symptoms (extreme weakness and heart problems) caregivers are asked and most closely align with the WHO clinical manifestations of severe malaria. We assumed these symptoms would not be confused by caregivers, even those with a limited education. However, we were unable to examine the reliability of reported signs and symptoms because caregivers were not asked questions on severe malaria symptoms for malaria negative children. In addition, by limiting our definition of severe malaria symptoms, there is the possibility that we may be missing cases.
This analysis only includes children with malaria according to RDT, which further minimizes the possibility that the child is sick with an illness other than severe malaria. However, as noted above, there is still a risk of including non-malaria cases in our proxy definition because malaria positivity is based on RDT-detectable antigen that circulates in the blood after the infection has cleared. More sensitive measures of malaria diagnosis than standard HRP-II RDTs should be explored, such as microscopy, highly sensitive RDTs, or polymerase chain reaction (PCR).