How do we know if a child died from malaria?

How many people die annually from malaria in the world? We don’t really know. In 2012, the Institute of Health Metrics and Evaluation (IHME) calculated global deaths to be 1.24 million, two times higher than the World Health Organisation (WHO) 2010 estimate of 655, 000 [1-2]. Discrepancies in estimates has been largely attributed to the use of verbal autopsies, which as malaria expert Bob Snow put it “is as good as flipping a coin for working out the causes of death” [3]. We know where the global malaria burden lies: 2024 estimates indicate that the WHO Region of Africa carried 95% of malaria deaths, with about three quarters of those deaths among children under five years [4].

There has been tremendous progress in the fight against malaria, including exciting scientific advancements benefiting African children that my colleague Pascal Omastone has been documenting in previous posts. However, assessing effectiveness of clinical and public health interventions requires valid estimates of malaria mortality, which begs the question: how do we know if a child has died from malaria?

in low and middle-income countries (LMICs), where the majority of deaths occur at home, there lacks robust Civil and Vital Registration Systems and clearly documented causes of death [5]. Comprehensive autopsies, the gold standard approach to attributing death, are generally not a viable option due to financial, infrastructural and cultural reasons [6]. Clinical reports and verbal autopsies are standard in LMICs but have limitations, especially if not used in conjunction with other tools for determining cause of death (COD). Clinical records contribute important information but often with errors due to limited diagnostic tools [6]. While high quality, standardized verbal autopsies can provide good population level assessments of COD, poorly done verbal autopsies lead to biased results, including misclassification [5-6]. While some COD can be easily captured by verbal autopsies, such as blunt force trauma, certain diseases are hard to capture due to overlapping syndromes. Malaria is a master masquerader. 

Malaria can be hard to distinguish from other common illnesses, such as pneumonia, meningitis and sepsis [7]. It is notably difficult among children under five years old, due to their non-specific symptoms (e.g. fevers, drowsiness) that cannot be articulated in the same manner as an adult or an older child. Furthermore, even a child with parasitemia in an endemic area may not necessarily be severely ill with or die from malaria. A study of 31 autopsies of children in Malawi who had clinical diagnoses of malaria found that 23% had died from other causes [8]. How can better results be achieved in a feasible, cost-effective manner?

Minimally invasive autopsies (MIAs), also known as minimally invasive tissue sampling (MITS) and simplified MIAs were developed by a collaboration between researchers at the Barcelona Institute for Global Health (ISGlobal) in Spain and the Manhiça Health Research Centre (CISM) in Mozambique. MIAs sample key organs using specialised biopsy needles to extract fluids and tissue fragments, followed by microbiological and histological analyses yielding a relatively safe, quick, simple and non-disfiguring investigation of causes of death [6]. Simplified MIAs provide cost-effective approaches that are feasible to implement in poor resource contexts, using strategies, such as avoiding high technology imaging and focusing on specific organs [9-10]. MIAs provide valid evidence on COD, particularly for cases related to infectious diseases, including malaria [9,11]. However, MIAs (which should be done following 24 hours after a death) are used largely in hospital-related deaths. While verbal autopsies can be done at large scale MIAs remain limited in scope and depend on local resources and capacities. There lies a methodological conundrum: how to expand the reach of valid assessments of COD?

Over the last ten years, collaborative efforts have aimed to expand capacities, scope and systems for conducting MIAs, such as the MITS Surveillance Alliance. In addition, multi-disciplinary, multi-tool approaches are being used for determining COD, through national efforts, such as the University of Witwatersrand in South Africa and multi-country initiatives, such as CHAMPS. MIAs are also being used to develop more robust verbal autopsy questionnaires by IHME and others. Finally, AI is increasingly used across all types of COD approaches to improve power and accuracy.

Methods matter. Especially for poor and subaltern children whose health needs tend to be extensive, complex and understudied. The development of tools for measuring death may not be considered the most glamourous sector of global health yet it is vital and requires continued investments. This information will guide effective policies to reduce Africa’s burden of child mortality from malaria and other causes. We also need to be able to tell a parent why their child died.

Hero image: Image courtesy of the ASH Image Bank. © American Society of Hematology.

References

1. Murray C.J., Rosenfeld L.C., Lim S.S., Andrews K.G., et al. (2012). Global malaria mortality between 1980 and 2010: a systematic analysis. The Lancet, 379:413-31. doi: 10.1016/S0140-6736(12)60034-8.

2. WHO (2010). World malaria report. Geneva: WHO. Available online: https://www.who.int/publications/i/item/9789241564106 (accessed June 30, 2026).

3. Cormier, Z. (2012). Malaria death toll disputed. Nature. doi:10.1038/nature.2012.9974

4. World Health Organization (2025). Malaria. Available from: https://www.who.int/news-room/fact-sheets/detail/malaria [accessed July 6, 2026].

5. Garenne M., Fauveau V. (2006). Potential and limits of verbal autopsies. Bulletin of the World Health Organsation, 84(3):164.

6. Bassat, Q., Castillo, P., Alonso, P. L., Ordi, J., & Menéndez, C. (2016). Resuscitating the Dying Autopsy. PLoS medicine, 13(1), e1001927. https://doi.org/10.1371/journal.pmed.1001927

7. Gwer, S., Newton, C. R., & Berkley, J. A. (2007). Over-diagnosis and co-morbidity of severe malaria in African children: a guide for clinicians. The American journal of tropical medicine and hygiene, 77(6 Suppl), 6–13.

8. Taylor, T. E., Fu, W. J., Carr, R. A., Whitten, R. O., et al. (2004). Differentiating the pathologies of cerebral malaria by postmortem parasite counts. Nature medicine, 10(2), 143–145. https://doi.org/10.1038/nm986

9. Castillo, P., Martínez, M. J., Ussene, E., Jordao, D., et al. (2016). Validity of a minimally invasive autopsy for cause of death determination in adults in Mozambique: an observational study. PLoS medicine, 13(11), e1002171. https://doi.org/10.1371/journal.pmed.1002171

10. Peñuelas, N., Saco, A., Hurtado, J. C., Marimon, L., et al. (2025). Diagnostic accuracy of a simplified minimally invasive tissue sampling protocol for stillbirths in low-resource settings. BMJ global health, 10(10), e018380. https://doi.org/10.1136/bmjgh-2024-018380.

11. Rakislova N., Jordao D., Ismail M.R., et al. (2021). Accuracy of verbal autopsy, clinical data and minimally invasive autopsy in the evaluation of malaria-specific mortality: an observational study. BMJ Global Health; 6(6):e005218. doi: 10.1136/bmjgh-2021-005218.