Accuracy of verbal autopsy, clinical data and minimally invasive autopsy in the evaluation of malaria-specific mortality: an observational study

Abstract

Background: Global malaria mortality estimates are hindered by the low reliability of the verbal autopsy (VA) and the clinical records, the most common sources of information used to estimate malaria-specific mortality. We aimed to determine the accuracy of these tools, as well as of the minimally invasive autopsy (MIA), a needle-based postmortem sampling method, to identify malaria-specific mortality in a large series of deceased patients from Mozambique, using complete autopsy as the gold standard.

Methods: Observational study that included 264 deaths, occurring at a tertiary level hospital in Mozambique, from 1 November 2013 to 31 March 2015 (17 months-long period). Clinical data were abstracted, a computer coded VA was completed using the clinical data as source of information, and an MIA followed by a complete autopsy were performed. Screening for malaria infection was conducted postmortem to all participants using molecular and histological techniques (PCR and immunohistochemistry).

Findings: Malaria infection was considered the cause of death in 6/264 (2.3%) cases: 2/54 children (3.7%, both less than 5 years old) and 4/57 (7.0%) maternal deaths. The sensitivity and specificity of the VA, the clinical data and the MIA to identify malaria-specific deaths were 33.3% and 96.1%, 66.7% and 96.1%, and 100% and 100%, respectively. In addition, malaria was identified as a possible contributor in 14 additional patients who died of other diseases. These cases were also accurately identified by the MIA (sensitivity 82.4%, specificity 100%).

Interpretation: The high sensitivity and specificity of the MIA in identifying malaria may help to improve current estimates of malaria-specific mortality in endemic areas.

Keywords: diseases; disorders; infections; injuries; malaria.

Figure 1

Massive sequestration of Plasmodium falciparum infected erythrocytes in the capillaries of the central nervous system. (A) Cortical vessel showing many parasitised erythrocytes (200×). (B) High power field of single capillaries showing massive parasitised erythrocytes adherent to the endothelium (1000×). Clear haemozoin pigment dots are clearly seen in almost all parasites, indicating that are mature forms. (C) Lung, showing abundant parasitised erythrocytes in the septal capillaries (200×). (D) Spleen showing abundant parasitised erythrocytes in the sinusoids of the red pulp. (E) Liver showing abundant parasitised erythrocytes in the sinusoids (200×). (A–E) Immunohistochemical stain, polyclonal rabbit anti-P. falciparum HPRT1/HPRT antibody. (F) Past malaria with abundant macrophages with malarial pigment in the portal tracts (H&E, 200×).