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Using minimally invasive autopsies in developing countries to determine infectious cause of death

January 04 2016

In developing countries, data on the aetiology of fatal infections is scarce, despite the high level of mortality associated with infectious diseases. Understanding which microorganisms are involved is a vital step in the development of effective preventative treatment such as vaccines, as well as improved treatment guidelines. In a recent study, Martinez et al. (2015) analysed thirty minimally invasive autopsies (MIAs) in order to develop and validate protocols for microbiological analysis in post-mortem samples. MIA is a proposed alternative to complete diagnostic autopsy (CDA), which remains the gold standard for the investigation of the cause of death. The MIA procedure differs significantly to the CDA procedure. For example, tissue samples during a CDA are obtained after evisceration of the body, whereas in the MIA procedure, the tissues are obtained through percutaneous puncture, obtaining a biopsy of target organs using specific needles. Though more research is required, in some studies MIA has been shown to have comparable results to CDA. In developing countries, where CDA may not be possible, MIA appears to be a promising alternative.

Removal of tissue using a minimally invasive autopsy (image from sciencemag feature 'Cause of Death' By Sam Keane)

The MIA protocol used in this study included the collection of samples for histological analysis and samples for microbiological analysis. Microbiological tests included universal screening for HIV, hepatitis B and C viruses, Plasmodium falciparum; bacterial/fungal culture; nucleic acid extraction and molecular assays. 14 of the 30 cases were diagnosed as having an infectious cause of death (ICoD) by the histological analysis, including 6 meningoencephalitis, 3 pyogenic pneumonia, 3 disseminated necrotizing granulomatosis, 1 pneumocystis pneumonia and 1 cryptococcal septicaemia. 2 further ICoD were identified by the microbiological analysis: 1 Streptococcus dysgalactiae septicaemia and 1 cerebral toxoplasmosis. Overall, the MIA procedure identified 17 out of 19 infectious deaths (89.5%). The two cases missed were further identified as necrotizing pneumonia due to adenovirus and meningoencephalitis due to M. tuberculosis by molecular testing of the CDA samples – suggesting that the MIA samples from these cases were probably not collected from infected tissue areas.

The results showed that a combination of standard culture and molecular assays allows the detection of an etiological agent in the majority (89%) of infectious deaths. The high diversity of aetiologies highlights the need for multiple samples and extensive microbiological investigations. It is important to note that when comparing molecular vs culture-based results, the majority of diagnoses were obtained by molecular assays. This could be due to the better performance of these techniques as well as the fact that most pathogens causing death in the 30 cases described were either not culturable, or required specific, non-cost-effective culture conditions.

In summary, the sampling scheme used in the MIA procedure, and the combination of tissue sampling and classical microbiology with molecular assays were shown to be a valid and powerful tool to investigate the aetiology of fatal infections. The authors note that their protocols could provide a detailed description of the ICoD in developing regions and have an impact in future public health interventions.

Original Article