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Subspecialties Forensics, Profession, Clinical care, Training and education, Microbiology and immunology

A Simpler System

The complete diagnostic autopsy (CDA) is often considered the gold standard of death investigation. But in many situations, such an examination is not possible – for instance, when necessary facilities are lacking or in areas with cultural or religious taboos. Unfortunately, less invasive methods are not always possible in resource-limited settings either, because many of them rely on expensive equipment and techniques, or on the availability of highly trained professionals. And yet, the need for death investigation is greater than ever in such settings – so what can be done to balance the importance of conducting such investigations against the difficulty in doing so? The answer lies in a simplified method of minimally invasive autopsy that requires less time, less training and less overall effect on the subject of the examination.

Figure 1. a) Blood sampling through supraclavicular puncture; b) tissue sampling with biopsy needle; c) formalin jar with tissue sample; d) H&E stain of MIA sample; e) MIA brain tissue showing severe cryptococcal infection; f) massive Plasmodium falciparum parasitization of erythrocytes in brain capillaries.

What is minimally invasive autopsy?

As the name suggests, a minimally invasive autopsy (MIA) aims to minimize the impact of the pathological examination on the body. The MIAs developed by our team are specifically designed for low- and middle-income areas with limited trained personnel and resources. In general, MIAs in high-income countries involve highly sophisticated imaging techniques, such as magnetic resonance or CT scan, combined with directed biopsies. Our simplified MIA procedure (see Figure 1) begins with a careful disinfection of the body surface (1),(2), after which we collect blood and cerebrospinal fluid samples and perform blind puncture of solid organs such as the liver, lungs, heart, and central nervous system using biopsy needles. Finally, we apply histological and microbiological techniques to analyze the samples.

Compared with the CDA, the MIA is much simpler and does not require a fully trained pathologist; medical agents, nurses, or even trained technicians can perform MIAs of adequate quality, which is a major advantage in many low- and middle-income countries. Additionally, the minimally invasive approach and strict disinfection offer some advantages in the realm of infectious disease. Indeed, those features allow a good assessment of the microorganisms present on the body, something seldom possible in the CDA because of the high contamination rate that ensues from dissection. Finally, MIA is a non-disfiguring technique and more rapidly completed than CDA, which represents a significant advantage in many cultural environments. Indeed, our team’s socio-behavioral studies indicate that MIA is more acceptable than CDA in a range of different geographical, cultural and religious communities.

When should it be used?

MIA has shown high accuracy for disseminated neoplasms, as well as in infectious disease diagnosis. One of its most notable advantages is that it allows the identification of the specific microorganisms causing mortality – meaning that it could significantly improve our understanding of causes of death in areas and age groups where infectious diseases are common (3)(4)(5). On the other hand, MIA is less accurate for some non-infectious illnesses, such as cardiovascular or digestive diseases, and for identifying internal malformations in the perinatal group. Our team is now working on new procedures to increase the tool’s accuracy in such cases.

MIA, as it currently stands, has one major caveat – it is still a costly procedure. Biopsy needles are very expensive, and in cases where infectious disease is the suspected cause of death, the technique requires molecular microbiological analyses to accurately identify the causative microorganism. The real obstacle here is that these tests necessitate frozen tissue, which is logistically complex in many settings. We haven’t found a good way around that yet – but we are analyzing the value of each specific sample and test to optimize and reduce the protocol.

With so many obstacles, why conduct autopsies?

Autopsies have a long history of correcting, clarifying and confirming ante-mortem clinical diagnosis. They help physicians improve their medical knowledge and ultimately lead to a higher rate of accurate clinical diagnoses. Despite the many diagnostic advances of recent decades, clinico-pathological discrepancies are relatively frequent even in high-resource settings with sophisticated laboratory and imaging techniques. Such inaccuracies occur at even higher rates in low-income countries, where pre-mortem diagnostic support is often very limited (6).

However, the value of the autopsy doesn’t end in the clinic; they are also an indispensable research tool. Many advances in medicine have been made possible through post-mortem examinations, including the investigation of emerging infections, genetic or metabolic diseases, or transplant-associated lesions. The routine practice of autopsies also offers an important epidemiological window to the health status of populations – vital in any country, but especially those with endemic infections and unevenly distributed access to medical care. For all of these reasons, I think increasing the number of autopsies performed in resource-limited settings can significantly impact medical practice and provide valuable research and epidemiological data to improve the health of their populations.

What’s unique about the settings in which you practice?

One interesting aspect is the difference in customs and practices surrounding death. Implementation of any post-mortem procedure in areas where such examinations are uncommon requires a profound understanding of what is culturally and religiously acceptable. Data from previous studies suggests that CDA has a low acceptability in many settings. When designing the project, we hypothesized that MIA would be more readily accepted than CDA – and we were right. We recently conducted a study in five distinct settings in Africa and Asia with different cultural and religious backgrounds: Gabon, Kenya, Mali, Mozambique, and Pakistan. The study revealed that over 70 percent of the participants interviewed would want to know the cause of death, and would be willing to have MIA performed on a relative, if this were requested in a real-world situation (7). Importantly, this was also the case for individuals who had recently experienced the death of a relative. Thus, MIA seems to be acceptable in places where post-mortem procedures were previously believed to be unfeasible.

Early community engagement, transparency and accuracy in terms of the information provided to family and community members are key for enhancing community acceptability of any procedure, but MIA in particular. Guaranteeing the necessary sensitivity and human rapport from health professionals when asking for consent and performing the MIA is also crucial – and a good example of where pathologists really do need to step out of the laboratory and connect.

Things are somewhat easier medically than they are culturally. Although some training on how to handle the small samples obtained during MIA is highly desirable, the histological processing only requires basic pathology lab tools, which are available – at least in tertiary hospitals – in most low-income countries. Transportation of the histological samples is also quite simple; for the most part, no special conditions are needed. The sole notable exception to this is infectious disease diagnosis; the accurate identification of causative microorganisms requires frozen tissue, which implies serious logistical difficulties in terms of storage and transportation. It also requires a central laboratory able to conduct complex molecular microbiological analyses, facilities that are scarce in most low-income countries and therefore overwhelmed by routine clinical work.

How can other pathologists get started with MIA?

As part of our research project funded by the Bill and Melinda Gates Foundation, we have developed a training and research center on post-mortem activities (TRePMA Center) with two aims: i) to promote the use of MIA in middle and low-income countries, and ii) to help scientists and pathologists include MIA in their research projects and activities. The center provides theoretical and practical training on how to conduct MIAs, together with guidance related to the essential pathological procedures required for preparation and interpretation of samples. The TRePMA Centre headquarters are located in Barcelona, Spain, and Maputo, Mozambique, and each conducts several courses a year on MIA procedure and sample processing. We have also put special effort into developing both technical and human resources in local pathology departments and into stimulating collaborative training and research activities. We also assess the socio-behavioral component of the implementation process; we find that it is critically important to put into place locally tailored recommendations before and during the introduction of MIA procedures.

In recent decades, we have witnessed a continuous decline in the use of CDA in most settings. Although the causes of this decline are multifactorial, one major barrier is the difficulty of obtaining consent from family members (8)(9). Over the last few years, we’ve seen increased interest in the use of imaging-based methods, such as magnetic resonance imaging, computerized scanning, or ultrasounds, to replace the CDA; these procedures can be complemented by imaging-directed biopsies when necessary. Such methods are noninvasive, highly acceptable to the general public, and can accurately identify many morbid conditions. The impetus to adopt them seems clear – but their elevated costs and reliance on sophisticated equipment and skilled personnel are critical limitations for their widespread introduction, particularly in low- and middle-income countries.

I believe that the use of autopsy – or robust substitutes – needs to be encouraged as a mechanism for the continuous improvement of clinical diagnosis and as a complement for cause-of-death investigation and surveillance. Though the many challenges for the feasibility of conventional autopsies in low- and middle-income countries are not likely to be overcome in the short-term, methods like MIA could easily be implemented on a wider scale. Such a process, coupled with programs to build the capacity of local pathologists, can increase our understanding of the diseases causing death in areas where this information is typically very limited.

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  1. P Castillo et al., “Pathological methods applied to the investigation of causes of death in developing countries: minimally invasive autopsy approach”, PLoS One, 10, e0132057 (2015). PMID 26126191.
  2. MJ Martínez et al., “Infectious cause of death determination using minimally invasive autopsies in developing countries”, Diagn Microbiol Infect Dis, 84, 80–86 (2016). PMID: 26508103.
  3. P Castillo et al., “Validity of a minimally invasive autopsy for cause of death determination in adults in Mozambique: an observational study”, PLoS Med, 13, e1002171 (2016). PMID: 27875530.
  4. Q Bassat et al., “Validity of a minimally invasive autopsy tool for cause of death determination in pediatric deaths in Mozambique: an observational study”, PLoS Med, 14, e1002317 (2017). PMID: 28632739.
  5. C Menendez et al., “Validity of a minimally invasive autopsy for cause of death determination in stillborn babies and neonates in Mozambique: an observational study”’ PLoS Med, 14, e1002318 (2017). PMID: 28632735.
  6. J Ordi et al., “Clinico-pathological discrepancies in the diagnosis of causes of maternal death in sub-Saharan Africa: retrospective analysis”, PLoS Med, 6, e1000036 (2009). PMID: 19243215.
  7. M Maixenchs et al., “Willingness to know the cause of death and hypothetical acceptability of the minimally invasive autopsy in six diverse African and Asian settings: a mixed methods socio-behavioural study”, PLoS Med, 13, e1002172 (2016). PMID: 27875532.
  8. Q Bassat et al., “Resuscitating the dying autopsy”, PLoS Med, 13, e1001927 (2016). PMID: 26756992.
  9. Q Bassat et al., “Development of a post-mortem procedure to reduce the uncertainty regarding causes of death in developing countries”, Lancet Glob Health, 1, e125–e126 (2013). PMID: 25104253.
About the Author
Jaume Ordi

Research Professor at the ISGlobal Barcelona Institute for Global Health, Barcelona, Spain.

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