Project: Validity of minimally invasive tissue sampling in determining the cause of death in stillbirths and neonates due to neurological insults in the brain: A study in a tertiary care center in India (MITS BiNS)

Location:Manipal, India

Team Members: Mary Mathew, Leslie Lewis, Shalini Nayak, Teddy Andrews, Muralidhar Pai, Athira Sreenivas, Manipal Academy of Higher Education/Kasturba Medical College

India has made incredible progress to reduce newborn mortality, but it still has the highest burden of stillbirths in the world and rates of neonatal deaths remain high.

Dr. Mary Mathew, a Pediatrician and Head of Pathology at Kasturba Medical College in Manipal, was interested in an unusual part about these statistics — that about one-quarter of babies who die in India show signs of injuries to their brain. "No baby should die...We should be able to support any type of eventuality that happens to a baby," said Dr. Mathew. "And so many pre-term and even term infants have signs of neurological insults, or injuries. We wanted to use the MITS technique to see if that could help provide answers as to why."

Starting in February 2020, the MITSBiNS team, led by Dr. Mathew, started their work exploring whether MITS could identify cause of death among stillbirths and neonatal deaths with brain injuries. The MITS Surveillance Alliance awarded an incentive grant to MITSBiNS, providing material support for the project's implementation to ensure the team can carry out the study as effectively as possible.

With the onset of COVID-19 and waves of lockdowns and disruptions, the team overcame immense obstacles to reach their goal of conducting 50 MITS procedures. Initial findings indicate that MITS indeed seems to be a feasible technique for brain biopsies, potentially avoiding the need for a full autopsy by providing a wide variety of information on the types of neurological lesions that contributed to cause of death.

"What started out as a research curiosity has now become something so much more," said Dr. Mathew. "We can save more babies if we can understand causes of injuries to the brain and then help inform interventions and care that avoid these injuries." For example, initial findings indicate that sepsis, a life-threatening illness caused by the body's response to an infection, may be contributing to neurological injuries in both preterm and term infants.

"I think health officials, doctors, and nurses would be surprised at what the research indicates about high rates of septic infection among stillbirths and neonates," said Dr. Mathew. "Findings like this one that could have a huge impact because then we would know that by improving hand hygiene and other sanitation measures in the NICU we could save lives."

Dr. Mathew is a rarity in her field — a combination of both pathologist and pediatrician.

"Pediatric pathology in India is a small field. There are maybe 15 others, and we all know each other by name," said Mathew. "There is hope for more research, but there is a lack of funding in pathology in general. But pathology is one of the basic things that we need to invest more in. If you need to treat a disease, you need to first understand the pathology."

Project: Effectiveness of MITS in Establishing the Cause of Death among patients after short-term hospitalizations at a tertiary hospital in northern Tanzania (EMECaD)

Location:Kilimanjaro, Tanzania

Team Members: Alex Mremi, Patrick Amsi, Ronald Mbwasi, Elichilia Shao, Cristina Costales and Matthew Rubach, Kilimanjaro Christian Medical Centre

In Tanzania, many people are born, live, and die without leaving any records. In particular, the deaths of patients that occur shortly after hospital admission are unlikely to be accurately documented because the hospital’s medical team likely did not have enough time to perform a comprehensive investigation of the patient’s illness, including histopathology, microbiology, or imaging.

To address this gap, the EMECaD project is exploring whether minimally invasive tissue sampling (MITS) can effectively establish cause of death among patients who die within three days of being admitted to hospital.

Dr. Alex Mremi, head of pathology at Kilimanjaro Christian Medical Centre (KCMC), a tertiary hospital in Northern Tanzania, is leading EMECaD. He first became interested in MITS when he was exposed to various autopsy techniques, including MITS, during an autopsy study that he was part of from 2016 to 2019.

“Before this study, very few autopsies were done at our hospital and almost all of them were forensic. But through the study, autopsy and particularly MITS had been demonstrated to be very useful and helpful,” says Dr. Mremi. “I learned that MITS is simple, requires less resources and personnel, is highly acceptable among people and is a nearly equal potential alternative to complete diagnostic autopsy.”

The MITS Surveillance Alliance awarded an incentive grant to EMECaD in 2019. The funding will provide financial and material support for the project’s implementation and will facilitate training and workshops to ensure the team can carry out the study as effectively as possible. EMECaD’s findings are expected by the end of 2020.

“Identifying the knowledge gap in terms of actual pathologic, evidence-based cause of death among patients with a short-term hospitalization will provide vital information to health care stakeholders, such as medical teams and policy makers, who can positively influence treatment outcomes for patients,” says Dr. Mremi. “And the study’s results may encourage clinicians in other health facilities in low- and middle-income countries to adopt the MITS technique and hence potentially improve their mortality data and improve patient management.”

Project: Determining Efficiently the Cause of Death among Adults and Generating Mortality Evidence at MITS Alliance Unit Nepal (DECODE-MAUN)

Team Members: Dr. Nuwadatta Subedi (Forensic Medicine expert); Dr. Suraj Bhattarai (Public Health specialist); Dr. Sunita Ranabhat (Pathologist); Dr. Binita Koirala (Microbiologist); Dr Madan Prasad Baral (Forensic Medicine expert)

In Nepal, relatives of the deceased often do not want the body of their loved ones disfigured by the incisions made during a full autopsy. The procedure is therefore challenging in Nepal, and is often conducted for legal, rather than clinical, purposes. In many cases, cause of death is based on patient history or clinical presentation.

Since minimally invasive tissue sampling (MITS) is a non-invasive procedure, Dr. Nuwadatta Subedi and Dr. Suraj Bhattarai of Gandaki Medical College and Teaching Hospital in Pokhara conceptualized a project called DECODE-MAUN to study how MITS can help overcome autopsy-related objections from relatives in Nepal.