# A study protocol for neonatal sepsis and gut microbiomics among preterm infants admitted at Muhimbili National Hospital, Tanzania

## TL;DR

This study aims to understand how gut bacteria in preterm infants in Tanzania relate to neonatal sepsis and antimicrobial resistance.

## Contribution

The study introduces a large-scale cohort analysis of gut microbiomes in preterm infants in Tanzania to explore sepsis and AMR associations.

## Key findings

- Gut dysbiosis is linked to neonatal sepsis in high-income countries, but this study explores it in a low-income setting.
- Next-generation sequencing will analyze microbial functions in preterm infants to identify sepsis risk factors.
- The study will provide insights into potential therapeutic strategies for neonatal sepsis in sub-Saharan Africa.

## Abstract

Neonatal mortality remains high in many low- and middle-income countries (LMICs), with neonatal sepsis and antimicrobial resistance (AMR) posing significant threats to newborns, particularly in sub-Saharan Africa (SSA). Tanzania is among the countries with the highest neonatal mortality rates, with sepsis being a major contributor.

Gut dysbiosis has been identified as a risk factor for neonatal sepsis in high-income countries, due to factors like abundance of pathogenic bacteria, decrease in microbiome diversity, intestinal barrier defects and bacterial translocation. Understanding gut dysbiosis in the local setting and its role in sepsis development may offer new prevention strategies, such as probiotics for high-risk preterm infants.

This prospective neonatal cohort, established at Muhimbili National Hospital (MNH) in Dar es Salaam, Tanzania, aims to analyze the gut microbiome of preterm infants and explore associations with neonatal late-onset sepsis (LOS). Additionally, data on bacterial pathogens of bloodstream infections and AMR prevalence will be identified. Secondary endpoints include clinical LOS, sepsis-related death, death from any cause, and hospital discharge outcomes.

Eligible preterm neonates (28 + 0 to <34 weeks of gestational age, birth weight ≥ 1000g) will be recruited with maternal consent. Socio-demographic and clinical data, microbiological details of blood pathogens, and a set of fresh frozen fecal samples during the 28 days observation period will be collected. The study targets a sample size of 1350 participants and we expect 72–135 culture-proven LOS during a study period of 18 months. Fecal samples will undergo next-generation sequencing (NGS) to analyze microbial community functions in comparison to matched controls.

This collaborative study between universities in Tanzania and Germany, aims to analyze the neonatal microbiome in relation to sepsis development and AMR of blood culture isolates to enhance neonatal sepsis care, improve diagnostics and treatment. The project will offer insights into potential therapeutic strategies for the future, promote academic exchange, capacity building and research on African microbiomes.