SHIGELLA PROJECT

A prospective health facility-based surveillance to estimate the burden of medically attended Shigellosis in children less than 5 years of age in Ghana.

Background

Diarrhea remains one of the top health threats for children under five in sub-Saharan Africa, causing about 525,000 deaths every year. While mortality has decreased since the 1990s, the prevalence is still high in low- and middle-income countries. Shigella, a gram-negative bacterium, is a leading cause of diarrheal deaths in this age group, accounting for roughly 60,000 deaths annually. In Africa and South Asia, diarrhea causes nearly a quarter of all under-five deaths, and about one-third of children in LMICs experience at least one Shigella-related diarrhea episode by age two.

Shigella incidence rates vary from 0.4 to 43 cases per 100 child-years depending on severity and diagnostic methods. Death risk is linked to co-morbidities, malnutrition, dehydration, lack of breastfeeding, immunosuppression, prolonged illness before hospital admission, and extended hospitalization. Beyond acute diarrhea, Shigella contributes to persistent diarrhea and growth faltering, which increases susceptibility to infections, reduces vaccine effectiveness, and has lifelong health impacts. Growth failure linked to Shigella leads to 28% more deaths than direct infection mortality and contributes to over two million moderate-to-severe stunting cases yearly.

In Africa, S. flexneri is most common, followed by S. sonnei, S. boydii, and S. dysenteriae. Many strains are resistant to commonly used antibiotics but remain susceptible to ciprofloxacin, ceftriaxone, and azithromycin. Transmission occurs mainly through direct contact, especially in areas with poor sanitation. Exclusive breastfeeding lowers the risk of moderate-to-severe diarrhea. Modern qPCR methods detect more Shigella cases than traditional culture methods.

Multiple Shigella vaccine candidates are in development, including a tetravalent biconjugate vaccine in Phase I/II trials in Kenya. Future Phase IIb/III trials will require LMIC sites with high incidence of medically attended diarrhea, good participant retention, and strong laboratory capacity. Updated, country-specific data is needed to guide policymakers. Current estimates for sub-Saharan Africa are outdated. This study will generate current data on Shigella in Ghana, strengthen surveillance systems, and prepare sites for vaccine trials.

Objective

Primary Objective

• Determine the incidence of Shigella-attributed medically attended diarrhea (SMAD) in children aged 0–59 months using stool or rectal swab culture over a 12-month period.

Secondary Objectives

1. Assess the occurrence of linear growth faltering within six months after SMAD episodes compared to control children.
2. Determine the clinical characteristics and complications of SMAD from presentation to recovery.
3. Estimate SMAD incidence by serotype, age group, and season in children under five years.
4. Determine the prevalence of antibiotic resistance among Shigella isolates.

Exploratory Objectives

1. Validate SMAD detection using culture-independent molecular diagnostic methods (qPCR).
2. Compare severity definitions for their ability to predict Shigella attribution and risk of death or hospitalization within six months.
3. Quantify the economic burden of Shigella morbidity and mortality on households and the health system.
4. Assess the molecular distribution of Shigella strains in SMAD patients.

Expected Outcomes

1. Reliable national incidence estimates for SMAD in children under five in Ghana.
2. Evidence on post-infection growth faltering and associated health risks.
3. Comprehensive clinical and epidemiological profiles of Shigella cases by serotype, age, and season.
4. Data on antibiotic resistance patterns to guide treatment protocols.
5. Validation of qPCR as an accurate tool for Shigella detection in surveillance and clinical settings.
6. Refined case definitions for research and public health purposes based on severity analysis.
7. Detailed cost estimates for Shigella-related illness to inform economic evaluations of vaccine programs.
8. Strengthened health facility capacity for conducting large-scale, high-quality Shigella surveillance and Phase IIb/III vaccine trials.

Funding Partners:  European and Developing Countries Clinical Trials Partnership (EDCTP) alongside International Vaccine Institute (IVI)