Long-term healthcare utilisation, costs and quality of life after invasive group B Streptococcus disease: a cohort study in five low-income and middle-income countries.

INTRODUCTION: There are no published data on the long-term impact of invasive group B Streptococcus disease (iGBS) on economic costs or health-related quality of life (HRQoL) in low-income and middle-income countries. We assessed the impact of iGBS on healthcare utilisation, costs and HRQoL in Argentina, India, Kenya, Mozambique and South Africa. METHODS: Inpatient and outpatient visits, out-of-pocket (OOP) healthcare payments in the 12 months before study enrolment, and health-state utility of children and caregivers (using the EuroQol 5-Dimensions-3-Level) were collected from iGBS survivors and an unexposed cohort matched on site, age at recruitment and sex. We used logistic or Poisson regression for analysing healthcare utilisation and zero-inflated gamma regression models for family and health system costs. For HRQoL, we used a zero-inflated beta model of disutility pooled data. RESULTS: 161 iGBS-exposed and 439 unexposed children and young adults (age 1-20) were included in the analysis. Compared with unexposed participants, iGBS was associated with increased odds of any healthcare utilisation in India (adjusted OR 11.2, 95% CI 2.9 to 43.1) and Mozambique (6.8, 95% CI 2.2 to 21.1) and more frequent healthcare visits (adjusted incidence rate ratio (IRR) for India 1.7 (95% CI 1.4 to 2.2) and for Mozambique 6.0 (95% CI 3.2 to 11.2)). iGBS was also associated with more frequent days in inpatient care in India (adjusted IRR 4.0 (95% CI 2.3 to 6.8) and Kenya 6.4 (95% CI 2.9 to 14.3)). OOP payments were higher in the iGBS cohort in India (adjusted mean: Int$682.22 (95% CI Int$364.28 to Int$1000.16) vs Int$133.95 (95% CI Int$72.83 to Int$195.06)) and Argentina (Int$244.86 (95% CI Int$47.38 to Int$442.33) vs Int$52.38 (95% CI Int$-1.39 to Int$106.1)). For all remaining sites, differences were in the same direction but not statistically significant for almost all outcomes. Health-state disutility was higher in iGBS survivors (0.08, 0.04-0.13 vs 0.06, 0.02-0.10). CONCLUSION: The iGBS health and economic burden may persist for years after acute disease. Larger studies are needed for more robust estimates to inform the cost-effectiveness of iGBS prevention.

Neurodevelopmental and growth outcomes after invasive Group B Streptococcus in early infancy: A multi-country matched cohort study in South Africa, Mozambique, India, Kenya, and Argentina.

Background: Data are limited regarding long-term consequences of invasive GBS (iGBS) disease in early infancy, especially from low- and middle-income countries (LMIC) where most cases occur. We aimed to estimate risk of neurodevelopmental impairment (NDI) in children with a history of iGBS disease. Methods: A multi-country matched cohort study was undertaken in South Africa, India, Mozambique, Kenya, and Argentina from October 2019 to April 2021. The exposure of interest was defined as a history of iGBS disease (sepsis or meningitis) before 90 days of age, amongst children now aged 1·5-18 years. Age and sex-matched, children without history of GBS were also recruited. Age-appropriate, culturally-adapted assessments were used to define NDI across multiple domains (cognitive, motor, hearing, vision, emotional-behaviour, growth). Pooled NDI risk was meta-analysed across sites. Association of iGBS exposure and NDI outcome was estimated using modified Poisson regression with robust variance estimator. Findings: Amongst 138 iGBS survivors and 390 non-iGBS children, 38·1% (95% confidence interval [CI]: 30·0% - 46·6%) of iGBS children had any NDI, compared to 21·7% (95% CI: 17·7% - 26·0%) of non- iGBS children, with notable between-site heterogeneity. Risk of moderate/severe NDI was 15·0% (95% CI: 3·4% - 30·8%) among GBS-meningitis, 5·6% (95% CI: 1·5% - 13·7%) for GBS-sepsis survivors. The adjusted risk ratio (aRR) for moderate/severe NDI among iGBS survivors was 1.27 (95% CI: 0.65, 2.45), when compared to non-GBS children. Mild impairment was more frequent in iGBS (27.6% (95% CI: 20.3 - 35.5%)) compared to non-GBS children (12.9% (95% CI: 9.7% - 16.4%)). The risk of emotional-behavioural problems was similar irrespective of iGBS exposure (aRR=0.98 (95% CI: 0.55, 1.77)). Interpretation: Our findings suggest that iGBS disease is on average associated with a higher risk of moderate/severe NDI, however substantial variation in risk was observed between sites and data are consistent with a wide range of values. Our study underlines the importance of long-term follow-up for at-risk neonates and more feasible, standardised assessments to facilitate diagnosis in research and clinical practice. Funding: This work was supported by a grant (INV-009018) from the Bill & Melinda Gates Foundation to the London School of Hygiene &Tropical Medicine.