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Achieving equitable outcomes while innovating for neglected tropical diseases: evidence from community-based intervention studies in Malawi and Ghana
Full text linkBackground: Global strategy for neglected tropical diseases (NTDs) is intrinsically linked to the challenge of improving health equity: as conditions that disproportionately affect the most disadvantaged communities, interventions addressing NTDs are anticipated to reduce unfair differences that exist in health and access to health services. However, while substantial gains in the control and elimination of NTDs have been achieved over the past two decades,interventions addressing NTDs are rarely explored and evaluated from an equity perspective. Using two contemporary research areas for NTDs – elimination of soil-transmitted helminths (STH) and improved control of skin NTDs – this thesis aims to explore how and amongst whom gains have been achieved, and assess whether new strategies necessary to meet ambitious NTD goals can do so equitably.
Methods: This thesis is nested within two intervention studies: DeWorm3 (2017-2022), a cluster-randomised trial of community-based mass drug administration (MDA) for elimination of STH in Malawi; and SHARP (2023-2024), a pre-post intervention study of an integrated approach for Buruli ulcer, leprosy, scabies and yaws in Ghana. In Malawi, I analyse data from community-based censuses, a cross-sectional parasitological survey, and longitudinal treatment registers to explore disparities in STH infection; and assess to what extent both routine and novel MDA strategies for STH can achieve equitable coverage amongst at those at greatest risk. In Ghana, I use routine health facility treatment records and a cross-sectional dermatological survey to explore demographic trends in changes in care seeking for skin
diseases, and compare this to the profile of those at greatest risk of skin disease to assess the equity of such a strategy.
Results: Despite sustained implementation of routine strategies for the control of STH in Malawi, a number of demographic groups, including out-of-school children and adult men, remain at greater odds of STH infection. Routine school-based MDA did not result in lower coverage amongst children with disabilities despite a strong association with lower school attendance, strengthening assertions for this platform as an equitable mechanism for delivery of basic health services. In contrast, adult men’s coverage remained substantially lower than women despite widening access through novel community-based MDA, demonstrating the potential for inequity where interventions fail to actively address the needs of those at greater risk. Strengthening the routine primary health system to diagnose and treat skin NTDs in Ghana resulted in substantial increases in care seeking across demographic groups, but those at greatest risk of disease remained disproportionately under-represented amongst those who sought care.
Conclusion: These findings demonstrate the nuanced and variable extent to which interventions for NTDs – whether through expanded community-based approaches or strengthening existing routine health systems – are achieving equitable outcomes with respect to the determinants of health. I conclude by discussing the need to better address health equity in the design and evaluation of both routine and novel NTD interventions, and propose operational and research priorities to achieve this
Treatment optimisation with dolutegravir-based antiretroviral treatment for children and adolescents with HIV
Full text linkAs of 2024, an estimated 2.4 million children and adolescents were living with HIV. While new infections and AIDS-related mortality have declined, paediatric virological suppression still lags behind adults, partly due to delays in evaluating and rolling out optimised antiretroviral formulations. With improved survival, treatment optimisation increasingly focuses on ensuring long-term safety and tolerability while maintaining efficacy. Dolutegravir (DTG), a potent, well-tolerated and low-cost integrase inhibitor, has transformed adult HIV treatment, but paediatric evidence was limited when my doctoral research began.
Using data from ODYSSEY, a phase II/III randomised controlled trial in 792 children across Africa, Europe and Thailand, I examined the safety of DTG-based ART, focusing on neuropsychiatric symptoms, weight gain and metabolic outcomes. A nested pharmacokinetic (PK) substudy, which I co-led, assessed the safety and efficacy of twice-daily DTG with rifampicin-based TB treatment.
Neuropsychiatric events were infrequent; however, suicidal ideation was more commonly reported in the DTG arm. Reassuringly, most participants reported this once. There were no group differences in other mood symptoms or sleep outcomes. In the ≥14 kg cohort, weight gain was modestly higher with DTG versus SOC (mean difference 1.0 kg over 240 weeks), particularly in first-line participants, alongside greater increases in height and body circumferences but no excess in height-adjusted measures of overweight/obesity. No differences in weight gain were observed in the <14 kg cohort. Lipid profiles were more favourable with DTG and DTG was not associated with hyperglycaemia.
The TB-PK substudy demonstrated that twice-daily DTG overcame rifampicin-related enzyme induction, achieving target exposures with no adverse events attributed to DTG and nearly all participants achieving virological suppression. Overall, the findings of my research supported continued DTG use in paediatric ART and informed clinical care and treatment guidelines.
Building on this work, I designed and initiated the D3/Penta 21 trial, the first paediatric RCT evaluating DTG/lamivudine dual therapy for maintenance of virological suppression. This trial, ongoing at thesis submission, aims to generate evidence for the simplified regimen for children