Tuberculosis (TB) among hospitalized patients is underdiagnosed. This study assessed systematic TB-screening, followed by an enhanced TB-diagnostic package for hospitalized patients implemented by trained lay health workers in KwaZulu-Natal, South Africa.
METHODS
In this before-and-after study we included patients ≥ 18 years. The intervention consisted of systematic clinical screening for TB, HIV and diabetes mellitus by lay health workers and provision of an enhanced TB-diagnostic package including sputum Xpert MTB/Rif Ultra, urine lateral-flow lipoarabinomannan assay (LF-LAM), chest x-ray, and sputum culture. We compared TB case findings with people hospitalized one year preceding the intervention.
RESULTS
In the pre-intervention phase, 5217 people were hospitalized. Among 4913 (94.2%) people not on TB treatment, 367 (7.5%) were diagnosed with TB. In the intervention phase, 4015 eligible people were hospitalized. Among 3734 (93.0%) people not on TB treatment, 560 (15.0%) were diagnosed with TB. The proportion of patients diagnosed with TB was higher in the intervention phase (15.0% vs. 7.5%, p < 0.001). Overall in-hospital mortality was lower in the intervention phase [166/3734(4.5%) vs. 336/4913(6.8%), p < 0.001].
CONCLUSION
Lay health worker-led implementation of systematic TB-screening, coupled with provision of an enhanced TB-diagnostic package significantly improved TB case detection and mortality among hospitalized adults.
Trypanosoma brucei rhodesiense human African trypanosomiasis (r-HAT), the zoonotic, acute form of sleeping sickness in eastern Africa, is lethal if untreated. Today, only one arsenic- based, neurotoxic drug, melarsoprol, is available for treatment of the advanced meningo-encephalitic stage. A new oral treatment would simplify HAT elimination as proposed by WHO. Fexinidazole was recommended by the European Medicines Agency (EMA) in 2018 as the first oral treatment for Trypanosoma brucei gambiense HAT, but it was not yet evaluated for r-HAT.
METHODS
This single-arm clinical trial, sponsored by DNDi, began in October 2019 and tested fexinidazole treatment in patients with r-HAT as an alternative to existing treatment in Malawi and Uganda. Patients (aged ≥6 years) with both stages of the disease were recruited up to the target of 34 patients with stage 2 disease evaluable at the end of hospitalization. Patients were hospitalised during the 10 days of treatment and followed up to 12 months after hospital discharge. The primary outcome was r-HAT-related or treatment-related fatality at the end of hospitalisation in patients with stage 2 disease and was compared with an unacceptable fatality rate of 8.5%, a threshold defined according to results from a previous clinical trial with melarsoprol. This trial is registered with ClinicalTrials.gov, NCT03974178.
RESULTS
45 patients received treatment between 1 October 2019 and 28 November 2021 (35 [78%] had stage 2 disease and ten [22%] stage 1, 31 [69%] were male and 14 [31%] female, with median age of 24 years). The primary efficacy result of the clinical trial, analysed among the 34 evaluable patients, was achieved, with no r-HAT-related or treatment-related deaths during hospitalisation (0.0%, 95% CI 0.0–8.4), compared with a benchmark of 8.5% lethality attributable to melarsoprol. Safety was acceptable, with no severe adverse events related to fexinidazole; and one patient relapsed.
CONCLUSION
Fexinidazole, an oral treatment, was shown to be a good alternative to existing injectable and toxic drugs. Results were submitted for EMA regulatory review in preparation for use in endemic countries, and a positive scientific opinion was received in December 2023 to extend the indication of fexinidazole for the treatment of r-HAT. Fexinidazole is expected to be deployed in 2024 as a new r-HAT therapeutic.
Optimizing nutrient supplementation among pregnant and reproductive age women in Kenya (VIRUTUBISHO)
INTRODUCTION
Hepatitis E causes high mortality among pregnant women, with case fatality risks over 30% and adverse fetal outcomes. There is an evidence gap on the safety of the only licensed vaccine, Hecolin®, in pregnancy. In 2015, WHO recommended vaccine use in response to outbreaks, including pregnant women. In 2022, the first mass reactive vaccination campaign against Hepatitis E was conducted in Bentiu displaced persons camp in South Sudan. We aimed to determine whether vaccination against hepatitis E in pregnancy increased the risk of fetal loss in a cohort of vaccinated and unvaccinated pregnant women.
METHODS
An exhaustive pregnancy census was conducted from 16 May 2022 until 30 June 2022 after the second vaccination round, and women were revisited 28 days after delivery date to document the pregnancy outcome. We used an emulated target trial framework to address biases inherent in observational studies. We matched (1:1, with replacement) vaccinated to unvaccinated women on age, gestational age, and vaccination propensity score, and we estimated cumulative incidence functions for fetal loss in vaccinated compared with unvaccinated women using the Nelson-Aalen estimator.
RESULTS
Among 2741 women who had a pregnancy outcome after the start of the vaccination campaign, 67 (2.4%) were vaccinated before conception, 2036 (74.3%) were vaccinated during pregnancy, and 638 (23.3%) were not vaccinated. Among the 2407 women retained in the matched analyses, the cumulative risk of fetal loss in women vaccinated during pregnancy was 6.38% (95% CI 4.93–7.26) compared with 6.26% (3.9–9.19) among unvaccinated women (risk ratio [RR] 1.02 [95% CI 0.64–1.53]). In an analysis restricted to women vaccinated during pregnancy with less than 90 days gestation, the cumulative risk of miscarriage was 11.01% (95% CI 8.45–13.13) among vaccinated women and 11.62% (6.45–17.09) among unvaccinated women (RR 0.95 [95% CI 0.59–1.66]). In sensitivity analyses, we explored the impact of different matching criteria on the estimated RR and found no qualitative differences with the main analyses, with no evidence of increased risk of fetal loss among vaccinated women.
CONCLUSION
We used an emulated target trial methodology with matching to simulate a vaccine trial in pregnant women after a reactive vaccination campaign. This robust analytical method simulating a vaccine trial attempts to control for bias inherent in observational data. We found no evidence for increased risk of fetal loss among women vaccinated during pregnancy.