Lancet Global Health最新文献

The Sudan 2023 Humanitarian Response Plan was revised in May, 2023, due to the escalating violence in the country. This revision increased the scale of assistance and protection activities and suspended the funding allocated for access to livelihood, access to basic services, and for the implementation of resilience solutions. We call to rethink Sudan's current humanitarian response through a pro-resilience and people-centred approach. A pro-resilience approach prioritises investments in national systems and institutions capable of delivering aid and anticipates, prevents, mitigates, and manages imminent and simultaneous shocks. A people-centred humanitarian response involves meaningful engagement of communities and collaborations with civil society organisations, which continue to be the key responders to the ongoing conflict in Sudan. Finally, we propose approaches to effectively operationalise health system resilience to enhance immediate and long-term health outcomes.

The negotiations for the WHO Pandemic Agreement have brought attention to issues of racism and colonialism in global health. Although the agreement aims to promote global solidarity, it fails to address these deeply embedded problems. This Viewpoint argues that not including the principle of subsidiarity into Article 4 of the agreement as a pragmatic strategy was a missed opportunity to decolonise global health governance and promote global solidarity. Subsidiarity, as a structural principle, empowers local units to make decisions and address issues at their level, fostering collaboration, coordination, and cooperation. By integrating subsidiarity, the agreement could have ensured contextually appropriate responses, empowered local communities, and achieved justice in global health. This paper discusses the elements of subsidiarity-namely, agency and non-abandonment-and highlights the need to strike a balance between them. It also maps the principle of subsidiarity within the Pandemic Agreement, emphasising the importance of creating a practical framework for its implementation. By integrating subsidiarity into the agreement, a just and decolonialised approach to pandemic prevention and response could have been closer to being realised, promoting global solidarity and addressing health inequities.

Background: Tuberculosis continues to be a leading cause of infectious disease mortality, and effective screening and diagnosis remains crucial. Despite progress made, diagnostic gaps remain due to poor access to diagnostic tools and testing, particularly in rural and remote areas. As such, the development of target product profiles is essential in guiding the development of new diagnostic tools, however target product profiles often lack evidence-based information and do not consider trade-offs between test accuracy and accessibility.

Methods: A simulation-based model, in the form of a decision tree, was used to map out the baseline patient tuberculosis diagnostic pathway for individuals in Kenya, South Africa, and India. The model was then used to adapt this pathway to evaluate the trade-offs between increased access to testing and varying accuracy of new tuberculosis diagnostic tools within the health-care contexts of Kenya, South Africa, and India. The model aims to support target product profile development by quantifying the impact of new diagnostics on the standard of care. The model considered three diagnostic attributes, namely sample type (sputum vs non-sputum), site of testing (point of care, near point of care, and health setting) and turnaround time.

Findings: Our results indicate that per sample type, novel point-of-care tests would be the most accessible and even with lower sensitivities can achieve comparable or better case detection than the current standard of care in each country. Non-sputum diagnostics also have lower sensitivity requirements. Overall, target product profile parameters with reduced sensitivities from 70% for non-sputum and 78% for sputum tests could be accepted.

Interpretation: Diagnostics which bring tuberculosis tests and test results closer to the patient could reduce overall diagnostic loss despite potential reductions in sensitivity. This work provides a novel framework for guiding the future development of diagnostics, with an approach towards balancing accessibility and test performance.

Funding: The Bill and Melinda Gates Foundation (INV-045721).

Background: Data on long-term neurodevelopmental outcomes of normocephalic children (born with normal head circumference) exposed to Zika virus in utero are scarce. We aimed to compare neurodevelopmental outcomes in normocephalic children up to age 48 months with and without Zika virus exposure in utero.

Methods: In this prospective cohort study, we included infants from two cohorts of normocephalic children born in León and Managua, Nicaragua during the 2016 Zika epidemic. In León, all women pregnant during the two enrolment periods were eligible. In Managua, mother-child pairs were included from three districts in the municipality of Managua: all women who became pregnant before June 15, 2016, and had a due date of Sept 15, 2016 or later were eligible. Infants were serologically classified as Zika virus-exposed or Zika virus-unexposed in utero and were followed up prospectively until age 48 months. At 36 months and 48 months of age, the Mullen Scales of Early Learning (MSEL) assessment was administered. Primary outcomes were MSEL early learning composite (ELC) scores at 30-48 months in León and 36-48 months in Managua. We used an inverse probability weighting generalised estimating equations model to assess the effect of Zika virus exposure on individual MSEL cognitive domain scores and ELC scores, adjusted for maternal education and age, poverty status, and infant sex.

Findings: The initial enrolment period for the León cohort was between Jan 31 and April 5, 2017 and the second was between Aug 30, 2017, and Feb 22, 2018. The enrolment period for the Managua cohort was between Oct 24, 2019, and May 5, 2020. 478 mothers (482 infants) from the León cohort and 615 mothers (609 infants) from the Managua cohort were enrolled, of whom 622 children (303 from the León cohort; 319 from the Managua cohort) were included in the final analysis; four children had microcephaly at birth and thus were excluded from analyses, two from each cohort. 33 (11%) of 303 children enrolled in León and 219 (69%) of 319 children enrolled in Managua were exposed to Zika virus in utero. In both cohorts, no significant differences were identified in adjusted mean ELC scores between Zika virus-exposed and unexposed infants at 36 months (between-group difference 1·2 points [95% CI -4·2 to 6·5] in the León cohort; 2·8 [-2·4 to 8·1] in the Managua cohort) or at 48 months (-0·9 [-10·8 to 8·8] in the León cohort; 0·1 [-5·1 to 5·2] in the Managua cohort). No differences in ELC scores between Zika virus-exposed and unexposed infants exceeded 6 points at any time between 30 months and 48 months in León or between 36 months and 48 months in Managua, which was considered clinically significant in other settings.

Interpretation: We found no significant differences in neurodevelopmental scores between normocephalic children with in-utero Zika virus exposure and Zika virus-unexposed children at age 36

Background: Nodding syndrome is a poorly understood neurological disorder that predominantly occurs in Africa. We hypothesised that nodding syndrome is a neuroinflammatory disorder, induced by antibodies to Onchocerca volvulus or its Wolbachia symbiont, cross-reacting with host neuronal proteins (HNPs), and that doxycycline can be used as treatment.

Methods: In this randomised, double-blind, placebo-controlled, phase 2 trial, we recruited participants from districts affected by nodding syndrome in northern Uganda. We included children and adolescents aged 8-18 years with nodding syndrome, as defined by WHO consensus criteria. Participants were randomly assigned (1:1) to receive either 100 mg doxycycline daily or placebo for 6 weeks via a computer-generated schedule stratified by skin microscopy results, and all parties were masked to group assignment. Diagnoses of O volvulus and antibodies to HNPs were made using luciferase immunoprecipitation system assays and immunohistochemistry. The primary outcome was change in the proportion with antibodies to HNPs, assessed at 24 months. All participants were included in safety analyses, and surviving participants (those with samples at 24 months) were included in primary analyses. Secondary outcomes were: change in concentrations of antibodies to HNPs at 24 months compared with baseline; proportion of participants testing positive for antibodies to O volvulus-specific proteins and concentrations of Ov16 or OVOC3261 antibodies at 24 months compared with baseline; change in seizure burden, proportion achieving seizure freedom, and the proportions with interictal epileptiform discharges on the diagnostic EEG; overall quality of life; disease severity at 24 months; and incidence of all-cause adverse events, serious adverse events, and seizure-related mortality by 24 months. This trial is registered with ClinicalTrials.gov, NCT02850913.

Findings: Between Sept 1, 2016, and Aug 31, 2018, 329 children and adolescents were screened, of whom 240 were included in the study. 140 (58%) participants were boys and 100 (42%) were girls. 120 (50%) participants were allocated to receive doxycycline and 120 (50%) to receive placebo. At recruitment, the median duration of symptoms was 9 years (IQR 6-10); 232 (97%) participants had O volvulus-specific antibodies and 157 (65%) had autoantibodies to HNPs. The most common plasma autoantibodies were to human protein deglycase DJ-1 (85 [35%] participants) and leiomodin-1 (77 [32%] participants) and, in cerebrospinal fluid (CSF), to human DJ-1 (27 [11%] participants) and leiomodin-1 (14 [6%] participants). On immunohistochemistry, 46 (19%) participants had CSF autoantibodies to HNPs, including leiomodin-1 (26 [11%]), γ-aminobutyric acid B receptors (two [<1%]), CASPR2 (one [<1%]), or unknown targets (28 [12%]). At 24 months, 161 (72%) of 225 participants had antibodies to HNPs compared with 157 (65%) of 240 at baseli

Background: There is an urgent need to improve breast cancer survival in sub-Saharan Africa. Geospatial barriers delay diagnosis and treatment, but their effect on survival in these settings is not well understood. We examined geospatial disparities in 4-year survival in the African Breast Cancer-Disparities in Outcomes cohort.

Methods: In this prospective cohort study, women (aged ≥18 years) newly diagnosed with breast cancer were recruited from eight hospitals in Namibia, Nigeria, South Africa, Uganda, and Zambia. They reported sociodemographic information in interviewer-administered questionnaires, and their clinical and treatment data were collected from medical records. Vital status was ascertained by contacting participants or their next of kin every 3 months. The primary outcome was all-cause mortality in relation to rural versus urban residence, straight-line distance, and modelled travel time to hospital, analysed using restricted mean survival time, Cox proportional hazards, and flexible parametric survival models.

Findings: 2228 women with breast cancer were recruited between Sept 8, 2014, and Dec 31, 2017. 127 were excluded from analysis (58 had potentially recurrent cancer, had previously received treatment, or had no follow-up; 14 from minority ethnic groups with small sample sizes; and 55 with missing geocoded home addresses). Among the 2101 women included in analysis, 928 (44%) lived in a rural area. 1042 patients had died within 4 years of diagnosis; 4-year survival was 39% (95% CI 36-42) in women in rural areas versus 49% (46-52) in urban areas (unadjusted hazard ratio [HR] 1·24 [95% CI 1·09-1·40]). Among the 734 women living more than 1 h from the hospital, the crude 4-year survival was 37% (95% CI 32-42) in women in rural areas versus 54% (46-62) in women in urban areas (HR 1·35 [95% CI 1·07-1·71] after adjustment for age, stage, and treatment status). Among women in rural areas, mortality rates increased with distance (adjusted HR per 50 km 1·04, 1·01-1·07) and travel time (adjusted HR per h 1·06, 1·02-1·10). Among women with early-stage breast cancer receiving treatment, women in rural areas had a strong survival disadvantage (overall HR 1·54, 1·14-2·07 adjusted for age and stage; >1 h distance adjusted HR 2·14, 1·21-3·78).

Interpretation: Geospatial barriers reduce survival of patients with breast cancer in sub-Saharan Africa. Specific attention is needed to support patients with early-stage breast cancer living in rural areas far from cancer treatment facilities.

Funding: US National Institutes of Health (National Cancer Institute), Susan G Komen for the Cure, and the International Agency for Research on Cancer.