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Breast cancer overall survival, annual risks of death, and survival gap apportionment in sub-Saharan Africa (ABC-DO): 7-year follow-up of a prospective cohort study.
Get PDFBACKGROUND: There are few estimates of breast cancer survival and its determinants at 5 years and beyond in sub-Saharan Africa. We aimed to estimate survival up to 7 years, estimate annual mortality risk, and apportion survival gaps. METHODS: The African Breast Cancer-Disparities in Outcomes (ABC-DO) prospective cohort study was done at eight hospitals across five sub-Saharan African countries (Namibia, Nigeria, South Africa, Uganda, and Zambia). We prospectively recruited women (aged ≥18 years) who attended hospital with suspected breast cancer. Vital status was updated telephonically once every 3 months for 7 years. We collected detailed sociodemographic, clinical, and treatment data. The primary outcome was overall survival. We estimated age-standardised net survival, conditional survival, and predicted survival gains if there were favourable shifts in the distribution of prognostic factors aligned with the WHO Global Breast Cancer Initiative (GBCI). FINDINGS: Between Sept 8, 2014, and Dec 31, 2017, 2313 women were recruited and followed up to Jan 1, 2022, and for a further year in South Africa. We excluded 87 women without breast cancer, 14 women from small racial groups (eight White and six Asian women in South Africa), 57 women with previous treatment or possible recurrences, and two women without follow-up data. The remaining 2153 (93%) women were categorised by country and race, as follows: three groups in Namibia (60 White women, 50 mixed race women, and 367 Black women), two in South Africa (37 mixed race women and 638 Black women), and one group of Black women in each of Uganda (419 women), Zambia (198 women), and Nigeria (384 women). During follow-up to at most 7 years, 1323 (61%) of 2153 women died, 672 (31%) were alive at administrative censoring, and 158 (7%) were lost to follow-up, giving crude survival at 3 years, 5 years, and 7 years of 51%, 40%, and 33%, respectively. Large between-country variations in 5-year age-standardised net survival were observed: 35-42% in Zambia and Nigeria; 52-58% in Black women in Uganda, South Africa, and Namibia; and over 83% in non-Black Namibian women. The annual probability of death (1-year conditional net survival, censored before the COVID-19 pandemic) declined generally from 2-3 years after diagnosis, but remained at 8-21% for Black women in Namibia, Uganda, and Nigeria during the fifth year after diagnosis. Reaching the GBCI 60% stage I or II target and accessing treatment would lead to an approximate reduction in deaths by a third among Black women in Namibia, Nigeria, South Africa, Uganda, and Zambia. INTERPRETATION: Survival after breast cancer is poor in several sub-Saharan African countries, with a substantial risk of death even among women who have survived beyond 3 years after diagnosis. Understanding and preventing deaths among longer-term breast cancer survivors requires further research. FUNDING: National Cancer Institute, Susan G Komen, and International Agency for Research on Cancer. TRANSLATIONS: For the Yoruba, Hausa, Igbo, Luganda and French translations of the abstract see Supplementary Materials section
Plasma proteomics for biomarker discovery in childhood tuberculosis.
Get PDFFailure to rapidly diagnose tuberculosis disease (TB) and initiate treatment is a driving factor of TB as a leading cause of death in children. Current TB diagnostic assays have poor performance in children, thus a global priority is the identification of novel non-sputum-based TB biomarkers. Here we use high-throughput proteomics to measure the plasma proteome for 511 children, with and without HIV, and across 4 countries, to distinguish TB status using standardized definitions. By employing a machine learning approach, we derive four parsimonious biosignatures encompassing 3 to 6 proteins that achieve AUCs of 0.87-0.88 and which all reach the minimum WHO target product profile accuracy thresholds for a TB screening test. This work provides insights into the unique host response in pediatric TB disease, as well as a non-sputum biosignature that could reduce delays in TB diagnosis and improve the detection and management of TB in children worldwide
Household cooking fuel use and risk of adverse birth outcomes: a prospective follow-up study in eastern Ethiopia.
Get PDFEvidence indicates that pregnant women's exposure to polluted air adversely affects the growing fetus leading to adverse birth outcomes including preterm birth, low birth weight, and stillbirth. There is a lack of evidence on the effects of air pollution and adverse birth outcomes in Ethiopia. This study examined the relationship between cooking fuel use and adverse pregnancy-related outcomes. The paper used data from pregnancy surveillance in Child Health and Mortality Prevention Surveillance in eastern Ethiopia form July 2021 to June 2023. A total of 15,778 women whose pregnancy outcomes were known were included in this analysis. Data were collected using Research Data Capture (Redcap) and analyzed using STATA 17. Self-reported fuel use for cooking was classified as "clean" (petroleum, biogas, and electricity) and "polluting (firewood, charcoal, crop residue, sawdust, and straw/shrubs/grass). A modified Poisson regression model was used to examine the association between adverse birth outcomes (preterm birth, stillbirth, low birth weight) and cooking fuel use. Women using polluting cooking fuel had higher rates of stillbirth (3.1%), preterm delivery (6.1%), and low birth weight (10.5%) compared to those using clean fuel (1.9%, 2.8%, and 8.3%, respectively). Utilization of polluting fuel had a significant effect on the occurrence of preterm birth Adjusted risk ratio (ARR): 2.16, 95% Confidence Intervals (CI): 1.16, 2.89), stillbirth (ARR: 1.50, 95% CI: 1.09, 2.06), and low birth weight (ARR: 1.23, 95% CI: 1.06, 1.43) respectively. The findings indicated that using polluting fuel during pregnancy has a strong association with adverse pregnancy outcomes. It is essential to provide education during ANC regarding the dangers of using polluting fuels and methods to reduce excessive exposure to them
Impact and cost-effectiveness of the community-led AMETHIST intervention among female sex workers in Zimbabwe.
Get PDFFemale sex workers (FSW) face high HIV risk of HIV transmission and acquisition. The AMETHIST ("Adapted Microplanning: Eliminating Transmissible HIV In Sex Transactions") trial enhanced Zimbabwe's Key Populations (KP) programme by providing targeted, community-based support for FSW. We used the HIV Synthesis Model to assess its long-term impact and cost-effectiveness. Given USAID's major role in funding, we also evaluated the effects of ending US support on the KP programme. We modelled a KP programme from 2010. From 2024 we compared (i) continuation of KP programme to (ii) continuation of KP programme + 'AMETHIST' intervention. We assessed HIV outcomes in 2030 and conducted cost-effectiveness analysis over a 50 year time horizon. Similar analyses were undertaken comparing continuation of the current KP programme to discontinuation. Here we show that AMETHIST had greater positive impact than the KP programme alone; a higher proportion of FSW tested for HIV in the past year, were diagnosed, on ART and had undetectable viral loads compared to the KP programme alone. Disability adjusted life years were averted with AMETHIST and it was cost-saving within 15 years. Continuing the current KP programme was also cost-saving compared to discontinuation of the KP programme
Strong Association Between HIV Incidence and Herpes Simplex Virus Type 2 in Zambia and South Africa: Prospective Data From the HPTN 071 (PopART) Trial.
Get PDFBACKGROUND: Herpes simplex virus type 2 (HSV2) is an important cofactor for HIV acquisition and transmission. Associations between the infections are reexamined in longitudinal data from an HIV prevention trial.
METHODS: The HPTN 071 (PopART) trial evaluated a combination prevention intervention in 21 urban communities in Zambia and South Africa. HIV incidence was measured in a cohort of approximately 2000 adults (age, 18-44 years) selected randomly from each community and followed up for 36 months. Incidence of HSV2 infection was estimated, and the effects of risk factors were examined. The association between HIV incidence and HSV2 infection was examined at individual and community levels.
RESULTS: An overall 10 539 participants were HSV2 negative at baseline and retested after 36 months. Estimated HSV2 incidence was 5.4 per 100 person-years (95% CI, 5.0-5.7) for women and 2.9 per 100 person-years (95% CI, 2.6-3.2) for men. When compared with those remaining HSV2 negative, HIV incidence was higher in those who were HSV2 positive at baseline (women: adjusted rate ratio [aRR], 3.24 [95% CI, 2.50-4.20]; men: aRR, 2.57 [95% CI, 1.60-4.11]) and even higher in those who seroconverted to HSV2 during follow-up (women: aRR, 5.94 [95% CI, 4.42-7.98]; men: aRR, 8.37 [95% CI, 5.18-13.52]). At the community level, strong associations were seen between HIV incidence and HSV2 prevalence (R 2 = 0.48, P < .001) and incidence (R 2 = 0.36, P = .004).
CONCLUSIONS: There were strong associations between HIV incidence and HSV2 prevalence and incidence at individual and community levels. HSV2 control could contribute to HIV prevention
Seroprevalence of SARS-CoV-2 in wet market workers in Dhaka, Bangladesh in 2022.
Get PDFOBJECTIVES: We assessed the transmission of SARS-CoV-2 and vaccine receipt in a representative sample of wet market workers in a highly dense, low-income setting. Wet markets are key in many Asian settings, including Dhaka, Bangladesh, for fresh food, including animal protein.
METHODS: During early 2022, we assessed the prevalence of anti-SARS-CoV-2 antibodies in a random sample of poultry and vegetable workers in 15 wet markets, and investigated associations with socio-demographic characteristics and COVID-19 vaccination.
RESULTS: In the 204 poultry workers and 87 vegetable sellers recruited, COVID-19 vaccine uptake was similar (69% vs 67%). The most common vaccines were whole inactivated vaccines (Sinopharm or Sinovac; 44%). Nearly all (99%) participants were positive for anti-SARS-CoV-2 spike antibodies. Anti-SARS-CoV-2 nucleocapsid antibodies, indicative of recent infection, was 59.4% (95% confidence interval 54.7-64.0%). There was no evidence that the latter was associated any characteristics, except vaccination (adjusted odds ratio 0.49; 95% confidence interval 0.23-1.02; P = 0.093).
CONCLUSIONS: The ubiquity of anti-spike and high prevalence of anti-nucleocapsid antibodies were consistent with high transmission after three previous pandemic waves. Wet markets have a potential role amplifying transmission of airborne pathogens, such as SARS-CoV-2 and Avian Influenza Viruses, and an important public-facing hotspot for close monitoring for future emerging infections
Cost-effectiveness of introducing a maternal vaccine or long-acting monoclonal antibody to prevent infant respiratory syncytial virus disease in Nepal.
Get PDFBACKGROUND: The World Health Organization recommends two passive immunisation strategies to prevent respiratory syncytial virus (RSV) disease in young infants. Both are being introduced in high-income settings, but their affordability and cost-effectiveness have not been evaluated in many low- and middle-income countries. Preliminary estimates of cost-effectiveness are needed to guide immunisation policy and planning in Nepal. METHODS: We estimated the potential health impact and cost-effectiveness of introducing a maternal vaccine (RSVpreF) or long-acting infant monoclonal antibody (mAb) (nirsevimab) over the period 2025-34 in Nepal. We compared both interventions to the status quo (no intervention) and to each other. Model inputs included health care cost estimates from a recent prospective cost-of-illness study in Kathmandu, as well as the latest efficacy data from clinical trials. The primary outcome measure was the incremental cost (2023 USD) per disability-adjusted life year (DALY) averted from a governmental health perspective. We conducted a range of deterministic analyses, including scenarios that incorporated a societal perspective and a seasonal approach. Additionally, we performed probabilistic uncertainty analyses to assess decision uncertainty and estimated the likelihood of cost-effectiveness for each intervention across a range of willingness-to-pay thresholds. RESULTS: Introducing a maternal vaccine (USD 5/dose, 81% coverage, 69% efficacy, 6 months protection) or long-acting infant mAb (USD 5/dose, 97% coverage, 77% efficacy, 5 months protection) could prevent >2300 deaths and >50 000 hospital admissions over ten years. The discounted immunisation programme costs were estimated to be USD 30 and USD 35 million, respectively. Compared to the status quo, the maternal vaccine and the long-acting infant mAb were estimated to cost USD 387 and USD 486 per DALY averted, respectively, which is around 0.3 times and 0.4 times the national gross domestic product (GDP) per capita. There was a 95% probability that the maternal vaccine would be cost-effective at USD 5 per dose, assuming a willingness-to-pay threshold of 0.5 times the national GDP per capita. With our base case assumptions, the maternal vaccine dominated the mAb (i.e. generated more health benefits at a lower cost). However, the results (and the rank order of interventions) were sensitive to the dose price, efficacy, duration of protection, and RSV disease burden estimates. Cost-effectiveness of the mAb improves with timely administration or when a seasonal approach is implemented. CONCLUSIONS: New passive immunisation strategies have the potential to prevent a substantial number of RSV-related hospitalisations and deaths in Nepal. Cost-effectiveness and product choice will heavily depend on the price negotiated for each product
Uptake and factors associated with cervical cancer screening among women aged 18–49 years at a public hospital in Coastal Kenya
Get PDFCervical cancer remains a public health concern in sub-Saharan Africa. In Kenya, data on cervical cancer screening is limited therefore hindering planning of targeted interventions. We aimed to determine the prevalence and factors associated with cervical cancer screening among women aged 18–49 years at a public hospital in Coastal Kenya.A cross-sectional design was used. Women attending outpatient departments were recruited using systematic random sampling and an interviewer-administered questionnaire administered (n = 315). Proportion of women reporting cervical cancer screening uptake was determined. Logistic regression was used to examine associations between cervical cancer screening uptake and sociodemographic characteristics.Overall, 56 (17.8% [95% CI: 13.7 – 22.5]) participants reported to have been screened for cervical cancer. Factors associated with cervical cancer screening uptake included older age (adjusted odds ratios, [95% CI], p – value: 2.3 [1.0 – 5.0], p = 0.034), secondary/tertiary level of education (3.3 [1.6 – 6.5], p < 0.001) and history of sexually transmitted infection (STI) (2.4 [1.2 – 4.7], p = 0.009).Uptake of cervical cancer screening was low. Intensifying education campaigns on cervical cancer screening especially among women who are young, uneducated and with no history of STI may help scale up cervical cancer screening uptake
Big databases and biobanks for studying the links between CKD, cognitive impairment, and dementia.
Get PDFResearch on cognitive function in individuals with chronic kidney disease (CKD) is critical due to the significant public health challenge posed by both CKD and cognitive impairment. CKD affects approximately 10-15% of the adult population, with higher prevalence in the elderly, who are already at increased risk for cognitive decline. Cognitive impairment is notably higher in CKD patients, particularly those with severe stages of the disease, and progresses more rapidly in those on dialysis. This review explores how data from large biobank studies such as the Alzheimer's Disease Neuroimaging Initiative, UK Biobank, and others could be used to enhance understanding the progression and interplay between CKD and cognitive decline. Each of these data sources has specific strengths and limitations. Strengths include large sample sizes and longitudinal data across different groups, and in different settings. Addressing limitations leads to challenges in dealing with heterogeneous data collection methods, and addressing missing data, which requires the use of sophisticated statistical techniques. Combining data from multiple databases can mitigate individual study limitations, particularly via the 'epidemiological triangulation' concept. Using such data appropriately holds immense potential to better understand the pathobiology underlying CKD and cognitive impairment. Addressing the inherent challenges with a clear strategy is crucial for advancing our understanding and improving the lives of those affected by both CKD and cognitive impairment
A clinical practice guideline for tuberculous meningitis.
Get PDFTuberculous meningitis is the most severe form of tuberculosis, causing death or disability in around half of those affected. There are no up-to-date international guidelines defining its optimal management. Therefore, the Tuberculous Meningitis International Research Consortium conducted a systematic review of available evidence to address key management questions and to develop practice guidance. The consortium includes representatives from India, Indonesia, South Africa, Uganda, Viet Nam, Australia, the Netherlands, the UK, and the USA. Questions were developed using the Population, Intervention, Comparator, Outcome (PICO) format for tuberculous meningitis diagnosis, anti-tuberculosis chemotherapy, adjunctive anti-inflammatory therapy, and neurocritical and neurosurgical care. A Grading of Recommendations, Assessment, Development and Evaluations approach was used to assess the certainty (or quality) of evidence and establish the direction and strength of recommendations for each PICO-based question. We provide evidence-based recommendations for the optimal treatment and diagnosis of tuberculous meningitis, alongside expert opinion. We expose substantial knowledge and evidence gaps, thereby highlighting current research priorities