Evidence of immune imprinting or the effect of selection bias?

People with booster vaccinations appear more prone to reinfection than those with primary series vaccination only; however, selection bias in the study design complicates interpretation.

Effect of the "universal test and treat" policy on the characteristics of persons registering for HIV care and initiating antiretroviral therapy in Uganda.

We examined the effect of the Universal Test and Treat (UTT) policy on the characteristics of people living with HIV (PLHIV) at enrolment in HIV care and initiation of antiretroviral therapy (ART) in Uganda using data from 11 nationally representative clinics of The AIDS Support Organisation (TASO). We created two retrospective PLHIV cohorts: pre-UTT (2004-2016), where ART initiation was conditional on CD4 cell count and UTT (2017-2022), where ART was initiated regardless of World Health Organisation (WHO) clinical stage or CD4 cell count. We used a two-sample test of proportions and Wilcoxon rank-sum test to compare proportions and medians, respectively, between the cohorts. A total of 244,693 PLHIV were enrolled at the clinics [pre-UTT, 210,251 (85.9%); UTT, 34,442 (14.1%)]. Compared to the pre-UTT cohort, the UTT cohort had higher proportions of PLHIV that were male (p < 0.001), aged 18-29 years (p < 0.001), aged >69 years, never married (p < 0.001), and educated to primary (p < 0.001) and post-primary (p < 0.001) school level at enrolment in HIV care and ART initiation. Overall, 97.9% of UTT PLHIV initiated ART compared to 45.2% under pre-UTT. The median time from enrolment in HIV care to ART initiation decreased from 301 [interquartile range (IQR): 58-878] pre-UTT to 0 (IQR: 0-0) under UTT. The median CD4 count at ART initiation increased from 254 cells/µL pre-UTT to 482 cells/µL under UTT (p < 0.001). Compared to the pre-UTT cohort, the UTT cohort had higher proportions of PLHIV with a CD4 count >500 cells/µL (47.3% vs. 13.2%, p < 0.001) and WHO stage 1 (31.7% vs. 4.5%, p < 0.001) at ART initiation. Adoption of the UTT policy in Uganda was successful in enrolling previously unreached individuals, such as men and younger and older adults, as well as those with less advanced HIV disease. Future research will investigate the effect of UTT on long-term outcomes such as retention in care, HIV viral suppression, morbidity, and mortality.

Prognosis in functional and recognised pathophysiological neurological disorders - a shared basis.

OBJECTIVE: To compare self-reported outcomes, clinical trajectory and utility of baseline questionnaire responses in predicting prognosis in functional and recognised pathophysiological neurological disorders. METHODS: Baseline data on 2581 patients included health-related quality of life, psychological and physical symptoms, illness perceptions, consultation satisfaction and demographics. The prospective cohort included neurology outpatients classified with a functional (reporting symptoms 'not at all' or 'somewhat explained' by 'organic disease'; n = 716) or recognised pathophysiological disorder ('largely' or 'completely explained'; n = 1865). Logistic regression and deep neural network models were used to predict self-reported global clinical improvement (CGI) at 12-months. RESULTS: Patients with functional and recognised pathophysiological disorders reported near identical outcomes at 12-months with 67% and 66% respectively reporting unchanged or worse CGI. In multivariable modelling 'negative expectation of recovery' and 'disagreement with psychological attribution' predicted same or worse outcome in both groups. Receipt of disability-related state benefit predicted same or worse CGI outcome in the functional disorder group only (OR = 2.28 (95%-CI: 1.36-3.84) in a group-stratified model) and was not related to a measure of economic deprivation. Deep neural network models trained on all 92 baseline features predicted poor outcome with area under the receiver-operator curve of 0.67 in both groups. CONCLUSIONS: Those with functional and recognised pathophysiological neurological disorder share similar outcomes, clinical trajectories, and poor prognostic markers in multivariable models. Prediction of outcome at a patient level was not possible using the baseline data in this study.

The burden of HIV, syphilis and schistosome infection and associated factors among adults in the fishing communities in northwestern Tanzania.

OBJECTIVES: To quantify the burden of HIV, syphilis and schistosome infection and associated risk factors among adults living in seven fishing communities of Lake Victoria in northwest Tanzania. METHODS: Cross-sectional study conducted between 2015 and 2016 in the selected communities. In each community, we randomly selected a sample of adults from the general population and from three putative risk groups including the following: (i) fishermen, (ii) fish processors and traders, and (iii) women working in the recreational facilities. Participants were interviewed to obtain information about potential risk factors, and venous blood was collected for detection of HIV, syphilis and schistosome infections. We used logistic regression models to quantify the associations between potential risk factors and HIV, and also between schistosome infection and HIV. RESULTS: We enrolled 1128 people from selected fishing communities. The overall prevalence of HIV, syphilis and schistosome infection was 14.2%, 15.6% and 83.1%, respectively. Female recreational facility workers had the highest prevalence of HIV (30.4%) and syphilis (24%). The odds of being HIV infected were generally higher in all age categories. Transactional sex was commonly reported and especially receiving gifts for sex was found to be strongly associated with HIV (adjusted OR = 2.50; 95% CI: 1.44-4.34, P = 0.008). Confirmed serological syphilis was associated with increased odds of having HIV infection. HIV was not associated with schistosome infection in a combined dataset and when we examined this separately for men and women alone. CONCLUSIONS: We observed a high burden of HIV, syphilis and schistosome infections in the fishing communities. Targeted efforts to treat and control infections have the potential to improve health among their residents.

OBJECTIFS: Quantifier la charge du VIH, de la syphilis et de l'infection à schistosomes et les facteurs de risque associés chez les adultes vivant dans sept communautés de pêcheurs du lac Victoria dans le nord-ouest de la Tanzanie. MÉTHODES: Etude transversale menée entre 2015-2016 dans les communautés sélectionnées. Dans chaque communauté, nous avons sélectionné aléatoirement un échantillon d'adultes de la population générale et de trois groupes à risque présumés, notamment: 1) les pêcheurs, 2) les transformateurs et commerçants de poisson et 3) les femmes travaillant dans les établissements de loisirs. Les participants ont été interrogés pour obtenir des informations sur les facteurs de risque potentiels, et du sang veineux a été collecté pour la détection du VIH, de la syphilis et des infections à schistosome. Nous avons utilisé des modèles de régression logistique pour quantifier les associations entre les facteurs de risque potentiels et le VIH, ainsi qu'entre l'infection à schistosome et le VIH. RÉSULTATS: Nous avons recruté 1.128 personnes dans une sélection de communautés de pêcheurs. La prévalence globale de l'infection par le VIH, la syphilis et les schistosomes était de 14,2%, 15,6% et 83,1% respectivement. Les travailleuses des établissements de loisirs avaient la prévalence la plus élevée du VIH (30,4%) et de la syphilis (24%). Les chances d'être infecté par le VIH étaient généralement plus élevées dans toutes les catégories d'âge. Les rapports sexuels transactionnels étaient fréquemment rapportés et surtout le fait de recevoir des cadeaux pour le sexe était fortement associé au VIH (OR ajusté = 2,50; IC95%: 1,44-4,34 ; P = 0,008). La syphilis sérologique confirmée était associée à une probabilité accrue d'être infecté par le VIH. Le VIH n'était pas associé à une infection à schistosome dans un ensemble de données combinées et lorsque nous avons examiné cela séparément pour les hommes et les femmes. CONCLUSIONS: Nous avons observé une charge élevée d'infections par le VIH, la syphilis et les schistosomes dans les communautés de pêcheurs. Des efforts ciblés pour traiter et contrôler les infections ont le potentiel d'améliorer la santé des résidents.

Operationalising kangaroo Mother care before stabilisation amongst low birth Weight Neonates in Africa (OMWaNA): protocol for a randomised controlled trial to examine mortality impact in Uganda.

BACKGROUND: There are 2.5 million neonatal deaths each year; the majority occur within 48 h of birth, before stabilisation. Evidence from 11 trials shows that kangaroo mother care (KMC) significantly reduces mortality in stabilised neonates; however, data on its effect among neonates before stabilisation are lacking. The OMWaNA trial aims to determine the effect of initiating KMC before stabilisation on mortality within seven days relative to standard care. Secondary objectives include exploring pathways for the intervention's effects and assessing incremental costs and cost-effectiveness between arms. METHODS: We will conduct a four-centre, open-label, individually randomised, superiority trial in Uganda with two parallel groups: an intervention arm allocated to receive KMC and a control arm receiving standard care. We will enrol 2188 neonates (1094 per arm) for whom the indication for KMC is 'uncertain', defined as receiving ≥ 1 therapy (e.g. oxygen). Admitted singleton, twin and triplet neonates (triplet if demise before admission of ≥ 1 baby) weighing ≥ 700-≤ 2000 g and aged ≥ 1-< 48 h are eligible. Treatment allocation is random in a 1:1 ratio between groups, stratified by weight and recruitment site. The primary outcome is mortality within seven days. Secondary outcomes include mortality within 28 days, hypothermia prevalence at 24 h, time from randomisation to stabilisation or death, admission duration, time from randomisation to exclusive breastmilk feeding, readmission frequency, daily weight gain, infant-caregiver attachment and women's wellbeing at 28 days. Primary analyses will be by intention-to-treat. Quantitative and qualitative data will be integrated in a process evaluation. Cost data will be collected and used in economic modelling. DISCUSSION: The OMWaNA trial aims to assess the effectiveness of KMC in reducing mortality among neonates before stabilisation, a vulnerable population for whom its benefits are uncertain. The trial will improve understanding of pathways underlying the intervention's effects and will be among the first to rigorously compare the incremental cost and cost-effectiveness of KMC relative to standard care. The findings are expected to have broad applicability to hospitals in sub-Saharan Africa and southern Asia, where three-quarters of global newborn deaths occur, as well as important policy and programme implications. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02811432. Registered on 23 June 2016.

Heterogeneity in District-Level Transmission of Ebola Virus Disease during the 2013-2015 Epidemic in West Africa.

The Ebola virus disease (EVD) epidemic in West Africa in 2013-2015 spread heterogeneously across the three hardest-hit countries Guinea, Liberia and Sierra Leone and the estimation of national transmission of EVD provides little information about local dynamics. To investigate district-level transmissibility of EVD, we applied a statistical modelling approach to estimate the basic reproduction number (R0) for each affected district and each country using weekly incident case numbers. We estimated growth rates during the early exponential phase of the outbreak using exponential regression of the case counts on the first eight weeks since onset. To take into account the heterogeneity between and within countries, we fitted a mixed effects model and calculated R0 based on the predicted individual growth rates and the reported serial interval distribution. At district level, R0 ranged from 0.36 (Dubréka) to 1.72 (Beyla) in Guinea, from 0.53 (Maryland) to 3.37 (Margibi) in Liberia and from 1.14 (Koinadugu) to 2.73 (Western Rural) in Sierra Leone. At national level, we estimated an R0 of 0.97 (95% CI 0.77-1.18) for Guinea, 1.26 (95% CI 0.98-1.55) for Liberia and 1.66 (95% CI 1.32-2.00) for Sierra Leone. Socio-demographic variables related to urbanisation such as high population density and high wealth index were found positively associated with R0 suggesting that the consequences of fast urban growth in West Africa may have contributed to the increased spread of EVD.

Adolescent seasonal allergic rhinitis and the impact of health-care professional training: cluster randomised controlled trial of a complex intervention in primary care.

BACKGROUND: Seasonal allergic rhinitis is typically poorly managed, particularly in adolescents, in whom it is responsible for considerable morbidity. Our previous work has demonstrated that if poorly controlled this can impair educational performance. AIM: The primary aim of this trial was to assess the impact of a primary care-based professional training intervention on clinical outcomes in adolescents with seasonal allergic rhinitis. METHODS: Cluster trial in which UK general practice staff were randomised to a short, intensive workshop on the evidence-based management of seasonal allergic rhinitis. The primary outcome measure was the change in the validated Rhinoconjunctivitis Quality of Life Questionnaire with Standardized Activities (RQLQ(S)) score between baseline and 6 weeks post intervention (minimal clinically important difference=0.5). Secondary outcome measures of interest included health-care professionals' knowledge and confidence in managing seasonal allergic rhinitis, number of seasonal allergic rhinitis-related consultations, relevant treatments prescribed and symptom scores. RESULTS: Thirty-eight general practices were randomised (20 in the intervention arm) and 246 patients (50.2% males, mean age 15 years) were included in the primary outcome analysis. Health-care professionals' knowledge and confidence of the clinical management of seasonal allergic rhinitis improved. This did not, however, result in clinically or statistically significant improvements in RQLQ(S): -0.15, (95% confidence interval, -0.5 to +0.2). There were no differences in consultation frequency, treatments issued for seasonal allergic rhinitis or symptom scores. CONCLUSIONS: Although associated with increases in professionals' self-assessed confidence and understanding of seasonal allergic rhinitis management, this intensive training workshop did not translate into improvements in adolescents' disease-specific quality of life or a reduction in rhinitis symptoms.