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Introduction: Noma is a gangrenous infection that destroys the orofacial structures and leaves the survivors with severe functional, psychosocial, and esthetic impairments. Malocclusion is one of the central sequelae that current Noma care often neglects. Aims: This study aimed to present the pattern of malocclusion in Noma survivors and highlight the role of orthodontic and orthognathic therapy in the management. Materials and Methods: This was a cross-sectional study conducted over 6 months. After obtaining institutional ethical approval, all noma survivors with permanent teeth, including complete upper and lower molars at least on one side, who presented for review were included in the study. Patients’ demographics, Angle class of malocclusion, and various malocclusions were recorded. Data obtained were analyzed using the statistical package for the social sciences (IBM SPSS) version 25. Results: There were 35 (54.7%) males and 29 (45.3%) females in the age range of 12–36 years and a mean ± standard deviation of 22.52 ± 6.01 years. Most patients, 52 (81.3%), have Angle class 1 molar relation. Protrusion of anterior teeth was present in 34 (53.1%), posterior crossbite in 8 (12.5%), upper and lower teeth crowding in 11 (17.2%), isolated upper anterior crowding in 9 (16.7%), isolated lower anterior crowding in 4 (6.3%), and open bite in 5 (7.8%). Other dental malalignments, such as rotations and tooth displacement, were invariably present in 34 (53.1%). Conclusion: Malocclusion in noma survivors constitutes one of the most observable problems of noma sequelae. Orthodontic and orthognathic therapy could promote these patients’ surgical, esthetic, and psychosocial rehabilitation.

Polytetrafluoroethylene (PTFE)-based composites are widely in demand for microwave substrate application due to their excellent dielectric properties and low power loss. In this work, PTFE matrix filled with different contents (5 wt.% – 25 wt.%) of soda lime silica (SLS) glass powder were prepared and fabricated via dry powder processing technique. The SLS glass powder was acquired through milling process. X-ray diffraction (XRD) was used to characterise the composites for phase identification. In addition, dielectric properties of the composites were measured using open-ended coaxial probe (OCP) technique at 1 GHz to 12 GHz microwave frequencies. The XRD pattern of the composites confirmed the phase of PTFE and highlighted the interaction between the PTFE and SLS phases. The results, also, revealed that relative permittivity (ε') and loss tangent (tanδ) decrease with frequency, while they appreciate with the SLS filler content. Furthermore, the composites exhibited optimum dielectric properties at 10 GHz for 10 wt.% SLS filler with ε' and tanδ values of 2.23 and 0.0011, respectively. This result was favourably compared with some reported PTFE-based composites characterised using other methods, thereby, indicating the suitability of OCP technique for characterising solid dielectric materials for microwave substrate application.

Background: COVID-19 disrupted the TB prevention programme in the UK, especially for TB infection (TBI) care. We explore whether experience of the COVID-19 pandemic impacted on patients' perceptions of TBI and its treatment. Methods: Semi-structured interviews were conducted as part of the Research to Improve Detection and Treatment of TBI (RID-TB) programme, exploring perceptual and practical barriers to TBI treatment. Nineteen people diagnosed with TBI were interviewed between August 2020 and April 2021. Recordings were transcribed and analysed using a constant comparative approach, allowing for a dynamic and iterative exploration of themes. Themes are organised using the Perceptions and Practicalities Approach. Findings: Some participants perceived TBI as a risk factor for increased susceptibility to COVID-19, while some thought that treatment for TBI might protect against COVID-19 or mitigate its effects. Adaptations to TB services (e.g., remote follow-up) and integrated practices during the COVID-19 restrictions (e.g., medication being posted) addressed some practical barriers to TBI treatment. However, we identified beliefs about TBI and COVID-19 that are likely to act as barriers to engagement with TBI treatment, including: interpreting service delays as an indication of TBI not being serious enough for treatment and concerns about contracting COVID-19 in TB clinics. Interpretation: COVID-19 and TBI service delays influence people's perceptions and practical barriers to TBI treatment adherence. Failure to address these beliefs may lead to people's concerns about their treatment not being fully addressed. Utilised service adaptations like remote consultations to address practical barriers may be relevant beyond COVID-19. Funding: NIHR RID-TB Program (RP-PG-0217-20009).

Photocatalytic nitrogen fixation (PNF) using nanostructured materials is a promising approach that is likely to rival the most expensive and high-energy-demanding Harber-Bosch method of ammonia synthesis. This is because the process is deemed the most sustainable method of nitrogen fixation, through the direct production of ammonia and/or nitrate from water and atmospheric nitrogen with the aid of sunlight; and the system has zero emission of carbon dioxide. The PNF process is receiving much attention making it among the hot research topics in recent years. There is, however, a knowledge gap between the photocatalytic processes and the nanostructured photocatalyst. In this review, therefore, recent breakthroughs and achievements in the photocatalytic reaction processes were discussed. In addition, the nanostructured photocatalysts used in nitrogen fixation were discussed in detail. This includes the importance of the nanomaterials in photocatalysis, the types used in photocatalytic nitrogen fixation, and the synthesis methods of the nanomaterials. Also, limitations that affect the photocatalytic reaction processes as well as the ways of overcoming them such as the creation of oxygen, sulphur, and nitrogen vacancies, doping techniques, formation of heterojunctions, and the use of cocatalysts were all discussed in detail. From the aforementioned discussions, PNF could be seen as the most eco-friendly and sustainable method of nitrogen fixation. However, understanding the mechanisms of PNF is very critical to identifying and designing an efficient photocatalytic system.

Flow driven by co-rotating disks, such as hard disk drives (HDD) have been studied in previous research using axisymmetric models. In our work, a unique non-axisymmetric 3.5" transparent HDD model for information storage was used to investigate the effect of the arm insertion angle on these flow-fields. After introducing the shroud opening region in our model, we focused and illustrated the nature of flow-fields at a parameter α , defined as the arm insertion angle. Comparison was made between α = 20° closer to the shroud opening and a deeper angle of α = 44° closer to the hub. We revealed the flow pattern at the disk-to-disk middle plane (mid-plane) as well as between the arm and the upper disk boundary layer (arm-upper disk plane) across the disk region from the edge of the hub to the edge of the disk, using both flow visualisation and particle image velocimetry (PIV). The visualisation results revealed an accelerated flow around the hub downstream of the arm insertion, with a higher magnitude at α = 44° compared to α = 20°. We observed a rigid body rotation around the hub for both insertion angles.

Arbuscular mycorrhizal fungi (AMF) confer both positive and negative effects on the plant symbionts, depending on the prevailing growth condition. We investigated the effect of concurrent variations in phosphorus and soil moisture on percentage root colonization (%RC), mycorrhizal growth response (MGR) and drought response index (DRI) of SAMMAZ-16 maize variety in timescale. The experimental factors were AMF inoculation (addition or no addition), P2O5 applications (30, 60 or 90 kg ha-1) and water regimes (100% and 50% of the soil’s field capacity introduced after 4WAS). The result shows that the overall %RC was 62.22% at 8 weeks after sowing (WAS) and 71.33% at 12 WAS. With 30 and 60 kg P2O5 ha-1 application a rate, %RC was significantly higher at 12 WAS than that of similar application rates at 8 WAS. However, %RC was not different between 8 WAS and 12 WAS in 90 kg P2O5 ha-1 application. AMF inoculation tended to equilibrate the shoot growth of the inoculated plants to that of non-inoculated plants that received 50% higher doses of P2O5 under amply watered conditions. Increasing phosphorus application progressively alleviated the negative mycorrhizal response of the plants at the early stage of growth (week 4) and in 50% FC category at the other sampling times. Higher doses of P2O5 application improved the DRI of the maize in both samplings but the trend was more consistent in AMF-inoculated plants. We conclude that AMF inoculation would be detrimental to the growth of SAMMAZ-16 when there is combined phosphorus and water stress factors.

Tuberculin skin test surveys in primary school children can be used to quantify Mycobacterium tuberculosis transmission at community level. KwaZulu-Natal province, South Africa, is home to 11.5 million people and suffers a burden of tuberculosis disease that is among the highest in the world. The last tuberculin survey in the province was undertaken in 1979. We performed a tuberculin skin test survey nested within a demographic and health household surveillance programme in Northern KwaZulu-Natal. We enrolled children aged between six and eight years of age attending primary schools in this community. Mixture analysis was used to determine tuberculin skin test thresholds and the Annual Risk of Tuberculous Infection derived from age at testing and infection prevalence. The Community Infection Ratio, a measure of the relative importance of within-household and community transmission, was calculated from data on tuberculin positivity disaggregated by household tuberculosis contact. Between June and December 2013, we obtained tuberculin skin test results on 1240 children. Mixture analysis proved unstable, suggesting two potential thresholds for test positivity. Using a threshold of ≥10mm or treating all non zero reactions as positive yielded estimates of the Annual Risk of Tuberculous Infection of 1.7% (1.4-2.1%) or 2.4% (2.0-3.0%). Using the same thresholds and including children reported to be receiving TB treatment as cases, resulted in estimates of 2.0% (1.6-2.5%) or 2.7% (2.2-3.3%). The Community Infection Ratio was 0.58 (0.33-1.01). The force of infection in this community is lower than that observed in Western Cape province, South Africa, but higher than that observed in community settings in most other parts of the world. Children in this community are commonly infected with Mycobacterium tuberculosis outside the home. Interventions to interrupt transmission are urgently needed.

Tuberculosis (TB) and non-communicable diseases (NCD) share predisposing risk factors. TB-associated NCD might cluster within households affected with TB requiring shared prevention and care strategies. We conducted an individual participant data meta-analysis of national TB prevalence surveys to determine whether NCD cluster in members of households with TB. We identified eligible surveys that reported at least one NCD or NCD risk factor through the archive maintained by the World Health Organization and searching in Medline and Embase from 1 January 2000 to 10 August 2021, which was updated on 23 March 2023. We compared the prevalence of NCD and their risk factors between people who do not have TB living in households with at least one person with TB (members of households with TB), and members of households without TB. We included 16 surveys (n = 740,815) from Asia and Africa. In a multivariable model adjusted for age and gender, the odds of smoking was higher among members of households with TB (adjusted odds ratio (aOR) 1.23; 95% CI: 1.11-1.38), compared with members of households without TB. The analysis did not find a significant difference in the prevalence of alcohol drinking, diabetes, hypertension, or BMI between members of households with and without TB. Studies evaluating household-wide interventions for smoking to reduce its dual impact on TB and NCD may be warranted. Systematically screening for NCD using objective diagnostic methods is needed to understand the actual burden of NCD and inform comprehensive interventions.

Background: We investigated perinatal outcomes among live births from international migrant and local-born mothers in a cohort of low-income individuals in Brazil. Methods: We linked nationwide birth registries to mortality records and socioeconomic data from the CIDACS Birth Cohort and studied singleton live births of women aged 10–49 years from 1st January 2011 to 31st December 2018. We used logistic regressions to investigate differences in antenatal care, adverse pregnancy outcomes, and neonatal (i.e., ≤28 days) mortality among international migrants compared to non-migrants in Brazil; and explored the interaction between migration, race/ethnicity and living in international border municipalities. Results: We studied 10,279,011 live births, of which 9469 (0.1 %) were born to international migrants. Migrant women were more likely than their Brazilian-born counterparts to have a previous foetal loss (ORadj: 1.16, 1.11–1.22), a delayed start of antenatal care (i.e., beyond 1st trimester) (1.22, 95%CI:1.16–1.28), a newborn who is large for gestational age (1.29, 1.22–1.36), or a newborn with congenital anomalies (1.37, 1.14–1.65). Conversely, migrant women were less likely to deliver prematurely (0.89, 0.82–0.95) or have a low birth weight infant (0.74, 0.68–0.81). There were no differences in neonatal mortality rates between migrants and non-migrants. Our analyses also showed that, when disparities in perinatal outcomes were present, disparities were mostly concentrated among indigenous mothers in international borders and among live births of Black mothers in non-borders. Conclusion: Although live births of international migrants generally have lower rates of adverse birth outcomes, our results suggest that indigenous and Black migrant mothers may face disproportionate barriers to accessing antenatal care.

Tuberculosis is an endemic disease in certain parts of the world. This disease typically presents in the lungs, but it may also appear within the abdomen, such as in the pancreas. There can be challenges in diagnosing isolated pancreatic tuberculosis as it may mimic other diseases radiologically. We present a 33-year-old female with intermittent abdominal pain and weight loss. Chest x-rays showed normal findings while noncontrast abdominal computed tomography (CT) showed a solid cystic mass in the pancreas and in the spleen. Contrast-enhanced CT showed an inhomogeneous cystic mass in the body and tail of the pancreas with peripheral rim enhancement. A laparotomy procedure was performed, and tuberculosis was confirmed histopathologically. In this case report, we highlight the challenging nature of diagnosing isolated pancreatic and splenic tuberculosis due to its presentation, which is similar to other neoplastic processes.

Abstract Background BCG vaccination, originally used to prevent tuberculosis, is known to “train” the immune system to improve defence against viral respiratory infections. We investigated whether a previous BCG vaccination is associated with less severe clinical progression of COVID-19 Methods A case-control study comparing the proportion with a BCG vaccine scar (indicating previous vaccination) in cases and controls presenting with COVID-19 to health units in Brazil. Cases were subjects with severe COVID-19 (O2 saturation < 90%, severe respiratory effort, severe pneumonia, severe acute respiratory syndrome, sepsis, and septic shock). Controls had COVID-19 not meeting the definition of “severe” above. Unconditional regression was used to estimate vaccine protection against clinical progression to severe disease, with strict control for age, comorbidity, sex, educational level, race/colour, and municipality. Internal matching and conditional regression were used for sensitivity analysis. Results BCG was associated with high protection against COVID-19 clinical progression, over 87% (95% CI 74–93%) in subjects aged 60 or less and 35% (95% CI − 44–71%) in older subjects. Conclusions This protection may be relevant for public health in settings where COVID-19 vaccine coverage is still low and may have implications for research to identify vaccine candidates for COVID-19 that are broadly protective against mortality from future variants. Further research into the immunomodulatory effects of BCG may inform COVID-19 therapeutic research.

Introduction Recent outbreaks of mpox are characterised by changes in the natural history of the disease, the demographic and clinical characteristics of the cases, and widening geographical distribution. We investigated the role of HIV and other sexually transmitted infections (STIs) coinfection among cases in the re-emergence of mpox to inform national and global response.Methods We conducted a national descriptive and case–control study on cases in the 2017–2019 Nigerian mpox outbreak. Mpox cases were age, sex and geographical area matched each with two randomly selected controls from a representative national HIV/AIDS survey. Logistic regression was used to investigate the association between HIV infection and the risk of mpox acquisition and death.Results Among 204 suspected mpox cases, 86 were confirmed (median age 31 years (IQR 27–38 years), mostly males (61 cases, 70.9%). Three-fifths of mpox cases had serological evidence of one or more STIs with 27.9% (24/86) coinfected with HIV. The case fatality rate was 9.4% (8/86) and 20.8% (5/24) overall and in HIV positive cases respectively. Mpox cases were more likely to have HIV coinfection compared with an age, gender and geography-matched control group drawn from the general population (OR 45 (95% CI 6.1 to 333.5, p=0.002) and when compared with non mpox rash cases (7.29 (95% CI 2.6 to 20.5, p

Objectives COVID-19 studies report on hospital admission outcomes across SARS-CoV-2 waves of infection but knowledge of the impact of SARS-CoV-2 variants on the development of Long COVID in hospital survivors is limited. We sought to investigate Long COVID outcomes, aiming to compare outcomes in adult hospitalised survivors with known variants of concern during our first and second UK COVID-19 waves, prior to widespread vaccination.Design Prospective observational cross-sectional study.Setting Secondary care tertiary hospital in the UK.Participants This study investigated Long COVID in 673 adults with laboratory-positive SARS-CoV-2 infection or clinically suspected COVID-19, 6 weeks after hospital discharge. We compared adults with wave 1 (wildtype variant, admitted from February to April 2020) and wave 2 patients (confirmed Alpha variant on viral sequencing (B.1.1.7), admitted from December 2020 to February 2021).Outcome measures Associations of Long COVID presence (one or more of 14 symptoms) and total number of Long COVID symptoms with SARS-CoV-2 variant were analysed using multiple logistic and Poisson regression, respectively.Results 322/400 (wave 1) and 248/273 (wave 2) patients completed follow-up. Predictors of increased total number of Long COVID symptoms included: pre-existing lung disease (adjusted count ratio (aCR)=1.26, 95% CI 1.07, 1.48) and more COVID-19 admission symptoms (aCR=1.07, 95% CI 1.02, 1.12). Weaker associations included increased length of inpatient stay (aCR=1.02, 95% CI 1.00, 1.03) and later review after discharge (aCR=1.00, 95% CI 1.00, 1.01). SARS-CoV-2 variant was not associated with Long COVID presence (OR=0.99, 95% CI 0.24, 4.20) or total number of symptoms (aCR=1.09, 95% CI 0.82, 1.44).Conclusions Patients with chronic lung disease or greater COVID-19 admission symptoms have higher Long COVID risk. SARS-CoV-2 variant was not predictive of Long COVID though in wave 2 we identified fewer admission symptoms, improved clinical trajectory and outcomes. Addressing modifiable factors such as length of stay and timepoint of clinical review following discharge may enable clinicians to move from Long COVID risk stratification towards improving its outcome.

Summary: Background: Non-communicable diseases (NCDs) and NCD risk factors, such as smoking, increase the risk for tuberculosis (TB). Data are scarce on the risk of prevalent TB associated with these factors in the context of population-wide systematic screening and on the association between NCDs and NCD risk factors with different manifestations of TB, where ∼50% being asymptomatic but bacteriologically positive (subclinical). We did an individual participant data (IPD) meta-analysis of national and sub-national TB prevalence surveys to synthesise the evidence on the risk of symptomatic and subclinical TB in people with NCDs or risk factors, which could help countries to plan screening activities. Methods: In this systematic review and IPD meta-analysis, we identified eligible prevalence surveys in low-income and middle-income countries that reported at least one NCD (e.g., diabetes) or NCD risk factor (e.g., smoking, alcohol use) through the archive maintained by the World Health Organization and by searching in Medline and Embase from January 1, 2000 to August 10, 2021. The search was updated on March 23, 2023. We performed a one-stage meta-analysis using multivariable multinomial models. We estimated the proportion of and the odds ratio for subclinical and symptomatic TB compared to people without TB for current smoking, alcohol use, and self-reported diabetes, adjusted for age and gender. Subclinical TB was defined as microbiologically confirmed TB without symptoms of current cough, fever, night sweats, or weight loss and symptomatic TB with at least one of these symptoms. We assessed heterogeneity using forest plots and I2 statistic. Missing variables were imputed through multi-level multiple imputation. This study is registered with PROSPERO (CRD42021272679). Findings: We obtained IPD from 16 national surveys out of 21 national and five sub-national surveys identified (five in Asia and 11 in Africa, N = 740,815). Across surveys, 15.1%–56.7% of TB were subclinical (median: 38.1%). In the multivariable model, current smoking was associated with both subclinical (OR 1.67, 95% CI 1.27–2.40) and symptomatic TB (OR 1.49, 95% CI 1.34–1.66). Self-reported diabetes was associated with symptomatic TB (OR 1.67, 95% CI 1.17–2.40) but not with subclinical TB (OR 0.92, 95% CI 0.55–1.55). For alcohol drinking ≥ twice per week vs no alcohol drinking, the estimates were imprecise (OR 1.59, 95% CI 0.70–3.62) for subclinical TB and OR 1.43, 95% CI 0.59–3.46 for symptomatic TB). For the association between current smoking and symptomatic TB, I2 was high (76.5% (95% CI 62.0–85.4), while the direction of the point estimates was consistent except for three surveys with wide CIs. Interpretation: Our findings suggest that current smokers are more likely to have both symptomatic and subclinical TB. These individuals can, therefore, be prioritised for intensified screening, such as the use of chest X-ray in the context of community-based screening. People with self-reported diabetes are also more likely to have symptomatic TB, but the association is unclear for subclinical TB. Funding: None.

Rhizosphere is a bio–influenced zone of soil where the interaction of microorganism and plant roots occurred tailored by the activity of soil enzymes. The activity of the enzymes depends largely on the physical and chemical characteristics of the soil environment. Experiment was carried out to examine the activity of phosphomonoesterases in the rhizosphere of cassava planted in two sites (Samaru and Minjibir) located in savanna ecologies of Nigeria. Soils from rhizosphere of the cassava were sampled from each treatment in an experiment involving split plot design. The treatments included 3 main plots (phosphorus rates at 0, 17.5 and 35 kg P2O5 ha–1) and 3 sub–plots (mycorrhizal inoculants: Glomygel and Mycodrip; and a Control). The Result of the analysis indicated higher activities of the phosphomonoesterases (acid and alkaline phosphatases) in Samaru site than Minjibir. The former recorded higher acid and alkaline phosphates activities over the latter with a magnitude of 96.84% and 43.65% respectively. This is attributed to the variability in the soil characteristics between the two sites. The main effect of P fertilizer indicated that 0 kg P2O5 ha–1 recorded a significantly (p

Nigeria had a confirmed case of COVID-19 on February 28, 2020. On March 17, 2020, the Nigerian Government inaugurated the Presidential Task Force (PTF) on COVID-19 to coordinate the country’s multisectoral intergovernmental response. The PTF developed the National COVID-19 Multisectoral Pandemic Response Plan as the blueprint for implementing the response plans. The PTF provided funding, coordination, and governance for the public health response and executed resource mobilization and social welfare support, establishing the framework for containment measures and economic reopening. Despite the challenges of a weak healthcare infrastructure, staff shortages, logistic issues, commodity shortages, currency devaluation, and varying state government cooperation, high-level multisectoral PTF coordination contributed to minimizing the effects of the pandemic through early implementation of mitigation efforts, supported by a strong collaborative partnership with bilateral, multilateral, and private-sector organizations. We describe the lessons learned from the PTF COVID-19 for future multisectoral public health response.

Abstract In South Korea, public–private mix (PPM) was launched in 2011. This retrospective cohort study sought to determine the rate of loss to follow-up (LTFU) among drug-susceptible tuberculosis (DS-TB) patients in all nationwide PPM institutions, and the risk factors for LTFU. National notification data for DS-TB patients diagnosed between August 2011 and July 2014 in PPM institutions were analysed. Determination of LTFU included detection of instances where patients were transferred out, but when they did not attend at other TB centres in the following two months. Univariable and multivariable competing risk models were used to determine risk factors for LTFU. 73,046 patients with 78,485 records were enrolled. Nominally, 3426 (4.4%) of records were LTFU. However, after linking the multiple records in each patient, the percentage of LTFU was 12.3% (9004/73,046). Risk factors for LTFU were: being foreign-born (3.13 (95% CI 2.77–3.53)), prior LTFU (2.31 (2.06–2.59)) and greater distance between the patient’s home and the TB centre (4.27 (4.03–4.53)). ‘Transfer-out’ was a risk factor in patients managed by treatment centres close to home (1.65 (1.49–1.83)), but protective for those attending centres further (0.77 (0.66–0.89)) or far-away (0.52 (0.46–0.59)) from home. By considering the complete picture of a patient’s interactions with healthcare, we identified a much higher level of LTFU than previously documented. This has implications for how outcomes of treatment are reported and argues for a joined-up national approach for the management and surveillance of TB patients, in nations with similar healthcare systems.

Summary: Background: To understand if migrants living in poverty in low and middle-income countries (LMICs) have mortality advantages over the non-migrant population, we investigated mortality risk patterns among internal and international migrants in Brazil over their life course. Methods: We linked socio-economic and mortality data from 1st January 2011 to 31st December 2018 in the 100 Million Brazilian Cohort and calculated all-cause and cause-specific age-standardised mortality rates according to individuals' migration status for men and women. Using Cox regression models, we estimated the age- and sex-adjusted mortality hazard ratios (HR) for internal migrants (i.e., Brazilian-born individuals living in a different Brazilian state than their birth) compared to Brazilian-born non-migrants; and for international migrants (i.e., people born in another country) compared to Brazilian-born individuals. Findings: The study followed up 45,051,476 individuals, of whom 6,057,814 were internal migrants, and 277,230 were international migrants. Internal migrants had similar all-cause mortality compared to Brazilian non-migrants (aHR = 0.99, 95% CI = 0.98–0.99), marginally higher mortality for ischaemic heart diseases (aHR = 1.04, 95% CI = 1.03–1.05) and higher for stroke (aHR = 1.11, 95% CI = 1.09–1.13). Compared to Brazilian-born individuals, international migrants had 18% lower all-cause mortality (aHR = 0.82, 95% CI = 0.80–0.84), with up to 50% lower mortality from interpersonal violence among men (aHR = 0.50, 95% CI = 0.40–0.64), but higher mortality from avoidable causes related to maternal health (aHR = 2.17, 95% CI = 1.17–4.05). Interpretation: Although internal migrants had similar all-cause mortality, international migrants had lower all-cause mortality compared to non-migrants. Further investigations using intersectional approaches are warranted to understand the marked variations by migration status, age, and sex for specific causes of death, such as elevated maternal mortality and male lower interpersonal violence-related mortality among international migrants. Funding: The Wellcome Trust.

Summary: Background: Evidence on the comparative performance of purified protein derivative tuberculin skin tests (TST) and interferon-gamma release assays (IGRA) for predicting incident active tuberculosis (TB) remains conflicting. We conducted an individual participant data meta-analysis to directly compare the predictive performance for incident TB disease between TST and IGRA to inform policy. Methods: We searched Medline and Embase from 1 January 2002 to 4 September 2020, and studies that were included in previous systematic reviews. We included prospective longitudinal studies in which participants received both TST and IGRA and estimated performance as hazard ratios (HR) for the development of all diagnoses of TB in participants with dichotomised positive test results compared to negative results, using different thresholds of positivity for TST. Secondary analyses included an evaluation of the impact of background TB incidence. We also estimated the sensitivity and specificity for predicting TB. We explored heterogeneity through pre-defined sub-group analyses (e.g. country-level TB incidence). Publication bias was assessed using funnel plots and Egger's test. This review is registered with PROSPERO, CRD42020205667. Findings: We obtained data from 13 studies out of 40 that were considered eligible (N = 32,034 participants: 36% from countries with TB incidence rate ≥100 per 100,000 population). All reported data on TST and QuantiFERON Gold in-Tube (QFT-GIT). The point estimate for the TST was highest with higher cut-offs for positivity and particularly when stratified by bacillus Calmette–Guérin vaccine (BCG) status (15 mm if BCG vaccinated and 5 mm if not [TST5/15 mm]) at 2.88 (95% CI 1.69–4.90). The pooled HR for QFT-GIT was higher than for TST at 4.15 (95% CI 1.97–8.75). The difference was large in countries with TB incidence rate

Evidence on the economic impact of novel skin tests for tuberculosis infection (TBST) is scarce and limited by study quality. We used estimates on the cost-effectiveness of the use of TBST compared to current tuberculosis infection (TBI) tests to assess whether TBST are affordable and feasible to implement under different country contexts. A Markov model parametrised to Brazil, South Africa and the UK was developed to compare the cost-effectiveness of three TBI testing strategies: (1) Diaskintest (DST), (2) TST test, and (3) IGRA QFT test. Univariate and probabilistic sensitivity analyses over unit costs and main parameters were performed. Our modelling results show that Diaskintest saves $5.60 and gains 0.024 QALYs per patient and $8.40, and 0.01 QALYs per patient in Brazil, compared to TST and IGRA respectively. In South Africa, Diaskintest is also cost-saving at $4.39, with 0.015 QALYs per patient gained, compared to TST, and $64.41, and 0.007 QALYs per patient, compared to IGRA. In the UK, Diaskintest saves $73.33, and gaines 0.0351 QALYs per patient, compared to TST. However, Diaskintest, compared to IGRA, showed an incremental cost of $521.45 (95% CI (500.94-545.07)) per QALY, below the willingness-to-pay threshold of $20.223 per QALY. Diaskintest potentially saves costs and results in greater health gains than the TST and IGRA tests in Brazil and South Africa. In the UK Diaskintest would gain health but also be more costly. Our results have potential external validity because TBST remained cost-effective despite extensive sensitivity analyses.

Lassa Fever is a rodent-borne viral haemorrhagic fever that is a public health problem in West Africa. Here, the authors develop a spatiotemporal model of the socioecological drivers of disease using surveillance data from Nigeria, and find evidence of climate sensitivity.

Introduction The successful scale-up of a latent tuberculosis (TB) infection testing and treatment programme is essential to achieve TB elimination. However, poor adherence compromises its therapeutic effectiveness. Novel rifapentine-based regimens and treatment support based on behavioural science theory may improve treatment adherence and completion.Methods and analysis A pragmatic multicentre, open-label, randomised controlled trial assessing the effect of novel short-course rifapentine-based regimens for TB prevention and additional theory-based treatment support on treatment adherence against standard-of-care. Participants aged between 16 and 65 who are eligible to start TB preventive therapy will be recruited in England. 920 participants will be randomised to one of six arms with allocation ratio of 5:5:6:6:6:6: daily isoniazid +rifampicin for 3 months (3HR), routine treatment support (control); 3HR, additional treatment support; weekly isoniazid +rifapentine for 3 months (3HP), routine treatment support; weekly 3HP, additional treatment support ; daily isoniazid +rifapentine for 1 month (1HP), routine treatment support; daily 1HP, additional treatment support. Additional treatment support comprises reminders using an electronic pillbox, a short animation, and leaflets based on the perceptions and practicalities approach. The primary outcome is adequate treatment adherence, defined as taking ≥90% of allocated doses within the pre-specified treatment period, measured by electronic pillboxes. Secondary outcomes include safety and TB incidence within 12 months. We will conduct process evaluation of the trial interventions and assess intervention acceptability and fidelity and mechanisms for effect and estimate the cost-effectiveness of novel regimens. The protocol was developed with patient and public involvement, which will continue throughout the trial.Ethics and dissemination Ethics approval has been obtained from The National Health Service Health Research Authority (20/LO/1097). All participants will be required to provide written informed consent. We will share the results in peer-reviewed journals.Trial registration number EudraCT 2020-004444-29.

BackgroundIn 2017, Korea implemented a nationwide project to screen and treat latent tuberculosis infection (LTBI) in high-risk for transmission public congregate settings. We aimed to assess programme success using a cascade of care framework.Materials and methodsWe undertook a cohort study of people from three congregate settings screened between March 2017 and December 2018: (1) first-grade high school students, (2) employees of educational institutions, (3) employees of social welfare facilities. We report percentages of participants with LTBI completing each step in the cascade of care model. Poisson regression models were used to determine factors associated with not visiting clinics, not initiating treatment, and not completing treatment.ResultsAmong the 96,439 participants who had a positive interferon-gamma release assay result, the percentage visiting clinics for further assessment, to initiate treatment, and who then completed treatment were 50.7, 34.7, and 28.9%, respectively. Compared to those aged 20–34 years, individuals aged < 20 years and aged ≥ 65 years were less likely to visit clinics, though more likely to complete treatment once initiated. Using public health centres rather than private hospitals was associated with people “not initiating treatment” (adjusted risk ratio [aRR], 3.72; 95% confidence interval [CI], 3.95–3.86). Nine-month isoniazid monotherapy therapy was associated with “not completing treatment,” compared to 3-month isoniazid and rifampin therapy (aRR, 1.28; 95% CI, 1.16–1.41).ConclusionAmong participants with LTBI from three congregate settings, less than one third completed treatment. Age, treatment centre, and initial regimen were important determinants of losses to care through the cascade.

Abstract Background HIV is known to increase the likelihood of reactivation of latent tuberculosis to active TB disease; however, its impact on tuberculosis infectiousness and consequent transmission is unclear, particularly in low-incidence settings. Methods National surveillance data from England, Wales and Northern Ireland on tuberculosis cases in adults from 2010 to 2014, strain typed using 24-locus mycobacterial-interspersed-repetitive-units–variable-number-tandem-repeats was used retrospectively to identify clusters of tuberculosis cases, subdivided into ‘first’ and ‘subsequent’ cases. Firstly, we used zero-inflated Poisson regression models to examine the association between HIV status and the number of subsequent clustered cases (a surrogate for tuberculosis infectiousness) in a strain type cluster. Secondly, we used logistic regression to examine the association between HIV status and the likelihood of being a subsequent case in a cluster (a surrogate for recent acquisition of tuberculosis infection) compared to the first case or a non-clustered case (a surrogate for reactivation of latent infection). Results We included 18,864 strain-typed cases, 2238 were the first cases of clusters and 8471 were subsequent cases. Seven hundred and fifty-nine (4%) were HIV-positive. Outcome 1: HIV-positive pulmonary tuberculosis cases who were the first in a cluster had fewer subsequent cases associated with them (mean 0.6, multivariable incidence rate ratio [IRR] 0.75 [0.65–0.86]) than those HIV-negative (mean 1.1). Extra-pulmonary tuberculosis (EPTB) cases with HIV were less likely to be the first case in a cluster compared to HIV-negative EPTB cases. EPTB cases who were the first case had a higher mean number of subsequent cases (mean 2.5, IRR (3.62 [3.12–4.19]) than those HIV-negative (mean 0.6). Outcome 2: tuberculosis cases with HIV co-infection were less likely to be a subsequent case in a cluster (odds ratio 0.82 [0.69–0.98]), compared to being the first or a non-clustered case. Conclusions Outcome 1: pulmonary tuberculosis-HIV patients were less infectious than those without HIV. EPTB patients with HIV who were the first case in a cluster had a higher number of subsequent cases and thus may be markers of other undetected cases, discoverable by contact investigations. Outcome 2: tuberculosis in HIV-positive individuals was more likely due to reactivation than recent infection, compared to those who were HIV-negative.

Tuberculosis (TB) remains a significant global health crisis and the number one cause of death for an infectious disease. The health consequences in high-burden countries are significant. Barriers to TB control and eradication are in part caused by difficulties in diagnosis. Improvements in diagnosis are required for organisations like the World Health Organisation (WHO) to meet their ambitious target of reducing the incidence of TB by 50% by the year 2025, which has become hard to reach due to the COVID-19 pandemic. Development of new tests for TB are key priorities of the WHO, as defined in their 2014 report for target product profiles (TPPs). Rapid triage and biomarker-based confirmatory tests would greatly enhance the diagnostic capability for identifying and diagnosing TB-infected individuals. Protein-based test methods e.g. lateral flow devices (LFDs) have a significant advantage over other technologies with regard to assay turnaround time (minutes as opposed to hours) field-ability, ease of use by relatively untrained staff and without the need for supporting laboratory infrastructure. Here we evaluate the diagnostic performance of nine biomarkers from our previously published biomarker qPCR validation study; CALCOCO2, CD274, CD52, GBP1, IFIT3, IFITM3, SAMD9L, SNX10 and TMEM49, as protein targets assayed by ELISA. This preliminary evaluation study was conducted to quantify the level of biomarker protein expression across latent, extra-pulmonary or pulmonary TB groups and negative controls, collected across the UK and India, in whole lysed blood samples (WLB). We also investigated associative correlations between the biomarkers and assessed their suitability for ongoing diagnostic test development, using receiver operating characteristic/area under the curve (ROC) analyses, singly and in panel combinations. The top performing single biomarkers for pulmonary TB versus controls were CALCOCO2, SAMD9L, GBP1, IFITM3, IFIT3 and SNX10. TMEM49 was also significantly differentially expressed but downregulated in TB groups. CD52 expression was not highly differentially expressed across most of the groups but may provide additional patient stratification information and some limited use for incipient latent TB infection. These show therefore great potential for diagnostic test development either in minimal configuration panels for rapid triage or more complex formulations to capture the diversity of disease presentations.

Introduction Globally, tuberculosis (TB) is a leading cause of death in women of reproductive age and there is high risk of reactivation of latent tuberculosis infection (LTBI) in pregnancy. The uptake of routine screening of migrants for LTBI in the UK in primary care is low. Antenatal care is a novel setting which could improve uptake and can lend insight into the feasibility and acceptability of offering opt-out screening for LTBI.Methods and analysis This is an observational feasibility study with a nested qualitative component. The setting will be the antenatal clinics in three hospitals in East London, UK . Inclusion criteria are pregnant migrant women aged 16–35 years attending antenatal clinics who are from countries with a TB incidence of greater than 150/100 000 including sub-Saharan Africa, and who have been in the UK for less than 5 years. Participants will be offered LTBI screening with an opt-out interferon gamma release assay blood test, and be invited to complete a questionnaire. Both participants and healthcare providers will be invited to participate in semistructured interviews or focus groups to evaluate understanding, feasibility and acceptability of routine opt-out LTBI screening. The primary analysis will focus on estimating the uptake of the screening programme along with the corresponding 95% CI. Secondary analysis will focus on estimating the test positivity. Qualitative analysis will evaluate the acceptability of offering routine opt-out LTBI screening to participants and healthcare providers.Ethics and dissemination The study has received the following approvals: Health Research Authority (IRAS 247388) and National Health Service Ethics Committee (19/LO/0557). The results will be made available locally to antenatal clinics and primary care physicians, nationally to NHS England and Public Health England and internationally through conferences and journals.Trial registration number NCT04098341.

Predicting vector abundance and seasonality, key components of mosquito-borne disease (MBD) hazard, is essential to determine hotspots of MBD risk and target interventions effectively. Japanese encephalitis (JE), an important MBD, is a leading cause of viral encephalopathy in Asia with 100,000 cases estimated annually, but data on the principal vector Culex tritaeniorhynchus is lacking. We developed a Bayesian joint-likelihood model that combined information from available vector occurrence and abundance data to predict seasonal vector abundance for C. tritaeniorhynchus (a constituent of JE hazard) across India, as well as examining the environmental drivers of these patterns. Using data collated from 57 locations from 24 studies, we find distinct seasonal and spatial patterns of JE vector abundance influenced by climatic and land use factors. Lagged precipitation, temperature and land use intensity metrics for rice crop cultivation were the main drivers of vector abundance, independent of seasonal, or spatial variation. The inclusion of environmental factors and a seasonal term improved model prediction accuracy (mean absolute error [MAE] for random cross validation = 0.48) compared to a baseline model representative of static hazard predictions (MAE = 0.95), signalling the importance of seasonal environmental conditions in predicting JE vector abundance. Vector abundance varied widely across India with high abundance predicted in northern, north-eastern, eastern, and southern regions, although this ranged from seasonal (e.g., Uttar Pradesh, West Bengal) to perennial (e.g., Assam, Tamil Nadu). One-month lagged predicted vector abundance was a significant predictor of JE outbreaks (odds ratio 2.45, 95% confidence interval: 1.52-4.08), highlighting the possible development of vector abundance as a proxy for JE hazard. We demonstrate a novel approach that leverages information from sparse vector surveillance data to predict seasonal vector abundance-a key component of JE hazard-over large spatial scales, providing decision-makers with better guidance for targeting vector surveillance and control efforts.

The observed epidemiology of SARS-CoV-2 in sub-Saharan Africa has varied greatly from that in Europe and the United States, with much lower reported incidence. Population-based studies are needed to estimate true cumulative incidence of SARS-CoV-2 to inform public health interventions. This study estimated SARS-CoV-2 seroprevalence in four selected states in Nigeria in October 2020. We implemented a two-stage cluster sample household survey in four Nigerian states (Enugu, Gombe, Lagos, and Nasarawa) to estimate age-stratified prevalence of SARS-CoV-2 antibodies. All individuals in sampled households were eligible for interview, blood draw, and nasal/oropharyngeal swab collection. We additionally tested participants for current/recent malaria infection. Seroprevalence estimates were calculated accounting for the complex survey design. Across all four states, 10,629 (96·5%) of 11,015 interviewed individuals provided blood samples. The seroprevalence of SARS-CoV-2 antibodies was 25·2% (95% CI 21·8-28·6) in Enugu State, 9·3% (95% CI 7·0-11·5) in Gombe State, 23·3% (95% CI 20·5-26·4) in Lagos State, and 18·0% (95% CI 14·4-21·6) in Nasarawa State. Prevalence of current/recent malaria infection ranged from 2·8% in Lagos to 45·8% in Gombe and was not significantly related to SARS-CoV-2 seroprevalence. The prevalence of active SARS-CoV-2 infection in the four states during the survey period was 0·2% (95% CI 0·1-0·4). Approximately eight months after the first reported COVID-19 case in Nigeria, seroprevalence indicated infection levels 194 times higher than the 24,198 officially reported COVID-19 cases across the four states; however, most of the population remained susceptible to COVID-19 in October 2020.

COVID-19 mortality rate has not been formally assessed in Nigeria. Thus, we aimed to address this gap and identify associated mortality risk factors during the first and second waves in Nigeria. This was a retrospective analysis of national surveillance data from all 37 States in Nigeria between February 27, 2020, and April 3, 2021. The outcome variable was mortality amongst persons who tested positive for SARS-CoV-2 by Reverse-Transcriptase Polymerase Chain Reaction. Incidence rates of COVID-19 mortality was calculated by dividing the number of deaths by total person-time (in days) contributed by the entire study population and presented per 100,000 person-days with 95% Confidence Intervals (95% CI). Adjusted negative binomial regression was used to identify factors associated with COVID-19 mortality. Findings are presented as adjusted Incidence Rate Ratios (aIRR) with 95% CI. The first wave included 65,790 COVID-19 patients, of whom 994 (1∙51%) died; the second wave included 91,089 patients, of whom 513 (0∙56%) died. The incidence rate of COVID-19 mortality was higher in the first wave [54∙25 (95% CI: 50∙98-57∙73)] than in the second wave [19∙19 (17∙60-20∙93)]. Factors independently associated with increased risk of COVID-19 mortality in both waves were: age ≥45 years, male gender [first wave aIRR 1∙65 (1∙35-2∙02) and second wave 1∙52 (1∙11-2∙06)], being symptomatic [aIRR 3∙17 (2∙59-3∙89) and 3∙04 (2∙20-4∙21)], and being hospitalised [aIRR 4∙19 (3∙26-5∙39) and 7∙84 (4∙90-12∙54)]. Relative to South-West, residency in the South-South and North-West was associated with an increased risk of COVID-19 mortality in both waves. In conclusion, the rate of COVID-19 mortality in Nigeria was higher in the first wave than in the second wave, suggesting an improvement in public health response and clinical care in the second wave. However, this needs to be interpreted with caution given the inherent limitations of the country's surveillance system during the study.

Effects of plants extract powders is the application of these extracts is to improved and increase the germination, emergence of the seedlings. Efficacy of Gmelina arborea bark and Azadirachta indica leaf powders on the germination and seedling vigour of Corchorus olitorius (jute mallow) was evaluated. Top loam soil was collected from Agriculture Research farmland of Ibrahim Badamasi Babangida University Lapai, Niger State, Nigeria and sterilized at 50 C for an hour. Gmelina arborea bark and Azadirachta indica leaf were obtained from Gmelina arborea and Azadirachta indica leaves were also collected from the farmland and pulverized into powder form. Two kilograms (2 kg) of sterile soil samples in twenty one (21) polythene bags were amended with Gmelina arborea bark powder and Azadirachta indica leaf powders at different concentrations (100 g, 150 g, and 200 g) each in triplicates. Soil samples contained in three of the polyethylene bags were left un-amended to serve as control. Corchorus olitorius seeds was procured from the harvested farmland and were planted and raised in each polythene bag for a period of twelve (12) weeks. Azadirachta indica leaf powder had a significant impact on the growth of Corchorus olitorius (shoot length = 26.52 cm; root collar diameter = 0.33 cm, number of leaves = 21) at p < 0.05 compared to the control group (20.60 cm, 0.24 cm and 16 respectively) and its effects improved with increase in concentration. Gmelina arborea bark powder also had a less significant impact on the plant growth parameters (6.45 cm, 0.14 cm and 9 respectively) compared to the control. Its effect decreased with increase in concentration. Azadirachta indica leaf powder is a much better and more effective organic amendment than Gmelina arborea bark powder and could be employed by Corchorus olitorius farmers to improve soil fertility and crop yield.

The October 2020 Global TB report reviews TB control strategies and United Nations (UN) targets set in the political declaration at the September 2018 UN General Assembly high-level meeting on TB held in New York. Progress in TB care and prevention has been very slow. In 2019, TB remained the most common cause of death from a single infectious pathogen. Globally, an estimated 10.0 million people developed TB disease in 2019, and there were an estimated 1.2 million TB deaths among HIV-negative people and an additional 208, 000 deaths among people living with HIV. Adults accounted for 88% and children for 12% of people with TB. The WHO regions of South-East Asia (44%), Africa (25%), and the Western Pacific (18%) had the most people with TB. Eight countries accounted for two thirds of the global total: India (26%), Indonesia (8.5%), China (8.4%), the Philippines (6.0%), Pakistan (5.7%), Nigeria (4.4%), Bangladesh (3.6%) and South Africa (3.6%). Only 30% of the 3.5 million five-year target for children treated for TB was met. Major advances have been development of new all oral regimens for MDRTB and new regimens for preventive therapy. In 2020, the COVID-19 pandemic dislodged TB from the top infectious disease cause of mortality globally. Notably, global TB control efforts were not on track even before the advent of the COVID-19 pandemic. Many challenges remain to improve sub-optimal TB treatment and prevention services. Tuberculosis screening and diagnostic test services need to be ramped up. The major drivers of TB remain undernutrition, poverty, diabetes, tobacco smoking, and household air pollution and these need be addressed to achieve the WHO 2035 TB care and prevention targets. National programs need to include interventions for post-tuberculosis holistic wellbeing. From first detection of COVID-19 global coordination and political will with huge financial investments have led to the development of effective vaccines against SARS-CoV2 infection. The world now needs to similarly focus on development of new vaccines for TB utilizing new technological methods.

Over a quarter of the individuals diagnosed with tuberculosis [TB] in the European Union region are born outside of the area and the proportion has been increasing steadily. Italy is a low TB incidence country with over 50% of TB cases in the foreign-born population primarily due to the high numbers of migrants entering the country via land or sea. As a case study to evaluate the value of screening in newly arrived migrants, the EDETECT-TB project in Italy implemented and evaluated active TB screening in the migrant population at first reception centres to ensure early diagnosis to avoid further spread. Based on a cost-effectiveness analysis from a program provider perspective, a decision tree model allowed the assessment of the value for money of case finding by estimating the cost per case of active TB detected compared with the status quo of no screening. The analysis confirmed that early case detection is a cost-effective intervention in areas with migrants arriving from high TB risk settings. Targeted post-arrival early screening of high TB risk vulnerable new entrants to Italy has a potential role in reducing the spread of TB among migrants.

Disruption of health services due to the COVID-19 pandemic threatens to derail progress being made in tuberculosis control efforts. Forcibly displaced people and migrant populations face particular vulnerabilities as a result of the COVID-19 pandemic, which leaves them at further risk of developing TB. They inhabit environments where measures such as “physical distancing” are impossible to realize and where facilities like camps and informal temporary settlements can easily become sites of rapid disease transmission. In this viewpoint we utilize three case studies—from Peru, South Africa, and Syria—to illustrate the lived experience of forced migration and mobile populations, and the impact of COVID-19 on TB among these populations. We discuss the dual pandemics of TB and COVID-19 in the context of migration through a syndemic lens, to systematically address the upstream social, economic, structural and political factors that - in often deleterious dynamics - foster increased vulnerabilities and risk. Addressing TB, COVID-19 and migration from a syndemic perspective, not only draws systematic attention to comorbidity and the relevance of social and structural context, but also helps to find solutions: the true reality of syndemic interactions can only be fully understood by considering a particular population and bio- social context, and ensuring that they receive the comprehensive care that they need. It also provides avenues for strengthening and expanding the existing infrastructure for TB care to tackle both COVID-19 and TB in migrants and refugees in an integrated and synergistic manner.

ABSTRACT Validated assays are essential for reliable serosurveys; however, most SARS-CoV-2 immunoassays have been validated using specimens from China, Europe, or U.S. populations. We evaluated the performance of five commercial SARS-CoV-2 immunoassays to inform their use in serosurveys in Nigeria. Four semiquantitative enzyme-linked immunosorbent assays (ELISAs) (Euroimmun anti-SARS-CoV-2 nucleocapsid protein [NCP] immunoglobulin G [IgG], Euroimmun spike SARS-CoV-2 IgG, Mologic Omega COVID-19 IgG, Bio-Rad Platelia SARS-CoV-2 Total Ab) and one chemiluminescent microparticle immunoassay (Abbott Architect SARS-CoV-2 IgG) were evaluated. We estimated the analytical performance characteristics using plasma from 100 SARS-CoV-2 PCR-positive patients from varied time points post-PCR confirmation and 100 prepandemic samples (50 HIV positive and 50 hepatitis B positive). The Bio-Rad assay failed the manufacturer-specified validation steps. The Euroimmun NCP, Euroimmun spike, and Mologic assays had sensitivities of 73.7%, 74.4%, and 76.9%, respectively, on samples taken 15 to 58 days after PCR confirmation and specificities of 97%, 100%, and 83.8%, respectively. The Abbott assay had 71.3% sensitivity and 100% specificity on the same panel. Parallel or serial algorithms combining two tests did not substantially improve the sensitivity or specificity. Our results showed lower sensitivity and, for one immunoassay, lower specificity compared to the manufacturers’ results and other reported validations. Seroprevalence estimates using these assays might need to be interpreted with caution in Nigeria and similar settings. These findings highlight the importance of in-country validations of SARS-CoV-2 serological assays prior to use to ensure that accurate results are available for public health decision-making to control the COVID-19 pandemic in Africa. IMPORTANCE This study used positive and negative sample panels from Nigeria to test the performance of several commercially available SARS-CoV-2 serological assays. Using these prepandemic and SARS-CoV-2-positive samples, we found much lower levels of sensitivity in four commercially available assays than most assay manufacturer reports and independent evaluations. The use of these assays with suboptimal sensitivity and specificity in Nigeria or countries with population exposure to similar endemic pathogens could lead to a biased estimate of the seroprevalence, over- or underestimating the true disease prevalence, and limit efforts to stop the spread of SARS-CoV-2. It is important to conduct in-country validations of serological SARS-CoV-2 assays prior to their widespread use, especially in countries with limited representation in published assay validations.

Approximately 85% of tuberculosis (TB) related deaths occur in low- and middle-income countries where health resources are scarce. Effective priority setting is required to maximise the impact of limited budgets. The Optima TB tool has been developed to support analytical capacity and inform evidence-based priority setting processes for TB health benefits package design. This paper outlines the Optima TB framework and how it was applied in Belarus, an upper-middle income country in Eastern Europe with a relatively high burden of TB. Optima TB is a population-based disease transmission model, with programmatic cost functions and an optimisation algorithm. Modelled populations include age-differentiated general populations and higher-risk populations such as people living with HIV. Populations and prospective interventions are defined in consultation with local stakeholders. In partnership with the latter, demographic, epidemiological, programmatic, as well as cost and spending data for these populations and interventions are then collated. An optimisation analysis of TB spending was conducted in Belarus, using program objectives and constraints defined in collaboration with local stakeholders, which included experts, decision makers, funders and organisations involved in service delivery, support and technical assistance. These analyses show that it is possible to improve health impact by redistributing current TB spending in Belarus. Specifically, shifting funding from inpatient- to outpatient-focused care models, and from mass screening to active case finding strategies, could reduce TB prevalence and mortality by up to 45% and 50%, respectively, by 2035. In addition, an optimised allocation of TB spending could lead to a reduction in drug-resistant TB infections by 40% over this period. This would support progress towards national TB targets without additional financial resources. The case study in Belarus demonstrates how reallocations of spending across existing and new interventions could have a substantial impact on TB outcomes. This highlights the potential for Optima TB and similar modelling tools to support evidence-based priority setting.

Abstract Background In the UK, hepatitis B virus (HBV) incidence is associated with migrants from particular high-burden countries and population groups deemed ‘hard-to-reach’ by standard healthcare services: the homeless, people who inject drugs and ex-prisoners. Currently, there is a national targeted HBV vaccine policy for such at-risk groups, but there is limited recent evidence about 1) the levels of vaccine uptake, 2) the factors associated with incomplete vaccination, and 3) reasons for incomplete vaccination. Methods A questionnaire capturing social and medical history, demographic factors and information about HBV vaccination status was completed by individuals deemed hard-to-reach due to socio-structural factors that criminalise, isolate and stigmatise who consented to participate in a randomised controlled trial of a peer intervention to promote engagement with hepatitis C services. The questionnaire also captured the reasons for incomplete vaccination. Descriptive, univariable and multivariable regression analyses were undertaken. Results Three hundred fourty six participants completed the questionnaire. 1) 52.3% (n = 181) reported full HBV vaccination. 2) Within a multivariable model adjusting for sociodemographic variables, the presence of one or two or more socio-structural factors that are included in the national targeted vaccination policy was associated with protection against incomplete HBV vaccination (51.7% vaccine coverage in those with one factor, odds ratio 0.43 [95% confidence interval 0.20–0.92]); 70.1% coverage with two or more factors, 0.19 [0.09–0.39]; overall p-value

Abstract Background Peer support can enable patient engagement with healthcare services, particularly for marginalised populations. In this randomised controlled trial, the efficacy of a peer support intervention at promoting successful engagement with clinical services for chronic hepatitis C was assessed. Methods In London, UK, potential participants were approached through outreach services for problematic drug use and homelessness. Individuals positive for hepatitis C virus (HCV) after confirmatory testing were randomised using an online service to the intervention (peer support) or standard of care. The primary outcome of interest was successful engagement with clinical hepatitis services. The study was non-blinded. Absolute differences were calculated using a generalised linear model and the results compared to logistic regression. Results Three hundred sixty-four individuals consented to participate. One hundred one had chronic hepatitis C and were randomised, 63 to receive the intervention (peer support). A successful outcome was achieved by 23 individuals in this arm (36.5%) and seven (18.4%) receiving the standard of care, giving an absolute increase of 18.1% (95% confidence interval 1.0–35.2%, p value = 0.04). This was mirrored in the logistic regression (odds ratio 2.55 (0.97–6.70), p = 0.06). No serious adverse events were reported. Conclusions Peer support can improve the engagement of patients with chronic HCV with healthcare services. Trial registration ISRCTN24707359. Registered 19th October 2012.

The identification of monkeypox in 3 separate patients in the United Kingdom in September raised media and political attention on an emerging public health threat. Nigeria, whose last confirmed case of monkeypox was in 1978, is currently experiencing an unusually large and outbreak of human monkeypox cases, a ‘One Human-Environmental-Animal Health’ approach is being effectively used to define and tackle the outbreak. As of 13th October 2018, there have been one hundred and sixteen confirmed cases the majority of whom are under 40 years. Over the past 20 years ten Central and West African countries have reported monkeypox cases which have risen exponentially. We review the history and evolution of monkeypox outbreaks in Africa and USA, the changing clinical presentations, and discuss possible factors underlying the increasing numbers being detected including the cessation of smallpox vaccination programs. Major knowledge gaps remain on the epidemiology, host reservoir, and emergence, transmission, pathogenesis and prevention of monkeypoz.

Abstract Background Transmission patterns in high tuberculosis incidence areas in England are poorly understood but need elucidating to focus contact tracing. We study transmission within and between age, ethnic and immigrant groups using molecular data from the high incidence West Midlands region. Methods Isolates from culture-confirmed tuberculosis cases during 2007–2011 were typed using 24-locus Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeats (MIRU-VNTR). We estimated the proportion of disease attributable to recent transmission, calculated the proportion of isolates matching those from the two preceding years (“retrospectively clustered”), and identified risk factors for retrospective clustering using multivariate analyses. We calculated the ratio (RCR) between the observed and expected proportion clustered retrospectively within or between age, ethnic and immigrant groups. Results Of the 2159 available genotypes (79% of culture-confirmed cases), 34% were attributed to recent transmission. The percentage retrospectively clustered decreased from 50 to 24% for 0–14 and ≥ 65 year olds respectively (p = 0.01) and was significantly lower for immigrants than the UK-born. Higher than expected clustering occurred within 15–24 year olds (RCR: 1.4 (95% CI: 1.1–1.8)), several ethnic groups, and between UK-born or long-term immigrants with the UK-born (RCR: 1.8 (95% CI: 1.1–2.4) and 1.6 (95% CI: 1.2–1.9) respectively). Conclusions This study is the first to consider “who clusters with whom” in a high incidence area in England, laying the foundation for future whole-genome sequencing work. The higher than expected clustering seen here suggests that preferential mixing between some age, ethnic and immigrant groups occurs; prioritising contact tracing to groups with which cases are most likely to cluster retrospectively could improve TB control.

Maintaining adherence to treatment for tuberculosis (TB) is essential if the disease is to be eliminated. As part of formative research to develop an intervention to improve adherence, we documented the lived experiences of adults receiving anti-TB treatment (ATT) in three UK cities and examined how personal, social, and structural circumstances interacted to impact on individuals’ adherence to treatment. Using a topic guide that explored social circumstances and experiences of TB care, we conducted in-depth interviews with 18 adults (six women) who were being or had been treated for TB (patients) and four adults (all women) who were caring for a friend, relative, or partner being treated for TB (caregivers). We analysed transcripts using an adapted framework method that classified factors affecting adherence as personal, social, structural, health systems, or treatment-related. Eleven of 18 patients were born outside the UK (in South, Central, and East Asia, and Eastern and Southern Africa); among the seven who were UK-born, four were Black, Asian, or Minority Ethnic and three were White British. TB and its treatment were often disruptive: in addition to debilitating symptoms and side effects of ATT, participants faced job insecurity, unstable housing, stigma, social isolation, worsening mental health, and damaged relationships. Those who had a strong support network, stable employment, a routine that could easily be adapted, a trusting relationship with their TB team, and clear understanding of the need for treatment reported finding it easier to adhere to ATT. Changes in circumstances sometimes had dramatic effects on an individual’s ability to take ATT; participants described how the impact of certain acute events (e.g., the onset of side effects or fatigue, episodes of stigmatisation, loss of income) were amplified by their timing or through their interaction with other elements of the individual’s life. We suggest that the dynamic and fluctuating nature of these factors necessitates comprehensive and regular review of needs and potential problems, conducted before and during ATT; this, coupled with supportive measures that consider (and seek to mitigate) the influence of social and structural factors, may help improve adherence.

Tuberculosis (TB) remains a major global threat and diagnosis of active TB ((ATB) both extra-pulmonary (EPTB), pulmonary (PTB)) and latent TB (LTBI) infection remains challenging, particularly in high-burden countries which still rely heavily on conventional methods. Although molecular diagnostic methods are available, e.g., Cepheid GeneXpert, they are not universally available in all high TB burden countries. There is intense focus on immune biomarkers for use in TB diagnosis, which could provide alternative low-cost, rapid diagnostic solutions. In our previous gene expression studies, we identified peripheral blood leukocyte (PBL) mRNA biomarkers in a non-human primate TB aerosol-challenge model. Here, we describe a study to further validate select mRNA biomarkers from this prior study in new cohorts of patients and controls, as a prerequisite for further development. Whole blood mRNA was purified from ATB patients recruited in the UK and India, LTBI and two groups of controls from the UK (i) a low TB incidence region (CNTRLA) and (ii) individuals variably-domiciled in the UK and Asia ((CNTRLB), the latter TB high incidence regions). Seventy-two mRNA biomarker gene targets were analyzed by qPCR using the Roche Lightcycler 480 qPCR platform and data analyzed using GeneSpring™ 14.9 bioinformatics software. Differential expression of fifty-three biomarkers was confirmed between MTB infected, LTBI groups and controls, seventeen of which were significant using analysis of variance (ANOVA): CALCOCO2, CD52, GBP1, GBP2, GBP5, HLA-B, IFIT3, IFITM3, IRF1, LOC400759 (GBP1P1), NCF1C, PF4V1, SAMD9L, S100A11, TAF10, TAPBP, and TRIM25. These were analyzed using receiver operating characteristic (ROC) curve analysis. Single biomarkers and biomarker combinations were further assessed using simple arithmetic algorithms. Minimal combination biomarker panels were delineated for primary diagnosis of ATB (both PTB and EPTB), LTBI and identifying LTBI individuals at high risk of progression which showed good performance characteristics. These were assessed for suitability for progression against the standards for new TB diagnostic tests delineated in the published World Health Organization (WHO) technology product profiles (TPPs).

In February 2020, Nigeria faced a potentially catastrophic COVID-19 outbreak due to multiple introductions, high population density in urban slums, prevalence of other infectious diseases and poor health infrastructure. As in other countries, Nigerian policymakers had to make rapid and consequential decisions with limited understanding of transmission dynamics and the efficacy of available control measures. We present an account of the Nigerian COVID-19 response based on co-production of evidence between political decision-makers, health policymakers and academics from Nigerian and foreign institutions, an approach that allowed a multidisciplinary group to collaborate on issues arising in real time. Key aspects of the process were the central role of policymakers in determining priority areas and the coordination of multiple, sometime conflicting inputs from stakeholders to write briefing papers and inform effective national decision making. However, the co-production approach met with some challenges, including limited transparency, bureaucratic obstacles and an overly epidemiological focus on numbers of cases and deaths, arguably to the detriment of addressing social and economic effects of response measures. Larger systemic obstacles included a complex multitiered health system, fragmented decision-making structures and limited funding for implementation. Going forward, Nigeria should strengthen the integration of the national response within existing health decision bodies and implement strategies to mitigate the social and economic impact, particularly on the poorest Nigerians. The co-production of evidence examining the broader public health impact, with synthesis by multidisciplinary teams, is essential to meeting the social and public health challenges posed by the COVID-19 pandemic in Nigeria and other countries.