A systematic review of the efficacy and safety of turmeric in the treatment of digestive disorders.

Turmeric has been gaining popularity as a treatment option for digestive disorders, although a rigorous synthesis of efficacy has not been conducted. This study aimed to summarize the evidence for the efficacy and safety of turmeric in the treatment of digestive disorders, including inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), dyspepsia, gastroesophageal reflux disease, and peptic ulcers. Literature searches were conducted in Medline, EMBASE, AMED, the Cochrane Central Register of Control Trials, and Dissertation Abstracts from inception to November 15, 2021. Dual independent screening of citations and full texts was conducted and studies meeting inclusion criteria were retained: randomized controlled trials (RCT) and comparative observational studies evaluating turmeric use in people of any age with one of the digestive disorders of interest. Extraction of relevant data and risk of bias assessments were performed by two reviewers independently. Meta-analysis was not conducted due to high heterogeneity. From 1136 citations screened, 26 eligible studies were retained. Most studies were assessed to have a high risk of bias, and many had methodological limitations. Descriptive summaries suggest that turmeric is safe, with possible efficacy in patients with IBD or IBS, but its effects were inconsistent for other conditions. The efficacy of turmeric in digestive disorders remains unclear due to the high risk of bias and methodological limitations of the included studies. Future studies should be designed to include larger sample sizes, use rigorous statistical methods, employ core outcome sets, and adhere to reporting guidance for RCTs of herbal interventions to facilitate more meaningful comparisons and robust conclusions.

Ofloxacin-Containing Multidrug Therapy in Ambulatory Leprosy Patients: A Case Series.

BACKGROUND: Standard dapsone and clofazimine-containing multidrug therapy (MDT) for leprosy is limited by drug tolerability, which poses treatment adherence barriers. Although ofloxacin-based regimens are promising alternatives, current efficacy and safety data are limited, particularly outside of endemic areas. We evaluated treatment outcomes in patients with leprosy receiving ofloxacin-containing MDT (OMDT) at our center. METHODS: We performed a retrospective chart review of patients treated for leprosy at our center over an 8-year period (2011-2019). Primary outcomes evaluated were clinical cure rate, occurrence of leprosy reactions, antibiotic-related adverse events, and treatment adherence. Analyses were descriptive; however, data were stratified by age, sex, spectrum of disease, region of origin, and treatment regimen, and odds ratios were reported to assess associations with adverse outcomes. RESULTS: Over the enrolment period, 26 patients were treated with OMDT (n = 19 multibacillary, n = 7 paucibacillary), and none were treated with clofazimine-based standard MDT. At the time of analysis, 23 patients (88%) had completed their course of treatment, and all were clinically cured, while 3 (12%) were still on treatment. Eighteen patients (69%) experienced either ENL (n = 7, 27%), type 1 reactions (n = 7, 27%), or both (n = 4, 15%). No patients stopped ofloxacin due to adverse drug effects, and there were no cases of allergic hypersensitivity, tendinopathy or rupture, or C. difficile colitis. CONCLUSIONS: We demonstrate a high cure rate and tolerability of OMDT in this small case series over an 8-year period, suggesting its viability as an alternative to standard clofazimine-containing MDT.

A systematic review of BCG vaccination policies among high-risk groups in low TB-burden countries: implications for vaccination strategy in Canadian indigenous communities.

BACKGROUND: Bacille Calmette-Guérin (BCG) vaccination against tuberculosis (TB) is widespread in high-TB-burden countries, however, BCG vaccination policies in low-burden countries vary. Considering the uncertainties surrounding BCG efficacy and the lower likelihood of TB exposure in low-incidence countries, most have discontinued mass vaccination, choosing instead a targeted vaccination strategy among high-risk groups. Given the increased risk of TB infection in Canadian Indigenous communities compared to the general Canadian population, these communities are a pertinent example of high-incidence groups in an otherwise low-burden country, warranting particular consideration regarding BCG vaccination strategy. This systematic review aims to synthesise and critically appraise the literature on BCG vaccination strategies in high-risk groups in low-incidence settings to provide policy considerations relevant to the Canadian Indigenous context. METHODS: A literature search of the Medline and Embase databases was conducted, returning studies pertaining to BCG vaccine efficacy, TB incidence under specific vaccination policies, BCG-associated adverse events, and vaccination policy guidelines in low-burden countries. Study screening was tracked using the Covidence systematic review software (Veritas Health Innovation, Melbourne, Australia), and data pertaining to the above points of interest were extracted. RESULTS: The final review included 49 studies, spanning 15 countries. Although almost all of these countries had implemented a form of mass or routine vaccination previously, 11 have since moved to targeted vaccination of selected risk groups, in most cases due to the low risk of infection among the general population and thus the high number of vaccinations needed to prevent one case in the context of low-incidence settings. Regarding identifying risk groups for targeted screening, community-based (rather than individual risk-factor-based) vaccination has been found to be beneficial in high-incidence communities within low-incidence countries, suggesting this approach may be beneficial in the Canadian Indigenous setting. CONCLUSIONS: Community-based vaccination of high-incidence communities may be beneficial in the Canadian Indigenous context, however, where BCG vaccination is implemented, delivery strategies and potential barriers to achieving adequate coverage in this setting should be considered. Where an existing vaccination program is discontinued, it is crucial that an effective TB surveillance system is in place, and that case-finding, screening, and diagnostic efforts are strengthened in order to ensure adequate TB control. This is particularly relevant in Canadian Indigenous and other remote or under-served communities, where barriers to surveillance, screening, and diagnosis persist.

The effect of HIV educational interventions on HIV-related knowledge, condom use, and HIV incidence in sub-Saharan Africa: a systematic review and meta-analysis.

BACKGROUND: As high stigmatization of HIV and relatively low knowledge of HIV transmission and prevention measures persist in Sub-Saharan Africa, the improvement of HIV-related knowledge, and the evaluation of which types of interventions are most effective in this regard, is an important aspect of further prevention efforts. In addition, it is of interest to assess whether improvements in HIV-related knowledge may actually lead to increased engagement in preventive behaviours and ultimately lower HIV transmission. This study therefore aims to systematically review and meta-analyse the evidence for the effect of HIV-related knowledge interventions on 1) the improvement of HIV-related knowledge, 2) subsequent risk reduction behaviour (condom use), 3) lower incidence of HIV infection. METHODS: A literature search was conducted using the Embase and Medline databases, returning 746 after duplicate removal. Following abstract and full-text screening, 36 studies were ultimately included in the final review. Meta-analyses were conducted in R, using random-effects models, for the HIV-related knowledge, condom use, and HIV incidence outcomes, where sufficient data were available. RESULTS: Interventions assessed in the reviewed studies varied, including computer-based interventions, mass media campaigns, and peer education interventions. The interventions were generally found to be effective at improving HIV-related knowledge in the target population, with 10 studies reporting improved knowledge of risk reduction through condom use in the intervention group (out of 11 studies reporting data for this outcome), with 6 reporting these differences as significant (p < 0.05). Regarding knowledge of transmission routes, studies assessing peer education interventions often reported significant improvements in the intervention group. Meta-analysis results showed significantly higher odds among the intervention groups of correct knowledge of: risk reduction through condom use (OR: 3.09, 95%CI: 1.83-5.22, p < 0.0001), sexual transmission of HIV (OR: 5.86, 95%CI: 2.65-12.97, p < 0.001) and transmission through sharps (OR: 4.35, 95%CI = 3.21-5.90, p < 0.001), but non-significantly lower odds of HIV infection (OR: 0.97, 95%CI: 0.66-1.41, p = 0.854). CONCLUSION: Peer-education-based interventions appear to be particularly effective in facilitating the uptake of HIV-related knowledge, particularly pertaining to transmission routes. There is some evidence that improved knowledge of HIV transmission and prevention facilitates increased subsequent engagement in preventive measures, although this requires further exploration. TRIAL REGISTRATION: PROSPERO Number: CRD42018090600.

Recommendations for the screening of paediatric latent tuberculosis infection in indigenous communities: a systematic review of screening strategies among high-risk groups in low-incidence countries.

BACKGROUND: Tuberculosis (TB) continues to be a global public health concern. Due to the presence of multiple risk factors such as poor housing conditions and food insecurity in Canadian Indigenous communities, this population is at particularly high risk of TB infection. Given the challenges of screening for latent TB infection (LTBI) in remote communities, a synthesis of the existing literature regarding current screening strategies among high-risk groups in low-incidence countries is warranted, in order to provide an evidence base for the optimization of paediatric LTBI screening practices in the Canadian Indigenous context. METHODS: A literature search of the Embase and Medline databases was conducted, and studies pertaining the evaluation of screening strategies or screening tools for LTBI in paediatric high-risk groups in low-incidence countries were included. Studies focusing on LTBI screening in Indigenous communities were also included, regardless of whether they focused on a paediatric population. Their results were summarized and discussed in the context of their relevance to screening strategies suitable to the Canadian Indigenous setting. Grey literature sources such as government reports or policy briefs were also consulted. RESULTS: The initial literature search returned 327 studies, with 266 being excluded after abstract screening, and 36 studies being included in the final review (original research studies: n = 25, review papers or policy recommendations: n = 11). In the examined studies, case identification and cost-effectiveness of universal screening were low in low-incidence countries. Therefore, studies generally recommended targeted screening of high-risk groups in low-incidence countries, however, there remains a lack of consensus regarding cut-offs for the incidence-based screening of high-risk communities, as well as regarding the utility and prioritization of individual risk-factor-based screening of high-risk groups. The utility of the TST compared to IGRAs for LTBI detection in the pediatric population also remains contested. CONCLUSIONS: Relevant strategies for targeted screening in the Canadian Indigenous context include community-level incidence-based screening (screening based on geographic location within high-incidence communities), as well as individual risk-factor-based screening, taking into account pertinent risk factors in Indigenous settings, such as poor housing conditions, malnutrition, contact with an active case, or the presence of relevant co-morbidities, such as renal disease.

Case fatality among people with drug-susceptible TB enrolled in a private health sector TB treatment support program in Bihar, India during the first year of the COVID-19 pandemic.

Experiencing 27% of the global tuberculosis (TB) burden, India's TB epidemic is the largest in the world. Due to COVID-19-related disruptions to TB programs, India has also seen the largest drop in TB case notifications of any country globally. We estimated case fatality among people treated for TB in India during the pandemic and compared these to pre-pandemic estimates. A random sample of 4,000 adults enrolled in World Health Partners (WHP), a private sector TB treatment support program (enrolling only people with drug-susceptible TB) in Bihar, India in the first year of COVID-19 (Mar 2020-Mar 2021) were contacted via phone to collect information on TB case fatality and other relevant covariates. Inverse probability of selection (IPS) weighting was used to obtain selection-bias-corrected in-treatment and post-treatment case fatality estimates. Covariates associated with (but not necessarily causal of) case fatality were identified by estimating adjusted hazard ratios (HRs) using the Cox proportional hazards model. WHP enrolled 19,826 adult drug-susceptible TB patients in the first year of COVID-19 (Mar 2020 to Mar 2021). Of our random sample of 4,000 patients, n = 2,962 (74.1%) answered the follow-up call. Unweighted and IPS-weighted in-treatment case fatality in the primary analysis were 6.12% (95%CI: 5.31-6.97%) and 6.07% (95%CI: 5.22-6.93%), respectively. Post-treatment case fatality estimates were 0.97% (95%CI: 0.61-1.33%) (unweighted) and 1.27% (95%CI: 0.79-1.79) (IPS-weighted). Our IPS-weighted estimates for in-treatment and post-treatment case fatality were similar to pre-pandemic IPS-weighted estimates (in-treatment: 7.27%, 95%CI: 5.97%- 8.49% and 12 months post-treatment: 1.23, 95%CI: 0.75-1.73). Although not higher than pre-pandemic estimates, the observed case fatality in this private sector cohort of people treated for drug-susceptible TB during COVID-19 in Bihar, India is above the level needed to reach the 2025 and 2030 End TB Strategy targets for reductions in TB deaths, underlining the extent of pandemic-related setbacks to TB elimination.

Tuberculosis case notifications and outcomes in Peruvian prisons prior to and during the COVID-19 pandemic: a national-level interrupted time series analysis.

Background: The COVID-19 pandemic has significantly disrupted tuberculosis (TB) programs, making it urgent to focus TB elimination efforts on key populations. People experiencing incarceration are at high risk for TB, however, how COVID-19-related disruptions have impacted incarcerated populations with TB is unknown. Methods: Using Peruvian National TB Program data from Jan 2018 to Dec 2021, an interrupted time series of drug-susceptible (DS) TB case notifications pre- and during COVID-19 was conducted (cut-off date: COVID-19 emergency declaration in Peru, 16 March 2020). The effect of TB care occurring pre-vs. during COVID-19 on TB treatment success in the incarcerated and non-incarcerated populations was explored using logistic regression. Findings: DS-TB cases notified in prisons from Jan 2018 to Dec 2021 (n = 10,134) represented 10% of all cases notified in the country (n = 101,507). In the first week of COVID-19, DS-TB case notifications dropped by 61.2% (95% CI: 59.9-62.7%) in the non-incarcerated population and 17.7% (95% CI: 17.5-17.9%) among the incarcerated population. TB treatment success was significantly lower in people receiving TB care entirely during the COVID-19 pandemic vs. before COVID-19 in the non-incarcerated population (OR: 0.81, 95% CI: 0.78-0.85), but not statistically significantly lower in the incarcerated population (OR: 0.88, 95% CI: 0.76-1.01). Incarceration status was not found to modify the effect of COVID-19 period on TB treatment outcomes (OR: 1.07, 95% CI: 0.92-1.25), although treatment success was higher in the incarcerated population (OR [incarcerated vs. not incarcerated, pre-COVID]: 1.52, 95% CI: 1.39-1.67). Interpretation: Both incarcerated and non-incarcerated populations experienced a large drop in DS-TB case notifications (although higher in the non-incarcerated population). Lower TB treatment success among those receiving care during COVID-19 indicates significant TB service disruptions in the overall population. The finding that incarceration at time of diagnosis was associated with treatment success is plausible in Peru given increased screening and stricter treatment monitoring in prisons. Funding: Canadian Institutes of Health Research (Funding Reference Number: 179418) .

The state of tuberculosis surveillance in Canada.

Tuberculosis incidence in Canada has remained essentially unchanged over the past decade. A strategic plan to reduce the burden of disease, underpinned by high-quality surveillance data, is sorely needed. However, tuberculosis surveillance data are lacking in Canada for multiple reasons. There is no single entity responsible for coordinating a tuberculosis response, including strategies for surveillance, thus inhibiting effective solutions. This in turn affects the timeliness and comprehensiveness of national tuberculosis surveillance reporting: between 2000 and 2020, there was an average 25-month delay to publication of annual surveillance data and the comprehensiveness of reports has precipitously fallen over time. Compounding these issues are case report forms for tuberculosis surveillance data which have not been updated since 2011, failing to keep up with the changing tuberculosis epidemiology and to provide information required for strategic planning. Common-sense steps can be taken to vastly improve the utility of collected tuberculosis surveillance data, and the development of a strategic plan for tuberculosis elimination. These include initiating a country-wide consultation on surveillance needs; allocating resources for data collection and analysis and data sharing; setting precise, measurable goals; and, importantly, establishing an oversight committee with representation from all provincial/territorial tuberculosis program leads who are held to account for performance.

RéSUMé: L'incidence de la tuberculose au Canada est demeurée essentiellement inchangée au cours de la dernière décennie. Un plan stratégique visant à réduire le fardeau de la maladie, étayé par des données de surveillance de haute qualité, est grandement nécessaire. Cependant, les données de surveillance de la tuberculose font défaut au Canada pour de multiples raisons. Il n'existe pas d'entité unique chargée de coordonner la réponse à la tuberculose, y compris les stratégies de surveillance, ce qui empêche de trouver des solutions efficaces. Cette situation a une incidence sur la rapidité et l'exhaustivité des rapports nationaux de surveillance de la tuberculose : entre 2000 et 2020, la publication des données annuelles de surveillance a été retardée de 25 mois en moyenne, et l'exhaustivité des rapports a chuté de façon vertigineuse au fil du temps. Ces problèmes sont aggravés par le fait que les formulaires de déclaration des cas pour les données de surveillance de la tuberculose n'ont pas été mis à jour depuis 2011, ce qui entrave leur capacité à suivre l'évolution de l'épidémiologie de la tuberculose et à fournir les informations nécessaires à la planification stratégique. Des mesures de bon sens peuvent être prises pour améliorer considérablement l'utilité des données de surveillance de la tuberculose collectées et le développement d'un plan stratégique pour l'élimination de la tuberculose. Il s'agit notamment de lancer une consultation à l'échelle du pays sur les besoins en matière de surveillance, d'allouer des ressources pour la collecte et l'analyse des données et leur partage, de fixer des objectifs précis et mesurables et, surtout, d'établir un comité de surveillance composé de représentants de tous les responsables provinciaux/territoriaux du programme de lutte contre la tuberculose qui sont tenus de rendre compte des performances.

Improving measurement of tuberculosis care cascades to enhance people-centred care.

Care cascades represent the proportion of people reaching milestones in care for a disease and are widely used to track progress towards global targets for HIV and other diseases. Despite recent progress in estimating care cascades for tuberculosis (TB) disease, they have not been routinely applied at national and subnational levels, representing a lost opportunity for public health impact. As researchers who have estimated TB care cascades in high-incidence countries (India, Madagascar, Nigeria, Peru, South Africa, and Zambia), we describe the utility of care cascades and identify measurement challenges, including the lack of population-based disease burden data and electronic data capture, the under-reporting of people with TB navigating fragmented and privatised health systems, the heterogeneity of TB tests, and the lack of post-treatment follow-up. We outline an agenda for rectifying these gaps and argue that improving care cascade measurement is crucial to enhancing people-centred care and achieving the End TB goals.

Gender differences in survival among low birthweight newborns and infants in sub-Saharan Africa: a systematic review.

In sub-Saharan Africa, low birthweight (LBW) accounts for three-quarters of under-five mortality and morbidity. However, gender differences in survival among LBW newborns and infants have not yet been systematically examined. This review examines gender differences in survival among LBW newborns and infants in the region. Ovid Medline, Embase, CINAHL, Scopus and Global Health databases were searched for qualitative, quantitative and mixed methods studies. Studies that presented information on differences in mortality or in morbidity between LBW male and female newborns or infants were eligible for inclusion. The database search yielded 4124 articles, of which 11 were eligible for inclusion. A narrative synthesis method was used to summarize the findings of the included studies. Seven studies reported more LBW male deaths, three studies reported more LBW female deaths and one study did not disaggregate the deaths by gender. Nine of the 11 studies that examined gender differences in mortality did not find significant evidence of gender differences in mortality among LBW newborns and infants. Likewise, no significant differences were found for gender differences in morbidity among this population. The review findings suggest a need for further research on this topic given the potential significance on child health and developmental goals.

The diagnostic performance of novel skin-based in-vivo tests for tuberculosis infection compared with purified protein derivative tuberculin skin tests and blood-based in vitro interferon-γ release assays: a systematic review and meta-analysis.

BACKGROUND: Novel skin-based tests for tuberculosis infection might present suitable alternatives to current tests; however, diagnostic performance of new tests compared with the purified protein derivative-tuberculin skin test (TST) or interferon-γ release assays (IGRA) needs systematic assessment. METHODS: In this systematic review and meta-analysis, we searched English (Medline OVID), Chinese (Chinese Biomedical Literature Database and the China National Knowledge Infrastructure), and Russian (e-library) databases from the inception of each database to May 15, 2019, (with updated search of the Russian and English databases on Oct, 20 2020) using terms "ESAT6" OR "CFP10" AND "skin test" AND "Tuberculosis" OR "C-Tb" OR "Diaskintest". We included studies reporting on the performance of index tests alone or compared with a comparator. Inclusion criteria varied according to review objectives and performance outcome, but reporting of test cut-offs for positivity applied to study population was required from all studies. We used a hierarchy of reference standards for tuberculosis infection consistent with the 2020 WHO framework to evaluate diagnostic performance. Two authors independently reviewed the titles and abstracts for English and Chinese (LF and MK) and Russian studies (MK and VN). Study quality was assessed with QUADAS-2. Pooled random-effects estimates are presented when appropriate for total agreement proportion, sensitivity in microbiologically confirmed tuberculosis and specificity in cohorts with low risk of tuberculosis infection. This study is registered with PROSPERO, CRD42019135572. FINDINGS: We identified 1466 original articles, of which 37 (2·5%) studies, including 10 915 individuals (7111 Diaskintest, 2744 C-Tb, 887 EC, 173 DPPD), were included in the qualitative analysis (29 [78%] studies of Diaskintest, five [15%] studies of C-Tb, two [5%] studies of EC-skintest, and one [3%] study of DPPD). 22 (1·5%) studies including 5810 individuals (3143 Diaskintest, 2129 C-Tb, 538 EC-skintest) were included in the quantitative analysis: 15 (68%) of Diaskintest, five (23%) of C-Tb, and two (9%) of EC-skintest. Tested sub-populations included individuals with HIV, children (0-18 years), and individuals exposed to tuberculosis. Studies were heterogeneous with moderate to high risk of bias. Nine head-to-head studies of index test versus TST and IGRA permitted direct comparisons and pooling. In a mixed cohort of people with and without tuberculosis, Diaskintest pooled agreement with IGRA was 87·16% (95% CI 79·47-92·24) and 55·45% (46·08-64·45) with TST-5 mm cut-off (TST5 mm). Diaskintest sensitivity was 91·18% (95% CI 81·72-95·98) compared with 88·24% (78·20-94·01) for TST5 mm, 89·66 (78·83-95·28) for IGRA QuantiFERON, and 90·91% (79·95-96·16) for TSPOT.TB. C-Tb agreement with IGRA in individuals with active tuberculosis was 79·80% (95% CI 76·10-83·07) compared with 78·92% (74·65-82·63) for TST5 mm/15 mm cut-off (TST5 mm/15 mm). TST5/15mm reflects threshold in cohorts that applied stratified cutoffs: 5 mm for HIV-infected, immunocompromised, or BCG-naive individuals, and 15mm for BCG-vaccinated immunocompetent individuals. C-Tb sensitivity was 74·52% (95% CI 70·39-78·25) compared with a sensitivity of 78·18% (67·75-85·94) for TST5 mm/15 mm, and 71·67% (63·44-78·68) for IGRA. Specificity was 97·85% (95% CI 93·96-99·25) for C-Tb versus 93·31% (90·22-95·48) for TST 15 mm cut-off and 99·15% (79·66-99·97) for IGRA. EC-skintest sensitivity was 86·06% (95% CI 82·39-89·07). INTERPRETATION: Novel skin-based tests for tuberculosis infection appear to perform similarly to IGRA or TST; however, study quality varied. Evaluation of test performance, patient-important outcomes, and diagnostic use in current clinical algorithms will inform implementation in key populations. FUNDING: StopTB (New Diagnostics Working Group) and FIND. TRANSLATIONS: For the Chinese and Russian translations of the abstract see Supplementary Materials section.

How are high burden countries implementing policies and tools for latent tuberculosis infection? A survey of current practices and barriers.

BACKGROUND AND AIMS: Despite the World Health Organization (WHO)'s updated guidelines on tuberculosis (TB) preventive treatment, the scale-up of TB preventive therapy remains low in many high-burden countries (HBCs). We conducted a survey to better understand the current status of policy implementation and barriers for scale-up. METHODS: Survey questions pertained to HBCs' current latent TB infection (LTBI) screening and treatment strategies, and the availability of LTBI tests and newer treatments (eg, isoniazid/rifapentine [3HP]). The 19-question survey was piloted and sent out via email in June 2019 as a protected Microsoft Word document to contacts [National TB Program (NTP) staff, researchers, and health officials] in the 30 TB HBCs. Responses were accepted until February 2020. RESULTS: Thirty-seven completed surveys from 24 HBCs were received. Respondents from five countries (Brazil, Lesotho, Mozambique, Russia, Zambia) reported having LTBI guidelines that are fully implemented. Among respondents who indicated their country currently has no LTBI guideline implementation (Angola, China, DRC, India, Indonesia, Kenya, Myanmar), the most often cited barrier to implementation was the prioritization of active TB over LTBI management (n = 5, Angola, China, DRC, India, Kenya). Of the 16 countries in which respondents reported using purified protein derivative (PPD), 9 reported having experienced a PPD shortage within the past year (from time of survey). Respondents from six countries reported currently using Interferon-gamma Release Assays (IGRAs) in their NTP, and 13 cited high cost as a barrier to IGRA use. Lastly, rifapentine was stated not be available in 8 HBCs. CONCLUSION: This survey indicates limited implementation of WHO LTBI guidelines in HBCs and provides some insight into barriers to implementation, including shortage of products (eg, PPD), high costs (eg, IGRAs), and lack of regulatory approval of newer treatments (eg, rifapentine). Thus, we should work towards price reductions for LTBI tests and treatments, and the development of tests that can be more easily implemented at peripheral healthcare levels.

Systematic review protocol examining sex differences in survival among low birthweight newborns and infants in sub-Saharan Africa.

INTRODUCTION: In sub-Saharan African countries, low birthweight (LBW) accounts for three-quarters of under-five mortality and morbidity. However, there is no systematic evidence of sex differences in LBW survival risk. The aim of this protocol is to outline the methodological process of a systematic review that will gather qualitative and quantitative data on sex differences in survival among LBW newborns and infants in sub-Saharan Africa. METHODS: This protocol adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols reporting guidelines. We will conduct a systematic review to retrieve all qualitative and quantitative studies. Electronic search strategies are being finalised on 24 February 2020 for Ovid Medline and EMBASE, and on 28 February 2020 for CINAHL, Scopus and Global Health in collaboration with a Health Sciences librarian. The primary outcome of interest is indicating sex differences in survival among LBW newborns and infants. Secondary outcomes are sex-disaggregated differences in morbidity among LBW newborns and infants. Screening, data extraction and assessments of risk of bias will be performed independently. Narrative synthesis and a meta-analysis will be conducted with studies that are compatible based on population and outcome. The systematic review is focused on the analysis of secondary data and does not require ethics approval. ETHICS AND DISSEMINATION: As it will be a systematic review, without human participants' involvement, there will be no requirement for ethical approval. The systematic review will present key evidence of sex-disaggregated differences in mortality and morbidity among LBW newborns and infants in sub-Saharan Africa. Programme managers, policy-makers and researchers can use the findings to evaluate LBW health outcomes in different sexes. The final manuscript will be disseminated through a peer-reviewed journal and scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42020163470.

The Roll-out of Child-friendly Fixed-dose Combination TB Formulations in High-TB-Burden Countries: A Case Study of STEP-TB.

Childhood tuberculosis (TB) has hitherto been treated through estimation of pediatric doses through the crushing of adult pills, but the bitter taste of the pills and the inaccuracy of this dosing method presents a challenge for both patients and healthcare providers, leading to poor treatment outcomes. The TB Alliance therefore launched the Speeding Treatments to End Pediatric-Tuberculosis (STEP-TB) project to incentivize the introduction of pediatric Fixed-Dose Combinations (FDCs) of TB drugs. This case study describes the elements of this project, evaluates its impact, and highlights future challenges for pediatric TB treatment. The impact assessment incorporates both market impact as well as projected public health impact, evaluating the availability, affordability, and quality of the FDCs, and lastly providing a projection of lives saved as a result of scale-up of the FDCs to near-universal availability and utilization, based on a publicly available pediatric TB-specific model. STEP-TB resulted in the development of two child-friendly FDCs that were successfully brought to market and made available in 20 of the project's 22 high-burden countries. On the basis of a country-specific projection of pediatric TB mortality in Kenya, scale-up to near-universal availability and utilization of the new FDCs could reduce pediatric TB-associated mortality by 2660 cases over the next 5 years. Future challenges include maintaining affordable prices for the FDCs and considering mechanisms to incentivize their introduction among high-risk groups in low-burden countries.

HIV-related knowledge in Nigeria: a 2003-2013 trend analysis.

BACKGROUND: Given Nigeria's status as the country with the second highest number of people living with HIV globally, and 9% of the total global burden of HIV being attributable to Nigeria alone in 2013, improving our understanding of the nature of the HIV epidemic in Nigeria is crucial. As HIV-related knowledge may be an important contributor to engagement in preventive behaviours, it is of interest to investigate trends in HIV-related knowledge in Nigeria with the purpose of informing future HIV prevention and education efforts. This study therefore aims to investigate trends in HIV-related knowledge in Nigeria between 2003 and 2013. METHODS: Data were derived from the 2003-2013 Nigerian Demographic and Health Surveys, and HIV-related knowledge scores were computed based on answers to HIV-related knowledge questions in the surveys. The significance of the difference between HIV-related knowledge across the time points was determined via the Kruskal-Wallis test, and changes in HIV-related knowledge were displayed graphically, stratified by relevant socio-demographic characteristics. ARIMA models were fit to the 2003 to 2013 trend data. RESULTS: Although there was generally a decrease in HIV-related knowledge across most knowledge domains in 2008, an overall increase was observed between 2003 and 2013. Unfortunately however, this was not the case for knowledge of mother-to-child transmission, which decreased between 2003 and 2013. The disparity in knowledge of HIV risk reduction between states also increased over time. CONCLUSION: These findings suggest that although HIV-related knowledge appears to be increasing overall, future HIV prevention and education programs should focus on specific knowledge domains such as mother-to-child transmission, and on specific states in which HIV-related knowledge remains low.

Evaluation of safety tool for ambulatory leprosy patients at risk of adverse outcome.

BACKGROUND: Leprosy is a potentially debilitating disease of the skin and nerves that requires a complex management approach consisting of laboratory monitoring, screening for factors that will adversely affect outcome with corticosteroids, engagement of allied health services, and prolonged follow-up. Given the complexities of leprosy management, a safety tool was developed and implemented in the Tropical Disease Unit at Toronto General Hospital. Our objective was to evaluate the utility of the tool using a retrospective chart review. METHODS: We reviewed the charts of patients with leprosy treated over a 3.5-year period: up to 3 years prior to tool implementation, and 6-months following implementation. Pre-determined outcomes of interest included: loss to follow-up; monitoring of laboratory parameters; allied health services engagement; baseline ophthalmologic assessment; and risk mitigation interventions. RESULTS: Of 17 patients enrolled, 8 were treated pre-implementation, and 9 post-implementation. Five (29.4%) pre-implementation patients were lost to follow-up compared to none post-implementation (p = 0.009). One (12.5%) pre-implementation patient was sent for baseline ophthalmologic assessment versus 8 (88.9%) post-implementation (p = 0.0034). Only post-implementation patients received referrals for occupational therapy and social work, with 77.8% (n = 7) receiving occupational therapy (p = 0.0023) and 33.3% (n = 3) social work (p = 0.2059). Laboratory parameters such as hemoglobin, hepatic transaminases, and methemoglobin were routinely monitored for patients on dapsone irrespective of tool implementation. CONCLUSIONS: Implementation of a leprosy-specific safety tool has established a user-friendly method for systemizing all elements of care, and ensuring the involvement of allied health services necessary for optimizing health outcomes.

Wealth inequality as a predictor of HIV-related knowledge in Nigeria.

INTRODUCTION: Considering the high state-level heterogeneity of HIV prevalence and socioeconomic characteristics in Nigeria, it is a relevant setting for studies into the socioeconomic correlates of HIV-related knowledge. Although the relationship between absolute poverty and HIV transmission has been studied, the role of wealth inequality in the dynamics of the HIV epidemic has yet to be investigated in Nigeria. The current study, therefore, investigates wealth inequality and other sociodemographic covariates as predictors of HIV-related knowledge, in order to identify subgroups of the Nigerian population that would benefit from HIV preventive interventions. METHODS: This study used the nationally representative 2013 Nigerian Demographic and Health Survey (NDHS). HIV-related knowledge was computed as a total score based on HIV-related knowledge indicators in the NDHS, dichotomised using the sample median as the cut-off. Wealth inequality and other relevant sociodemographic variables were introduced into a logistic regression model based on their significance in bivariate analyses. ORs derived from the model were interpreted to identify risk groups for low HIV-related knowledge after adjusting for confounding factors. RESULTS: The regression model indicated that individuals with lower literacy levels were almost twice as likely as literate respondents to have low HIV-related knowledge (adjusted OR (AOR): 1.95, 95% CI 1.85 to 2.05, P<0.001), and individuals in the upper wealth quintile were less than half as likely than those in the lower wealth quintile to have low HIV-related knowledge (AOR: 0.40, 95% CI 0.35 to 0.46, P<0.001). Women were also more than twice as likely as men to have low HIV-related knowledge at each level of wealth inequality. In addition, women were 80% less likely to have low mother-to-child transmission knowledge than men, but had over 1.5 times higher odds of having poor knowledge of HIV risk reduction measures. Ethnicity, religious affiliation, relationship status and residing in rural areas were additional significant predictors of HIV-related knowledge. CONCLUSION: HIV-related knowledge in this sample is generally low among women, those with low literacy levels, the poor, the unemployed, those residing in rural areas, those with traditional religious beliefs and those living in states with the highest wealth inequality ratios. The identification of these risk groups for low HIV-related knowledge facilitates the implementation of future evidence-based interventions among these groups in order to potentially reduce HIV transmission.

Performance of honey bee colonies under a long-lasting dietary exposure to sublethal concentrations of the neonicotinoid insecticide thiacloprid.

BACKGROUND: Substantial honey bee colony losses have occurred periodically in the last decades. The drivers for these losses are not fully understood. The influence of pests and pathogens are beyond dispute, but in addition, chronic exposure to sublethal concentrations of pesticides has been suggested to affect the performance of honey bee colonies. This study aims to elucidate the potential effects of a chronic exposure to sublethal concentrations (one realistic worst-case concentration) of the neonicotinoid thiacloprid to honey bee colonies in a three year replicated colony feeding study. RESULTS: Thiacloprid did not significantly affect the colony strength. No differences between treatment and control were observed for the mortality of bees, the infestation with the parasitic mite Varroa destructor and the infection levels of viruses. No colony losses occurred during the overwintering seasons. Furthermore, thiacloprid did not influence the constitutive expression of the immunity-related hymenoptaecin gene. However, upregulation of hymenoptaecin expression as a response to bacterial challenge was less pronounced in exposed bees than in control bees. CONCLUSION: Under field conditions, bee colonies are not adversely affected by a long-lasting exposure to sublethal concentrations of thiacloprid. No indications were found that field-realistic and higher doses exerted a biologically significant effect on colony performance. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.