Study protocol: a pragmatic, cluster-randomized controlled trial to evaluate the effect of implementation of the Truenat platform/MTB assays at primary health care clinics in Mozambique and Tanzania (TB-CAPT CORE).

BACKGROUND: In 2020, the WHO-approved Molbio Truenat platform and MTB assays to detect Mycobacterium tuberculosis complex (MTB) and resistance to rifampicin directly on sputum specimens. This primary health care center-based trial in Mozambique and Tanzania investigates the effect of Truenat platform/MTB assays (intervention arm) combined with rapid communication of results compared to standard of care on TB diagnosis and treatment initiation for microbiologically confirmed TB at 7 days from enrolment. METHODS: The Tuberculosis Close the Gap, Increase Access, and Provide Adequate Therapy (TB-CAPT) CORE trial employs a pragmatic cluster randomized controlled design to evaluate the impact of a streamlined strategy for delivery of Truenat platform/MTB assays testing at primary health centers. Twenty-nine centers equipped with TB microscopy units were selected to participate in the trial. Among them, fifteen health centers were randomized to the intervention arm (which involves onsite molecular testing using Truenat platform/MTB assays, process process optimization to enable same-day TB diagnosis and treatment initiation, and feedback on Molbio platform performance) or the control arm (which follows routine care, including on-site sputum smear microscopy and the referral of sputum samples to off-site Xpert testing sites). The primary outcome of the study is the absolute number and proportion of participants with TB microbiological confirmation starting TB treatment within 7 days of their first visit. Secondary outcomes include time to bacteriological confirmation, health outcomes up to 60 days from first visit, as well as user preferences, direct cost, and productivity analyses. ETHICS AND DISSEMINATION: TB-CAPT CORE trial has been approved by regulatory and ethical committees in Mozambique and Tanzania, as well as by each partner organization. Consent is informed and voluntary, and confidentiality of participants is maintained throughout. Study findings will be presented at scientific conferences and published in peer-reviewed international journals. TRIAL REGISTRATION: US National Institutes of Health's ClinicalTrials.gov, NCT04568954. Registered 23 September 2020.

Prevalence and clinical characteristics of pulmonary TB among pregnant and post-partum women.

SETTING: Antenatal care (ANC) and postpartum care (PPC) clinic in Manhiça District, Mozambique.OBJECTIVE: To estimate the prevalence of TB among pregnant and post-partum women and describe the clinical characteristics of the disease in a rural area of Southern Mozambique.METHODS: We conducted a cross-sectional TB prevalence study among pregnant and post-partum women recruited from September 2016 to March 2018 at the Manhiça Health Care Center (MHC). We recruited two independent cohorts of women consecutively presenting for routine pregnancy or post-partum follow-up visits.RESULTS: A total of 1,980 women from the ANC clinic and 1,010 from the PPC clinic were enrolled. We found a TB prevalence of 505/100,000 (95% CI: 242-926) among pregnant women and 297/100,000 (95% CI: 61-865) among post-partum women. Among HIV-positive pregnant women, TB prevalence was 1,626/100,000 (95% CI: 782-2,970) and among postpartum HIV-positive women, TB prevalence was 984/100,000 (95% CI: 203-2,848).CONCLUSIONS: The burden of TB was not higher in postpartum women than in pregnant women. Most TB cases were detected in HIV-positive women. TB screening and diagnostic testing among pregnant and postpartum women attending ANC and PPC clinics in Manhiça District is acceptable and feasible.

Clinical standards for the diagnosis, treatment and prevention of TB infection.

BACKGROUND: Tuberculosis (TB) preventive therapy (TPT) decreases the risk of developing TB disease and its associated morbidity and mortality. The aim of these clinical standards is to guide the assessment, management of TB infection (TBI) and implementation of TPT.METHODS: A panel of global experts in the field of TB care was identified; 41 participated in a Delphi process. A 5-point Likert scale was used to score the initial standards. After rounds of revision, the document was approved with 100% agreement.RESULTS: Eight clinical standards were defined: Standard 1, all individuals belonging to at-risk groups for TB should undergo testing for TBI; Standard 2, all individual candidates for TPT (including caregivers of children) should undergo a counselling/health education session; Standard 3, testing for TBI: timing and test of choice should be optimised; Standard 4, TB disease should be excluded prior to initiation of TPT; Standard 5, all candidates for TPT should undergo a set of baseline examinations; Standard 6, all individuals initiating TPT should receive one of the recommended regimens; Standard 7, all individuals who have started TPT should be monitored; Standard 8, a TBI screening and testing register should be kept to inform the cascade of care.CONCLUSION: This is the first consensus-based set of Clinical Standards for TBI. This document guides clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage TBI.

Integration of TB into child health policies in Africa's high-burden countries: a normative analysis.

Integration of paediatric TB care into decentralised child health services has the potential to reduce the large proportion of childhood TB that remains undiagnosed. We performed a review of national guidelines and policies for TB and child health to evaluate the normative integration of paediatric TB into existing child health programmes in 15 high TB burden countries in Africa. While integration is addressed in 80% of the national strategic plans for TB, the child health strategies insufficiently address TB in their plans to reduce child mortality. Emphasis needs to be put on multi-sectoral collaboration among national health programmes.

Intégrer la prise en charge antituberculeuse de l'enfant aux services de soins pédiatriques décentralisés pourrait permettre de réduire la proportion élevée de cas de TB pédiatriques qui restent non diagnostiqués. Nous avons examiné les politiques et recommandations nationales en matière de TB et de soins pédiatriques afin d'évaluer l'intégration normative de la TB pédiatrique aux programmes de prise en charge pédiatrique existant dans 15 pays africains à forte prévalence de TB. Cette intégration est abordée dans 80% des plans stratégiques nationaux pour la TB, mais les stratégies relatives aux soins pédiatriques ne tiennent pas suffisamment compte de la TB dans leurs plans visant à réduire la mortalité infantile. Il convient de mettre l'accent sur la collaboration multisectorielle entre les programmes de santé nationaux.

Acute phase proteins and IP-10 as triage tests for the diagnosis of tuberculosis: systematic review and meta-analysis.

OBJECTIVES: We examined the data reported in studies for diagnostic purposes and to discuss whether their intended use could be extended to triage, as rule-in or rule-out tests to select individuals who should undergo further confirmatory tests. METHODS: We searched Scopus, PubMed and Web of Science with the terms 'acute phase proteins,' 'IP-10,' 'tuberculosis,' 'screening' and 'diagnosis,' extracted the sensitivity and specificity of the biomarkers and explored methodologic differences to explain performance variations. Summary estimates were calculated using random-effects models for overall pooled accuracy. The hierarchical summary receiver operating characteristic model was used for meta-analysis. RESULTS: We identified 14, four and one studies for C-reactive protein (CRP), interferon γ-induced protein 10 (IP-10) and alpha-1-acid glycoprotein (AGP). The pooled CRP sensitivity/specificity (95% confidence interval) was 89% (80-96) and 57% (36-65). Sensitivity/specificity were higher in high-tuberculosis-burden countries (90%/64%), HIV-infected individuals (91%/61%) and community-based studies (90%/62%). IP-10 sensitivity/specificity in TB vs. non-TB studies was 85%/63% and in TB and HIV coinfected vs. other lung conditions 94%/21%. However, IP-10 studies included diverse populations and a high risk of bias, resulting in very low-quality evidence. AGP had 86%/93% sensitivity/specificity. CONCLUSIONS: Few studies have evaluated CRP, IP-10 and AGP for the triage of symptomatic patients. Their high sensitivity and moderate specificity warrant further prospective studies exploring whether their combined use could optimize performance.

Point of care diagnostics for tuberculosis.

The goals of the End TB strategy, which aims to achieve a 90% reduction in tuberculosis (TB) incidence and a 95% reduction in TB mortality by 2035, will not be achieved without new tools to fight TB. These include improved point of care (POC) diagnostic tests that are meant to be delivered at the most decentralised levels of care where the patients make the initial contact with the health system, as well as within the community. These tests should be able to be performed on an easily accessible sample and provide results in a timely manner, allowing a quick treatment turnaround time of a few minutes or hours (in a single clinical encounter), hence avoiding patient loss-to-follow-up. There have been exciting developments in recent years, including the WHO endorsement of Xpert MTB/RIF, Xpert MTB/RIF Ultra, loop-mediated isothermal amplification (TB-LAMP) and lateral flow lipoarabinomannan (LAM). However, these tests have limitations that must be overcome before they can be optimally applied at the POC. Furthermore, worrying short- to medium-term gaps exist in the POC diagnostic test development pipeline. Thus, not only is better implementation of existing tools and algorithms needed, but new research is required to develop new POC tests that allow the TB community to truly make an impact and find the "missed TB cases".

Tuberculosis drug resistance in Southern Mozambique: results of a population-level survey in the district of Manhiça.

SETTING: Mozambique, one of the world's high tuberculosis (TB) burden countries, has conducted only one national-level drug resistance survey, in 2007-2008. OBJECTIVE: To determine the drug resistance patterns of laboratory-confirmed TB cases. DESIGN: This was a population-level survey conducted over a 1-year period in the district of Manhiça. All laboratory-confirmed cases were evaluated for first-line anti-tuberculosis drug susceptibility testing using liquid culture. RESULTS: Resistance to at least one first-line drug was observed in 44 of 276 isolates (15.9%). Prevalence of drug resistance to each of the five anti-tuberculosis drugs tested was 4.0% for streptomycin, 10.1% for isoniazid (INH), 6.2% for rifampicin, 3.6% for ethambutol and 1.1% for pyrazinamide. The overall prevalence of multidrug-resistant TB (MDR-TB) was 5.1%: 3.8% (95%CI 2.0-7.0) in new and 13.2% (95%CI 5.8-27.3) in retreatment cases. Respectively 4.6% and 2.6% of new and retreatment cases were INH-monoresistant. Previous history of anti-tuberculosis treatment was associated with having MDR-TB (OR 4.3, 95%CI 1.3-14.1). CONCLUSION: The prevalence of drug resistance in the district of Manhiça is slightly higher than, but still compatible with, previous national estimates. INH monoresistance was high, posing the risk of hidden monotherapy in the continuation phase.

Hepatitis B and A vaccination in HIV-infected adults: A review.

Hepatitis B and A account for considerable morbidity and mortality worldwide. Immunization is the most effective means of preventing hepatitis B and A. However, the immune response to both hepatitis vaccines seems to be reduced in HIV-infected subjects. The aim of this review was to analyze the immunogenicity, safety, long-term protection and current recommendations of hepatitis B and A vaccination among HIV-infected adults. The factors most frequently associated with a deficient level of anti-HBs or IgG anti-HAV after vaccination are those related to immunosuppression (CD4 level and HIV RNA viral load) and to the frequency of administration and/or the amount of antigenic load per dose. The duration of the response to both HBV and HAV vaccines is associated with suppression of the viral load at vaccination and, in the case of HBV vaccination, with a higher level of antibodies after vaccination. In terms of safety, there is no evidence of more, or different, adverse effects compared with HIV-free individuals. Despite literature-based advice on the administration of alternative schedules, revaccination after the failure of primary vaccination, and the need for periodic re-evaluation of antibody levels, few firm recommendations are found in the leading guidelines.