Symptom- and chest-radiography screening for active pulmonary tuberculosis in HIV-negative adults and adults with unknown HIV status.

BACKGROUND: Systematic screening in high-burden settings is recommended as a strategy for early detection of pulmonary tuberculosis disease, reducing mortality, morbidity and transmission, and improving equity in access to care. Questioning for symptoms and chest radiography (CXR) have historically been the most widely available tools to screen for tuberculosis disease. Their accuracy is important for the design of tuberculosis screening programmes and determines, in combination with the accuracy of confirmatory diagnostic tests, the yield of a screening programme and the burden on individuals and the health service. OBJECTIVES: To assess the sensitivity and specificity of questioning for the presence of one or more tuberculosis symptoms or symptom combinations, CXR, and combinations of these as screening tools for detecting bacteriologically confirmed pulmonary tuberculosis disease in HIV-negative adults and adults with unknown HIV status who are considered eligible for systematic screening for tuberculosis disease. Second, to investigate sources of heterogeneity, especially in relation to regional, epidemiological, and demographic characteristics of the study populations. SEARCH METHODS: We searched the MEDLINE, Embase, LILACS, and HTA (Health Technology Assessment) databases using pre-specified search terms and consulted experts for unpublished reports, for the period 1992 to 2018. The search date was 10 December 2018. This search was repeated on 2 July 2021. SELECTION CRITERIA: Studies were eligible if participants were screened for tuberculosis disease using symptom questions, or abnormalities on CXR, or both, and were offered confirmatory testing with a reference standard. We included studies if diagnostic two-by-two tables could be generated for one or more index tests, even if not all participants were subjected to a microbacteriological reference standard. We excluded studies evaluating self-reporting of symptoms. DATA COLLECTION AND ANALYSIS: We categorized symptom and CXR index tests according to commonly used definitions. We assessed the methodological quality of included studies using the QUADAS-2 instrument. We examined the forest plots and receiver operating characteristic plots visually for heterogeneity. We estimated summary sensitivities and specificities (and 95% confidence intervals (CI)) for each index test using bivariate random-effects methods. We analyzed potential sources of heterogeneity in a hierarchical mixed-model. MAIN RESULTS: The electronic database search identified 9473 titles and abstracts. Through expert consultation, we identified 31 reports on national tuberculosis prevalence surveys as eligible (of which eight were already captured in the search of the electronic databases), and we identified 957 potentially relevant articles through reference checking. After removal of duplicates, we assessed 10,415 titles and abstracts, of which we identified 430 (4%) for full text review, whereafter we excluded 364 articles. In total, 66 articles provided data on 59 studies. We assessed the 2 July 2021 search results; seven studies were potentially eligible but would make no material difference to the review findings or grading of the evidence, and were not added in this edition of the review. We judged most studies at high risk of bias in one or more domains, most commonly because of incorporation bias and verification bias. We judged applicability concerns low in more than 80% of studies in all three domains. The three most common symptom index tests, cough for two or more weeks (41 studies), any cough (21 studies), and any tuberculosis symptom (29 studies), showed a summary sensitivity of 42.1% (95% CI 36.6% to 47.7%), 51.3% (95% CI 42.8% to 59.7%), and 70.6% (95% CI 61.7% to 78.2%, all very low-certainty evidence), and a specificity of 94.4% (95% CI 92.6% to 95.8%, high-certainty evidence), 87.6% (95% CI 81.6% to 91.8%, low-certainty evidence), and 65.1% (95% CI 53.3% to 75.4%, low-certainty evidence), respectively. The data on symptom index tests were more heterogenous than those for CXR. The studies on any tuberculosis symptom were the most heterogeneous, but had the lowest number of variables explaining this variation. Symptom index tests also showed regional variation. The summary sensitivity of any CXR abnormality (23 studies) was 94.7% (95% CI 92.2% to 96.4%, very low-certainty evidence) and 84.8% (95% CI 76.7% to 90.4%, low-certainty evidence) for CXR abnormalities suggestive of tuberculosis (19 studies), and specificity was 89.1% (95% CI 85.6% to 91.8%, low-certainty evidence) and 95.6% (95% CI 92.6% to 97.4%, high-certainty evidence), respectively. Sensitivity was more heterogenous than specificity, and could be explained by regional variation. The addition of cough for two or more weeks, whether to any (pulmonary) CXR abnormality or to CXR abnormalities suggestive of tuberculosis, resulted in a summary sensitivity and specificity of 99.2% (95% CI 96.8% to 99.8%) and 84.9% (95% CI 81.2% to 88.1%) (15 studies; certainty of evidence not assessed). AUTHORS' CONCLUSIONS: The summary estimates of the symptom and CXR index tests may inform the choice of screening and diagnostic algorithms in any given setting or country where screening for tuberculosis is being implemented. The high sensitivity of CXR index tests, with or without symptom questions in parallel, suggests a high yield of persons with tuberculosis disease. However, additional considerations will determine the design of screening and diagnostic algorithms, such as the availability and accessibility of CXR facilities or the resources to fund them, and the need for more or fewer diagnostic tests to confirm the diagnosis (depending on screening test specificity), which also has resource implications. These review findings should be interpreted with caution due to methodological limitations in the included studies and regional variation in sensitivity and specificity. The sensitivity and specificity of an index test in a specific setting cannot be predicted with great precision due to heterogeneity. This should be borne in mind when planning for and implementing tuberculosis screening programmes.

Perspectives and practices of health workers around diagnosis of paediatric tuberculosis in hospitals in a resource-poor setting - modern diagnostics meet age-old challenges.

BACKGROUND: Detection of tuberculosis (TB) in children in Kenya is sub-optimal. Xpert MTB/RIF® assay (Xpert®) has the potential to improve speed of TB diagnosis due to its sensitivity and fast turnaround for results. Significant effort and resources have been put into making the machines widely available in Kenya, but use remains low, especially in children. We set out to explore the reasons for the under-detection of TB and underuse of Xpert® in children, identifying challenges that may be relevant to other newer diagnostics in similar settings. METHODS: This was an exploratory qualitative study with an embedded case study approach. Data collection involved semi-structured interviews; small-group discussions; key informant interviews; observations of TB trainings, sensitisation meetings, policy meetings, hospital practices; desk review of guidelines, job aides and policy documents. The Capability, Opportunity and Motivation (COM-B) framework was used to interpret emerging themes. RESULTS: At individual level, knowledge, skill, competence and experience, as well as beliefs and fears impacted on capability (physical & psychological) as well as motivation (reflective) to diagnose TB in children and use diagnostic tests. Hospital level influencers included hospital norms, processes, patient flows and resources which affected how individual health workers attempted to diagnose TB in children by impacting on their capability (physical & psychological), motivation (reflective & automatic) and opportunity (physical & social). At the wider system level, community practices and beliefs, and implementation of TB programme directives impacted some of the decisions that health workers made through capability (psychological), motivation (reflective & automatic) and opportunity (physical). CONCLUSION: We used comprehensive approaches to identify influencers of TB case detection and use of TB diagnostic tests in children in Kenya. These results are being used to design a contextually-appropriate intervention to improve TB diagnosis, which may be relevant to similar low-resource, high TB burden countries and can be feasibly implemented by the National TB programme.

The prominent role of informal medicine vendors despite health insurance: a weekly diaries study in rural Nigeria.

In sub-Saharan Africa, accessibility to affordable quality care is often poor and health expenditures are mostly paid out of pocket. Health insurance, protecting individuals from out-of-pocket health expenses, has been put forward as a means of enhancing universal health coverage. We explored the utilization of different types of healthcare providers and the factors associated with provider choice by insurance status in rural Nigeria. We analysed year-long weekly health diaries on illnesses and injuries (health episodes) for a sample of 920 individuals with access to a private subsidized health insurance programme. The weekly diaries capture not only catastrophic events but also less severe events that are likely underreported in surveys with longer recall periods. Individuals had insurance coverage during 34% of the 1761 reported health episodes, and they consulted a healthcare provider in 90% of the episodes. Multivariable multinomial logistic regression analyses showed that insurance coverage was associated with significantly higher utilization of formal health care: individuals consulted upgraded insurance programme facilities in 20% of insured episodes compared with 3% of uninsured episodes. Nonetheless, regardless of insurance status, most consultations involved an informal provider visit, with informal providers encompassing 73 and 78% of all consultations among insured and uninsured episodes, respectively, and individuals spending 54% of total annual out-of-pocket health expenditures at such providers. Given the high frequency at which individuals consult informal providers, their position within both the primary healthcare system and health insurance schemes should be reconsidered to reach universal health coverage.

Diagnostic practices and estimated burden of tuberculosis among children admitted to 13 government hospitals in Kenya: An analysis of two years' routine clinical data.

BACKGROUND: True burden of tuberculosis (TB) in children is unknown. Hospitalised children are low-hanging fruit for TB case detection as they are within the system. We aimed to explore the process of recognition and investigation for childhood TB using a guideline-linked cascade of care. METHODS: This was an observational study of 42,107 children admitted to 13 county hospitals in Kenya from 01Nov 15-31Oct 16, and 01Nov 17-31Oct 18. We estimated those that met each step of the cascade, those with an apparent (or "Working") TB diagnosis and modelled associations with TB tests amongst guideline-eligible children. RESULTS: 23,741/42,107 (56.4%) met step 1 of the cascade (≥2 signs and symptoms suggestive of TB). Step 2(further screening of history of TB contact/full respiratory exam) was documented in 14,873/23,741 (62.6%) who met Step 1. Step 3(chest x-ray or Mantoux test) was requested in 2,451/14,873 (16.5%) who met Step 2. Step 4(≥1 bacteriological test) was requested in 392/2,451 (15.9%) who met Step 3. Step 5("Working TB" diagnosis) was documented in 175/392 (44.6%) who met Step 4. Factors associated with request of TB tests in patients who met Step 1 included: i) older children [AOR 1.19(CI 1.09-1.31)]; ii) co-morbidities of HIV, malnutrition or pneumonia [AOR 3.81(CI 3.05-4.75), 2.98(CI 2.69-3.31) and 2.98(CI 2.60-3.40) respectively]; iii) sicker children, readmitted/referred [AOR 1.24(CI 1.08-1.42) and 1.15(CI 1.04-1.28) respectively]. "Working TB" diagnosis was made in 2.9%(1,202/42,107) of all admissions and 0.2%(89/42,107) were bacteriologically-confirmed. CONCLUSIONS: More than half of all paediatric admissions had symptoms associated with TB and nearly two-thirds had more specific history documented. Only a few amongst them got TB tests requested. TB was diagnosed in 2.9% of all admissions but most were inadequately investigated. Major challenges remain in identifying and investigating TB in children in hospitals with access to Xpert MTB/RIF and a review is needed of existing guidelines.

Patients' and healthcare providers' perceptions and practices regarding hypertension, pharmacy-based care, and mHealth in Lagos, Nigeria: a mixed methods study.

BACKGROUND: In sub-Saharan Africa, cardiovascular disease is becoming a leading cause of death, with high blood pressure as number one risk factor. In Nigeria, access and adherence to hypertension care are poor. A pharmacy-based hypertension care model with remote monitoring by cardiologists through mHealth was piloted in Lagos to increase accessibility to quality care for hypertensive patients. OBJECTIVES: To describe patients' and healthcare providers' perceptions and practices regarding hypertension, pharmacy-based care, and mHealth and explore how this information may improve innovative hypertension service delivery. METHODS: This study consisted of observations of patient-pharmacy staff interactions and hypertension care provided, four focus group discussions and in-depth interviews with 30 hypertensive patients, nine community pharmacists, and six cardiologists, and structured interviews with 328 patients. RESULTS: Most patients were knowledgeable about biomedical causes and treatment of hypertension, but often ignorant about the silent character of hypertension. Reasons mentioned for not adhering to treatment were side effects, financial constraints, lack of health insurance, and cultural or religious reasons. Pharmacists additionally mentioned competition with informal, cheaper healthcare providers. Patients highly favored pharmacy-based care, because of the pharmacist-patient relationship, accessibility, small-scale, and a pharmacy's registration at an association. The majority of respondents were positive towards mHealth. CONCLUSION: Facilitating factors for innovative pharmacy-based hypertension care were: patients' biomedical perceptions, pharmacies' strong position in the community, and respondents' positive attitude towards mHealth. We recommend health education and strengthening pharmacists' role to address barriers, such as misperceptions that hypertension always is symptomatic, treatment nonadherence, and unfamiliarity with mHealth. Future collaboration with insurance providers or other financing mechanisms may help diminish patients' financial barriers to appropriate hypertension treatment.

Pharmacy-based hypertension care employing mHealth in Lagos, Nigeria - a mixed methods feasibility study.

BACKGROUND: Access to quality hypertension care is often poor in sub-Saharan Africa. Some community pharmacies offer hypertension monitoring services, with and without involvement of medical doctors. To directly connect pharmacy staff and cardiologists a care model including a mobile application (mHealth) for remote patient monitoring was implemented and pilot tested in Lagos, Nigeria. Pharmacists provided blood pressure measurements and counselling. Cardiologists enrolled patients in the pilot program and remotely monitored them, for which patients paid a monthly fee. We evaluated the feasibility of this care model at five private community pharmacies. Outcome measures were retention in care, blood pressure change, quality of care, and patients' and healthcare providers' satisfaction with the care model. METHODS: Patients participated in the care model's pilot at one of the five pharmacies for approximately 6-8 months from February 2016. We conducted structured patient interviews and blood pressure measurements at pilot entry and exit, and used exports of the mHealth-application, in-depth interviews and focus group discussions with patients, pharmacists and cardiologists. RESULTS: Of 336 enrolled patients, 236 (72%) were interviewed at pilot entry and exit. According to the mHealth data 71% returned to the pharmacy after enrollment, with 3.3 months (IQR: 2.2-5.4) median duration of activity in the mHealth-application. Patients self-reported more visits than recorded in the mHealth data. Pharmacists mentioned use of paper records, understaffing, the application not being user-friendly, and patients' unwillingness to pay as reasons for underreporting. Mean systolic blood pressure decreased 9.9 mmHg (SD: 18). Blood pressure on target increased from 24 to 56% and an additional 10% had an improved blood pressure at endline, however this was not associated with duration of mHealth activity. Patients were satisfied because of accessibility, attention, adherence and information provision. CONCLUSION: Patients, pharmacists and cardiologists adopted the care model, albeit with gaps in mHealth data. Most patients were satisfied, and their mean blood pressure significantly reduced. Usage of the mHealth application, pharmacy incentives, and a modified financing model are opportunities for improvement. In addition, costs of implementation and availability of involved healthcare providers need to be investigated before such a care model can be further implemented.

Cost-effectiveness of triage testing for facility-based systematic screening of tuberculosis among Ugandan adults.

BACKGROUND: Systematic screening is often proposed as a way to improve case finding for tuberculosis (TB), but the cost-effectiveness of specific strategies for systematic screening remains poorly studied. METHODS: We constructed a Markov-based decision analytic model to analyse the cost-effectiveness of triage testing for TB in Uganda, compared against passive case detection with Xpert MTB/RIF. We assumed a triage algorithm whereby all adults presenting to healthcare centres would be screened for cough, and those with cough of at least 2 weeks would receive the triage test, with positive triage results confirmed by Xpert MTB/RIF. We adopted the perspective of the TB control sector, using a primary outcome of the cost per year of life gained (YLG) over a lifetime time horizon. RESULTS: Systematic screening in a population with a 5% underlying prevalence of TB was estimated to cost US$610 per YLG (95% uncertainty range US$200-US$1859) with chest X-ray (CXR) (US$5 per test, specificity 0.67), or US$588 (US$221-US$1746) with C reactive protein (CRP) (US$3 per test, specificity 0.59). In addition to the cost and specificity of the triage test, cost-effectiveness was most sensitive to the underlying prevalence of TB, monthly risk of mortality in people with untreated TB and the proportion of patients with TB who would be treated in the absence of systematic screening. CONCLUSIONS: To optimise the cost-effectiveness of facility-based systematic screening of TB with a triage test, it must be carried out in a high-risk population, or use triage tests that are cheaper or more specific than CXR or CRP.