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Background: Infants are a target population for new tuberculosis (TB) vaccines. TB incidence estimates are needed to guide the design of trials. To determine the TB incidence and cohort retention among young children using comprehensive diagnostic methods in a high burden area., Methods: Infants 0-42 days were enrolled. Through 4 monthly follow-up and unscheduled (sick) visits up to the age of 2 years, infants with presumptive TB based on a history of contact, TB symptoms or pre-determined hospitalization criteria were admitted to a case verification ward. Two induced sputa and gastric aspirates were collected for culture and GeneXpert. Mantoux and HIV tests were done. Clinical management was based on the Keith Edwards score. Cases were classified into microbiologically confirmed or radiologic, diagnosed by blinded expert assessment. Cox regression was used to identify risk factors for incident TB and study retention., Results: Of 2900 infants enrolled, 927 (32%) developed presumptive TB, 737/927 (80%) were investigated. Sixty-nine TB cases were diagnosed (bacteriologic and radiologic). All TB incidence was 2/100 person-years of observation (pyo) (95% CI: 1.65-2.65). Nine were bacteriologic cases, incidence 0.3/100 pyo. The radiologic TB incidence was 1.82/100 pyo. Bacteriologic TB was associated with infant HIV infection, higher Keith Edwards scores. Completeness of 4-month vaccinations and HIV infection were positively associated with retention., Conclusions: TB incidence was high. An all TB endpoint would require a sample size of a few thousand children, but tens of thousands, when limited to bacteriologic TB.

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., (© The Author(s) 2020. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.)

Objective: To better understand factors contributing to underutilization of laboratory services for health care delivery in sub-Saharan Africa, we conducted a study in Senegalese Antenatal Care clinics (ANC) and laboratories to determine the extent of underutilization, contributing factors, and bottlenecks in the cascade of care from first ANC visit, test uptake, to availability of test results and appropriate clinical management., Methods: At 16 health facilities, pregnant women attending for their first ANC visit were consecutively recruited and information was prospectively collected on the request, execution, results and clinical management of seven nationally recommended laboratory screening tests for normal pregnancy: hemoglobin concentration (Hb), syphilis serology, HIV serology, determination of proteinuria (PU), determination of blood group and Rhesus factor, Emmel test to detect sickle cell disease, and glycaemia. Health facility staff were interviewed on human resource capacity, management of the ANC and the laboratory, and availability and use of guidelines., Results: Of 1246 ANC attendants, 400 (32%) had complete results. Completeness varied between facilities from 0-99%. In multilevel logistic regression analysis of women nested in facilities, complete uptake was lower if women started ANC later in pregnancy; very low in rural ANC attendants who ever delivered compared to urban primigravidae (OR 0.064; 95%CI 0.00-0.52); and higher if the facility routinely recommended all seven tests. In the cascade from test request to clinical management, the most frequent bottleneck was non-execution of requested tests, while unavailability of results for executed test was uncommon (<2%). Overall, of 525 abnormal test results 97(18%) had a record of adequate clinical management., Conclusion: Our study illustrates challenges to test uptake even when laboratory testing capacity is in place, with large differences between facilities, and underscores the importance of management, policy, and the importance of considering local context in order to improve service delivery to expectant mothers., Competing Interests: The authors have declared that no competing interests exist.

Background: Adolescents are a prime target group for tuberculosis (TB) vaccine trials that include prevention of infection (POI). The BCG vaccine is given at birth and does not prevent TB infection. TB infection, a critical endpoint for POI vaccine trials would need to be documented to estimate sample sizes in target populations., Methods: Adolescents aged 12-18 years of age were enrolled in an area under continuous demographic surveillance. A tuberculin skin test (TST) survey was conducted as part of a study on TB prevalence and incidence. All adolescents got TSTs at enrolment and returned after 72 h for reading. A TST of ≥10 mm if HIV negative or ≥ 5 mm if HIV positive, was considered positive., Results: Of 4808 adolescents returning for TST readings (96% of those enrolled), mean age was 14.4 (SD 1.9), 4518(94%) were enrolled in school and 21(0.4%) gave a previous history of tuberculosis. Among adolescents with TST reactivity, the mean TST induration was 13.2 mm (SD 5.4). The overall prevalence of latent TB infection was 1544/4808 (32.1, 95% CI 29.2-35.1) with a corresponding annual risk of TB infection (ARTI) of 2.6% (95% CI 2.2-3.1). Risk factors for a positive TST included being male (OR 1.3, 95% CI 1.2,1.5), history of having a household TB contact (OR 1.5, 95% CI 1.2,1.8), having a BCG scar (OR 1.5,95% CI 1.2,1.8), living in a rural area (OR 1.4, 95% CI 1.1,1.9), and being out of school (OR 1.8, 95% CI 1.4,2.3)., Conclusion: We conclude that the high TB transmission rates we found in this study, suggest that adolescents in this region may be an appropriate target group for TB vaccine trials including TB vaccine trials aiming to prevent infection.

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.

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.

Background: Globally, 40% of all tuberculosis (TB) cases, 65% paediatric cases and 75% multi-drug resistant TB (MDR-TB) cases are missed due to underreporting and/or under diagnosis. A recent Kenyan TB prevalence survey found that a significant number of TB cases are being missed here. Understanding spatial distribution and patterns of use of TB diagnostic tests as per the guidelines could potentially help improve TB case detection by identifying diagnostic gaps., Methods: We used 2015 Kenya National TB programme data to map TB case notification rates (CNR) in different counties, linked with their capacity to perform diagnostic tests (chest x-rays, smear microscopy, Xpert MTB/RIF®, culture and line probe assay). We then ran hierarchical regression models for adults and children to specifically establish determinants of use of Xpert® (as per Kenyan guidelines) with county and facility as random effects., Results: In 2015, 82,313 TB cases were notified and 7.8% were children. The median CNR/100,000 amongst 0-14yr olds was 37.2 (IQR 20.6, 41.0) and 267.4 (IQR 202.6, 338.1) for ≥15yr olds respectively. 4.8% of child TB cases and 12.2% of adult TB cases had an Xpert® test done, with gaps in guideline adherence. There were 2,072 microscopy sites (mean microscopy density 4.46/100,000); 129 Xpert® sites (mean 0.31/100,000); two TB culture laboratories and 304 chest X-ray facilities (mean 0.74/100,000) with variability in spatial distribution across the 47 counties. Retreatment cases (i.e. failures, relapses/recurrences, defaulters) had the highest odds of getting an Xpert® test compared to new/transfer-in patients (AOR 7.81, 95% CI 7.33-8.33). Children had reduced odds of getting an Xpert® (AOR 0.41, CI 0.36-0.47). HIV-positive individuals had nearly twice the odds of getting an Xpert® test (AOR 1.82, CI 1.73-1.92). Private sector and higher-level hospitals had a tendency towards lower odds of use of Xpert®., Conclusions: We noted under-use and gaps in guideline adherence for Xpert® especially in children. The under-use despite considerable investment undermines cost-effectiveness of Xpert®. Further research is needed to develop strategies enhancing use of diagnostics, including innovations to improve access (e.g. specimen referral) and overcoming local barriers to adoption of guidelines and technologies.

Background: In Lagos, Nigeria, approximately 33% of the population suffers from hypertension, yet antihypertensive treatment coverage is low. To improve access to care, a decentralized pharmacy-based hypertension care model was piloted. This study reports on the recruitment strategies used and is part of a larger study to evaluate the feasibility of the care model., Objective: To describe our experience executing three different strategies to recruit hypertensive patients in the program: community hypertension screenings, hospital and pharmacy referral., Methods: Individuals with elevated blood pressure and no history of cardiovascular disease were referred to the program's recruitment days to see a medical doctor for hypertension diagnosis and enrollment. Individuals were referred from community screenings, tertiary hospital outpatient clinics, and pharmacies participating in the program. For the community screenings, we report the number needed to screen (NNS) to find one individual with elevated blood pressure, the NNS to enroll one individual in the program, and factors associated with enrollment in the program among participants referred., Results: We recruited 226 individuals (69%) in the program via the pharmacies, 97 (30%) via the community screenings, and 2 (<1%) via hospital referral. At the community screenings 3,204 individuals participated, 729 (23%) had elevated blood pressure and 618 (85%) were eligible for referral of whom 142 (23%) visited the recruitment days, and 97 (16%) enrolled. The NNS to find one individual with elevated blood pressure was 5, and the NNS to enroll one individual was 34. Enrollment in the program was associated with advancing age, blood pressure ≥160/100 and currently using antihypertensive medication., Conclusions: Despite the potential attractiveness of community screenings to identify and refer individuals with hypertension, enrollment in the program was low. For future programs we recommend pharmacy referral as individuals seem more inclined to access care through healthcare providers they are familiar with.

Setting: Siaya County, with the highest tuberculosis notification rates in Kenya., Objectives: To determine the incidence of active tuberculosis and 1-year cohort retention in 12-18-year-old adolescents, in preparation for phase III tuberculosis vaccine trials., Methods: Adolescents were enrolled and followed up for 1-2 years to determine tuberculosis incidence. Adolescents with a positive tuberculin skin test, history of cohabitation with a tuberculosis case or at least 1 tuberculosis symptom received clinical and sputum examination and a chest radiograph. Definite tuberculosis cases were bacteriologically confirmed and clinical cases diagnosed by a clinician based on a suggestive chest radiograph and having clinical symptoms. Risk factors were explored using Poisson regression., Results: Among 4934 adolescents without tuberculosis at baseline, 26 tuberculosis cases were identified during follow-up with a corresponding incidence density of 4.4 [95% confidence interval (CI): 3.0-6.4] events per 1000 person-years of observation, 12 definite tuberculosis cases; incidence density of 2.0 (95% CI: 0.9-3.1). Having previous tuberculosis (rate ratio: 12.5; CI: 1.8-100) and presence of tuberculin skin test conversion (rate ratio: 3.4; CI: 1.5-7.7) were significantly associated with higher risk of tuberculosis. Overall (4086/4925), 83.0% of adolescents were retained in the study after 1 year of follow-up. Being female, older, out of school and being orphaned were significant risk factors for loss to follow-up., Conclusion: The tuberculosis incidence in adolescents will help inform future tuberculosis vaccine trial sample size calculations for this setting. The predictive factors for tuberculosis and retention can be further explored in future trials.

Setting: Enhanced tuberculosis (TB) case finding using detection rats in Tanzania., Objectives: To assess the diagnostic accuracy of detection rats compared with culture and Xpert® MTB/RIF, and to compare enhanced case-finding algorithms using rats in smear-negative presumptive TB patients., Design: A fully paired diagnostic accuracy study in which sputum of new adult presumptive TB patients in Tanzania was tested using smear microscopy, 11 detection rats, culture and Xpert., Results: Of 771 eligible participants, 345 (45%) were culture-positive for Mycobacterium tuberculosis, and 264 (34%) were human immunodeficiency virus (HIV) positive. The sensitivity of the detection rats was up to 75.1% (95%CI 70.1-79.5) when compared with culture, and up to 81.8% (95%CI 76.0-86.5) when compared with Xpert, which was statistically significantly higher than the sensitivity of smear microscopy. Corresponding specificity was 40.6% (95%CI 35.9-45.5) compared with culture. The accuracy of rat detection was independent of HIV status. Using rats for triage, followed by Xpert, would result in a statistically higher yield than rats followed by light-emitting diode fluorescence microscopy, whereas the number of false-positives would be significantly lower than when using Xpert alone., Conclusion: Although detection rats did not meet the accuracy criteria as standalone diagnostic or triage testing for presumptive TB, they have additive value as a triage test for enhanced case finding among smear-negative TB patients if more advanced diagnostics are not available.

Setting: Of 18 sites that participated in an implementation study of the Xpert® MTB/RIF assay in India, we selected five microscopy centres and two reference laboratories., Objective: To obtain unit costs of diagnostic tests for tuberculosis (TB) and drug-resistant TB., Design: Laboratories were purposely selected to capture regional variations and different laboratory types. Both bottom-up and the top-down methods were used to estimate unit costs., Results: At the microscopy centres, mean bottom-up unit costs were respectively US$0.83 (range US$0.60-US$1.10) and US$12.29 (US$11.61-US$12.89) for sputum smear microscopy and Xpert. At the reference laboratories, mean unit costs were US$1.69 for the decontamination procedure, US$9.83 for a solid culture, US$11.06 for a liquid culture, US$29.88 for a drug susceptibility test, and US$18.18 for a line-probe assay. Top-down mean unit cost estimates were higher for all tests, and for sputum smear microscopy and Xpert these increased to respectively US$1.51 and US$13.58. The difference between bottom-up and top-down estimates was greatest for tests performed at the reference laboratories., Conclusion: These unit costs for TB diagnostics can be used to estimate resource requirements and cost-effectiveness in India, taking into account geographical location, laboratory type and capacity utilisation.

Background: Molecular resistance detection (MRD) of resistance to second-line anti-tuberculous drugs provides faster results than phenotypic tests, may shorten treatment and allow earlier separation among patients with and without second-line drug resistance., Methods: In a decision-analytical model we simulated a cohort of patients diagnosed with TB in a setting where drug resistant TB is highly prevalent and requires initial hospitalization, to explore the potential benefits of a high-throughput MRD-assay for reducing potential nosocomial transmission of highly resistant strains, and total costs for diagnosis of drug resistance, treatment and hospitalization. In the base case scenario first-line drug resistance was diagnosed with WHO-endorsed molecular tests, and second-line drug resistance with culture and phenotypic methods. Three alternative scenarios were explored, each deploying high-throughput MRD allowing either detection of second-line mutations in cultured isolates, directly on sputum, or MRD with optimized markers., Results: Compared to a base case scenario, deployment of high-throughput MRD reduced total costs by 17-21 %. The period during which nosocomial transmission may take place increased by 15 % compared to the base case if MRD had currently reported suboptimal sensitivity and required cultured isolates; increased by 7 % if direct sputum analysis were possible including in patients with smear-negative TB, and reduced by 24 % if the assay had improved markers, but was still performed on cultured isolates. Improved clinical sensitivity of the assay (additional markers) by more than 35 % would be needed to avoid compromising infection control., Conclusions: Further development of rapid second-line resistance testing should prioritize investment in optimizing markers above investments in a platform for direct analysis of sputum.

Objective: The aim of this study was to determine the prevalence of tuberculosis (TB) in adolescents in western Kenya., Methods: A cohort study of 5004 adolescents aged 12-18 years was conducted. Adolescents were screened for prevalent TB using clinical criteria, history of TB contact, and a Mantoux test. Cases of suspected TB were investigated through two sputum examinations (microscopy and liquid culture) and chest radiography., Results: Out of 5004 adolescents enrolled, 1960 (39.2%) were identified with suspected TB, including 1544 with a positive Mantoux (prevalence 1544/4808, 32.1%), 515 with symptoms suggestive of TB (10.3%), and 144 (2.9%) with household TB contact. Sixteen culture-confirmed (definite) and 18 probable pulmonary TB (PTB) cases were identified, reflecting a prevalence estimate of 3.2/1000 (definite) and 6.8/1000 all PTB, respectively. Only one smear-positive case was detected. The case notification rate among 12-18-year-old adolescents for all TB was 101/100000, yielding a patient diagnostic rate of 0.13 (95% confidence interval 0.03-3.7) cases detected per person-year for all TB., Conclusion: The prevalence of PTB among adolescents is high, with the majority of cases not detected routinely. Innovative active case finding including the wider use of Xpert MTB/RIF is needed to detect smear-negative TB among adolescents., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Xpert MTB/RIF, the first automated molecular test for tuberculosis, is transforming the diagnostic landscape in high-burden settings. This study assessed the impact of up-front Xpert MTB/RIF testing on detection of pulmonary tuberculosis (PTB) and rifampicin-resistant PTB (DR-TB) cases in India., Methods: This demonstration study was implemented in 18 sub-district level TB programme units (TUs) in India in diverse geographic and demographic settings covering a population of 8.8 million. A baseline phase in 14 TUs captured programmatic baseline data, and an intervention phase in 18 TUs had Xpert MTB/RIF offered to all presumptive TB patients. We estimated changes in detection of TB and DR-TB, the former using binomial regression models to adjust for clustering and covariates., Results: In the 14 study TUs, which participated in both phases, 10,675 and 70,556 presumptive TB patients were enrolled in the baseline and intervention phase, respectively, and 1,532 (14.4%) and 14,299 (20.3%) bacteriologically confirmed PTB cases were detected. The implementation of Xpert MTB/RIF was associated with increases in both notification rates of bacteriologically confirmed TB cases (adjusted incidence rate ratio [aIRR] 1.39; CI 1.18-1.64), and proportion of bacteriological confirmed TB cases among presumptive TB cases (adjusted risk ratio (aRR) 1.33; CI 1.6-1.52). Compared with the baseline strategy of selective drug-susceptibility testing only for PTB cases at high risk of drug-resistant TB, Xpert MTB/RIF implementation increased rifampicin resistant TB case detection by over fivefold. Among, 2765 rifampicin resistance cases detected, 1055 were retested with conventional drug susceptibility testing (DST). Positive predictive value (PPV) of rifampicin resistance detected by Xpert MTB/RIF was 94.7% (CI 91.3-98.1), in comparison to conventional DST., Conclusion: Introduction of Xpert MTB/RIF as initial diagnostic test for TB in public health facilities significantly increased case-notification rates of all bacteriologically confirmed TB by 39% and rifampicin-resistant TB case notification by fivefold.

Background: To inform the choice of an appropriate screening and diagnostic algorithm for tuberculosis (TB) screening initiatives in different epidemiological settings, we compare algorithms composed of currently available methods., Methods: Of twelve algorithms composed of screening for symptoms (prolonged cough or any TB symptom) and/or chest radiography abnormalities, and either sputum-smear microscopy (SSM) or Xpert MTB/RIF (XP) as confirmatory test we model algorithm outcomes and summarize the yield, number needed to screen (NNS) and positive predictive value (PPV) for different levels of TB prevalence., Results: Screening for prolonged cough has low yield, 22% if confirmatory testing is by SSM and 32% if XP, and a high NNS, exceeding 1000 if TB prevalence is ≤0.5%. Due to low specificity the PPV of screening for any TB symptom followed by SSM is less than 50%, even if TB prevalence is 2%. CXR screening for TB abnormalities followed by XP has the highest case detection (87%) and lowest NNS, but is resource intensive. CXR as a second screen for symptom screen positives improves efficiency., Conclusions: The ideal algorithm does not exist. The choice will be setting specific, for which this study provides guidance. Generally an algorithm composed of CXR screening followed by confirmatory testing with XP can achieve the lowest NNS and highest PPV, and is the least amenable to setting-specific variation. However resource requirements for tests and equipment may be prohibitive in some settings and a reason to opt for symptom screening and SSM. To better inform disease control programs we need empirical data to confirm the modeled yield, cost-effectiveness studies, transmission models and a better screening test.

Background: High costs are a limitation to scaling up the Xpert MTB/RIF assay (Xpert) for the diagnosis of tuberculosis in resource-constrained settings. A triaging strategy in which a sensitive but not necessarily highly specific rapid test is used to select patients for Xpert may result in a more affordable diagnostic algorithm. To inform the selection and development of particular diagnostics as a triage test we explored combinations of sensitivity, specificity and cost at which a hypothetical triage test will improve affordability of the Xpert assay., Methods: In a decision analytical model parameterized for Uganda, India and South Africa, we compared a diagnostic algorithm in which a cohort of patients with presumptive TB received Xpert to a triage algorithm whereby only those with a positive triage test were tested by Xpert., Findings: A triage test with sensitivity equal to Xpert, 75% specificity, and costs of US$5 per patient tested reduced total diagnostic costs by 42% in the Uganda setting, and by 34% and 39% respectively in the India and South Africa settings. When exploring triage algorithms with lower sensitivity, the use of an example triage test with 95% sensitivity relative to Xpert, 75% specificity and test costs $5 resulted in similar cost reduction, and was cost-effective by the WHO willingness-to-pay threshold compared to Xpert for all in Uganda, but not in India and South Africa. The gain in affordability of the examined triage algorithms increased with decreasing prevalence of tuberculosis among the cohort., Conclusions: A triage test strategy could potentially improve the affordability of Xpert for TB diagnosis, particularly in low-income countries and with enhanced case-finding. Tests and markers with lower accuracy than desired of a diagnostic test may fall within the ranges of sensitivity, specificity and cost required for triage tests and be developed as such.

Background: The findings of a prevalence survey conducted in western Kenya, in a population with 14.9% HIV prevalence suggested inadequate case finding. We found a high burden of infectious and largely undiagnosed pulmonary tuberculosis (PTB), that a quarter of the prevalent cases had not yet sought care, and a low case detection rate., Objective and Methods: We aimed to identify factors associated with inadequate case finding among adults with PTB in this population by comparing characteristics of 194 PTB patients diagnosed in a health facility after self-report, i.e., through passive case detection, with 88 patients identified through active case detection during the prevalence survey. We examined associations between method of case detection and patient characteristics, including HIV-status, socio-demographic variables and disease severity in univariable and multivariable logistic regression analyses., Findings: HIV-infection was associated with faster passive case detection in univariable analysis (crude OR 3.5, 95% confidence interval (CI) 2.0-5.9), but in multivariable logistic regression this was largely explained by the presence of cough, illness and clinically diagnosed smear-negative TB (adjusted OR (aOR) HIV 1.8, 95% CI 0.85-3.7). Among the HIV-uninfected passive case detection was less successful in older patients aOR 0.76, 95%CI 0.60-0.97 per 10 years increase), and women (aOR 0.27, 95%CI 0.10-0.73). Reported current or past alcohol use reduced passive case detection in both groups (0.42, 95% CI 0.23-0.79). Among smear-positive patients median durations of cough were 4.0 and 6.9 months in HIV-infected and uninfected patients, respectively., Conclusion: HIV-uninfected patients with infectious TB who were older, female, relatively less ill, or had a cough of a shorter duration were less likely found through passive case detection. In addition to intensified case finding in HIV-infected persons, increasing the suspicion of TB among HIV-uninfected women and the elderly are needed to improve TB case detection in Kenya.

Objectives: To evaluate excess mortality and risk factors for death during anti-tuberculosis treatment in Western Kenya., Methods: We abstracted surveillance data and compared mortality rates during anti-tuberculosis treatment with all-cause mortality from a health and demographic surveillance population to obtain standardised mortality ratios (SMRs). Risk factors for excess mortality were obtained using a relative survival model, and for death during treatment using a proportional hazards regression model., Results: The crude mortality rate during anti-tuberculosis treatment was 18.0 (95%CI 16.8-19.2) per 100 person-years. The age and sex SMR was 8.8 (95%CI 8.2-9.4). Excess mortality was greater in human immunodeficiency virus (HIV) positive TB patients (excess hazard ratio [eHR] 2.1, 95%CI 1.5-3.1), and lower in patients who were female or started treatment in a later year. Mortality was high in patients with unknown HIV status (HR 2.9, 95%CI 2.2-3.8) or, if HIV-positive, not on antiretroviral treatment (ART; HR 3.3, 95%CI 2.5-4.5) or not known to be on ART (HR 2.8, 95%CI 2.1-3.7). The attributable fraction of incomplete uptake of HIV testing and ART on mortality was 31% (95%CI 15-45) compared to HIV-positive patients on ART., Conclusion: Increasing the uptake of HIV testing and ART would further reduce mortality during anti-tuberculosis treatment by an estimated 31%.

Background: We conducted a tuberculosis (TB) prevalence survey and evaluated the screening methods used in our survey, to assess if screening in TB prevalence surveys could be simplified, and to assess the accuracy of screening algorithms that may be applicable for active case finding., Methods: All participants with a positive screen on either a symptom questionnaire, chest radiography (CXR) and/or sputum smear microscopy submitted sputum for culture. HIV status was obtained from prevalent cases. We estimated the accuracy of modified screening strategies with bacteriologically confirmed TB as the gold standard, and compared these with other survey reports. We also assessed whether sequential rather than parallel application of symptom, CXR and HIV screening would substantially reduce the number of participants requiring CXR and/or sputum culture., Results: Presence of any abnormality on CXR had 94% (95%CI 88-98) sensitivity (92% in HIV-infected and 100% in HIV-uninfected) and 73% (95%CI 68-77) specificity. Symptom screening combinations had significantly lower sensitivity than CXR except for 'any TB symptom' which had 90% (95%CI 84-95) sensitivity (96% in HIV-infected and 82% in HIV-uninfected) and 32% (95%CI 30-34) specificity. Smear microscopy did not yield additional suspects, thus the combined symptom/CXR screen applied in the survey had 100% (95%CI 97-100) sensitivity. Specificity was 65% (95%CI 61-68). Sequential application of first a symptom screen for 'any symptom', followed by CXR-evaluation and different suspect criteria depending on HIV status would result in the largest reduction of the need for CXR and sputum culture, approximately 36%, but would underestimate prevalence by 11%., Conclusion: CXR screening alone had higher accuracy compared to symptom screening alone. Combined CXR and symptom screening had the highest sensitivity and remains important for suspect identification in TB prevalence surveys in settings where bacteriological sputum examination of all participants is not feasible.

Background: Chest radiographs (CXRs) are used in tuberculosis (TB) prevalence surveys to identify participants for bacteriological examination. Expert readers are rare in most African countries. In our survey, clinical officers scored CXRs of 19 216 participants once. We assessed to what extent missed CXR abnormalities affected our TB prevalence estimate., Methods: Two experts, a radiologist and pulmonologist, independently reviewed 1031 randomly selected CXRs, mixed with lms of confirmed TB cases. CXRs with disagreement on 'any abnormality' or 'abnormality consistent with TB' were jointly reviewed during a consensus panel. We compared the nal expert and clinical of cer classifications with bacteriologically confirmed TB as the gold standard., Results: After the panel, 199 (19%) randomly selected CXRs were considered abnormal by both expert reviewers and another 82 (8%) by one reviewer. Agreement was good among the experts (κ 0.78, 95%CI 0.73-0.82) and moderate between the clinical officers and experts (κ range 0.50-0.62). The sensitivity of 'any abnormality' was 95% for the clinical officers and 83% and 81% for the respective experts. The specificities were respectively 73%, 74% and 80%. TB prevalence was underestimated by 1.5-5.0%., Conclusions: Acceptable CXR screening can be achieved with clinical officers. Reviewing a sample of CXRs by two experts allows an assessment of prevalence underestimation.

Background: The two issues mostly affecting the success of tuberculosis (TB) control programmes are delay in presentation and non-adherence to treatment. It is important to understand the factors that contribute to these issues, particularly in resource limited settings, where rates of tuberculosis are high. The objective of this study is to assess health-seeking behaviour and health care experiences among persons with pulmonary tuberculosis, and identify the reasons patients might not complete their treatment., Methods: We performed qualitative one-on-one in-depth interviews with pulmonary tuberculosis patients in nine health facilities in rural western Kenya. Thirty-one patients, 18 women and 13 men, participated in the study. All reside in an area of western Kenya with a Health and Demographic Surveillance System (HDSS). They had attended treatment for up to 4 weeks on scheduled TB clinic days in September and October 2005.The nine sites all provide diagnostic and treatment services. Eight of the facilities were public (3 hospitals and 5 health centres) and one was a mission health centre., Results: Most patients initially self-treated with herbal remedies or drugs purchased from kiosks or pharmacies before seeking professional care. The reported time from initial symptoms to TB diagnosis ranged from 3 weeks to 9 years. Misinterpretation of early symptoms and financial constraints were the most common reasons reported for the delay.We also explored potential reasons that patients might discontinue their treatment before completing it. Reasons included being unaware of the duration of TB treatment, stopping treatment once symptoms subsided, and lack of family support., Conclusions: This qualitative study highlighted important challenges to TB control in rural western Kenya, and provided useful information that was further validated in a quantitative study in the same area.

Addressing social determinants in the field of tuberculosis (TB) has received great attention in the past years, mainly due to the fact that worldwide TB incidence has not declined as much as expected, despite highly curative control strategies. One of the objectives of the World Health Organization Global Task Force on TB Impact Measurement is to assess the prevalence of TB disease in 22 high-burden countries by active screening of a random sample of the general population. These surveys provide a unique opportunity to assess socio-economic determinants in relation to prevalent TB and its risk factors. This article describes methods of measuring the socio-economic position in the context of a TB prevalence survey. An indirect measurement using an assets score is the most feasible way of doing this. Several examples are given from recently conducted prevalence surveys of the use of an assets score, its construction, and the analyses of the obtained data.

Rationale: Limited information exists on the prevalence of tuberculosis and adequacy of case finding in African populations with high rates of HIV., Objectives: To estimate the prevalence of bacteriologically confirmed pulmonary tuberculosis (PTB) and the fraction attributable to HIV, and to evaluate case detection., Methods: Residents aged 15 years and older, from 40 randomly sampled clusters, provided two sputum samples for microscopy; those with chest radiograph abnormalities or symptoms suggestive of PTB provided one additional sputum sample for culture., Measurements and Main Results: PTB was defined by a culture positive for Mycobacterium tuberculosis or two positive smears. Persons with PTB were offered HIV testing and interviewed on care-seeking behavior. We estimated the population-attributable fraction of HIV on prevalent and notified PTB, the patient diagnostic rate, and case detection rate using provincial TB notification data. Among 20,566 participants, 123 had PTB. TB prevalence was 6.0/1,000 (95% confidence interval, 4.6-7.4) for all PTB and 2.5/1,000 (1.6-3.4) for smear-positive PTB. Of 101 prevalent TB cases tested, 52 (51%) were HIV infected, and 58 (64%) of 91 cases who were not on treatment and were interviewed had not sought care. Forty-eight percent of prevalent and 65% of notified PTB cases were attributable to HIV. For smear-positive and smear-negative PTB combined, the patient diagnostic rate was 1.4 cases detected per person-year among HIV-infected persons having PTB and 0.6 for those who were HIV uninfected, corresponding to case detection rates of 56 and 65%, respectively., Conclusions: Undiagnosed PTB is common in this community. TB case finding needs improvement, for instance through intensified case finding with mobile smear microscopy services, rigorous HIV testing, and improved diagnosis of smear-negative TB.

For some diseases, the transmission of infection can cause spatial clustering of disease cases. This clustering has an impact on how one estimates the rate of the spread of the disease and on the design of control strategies. It is, however, difficult to assess such clustering, (local effects on transmission), using traditional statistical methods. A stochastic Markov-chain model that takes into account possible local or more dispersed global effects on the risk of contracting disease is introduced in the context of the transmission dynamics of tuberculosis. The model is used to analyse TB notifications collected in the Asembo and Gem Divisions of Nyanza Province in western Kenya by the Kenya Ministry of Health/National Leprosy and Tuberculosis Program and the Centers for Disease Control and Prevention. The model shows evidence of a pronounced local effect that is significantly greater than the global effect. We discuss a number of variations of the model which identify how this local effect depends on factors such as age and gender. Zoning/clustering of villages is used to identify the influence that zone size has on the model's ability to distinguish local and global effects. An important possible use of the model is in the design of a community randomised trial where geographical clusters of people are divided into two groups and the effectiveness of an intervention policy is assessed by applying it to one group but not the other. Here the model can be used to take the effect of case clustering into consideration in calculating the minimum difference in an outcome variable (e.g. disease prevalence) that can be detected with statistical significance. It thereby gauges the potential effectiveness of such a trial. Such a possible application is illustrated with the given time/spatial TB data set.

Setting: Health facilities providing tuberculosis (TB) treatment in two districts in rural western Kenya with a high TB and human immunodeficiency virus (HIV) burden., Objective: To evaluate TB and HIV/acquired immune-deficiency syndrome (AIDS) services at the facilities and identify barriers to providing quality diagnostic HIV testing and counseling (DTC) and HIV treatment for TB patients in anticipation of the introduction of TB-HIV collaborative services., Methods: We performed a standard interview with health workers responsible for TB care, inspected the facilities and collected service delivery data. A self-administered questionnaire on training attended was given to all health workers. Results were shared with stakeholders and plans for implementation were developed., Results: Of the 59 facilities, 58 (98%) provided TB treatment, 19 (32%) offered sputum microscopy and 24 (41%) HIV testing. Most facilities (72%) advised HIV testing only if TB patients were suspected of having AIDS. Barriers identified included unaccommodating TB clinic schedules and lack of space, which was an obstacle to holding confidential discussions. The need to refer for HIV testing and/or HIV care was a perceived barrier to recommending these services. Activities implemented following the assessment aimed 1) to provide HIV testing and cotrimoxazole prophylaxis at all TB treatment clinics, 2) to increase availability of HIV treatment services, and 3) to address structural needs at each facility., Conclusion: This evaluation identified barriers to the implementation of HIV testing and care services within facilities providing TB treatment.

Objectives: To improve uptake in a program to prevent mother-to-child HIV transmission and describe lessons relevant for prevention of mother-to-child transmission programs in resource-poor settings., Methods: Implementation of a pilot project that evaluates approaches to increase program uptake at health facility level at New Nyanza Provincial General Hospital, a public hospital in western Kenya, an area with high HIV prevalence. Client flow was revised to integrate counseling, HIV testing, and dispensing of single-dose nevirapine into routine antenatal services. The number of facilities providing PMCT services was expanded to increase district-wide coverage. Main outcome measures were uptake of counseling, HIV testing, nevirapine, and estimated program impact., Results: Uptake of counseling and testing improved from 55 to 68% (P < 0.001), nevirapine uptake from 57% to 70% (P < 0.001), and estimated program impact from 15% to 23% (P = 0.03). Aggregate reports compare well with computer-entered data., Conclusion: Addressing institutional factors can improve uptake, but expected program impact remains low for several reasons, including relatively low efficacy of the intervention and missed opportunities in the labor room.