Matthew J Saunders

A score to predict and stratify risk of tuberculosis in adult contacts of tuberculosis index cases: a prospective derivation and external validation cohort study

BACKGROUND Contacts of tuberculosis index cases are at increased risk of developing tuberculosis. Screening, preventive therapy, and surveillance for tuberculosis are underused interventions in contacts, particularly adults. We developed a score to predict risk of tuberculosis in adult contacts of tuberculosis index cases. METHODS In 2002-06, we recruited contacts aged 15 years or older of index cases with pulmonary tuberculosis who lived in desert shanty towns in Ventanilla, Peru. We followed up contacts for tuberculosis until February, 2016. We used a Cox proportional hazards model to identify index case, contact, and household risk factors for tuberculosis from which to derive a score and classify contacts as low, medium, or high risk. We validated the score in an urban community recruited in Callao, Peru, in 2014-15. FINDINGS In the derivation cohort, we identified 2017 contacts of 715 index cases, and median follow-up was 10·7 years (IQR 9·5-11·8). 178 (9%) of 2017 contacts developed tuberculosis during 19 147 person-years of follow-up (incidence 0·93 per 100 person-years, 95% CI 0·80-1·08). Risk factors for tuberculosis were body-mass index, previous tuberculosis, age, sustained exposure to the index case, the index case being in a male patient, lower community household socioeconomic position, indoor air pollution, previous tuberculosis among household members, and living in a household with a low number of windows per room. The 10-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 2·8% (95% CI 1·7-4·4), 6·2% (4·8-8·1), and 20·6% (17·3-24·4). The 535 (27%) contacts classified as high risk accounted for 60% of the tuberculosis identified during follow-up. The score predicted tuberculosis independently of tuberculin skin test and index-case drug sensitivity results. In the external validation cohort, 65 (3%) of 1910 contacts developed tuberculosis during 3771 person-years of follow-up (incidence 1·7 per 100 person-years, 95% CI 1·4-2·2). The 2·5-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 1·4% (95% CI 0·7-2·8), 3·9% (2·5-5·9), and 8·6%· (5·9-12·6). INTERPRETATION Our externally validated risk score could predict and stratify 10-year risk of developing tuberculosis in adult contacts, and could be used to prioritise tuberculosis control interventions for people most likely to benefit. FUNDING Wellcome Trust, Department for International Development Civil Society Challenge Fund, Joint Global Health Trials consortium, Bill & Melinda Gates Foundation, Imperial College National Institutes of Health Research Biomedical Research Centre, Foundation for Innovative New Diagnostics, Sir Halley Stewart Trust, WHO, TB REACH, and Innovation for Health and Development.

A randomized controlled study of socioeconomic support to enhance tuberculosis prevention and treatment, Peru.

Abstract Objective To evaluate the impact of socioeconomic support on tuberculosis preventive therapy initiation in household contacts of tuberculosis patients and on treatment success in patients. Methods A non-blinded, household-randomized, controlled study was performed between February 2014 and June 2015 in 32 shanty towns in Peru. It included patients being treated for tuberculosis and their household contacts. Households were randomly assigned to either the standard of care provided by Peru’s national tuberculosis programme (control arm) or the same standard of care plus socioeconomic support (intervention arm). Socioeconomic support comprised conditional cash transfers up to 230 United States dollars per household, community meetings and household visits. Rates of tuberculosis preventive therapy initiation and treatment success (i.e. cure or treatment completion) were compared in intervention and control arms. Findings Overall, 282 of 312 (90%) households agreed to participate: 135 in the intervention arm and 147 in the control arm. There were 410 contacts younger than 20 years: 43% in the intervention arm initiated tuberculosis preventive therapy versus 25% in the control arm (adjusted odds ratio, aOR: 2.2; 95% confidence interval, CI: 1.1–4.1). An intention-to-treat analysis showed that treatment was successful in 64% (87/135) of patients in the intervention arm versus 53% (78/147) in the control arm (unadjusted OR: 1.6; 95% CI: 1.0–2.6). These improvements were equitable, being independent of household poverty. Conclusion A tuberculosis-specific, socioeconomic support intervention increased uptake of tuberculosis preventive therapy and tuberculosis treatment success and is being evaluated in the Community Randomized Evaluation of a Socioeconomic Intervention to Prevent TB (CRESIPT) project.

Effectiveness of Protease Inhibitor/Nucleos(t)ide Reverse Transcriptase Inhibitor-Based Second-line Antiretroviral Therapy for the Treatment of Human Immunodeficiency Virus Type 1 Infection in Sub-Saharan Africa: A Systematic Review and Meta-analysis

In sub-Saharan Africa, second-line ritonavir-boosted protease inhibitor–based antiretroviral therapy led to virological suppression in 69.3% of participants at week 48 and 61.5% at week 96, based on an intention-to-treat meta-analysis of 4558 participants (14 studies) and 2145 participants (8 studies), respectively.

Socioeconomic support to improve initiation of tuberculosis preventive therapy and increase tuberculosis treatment success in Peru: a household-randomised, controlled evaluation

Abstract Background For the first time in the modern era of tuberculosis control, the WHOs End TB strategy specifically integrates socioeconomic support for people affected by tuberculosis with existing biomedical interventions. However, there is little evidence of the impact of this approach on tuberculosis outcomes. We designed and implemented one of the worlds first tuberculosis-specific socioeconomic support interventions, assessed its impact on tuberculosis prevention measures and treatment success, and refined the support for use in the Community Randomized Evaluation of a Socioeconomic Intervention to Prevent Tuberculosis (CRESIPT) project. Methods This unmasked household-randomised controlled study was done in 32 peri-urban shanty towns in Callao, Peru. Households with patients treated for tuberculosis by Perus Tuberculosis Program were randomly assigned (1:1, computer-assisted randomisation) to receive the Peruvian Tuberculosis Program standard of care (control group) or to additionally receive socioeconomic support (intervention group). Socioeconomic support consisted of conditional cash transfers (≤US

Addressing social determinants to end tuberculosis

230) and social support (household visits and community meetings). Primary outcome was initiation of tuberculosis preventive therapy in contacts younger than 20 years available for follow-up assessment. 400 contacts were needed for 80% power at the 95% (two-sided) confidence level to detect a 50% increase in the primary outcome. Secondary outcome was treatment success in patients with tuberculosis by intention to treat. Ethics approval was given by the ethics committees of DIRESA Callao (Regional Ministry of Health) and Asociacion Benefica PRISMA, Lima, Peru, and Imperial College London, UK. All participants gave written informed consent. This study has been registered with the ISCTRN registry, number pending. Findings From Feb 10 to Aug 14, 2014, 282 patients (410 eligible contacts) were recruited. 135 patients were randomised to the intervention group (206 eligible contacts) and 147 to the control group (204 eligible contacts). Follow-up continued to June 30, 2015. Compared with controls, intervention contacts were more likely to start preventive therapy (91/206 [44%] vs 53/204 [26%], adjusted odds ratio 2·2 [95% CI 1·1–4·2]; p=0·02); and intervention patients were more likely to have treatment success (87 [64%] vs 78 [53%], 1·8 [1·1–2·9]; p=0·02). Interpretation Tuberculosis-specific socioeconomic support improved initiation of tuberculosis preventive therapy and treatment success. The CRESIPT study will now evaluate the impact of this socioeconomic support on tuberculosis control. Funding Joint Global Health Trials consortium of Wellcome Trust, Medical Research Council, and Department For International Development; British Infection Association; Bill and Melinda Gates Foundation; Innovation For Health And Development; Wellcome Trust.

Effectiveness of protease inhibitor/nucleos(t)ide reverse transcriptase inhibitor-based second-line antiretroviral therapy for the treatment of HIV-1 infection in sub-Saharan Africa: systematic review and meta-analysis.

Leave no one behind. This is the overarching pledge of the Sustainable Development Goals; a pledge that is far from being realised. In 2016, more than 4 million people with tuberculosis were estimated to be undiagnosed or their care and treatment were unknown.1 In the same year, nearly a fifth of the people who were diagnosed and known to be treated for tuberculosis had adverse outcomes, including 1·3 million deaths.1 One reason that millions of people affected by tuberculosis are left behind is an absence of coordinated, international action to combat poverty and inequality.

Pragmatic tuberculosis prevention policies for primary care in low- and middle-income countries

In sub-Saharan Africa, second-line ritonavir-boosted protease inhibitor–based antiretroviral therapy led to virological suppression in 69.3% of participants at week 48 and 61.5% at week 96, based on an intention-to-treat meta-analysis of 4558 participants (14 studies) and 2145 participants (8 studies), respectively.

Socioeconomic and Behavioral Factors Associated with Tuberculosis Diagnostic Delay in Lima, Peru

Despite being a curable and preventable disease, tuberculosis is the leading cause of death from infection worldwide and is one of the top 10 causes of death from any cause, including in children [1]. Incidence is at best barely declining, increasing in some countries, and some prevalence surveys in high-burden countries have demonstrated a significantly higher tuberculosis burden than estimated [1]. Between a quarter and a third of the worlds population is estimated to be infected with tuberculosis, representing a vast reservoir from which new cases arise [1]. Many of these people are never identified or tested, and even among those who are, only a small proportion receive preventive treatment [2]. Interventions that aim to increase preventive treatment uptake and completion are likely to have a greater impact on tuberculosis control and elimination than those focussing on improving completion of treatment by patients [3]. Improving tuberculosis prevention in low- and middle-income countries requires scaling up of simple policies, not better laboratory tests http://ow.ly/VPLL30iPiZA

Why wait? The social determinants underlying tuberculosis diagnostic delay

Abstract. Early detection and diagnosis of tuberculosis (TB) is a global priority. Prolonged symptom duration before TB diagnosis is associated with increased morbidity, mortality, and risk of transmission. We aimed to determine socioeconomic and behavioral factors associated with diagnostic delays among patients with TB. Data were collected from 105 patients with TB using a semi-structured interview guide in Lima, Peru. Factors associated with diagnostic delay were analyzed using negative binomial regression. The median delay from when symptoms commenced and the first positive diagnostic sample in public health facilities was 57 days (interquartile range: 28–126). In multivariable analysis, greater diagnostic delay was independently associated with patient older age, female gender, lower personal income before diagnosis, living with fewer people, and having more visits to professional health facilities before diagnosis (all P < 0.05). Patients who first sought care at a private health facility had more visits overall to professional health facilities before diagnosis than those who first sought care from public or insured employee health facilities and had longer diagnostic delay in analysis adjusted for age and gender. Patients with TB were significantly more likely to first self-medicate than to visit professional health facilities before diagnosis (P = 0.003). Thus, diagnostic delay was prolonged, greatest among older, low-income women, and varied according to the type of care sought by individuals when their symptoms commenced. These findings suggest that TB case-finding initiatives should target vulnerable groups in informal and private health facilities, where many patients with TB first seek health care.

Improving tuberculosis diagnosis: Better tests or better healthcare?

Background Early detection and diagnosis of tuberculosis remain major global priorities for tuberculosis control. Few studies have used a qualitative approach to investigate the social determinants contributing to diagnostic delay and none have compared data collected from individual, community, and health-system levels. We aimed to characterize the social determinants that contribute to diagnostic delay among persons diagnosed with tuberculosis living in resource-constrained settings. Methods/Principle findings Data were collected in public health facilities with high tuberculosis incidence in 19 districts of Lima, Peru. Semi-structured interviews with persons diagnosed with tuberculosis (n = 105) and their family members (n = 63) explored health-seeking behaviours, community perceptions of tuberculosis and socio-demographic circumstances. Focus groups (n = 6) were conducted with health personnel (n = 35) working in the National Tuberculosis Program. All interview data were transcribed and analysed using a grounded theory approach. The median delay between symptom onset and the public health facility visit that led to the first positive diagnostic sample was 57 days (interquartile range 28–126). The great majority of persons diagnosed with tuberculosis distrusted the public health system and sought care at public health facilities only after exhausting other options. It was universally agreed that persons diagnosed with tuberculosis faced discrimination by public and health personnel. Self-medication with medicines bought at local pharmacies was reported as the most common initial health-seeking behaviour due to the speed and low-cost of treatment in pharmacies. Most persons diagnosed with tuberculosis initially perceived their illness as a simple virus. Conclusions Diagnostic delay was common and prolonged. When individuals reached a threshold of symptom severity, they addressed their health with the least time-consuming, most economically feasible, and well-known healthcare option available to them. In high-burden settings, more human and material resources are required to promote tuberculosis case-finding initiatives, reduce tuberculosis associated stigma and address the social determinants underlying diagnostic delay.