Effects of social protection on tuberculosis treatment outcomes in low or middle-income and in high-burden countries: systematic review and meta-analysis

Andrade, Kaio Vinicius Freitas de; Nery, Joilda Silva; Souza, Ramon Andrade de; Pereira, Susan Martins

doi:10.1590/0102-311X00153116

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Sumário

REVIEW • Cad. Saúde Pública 34 (1) • 2018 • https://doi.org/10.1590/0102-311X00153116 linkcopy

Effects of social protection on tuberculosis treatment outcomes in low or middle-income and in high-burden countries: systematic review and meta-analysis

Efeitos da proteção social sobre os desfechos do tratamento da tuberculose em países de renda baixa e média ou de carga alta da doença: uma revisão sistemática e meta-análise

Efectos de la protección social en los resultados del tratamiento contra la tuberculosis en países con baja o media renta y gravemente afectados: revisión sistemática y metaanálisis

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Tuberculosis (TB) is a poverty infectious disease that affects millions of people worldwide. Evidences suggest that social protection strategies (SPS) can improve TB treatment outcomes. This study aimed to synthesize such evidences through systematic literature review and meta-analysis. We searched for studies conducted in low- or middle-income and in high TB-burden countries, published during 1995-2016. The review was performed by searching PubMed/MEDLINE, Scopus, Web of Science, ScienceDirect and LILACS. We included only studies that investigated the effects of SPS on TB treatment outcomes. We retained 25 studies for qualitative synthesis. Meta-analyses were performed with 9 randomized controlled trials, including a total of 1,687 participants. Pooled results showed that SPS was associated with TB treatment success (RR = 1.09; 95%CI: 1.03-1.14), cure of TB patients (RR = 1.11; 95%CI: 1.01-1.22) and with reduction in risk of TB treatment default (RR = 0.63; 95%CI: 0.45-0.89). We did not detect effects of SPS on the outcomes treatment failure and death. These findings revealed that SPS might improve TB treatment outcomes in lower-middle-income economies or countries with high burden of this disease. However, the overall quality of evidences regarding these effect estimates is low and further well-conducted randomized studies are needed.

Tuberculosis; Treatment Outcome; Social Welfare; Public Policy

Study/Country	Income/TB-burden	n	Study location	Study design (score) *	Population and study period	Intervention	Main outcome
Baral et al. ²²/Nepal	Low-income	I₁: 33 I₂: 42 C: 81	7 DOTS-plus centers	Mixed-method (intervention and qualitative)	MDR-TB patients (Jan-Dec 2008)	I₁: counselling. I₂: counselling and financial support	Cure (I₁: 85%; I₂: 76%; C: 67%)
Cantalice Filho ³⁷/Brazil	Upper middle-income High TB-burden	142 (I: 74, C: 68)	Primary care clinics in Duque de Caxias, Rio de Janeiro State	Retrospective comparative study (7 points)	≥ 15 years old with confirmed TB diagnosis (Jan 2004-Jul 2006)	Monthly food baskets delivered in the healthcare clinic	Cure (I: 87.1%; C: 69.7%)
Ciobanu et al. ²⁷/Republic of Moldova	Lower middle-income	4,870 (I: 2378, C: 2492)	National data, before (2008) and after (2011) incentives	Retrospective cohort study (14 points)	≥ 18 years old, TB patients treated in 2008 and in 2011	Cash, non-cash or both incentives. (I: groups that received cash)	TSR (I: 88%; C: 79%; p < 0.001)
Clarke et al. ³¹/South Africa	Upper middle-income High TB-burden	89 (I: 47, C: 42)	211 farms (I: 106; C: 105)	Cluster randomized controlled trial	Permanent farm dwellers ≥ 15 years old treated (from Nov 1, 2000 to Oct 31, 2001)	Adult farm dwellers trained as lay health workers	TSR (I: 83%; C: 64.3%; p = 0.042)
Datiko & Lindtjørn ¹⁹/Ethiopia	Low-income High TB-burden	318 (I: 230, C: 88)	51 kebeles in two rural districts of Southern Ethiopia	Community-randomized trial	All new smear-positive pulmonary TB cases	Trained community health workers	TSR (I: 89.3%; C: 81.3%; p = 0.012)
Demissie et al. ²⁰/Ethiopia	Low-income High TB-burden	128 (I: 64, C: 64)	2 rural districts of Northern Ethiopia	Mixed-method - cohort and qualitative (12 points)	Smear-positive TB patients (from July 1 to Oct 15, 1998)	TB patients in rural kebeles organized in “TB clubs”	TCR (I: 68.7%; C: 46.8%; p = 0.02)
Gärden et al. ²³/Russia	High-income High TB-burden	518 (I: 142, C: 376)	St. Petersburg’s TB dispensary	Historical controlled intervention study (11 points)	Homeless patients referred to TB dispensary (from Dec 2001 to Jan 2004)	Food packages delivered once a day 5 days a week and support from a social worker	TSR (I: 78.2%; C: 31.0%)
Jakubowiak et al. ²⁴/Russia	High-income High TB-burden	1,389 (I: 382, C: 1,007)	4 regions with TB services	Cross-sectional study (5 points)	New pulmonary TB patients ≥ 15 years old treated (from Jan 1, 2004 to Mar 31, 2005)	Social support during TB treatment (food packs, hygiene kits, transportation incentives, etc.)	28.1% of adherents and 18.4% of non-adherents with incentives
Kliner et al. ²⁹/Swaziland	Lower middle-income	1,077 (I: 161, C: 916)	Hospital in a rural district	Pragmatic controlled interventional study (12 points)	TB patients (Jan 2010-Sep 2011)	Treatment support from community workers	TSR (I: 73% vs. C: 60%; p = 0.003)
Lönnroth et al. ³⁸/Myanmar	Lower middle-income High TB-burden	253 (non-controlled)	National case notification data and survey in clinics in Yangon	Cross-sectional study (10 points)	All patients treated in Sun Quality Health (SQH) clinics in Yangon (from Sep 1 to Oct 30 2004)	Sun Quality Health (SQH), a social franchise that licensed practitioners with clinics serving low-income people	TSR for new smear-positive cases was 84%
Lutge et al. ⁴³/South Africa	Upper middle-income High TB-burden	4,091 (I: 2,107, C: 1,984)	20 public sector clinics in Kwazulu-Natal	Cluster-randomized controlled trial	TB patients within (July 1, 2009 to Mar 31, 2010)	Monthly vouchers (US$ 15) redeemable at specific general stores	TSR (I: 76.2% vs. C: 70.7%; p = 0.107)
Martins et al. ³⁰/Timor-Leste	Lower-middle income	265 (I: 136, C: 129)	3 primary clinics in Dili: government, private and church operated)	Randomized controlled trial	TB patients aged ≥ 18 and that agree to treatment at diagnostic clinic for eight months	Daily meal in attendance to the clinic and unprepared food to take home, in continuation phase	TSR (I: 76% vs. C: 78%; p = 0.7)
Ngamvithayapong-Yanai et al. ³⁵/Thailand	Upper middle-income High TB-burden	759 (I: 192, C: 567)	Chiang Rai, Thailand’s northern province	Intervention study - before and after (7 points)	Extremely poor TB patients, living alone, with elderly caregivers or isolated from community	Engagement of Chiang Rai women’s organization to support them financially and socially	TSR (I: 69.3% vs. C: 51.6%; p < 0.00)
Ritchie et al. ²¹/Malawi	Low-income	110 (I: 30, C: 80)	28 health centers in Zomba district	Cluster randomized controlled trial	All lay health workers involved in providing care to TB patients	Two knowledge translation interventions: educational outreach and reminders	TSR (I: 70% vs. C: 58%; p = 0.578)
Rocha et al. ²⁸/Peru	Upper middle-income	1,861 (I: 307, C: 1,554)	Eight contiguous slums in Northern Lima	Intervention study (4 points)	Subsequently diagnosed TB patients and their household contacts (Dec 2007-Oct 2010)	Household visits, counselling, food and cash transfers, microenterprise, microcredits and training	TSR (91% before vs. 97% after intervention)
Singh et al. ³²/India	Lower middle-income High TB-burden	617 (I:1 41, C: 476)	One tuberculosis unit covering a population of 600,000 in Haryana State	Intervention study (10 points)	New sputum smear-positive patients registered in the tuberculosis unit for treatment	Directly Observed Treatment (DOT) from community volunteers vs. government health workers	TSR (I: 78% vs. C: 77%)
Soares et al. ³³/Brazil	Upper middle-income High TB-burden	2,623 (I: 1,771, C: 852)	Rocinha Favela, the largest urban slum in South America	Intervention study (before and after) (13 points)	All patients with pulmonary or extra-pulmonary TB who started treatment between 2001 and 2008	DOT implementation and training 40 lay persons as community health workers	TSR (83.2% vs. 67.6%; p < 0.001) pre- and post-intervention
Sripad et al. ²⁵/Ecuador	Upper middle-income	191 (I: 105, C: 86)	Ecuador’s NTP	Non-randomized trial with historical controls (8 points)	Drug-resistant (DR-TB) patients (from Aug 2011 to Jan 2012 - intervention and from Jan to Aug 2010 - pre-program)	Ecuador’s NTP enacted a monetary incentive program giving adherent DR-TB patients a USD 240 bonus each month	1-year default rate (9.5% vs. 26.7%; p < 0.05), in program and pre-program
Sudarsanam et al. ³⁶/India	Lower middle-income High TB-burden	97 (I: 48, C: 49)	One of four clinics in Vellore town, southern Indian state of Tamil Nadu	Randomized controlled trial	Patients aged > 12 years diagnosed with TB (recruited between Jan and Nov 2005)	Macronutrient supplement (cereal and lentil mixture) and micronutrients (one-a-day multivitamin table)	Higher poor outcomes in the non-supplemented HIV-TB co-infected group
Torrens et al. ⁴²/Brazil	Upper middle-income High TB-burden	7,255 (I: 5,788, C: 1,467)	Brazilian national databases (SINAN and CadÚnico)	Retrospective cohort (14 points)	All new TB cases diagnosed in 2010, recorded in SINAN database and registered in CadÚnico	Brazilian national conditional cash transfer (Brazilian Income Transfer Program)	Cure rates (I: 82.1% vs. C: 76.9%; p < 0.001)
Wei et al. ³⁹/China	Upper middle-income High TB-burden	183 (I: 90, C: 93)	2 districts of Shanghai (1 intervention/1 control)	Controlled intervention study - before and after (8 points)	Poor migrants TB patients	Financial incentives to poor migrant TB patients (transportation and living subsidies)	TCR (I: from 78% to 89%; and C: from 73% to 76%; p = 0.03)
Yao et al. ⁴⁰/China	Upper middle-income High TB-burden	9,194 (I: 5,449, C: 3,745)	Fifty poor counties of Shanxi (Fidelis project) and 51 control counties	Pilot evaluation study (8 points)	New TB cases in baseline (Jan-Sep 2004) and during the intervention (Jan-Sep 2005) using routine TB reporting data	Financial incentives for doctors. Incentives to village leaders for community health education	TSR baseline (I: 95.3 vs. C: 93.9%; p < 0.01); project (I: 96.9 vs. C: 96.9%; p > 0.05)
Zou et al. ⁴¹/China	Upper middle-income High TB-burden	356 (I: 263, C: 93)	Three districts located in Shanghai: (i) Communicable Disease Research Consortium (COMDIS), (ii) The Global Fund Project, (iii) control	Intervention study (case study) - before and after (8 points)	Poor migrants TB patients living in Shanghai, China, targeted by two projects involving financial incentives (introduced in Oct 2007)	COMDIS: single living and transportation subsidies Global Fund Project: living and, transportation incentives, plus incentives to clinic staff for each extended working hour	TCR District I (78 vs. 89%); District II (73 vs. 88%); Control (73 vs. 76%).
Zwarenstein et al. ³⁴/South Africa	Upper middle-income High TB-burden	98 (I: 54, C: 44)	Four clinics in Elsies River, suburb (20km from Cape Town)	Randomized controlled trial	Adult (aged > 15 years) pulmonary TB patients, who started TB treatment (new and retreatment)	Supervision by volunteers lay health workers in a poor community/Supervision by clinic nurse/Self-supervision	% of success: lay health workers (74%), clinic DOT (57%) and self-supervision (59%)
Álvarez Gordillo et al. ²⁶/Mexico	Upper middle-income	87 (I: 44, C: 43)	Health centers in Chiapas	Controlled intervention study	>15 years old with sputum smear-positive pulmonary TB (Feb 2001-Jan 2002)	Training program for health professionals and self-help groups for TB patients	TSR (I: 97.7%; C: 81.4%)

Outcomes	Number of participants (studies) - follow-up	Quality of the evidence (GRADE)	RR (95%CI)	Anticipated absolute effects
Outcomes	Number of participants (studies) - follow-up	Quality of the evidence (GRADE)	RR (95%CI)	Risk with TB usual care	Risk difference with social protection interventions
Treatment success	1,687 (9 RCTs)	⨁⨁◯◯ LOW ^a,b	1.09 (1.03-1.14)	723 per 1,000	65 more per 1,000 (22 more to 101 more)
Cure	1,590 (8 RCTs)	⨁◯◯◯ VERY LOW ^a,b,c	1.11 (1.01-1.22)	493 per 1,000	54 more per 1,000 (5 more to 109 more)
Treatment default	1,325 (7 RCTs)	⨁⨁◯◯ LOW ^a,b	0.63 (0.45-0.89)	126 per 1,000	46 fewer per 1,000 (69 fewer to 14 fewer)
Treatment failure	1,245 (6 RCTs)	⨁⨁◯◯ LOW ^a,b	0.78 (0.44-1.40)	50 per 1,000	11 fewer per 1,000 (28 fewer to 20 more)
Death	1,238 (6 RCTs)	⨁⨁◯◯ LOW ^a,b	0.98 (0.61-1.57)	68 per 1,000	1 fewer per 1,000 (27 fewer to 39 more)

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[TFN1] C: control group; CadÚnico: Unified Registry for Social Programmes; I: intervention group; NTP: National Tuberculosis Programme; SINAN: Notifiable Diseases Information System; TCR: treatment completion rates; TSR: treatment success rates.

[TFN2] * Quality scores with Downs & Black ¹⁵ tool, except for randomized controlled trials - RCTs (in this review, we arbitrarily established that scores < 9 indicates bad quality evidences and ≥ 9 indicates good quality evidences).