Tuberculosis symptom screening for children and adolescents living with HIV in six high HIV/TB burden countries in Africa

Vonasek, Bryan; Kay, Alexander; Devezin, Tara; Bacha, Jason; Kazembe, Peter N.; Dhillon, Dilsher; Dlamini, Sandile; Haq, Heather; Thahane, Lineo; Simon, Katie; Matshaba, Mogomotsi; Sanders, Jill; Minde, Mercy; Wanless, Sebastian; Nyasulu, Phoebe; Mandalakas, Anna M.

doi:10.1097/qad.0000000000002715

Cited by 17 publications

(13 citation statements)

References 19 publications

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“…Guidelines recommend that children living with HIV complete assessment for tuberculosis exposure and symptom screening at every clinical encounter [33]. Nevertheless, emerging data from children and adolescents living with HIV demonstrates sub-optimal performance of facility-based symptom screening [34,35]. In contrast, evidence from household contact tracing studies conducted in communities with high burdens of tuberculosis and HIV-infection demonstrates a 1.5-fold increase in disease identification in HIV-affected households compared to unaffected households [35].…”

Section: Discussionmentioning

confidence: 99%

Tuberculosis prevention in children: a prospective community-based study in South Africa

et al. 2020

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Tuberculosis preventive therapy reduces tuberculosis risk in children. However, the effectiveness of tuberculosis preventive therapy in children living in high burden settings is unclear.In a prospective observational community-based cohort study in Cape Town, South Africa, we assessed the effectiveness of routine tuberculosis preventive therapy in children ≤15 years of age in a tuberculosis and HIV high-prevalence setting.Among 966 children (median age 5.07 years; inter-quartile range [IQR] 2.52,8.72), 676 (70%) reported exposure to an adult with tuberculosis in the past 3 months and 240/326 (74%) of eligible children initiated isoniazid preventive therapy (IPT) under programmatic guidelines. Prevalent (n=73) and incident (n=27) tuberculosis were diagnosed among 100/966 (10%) of children. Children who initiated IPT were 82% less likely to develop incident tuberculosis than children who did not (aOR=0.18; 95% confidence-interval [CI] 0.06,0.52; p=0.0014). Children's risk of incident tuberculosis increased if they were younger than 5 years, living with HIV, had a positive M.tuberculosis specific immune response, or recent tuberculosis exposure. The risk of incident tuberculosis was not associated with gender or M. bovis-BCG vaccination status. Number needed to treat (NNT) was lowest in children living with HIV (NNT=15) and children less than 5 years of age (NNT=19) compared to children of all ages (NNT=82).In communities with high tuberculosis prevalence, tuberculosis preventive therapy substantially reduces the risk of tuberculosis among children who are younger than 5 years or living with HIV, especially those with recent tuberculosis exposure or a positive M.tuberculosis specific immune response in the absence of disease (Mtb-sir-nodis).

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Section: Discussionmentioning

confidence: 99%

Tuberculosis prevention in children: a prospective community-based study in South Africa

et al. 2020

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“…A study done in Eswatini in 2015 that assessed the performance of TB screening and diagnostic tests among pregnant and postpartum women found that the national TB symptom screening tool failed to identify women who tested TB-culture positive and had a sensitivity of 0% [22]. TB symptoms, such as weight loss, may be masked during pregnancy, but TB symptom screening has performed poorly in other populations, including among PLHIV on ART [24,25], and in general has had mixed results in terms of sensitivity [26][27][28]. Others have suggested enhancing the TB screening process, through addition of questions to the screening tool, such as if a household member has a positive WHO TB symptom screen [23], or inclusion of diagnostics like Xpert MTB/RIF or chest radiograph as part of screening, as has been recommended by the WHO [21,29].…”

Section: Discussionmentioning

confidence: 99%

Enhanced Integration of TB Services in Reproductive Maternal Newborn and Child Health (RMNCH) Settings in Eswatini

Teasdale

Pasipamire²,

Ao³

et al. 2022

PLOS Glob Public Health

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Tuberculosis (TB) primarily affects women during their reproductive years and contributes to maternal mortality and poor pregnancy outcomes. For pregnant women living with HIV (WLHIV), TB is the leading cause of non-obstetric maternal mortality, and pregnant WLHIV with TB are at increased risk of transmitting both TB and HIV to their infants. TB diagnosis among pregnant women, particularly WLHIV, remains challenging, and TB preventive treatment (TPT) coverage among pregnant WLHIV is limited. This project aimed to strengthen integrated TB and reproductive, maternal, neonatal and child health (RMNCH) services in Eswatini to improve screening and treatment for TB disease, TPT uptake and completion among women receiving RMNCH services. The project was conducted from April-December 2017 at four health facilities in Eswatini and introduced enhanced monitoring tools and on-site technical support in RMNCH services. We present data on TB case finding among women, and TPT coverage and completion among eligible WLHIV. A questionnaire (S1 Appendix) measured healthcare provider perspectives on the project after three months of project implementation, including feasibility of scaling-up integrated TB and RMNCH services. A total of 5,724 women (HIV-negative or WLHIV) were screened for active TB disease while attending RMNCH services; 53 (0.9%) were identified with presumptive TB, of whom 37 (70%) were evaluated for TB disease and 6 (0.1% of those screened) were diagnosed with TB. Among 1,950 WLHIV who screened negative for TB, 848 (43%) initiated TPT and 462 (54%) completed. Forty-three healthcare providers completed the questionnaire, and overall were highly supportive of integrated TB and RMNCH services. Integration of TB/HIV services in RMNCH settings was feasible and ensured high TB screening coverage among women of reproductive age, however, symptom screening identified few TB cases, and further studies should explore various screening algorithms and diagnostics that optimize case finding in this population. Interventions should focus on working with healthcare providers and patients to improve TPT initiation and completion rates.

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“…Of note, the pediatric WHO TB screen achieved much higher specificity (94%) in prior studies of CHIV who were screened in the outpatient setting; our finding of much lower specificity with the WHO TB screen (4%) likely relates to the severe immunosuppression and pulmonary comorbidities in our population of hospitalized, ART-naive CHIV. 8–10…”

Section: Discussionmentioning

confidence: 99%

“…7 A subsequent meta-analysis including 2 studies among CHIV found that the pediatric WHO symptom screen had overall low sensitivity (61%) and high specificity (94%) among children with clinical TB in outpatient settings; both studies had low rates of microbiologic confirmation that was not ascertained independently of clinical symptoms. [8][9][10] Alternate symptom combinations to identify pediatric TB suspects have been recommended by the Kenyan Ministry of Health (cough, fever, poor weight gain, or lethargy for .2 weeks) and a published TB treatment algorithm for CHIV (cough or fever for .2 weeks, failure to thrive, or failure of antibiotics for pulmonary infection), although performance of these symptom combinations has not been widely validated. 11,12 We performed microbiologic TB testing regardless of clinical signs or symptoms among hospitalized Kenyan CHIV before ART initiation.…”

Section: Introductionmentioning

confidence: 99%

Brief Report: Performance of Tuberculosis Symptom Screening Among Hospitalized ART-Naive Children With HIV in Kenya

Cranmer

Njuguna

LaCourse

et al. 2022

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background:The World Health Organization (WHO) recommends tuberculosis (TB) diagnostic evaluation for children with HIV (CHIV) who have history of TB contact, poor weight gain, cough, or fever. These screening criteria were developed based on studies of symptomatic CHIV with incomplete microbiologic confirmation. We performed routine TB microbiologic evaluation of hospitalized CHIV with and without symptoms to develop a data-driven TB symptom screen.Methods: Among hospitalized antiretroviral therapy-naive Kenyan CHIV enrolled in the Pediatric Urgent Start of Highly Active Antiretroviral Therapy (PUSH) trial, we performed Xpert MTB/RIF and mycobacterial culture of respiratory and stool specimens independent of TB symptoms. We evaluated performance of WHO and other published pediatric TB screening criteria and derived optimized criteria using a combination of symptoms.Results: Of 168 CHIV who underwent TB microbiologic evaluation, 13 (8%) had confirmed TB. WHO TB symptom screening had 100% sensitivity and 4% specificity to detect confirmed TB. Published TB screening criteria that relied on prolonged symptoms missed cases of confirmed TB (sensitivity 85%-92%). An optimized symptom screen including weight loss, cough, anorexia, or TB contact had 100% sensitivity and improved specificity (31%) compared with the WHO pediatric TB symptom screen. Conclusions:The WHO TB symptom screen was highly sensitive but resulted in a high proportion of hospitalized CHIV who would require TB diagnostic evaluation. Other published TB screening criteria missed CHIV with confirmed TB. Our optimized screening tool increased specificity while preserving sensitivity. Future multicenter studies are needed to improve TB screening tools for CHIV in both inpatient and outpatient settings.

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Tuberculosis symptom screening for children and adolescents living with HIV in six high HIV/TB burden countries in Africa

Cited by 17 publications

References 19 publications

Tuberculosis prevention in children: a prospective community-based study in South Africa

Tuberculosis prevention in children: a prospective community-based study in South Africa

Enhanced Integration of TB Services in Reproductive Maternal Newborn and Child Health (RMNCH) Settings in Eswatini

Brief Report: Performance of Tuberculosis Symptom Screening Among Hospitalized ART-Naive Children With HIV in Kenya

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