Mycobacterium tuberculosis infection burden in poor urban communities
Authors: Ben J Marais
Journal: The Lancet Child & Adolescent Health (2017)

Global urbanisation accelerated during the 21st century, leading to more than half of the world's population living in cities.1UN HabitatUN World Cities Report 2016. United Nations Human Settlements Programme, Kenya2016Crossref Google Scholar Although moving to the city helped millions of people escape poverty through better access to employment and education, informal urban settlements often act as a poverty trap, with poor education prospects and deteriorated living conditions. The opportunities brought by urbanisation across diverse sociocultural backgrounds, which historically characterised urban dynamics, have stalled in many regions of the world.1UN HabitatUN World Cities Report 2016. United Nations Human Settlements Programme, Kenya2016Crossref Google Scholar Burgeoning informal settlements pose a particular challenge in Africa and Asia, where 90% of the expected increase in the world's urban population will occur between now and 2050.2UNWorld Urbanization Prospects, 2014 revision. United Nations, New York2014Google Scholar Establishing liveable urban environments that promote health and limit risk of disease is a key challenge of the 21st century. Historically, tuberculosis has been a marker of social inequality, and tuberculosis incidence is an important indicator of progress in the Sustainable Development Goals (SDGs).3Raviglione M Marais B Floyd K et al.Scaling up interventions to achieve global tuberculosis control: progress and new developments.Lancet. 2012; 379: 1902-1913Summary Full Text Full Text PDF PubMed Scopus (264) Google Scholar Apart from diagnostic constraints, Mycobacterium tuberculosis infection and primary progressive disease in young children provide an important measure of tuberculosis transmission within communities.4Perez-Velez CM Marais BJ Tuberculosis in children.N Engl J Med. 2012; 367: 348-361Crossref PubMed Scopus (376) Google Scholar Tuberculosis is also a major, albeit under-appreciated, cause of under-5 morbidity and mortality in areas with uncontrolled tuberculosis transmission,5Jenkins HE Yuen CM Rodriguez CA et al.Mortality among children diagnosed with tuberculosis: Systematic review and meta-analysis.Lancet Infect Dis. 2017; 17: 285-295Summary Full Text Full Text PDF PubMed Scopus (132) Google Scholar but few studies have prospectively documented this burden. In The Lancet Child & Adolescent Health, Leonardo Martinez and colleagues6Martinez L le Roux DM Barnett W Stadler A Nicol MP Zar HJ Tuberculin skin test conversion and primary progressive tuberculosis disease in the first 5 years of life: a birth cohort study from Cape Town, South Africa.Lancet Child Adolesc Health. 2017; (published online Nov 17.)http://dx.doi.org/10.1016/S2352-4642(17)30149-9Google Scholar report M tuberculosis infection and primary disease progression during the first 5 years of life in the Drakenstein birth cohort. The incidence of tuberculosis in the study communities outside Cape Town, South Africa, was high (880 per 100 000 population per year) but nationally representative. Similarly, HIV infection rates were high, especially in Mbekweni township, but were broadly representative of the situation in southern Africa. Encouragingly, the prevention of mother-to-child transmission of HIV was highly effective, with less than 1% of babies born to mothers living with HIV becoming HIV infected. M tuberculosis infection was measured by tuberculin skin test conversion, using an induration cut-off of 10 mm or greater. For the 915 children included in the infection analysis, the cumulative hazard of tuberculin skin test conversion at 6 months of age was 0·08, increasing to 0·35 after 36 months. Since more specific γ-interferon release assays were not used, BCG vaccination might have accounted for the large proportion of positive tuberculin skin test conversions recorded at 6 months. However, to limit additional false positives from BCG vaccination or boosted immune responses from repeated tuberculin testing, no repeat testing was done in children with a reactive but negative tuberculin skin test (indurations 1–9 mm). Censoring a large number of children complicates the interpretation of results, but represents a prudent approach and limits the influence of false-positive reactions. The incidence of tuberculin conversion was 11·8 (95% CI 10·0–13·8) per 100 child-years, which is broadly equivalent to an annual risk of infection of 11·8%. The high burden of M tuberculosis infection recorded during the first 3 years of life supports similar findings from an isoniazid preventive therapy trial in HIV-exposed infants,7Maritz ER Montepiedra G Liu L et al.Source case identification in HIV-exposed infants and tuberculosis diagnosis in an isoniazid prevention study.Int J Tuberc Lung Dis. 2016; 20: 1060-1064Crossref PubMed Scopus (6) Google Scholar which showed that excessive tuberculosis exposure is not restricted to HIV-affected households. The high incidence of M tuberculosis infection recorded in young children, who have less mobility within the community than adolescents and young adults, suggests even higher annual rates of infection among these older age groups. This finding indicates that people living in areas with uncontrolled tuberculosis transmission are likely to have multiple M tuberculosis infections during their lifetime, potentially even multiple infections per year. It also explains the high rate of reinfection that has been observed in patients presenting with a second episode of tuberculosis in Cape Town.8Marx FM Dunbar R Enarson DA et al.The temporal dynamics of relapse and reinfection tuberculosis after successful treatment: a retrospective cohort study.Clin Infect Dis. 2014; 58: 1676-1683Crossref PubMed Scopus (89) Google Scholar The incidence of all diagnosed primary progressive disease was 2·9 (95% CI 2·4–3·7) per 100 child-years, which suggests a considerable burden of unidentified transmission and undiagnosed tuberculosis among young children in settings with uncontrolled tuberculosis transmission. Despite poor diagnostic yield in children who typically develop paucibacillary disease,4Perez-Velez CM Marais BJ Tuberculosis in children.N Engl J Med. 2012; 367: 348-361Crossref PubMed Scopus (376) Google Scholar the incidence of microbiologically confirmed tuberculosis was 0·7 (0·4–1·0) per 100 child-years, with a cumulative hazard of 0·02 over 3 years. Many children developed tuberculosis after missed opportunities for prevention, as was the case with the child who developed tuberculous meningitis during the study period. The authors rightly call for a strengthening of current prevention programmes and new strategies to improve adherence to preventive therapy. The fact that adult source cases were frequently only detected after a child had been diagnosed with tuberculosis, which is similar to findings from other tuberculosis-endemic settings,7Maritz ER Montepiedra G Liu L et al.Source case identification in HIV-exposed infants and tuberculosis diagnosis in an isoniazid prevention study.Int J Tuberc Lung Dis. 2016; 20: 1060-1064Crossref PubMed Scopus (6) Google Scholar, 9Nguyen PTK Nguyen NV Phung TD Marais B X-pert MTB/RIF diagnosis of twin infants with tuberculosis in Da Nang, Vietnam.J Clin Med. 2017; 6DOI:10.3390/jcm6100096Crossref Scopus (2) Google Scholar emphasises the need for enhanced active case-finding strategies. Although everything possible should be done to improve children's access to tuberculosis preventive therapy and treatment,10Marais BJ Improving access to tuberculosis preventive therapy and treatment for children.Int J Infect Dis. 2017; 56: 122-125Summary Full Text Full Text PDF PubMed Scopus (25) Google Scholar Martinez and colleagues' study highlights the immense social challenges facing developing countries during a period of rapid urbanisation. The positive vision of cities as hubs of creativity and productivity, where healthy communities live in an ecologically sustainable manner, is challenged by the reality in tuberculosis-endemic settings. Poorly coordinated urban expansion poses particular challenges in resource-limited settings, in which it creates conditions conducive to the spread of infectious diseases; tuberculosis transmission is a prime example. Finding comprehensive solutions to safeguard the health of children in these settings is a major challenge that requires urgent consideration. Birth cohort studies, such as the Drakenstein cohort study, that monitor the influence of multiple harmful exposures are important to provide mechanistic insight and guide decision-making processes. They also present an opportunity to assess the effect of holistic, community-wide interventions on the health of populations. I declare no competing interests. Tuberculin skin test conversion and primary progressive tuberculosis disease in the first 5 years of life: a birth cohort study from Cape Town, South AfricaGreater focus should be placed on the first years of life as a period of high burden of transmission and clinical expression of tuberculosis infection and disease. Multifaceted interventions, such as isoniazid preventive therapy and tuberculosis screening of infants with LRTIs, beginning early in life, are needed in high-burden settings. 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