Transmission of tuberculosis (TB) from children is thought to be rare,1 although transmissions from very young children (age 12 weeks) have been documented.2 In outbreak settings involving schools, transmission is reported to vary from 1 in 3 to 1 in 50 contacts,3 which may be influenced by Bacillus Calmette-Guérin (BCG) status,4 the virulence of the organism, or degree of exposure to environmental factors such as second-hand smoke.1,5,6 Studies looking at transmission to children where contact has occurred in a household setting (from an adult source) estimate transmission rates between 30% and 50% to close contacts7; however, little is known on transmission from a child source or in settings outside the house. As tests to determine transmission have evolved and the interferon-gamma release assays (IGRAs) are now available for routine use, there are new opportunities to accurately study the transmission of TB which have not been possible due to limitations of the tuberculin skin test (TST) method, such as confounding with previous BCG, sensitivity, and the boosting effect of repeated tests.8
Systems for capturing data on all TB diagnoses and contact tracing are often limited due to a lack of detail of contact screening method, case definitions, and low participation rates.5,9,10 Published outbreak reports therefore represent an opportunity to study transmission in school settings where there are also likely to be additional pressures for information from public health officials from concerned parents, teachers, and the local media, in addition to multicultural needs and fear and anxiety.11
In this article, we report a systematic analysis of published reports of outbreaks of TB in school settings to calculate transmission rates, with the aim of informing public health officials.
MATERIALS AND METHODS
We searched the following databases: Medline (1950–February 2011), Embase (1960–February 2011), CINHAL (1980–February 2011). Search strategies were adapted for each database but limited to English language studies. Bibliographies of studies identified were checked for any additional references.
Inclusion and Exclusion Criteria.
We included studies that described screening contacts after an index case with TB (adult or child) had contact with children in a school setting. We defined close contacts as classroom contacts of the index case and wider contacts as children outside this group. Individual case studies, non-English language studies, and reports with limited detail were excluded. A full list of excluded studies can be obtained from the authors.
Data extraction was independently carried out by 2 reviewers. Data were collected on the type of setting (eg, nursery, nursery school, infant, or junior school), transmission rate, and factors associated with the transmission rates (including infection status of the incident case and strain of TB). Population characteristics including ethnicity, gender, and socioeconomic status were also recorded.
Transmission rates were summarized by calculating a weighted average and corresponding 95% confidence interval (CI). Studies were weighted by the number of contacts screened as transmission rate would be less precise if only a small number of contacts were screened. The weight of each study was calculated as the inverse of the variance for that study. The 95% CIs were calculated from the standard error (obtained from the variance) using standard statistical formula.
Results are presented separately according to whether the index case was a child or adult. All transmission rates described relate to transmission to children.
Twenty-nine studies were identified after reviewing the titles and abstracts of the database searches. Twelve studies met the inclusion criteria.6,12 – 22 Data flow of studies and data extracted from the studies are presented in the online supplementary materials (Table, Supplemental Digital Content 1, http://links.lww.com/INF/A951; Fig., Supplemental Digital Content 2, http://links.lww.com/INF/A952).
Ten studies (83%) described the index cases smear status, but sociodemographic details were not always present. All studies gave details of the screening test used (Table 1).
Confirmation of Transmission.
In 2 studies,6,19 the strain of TB was identified by DNA typing to confirm contacts were infected with the same clone as the index case. Four studies reported the baseline (expected) TST reactivity prevalence for the populations where the incident occurred. This information demonstrates that transmission is likely to have occurred from the source case and positive tests are not likely to be simply identification of previously unidentified infection. In 3 studies, the baseline level of TST positives was below 2% in their respective populations, increasing to 13%, 42.5%, and 51% within the studies.15,16,19In the fourth study,20 the baseline level was higher at 9.8% and increased to 15.8% within the study.
Overall Rate of Transmission.
The number of close contacts screened ranged from 24 to 43 and transmission rates varied between 9.8% and 69.8%. In wider contacts, the range was 29 to 722 and transmission rates varied between 2.9% and 72.4%.
Transmission From a Child Index.
Five studies6,15,17,19,20 reported on an index case who was a child in the school. Three studies6,17,19 reported screening close contacts of children and the number of contacts screened ranged from 24 to 43. The transmission rates varied between 66.7% and 72.4%. The weighted average transmission was 69.8% (95% CI: 60.7%–79%). Four studies15,17,19,20 extended tracing or only screened wider contacts and the numbers screened ranged from 156 to 722. Transmission varied between 13% and 41.7%. The weighted average was 14.8% (95% CI: 12.9%–16.9%).
Transmission From an Adult Index.
Seven studies12 – 14,16,18,21,22 report on an index case who was an adult at the school. Four studies12,13,16,21 report on contact tracing in both close and wider contacts, the remaining 314,18,22 only screened wider contacts. In close contacts, the number screened ranged from 28 to 49 with transmission from 27% to 52.5%. The weighted average transmission rate in close contacts was 39.3% (95% CI: 26.8%–51.8%). In wider contacts, the number screened ranged from 55 to 388 and transmission from 3% to 67.2%. The weighted average transmission in wider contacts was 39.3% (95% CI: 35.7%–43%). The weighted transmission data is summarized graphically in the supplementary material (Fig., Supplemental Digital Content 3, http://links.lww.com/INF/A953).
Comparison of TST With IGRA Tests.
To determine whether detection rates differ with the testing method used, we looked at studies comparing IGRA with TST in addition to varying cutoff criteria for TST.
One study did use the contact tracing exercise to compare the TST test with an IGRA7 and found higher initial evidence of transmission using IGRA. This was thought to be due to the delay in Mantoux test conversion. Overall, IGRA was more sensitive, and in this group of contacts all of whom had BCG, the IGRA test detected transmission in 9.8% and resulted in treatment for 9 cases, compared with 65% (200 cases) if the Mantoux 5-mm criteria had been adopted. This suggests IGRA may be more suitable for use in larger contact screening exercises particularly where BCG may confound testing and where costs are feasible.
This is the first systematic review of evidence of TB transmission in children aged 3 to 11 years. This age group was chosen because children in schools in this age range tend to stay within the same class and not mix between classes as is the case in secondary education. This allows the analysis of transmission rates with some consistency between exposure time and proximity of contacts.
The “stone in the pond”23 approach to contact screening is difficult where there is no consensus on a threshold of when to move to next level of contacts. The evidence identified in this review suggests that in primary school settings where there is an adult source, the proportion of contacts screening positive is likely to be higher overall, but similar between close and wider contacts. In contrast transmission to close contact was substantially higher from a child index, although the risk of transmission to wider contacts was substantially lower. This seems to be logical, given the nature of contact between children and adults in school settings. A recent retrospective cohort study of secondary school pupils in contact with a smear positive student found transmission is more likely in school year contacts and not wider contacts.24
The method and criteria used for screening is key in the likely number of contacts identified. Studies using a lower Mantoux cutoff tended to identify more positive contacts,16 whereas more conservative cutoffs detected less positive reactors as expected,15 demonstrating the criteria used to determine a positive screening result is a key factor in the likely number of individuals who will be detected.
IGRA tests were used in 3 studies and offered benefits in populations in which there was high prevalence of vaccination with BCG21 and allowed for rapid testing without waiting for Mantoux-test conversion,6,19 these benefits have also been demonstrated in older children 11 to 15 years of age.25
It was not possible to get detailed information on sociodemographic factors that may influence the transmission rate across the studies identified. Smear status did not correlate with transmission, and indeed, the one study with a smear negative index had a high transmission rate, suggesting smear status alone is not a reliable risk factor for transmission in this setting.19
In summary, evidence from outbreaks suggest that where the index is a child, risk of transmission is high (over 60%) to close contacts, but limited for wider contacts. In contrast, where the index case is an adult, transmission may be uniform across close and wider contact groups. This information should be useful in informing decisions around how wide to extended contact tracing in such settings.
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