Edition 1: Contact Tracing

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Case Study: Transmission of Mycobacterium Tuberculosis

Extensive transmission of Mycobacterium tuberculosis from a 9-year-old child with pulmonary tuberculosis and negative sputum smear

Considerable resource is directed towards tracing contacts of adult pulmonarytuberculosis cases. Much less attention is given to young children who are generally regarded as being less infectious due to their inability to generate the required force to aerosolize organisms into droplet nuclei1,2. Numerous published reports of school-based outbreaks support the notion that children are not infectious since the source of infection has consistently been an adult or adolescent, rather than a child3-7.
Dr. Michael Eisenhut

However, although the chance of a child transmitting this disease is less likely, the possibility cannot be excluded entirely. This report of extensive transmission by a 9-year-old boy from a Luton Primary School, England, is particularly noteworthy as it involved a case of smearnegative pulmonary tuberculosis, which in itself is significantly less infectious than smearpositive disease. This case has been reported in detail by Paranjothy and colleagues and published in the BMJ8. Their findings are summarised here.
The index case

The index case was a 9-year-old boy born in the United Kingdom, of Black African decent. He was investigated following a six year history of recurrent cough which had evolved into a daily chronic cough, occasionally productive with one episode of haemoptysis, night sweats and weight loss. Chest X-ray revealed a right upper lobe consolidation and multiple poorly defined opacities in the right lower lobe. Three sputum collections were smear negative, and culture showed Mycobacterium tuberculosis, fully sensitive to the drugs tested. Chemotherapy was initiated using pyrazinamide, rifampicin, and isoniazid for two months, followed by four months of isoniazid and rifampicin. Screening of all family members revealed positive Mantoux and T-SPOT.TB tests and normal chest X-ray examinations in three siblings and two children from the extended family. All received chemoprophylaxis. A third asymptomatic child from the extended family had bilateral hilar lymphadenopathy on chest radiography and started chemotherapy. In addition, all five adults in the immediate and extended family screened positive and required chemoprophylaxis.
Expanding the contact tracing programme

The contact tracing programme was extended to all pupils and teachers in the same school year as the index case. This action, although not in line with current guidelines, was taken because of the high rate of infection among the children who were household contacts of the index case. Screening was undertaken using Mantoux tests with all positive tests confirmed using TSPOT.TB assay. A high infection rate led to the wider screening of all 200 pupils at the school, using the TSPOT.TB test and chest radiography. The decision to omit Mantoux tests and move straight to the more accurate T-SPOT.TBtest was taken primarily for logistical reasons. It was easier to screen such large numbers with a simple blood test than to undertake the skin test, especially since it was almost the end of term and therefore unlikely that many would return for the reading or repeat testing. Previous exposure to BCG immunisation in 28% of pupils at this school would also have led to difficulties with interpretation of the Mantoux test results, generating additional difficulties in investigating the epidemiology of this outbreak and imposing a second uncomfortable procedure (blood sampling) for the confirmatory T-SPOT.TB test in young pupils with a possibly falsepositive Mantoux test. Children with pulmonary parenchymal changes on chest radiography were regarded as potentially infectious and investigated by obtaining three sputum and three gastric lavage samples. Since an adult was considered the most likely source of infection, all adults with at least

eight hours cumulative contact with the school during the previous eight months were invited for chest radiography. Infection rates were significantly higher in the class of the index case than among the other pupils at the school (79% vs 35%, P<0.01). Despite a wide range of racial groups at the school, no correlation between ethnicity and infection rate was observed. In total, 42% of all school pupils (85 children) had positive T-SPOT.TB tests and of these, 16 had hilar lymphadenopathy, but were asymptomatic, and two had pulmonary parenchymal changes and were admitted for gastric lavage and sputum collection. One of these two, an 8-year old boy, had acid fast bacilli on gastric lavage. All adult chest X-ray examinations were normal, and no additional cases of active or latent tuberculosis were detected among the household contacts of the children diagnosed with active TB on screening. Several factors led the authors to conclude that the index case was the source case for the infected school children. Firstly, the infection rate in the class of the index case was significantly higher than the rates in the other classes. Secondly, epidemiological and DNA fingerprinting of the index case discovered a genetic match to a strain isolated six years previously in an adult from the extended family of the index case. However, this individual had no contact with the school. Furthermore, the shared strain type between the two children at the junior school provided good evidence to support child-to-child transmission. Thirdly, the strain identified is relatively rare in England and was found in only two other patients in the National Strain Typing Database. Both cases were from the same West African country as the index case, but had no epidemiological link with the index case or the school. Finally, the area of Luton where the school is located is classified as a high-incidence area, with an annual incidence of tuberculosis of 45 per 100 000 people9. Analysis of school screening results following cases of positive sputum smear pulmonary tuberculosis in children during the previous two years found rates of positive Mantoux tests of pupils between 0% and 2.4%. Since this episode produced an infection rate of 42%, it far exceeds the expected rate of infection in the area.
Conclusion

This is an interesting case of extensive transmission of M. tuberculosis from a young child with smear-negative tuberculosis and may have far- reaching implications. In particular, National Guidelines, which place emphasis on sputum smear positivity as main indicator of infectivity for starting contact tracing outside the household setting, may need to be reviewed.

Past Articles

CONTACT TRACING: Conducting Contact Tracing Among the Homeless CONTACT TRACING: Reduction in the Unnecessary Use of Isoniazid Chemoprophylaxis with T-SPOT.TB Case Study: Miliary Tuberculosis T-SPOT.TB Screening for Anti-TNF Therapy in Severe Psoriasis A History of TB

Recent News
2010 World TB Day New study confirms 98.9% specificity of the T-SPOT.TBassay

Independent peer-reviewed study demonstrates that TB contact tracing based on use of the T-SPOT.TB assay is more cost effective
For more information, visit http://www.oxfordimmunotec.com/Oxford_International Made possible with an educational grant from Oxford Immunotec Ltd. 2010 Oxford Immunotec Ltd.