Pediatric TB: What to Expect and When to Expect it

 

 

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Case History

12/18/2010—A 34 year old Hispanic male was diagnosed with pulmonary tuberculosis based on clinical findings, positive AFB sputum smears and a Nucleic Acid Amplification test (NAAT) positive for M. tuberculosis. During the course of the subsequent contact investigation three pediatric contacts were identified aged 11 months, 4 years old and 15 years old. The contacts were the case’s children and had been co-habitating with him.

12/22/2010—The children are evaluated for TB disease. The 11 month old and the 4 year old were asymptomatic but the 15 year old complained of cough. The 11 month old and the 4 year old children had tuberculin skin tests (TST) with 0mm induration while the 15 year old patient had a TST with 13 mm induration. All tests were read as negative.

The 15 year old contact was examined radiographically due to cough and the chest radiograph showed right upper lobe abnormalities consistent with cavitary tuberculosis. After cultures were obtained, the adolescent patient was started on a treatment regimen for active pulmonary tuberculosis consisting of rifampin, isoniazid, pyrazinamide, and ethambutol.

The four year old contact was examined clinically and radiographically and the findings were not indicative of active tuberculosis disease. The patient was initiated on daily isoniazid mono-therapy as window prophylaxis.

After clinical and radiographic examination the infant contact was diagnosed with miliary pulmonary tuberculosis along with subcarinal and hilar lymphadenopathy. The patient was admitted for gastric aspirates and underwent a lumbar puncture and cerebrospinal fluid (CSF) findings were not indicative of TB meningitis. The infant was started on isoniazid, rifampin, ethambutol and pyrazinamide.

On 2/24/11 the 4 year old contact was tuberculin skin tested a second time and the results were read as 10 mm (positive). Based on these findings the child was diagnosed with LTBI and treatment was extended to 9 months (including the 2 months already received). He completed treatment in September of 2011.

The adolescent completed 6 months of short course therapy in May of 2011. The infant completed a 9 month treatment regimen. Both children improved clinically and radiographically. The treatment courses of both children were uneventful.

Epidemiology

The World Health Organization (WHO) estimated in 2009 there were approximately 1 million cases of pediatric (patients < 18 years of age) TB globally; given disparities in reporting and diagnostic difficulties in children, this likely represents an underestimate. The majority of these cases are found in the developing world. In countries with a high TB burden, pediatric TB constitutes 20-40% of the case load, as opposed to low burden settings where it only constitutes 4 - 7% (1, 3).

The global epidemiology of pediatric tuberculosis is difficult to describe accurately. Pediatric TB is significantly under diagnosed. Until recently only AFB smear positive cases were reported under the WHO DOTS strategy (3), however only 5% of children with TB are AFB smear positive and therefore most cases were not counted. Pediatric TB is more challenging to diagnose because children are less likely to be either smear or culture positive and providers must rely on clinical and radiographic findings as well as identification of exposure to adult cases. This challenge is magnified by limited diagnostic resources in many low income countries. These are the same countries which have the highest burden of pediatric TB and often lack the resources to conduct active case finding and good contact investigations.

Both the global TB epidemic and pediatric TB are fueled by many of the same factors. The HIV pandemic, malnutrition and the emergence of drug resistant disease are all factors sustaining pediatric TB globally.

A child’s risk for contracting tuberculosis is directly related to the degree of contact and proximity to an active infectious case. The source of infection is usually an adult with cavitary tuberculosis. Children are generally not infectious, unless they have cavitary radiographs, draining skin lesions, or are smear positive. Although older adolescents have been known to transmit infection. Younger children tend to be infected by a household source and as they become older they become increasingly more likely to be infected outside the home , making source case identification more challenging (3). Social factors also play a role in the likelihood of a child being exposed to Mycobacterium tuberculosis. Children living in impoverished areas, in poor housing, and crowded urban environments are subject to increased rates of transmission (3).

Pathophysiology/Immunology

Children are at increased risk of developing active tuberculosis once infected. They are also at increased risk for disseminated disease and poor outcomes (3). Infants are particularly vulnerable and have notably high morbidity and mortality rates. Young children, especially infants, are at an increased risk of acute hematogenous dissemination and tuberculous meningitis.

Most children and adults infected with TB do not progress to active disease. Progression to active disease is prevented by a successful immune response, associated with a strong T-Helper cell/CD4 lymphocyte response and adequate levels of interferon gamma. The response begins after the inhalation of Mycobacterium tuberculosis into the pulmonary alveoli. The tubercle bacilli are then phagocytized by the alveolar macrophages, dendritic cells and interstitial monocytes. During this period the mycobacteria undergo a period of uninhibited growth in the alveolar spaces or within non-activated macrophages. A complex response of cytokines develops, involving interferon gamma, TNF-alpha, interleukin-2 and -12. As a result of this response during the next 4 to 12 weeks an influx of CD4+ and CD8+ lymphocytes and activated macrophages occurs and they surround the tubercle bacilli causing granuloma formation (Ghon focus). This effectively halts replication of the mycobacterium. This stage is known as Latent Tuberculosis Infection (LTBI) and is achieved in 90-95% of healthy individuals. This is not always the case in young children.

TBeat :: Vol 7 :: Issue 2