Clinical trial NCT01422798: An Open Cohort of Childhood Tuberculosis in Mbarara National Referral Hospital, Uganda
Official title: An Open Cohort of Childhood Tuberculosis in Mbarara National Referral Hospital, Uganda
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Tuberculosis
Lead sponsor: Epicentre
Sponsor class: OTHER
Collaborators: name: Mbarara University of Science and Technology
name: Medecins Sans Frontieres, Netherlands
First posted: 2011-08-24
Enrollment: 396
Sex: ALL
Minimum age (years): 1
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children aged one month to 14 years and identified as TB suspect will be eligible to the study. Definition of TB suspect was adapted from the definitions proposed by WHO guidelines (World Health Organisation 2006).

Brief summary: The aims at investigating how the diagnosis of Tuberculosis in children in a setting of high TB and HIV prevalence can be improved and to assess the treatment outcomes and tolerance of the new WHO recommended TB drug dosages.

Detailed description: Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide. The situation for children in this epidemic is complex because they are usually considered less infectious and therefore, not to represent an important public health problem. Uganda ranks among the countries with the highest TB burden with 330/100,000 person-year TB incidence. Up to 16% of new TB infections are estimated to occur in children. Diagnosis of childhood TB is usually based on exposure history and a set of clinical, radiological and biological signs that considered separately have rather low predictive values. There is no consensus on the optimal way to combine these signs. This is even more complex when the child is infected with HIV. The risk of TB infection and disease, and the TB clinical presentation depend on the child's age, the youngest being at highest risk. An important first step in improving the management of childhood TB is to better define the clinical and radiological characteristics of children with suspected TB at first presentation to a health service in an endemic setting; also to document the feasibility and tolerability of TB treatment in this age cohort. This initial descriptive study would help to pave the way for more rigorous studies evaluating novel diagnostics and conducting clinical trials on first and second line TB treatment in children, in the future.

The main objective of the study is to improve the diagnosis of TB in children in a setting of high TB and HIV prevalence and to assess the treatment outcomes and tolerance of the new WHO recommended TB drug dosages.

The investigators will conduct an observational cohort study of paediatric TB suspects attending the Mbarara National Reference Hospital (MNRH). All included TB suspects will have an initial comprehensive assessment including clinical examination, chest X-ray, tuberculin skin test, smear microscopy, Mycobacterium tuberculosis culture, XpertMTB/RIF® of respiratory or extra-pulmonary specimen for diagnosis of tuberculosis. For children who cannot produce sputum, sputum induction will be proposed. Children with indication of TB treatment will be followed up to 6 months after completion of TB treatment (total 12 months) with treatment efficiency, tolerability and acceptability assessment. Children without indication of TB treatment will undergo a systematic clinical assessment after 3 months. Finally, clinical files from all TB suspects will be retrospectively reviewed by 2 independent paediatric TB experts in order to classify the cases as Confirmed TB, Certain TB, Probable TB and Unlikely TB cases. A total of 385 paediatric TB suspects (1 month-14 years) will be screened from the paediatric ward, OPD, HIV clinic of the MNRH, Holy Innocents children's hospital and The AIDS support organisation (TASO) in Mbarara.

Eligibility criteria: Inclusion Criteria:

Any child with at least one of the following criteria:

* Unexplained weight loss or documented failure to thrive or stagnant weight or Growth faltering on the growth charts over the past 3 months despite adequate nutrition and deworming,
* Non - remittent cough or wheeze for more than 2 weeks,
* Night sweats persistent or intermittent during the last 2 weeks
* Prolonged fever (temperature \> 38°C) for 7 days, after common causes such malaria or pneumonia has been excluded.
* Wheeze/Stridor - persistent, non remitting during the last 2 weeks
* Chest pain - Persistent, localized, pleuritic in nature during the last 2 weeks
* Unexplained fatigue, weakness, apathy, lethargy or reduced playfulness during the last 2 weeks
* Painless superficial lymph node mass (\>2x2cm)-
* Chronic onset meningitis (\>5days), lymphocytic predominance in CSF or meningitis not responding to antibiotic treatment (ref 8)
* Recent gibbus
* Abdominal distention with ascites OR
* Any child with an abnormal chest X-ray (CXR) suggestive of TB (hilar/paratracheal adenopathy with/without airway compression, airspace opacification not responding to antibiotics or documented TB contact, lung cavities or miliary infiltrates) OR
* Asymptomatic child with a history of recent contact (within past year) with a pulmonary TB smear or culture positive patient and an abnormal chest X-ray AND
* Informed Consent signed by parent or legal representative

Exclusion Criteria:

* Current TB treatment (patient who received \< 3 days of treatment or patients receiving IPT could be still included) or TB treatment completed within the past 6 months.
* Absence of informed consent
* Living outside of Greater Mbarara region.
* Unable or unwilling to attend to the follow-up visits

Primary outcomes:
measure: Number of confirmed, certain, probable and unlikely TB cases among TB suspects
timeFrame: Week 48
Secondary outcomes:
measure: Baseline clinical presentation of TB suspects
timeFrame: Week 12 and 24
measure: Baseline biological characteristics (smear microscopy, culture and XpertMTB/RIF® of sputum and other specimen for EPTB suspects) of TB suspects
timeFrame: Week 12 and 24
measure: XpertMTB/RIF® and culture results in stools of TB suspects
timeFrame: Week 12 and 24
measure: Number of children started on TB treatment among TB suspects
timeFrame: Week 24
measure: Number of TB suspect cases who were initially diagnosed as non TB who died or eventually received a TB diagnosis within the first 3 months of clinical follow-up
timeFrame: Week 12
measure: Treatment successes (cured and completed), failures, defaulters and deaths
timeFrame: Week 48
measure: TB recurrence 6 months after completion of TB treatment
timeFrame: Week 48
measure: Antiretroviral treatment (ART) regimen and time to initiation in co-infected children
timeFrame: Week 48
measure: Occurrence and clinical description of IRIS episodes
timeFrame: Within 2 months of ART initiation
measure: Type and frequency of grade 3 and 4 adverse events during TB treatment, with/without concomitant ART
timeFrame: Week 2, 4, 8, 16, 24
measure: Pill burden, adherence rate and drugs errors with the use of new paediatric dosages
timeFrame: Week 2, 4, 6, 8, 12, 16, 20, 24
Other outcomes:
Locations:
Study officials:
affiliation: Epicentre
name: Margaret Nansumba, MD
role: PRINCIPAL_INVESTIGATOR
References: