Evaluating Diagnostics for Paediatric Tuberculosis by Blood Culture

Tuberculosis Infection Clinical Trial

Official title:

Evaluating Diagnostics for Paediatric Tuberculosis by Blood Culture

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01434758
• Other study ID #: 09TB
• Status: Completed
• Phase: N/A
• First received: April 6, 2011
• Last updated: November 13, 2016
• Start date: April 2011
• Est. completion date: September 2015

Study information

• Verified date: November 2013
• Source: Oxford University Clinical Research Unit, Vietnam
• Contact: n/a
• Is FDA regulated: No
• Health authority: Vietnam: Ministry of Health
• Study type: Observational

Clinical Trial Summary

Detection of M. tuberculosis in clinical specimens of children has a low sensitivity because specimens are either difficult to collect or contain low levels of M. tuberculosis. Diagnostic criteria are non-specific and culture confirmation is challenging, as sputum samples are not often obtainable from small children and specimens typically have low yield. Although children are typically thought to have paucibacillary disease, they are at greater risk for dissemination of TB. This may allow for detection of Mycobacterium tuberculosis from other bodily fluids than sputum or gastric aspirate, including blood and urine. Unfortunately, little is known about the overall yield from these various specimens. From pilot data collected among adults and children in Tugela Ferry, we know that it is feasible to collect and test various bodily fluid specimens for TB culture. This study aim to test the hypothesis that blood and urine cultures will detect Mycobacterium tuberculosis from children suspected of disseminated TB, and that a proportion of these non-sputum bodily fluids will detect both drug-susceptible and drug-resistant tuberculosis when sputum or gastric culture does not.

Description:

Tuberculosis (TB) is a major cause of morbidity and mortality among children in developing nations. Symptom-based diagnostic criteria are non-specific and culture confirmation is challenging, as sputum samples are often believed to be to too cumbersome to obtain from small children and specimens typically have low yield due to the paucibacillary nature of pediatric TB. Culture confirmation may be obtained in as few as 10% of cases of suspected pediatric TB. For these reasons, the true extent of the (drug-resistant) TB epidemic in children is unknown. Thus, either clinicians begin empiric treatment without diagnosis or no treatment is given at all. Current laboratory methods, if available at all in resource poor settings, employ smears from expectorated sputa or gastric aspirates which have low sensitivity in children. While more rapid diagnostic techniques such as PCR based tests have been developed, there is still poor sensitivity in children. Improving the diagnosis of pediatric TB must focus on better efforts, including more aggressive strategies to uncover disseminated disease.

Culture confirmation of disseminated disease can be obtained from blood, urine, cerebrospinal fluid (CSF), peritoneal and pleural fluid, or purulent material from lymph node aspirates, abscesses or otorrhea. Unfortunately, little is known about the overall yield from these various specimens in children. From pilot data collected among children at NHP, we know that it is feasible to collect and test various bodily fluid specimens for TB culture.

Although WHO guidelines encourage body fluid collection in order to make a diagnosis of TB in children, at present in NHP, blood and urine cultures are not obtained for mycobacterial culture. However, this study seeks to demonstrate that routine investigation of blood and urine will augment the yield of traditional sputum culture for children in whom disseminated disease is more likely. Improved culture confirmation will allow DST and a more accurate description of the drug-resistant TB epidemic for children in the region.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 560
• Est. completion date: September 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 15 Years

Eligibility

Inclusion Criteria:

• Aged 0-15, presenting at NHP;

• Unexplained fever for more than 2 weeks; and

• Any form of TB suspected based on at least two of the following findings:

• unexplained cough for more than 2 weeks

• radiographic findings suggestive of tuberculosis.

• failure to thrive/weight loss

• enlarged non-tender lymph nodes or lymph node abscess, especially of the neck

• signs of meningitis with prodromal stage of at least one week

• HIV positive

• malnourished

• TB contact history

• Clinical judgment treating doctor.

• Relevant material (sputum or gastric aspirate, blood, and urine) available for microbiological diagnosis.

• Informed consent obtained from the patient's legal guardian(s).

Exclusion Criteria:

• Age >15 years

• Diagnosed or treated for TB in the past year, received drugs effective against TB in last 3 months.

• Clinical contra-indications to collect the required study specimens

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Tuberculosis
• Tuberculosis Infection

Locations

Country	Name	City	State
Vietnam	National Hospital of Pediatrics	Hanoi

Sponsors (2)

Lead Sponsor	Collaborator
Oxford University Clinical Research Unit, Vietnam	National Hospital of Pediatrics, Vietnam

Country where clinical trial is conducted

Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diagnostic yield of TB culture	Number of positive TB cultures versus number of positive TB direct smears for expectorate and/or gastric aspirate.	At baseline - day 1 of study	No
Primary	Diagnostic yield of TB culture	Number of positive TB cultures versus number of positive MODS cultures for expectorate and/or gastric aspirate.	At baseline - day 1 of study	No
Primary	Diagnostic yield of urine versus expectorate or gastric aspirate for TB culture	Number of positive TB cultures in urine versus expectorate and/or gastric aspirate.	At baseline - day 1 of study	No

External Links

•   OUCRU studies public site