Evaluating Diagnostics for Paediatric Tuberculosis by Blood Culture

This study is currently recruiting participants.
Verified November 2013 by Oxford University Clinical Research Unit, Vietnam
Sponsor:
Collaborator:
National Hospital of Pediatrics, Vietnam
Information provided by (Responsible Party):
Oxford University Clinical Research Unit, Vietnam
ClinicalTrials.gov Identifier:
NCT01434758
First received: April 6, 2011
Last updated: November 22, 2013
Last verified: November 2013
  Purpose

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.


Condition
Tuberculosis Infection

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Evaluating Diagnostics for Paediatric Tuberculosis by Blood Culture

Resource links provided by NLM:


Further study details as provided by Oxford University Clinical Research Unit, Vietnam:

Primary Outcome Measures:
  • Diagnostic yield of TB culture [ Time Frame: At baseline - day 1 of study ] [ Designated as safety issue: No ]
    Number of positive TB cultures versus number of positive TB direct smears for expectorate and/or gastric aspirate.

  • Diagnostic yield of TB culture [ Time Frame: At baseline - day 1 of study ] [ Designated as safety issue: No ]
    Number of positive TB cultures versus number of positive MODS cultures for expectorate and/or gastric aspirate.

  • Diagnostic yield of urine versus expectorate or gastric aspirate for TB culture [ Time Frame: At baseline - day 1 of study ] [ Designated as safety issue: No ]
    Number of positive TB cultures in urine versus expectorate and/or gastric aspirate.


Biospecimen Retention:   Samples With DNA
  • sputum
  • gastric aspirate
  • blood
  • urine
  • cerebrospinal fluid

Estimated Enrollment: 795
Study Start Date: April 2011
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Children
Children age 0-15 years presenting to NHP thought to have TB infection

Detailed 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.

  Eligibility

Ages Eligible for Study:   up to 15 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Study population is children aged 0-15 years presenting to NHP thought to have TB infection according to inclusion criteria listed in this protocol.

Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01434758

Contacts
Contact: Heiman F Wertheim, PhD +84 4 3576 4320 heiman.wertheim@gmail.com
Contact: Annette Fox, PhD +84 4 3576 4320 afox@oucru.org

Locations
Vietnam
National Hospital of Pediatrics Recruiting
Hanoi, Vietnam
Contact: Hai T Le, PhD    098 906 3658      
Contact: Sinh T Tran, Master    0903208804    ttsinh@yahoo.com   
Principal Investigator: Hai T Le, PhD         
Sub-Investigator: Liem T Nguyen, Prof. PhD.         
Sub-Investigator: An N Nguyen, Dr         
Sub-Investigator: Lam V Nguyen, Dr         
Sub-Investigator: Tuan M Dao, Dr         
Sub-Investigator: San T Luong, Dr         
Sub-Investigator: Hang TT Dang, Dr         
Sub-Investigator: Sinh T Tran, Master         
Sub-Investigator: Peter Horby, Dr         
Sub-Investigator: Annette Fox, PhD         
Principal Investigator: Heiman F Wertheim, PhD         
Sponsors and Collaborators
Oxford University Clinical Research Unit, Vietnam
National Hospital of Pediatrics, Vietnam
Investigators
Principal Investigator: Heiman F Wertheim, PhD Oxford University Clinical Research Unit - Hanoi
  More Information

Additional Information:
No publications provided

Responsible Party: Oxford University Clinical Research Unit, Vietnam
ClinicalTrials.gov Identifier: NCT01434758     History of Changes
Other Study ID Numbers: 09TB
Study First Received: April 6, 2011
Last Updated: November 22, 2013
Health Authority: Vietnam: Ministry of Health

Keywords provided by Oxford University Clinical Research Unit, Vietnam:
Mycobacterium tuberculosis
Culture yield

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on April 17, 2014