Beijing and Haarlem genotypes are overrepresented among children with drug-resistant tuberculosis in the Western Cape Province of South Africa

Drug resistance among children with culture-confirmed tuberculosis (TB) provides an accurate measure of transmitted drug resistance within the community. We describe the genotype diversity in children with culture-confirmed TB and investigate the relationship between genotype and drug resistance. A prospective study was conducted from March 2003 through August 2005 at Tygerberg Children's Hospital, in the Western Cape Province of South Africa. All children (<13 years of age) diagnosed with culture-confirmed TB were included. Genotype analysis and phenotypic drug susceptibility testing were performed on the first culture-positive isolate from each patient. Mutation analysis was performed on all drug-resistant isolates. Spoligotyping was successfully performed on isolates from 391/399 (98%) children diagnosed with culture-confirmed TB. Drug susceptibility testing was also performed on 391 isolates; 49 (12.5%) were resistant to isoniazid, and 20 (5.1%) of these were resistant to both isoniazid and rifampin. Beijing was the most common genotype family, identified in 130/391 (33.2%) cases, followed by LAM in 114/391 (29.2%) cases. The presence of both Beijing and Haarlem genotype families was significantly associated with drug resistance (26/49 [53.1%] versus 113/342 [33.0%]; odds ratio, 1.7; 95% confidence interval, 1.0 to 2.9). The high prevalence of Beijing and LAM in children with culture-confirmed TB reflects considerable transmission of these genotype families within the community. The overrepresentation of Beijing and Haarlem genotype families in children with drug-resistant TB demonstrates their contribution to transmitted drug resistance and their potential importance in the emergent drug-resistant TB epidemic.     

Primary drug-resistant tuberculosis in children.

SETTING: The Western Cape Province of South Africa, an area with a high tuberculosis (TB) incidence where initial isoniazid (INH) resistance and multidrug resistance (MDR) among adults was 3.9% and 1.1%, respectively, during 1992-1993. OBJECTIVE: To determine the drug resistance incidence among children as compared to adults, to compare the clinical features of drug-resistant and drug-susceptible TB, and the degree of INH resistance in isoniazid-resistant isolates. METHODS: All Mycobacterium tuberculosis cultures obtained from children (0-13 years) at a regional hospital were prospectively collected from August 1994 to April 1998 and susceptibility testing done on each child's specimens. Degree of INH resistance was determined in available resistant isolates. The children's clinical records were reviewed. RESULTS: Susceptibility results were available in 306/338 children with cultures of M. tuberculosis; 21 isolates (6.9%) were INH-resistant, and seven were MDR. Taking into account study limitations, the incidence of INH resistance was 5.6% and MDR 1% in children aged <5 years. Clinical features were similar in children with drug-susceptible and drug-resistant TB. CONCLUSION: The incidence of drug resistance in childhood tuberculosis in Western Cape is low, and probably reflects the level of primary drug resistance amongst organisms currently circulating in the community.     

Routine programmatic delivery of isoniazid preventive therapy to children in Cape Town,South Africa

Setting:

Fourteen primary health care facilities in Cape Town, South Africa.

Objective:

To determine the proportion and characteristics of infectious adult tuberculosis (TB) cases that identify children aged <5 years who qualify for isoniazid preventive therapy (IPT), and to determine the proportion of children who initiate and complete IPT.

Design:

A retrospective clinical record review conducted as a stratified cluster survey.

Results:

Of 1179 records of infectious adult cases, 33.3% had no documentation of contacts. Of the remaining 786 records, 525 contacts aged <5 years were identified, representing 0.7 child contacts per infectious adult case. Older age, male, human immunodeficiency virus (HIV) positive, smear-negative and retreatment TB cases were all associated with no documentation of contacts. Of the 525 child contacts identified, less than half were screened for TB, 141 initiated IPT and 19 completed it.

Conclusion:

Less than 67% of infectious TB case records had documentation of contacts. Younger, female, HIV-negative and new smear-positive TB cases were more likely to have had contacts identified. Less than 14% of children already initiated on IPT completed 6 months of treatment.     

Absence of an association between Mycobacterium tuberculosis genotype and clinical features in children with tuberculous meningitis

OBJECTIVES: Animal studies point to increased virulence of certain mycobacterial strains, notably those of the Beijing genotype. There are limited data on mycobacterial genotypic diversity in children with tuberculous meningitis (TBM). We investigated mycobacterial genotypic diversity in children with TBM and analyzed the relationship among genotype, clinical presentation and outcome. PATIENTS AND METHODS: Data were extracted from an ongoing prospective study on children with confirmed TBM from 1992 through 2003 at a referral hospital in the Western Cape Province, South Africa. Mycobacterial isolates were genotyped by standardized restriction fragment length polymorphism methodology. Clinical data at diagnosis, inflammatory progression during the first month of antituberculosis therapy and neurologic outcomes after 6 months of therapy were analyzed according to the principal genetic group of the strain and the presence of the Beijing strain, respectively. RESULTS: Fifty-nine children were included (median age at diagnosis, 23 months); 37 presented with stage II and 22 with stage III presented with TBM. At completion of antituberculosis therapy, 6 children were neurologically normal, 22 were moderately neurologically impaired, 23 were severely neurologically impaired and 6 children died; detailed outcomes were not available in 2 children. All 3 principal genetic groups were represented (group 1, 27.1%; group 2, 59.3%; group 3, 13.6%); the most prevalent strains were of the Beijing genotype (family 29; 25.4%), followed by family 28 (10.2%) and family 11 (8.5%). Predictors of poor neurologic outcome included advanced disease at diagnosis and male gender. There was no association between the principal genetic group of the strain or the presence of the Beijing genotype, and clinical presentation or outcome. CONCLUSIONS: We found no association between Mycobacterium tuberculosis genotypes and clinical presentation or outcome.     

Immunogenicity and safety of intradermal delivery of hepatitis B booster vaccine using the novel drug delivery device VAX-ID™

Background

Although intramuscular (IM) injection is still the most preferred method for vaccination, intradermal (ID) delivery may have several advantages over intramuscular and subcutaneous (SC), including an improved immune response and antigen dose sparing effect. However it is currently limited due to the difficulty in standardizing the injection technique often based on the Mantoux technique. Difficulties encountered using the Mantoux technique could be overcome by the use of alternative ID delivery systems that confer more uniform and standardized procedures.The aim of this study was to evaluate the performance of a newly developed intradermal injection device, VAX-ID?, via a proof-of-concept to assess the immunogenicity of a commercially available hepatitis B booster vaccination in healthy hepatitis B pre-immunised subjects. Additionally, device safety and tolerability was evaluated.