Maurice Kibel

Neonatal mycobacterial specific cytotoxic T-lymphocyte and cytokine profiles in response to distinct BCG vaccination strategies.

This study evaluated whether different bacillus Calmette–Gue´rin (BCG) strains, routes of administration, vaccination age and percutaneous tools influenced immune responses to BCG vaccination in infants. Proliferative responses, cytokine production and cell‐mediated cytotoxicity obtained in post‐vaccinated children were compared to baseline cord bloods and unvaccinated 10‐week‐old infants. BCG vaccination generally induced strong lymphoproliferative and T helper type 1 (Th1)‐type cytokine responses. There was a trend for greater responsiveness following the intradermal route of vaccination, with Japanese‐172 strain and with delaying vaccination until 10 weeks. Cord mononuclear cells differentially stimulated the Th2‐type cytokines interleukin‐5 (IL‐5) and IL‐10 selectively in response to BCG, as compared to H37Rv or purified protein derivative stimulation. We document for the first time the generation of mycobacterium‐specific cytotoxic T lymphocytes in neonates, following BCG vaccination. Cytotoxic activity correlated with the ratio of interferon‐γ to IL‐5, aside from a single instance where use of the Biovac® tool resulted in a striking dissociation selectively against H37Rv targets. These data have implications for correlates of protective immunity in design of vaccine studies.

The Impact of a Change in Bacille Calmette-guérin Vaccine Policy on Tuberculosis Incidence in Children in Cape Town, South Africa

Background: A decision by the South African National Department of Health to change the route of administration and strain of bacille Calmette-Guérin (BCG) vaccine was implemented in Cape Town, South Africa, between July and December 2000. This provided an opportunity to compare the incidence of tuberculosis and proportion with disseminated disease in children less than 2 years old before and after the changeover from percutaneous (PC) Tokyo 172 BCG to intradermal (ID) 1331 Danish BCG immunization. Methods: Clinical records of all tuberculosis patients aged less than 2 years at diagnosis and born between January 1, 1999, and June 30, 2000 (PC cohort) and between January 1, 2001, and June 30, 2002 (ID cohort) were collected. All cases were reviewed for likelihood of TB, its severity and disease dissemination. Results: The number of reported patients with tuberculosis in the PC cohort was 1369 and in the ID cohort 1397, giving incidence rates of 866 (95% confidence interval [CI], 821–913) and 858 (95% CI, 814–904) per 100,000 person-years, respectively. The proportion who had disseminated disease (meningitis and/or miliary spread) was significantly lower in the ID cohort (4.7%) than in the PC cohort (8.6%) (relative risk, 0.54; 95% CI, 0.40–0.72). Those not vaccinated had a significantly higher proportion of disseminated disease cases (29.2%) than the PC and ID groups combined (6.6%) (relative risk, 4.4; 95% CI, 2.7–6.7). Conclusion: A program using Danish 1331 BCG given intradermally did not prevent more tuberculosis cases in children overall as compared with a program using Tokyo 172 BCG given percutaneously but reduced the proportion with disseminated disease.

The serodiagnosis of tuberculosis in children: an evaluation of an ELISA test using IgG antibodies to M. tuberculosis, strain H37 RV.

An enzyme-linked immunosorbent assay (ELISA) for detecting serum IgG antibodies to an autoclaved suspension of Mycobacterium tuberculosis H37 RV was evaluated as a diagnostic tool in 132 clinical cases of childhood tuberculosis. The mean (SD) optical density value in these patients was 0.115 (0.122) compared with 0.022 (0.017) in the control group of patients who had non-tuberculous acute respiratory tract infections. Using as a cut-off level the mean of the control plus 2 standard deviations, the test sensitivity was 62% and the specificity was 98% in all the patients with a clinical diagnosis of tuberculosis. In the culture-positive group (n = 35), the sensitivity was 69%. A positive correlation was shown between the optical density levels and increasing age and chronicity of infection but not with respect to tuberculin skin reactivity, nutritional status and the duration of prior therapy. In addition, BCG vaccination (presence of a scar) did not affect the ELISA result. We conclude that this ELISA test is a useful diagnostic test in children.

Determining causes of mortality in children enrolled in a vaccine field trial in a rural area in the Western Cape Province of South Africa.

Aim:  A mortality surveillance system was developed to identify and document causes of death among children enrolled in a tuberculosis vaccine field trial in South Africa. The aims of this study were to describe causes of mortality in children enrolled in a phase IV trial comparing intradermal with percutaneous administration of Bacille Calmette Guerin, and to compare causes of mortality recorded on death certificates with those obtained by clinical record review combined with verbal autopsies (CR/VA).

Digital radiographic measurement of the main bronchi: a pilot study.

Abstract Background: Conventional chest radiographs do not afford consistently good visualisation of the main bronchi and sub-carinal angle. Improved visualisation would facilitate accurate measurement of the airways, definition of normal radiographic anatomy and, possibly, earlier identification of extrinsic compression or displacement. Aim: The main objective of this study was to establish whether the paediatric main bronchi and sub-carinal angle could be measured consistently on AP supine chest images obtained using a specific digital radiographic system (DRS). Subjects and Methods: The proximal bronchial diameters were measured on supine DRS chest images of 102 children between the ages of 6 months and 13 years. Results: The left and right main bronchi could be seen clearly and measured in over 90% of cases, with intraclass correlation co-efficients of reliability indicating high intra- and inter-observer agreement. The sub-carinal angle had lower intra- and inter-observer agreement. Conclusion: Supine chest images acquired using DRS facilitate accurate measurement of the main bronchi and sub-carinal angle in children. Further work is required to establish population-specific age-related norms for bronchial dimensions. These could serve as reference standards for early detection of deviations from normal.

Blood-lead levels of children in the Western Cape

The detrimental effects of low-level lead loads on the cognitive function of young chil dren are now well accepted. Most such studies have been carried out in western coun tries, and there is as yet little information from less developed areas on the environ mental impact of lead or on its role in furthering disadvantage in childhood. In such countries, the small, but significant, lead effect on intelligence may well be additive to other harmful factors - low birth weight, repeated infections, suboptimal nutrition, emotional deprivation and poor intellectual stimulation. In Southern Africa leaded gasoline is still the only form available. The recent lowering of petrol lead levels has provided the opportunity to assess its contribution to lead load. The results of pre vious studies on Cape preschool children and teenagers are briefly reviewed. Two fur ther studies on children attending primary schools are reported. The first compared blood lead levels in children from inner city Cape Town schools before, and some years after, petrol lead was lowered. The second compared groups living in three deep rural villages, one of which is involved in lead mining. Mean blood lead levels in all groups were above internationally accepted standards, and levels in the rural chil dren were surprisingly high.