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Biomedical subjects

G D Hussey

Publications and source records attributed to G D Hussey.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of mantoux skin test with three generations of a whole blood IFN-gamma assay for tuberculosis infection.

SETTING: A rural town in South Africa. OBJECTIVE: To compare the performance of Quanti-FERON assays with the tuberculin skin test (TST) for identifying latent tuberculosis infection (LTBI) in a high TB burden community. DESIGN: In a cross-sectional study in healthy adults, we applied the TST and took blood for the three generations of QuantiFERON assays. RESULTS: Of 358 participants whose results were analysed, 291 (81%) had a TST result of > or = 10 mm induration, and 187 (52%) > or = 15 mm. QuantiFERON-TB was positive in 215 (60%), QuantiFERON-TB Gold in 137 (38%), and QuantiFERON-TB Gold (In-Tube method) in 201 (56%). There was poor agreement between TST and QuantiFERON tests, and between the different generations of QuantiFERON tests (kappa = 0.12-0.50). Of the subset with TST indurations > or = 15 mm, 30-56% had negative QuantiFERON tests. However, positive Quanti-FERON tests were associated with males, who have a higher incidence of TB in this area. CONCLUSION: We showed poor agreement between TST and the different QuantiFERON tests in diagnosing LTBI. The surprising discordance between the Quanti-FERON TB Gold and QuantiFERON TB Gold (In-Tube method) tests needs to be investigated further.

Adolescent↗
PubMed2005

Outcome of HIV infected children with culture confirmed tuberculosis.

BACKGROUND: Tuberculosis (TB) is an important disease in human immunodeficiency virus (HIV) infected children living in regions where TB is endemic. There are limited data on the outcome of culture confirmed TB in HIV infected children. AIMS AND METHODS: To describe the outcome on TB therapy and overall mortality in HIV infected children with culture confirmed TB through a retrospective cohort study. RESULTS: Eighty seven children, median age 24 months, contributed to 93 TB episodes; six children had two confirmed episodes. Pulmonary disease (PTB) was present in 71 episodes (76.3%), extrapulmonary disease (EPTB) in 43 (46.2%), and of these, both PTB and EPTB were present in 21 (22.6%). There was cure based on bacteriological and/or radiological criteria in 54 episodes (58.1%). Eighteen children died during TB therapy and there were a total of 34 deaths (39.1%). In univariate analysis (n = 87 patients), severe malnutrition, age < or =1 year, and a negative tuberculin skin test were significant risk factors for death during TB therapy. In multivariate survival analysis (n = 87 patients), HIV disease category, severe malnutrition at diagnosis, and lack of cure at the end of TB therapy were significantly associated with overall mortality. CONCLUSION: In the absence of antiretroviral therapy, HIV infected children with confirmed TB have poor outcomes on antituberculosis therapy and are at high risk of death during and after completion of antituberculosis therapy, especially due to non-TB related causes. There is an urgent need to optimise and monitor antituberculosis therapy in HIV infected children and to improve access to TB and other preventative therapy.

AIDS-Related Opportunistic Infections↗
PubMed2003

Plasma vitamin A and zinc levels in HIV-infected adults in Cape Town, South Africa.

A cross-sectional study of 132 adults attending an HIV clinic in Cape Town, South Africa, was conducted to determine predictors of low plasma vitamin A and Zn levels. No patients were on antiretroviral therapy. The possible confounding effect of the acute-phase response was controlled by including C-reactive protein levels in multivariate analysis and by excluding active opportunistic infections. Retinol levels were low (<1.05 micromol/l) in 39 % of patients with early disease (WHO clinical stages I and II) compared with 48 and 79 % of patients with WHO stage III and IV respectively (P<0.01). Plasma Zn levels were low (<10.7 micromol/l) in 20 % of patients with early disease v. 36 and 45 % with stage III and IV disease respectively (P<0.05). C-reactive protein levels were normal in 63 % of subjects. Weak, positive associations were found between CD4+ lymphocyte count and plasma levels of retinol (r 0.27; 95 % CI 0.1, 0.43) and Zn (r 0.31; 95 % CI 0.25, 0.46). Multivariate analysis showed the following independent predictors of low retinol levels: WHO stage IV (odds ratio 3.4; 95 % CI 2.1, 5.7) and body weight (odds ratio per 5 kg decrease 1.15; 95 % CI, 1.08, 1.25), while only body weight was significantly associated with low Zn levels (OR per 5 kg decrease 1.19; 95 % CI 1.09, 1.30). CD4+ lymphocyte count <200/microl was not significantly associated with either low retinol or Zn levels. In resource-poor settings, simple clinical features (advanced disease and/or weight loss) are associated with lowered blood concentrations of vitamin A and/or Zn. The clinical significance of low plasma retinol and/or Zn levels is unclear and more research is required to establish the role of multiple micronutrient intervention strategies in HIV disease.

Adult↗
PubMed2001

The immunomodulatory effects of thalidomide on human immunodeficiency virus-infected children.

The safety and immune effects of low-dose thalidomide treatment (3 mg/kg/day for 28 days) were evaluated in a study involving 8 South African human immunodeficiency virus (HIV)-infected children. The children were 7-69 months old and in disease stages A1-C3. Thalidomide therapy did not affect virus load, even though none of the children was receiving antiretroviral therapy. Thalidomide stimulated CD8+ T cells in peripheral blood, which increased expression of the activation markers CD38 and human leukocyte antigen DR and of the memory cell marker CD45RO. The frequency of HIV gag-specific CD8+ T cells in peripheral blood increased in 3 of 4 children who were evaluated during treatment with thalidomide. Clinical adverse events were mild. In this study, thalidomide was found to be safe and well tolerated and caused significant immunomodulation at a low dose. This is the first report describing use of an oral drug that may enhance HIV-specific CD8+ T cell function in HIV-infected children.

Anti-HIV Agents↗
PubMed2000

Duration of illness in ambulatory children diagnosed with bronchiolitis.

OBJECTIVES: To measure the duration of illness in ambulatory children diagnosed with bronchiolitis and to examine clinical predictors of duration of illness. DESIGN: Validation inception cohort study. Duration of follow up was 28 days. SETTING: A primary-level ambulatory department of a public sector children's hospital in Cape Town, South Africa. PATIENTS: One hundred eighty-one children aged 2 to 23 months who went to the hospital as their first contact for that episode of illness, and had a clinical diagnosis of bronchiolitis were enrolled consecutively on weekday mornings if their guardian stated that they were contactable by telephone. MAIN OUTCOME MEASURE: Resolution of symptoms, as judged by the guardian, measured by twice-weekly telephone interviews. RESULTS: Median duration of illness (calculated as the reported duration of symptoms before initial hospital visit plus the time from first consultation to recovery) was 12 days (95% confidence interval, 11-14 days). After 21 days, 18% were still ill and after 28 days, 9% were still ill. Sixty-two patients (34.2%) had unscheduled consultations within 28 days, a median of 13 days after the first consultation. There was no association of duration of illness with age, sex, z score for weight for age, or respiratory rate. CONCLUSIONS: Ambulatory children diagnosed with bronchiolitis recover with few complications, but the resolution of symptoms may take several weeks. Providing parents with this information could help reduce the high rate of unscheduled return visits as observed in this cohort.

Ambulatory Care↗
PubMed2000

Effect of vitamin A therapy on serologic responses and viral load changes after influenza vaccination in children infected with the human immunodeficiency virus.

Vitamin A administered to children infected with the human immunodeficiency virus before influenza vaccination in a double-blind randomized study did not enhance vaccine serologic responses but did dampen the increase in the human immunodeficiency virus viral load 14 days after immunization (vitamin A, decrease of 0.13 +/- 0.09 log(10) copies/mL; placebo, increase of 0.14 +/- 0.08, P =.02).

Adolescent↗
PubMed2000

Twice weekly vs. daily chemotherapy for childhood tuberculosis.

BACKGROUND: Treating childhood tuberculosis places a large burden on health services, and ways of lessening this were sought. METHODS: A randomized controlled trial was conducted to determine the effectiveness of fully intermittent twice weekly treatment for intrathoracic childhood tuberculosis and its effect on adherence to treatment, in comparison with daily (weekday) treatment. The setting was a district of Cape Town, South Africa, an area of high incident tuberculosis. We randomized 206 children with confirmed (4%), probable (94%) and suspected (2%) intrathoracic tuberculosis: 89 (median age, 25 months) received intermittent treatment; and 117 (median age, 28 months) received daily treatment. Intermittent treatment (twice weekly for 6 months) was isoniazid 15 mg/kg/dose, rifampin 15 mg/kg/dose and pyrazinamide 55 mg/kg/dose for 2 months, followed by isoniazid and rifampin only for 4 months. Daily treatment was isoniazid 10 mg/kg/day, rifampin 10 mg/kg/day and pyrazinamide 25 mg/kg/day on weekdays for 6 months. RESULTS: At 6 months 97% of subjects were discharged, with treatment outcomes in the two groups equivalent at that time (P = 0.90) and at the 18- to 30-month follow-up. One relapse occurred in the twice weekly group (P = 0.25). Adherence was equivalent; 70 children (79%) on intermittent and 90 (77%) on daily treatment took 75% or more of the prescribed doses (P = 0.90). Nonadherence over the full course of therapy was significantly associated with nonadherence during the first month of treatment (P = 0.0002) and household crowding (P = 0.002). CONCLUSIONS: Six month fully intermittent antituberculosis treatment is an effective and acceptable alternative to daily treatment.

Antitubercular Agents↗
PubMed2000

Respiratory syncytial virus infection in children hospitalised with acute lower respiratory tract infection.

BACKGROUND: Data are lacking on respiratory syncytial virus. (RSV) respiratory tract infections in children from developing countries. OBJECTIVE: To determine the importance of RSV as a cause of acute lower respiratory tract infection (ALRTI) in Cape Town children. METHODS: Children younger than 2 years of age admitted to hospital with ALRTI over a 15-month period from 1 June 1995 to 31 August 1996 were studied prospectively. Sociodemographic data, risk factors for severe RSV disease, clinical signs, diagnosis and hospital course were documented. A nasopharyngeal aspirate (NPA) for detection of RSV by enzyme immunoassay (EIA) was obtained in all cases. The NPA of every fifth child was sent for viral culture. RESULTS: A total of 1,288 patients (60% male, 40% female) with a median age (25th-75th percentile) of 6 months (2-11 months) was enrolled; 32.4 had one or more risk factors for severe RSV infection. Pneumonia was diagnosed in 62.2%, bronchiolitis in 20.6%, laryngotracheobronchitis (LTB) in 8% and other respiratory illnesses in 9.2%. Mild disease, requiring admission to an overnight ward, was documented in 38.1%, while 48.9% and 13% respectively had moderate and severe disease requiring admission to a general ward and intensive care unit (ICU). Supplemental oxygen and mechanical ventilation were required by 68.9% and 8.5% of patients, respectively. The median duration of hospital stay was 5 days (range 1-10 days). RSV EIA was positive in 16.4% of cases, and there was no difference in detection rates according to diagnosis. Viral culture performed in 162 of the 1,288 study patients (12.6%) grew RSV in 11.7% of cases, adenovirus in 3.7%, para-influenza virus type 3 in 2.5% and influenza B virus in 0.6%. Patients who tested RSV EIA-positive did not significantly differ from those who tested negative with regard to demographic variables, clinical diagnoses, risk factors for RSV or length of hospitalisation. The only significant difference noted was the presence of hyperinflation, which occurred in 70.1% of EIA-positive patients compared with 57.1% of those testing negative (P = 0.0005). The mortality rate (2%) was similar for both groups. CONCLUSION: This study indicates that RSV is an important cause of hospitalisation in infants and young children with ALRTI. Distinguishing RSV from other ALRTIs is difficult because of similarity in clinical presentation among children.

Data Interpretation, Statistical↗
PubMed1999

Immunological manifestations of HIV-infected children.

This cross-sectional study of stable HIV-infected children was designed to document the immunological manifestations of paediatric HIV infection and to determine whether inexpensive markers of immunosuppression could be identified. Investigations included lymphocyte count and subset analysis, levels of total protein, albumin, immunoglobulins, beta-2 microglobulin and neopterin. The median age of the 74 children studied was 16.5 months and 76% and 39% had subnormal percentage CD4+ counts and absolute CD4+ counts, respectively. According to the Centers for Disease Control (CDC) guidelines, 85% were moderately or severely immunosuppressed. The majority had elevated neopterin, beta-2 microglobulin, IgG, IgM and IgA concentrations. The IgG concentration correlated positively with total globulin, IgG1 and IgG3 concentrations. On bivariate analysis, the absolute CD4+ count correlated positively with total lymphocyte count (r = 0.28 < 0.48 < 0.64) and negatively with total IgG concentration (r = -0.47 < -0.27 < -0.04), IgG1 concentration (r = -0.51 < -0.31 < -0.08), and neopterin concentration (r = -0.49 < -0.28 < -0.04). There was no correlation between CD4+ count, total globulin or beta-2 microglobulin concentration. On multiple linear regression analysis only the total lymphocyte count correlated with CD4+ count. Furthermore, on bivariate analysis total lymphocyte count correlated positively with absolute CD8+ count (r = 0.82 < 0.88 < 0.92). In conclusion, although there was a positive correlation between absolute CD4+ count and total lymphocyte count, the clinical significance is questionable as the total lymphocyte count correlated more strongly with the absolute CD8+ count.

Analysis of Variance↗
PubMed1999

Plasma-soluble CD30 in childhood tuberculosis: effects of disease severity, nutritional status, and vitamin A therapy.

Plasma-soluble CD30 (sCD30) is the result of proteolytic splicing from the membrane-bound form of CD30, a putative marker of type 2 cytokine-producing cells. We measured sCD30 levels in children with tuberculosis, a disease characterized by prominent type 1 lymphocyte cytokine responses. We postulated that disease severity and nutritional status would alter cytokine responses and therefore sCD30 levels. Samples from South African children enrolled prospectively at the time of diagnosis of tuberculosis were analyzed. (Patients were originally enrolled in a randomized, double-blind placebo-controlled study of the effects of oral vitamin A supplementation on prognosis of tuberculosis.) Plasma samples collected at the time of diagnosis and 6 and 12 weeks later (during antituberculosis therapy) were analyzed. sCD30 levels were measured by enzyme immunoassay. The 91 children included in the study demonstrated high levels of sCD30 at diagnosis (median, 98 U/liter; range, 11 to 1,569 U/liter). Although there was a trend toward higher sCD30 levels in more severe disease (e.g., culture-positive disease or miliary disease), this was not statistically significant. Significantly higher sCD30 levels were demonstrated in the presence of nutritional compromise: the sCD30 level was higher in patients with a weight below the third percentile for age, in those with clinical signs of kwashiorkor, and in those with a low hemoglobin content. There was minimal change in the sCD30 level after 12 weeks of therapy, even though patients improved clinically. However, changes in sCD30 after 12 weeks differed significantly when 46 patients (51%) who received vitamin A were compared with those who had received a placebo. Vitamin A-supplemented children demonstrated a mean (+/- standard error of the mean) decrease in sCD30 by a factor of 0.99 +/- 0.02 over 12 weeks, whereas a factor increase of 1.05 +/- 0.02 was demonstrated in the placebo group (P = 0.02). We conclude that children with tuberculosis had high sCD30 levels, which may reflect the presence of a type 2 cytokine response. Nutritional compromise was associated with higher sCD30 levels. Vitamin A therapy resulted in modulation of sCD30 levels over time.

Adolescent↗
PubMed1998

Randomised controlled trial of clinical outcome after chest radiograph in ambulatory acute lower-respiratory infection in children.

BACKGROUND: When available, chest radiographs are used widely in acute lower-respiratory-tract infections in children. Their impact on clinical outcome is unknown. METHODS: 522 children aged 2 to 59 months who met the WHO case definition for pneumonia were randomly allocated to have a chest radiograph or not. The main outcome was time to recovery, measured in a subset of 295 patients contactable by telephone. Subsidiary outcomes included diagnosis, management, and subsequent use of health facilities. FINDINGS: There was a marginal improvement in time to recovery which was not clinically significant. The median time to recovery was 7 days in both groups (95% CI 6-8 days and 6-9 days in the radiograph and control groups respectively, p=0.50, log-rank test) and the hazard ratio for recovery was 1.08 (95% CI 0.85-1.34). This lack of effect was not modified by clinicians' experience and no subgroups were identified in which the chest radiograph had an effect. Pneumonia and upper-respiratory infections were diagnosed more often and bronchiolitis less often in the radiograph group. Antibiotic use was higher in the radiograph group (60.8% vs 52.2%, p=0.05). There was no difference in subsequent use of health facilities. INTERPRETATION: Chest radiograph did not affect clinical outcome in outpatient children with acute lower-respiratory infection. This lack of effect is independent of clinicians' experience. There are no clinically identifiable subgroups of children within the WHO case definition of pneumonia who are likely to benefit from a chest radiograph. We conclude that routine use of chest radiography is not beneficial in ambulatory children aged over 2 months with acute lower-respiratory-tract infection.

Acute Disease↗
PubMed1998

Survival of children in Cape Town known to be vertically infected with HIV-1.

OBJECTIVE: To determine the survival patterns of children in Cape Town known to be vertically infected with HIV. DESIGN: Retrospective record review of children diagnosed with symptomatic HIV infection during the period 1 December 1990-31 May 1995. SETTING: Hospitals in the Cape Town metropolitan area. PATIENTS: 193 children were known to be vertically HIV-infected. HIV diagnosis was based on the following criteria: two positive HIV enzyme-linked immunosorbent assays (ELISAs) in children older than 15 months and a positive ELISA together with a positive polymerase chain reaction (PCR) in younger children. The mothers of the children were known to be HIV-positive. On the basis of the presenting clinical findings children were assigned to a disease severity category (A, B or C) according to the Centers for Disease Control and Prevention (CDC)'s 1994 revised classification system for HIV infection in children. OUTCOME MEASURES: Survival was analysed according to the Kaplan-Meier method. Survival time was defined as the length of time between clinical diagnosis of HIV and death or last contact with the health services. Mortality risk in relation to specific variables at diagnosis such as age and clinical manifestations was determined by calculation of odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: The median age at diagnosis was 5 months; 72% of children were aged less than 1 year at diagnosis. According to the CDC clinical classification, 47 (24%) fell into category A, 111 (58%) into category B and 35 (18%) into category C. Of the 193 patients 85 (44%) were alive at the time of review, 65 (34%) had died and 43 (22%) were lost to follow-up. Risk of death was significantly associated with age less than 6 months (OR 4.7, CI 2.1-10.3) and severe disease, i.e. CDC category C (OR 2.7; CI 1.1-6.9) at time of diagnosis. The median survival for all the children from time of diagnosis was 32 months. Infants diagnosed before 6 months of age had significantly shorter median survival (10 months) compared with 36 months for those diagnosed at 7-12 months of age. For the children over the age of 12 months the cumulative proportion surviving at 48 months was 78%. Children with severe disease (category C) had a median survival of 21 months, significantly lower than that in category B (32 months). For the children in category A the cumulative proportion surviving at 48 months was 66%. CONCLUSION: The median survival of children with HIV was 32 months from time of diagnosis, and survival was influenced by age and disease severity.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Vitamin A status and therapy in childhood pulmonary tuberculosis.

Low plasma vitamin A levels (mean, 18.1 +/- 10.3 micrograms/dl, 62% below normal) were demonstrated in South African children with pulmonary tuberculosis. More extensive or severe disease (e.g., additional extrapulmonary tuberculosis) and low levels of retinol binding protein, prealbumin, and albumin were associated with low vitamin A levels. High-dose vitamin A therapy had no effect on disease outcome.

Child↗
PubMed1996

Changes within T cell receptor V beta subsets in infants following measles vaccination.

Measles produces immune suppression which contributes to an increased susceptibility to other infections. Recently, high titered measles vaccines have been linked to increased long-term mortality among some female recipients. Because the mechanisms by which wild-type or attenuated live-vaccine strains of measles virus alter subsequent immune responses are not fully understood, this prompted an examination of the changes within the peripheral blood T cell receptor V beta repertoire following measles immunization. Twenty-four 6- and 9-month-old infants were studied at 2 weeks and 3 months following immunization by semiquantitative reverse transcription-polymerase chain reaction. There was a significant increase in V beta 2 expression (P less than 0.05), and a decrease in the V beta 4 subset (P less than 0.03) 2 weeks following vaccination with subsequent return to baselines at 3 months in vaccine recipients who seroconverted. These data suggest that measles virus may affect immune responses in part by altering the T cell receptor repertoire.

Base Sequence↗
PubMed1996

Clinical problems in measles case management.

Measles remains one of the leading causes of childhood morbidity and mortality in developing countries. The World Health Organization has identified effective case management as one of the specific strategies to reduce the burden of this disease. The purpose of this article is to review the aetiology, natural history, treatment and outcome of the common clinical problems associated with measles with a view to identifying possible deficiencies in case management. Complications such as pneumonia, diarrhoea, croup and malnutrition have been well defined in terms of their relative contribution to morbidity and mortality. However, there are few published data on the aetiology and natural history of these specific complications. Such data are crucial for rational case management strategies. Data on treatment of measles and its complications are limited and the role of antibiotic prophylaxis and therapy is unclear. The only specific research focus on case management during the last decade has been vitamin A therapy. There is a continuing need for community and hospital-based studies on the natural history of measles and its complications, the aetiology of these complications and intervention strategies that will improve measles case management.

Developing Countries↗
PubMed1996

The effect of Edmonston-Zagreb and Schwarz measles vaccines on immune response in infants.

The effects of measles immunization on immune responses in infants and the roles of vaccine strain and age of immunization are not known. Eighty-eight children were immunized at 6 or 9 months of age with the Edmonston-Zagreb (EZ) or Schwarz (SW6, SW9) strain of measles vaccine. Children were studied before and 2 weeks and 3 months after immunization. Seroconversion was similar, but geometric mean neutralizing titers at 3 months differed by vaccine group: SW9, 1367 mIU/mL; SW6, 982; and EZ, 303 (P = .003). Mitogen-induced lymphoproliferation was decreased at 2 weeks in the SW9 group and at 3 months in all groups and was negatively correlated with measles antibody level at 3 months (r = -.387, P = .003). CD8 T cells, soluble CD8, neopterin, and beta2-microglobulin were increased at 2 weeks in the SW9 group, and soluble CD8 and beta2-microglobulin remained elevated at 3 months. Therefore, measles immunization resulted in suppression of lymphoproliferation, which was most evident in infants with the highest antibody responses and most immune activation.

Age Factors↗
PubMed1995

The costs and benefits of a vaccination programme for Haemophilus influenzae type B disease.

Haemophilus influenzae type b (Hib) infection is a major cause of severe bacterial infection in young children in South Africa and world-wide. These diseases can be prevented by immunisation with conjugate Hib vaccines. In South Africa, unlike some developed countries, Hib vaccines are not part of the routine immunisation schedule. The objective of this study was to measure the expected net benefits from a hypothetical programme of vaccination of the 1992 Cape Town birth cohort (N = 46,537). Costs were calculated by summing the estimated direct medical care costs together with the indirect costs of Hib disease. The latter were calculated by valuing human life using alternative, and conservative human capital and willingness-to-pay measures. The difference between Hib disease costs (i.e. the benefits which would be gained from a successful vaccination programme) and the costs of the vaccination programme itself (HibTITER, Praxis Biologicals) defined the expected net benefits. In the absence of an immunisation programme, the estimated economic costs of Hib disease in the 1992 Cape Town cohort ranged from R10.7 million to R11.8 million. The costs of introducing the vaccine would have amounted to R8.3 million. Had the vaccine been administered to the 1992 birth cohort, benefits would have exceeded costs by between R2.4 million and R3.5 million.

Bacterial Proteins↗