Browsing by Author "Madhi S.A."

Now showing 1 - 8 of 8
  • No Thumbnail Available
    Item
    Early antiretroviral therapy and mortality among HIV-infected infants
    (2008) Violari A.; Cotton M.F.; Gibb D.M.; Babiker A.G.; Steyn J.; Madhi S.A.; Jean-Philippe P.; McIntyre J.A.
  • No Thumbnail Available
    Item
    Early antiretroviral treatment reduces risk of bacille Calmette- Guérin immune reconstitution adenitis
    (2011) Rabie H.; Violari A.; Duong T.; Madhi S.A.; Josipovic D.; Innes S.; Dobbels, Els; Lazarus E.; Panchia R.; Babiker A.G.; Gibb D.M.; Cotton M.F.
    SETTING: Two centres in Soweto and Cape Town, South Africa. OBJECTIVE: To assess the effects of timing of initiation of antiretroviral treatment (ART) and other factors on the risk of bacille Calmette-Guérin (BCG) related regional adenitis due to immune reconstitution infl ammatory syndrome (BCG-IRIS) in human immunodefi ciency virus (HIV) infected infants. DESIGN: HIV-infected infants aged 6-12 weeks with CD4 count ≥25% enrolled in the Children with HIV Early Antiretroviral Therapy (CHER) Trial received early (before 12 weeks) or deferred (after immunological or clinical progression) ART; infants with CD4 count <25% all received early ART. All received BCG vaccination after birth. Reactogenicity to BCG was assessed prospectively during routine study follow-up. RESULTS: Of 369 infants, 32 (8.7%) developed BCGIRIS within 6 months of starting ART, 28 (88%) within 2 months after ART initiation. Of the 32 cases, 30 (93.8%) had HIV-1 RNA > 750 000 copies/ml at initiation. Incidence of BCG-IRIS was 10.9 and 54.3 per 100 personyears (py) among infants with CD4 count ≥25% at enrolment receiving early (at median age 7.4 weeks) vs. deferred (23.2 weeks) ART, respectively (HR 0.24, 95%CI 0.11-0.53, P < 0.001). Infants with CD4 count <25% receiving early ART had intermediate incidence (41.7/ 100 py). Low CD4 counts and high HIV-1 RNA at initiation were the strongest independent risk factors for BCG-IRIS. CONCLUSIONS: Early ART initiation before immunological and/or clinical progression substantially reduces the risk of BCG-IRIS regional adenitis. © 2011 The Union.
  • No Thumbnail Available
    Item
    Effect of HIV infection status and Anti-retroviral treatment on quantitative and qualitative antibody responses to pneumococcal conjugate vaccine in infants
    (2010) Madhi S.A.; Adrian P.; Cotton M.F.; McIntyre J.A.; Jean-Philippe P.; Meadows S.; Nachman S.; Kayhty H.; Klugman K.P.; Violari A.
    Serotype-specific antibody concentration and opsonophagocytic activity (OPA) were evaluated after 3 doses of pneumococcal conjugate vaccine. Groups included human immunodeficiency virus (HIV)-positive infants with CD4+ cell percentages ≥25% who initiated immediate antiretroviral treatment (the HIV+/ART+ group) or whose antiretroviral treatment was deferred until clinically or immunologically indicated (the HIV+/ART+ group). Immune responses were also evaluated in HIV-noninfected infants born to HIV-seronegative (M+/I+) or HIV-positive mothers (M+/I+). Antibody concentrations were similar between HIV+/ART+ and HIV+/ART+ infants. However, antibody concentrations were lowerin M+/I+ infants than in M+/I+ infants. Nevertheless, M+/I+ infants had superior OPA responses, compared with those in HIV+/ART+ infants, who in turn had better OPA responses, compared with those in HIV+/ART+ infants. © 2010 by the Infectious Diseases Society of America.
  • No Thumbnail Available
    Item
    HIV and childhood tuberculosis: The way forward
    (2004) Cotton M.F.; Schaaf H.S.; Hesseling A.C.; Madhi S.A.
    Tuberculosis has been a major cause of morbidity and mortality in under-resourced communities. By causing progressive immunodeficiency, the human immunodeficiency virus (HIV) increases susceptibility to tuberculosis in an already vulnerable community. Similarities in clinical presentation and radiological appearance contribute to diagnostic difficulties, as even in the absence of HIV childhood tuberculosis is not easy to diagnose. The majority of studies thus far have been descriptive and often cross-sectional, but have defined the extent of this complex interaction. There is now a need to undertake prospective diagnostic, therapeutic and prevention studies. An emerging concern is how to integrate antiretroviral with anti-tuberculosis treatment and to explore whether lessons learned in tuberculosis can support antiretroviral therapy. Interactions between therapies for both conditions also need careful study.
  • No Thumbnail Available
    Item
    Inferior quantitative and qualitative immune responses to pneumococcal conjugate vaccine in infants with nasopharyngeal colonization by Streptococcus pneumoniae during the primary series of immunization
    (2011) Madhi S.A.; Violari A.; Klugman K.P.; Lin G.; McIntyre J.A.; von Gottberg A.; Jean-Philippe P.; Cotton M.F.; Adrian P.
    Background: Heightened immunogenicity, measured one month after the primary series of pneumococcal conjugate vaccine (PCV), in African children was previously hypothesized to be due to increased rates of nasopharyngeal pneumococcal colonization during early infancy. Methods: We analyzed the effect of selected vaccine-serotype (6B, 19F and 23F) nasopharyngeal colonization prior to the first PCV dose or when colonized for the first time prior to the second or third (2nd/3rd) PCV dose on serotype quantitative and qualitative antibody responses. Results: Colonization prior to receiving the first PCV was associated with lower geometric mean antibody concentrations (GMCs) one month after the third dose of PCV and six months later to the colonizing-serotype. Colonized infants also had lower geometric mean titers (GMTs) on opsonophagocytosis activity assay (OPA) and a lower proportion had titers ≥8 against the colonizing serotypes (19F and 23F) post vaccination. Colonization occurring only prior to the 2nd/3rdPCV dose was also associated with lower GMCs and OPA GMTs to the colonizing-serotype. The effect of colonization with serotypes 19F and 23F prior to PCV vaccination had a greater effect on a lower proportion of colonized infants having OPA titers ≥8 than the effect of colonization on the lower proportion with antibody ≥0.35 μg/ml. Conclusion: Infant nasopharyngeal colonization at any stage before completing the primary series of PCV vaccination was associated with inferior quantitative and qualitative antibody responses to the colonizing-serotype. © 2011 Elsevier Ltd.
  • No Thumbnail Available
    Item
    Isoniazid pharmacokinetics, pharmacodynamics, and dosing in South African infants
    (2012) Kiser J.J.; Zhu R.; D'Argenio D.Z.; Cotton M.F.; Bobat R.; McSherry G.D.; Madhi S.A.; Carey V.J.; Seifart H.I.; Werely C.J.; Fletcher C.V.
    AIMS: There are limited data on isoniazid (INH) pharmacokinetics in infants and young children and, therefore, uncertainty on appropriate dosing. METHODS: Pharmacokinetic data were obtained from perinatally HIV-exposed South African infants aged 3-24 months receiving INH 10-20 mg·kg·d orally for Mycobacterium tuberculosis prophylaxis. INH pharmacokinetic parameters were characterized using a population pharmacokinetic approach. Dosing simulations were performed to evaluate weight-based INH doses in children based on N-acetyltransferase 2 enzyme (NAT2) genotype, age, maximum concentrations (Cmax) ≥3 mg/L, and area under the curve (AUC0-24) ≥10.52 mg·h/L. RESULTS: In 151 infants (53% female, 48% HIV positive) receiving a mean INH dose of 14.5 mg·kg·d, mean (±SD) Cmax at 3, 6, and 23 months of age were 10.0 (3.5), 8.6 (2.6), and 9.3 (3.8) mg/L, respectively, mean (±SD) AUC0-24 were 53.6 (26.8), 42 (19.9), and 44 (30.7) mg·h/L, respectively, and mean (±SD) half-lives were 2.1 (0.7), 1.9 (0.6), and 1.8 (0.9) hours, respectively. A trimodal apparent oral clearance of INH as a function of the NAT2 genotype was apparent as early as 3 months. INH was well tolerated. At an average INH dose of 14.5 mg·kg·d, 99% of infants aged 3-24 months have an INH Cmax ≥3 mg/L, and 98% have an INH AUC0-24 ≥10.52 mg·h/L. CONCLUSIONS: INH at an average dose of 14.5 mg/kg once daily was well tolerated in infants and achieved INH Cmax values ≥3 mg/L and AUC0-24 values ≥10.52 mg·h/L. Copyright © 2012 by Lippincott Williams & Wilkins.
  • No Thumbnail Available
    Item
    Primary isoniazid prophylaxis against tuberculosis in HIV-exposed children
    (2011) Madhi S.A.; Nachman S.; Violari A.; Kim S.; Cotton M.F.; Bobat R.; Jean-Philippe P.; McSherry G.; Mitchell C.
    BACKGROUND: The dual epidemic of human immunodeficiency virus (HIV) and tuberculosis is a major cause of sickness and death in sub-Saharan Africa. We conducted a double-blind, randomized, placebo-controlled trial of preexposure isoniazid prophylaxis against tuberculosis in HIV-infected children and uninfected children exposed to HIV during the perinatal period. METHODS: We randomly assigned 548 HIV-infected and 804 HIV-uninfected infants (91 to 120 days of age) to isoniazid (10 to 20 mg per kilogram of body weight per day) or matching placebo for 96 weeks. All patients received bacille Calmette-Guérin (BCG) vaccination against tuberculosis within 30 days after birth. HIV-infected children had access to antiretroviral therapy. The primary outcome measures were tuberculosis disease and death in HIV-infected children and latent tuberculosis infection, tuberculosis disease, and death in HIV-uninfected children within 96 to 108 weeks after randomization. RESULTS: Antiretroviral therapy was initiated in 98.9% of HIV-infected children during the study. Among HIV-infected children, protocol-defined tuberculosis or death occurred in 52 children (19.0%) in the isoniazid group and 53 (19.3%) in the placebo group (P = 0.93). Among HIV-uninfected children, there was no significant difference in the combined incidence of tuberculosis infection, tuberculosis disease, or death between the isoniazid group (39 children, 10%) and the placebo group (45 children, 11%; P = 0.44). The rate of tuberculosis was 121 cases per 1000 child-years (95% confidence interval [CI], 95 to 153) among HIV-infected children as compared with 41 per 1000 child-years (95% CI, 31 to 52) among HIV-uninfected children. There were no significant differences in clinical or severe laboratory toxic effects between treatment groups. CONCLUSIONS: Primary isoniazid prophylaxis did not improve tuberculosis-disease- free survival among HIV-infected children or tuberculosis-infection-free survival among HIV-uninfected children immunized with BCG vaccine. Despite access to antiretroviral therapy, the burden of tuberculosis remained high among HIV-infected children. (Funded by the National Institutes of Health and Secure the Future; ClinicalTrials.gov number, NCT00080119.) Copyright © 2011 Massachusetts Medical Society.
  • No Thumbnail Available
    Item
    Updated guideline for the management of upper respiratory tract infections in South Africa: 2008
    (2009) Brink A.J.; Cotton M.F.; Feldman C.; Finlayson H.; Geffen L.; Green R.; Hendson W.; Hockman M.H.; Maartens G.; Madhi S.A.; Mutua-Mpungu M.; Swingler G.H.
    Introduction: Inappropriate use of antibiotics for non-severe upper respiratory tract infections (URTIs), many of which are viral, adds to the burden of antibiotic resistance. Antibiotic resistance is increasing in Streptococcus pneumoniae, the microorganism responsible for most cases of acute otitis media (AOM) and acute bacterial sinusitis (ABS). Method: The Infectious Diseases Society of Southern Africa held a multidisciplinary meeting to draw up a national guideline for the management of URTIs in 2003. Background information reviewed included randomised controlled trials, existing URTI guidelines and local antibiotic susceptibility patterns. The initial document was drafted at the meeting. Subsequent drafts were circulated to members of the working group for modification. The guideline was published in the South African Medical Journal in 2004 and was a consensus document based upon the opinions of the working group. In 2008 it was decided to update and republish the guideline. This was done electronically using the same working group members, including overseas experts. Output: Penicillin remains the drug of choice for tonsillopharyngitis. Single-dose parenteral administration of benzathine penicillin is effective, but many favour oral administration twice daily for 10 days. Amoxycillin remains the drug of choice for both AOM and ABS. A dose of 90 mg/kg/day is recommended in general, which should be effective for pneumococci with high-level penicillin resistance (this is particularly likely in children ≤2 years of age, in day-care attendees, in cases with prior AOM within the past six months, and in children who have received antibiotics within the last three months). Alternative antibiotic choices are given in the guideline with recommendations for their specific indications. These antibiotics include amoxycillin-clavulanate, some cephalosporins, the macrolide/azalide and ketolide groups of agents and the respiratory fluoroquinolones. Conclusion: The guideline should assist rational antibiotic prescribing for URTIs. However, it should be continuously updated when new information becomes available from randomised controlled trials and surveillance studies of local antibiotic susceptibility patterns.