The pharmacokinetics and toxicity of antituberculosis agents and other co-administered drugs in children with tuberculosis, with and without HIV infection, and their relationship to nutritional status

Cilliers, Karien (2011-03)

Thesis (MNutr)--University of Stellenbosch, 2011.

Thesis

ENGLISH ABSTRACT: Problem definition: Malnutrition increases the incidence and exacerbates the clinical manifestations of TB. Hepatotoxicity is one of the most serious and most frequent side-effects of anti-tuberculosis drugs and may be three times higher in malnourished patients. Objective: The influence of nutritional and retroviral status on the bio-availability and toxicity of anti-tuberculosis agents was studied and a possible relationship between abdominal lymph node enlargement and the occurrence of malnutrition investigated. Subjects and setting: The study subjects were 53 children, 19 HIV-infected and 34 HIV-uninfected, aged 3 months to 13 years with probable or confirmed tuberculosis admitted to the paediatric ward of Brooklyn Hospital for Chest Diseases in Cape Town, South Africa. The nutritional status of the children was assessed over the first four months of tuberculosis treatment by nutrient intake, anthropometric status and biochemical parameters. The relationship between abdominal lymph node enlargement and the occurrence of malnutrition was also evaluated. Pharmacokinetic studies were performed to evaluate the bio-availability of anti-tuberculosis agents and drug hepato-toxicity was evaluated by liver function. Results: Stunting (46.27%) and underweight (34.51%) were the most common types of malnutrition in the children studied. HIV-infection did not have a significant effect on stunting or wasting, but had a significant effect (p=0.003) on underweight for age with 31.5% HIV-infected compared to 2.9% HIV-uninfected at enrolment, but the effect was not statistically significant at month 4. There was no change in the number of stunted, wasted or underweight children from enrolment after 1 month of treatment to month 4 of treatment. HIV-infection did not have a significant effect on abdominal TB involvement (p=0.43354), and nutritional status was not significantly affected by abdominal lymph-node involvement. At enrolment weight for age had a significant effect on AST and ALT with p-values of 0.02166 and 0.02765 respectively and wasting had a significant effect on GGT at enrolment (p=0.03014). However on enrolment only two HIV-infected and two HIV-uninfected children had ALT values increased >X2 normal. Similarly AST values >X3 normal were found in only one HIV-infected child and two HIV-uninfected children. Stunting did not significantly affect liver enzymes. Anthopometric status did not have a significant effect on liver enzymes at month 4. None of the parameters used to determine nutritional status had a statistically significant effect on INH-levels or RMP-levels. HIV-infection had a significant negatve effect on selenium (p=0.030 and 0.012) and ferritin (p=0.026 and 0.002) at enrolment and month 4 and on IBC (p=0.025) at enrolment. At month 4 HIV-infection had a significant negative effect on the mean vitamin C-levels (p=0.005). Conclusions: HIV co-infection did not affect the extent or distribution of body composition changes in this study. Stunting was the most prevalent form of malnutrition in the study group, indicating longstanding undernutrition, which may be due to factors other than the present TB infection. Appropriate treatment of tuberculosis did not appear to affect the nutritional status over the four month period of the study.

AFRIKAANSE OPSOMMING: Probleemstelling: Wanvoeding verhoog die insidensie en vererger die kliniese beeld van TB. Hepatotoksisiteit is een van die ernstigste en algemeenste newe-effekte van anti-tuberkulose middels en mag tot drie keer hoër wees in wangevoede pasiënte. Doelwit: Die invloed van die kinders se voedings- en retrovirale status op die bio-beskikbaarheid en toksisiteit van anti-tuberkulose middels was ondersoek en 'n moontlike verband tussen vergrote abdominale limfnodes en die voorkoms van wanvoeding was ondersoek. Deelnemers en omgewing: Die deelnemers aan die studie was 53 kinders, 19 HIV-positief en 34 HIV-negatief, tussen die ouderdomme van 3 maande en 13 jaar met moontlike of bevestigde tuberkulose toegelaat tot die pediatriese saal van Brooklyn Hospitaal vir Borskwale in Kaapstad, Suid Afrika. Die voedingstatus van die kinders was bepaal oor die eerste vier maande van tuberkulose behandeling ten opsigte van nutriëntinname, antropometriese status en biochemiese parameters. Die verhouding tussen vergrootte abdominale limfnodes en die voorkoms van wanvoeding was ook geëvalueer. Farmakokinetiese studies was uitgevoer om die bio-beskikbaarheid van anti-tuberkulose middels te evalueer en hepatotoksisiteit was deur lewerfunksie geëvalueer. Resultate: Dwerggroei (46.27%) en ondergewig (34.51%) was die algemeenste tipes wanvoeding teenwoordig by die kinders bestudeer. HIV-infeksie het nie 'n noemenswaardige effek op dwerggroei of uittering gehad nie, maar het wel 'n noemenswaardige effek (p=0.003) getoon op ondergewig vir ouderdom met 31.5% HIV-positief vergeleke met 2.9% HIV-negatief by inskrywing, wat nie statisties noemenswaardig was teen maand 4 nie. Daar was geen verandering in die hoeveelheid kinders met dwerggroei, uittering of ondergewig vanaf inskrywing na 1 maand van behandeling tot maand 4 van behandeling nie. HIV-infeksie het nie 'n noemenswaardige effek op abdominale TB gehad nie (p=0.43354), en vergrootte abdominale limfnodes het nie 'n noemenswaardige effek op voedingstatus gehad nie. By inskrywing het gewig vir ouderdom 'n noemenswaardige effek op AST en ALT gehad met p-waardes van 0.02166 en 0.02765 onderskeidelik en uittering het 'n noemenswaardige effek op GGT by inskrywing gehad (p=0.03014). Dwerggroei het nie die lewerensieme noemenswaardig beïnvloed nie. Antropometriese status het nie 'n noemenswaardige effek op lewerensieme teen maand 4 gehad nie. Geen van die parameters wat gebruik is om voedingstatus te bepaal het 'n noemenswaardige statistiese effek op INH-vlakke of RMP-vlakke gehad nie. HIV-infeksie het 'n noemenswaardige effek op selenium (p=0.030 en 0.012) en ferritien (p=0.026 en 0.002) by inskrywing en maand 4 gehad en op IBC (p=0.025) by inskrywing. HIV-infeksie het 'n statisties noemenswaardige effek op die gemiddelde vitamien C-vlakke (p=0.005). Gevolgtrekking: HIV ko-infeksie het nie die verspreiding of mate van liggaamsamestelling veranderinge in hierdie studie geaffekteer nie. Dwerggroei was die algemeenste vorm van wanvoeding in die studiegroep, wat langstaande wanvoeding aandui en toegeskryf mag word aan faktore buiten die huidige TB infeksie. Toepaslike tuberkulose behandeling het nie 'n wesenlike effek op voedingstatus gehad tydens die vier maande periode van die studie nie.

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