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Biomedical subjects

G Kokwaro

Publications and source records attributed to G Kokwaro.

6 recordsLinked to original sources
PubMed2005

Characterisation of metabolic acidosis in Kenyan children admitted to hospital for acute non-surgical conditions.

Metabolic acidosis is associated with most severe malaria deaths in African children, and most deaths occur before maximum antimalarial action is achieved. Thus, specific acidosis treatment may reduce mortality. However, the underlying mechanisms remain poorly understood and no specific interventions have been developed. A detailed characterisation of this acidosis is critical in treatment development. We used the traditional and Stewart's approach to characterise acidosis in consecutive paediatric admissions for malaria and other acute non-surgical conditions to Kilifi District Hospital in Kenya. The overall acidosis prevalence was 21%. Gastroenteritis had the highest prevalence (61%). Both the mean albumin-corrected anion gap and the strong ion gap were high (>13 mmol/l and >0 mmol/l, respectively) in malaria, gastroenteritis, lower respiratory tract infection and malnutrition. Presence of salicylate in plasma was not associated with acidosis but was associated with signs of severe illness (odds ratio 2.11, 95% CI 1.1-4.2). In malaria, mean (95% CI) strong ion gap was 15 (14-7) mmol/l, and lactate, creatinine and inorganic phosphorous explained only approximately 40% of the variability in base excess (adjusted R2 = 0.397). Acidosis may be more common than previously recognised amongst paediatric admissions in Africa and is characterised by the presence of currently unidentified strong anions. In malaria, lactate and ketones, but not salicylate, are associated with acidosis. However, unidentified anions may be more important.

3-Hydroxybutyric Acid↗
PubMed2004

A randomised, controlled trial of once daily and multi-dose daily gentamicin in young Kenyan infants.

AIMS: To test the suitability of a simple once daily (OD) gentamicin regimen for use in young infants where routine therapeutic drug monitoring is not possible. METHODS: In an open, randomised, controlled trial, infants with suspected severe sepsis admitted to a Kenyan, rural district hospital received a novel, OD gentamicin regimen or routine multi-dose (MD) regimens. RESULTS: A total of 297 infants (over 40% < or =7 days) were randomised per protocol; 292 contributed at least some data for analysis of pharmacological endpoints. One hour after the first dose, 5% (7/136) and 28% (35/123) of infants in OD and MD arms respectively had plasma gentamicin concentrations <4 microg/ml (a surrogate of treatment inadequacy). Geometric mean gentamicin concentrations at this time were 9.0 microg/ml (95% CI 8.3 to 9.9) and 4.7 microg/ml (95% CI 4.2 to 5.3) respectively. By the fourth day, pre-dose concentrations > or =2 microg/ml (a surrogate of potential treatment toxicity) were found in 6% (5/89) and 24% (21/86) of infants respectively. Mortality was similar in both groups and clinically insignificant, although potential gentamicin induced renal toxicity was observed in <2% infants. CONCLUSIONS: A "two, four, six, eight" OD gentamicin regime, appropriate for premature infants and those in the first days and weeks of life, seems a suitable, safe prescribing guide in resource poor settings.

Anti-Bacterial Agents↗
PubMed2000

Chloroquine is not a risk factor for seizures in childhood cerebral malaria.

OBJECTIVES: There are a number of case reports in the medical literature suggesting an association between the ingestion of chloroquine and subsequent seizure activity. Our study was designed to investigate the relationship between blood levels of chloroquine (CQ), its metabolite desethylchloroquine (DCQ), and seizures in children admitted to hospital with cerebral malaria. METHODS: Serial blood levels of CQ and DCQ were measured over the first 24 h of hospital admission in children with cerebral malaria. The number and duration of all seizures was recorded, and statistical analysis subsequently performed to determine the relationship between seizure activity and blood concentrations of CQ and DCQ. RESULTS: Chloroquine was detected in 92% (100/109) of admission blood samples. 54% (59/109) of the patients had one or more seizures after admission, while 8% (9/109) had an episode of status epilepticus. Median (interquartile range) baseline concentrations of CQ and DCQ were, respectively, 169.4 microg/ml (75.1-374.9) and 352.3 microg/ml (81.9-580.1) for those children who had seizures after admission, compared to CQ 227.5 microg/ml (79.4-430.2) and DCQ 364.0 microg/ml (131.3-709.4) for those who did not have seizures (P > 0.5 for all comparisons). Baseline concentrations of CQ and DCQ were not significantly associated with the occurrence of seizures lasting for 5 min or more. The nine children who had an episode of status epilepticus had significantly lower median admission levels of CQ than those without status epilepticus: 75.1 microg/l (7.4-116.5) vs. 227.5 microg/l (85.6-441.2), P = 0.02. Multivariate logistic regression analysis, taking into account factors likely to affect the risk of seizures in hospital, failed to change the significance of these results. CONCLUSIONS: These findings suggest that chloroquine does not play an important role in the aetiology of seizures in childhood cerebral malaria.

Adolescent↗
PubMed1997

Infection with Plasmodium berghei alters benzodiazepine receptor in rat brain.

The purpose of this study was to assess the effect of malaria infection on benzodiazepine binding in rat brain. Young male Wistar rats were infected with the rodent parasite Plasmodium berghei, while age-matched control rats (n = 5) received normal saline intraperitoneally. Parasitemia was determined in blood of infected animals. Animals were killed after two weeks, and synaptosomal brain membrane homogenate was prepared from cerebral cortex. Membrane homogenate was incubated in duplicate with 3H-flunitrazepam (0.2-10 nM in buffer, pH 7.4) and binding parameters determined. The number of receptors (Bmax) was decreased marginally but significantly (P = 0.047) in malaria-infected (MI) rats (MI rats: 1.12 +/- 0.1 pmol.mg-1 protein; control rats: 1.42 +/- 0.08 pmol.mg-1 protein) while binding affinity (Kd) was not altered (MI rats: 1.18 +/- 0.3 nM; control rats: 1.02 +/- 0.15 nM). These results suggest that malaria may be associated with decreased benzodiazepine activity.

Animals↗
PubMed1995

Halofantrine pharmacokinetics in Kenyan children with non-severe and severe malaria.

1. Kenyan children with uncomplicated malaria given oral halofantrine (HF; non-micronised suspension; 8 mg base kg-1 body weight 6 hourly for three doses) showed wide variation in the disposition of HF and desbutylhalofantrine (HFm). 2. Eight Kenyan children with severe (prostrate) falciparum malaria who were receiving intravenous quinine, were given the same HF regimen by nasogastric tube. One patient had undetectable HF and two had undetectable HFm at all times after drug administration. 3. The mean AUC(0,24 h) of HF in prostrate children was half (7.54 compared with 13.10 micrograms ml-1 h) (P = 0.06), and that for HFm one-third (0.84 compared with 2.51 micrograms ml-1 h) (P < 0.05) of the value in children with uncomplicated malaria. 4. Oral HF may be appropriate for some cases of uncomplicated falciparum malaria in Africa, but in patients with severe malaria, the bioavailability of HF and HFm may be inadequate.

Administration, Oral↗