Comparison of chlorproguanil-dapsone with sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in young African children: double-blind randomised controlled trial.

BACKGROUND: Increasing resistance to sulfadoxine-pyrimethamine is leading to a decline in its effectiveness. We aimed to assess the safety profile of chlorproguanil-dapsone (CD), and to compare the safety and efficacy of this drug with that of sulfadoxine-pyrimethamine (SP) as treatment for uncomplicated falciparum malaria. METHODS: We undertook a double-blind, randomised trial in 1850 consecutively recruited children with uncomplicated falciparum malaria, pooling data from five African countries. Analyses were based on all randomised patients with available data. FINDINGS: CD was significantly more efficacious than SP (odds ratio 3.1 [95% CI 2.0-4.8]); 1313 patients (96%) given CD and 306 (89%) given SP achieved acceptable clinical and parasitological response by day 14. Adverse events were reported in 46% and 50% of patients randomised to CD and SP, respectively (treatment difference -4.4%, [95% CI -10.1 to 1.3]). Haemoglobin in the CD group was significantly lower than in the SP group at day 7, a difference of -4 g/L (95% CI -6 to -2). Mean day 14 haemoglobin (measured only for the small number of patients whose day 7 data caused concern) was 94 g/L (92-96) and 97 g/L (92-102) after CD and SP, respectively. Glucose-6-phosphate dehydrogenase deficient patients on CD had greater odds than those on SP of having a fall of 20 g/dL or more in haemoglobin when baseline temperature was high. Methaemoglobinaemia was seen in the CD group (n=320, mean 0.4% [95% CI 0.4-0.4]) before treatment, 4.2% (95% CI 3.8-4.6) (n=301) at day 3, and 0.6% (0.6-0.7) (n=300) at day 7). INTERPRETATION: CD had greater efficacy than SP in Africa and was well tolerated. Haematological adverse effects were more common with CD than with SP and were reversible. CD is a useful alternative where SP is failing due to resistance.

Causes and outcome of young infant admissions to a Kenyan district hospital.

AIMS: To provide a comprehensive description of young infant admissions to a first referral level health facility in Kenya. These data, currently lacking, are important given present efforts to standardise their care through the integrated management of childhood illness (IMCI) and for prioritising both health care provision and disease prevention strategies. METHODS: Prospective, 18 month observational study in a Kenyan district hospital of all admissions less than 3 months of age to the paediatric ward. RESULTS: A total of 1080 infants were studied. Mortality was 18% overall, though in those aged 0-7 days it was 34%. Within two months of discharge a further 5% of infants aged <60 days on admission had died. Severe infection and prematurity together accounted for 57% of inpatient deaths in those aged <60 days, while jaundice and tetanus accounted for another 27%. S pneumoniae, group B streptococcus, E coli, and Klebsiella spp. were the most common causes of invasive bacterial disease. Hypoxaemia, hypoglycaemia, and an inability to feed were each present in more than 20% of infants aged 0-7 days. Both hypoxaemia and the inability to feed were associated with inpatient death (OR 3.8 (95% CI 2.5 to 5.8) and 7.4 (95% CI 4.8 to 11.2) respectively). CONCLUSIONS: Young infants contribute substantially to paediatric inpatient mortality at the first referral level, highlighting the need both for basic supportive care facilities and improved disease prevention strategies.