Pharmacokinetics of Artesunate Alone and in Combination with Sulfadoxine/Pyrimethamine in Healthy Sudanese Volunteers

Artesunate (AS) in combination with sulfadoxine/pyrimethamine (SP) is the first-line therapy for management of uncomplicated Plasmodium falciparum malaria in Sudan. The objective of this study was to assess the potential impact of SP on the pharmacokinetics of AS and its active metabolite, dihydroartemisinin (DHA), in healthy adults. A single-dose, randomized, open-label, crossover study design with a washout period of three weeks was performed with 16 volunteers. After oral administration of AS alone or in combination with SP, T_max values of AS and DHA were significantly prolonged in the combination group (P < 0.05). However, there was no significant effect on the other pharmacokinetic parameters (P > 0.05). The t_1/2 values of AS and DHA were significantly higher in females than in males (P < 0.05). The present findings suggest that co-administration of SP with AS has no clinically relevant impact on the pharmacokinetics of AS or DHA in healthy persons.     

Facilitating the WHO expanded program of immunization: the clinical profile of a combined diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae type b vaccine.

BACKGROUND: Vaccines are important weapons in the fight against infectious diseases. The World Health Organization (WHO) Expanded Program on Immunization (EPI) has been extended to include recommendations for hepatitis B and Haemophilus influenzae type b (Hib) vaccinations. The WHO has recommended that combined vaccines be used where possible, to reduce the logistic costs of vaccine delivery. This paper reviews the efficacy, safety and cost-effectiveness of Tritanrix-HB/Hib, the only commercially available combined diphtheria, tetanus, whole cell pertussis, hepatitis B and conjugated Hib vaccine. METHODS: The immunogenicity and reactogenicity results of five published clinical trials involving Tritanrix-HB/Hib in a variety of immunization schedules and countries were reviewed. Based on these data and cost-effectiveness studies, an assessment of its suitability for use in national immunization programs was made. RESULTS: Tritanrix-HB/Hib has shown excellent immunogenicity in clinical trials using a variety of schedules, with no reduced immunogenicity observed for any of the components of the combined vaccine. It has similar reactogenicity to DTPw vaccines alone. Pharmacoeconomic analyses have shown combined DTP-HB/Hib vaccines to be cost-effective compared to separate vaccines. CONCLUSIONS: Replacement of DTPw vaccination by Tritanrix-HB/Hib can be done without modifying the existing national immunization programs. This should facilitate widespread coverage of hepatitis B and Hib vaccinations and their rapid incorporation into the EPI.     

The use of non-prescribed medication in the first 3 months of life in rural South Africa

OBJECTIVE: This paper describes the use of non-prescribed medications given to a cohort of infants in the first 3 months of life in a rural South African district, and discusses some of the implications for primary health care. METHODS: As part of an ongoing study on breastfeeding, a cohort of 110 infants were visited at home at 6 and 12 weeks of age. Any medications given to the infant since the last visit, the reasons for their administration, and any visits made to traditional healers were recorded via a semi-structured questionnaire. Determinants of administration of non-prescribed medication were analysed, including maternal age, education, infant gender and socio-economic factors. RESULTS: A total of 107 (97%) infants received non-prescribed medications in the first 3 months of life: 98 (89%) rectally and 64 (58%) orally. The most common enema contained traditional Zulu medicine made from herbs, given more than once weekly, usually for perceived constipation; the most common oral medication was gripe water, given once daily, mainly for 'colic' or 'wind'. Twenty-nine (26%) mothers had consulted a traditional healer, most commonly because of concerns about a capillary naevus, thought to cause pain. Mothers with a 'clean' water supply were more likely to give non-prescribed oral medications than those without (OR=2.7 and P=0.0223), whilst those who had no education were less likely to administer them than those who had completed school (OR=0.19 and P=0.0326). CONCLUSIONS: Non-prescribed medications are given almost universally to young infants in our area, irrespective of socio-economic class. Health professionals need to be aware of the extent of, and reasons for, administration of non-prescribed medications to young infants, so that effective health messages can be targeted at mothers and caregivers.     

A study of urinary and intracellular sodium and potassium, renin, aldosterone, and hypertension in blacks and indians in natal

The prevalence of hypertension in the urban black population in Sub-Saharan Africa is high and varies from 20% to 25%. In contrast, the prevalence of hypertension in the rural black is relatively low. In Natal the prevalence of hypertension in a large metropolitan city, Durban, is 25% in the adult Zulu, 17.2% in whites, and 14.2% in Indians. The prevalence of hypertension in the rural Zulu of Natal is 10%. Work on the pathogenesis of hypertension in the Zulu and Indian ethnic groups related to renin, aldosterone, dietary sodium and potassium, and intracellular sodium and potassium was virtually nonexistent. This review paper summarizes the salient features that were found. This paper is a summary of the work undertaken by Dr. S. Hoosen in partial fulfillment of the requirements for the Degree of Doctor of Medicine in the University of Natal, 1988.     

Drug resistance and coreceptor usage in HIV type 1 subtype C-infected children initiating or failing highly active antiretroviral therapy in South Africa

HIV-1 drug resistance monitoring in resource-poor settings is crucial due to limited drug alternatives. Recent reports of the increased prevalence of CXCR4 usage in subtype C infections may have implications for CCR5 antagonists in therapy. We investigated the prevalence of drug resistance mutations and CXCR4 coreceptor utilization of viruses from HIV-1 subtype C-infected children. Fifty-one children with virological failure during highly active antiretroviral therapy (HAART) and 43 HAART-naive children were recruited. Drug resistance genotyping and coreceptor utilization assessment by phenotypic and genotypic methods were performed. At least one significant drug resistance mutation was present in 85.4% of HAART-failing children. Thymidine analogue mutations (TAMs) were detected in 58.5% of HAART-failing children and 39.0% had ≥3 TAMs. CXCR4 (X4) or dual (R5X4)/mixed (R5, X4) (D/M)-tropic viruses were found in 54.3% of HAART-failing and 9.4% of HAART-naive children (p<0.0001); however, the HAART-failing children were significantly older (p<0.0001). In multivariate logistic regression, significant predictors of CXCR4 usage included antiretroviral treatment, older age, and lower percent CD4(+) T cell counts. The majority of genotypic prediction tools had low sensitivity (≤65.0%) and high specificity (≥87.5%) for predicting CXCR4 usage. Extensive drug resistance, including the high percentage of TAMs found, may compromise future drug choices for children, highlighting the need for improved treatment monitoring and adherence counseling. Additionally, the increased prevalence of X4/D/M viruses in HAART-failing children suggests limited use of CCR5 antagonists in salvage therapy. Enhanced genotypic prediction tools are needed as current tools are not sensitive enough for predicting CXCR4 usage.     

Psychotherapy through the phases of bipolar disorder: evidence for general efficacy and differential effects

The obstacle facing pharmacotherapy for bipolar disorder is that almost half of the patients do not achieve recovery over the duration of treatment. Although the reason for this disappointing clinical outcome remains unclear, structured psychotherapy has helped to fill these gaps in the treatment of bipolar disorder. Psychoeducation, family-focused therapy, interpersonal and social rhythm therapy, and cognitive behavior therapy have all received attention in the research literature. In this review, by assessing the outcomes from randomized control trials across the phases of bipolar disorder, we demonstrate that psychotherapy is an effective adjunctive treatment. We also show that the use of psychotherapy for bipolar disorder has differential results depending on when and under what conditions it is administered.     

Trajectories of glycaemia following acute pancreatitis: a prospective longitudinal cohort study with 24 months follow-up

Journal of Gastroenterology - New-onset diabetes is the most common sequela of acute pancreatitis (AP). Yet, prospective changes in glycaemia over time have never been investigated comprehensively...