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Biomedical subjects

Z Premji

Publications and source records attributed to Z Premji.

25 records · Page 2Linked to original sources

Standard and reduced doses of sulfadoxine-pyrimethamine for treatment of Plasmodium falciparum in Tanzania, with determination of drug concentrations and susceptibility in vitro.

88 asymptomatic Tanzanian schoolchildren with Plasmodium falciparum parasitaemia were given all, half or quarter of the recommended standard therapeutic dose of sulfadoxine-pyrimethamine (Fansidar). All children cleared the parasites by day 3 and all remained negative during 28-42 days of follow-up. All 32 successful in vitro micro-tests showed full sensitivity. High performance liquid chromatographic methods were applied for drug determinations. Using 100 microliter capillary blood dried on filter paper for sulfadoxine determination the inter-individual variation during follow-up of the standard dose group was 2-4 fold and the median half life was 8.9 d. Sulfadoxine concentrations in the half and quarter dose groups were roughly proportional to those in the standard dose group. The median whole blood to plasma concentration ratio for sulfadoxine was 0.72 and the correlation coefficient 0.95. There was only a weak correlation (r=0.46) between plasma concentrations of sulfadoxine and pyrimethamine. The uniform efficacy of sulfadoxine-pyrimethamine in vivo, even when reduced doses were used, makes this combination a good alternative for treatment of P. falciparum in Tanzania.

Adolescent↗

The rapid manual ParaSight-F test. A new diagnostic tool for Plasmodium falciparum infection.

A rapid manual test for Plasmodium falciparum, the ParaSight-F test, has been used on a series of patients in a holoendemic malaria area of coastal Tanzania. The test, which is an antigen capture test detecting trophozoite-derived histidine rich protein-II, is simple to perform and provides a definitive answer in about 10 min. It requires no special equipment and is read using a single drop of blood. When compared with 272 thick blood films examined microscopically by 2 observers and confirmed by the QBC malaria test, the ParaSight-F test had 88.9% sensitivity and 87.5% specificity. Detectable antigenaemia in a group of 40 people declined following treatment with Fansidar and by 10 d after treatment all but 4 individuals were antigen free. The remaining 4, although clear of peripheral parasitaemia, remained antigenaemic for 14 d. The test shows great promise for rapid effective diagnosis of P. falciparum in clinics and village health centres where there is no facility for microscopy. Because of its accuracy and rapid action it may even obviate the need for microscopical examination of blood films to diagnose P. falciparum malaria.

Adolescent↗

Acute haemolysis in childhood falciparum malaria.

Acute haemolysis associated with clinical episodes of high-level Plasmodium falciparum parasitaemia was studied in 20 children from an holoendemic area (coastal Tanzania). The change in blood haemoglobin (Hb) concentration ranged from -46 to g/L during the 72-h observation period and was linearly related to maximum parasitaemia. Balance studies between loss of blood Hb, increase in plasma Hb and appearance of Hb in the urine indicated that extravascular clearance of red cells was the predominant mode of erythrocyte clearance. Most subjects, however, showed minor signs of intravascular haemolysis. The plasma Hb was << 1% of blood Hb and haemoglobinuria was detected in 14/20 children but the excretion of Hb in urine was < 0.5% of total Hb loss. Haemoglobinuria was, however, a marker of severe haemolysis, since the maximum blood Hb loss in children without haemoglobinuria was 10 g/L. Erythrocyte-bound opsonins known to induce erythrophagocytosis, i.e., complement C3c fragments and autologous IgG, were increased in all patients. In the patients with major haemolysis, the changes correlated to the haemolysis over time. Hence, a similar mechanism for predominantly extravascular erythrocyte clearance may be operative in acute malarial anaemia, normal erythrocyte senescence and other forms of acute haemolysis.

Acute Disease↗

Changes in weight gain and anaemia attributable to malaria in Tanzanian children living under holoendemic conditions.

We investigated the effect of Plasmodium falciparum malaria on weight gain and haematocrit in Tanzanian children aged 6-40 months following a malaria control scheme which combined insecticide-impregnated bed nets with chloroquine chemotherapy on demand. Data from 7 villages (3 intervention and 4 control) were collected before, and one year after, the implementation of the programme. Initially, 82% of the children were parasitaemic, 78% were anaemic (i.e., packed cell volume < 33%) and 38% were underweight (i.e., 2 standard deviations below their weight-for-age Z score). One year after implementation of the programme, children not protected by the bed nets grew 286 g less (95% confidence interval [CI] 171-402 g) in a 5 months period and were twice as likely to be anaemic (95% CI 1.4-2.7) than were children not using impregnated bed nets. Our results indicated that, under holoendemic conditions, P. falciparum infection has a marked effect on both weight gain and anaemia.

Age Distribution↗

Chloroquine treatment for uncomplicated childhood malaria in an area with drug resistance: early treatment failure aggravates anaemia.

Childhood anaemia is a major public health problem in malaria holoendemic areas. We assessed the effects of antimalarial treatment in an area with drug-resistant falciparum malaria on haemoglobin levels in small children by applying the 1996 World Health Organization in vivo method for the evaluation of standard chloroquine treatment at the community level. In Fukayosi village, coastal Tanzania, 117 children aged 5-36 months with clinical malaria episodes were treated with chloroquine syrup (25 mg/kg). Early treatment failure (ETF) occurred in 20% and late treatment failure (LTF) in 22% of cases. Age > 1 year and malnutrition were protective factors against ETF. The evidence that chloroquine treatment could not prevent an exacerbation of anaemia was (i) the fact that the fall in haemoglobin level after 72 h was significantly greater in ETF than in children with LTF and an adequate clinical response, and (ii) the absence of any haematological improvement at follow-up in children receiving chloroquine alone, even in true treatment successes. In contrast, pyrimethamine/sulfadoxine administered to treatment failures improved the haemoglobin level significantly > 21 d after treatment started (mean difference 14 g/L, 95% confidence interval 2.1-27). We conclude that, when chloroquine treatment of childhood malaria is associated with a 20% ETF rate, the haemoglobin response is unsatisfactory and there is a need to change the recommended first-line treatment.

Anemia↗

Hemoglobin concentration in children in a malaria holoendemic area is determined by cumulated Plasmodium falciparum parasite densities.

In malaria holoendemic areas children are anemic, but the exact influence of falciparum malaria on hemoglobin (Hb) concentration remains largely unsettled. Prospective data were therefore collected in children < 24 months of age during five months in a Tanzanian village. Children with mean asymptomatic parasitemia > or = 400/microl had lower median Hb levels during the study than those with mean density < 400/microl. The difference was 9.7 g/L (95% confidence interval [CI] 2.8-17). In children with one or more clinical malaria episodes, the median Hb was 8.3 g/L (95% CI 0.9-16) lower than those without episode. If early treatment failure was recorded, the immediate effect on Hb was particularly important with a mean drop of 17 g/L. Interestingly, at study-end the Hb concentration represented a function of the area under the parasitemia curve (AUPC) during the previous five months, adjusting for age. In conclusion, stepwise deterioration in median Hb levels was found by asymptomatic parasitemia, clinical malaria episode, and most significantly, treatment failure.

Animals↗