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Biomedical subjects

Z Premji

Publications and source records attributed to Z Premji.

At least 19 recordsLinked to original sources
PubMed2004

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.

Africa↗
PubMed2004

Higher IL-10 levels are associated with less effective clearance of Plasmodium falciparum parasites.

The implications of high levels of the immune regulatory cytokine IL-10 in Plasmodium falciparum malaria are unclear. IL-10 may down-regulate pro-inflammatory responses and also exacerbate disease by inhibiting anti-parasitic immune functions. To study possible inhibiting effects on parasite clearance, IL-10 plasma levels were determined in 104 Tanzanian children, 1 to 4 years old, with acute uncomplicated P. falciparum malaria, and analysed for association with parasite densities during 3 days of anti-malarial treatment. Higher baseline IL-10 plasma levels were associated with statistically significantly higher parasite densities after 24, 48 and 72 h of treatment. These associations could not be explained by differences in initial parasitaemia, temperature, age, sex or type of treatment. Induction of high IL-10 production might be a direct or indirect mechanism whereby the parasite evades the immune response.

Animals↗
PubMed2002

Acridine Orange for malaria diagnosis: its diagnostic performance, its promotion and implementation in Tanzania, and the implications for malaria control.

One hundred years ago, Giemsa's stain was employed for the first time for malaria diagnosis. Giemsa staining continues to be the method of choice in most malarious countries, although, in the recent past, several alternatives have been developed that exhibit some advantages. Considerable progress has been made with fluorescent dyes, particularly with Acridine Orange (AO). The literature on the discovery, development and validation of the AO method for malaria diagnosis is reviewed here. Compared with conventional Giemsa staining, AO shows a good diagnostic performance, with sensitivities of 81.3%-100% and specificities of 86.4%-100%. However, sensitivities decrease with lower parasite densities, and species differentiation may occasionally be difficult. The most notable advantage of the AO method over Giemsa staining is its promptness; results are readily available within 3-10 min, whereas Giemsa staining may take 45 min or even longer. This is an important advantage for the organization of health services and the provision of effective treatment of malaria cases. The national malaria control programme of Tanzania, together with the Japan International Co-operation Agency, began to introduce the AO method in Tanzania in 1994. So far, AO staining has been introduced in 70 regional and district hospitals, and 400 laboratory technicians have been trained to use the method. The results of this introduction, which are reviewed here and have several important implications, indicate that AO is a viable alternative technique for the laboratory diagnosis of malaria in highly endemic countries.

Acridine Orange↗
PubMed2001

An analysis of anemia and child mortality.

The relationship of anemia as a risk factor for child mortality was analyzed by using cross-sectional, longitudinal and case-control studies, and randomized trials. Five methods of estimation were adopted: 1) the proportion of child deaths attributable to anemia; 2) the proportion of anemic children who die in hospital studies; 3) the population-attributable risk of child mortality due to anemia; 4) survival analyses of mortality in anemic children; and 5) cause-specific anemia-related child mortality. Most of the data available were hospital based. For children aged 0-5 y the percentage of deaths due to anemia was comparable for reports from highly malarious areas in Africa (Sierra Leone 11.2%, Zaire 12.2%, Kenya 14.3%). Ten values available for hemoglobin values <50 g/L showed a variation in case fatality from 2 to 29.3%. The data suggested little if any dose-response relating increasing hemoglobin level (whether by mean value or selected cut-off values) with decreasing mortality. Although mortality was increased in anemic children with hemoglobin <50 g/L, the evidence for increased risk with less severe anemia was inconclusive. The wide variation for mortality with hemoglobin <50 g/L is related to methodological variation and places severe limits on causal inference; in view of this, it is premature to generate projections on population-attributable risk. A preliminary survival analysis of an infant cohort from Malawi indicated that if the hemoglobin decreases by 10 g/L at age 6 mo, the risk of dying becomes 1.72 times higher. Evidence from a number of studies suggests that mortality due to malarial severe anemia is greater than that due to iron-deficiency anemia. Data are scarce on anemia and child mortality from non-malarious regions. Primary prevention of iron-deficiency anemia and malaria in young children could have substantive effects on reducing child mortality from severe anemia in children living in malarious areas.

Adolescent↗
PubMed2000

Micronutrient and iron supplementation and effective antimalarial treatment synergistically improve childhood anaemia.

The control of childhood anaemia in malaria holoendemic areas is a major public health challenge for which an optimal strategy remains to be determined. Malaria prevention may compromise the development of partial immunity. Regular micronutrient supplementation has been suggested as an alternative but its effectiveness remains unsettled. We therefore conducted a randomised placebo-controlled intervention trial with 207 Tanzanian children aged 5 months to 3 years on the efficacy of supervised supplementation of low-dose micronutrients including iron (Poly Vi-Sol with iron) three times per week, with an average attendance of >/= 90%. The mean haemoglobin (Hb) level increased by 8 g/l more in children on supplement (95% CI 3-12) during the 5-month study. All age groups benefited from the intervention including severely anaemic subjects. The mean erythrocyte cell volume (MCV) increased but Hb in children >/= 24 months improved independently of MCV and no relation was found with hookworm infection. The data therefore suggest that micronutrients other than iron also contributed to Hb improvement. In the supplement group of children who had received sulfadoxine-pyrimethamine (SP) treatment, the mean Hb level increased synergistically by 22 g/l (95% CI 13-30) compared to 7 g/l (95% CI 3-10) in those without such treatment. Supplementation did not affect malaria incidence. In conclusion, micronutrient supplementation improves childhood anaemia in malaria holoendemic areas and this effect is synergistically enhanced by temporary clearance of parasitaemia.

Anemia, Iron-Deficiency↗
PubMed1999

Current clinical efficacy of chloroquine for the treatment of Plasmodium falciparum infections in urban Dar es Salaam, United Republic of Tanzania.

Reported is the use of a 14-day WHO protocol, which takes into account the clinical, parasitological and haematological responses to antimalarial drugs, to determine the efficacy of chloroquine in the treatment of uncomplicated malaria in young children (n = 200) in urban Dar es Salaam. Chloroquine failure was found in 43% of the children. Of these, 12.5% were considered to be early treatment failures and were given a single dose of sulfadoxine-pyrimethamine. Fever subsided in all children treated with sulfadoxine-pyrimethamine and there were no parasitological failures. In addition, children treated with sulfadoxine-pyrimethamine because of early treatment failure with chloroquine had better haematological recovery than the chloroquine-sensitive group. It is concluded that chloroquine can no longer be considered an effective therapy for P. falciparum malaria in young children in Dar es Salaam.

Age Factors↗
PubMed1997

Community based studies on childhood mortality in a malaria holoendemic area on the Tanzanian coast.

Demographic surveillance of children under 5 years of age was undertaken over a 2 year period in a rural area of coastal Tanzania where holoendemic malaria conditions exist. The mean annual entomological innoculation rate (EIR) during the period under study was 234 infective bites per person. There were 192 deaths in children and 1130 live births during the 2 years. Of these, 148 were infant deaths giving an infant mortality rate of 131/1000 live births (95% CI 101, 154). There were 44 deaths in children 1-4 years of age and the overall child mortality rate was 10/1000 (95% CI 6.1, 14.3). Using verbal autopsy questionnaires, 56% of the deaths under 4 years were tentatively attributed to malaria.

Autopsy↗
PubMed1997

Social and cultural factors affecting rates of regular retreatment of mosquito nets with insecticide in Bagamoyo District, Tanzania.

Insecticide-treated mosquito nets have an impact on mortality and morbidity in young children under controlled conditions. When integrated into larger control programs, there is the danger that rates of regular retreatment of the nets with insecticide will drop, greatly limiting their effectiveness as a public health intervention. In Bagamoyo District, Tanzania, rates of retreatment dropped significantly when payment for the insecticide was introduced. A series of neighbourhood (hamlet) meetings were held in all study villages to discuss people's concerns about the insecticide and ways to increase rates of retreatment. Although changes were made in the procedure for retreatment, rates of retreatment remained lower than expected and showed marked variation within as well as between villages. We then conducted unstructured key informant interviews as well as informal discussions in a village with strong variation between different sectors of the villages in rates of retreatment. While logistical problems were most frequently cited as reasons not to bring nets for retreatment, political and social divisions within the community provided a better explanation. This is borne out by the low response to rearrangements in logistics which made retreating the nets significantly easier for households, and the higher response when changes were made in the channels of communication as well as the logistic features. It is clearly more difficult for villagers to appreciate the benefits of the insecticide than those of the nets. Great emphasis needs to be placed on the insecticide and its beneficial effects from the outset for any large-scale programme to be sustainable.

Bedding and Linens↗
PubMed1997

Mosques against malaria.

In a community-based malaria control project covering a predominantly Muslim population in the United Republic of Tanzania, difficulty was encountered in motivating people to have their mosquito nets reimpregnated with insecticide at six-monthly intervals. Education on this subject was therefore provided in mosques during Friday noon prayers. People who attended these services considered them an appropriate forum for discussing health concerns and viewed them as a credible source of information.

Adult↗
PubMed1996

Local terminology for febrile illnesses in Bagamoyo District, Tanzania and its impact on the design of a community-based malaria control programme.

This paper reviews results of several ethnographic studies that have examined the issue of local terminology for malaria in Africa, then presents findings from an on-going study in Bagamoyo District, Tanzania. The study used a mixture of qualitative and quantitative interview methods to examine local perceptions of malaria and malaria treatment practices. Although the local term homa ya malaria or malaria fever appeared on the surface to correspond closely with the biomedical term malaria, significant and often subtle differences were found between the two terms. Of perhaps greatest importance, common consequences of malaria in endemic areas such as cerebral malaria in young children, severe anaemia and malaria in pregnancy were not connected with homa ya malaria by many people. A set of guidelines are described that were used to determine how best to promote acceptance and use of insecticide-impregnated mosquito nets, given these results. It is demonstrated that the position of the term used to denote malaria in the local taxonomy of febrile illnesses has important implications for the design of health education interventions.

Adolescent↗
PubMed1996

Treatment practices for degedege, a locally recognized febrile illness, and implications for strategies to decrease mortality from severe malaria in Bagamoyo District, Tanzania.

Malaria remains one of the chief causes of mortality among young children in sub-Saharan Africa. Verbal autopsies for cases of childhood mortality in Bagamoyo District, Tanzania demonstrated that degedege, a locally defined illness of children characterized by fever and convulsions, is frequently treated by traditional healers. To investigate this further, an ethnographic study was carried out in one village that included in-depth interviews with 14 traditional healers and 3 focus groups with parents. Parents and traditional healers were unanimous in their conviction that degedege requires traditional treatments, at least initially, and that these treatments are effective. While traditional healers do refer cases that are not improving to the District Hospital, this frequently occurs late in the course of the illness, after one or more stages of traditional treatments. The prognosis will thus be poor for those children who are suffering from severe malaria. Consideration should be given to enlisting the support of traditional healers in efforts to improve treatment for severe malaria, including teaching them how to distinguish febrile convulsions from cases of severe malaria.

Adult↗
PubMed1995

Anaemia and Plasmodium falciparum infections among young children in an holoendemic area, Bagamoyo, Tanzania.

Although the aetiology of anaemia in tropical areas is multifactorial, Plasmodium falciparum malaria is commonly associated with anaemia in children living in holoendemic malaria areas. Such an association was examined in a population based study of 338 children 6 to 40 months of age living in the Bagamoyo area of Tanzania. Stepwise regression analysis showed that fever and parasitaemia were effective in predicting anaemia and that the anaemic condition was age dependent. The majority of the children were iron deficient, followed by normochromic macrocytic anaemias. There was strong evidence in this age group that the anaemia was associated with malaria and not geohelminth infection. The importance of malaria and anaemia as a cause of childhood morbidity in Africa is discussed. This condition has taken on new significance with the realization that blood transfusions commonly used to treat severe anaemia are a major vehicle for Human Immunodeficiency Virus (HIV) transmission.

Age Factors↗
PubMed1995

Efficacy of oral and intravenous artesunate in male Tanzanian adults with Plasmodium falciparum malaria and in vitro susceptibility to artemisinin, chloroquine, and mefloquine.

The clinical efficacy of oral and intravenous (iv) artesunate was compared in an open randomized trial in 50 male adult patients with uncomplicated Plasmodium falciparum malaria in Kibaha, Tanzania. Oral artesunate treatment was started with 2 x 50 mg initially followed by 50 mg 12 hr later and then 50 mg twice a day for four days (total dose = 550 mg or 9.6 mg/kg). Intravenous artesunate administration began with 2 x 0.8 mg/kg initially followed by 0.8 mg/kg 12 hr later and then 0.8 mg/kg twice a day for four days (total dose = 8.8 mg/kg). The mean +/- SD parasite clearance times (PCTs) were nearly identical at 23.4 +/- 5.9 hr and 24.2 +/- 7.2 hr after oral and iv administration, respectively. Mean +/- SD fever subsidence times (FSTs) were also similar at 18.7 +/- 8.3 hr and 21.0 +/- 4.8 hr, respectively. All patients remained negative for P. falciparum for at least 14 days. Recrudescence/reinfection occurred between days 21 and 28 in five of 25 patients (20%) after oral treatment and in four of 25 patients (16%) after iv treatment. The mean erythrocyte count and hemoglobin concentration were slightly reduced after iv treatment but remained in the normal range. Otherwise, there was no change in blood biochemistry, hematology, and electrocardiograms monitored prior to and during the last dose. It is concluded that treatment with oral and iv artesunate was equally efficacious and well tolerated. A 24-hr in vitro susceptibility test of P. falciparum to artemisinin, chloroquine, and mefloquine was performed in samples from all patients. The three compounds exhibited 100% inhibition with the exception of three isolates, which showed chloroquine resistance. Parameter estimates of a sigmoid Emax model (drug concentration at which 50% of the growth inhibition occurs [EC50]), the sigmoidicity factor s and EC95 fitted to the growth inhibition data differed between compounds and isolates, indicating different sensitivity of P. falciparum isolates. There was no correlation between artemisinin and mefloquine EC50 values, while artemisinin and chloroquine EC50 values showed weak correlation (r2 = 0.223, P = 0.006). There was no correlation between parameters describing clinical outcome (the PCT, the time needed for reduction of the parasite density to 50% and 95% of the initial parasitemia, and the FST) and those describing in vitro susceptibility.

Administration, Oral↗
PubMed1995

Changes in malaria associated morbidity in children using insecticide treated mosquito nets in the Bagamoyo district of coastal Tanzania.

A community based malaria control intervention using insecticide treated mosquito nets (IMN) has been implemented and tested in 13 villages of the Yombo Division, Bagamoyo District in the Coastal Region, Tanzania, an area holoendemic for P. falciparum malaria. Following extensive sociological research into local perceptions of malaria, the programme was implemented. It wa decided by consensus that village mosquito net committees would be the appropriate local level implementors. These were formed and provided with IMN's which were sold to villagers at subsidised cost. The income was invested for use by the committees for sustaining the activity. Use patterns were determined and high coverages were obtained among the community, particularly after promotions e.g. plays, school meetings etc. Malaria morbidity was measured among children 6-40 months of age in 7 index villages prior to the intervention in 1992 and in a comparison study between 3 villages using nets and 4 villages not using nets in 1993. Examination of the 7 cohorts of children was done from June to October each year covering the period of most severe transmission. The children using nets showed marked improvement in several malariometric indices. Following an initial clearance of parasitaemia with sulphadoxine/pyrimethamine, when compared with unprotected children, those with nets were slower to become re-infected (Relative Risk 0.45), had lower parasitaemias and showed marked improvement in anaemia (RR 0.47). Use of IMN's produced a 54% reduction in the prevalence of anaemia among young children. Attempts are being made to ensure that the programme is locally sustained.

Anemia↗
PubMed1994

Chloroquine resistant Plasmodium falciparum in coastal Tanzania. A challenge to the continued strategy of village based chemotherapy for malaria control.

An in vivo study to assess Plasmodium falciparum sensitivity to chloroquine was conducted in two villages of the Bagamoyo District, Tanzania in December 1992. The WHO standard field test (7 days) and the extended test (28 days) were carried out on symptom free children. The presence of chloroquine resistance was confirmed with 59% of infections being found resistant. Fifty-three percent were RI, 2% were at RII and 4% at RIII levels of resistance. Dosage was 25 mg/kg chloroquine base delivered over three days.

Animals↗
PubMed1989

Local anaesthetic cream for the alleviation of pain during venepuncture in Tanzanian schoolchildren.

The analgesic effect and the usefulness of EMLA cream 5% in connection with venous blood-sampling was investigated in 42 Tanzanian schoolchildren. Approximately 2.5 g EMLA was applied to the right cubital fossa for a minimum of 120 min. The analgesic effect was pronounced--93% of the venepunctures were pain-free and no child experienced severe pain. No adverse reactions were observed and the children could continue normal school work during the application time.

Adolescent↗