Risk factors for anaemia in schoolchildren in Tanga Region, Tanzania.

Anaemia is one of the major public health problems affecting more than half of school children along the coast in Tanzania. Due to the multiplicity of its causes it sometimes becomes difficult to find appropriate intervention measures. In order to assist schools in implementing appropriate public health measures for anaemia in Tanga Region of Tanzania risk factors were investigated in school children. A total of 845 schoolchildren age 7-14 years were randomly selected in a cross-sectional survey conducted in 20 randomly selected schools for inclusion in the investigations. Socio-economic, environmental and biological data were collected, as well as academic information, health care and feeding practices. Diagnosis of anaemia was based on haemoglobin concentration below 115 g/L determined by HemoCue meter. Serum Retinol was determined by High performance liquid chromatography and serum ferritin by an Enzyme linked immunosorbent assay. Urine from each child was tested for blood using a haematest reagent strip and those testing positive were examined microscopically by filtration method for Schistosoma haematobium ova. A faecal sample collected from them was also examined microscopically for ova and larvae of intestinal worms. To analyse variables associated with anaemia a stepwise multiple regression model was used. The prevalence of anaemia was 79.6%. Micronutrient deficiencies were highly prevalent. Iron deficiency (SF <20 microg/dl) was affecting 33%, vitamin A deficiency (SR < 20 microg/dL) 31.9% and 25% of the children had mild iodine deficiency (UIE < 20 microg/L). Intestinal helminths were also highly prevalent; 68% of children had hookworm and 54% had urinary schistosomiasis. Inadequate diet was a feature in >50% of children. About 10% of households had no latrines and multiple infection rank score was high especially in older age children. The risk of having anaemia was two times higher in children with iron deficiency (RR=2.1) and 49% higher in those with vitamin A deficiency. These deficiencies correlated significantly with the anaemia (P<0.05). Vitamin A deficiency and infections with hookworm and schistosomiasis were the most significant factors predicting for anaemia (r=0.318 and r2=0.101). We therefore conclude that high prevalence of infections and nutritional deficiencies are important risk factors for anaemia in this community. The high attributable fractions for hookworm, schistosomiasis, iron deficiency and vitamin A confirms that these are significant risk factors to be considered when designing public health measures for anaemia prevention in this community.

Anthelmintic treatment improves the hemoglobin and serum ferritin concentrations of Tanzanian schoolchildren.

To investigate the relationships between helminth infections and iron status among school-aged children, 1,115 Tanzanian children in grades 2 through 5 were randomly assigned to treatment or control groups. The children in the treatment group were screened for infection with Schistosoma haematobium and hookworm at baseline, 3 months, and 15 months; infected children were given albendazole against hookworm and praziquantel against schistosomiasis. The control group received a placebo and did not undergo parasitological screening until 15 months after the baseline. Hematological variables were compared between the treatment and control groups. The main results were, first, that the hemoglobin concentration significantly improved after treatment for hookworm (p < .001) by 9.3 g/L in children treated for hookworm only and by 8.8 g/L in children treated for hookworm and schistosomiasis. The ferritin concentration also improved in children treated for schistosomiasis (p = .001) or hookworm (p = .019). Second, a longitudinal analysis of the data from the children in the control group showed that hookworm and schistosomiasis loads were negatively associated with hemoglobin and ferritin concentrations. Moreover, ferritin concentrations increased as C-reactive protein levels increased. Overall, the results showed that anthelmintic treatment is a useful tool for reducing anemia in areas with high hookworm and schistosomiasis endemicity. The empirical relationship between ferritin and C-reactive protein indicated that simple procedures for adjusting cutoff points for the use of ferritin as an indicator of low iron stores were unlikely to be useful in this population.

Predicting the distribution of urinary schistosomiasis in Tanzania using satellite sensor data.

In this paper, remotely sensed (RS) satellite sensor environmental data, using logistic regression, are used to develop prediction maps of the probability of having infection prevalence exceeding 50%, and warranting mass treatment according to World Health Organization (WHO) guidelines. The model was developed using data from one area of coastal Tanzania and validated with independent data from different areas of the country. Receiver operating characteristic (ROC) analysis was used to evaluate the model's predictive performance. The model allows reasonable discrimination between high and low prevalence schools, at least within those geographical areas in which they were originally developed, and performs reasonably well in other coastal areas, but performs poorly by comparison in the Great Lakes area of Tanzania. These results may be explained by reference to an ecological zone map based on RS-derived environmental data. This map suggests that areas where the model reliably predicts a high prevalence of schistosomiasis fall within the same ecological zone, which has common intermediate-host snail species responsible for transmission. By contrast, the model's performance is poor near Lake Victoria, which is in a different ecological zone with different snail species. The ecological map can potentially define a template for those areas where existing models can be applied, and highlight areas where further data and models are required. The developed model was then used to provide estimates of the number of schoolchildren at risk of high prevalence and associated programme costs.

Community perception of school-based delivery of anthelmintics in Ghana and Tanzania.

This paper presents the results of an evaluation of community perception of two large-scale, government-run, school-based health programmes delivering anthelmintic drugs to primary school children, in Ghana (80 442 children in 577 schools) and Tanzania (110 000 children in 352 schools). Most teachers (96% in Ghana and 98% in Tanzania) were positive about their role in the programme, including administration of anthelmintic drugs, and parents and children fully accepted their taking on this role. The benefits of the programme were apparent to teachers, parents and children in terms of improved health and well-being of the children. Over 90% of parents in both Ghana and Tanzania indicated a willingness to pay for the continuation of drug treatment. The evaluation also highlighted areas that are critical to programme effectiveness, such as communication between schools and parents, the issue of collaboration between the health and education sectors, parents' perception of the importance of helminth infection as a serious and chronic health problem (compared with more acute and life threatening illnesses such as malaria), and who should pay for treatment of side-effects.

Evaluation of efficacy of school-based anthelmintic treatments against anaemia in children in the United Republic of Tanzania.

OBJECTIVE: To determine the impact of deworming on anaemia as part of a large-scale school-based anthelmintic treatment programme in the Tanga Region of the United Republic of Tanzania. METHODS: Both the reduction in the prevalence of anaemia and the cost per case prevented were taken into consideration. Cross-sectional studies involved parasitological examination and anaemia evaluation before and at 10 months and 15 months after schoolchildren were dewormed. FINDINGS: Baseline studies indicated that the prevalence of anaemia (haemoglobin < 110 g/l) was high (54%) among schoolchildren, particularly those with high intensities of hookworm and schistosomiasis. Attributable fraction analysis suggested that hookworm and schistosomiasis were responsible for 6% and 15% of anaemia cases, respectively. Fifteen months after deworming with albendazole and praziquantel the prevalence of anaemia was reduced by a quarter and that of moderate-to-severe anaemia (haemoglobin <90 g/l) was reduced by nearly a half. The delivery of these anthelmintics through the school system was achieved at the relatively low cost of US$ 1 per treated child. The cost per anaemia case prevented by deworming schoolchildren was in the range US$ 6-8, depending on the haemoglobin threshold used. CONCLUSIONS: The results suggested that deworming programmes should be included in public health strategies for the control of anaemia in schoolchildren where there are high prevalences of hookworm and schistosomiasis.

The impact of weekly iron supplementation on the iron status and growth of adolescent girls in Tanzania.

We evaluated the effect of weekly doses of 400 mg of ferrous sulphate for 4 months on the iron status of adolescent girls in a controlled trial in Tanga, Tanzania. Supplementation led to a significantly greater increase in serum ferritin compared with the control group (+ 15.6 microg/l vs. 8.6 microg/l) (P = 0.002) but there was no significant difference in change in haemoglobin. Children given iron showed a significantly greater weight gain than controls (+ 2.4 kg vs. + 1.4 kg) (P = 0.03). Weekly iron supplementation may be an effective means of increasing iron stores and growth in children vulnerable to iron deficiency.

The health of enrolled and non enrolled children of school age in Tanga, Tanzania.

The health of 227 children enrolled at primary school was compared with that of 214 non enrolled children living in rural Tanga, Tanzania. No consistent difference was observed with respect to prevalence and intensity of parasitic infection (hookworm, T. trichiura, A. lumbricoides, S. haematobium and P. falciparum). Since enrolled children were as commonly and as heavily infected as non enrolled children, treatment of enrolled children would be effective in reducing transmission throughout the total population. Non enrolled children were more stunted (P=0.0001) and wasted (P=0.0001) than enrolled children and also tended to be more anaemic (P=0.080) showing that poor nutrition is not only associated with delayed enrolment but continues to be associated with non enrolment throughout the school age years. Given that treatment has the greatest impact on the most malnourished children, additional measures to extend treatment to non enrolled children would be justified.

The impact of population level deworming on the haemoglobin levels of schoolchildren in Tanga, Tanzania.

The impact of albendazole (400 mg) and praziquantel (40 mg/kg body weight) treatment of schoolchildren was compared with placebo according to the presence of anaemia (haemoglobin concentration < 11. 0 g/dl) and heavy (> 5000 epg) or light (< 5000 epg) hookworm egg load. The study was conducted in rural Tanga. Medication was administered in September 1994 and children were followed-up in January 1995. Overall, anthelminthic treatment reduced the fall in haemoglobin concentration compared with that observed in the placebo group (- 0.11 g/dl vs. - 0.35 g/dl; P = 0.02). Anthelminthic treatment was of greatest benefit to the 9% of children with both anaemia and heavy hookworm egg load (+ 0.67 g/dl vs. - 0.67 g/dl) and was also of significant benefit to the 38% of children with anaemia and light hookworm egg load (+ 0.07 g/dl vs. - 0.21 g/dl). It was of no significant benefit to children who were not anaemic. This study suggests that single-dose anthelminthic treatment distributed in schools in this area achieves haematological benefits in nearly half of children infected with S. haematobium and geohelminths (37% of total population).

Bancroftian filariasis on Pemba Island, Zanzibar, Tanzania: an update on the status in urban and semi-urban communities.

Cross-sectional clinical, parasitological and entomological surveys for bancroftian filariasis were conducted in Konde, Chake Chake and Kengeja, three urban and semiurban communities on Pemba Island, and the results were compared with similar surveys done 15 years earlier. The overall prevalences of clinical manifestations among males aged 15 years or more (n = 614) was remarkably similar to those recorded 15 years earlier: elephantiasis 1.4% in 1975 and 1.1% in 1990; hydrocele, 22.4% and 21.8%, respectively. However, when the communities were compared individually, there was a reduction in the hydrocele prevalence in Konde from 22.4% to 11.5% and an increase in Kengeja from 27.0% to 35.5%. The overall microfilarial prevalence found during night blood surveys of all individuals aged 1 year or more (n = 2687) was 9.7%, compared to 14.2% recorded in 1975. The reduction was most pronounced in Konde. Of 1052 female mosquitoes caught with CDC light traps, 95% were Culex quinquefasciatus and 5% Anopheles gambiae s.l. Infective larvae of Wuchereria bancrofti were found only in the former. The filariasis situation in urban and semiurban communities on Pemba Island appears not to have changed considerably over the last 15 years.

Potential for diagnosis of intestinal nematode infections through antibody detection in saliva.

The present study was the first to investigate the potential of saliva in community diagnosis of the major human intestinal nematode infections, Trichuris trichiura, Ascaris lumbricoides, and the hookworms. Immunoglobulin G (IgG) antibodies specific to parasite antigens were quantified in saliva samples of 187 individuals (all ages) from a St Lucian community, and 120 school-aged children from Tanga region, Tanzania, and relationships with current infection status (determined by numbers of parasite eggs in stool) were examined. For T. trichiura infection, the age relationships of parasite-specific salivary IgG antibodies mirrored those of infection intensity at the community level. Within both areas, children with current T. trichiura infection exhibited significantly higher anti-T. trichiura salivary IgG responses than uninfected children. Similar trends were apparent for A. lumbricoides and hookworm infections, though not to a level of statistical significance. Comparison of mean T. trichiura infection levels and antibody responses in age-matched children from St Lucia and Tanzania suggested that measurement of parasite-specific salivary IgG may have potential as a marker of transmission intensity at the community level.

Clinical efficacy and pharmacokinetics of artemisinin monotherapy and in combination with mefloquine in patients with falciparum malaria.

1. The aim of this study was to assess the pharmacokinetics, clinical efficacy and safety of artemisinin alone and in combination with mefloquine. 2. Thirty-eight adults with symptomatic Plasmodium falciparum malaria were randomly assigned to receive either artemisinin (500 mg single dose followed by another 500 mg on day 1 and then 250 mg twice daily for 4 days) or artemisinin (500 mg single dose followed by 750 mg on day 1 and then 250 mg three times daily for one more day) in co-administration with mefloquine (250 mg three times daily for the first day). All drug administration was by the oral route. Patients were hospitalized at the Kibaha Designated District Hospital, Kibaha, Tanzania, for 6 days and a follow up for 3 weeks was performed. 3. Treatment with the artemisinin/mefloquine combination resulted in a shorter parasite clearance time (PCT) of 24 (22, 27; 95% confidence interval) h vs 31 (27, 36) h and fever subsidence time (FST) of 14 (12, 16) h vs 20 (18, 23) h compared with artemisinin monotherapy. The 95% CI for the difference of the PCT and FST were 1.7, 12 and 3, 10, respectively. Parasites were detected in 7 out of 17 patients (41%) receiving artemisinin monotherapy at the 3rd and 4th week follow up visits. No parasites were detected after the combination therapy. 4. The maximum plasma concentrations (Cmax) were similar after artemisinin monotherapy (615.4 +/- 387.0 ng ml-1) and in combination with mefloquine (851.8 +/- 523.6 ng ml-1). Elimination half-lives (t1/2) were also identical at 2.2 +/- 0.6 h and 2.5 +/- 0.7 h, respectively. However, the AUC values were higher (P < 0.05) after combination therapy (3252 +/- 1873 ng ml-1 h) than after monotherapy (2234 +/- 1502 ng ml-1 h). The oral clearance values were lower (P < 0.05) after combination therapy (195.4 +/- 86.9 l h-1) than after monotherapy (314.3 +/- 189.4 l h-1). PCT and FST normalized to initial parasitaemia correlated with AUC(0, t) (rs = 0.56, P = 0.02, rs = 0.58, P = 0.01, respectively) and with Cmax (rs = 0.62, P = 0.01, rs = 0.68, P = 0.005, respectively) in the artemisinin monotherapy only. 5. One patient on the combination therapy developed a psychiatric condition and two patients on the monotherapy developed skin itch.

Multiple dose pharmacokinetics of oral artemisinin and comparison of its efficacy with that of oral artesunate in falciparum malaria patients.

The study compared the clinical efficacy and safety of oral artemisinin and oral artesunate as well as artemisinin pharmacokinetics during and after resolution of falciparum malaria. Forty adults with symptomatic falciparum malaria were allocated at random to treatment with either oral artemisinin (500 mg single dose on day 1 followed by 250 mg twice daily for 4 d and then another 500 mg single dose on day 6) or with oral artesunate (100 mg single dose on day 1 followed by 50 mg twice daily for 5 d). Patients were admitted to hospital at the Kibaha Designated District Hospital, Kibaha, Tanzania for the duration of treatment. The patients were seen once weekly for 3 more weeks. The time to parasite clearance (PCT) after oral artesunate (26.4 +/- 3.6 h) was shorter (P = 0.002) than after artemisinin (31 +/- 3.6 h). The fever subsidence time (FST) after oral artesunate (18.9 +/- 4.0 h) was also shorter (P = 0.04) than after artemisinin (21.8 +/- 4.6 h). Parasites were detected in 4 (20%) and 7 (35%) patients after completing treatment with artesunate and artemisinin respectively. In these patients the parasitaemia reappeared at the 3rd or 4th week of follow-up. Standard haematology, blood biochemistry and urinalysis, performed before drug intake and again on days 6 and 14, were normal. No clinical abnormality was observed during the study period. Artemisinin plasma concentrations, determined by high performance liquid chromatography with post-column derivatization and detection by ultraviolet light, were followed up to 8 h after drug administration on days 1 and 6. Artemisinin absorption was rapid, the maximum plasma concentrations (Cmax) being attained at about 3 h. Artemisinin areas under the plasma concentration-time curve (AUC) and the Cmax values were about 6 times higher after the first dose on day 1 than on day 6. This decrease in artemisinin plasma concentration is suggestive of an increase in metabolic capacity due to pronounced autoinduction.

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.

Malaria parasites and chloroquine concentrations in Tanzanian schoolchildren.

Subtherapeutic doses of chloroquine (CQ) are considered to promote development of Plasmodium falciparum resistance but little is actually known about the drug levels in the population in endemic areas. We have therefore measured blood concentrations of CQ in Tanzanian schoolchildren and related these to parasite microscopy. A total of 163 children (median age 11 years) in a suburb outside Dar es Salaam were followed during four weeks. Thick and thin blood films were obtained once weekly. Parasites were counted in 200 visual fields. CQ and desethyl-chloroquine (DECQ) were determined with HPLC in 100 microliters of capillary blood. During the study P. falciparum trophozoites were detected in a mean of 78% of the children, P. falciparum gametocytes in 7.7% and P. malariae parasites in a mean of 13%. The cumulative prevalence of P. falciparum trophozoites and P. malariae parasites was 96% and 28% respectively. On day 0 and day 28, CQ was found in 78% and 80% of the children and DECQ in 21% and 31% of them. A total of 19% of all children had a verified CQ intake during the study and 35% had probably taken CQ. With a few exceptions (9% had CQ concentrations > 100 nmol/l) drug levels were not sufficient to affect parasites with a reduced CQ susceptibility but could possibly promote development of resistance by eradicating the most susceptibility part of the parasite population.

Standard and reduced doses of mefloquine for treatment of Plasmodium falciparum in Tanzania: whole blood concentrations in relation to adverse reactions, in vivo response, and in vitro susceptibility.

Fifty-three asymptomatic Tanzanian school children with 400-31,000 asexual Plasmodium falciparum parasites/microliter of blood were given standard, one-half, one-quarter, or one-eighth of the recommended mefloquine treatment dose of 25 mg base/kg body weight. Mefloquine and main metabolite concentrations were determined in 100 microliters of capillary blood using a high performance liquid chromatographic method. In the standard, one-half, and one-quarter dose groups, all children cleared the parasites within three days after treatment. Reappearance was noted in one of the children in the one-quarter dose group during 49-56 days of followup. Among the children given one-eighth of a dose, two had an RII response and four had an RI response with early recrudescence. All 24-hour in vitro micro-tests (n = 30) showed full susceptibility for mefloquine. Adverse gastrointestinal reactions were reported by eight children on the first day after treatment, four of whom had been given a standard dose. These children had higher mefloquine concentrations one day after treatment than the other children in this group (P less than 0.05). In the standard dose group (n = 13), the area under the curve of capillary whole blood concentrations of mefloquine versus time was 52.4-112.1 mumol/liter x days. The highest concentration on day 1 was 2.75-7.20 mumol/liter and the median terminal half-life was 17.4 days. The highest concentrations of the main metabolite were observed 1-2 weeks after treatment and the median half-life was 18.9 days. The concentrations in the other groups were approximately proportional to those in the standard dose group both for mefloquine and the metabolite.(ABSTRACT TRUNCATED AT 250 WORDS)

Chloroquine-induced pruritus: its impact on chloroquine utilization in malaria control in Dar es Salaam.

To confirm reports that chloroquine-induced pruritus might have a negative impact on chloroquine utilization on malaria control in Dar es Salaam, a precoded questionnaire was administered to 300 malaria patients and the respondents were then followed up at their homes during the period of their malaria treatment. It was found that 45% of the study population had suffered from chloroquine-induced pruritus at some time in their life and 27% complained of it during the study. Chloroquine-induced pruritus was found to have a significant negative impact on chloroquine utilization on malaria control in Dar es Salaam, Tanzania (P less than 0.001). The defaulting rate attributable to chloroquine-induced pruritus was 64%. The high defaulting rate (91%) among the patients with chloroquine-induced pruritus is suspected to be among the factors that contribute to the emergence and spread of resistant malaria parasites in Dar es Salaam. However, studies are needed to confirm this point. Studies are also needed to determine if there may be familial predisposition to chloroquine-induced pruritus as hypothesized in this study.

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.