Atovaquone and proguanil versus pyrimethamine/sulfadoxine for the treatment of acute falciparum malaria in Zambia.

Atovaquone and proguanil hydrochloride are blood schizonticides that demonstrate in vitro synergy against drug-resistant strains of Plasmodium falciparum. When coadministered, they may therefore be effective for the treatment of malaria in regions where there is known or suspected drug resistance. In an open-label, randomized, parallel-group, clinical trial conducted in Zambia, 163 patients (age range, 14 to 54 years) with acute P falciparum malaria were randomly assigned to receive treatment with atovaquone and proguanil hydrochloride (1000 and 400 mg, respectively, administered orally at 24-hour intervals for 3 doses; n = 82) or pyrimethamine/sulfadoxine (75/1500 mg administered orally as a single dose; n = 81). Efficacy was assessed by cure rate (the percentage of patients in whom parasitemia was eliminated and did not recur during 28 days of follow-up), parasite clearance time (PCT), and fever clearance time (FCT). Safety was determined by sequential clinical and laboratory assessments over 28 days. Cure rates did not differ significantly between patients treated with atovaquone and proguanil (100%) and those treated with pyrimethamine/sulfadoxine (98.8%). Patients in the atovaquone and proguanil group had a significantly shorter FCT than patients in the pyrimethamine/sulfadoxine group (mean, 30.4 vs 44.9 hours; P < 0.05) but a longer PCT (mean, 64.0 vs 51.4 hours; P < 0.05). Both treatments were well tolerated; adverse events and laboratory abnormalities were typical of those normally observed in patients with malaria. In this study, the combination of atovaquone and proguanil was equally effective and as well tolerated as pyrimethamine/sulfadoxine for the treatment of acute, uncomplicated, drug-resistant falciparum malaria in Zambia.

A randomized, double-blind, placebo-controlled field trial to determine the efficacy and safety of Malarone (atovaquone/proguanil) for the prophylaxis of malaria in Zambia.

Malaria poses a major health risk to people who are exposed to infection in malaria-endemic areas. A randomized, double-blind, placebo-controlled study was conducted to determine the efficacy and safety of Malarone (250 mg of atovaquone/100 mg of proguanil hydrochloride per tablet) for the chemoprophylaxis of Plasmodium falciparum malaria in Zambia. Adult volunteers received a three-day treatment course of Malarone to eliminate pre-existing parasitemia and were then immediately randomized to treatment with either one Malarone tablet daily (n = 136), or one placebo tablet daily (n = 138) for at least 10 weeks. Malaria blood smears were prepared on a weekly basis and a failure of chemoprophylaxis was defined as any subject who had a positive blood smear, or who withdrew from the study due to a treatment-related adverse event. The prophylaxis success rates in the Malarone and placebo groups were 98% and 63%, respectively (P < 0.001). The most commonly reported adverse events with at least a possible causal relationship to study medication were headache and abdominal pain, which occurred with a higher incidence in the placebo group. No subjects were withdrawn from the study due to a treatment-related adverse event. Thus, Malarone appears to have an excellent safety and efficacy profile for the chemoprophylaxis of P. falciparum infection.

Atovaquone and proguanil hydrochloride for prophylaxis of malaria.

BACKGROUND: The spread of drug-resistant malaria and appreciation of side effects associated with existing antimalarial drugs emphasize the need for new drugs to prevent malaria. The combination of atovaquone and proguanil hydrochloride was previously shown to be safe and highly effective for treatment of malaria, including multi-drug-resistant Plasmodium falciparum. METHODS: We reviewed results of clinical trials that evaluated either a fixed-dose combination of atovaquone and proguanil hydrochloride for malaria prophylaxis or atovaquone alone for causal prophylactic activity against P. falciparum. RESULTS: In three placebo-controlled trials, 331 subjects received 250 mg atovaquone and 100 mg proguanil hydrochloride (or an equivalent dose based on body weight in children) once daily for 10 to 12 weeks. The overall efficacy for preventing parasitemia was 98%. Among 175 nonimmune volunteers taking the same dose of atovaquone/proguanil once daily for 10 weeks while temporarily residing in a malaria-endemic area, malaria developed in one patient who was noncompliant with therapy. Results of volunteer challenge studies indicate that both atovaquone and proguanil have causal prophylactic activity directed against the liver stages of P. falciparum. Adverse events occurred with similar or lower frequencies in subjects treated with atovaquone/proguanil compared to placebo. Less than 1% of patients discontinued from these studies due to a treatment-related adverse event. CONCLUSION: A fixed-dose combination of atovaquone and proguanil hydrocloride is a promising new alternative for malaria prophylaxis.

Effect of human immigration on the age distribution of schistosome infections in Siavonga community, Lake Kariba, Zambia.

A study on the distribution of schistosomiasis in the community at Siavonga revealed Schistosoma haematobium infection in 35.5% of 338 subjects and a geometric mean egg count (GMEC) and (S.D.) of 13.7 (7.2) eggs/10 ml urine. The prevalence of S. mansoni infection among 323 subjects was 60.1%, with a GMEC of 336.8 (4.8) eggs/g stool. Among the infected, 69.5% carried both schistosome species. Although prevalence of infection with either species was highest in those aged 10-14 years, high prevalences of infection were found in older age groups and egg intensities were uniformly distributed throughout all age-groups. The observed diversion from the typically age-dependent distribution of schistosome infections probably reflects exposure to infection relatively late in life, as the result of immigration from non-endemic areas.

Maternal human immunodeficiency virus infection and pregnancy outcome.

OBJECTIVE: A longitudinal study to determine the natural history of HIV-1 infection in pregnancy, infancy and early childhood was carried out in Ndola, Zambia. DESIGN: Prospective study. SETTING: Kabushi and Chifubu clinics. SUBJECTS: A total of 965 women attending antenatal care were screened for anti-HIV antibodies using the Welcozyme test. All reactive sera were confirmed by Western Blot. One hundred and fifty seropositive pregnant women (cases) with their age and parity matched pregnant control (seronegative) were recruited into the study. They were followed up through delivery. MAIN OUTCOME MEASURE: personal characteristics, socio-economic and other risk factors. RESULTS: The prevalence of anti HIV-1 antibodies among the 965 women was 15.5pc. Results of baseline data between the two groups of women indicate significant differences (p < 0.05) in the following variables; marital status, outcome of last pregnancy, whether last child is still alive, history of herpes zoster, lymphadenopathy, dermatitis, oral thrush and mean haemoglobin level. There were no differences in the incidence of abortions, stillbirths and neonatal deaths. However, the mean birth weight of babies born out of seropositive women was significantly lower than babies of seronegative women. CONCLUSION: It is concluded that HIV-1 infection in pregnancy is associated with low birth weight.

PIP: Data on 130 HIV-1 infected pregnant women were compared with data on 150 HIV-1 negative pregnant women to determine the effect of HIV-1 infection on pregnancy outcomes. All the women were recruited while seeking prenatal services at Chifubu and Kabushi clinics in Ndola, Zambia, during 1991-1993. None of the HIV-1 infected women had AIDS. The HIV- 1 prevalence rate for the recruited pregnant women was 15.5%. The socioeconomic characteristics of the women in both suburbs were similar. Yet, pregnant women at Chifubu were more likely to be HIV-1 positive than those at Kabushi (p 0.001). The proximity to the border with Zaire and the higher inward and outward migration rates in Chifubu may contribute to the higher HIV-1 prevalence rate in Chifubu. HIV-1 infected women were more likely than controls to have a history of Herpes zoster, cervical lymphadenopathy, axillary lymphadenopathy, skin rash, and oral thrush (p 0.05). They were less likely than controls to be married, to have the outcome of their last birth be a live birth, and to have their last child still be alive (p = 0.01). HIV-1 pregnant women had a lower hemoglobin level and smaller newborns than controls (10.3 vs. 10.9 g % and 2.76 vs. 3.03 kg, respectively; p 0.03). When the researchers controlled for gestation, there was no difference in mean birth weights between the groups. Both groups had similar perinatal mortality outcomes (1 stillbirth each and 2 neonatal deaths each). The most significant finding is that HIV-1 infection in pregnancy contributes to low birth weight.

The vitamin A status of Zambian children attending an under five clinic as evaluated by the modified relative dose response (MRDR) test.

The vitamin A status of 87 children, 7-29 months of age, who were randomly selected from attendees at a pediatric clinic in Ndola, Zambia, were evaluated by the modified relative dose response (MRDR) test. By using a MRDR ratio cut-off point of 0.06, 78% of the children had inadequate vitamin A status. Both male and female children were equally affected. Of those with inadequate vitamin A status, 82% were between 7-19 months of age. A significant inverse relationship (p < 0.005) existed between vitamin A inadequacy and Z scores for height for age, weight for age and weight for height. Children with lower Z scores showed a better vitamin A status in comparison to those with a higher Z score. This unexpected relationship is probably due to an increased demand for vitamin A in children with a higher weight and rapid growth rate. Serum vitamin A values correlated poorly with MRDR values except at extreme ends of the distribution. Although clinical vitamin A deficiency is relatively infrequent in Zambia, we conclude that the vitamin A status of our children nonetheless needs to be improved.

A community-based randomized trial of praziquantel to control schistosomiasis morbidity in schoolchildren in Zambia.

A community-based, double-blind, randomized trial of praziquantel was carried out in an area of Zambia endemic for schistosomiasis. The aim of the study was to assess the impact of the treatment on Schistosoma mansoni morbidity. A total of 377 infected children, aged seven to 19 years, was randomized into two groups: one of 190 (group A) and one of 187 (group B). All children were treated with 40 mg praziquantel/kg at the start of the study. Six months later, the children in group A were re-treated with the same dose of praziquantel, while the children in group B were given placebos. All children were followed up three, six and 12 months after the initial treatment, morbidity being clinically evaluated at the six- and 12-month follow-ups. The results show that, in both groups of children, there were significant reductions in splenomegaly, hepatomegaly, and subjective symptoms of morbidity six and 12 months after initial treatment. However, there were no significant differences, between the two groups, in the prevalences of these symptoms of morbidity. It therefore appears that once-yearly treatment of children, in this and similar endemic areas, is sufficient to reduce schistosomiasis morbidity to, and maintain it at, a tolerable level.

The distribution of Schistosoma haematobium in the Isoka district, Zambia; and a possible strategy for its control.

The distribution of schools prevalent for Schistosoma haematobium in the Isoka district, Zambia was estimated by examining haematuria in the urine of the pupils found in Grades Three, Four or Five using reagent sticks. Thirty three (57 pc) schools had prevalence rates of 25 pc or more. The distribution of S. haematobium was patchy with significant differences in prevalence rates between some areas only short distances apart. A sociological study in the same schools showed that 68 (97 pc) head/senior teachers associated the disease with blood in urine and agreed to perform a reagent stick test on their pupils' urine. Thirty five (50 pc) of these respondents considered S. haematobium infection as a major problem and 66 (94 pc) of them were ready to administer a diagnostic questionnaire to their pupils in a study to identify high risk schools for S. haematobium. We conclude that the identification of high risk schools in the Isoka district, Zambia, using a diagnostic questionnaire and reagent stick testing by teachers, should proceed as a step to controlling S. haematobium infection in the district.

Prevalence and distribution of trachoma in the Luapula Valley, Zambia.

A cross-sectional population based study was done to provide information on the extent to which xerophthalmia and trachoma contribute to blindness in the valley population. A total of 4271 children aged under 6 years and 2503 individuals aged 6 years and more were examined. The overall prevalence of trachoma for those under 6 years of age was 17.6%, the majority of which were graded as follicular trachomatous inflammation. The trend in age specific prevalence was highly significant (x2 = 160.6, p = 0.000). Prevalence by sex was also significantly different (z = 2.0, P less than 0.05). Among those aged greater or equal to 6 years, 331 (13.2%) had trachoma. Complications of trachoma (trichiasis and opacities) were common in this age group compared to those under 6 years of age. There were no differences in prevalence by district either in children or adults. This survey provides some of the first reliable data on prevalence of trachoma in this population and that it is a significant public health problem in the valley. The magnitude of severe complications from trachoma is low in this community, this may mean that the trachoma seen is the non-blinding type. We conclude that trachoma is of public health importance in the valley but is not a major cause of blindness.

PIP: A cross-sectional, population-based study was undertaken to provide information on the extent to which xerophthalmia and trachoma contribute to blindness in the valley population. A total of 4271 children aged under 6 and 2503 individuals ages 6 and up were examined. The overall prevalence of trachoma for those under age 6 was 17.6%, the majority of which were graded as follicular trachomatous inflammation. The trend in age-specific prevalence was highly significant (chi squared=160.6, p=0.000). Prevalence by sex was also significantly different (z=2.0, p0.05). Among those ages or= 6 years, 331 (13.2%) had trachoma. Complications of trachoma (trichiasis and opacities) were common in this age group compared with those under age 6. There were no differences in prevalence by district in either adults or children. This survey provides some of the 1st reliable data on prevalence of trachoma in this population and that is a significant public health problem in the valley. The magnitude of severe complications from trachoma is low in this community and this may mean that the trachoma seen is the nonblinding type. The authors conclude that trachoma is a public health issue in the valley but not a major cause of blindness.

Prevalence of blindness and visual impairment in the Luapula Valley, Zambia.

A community based cross-sectional study on the prevalence and causes of blindness and visual impairment was carried out between August and December 1985 in the Luapula Valley. The study population consisted of 2503 villagers aged 6 years and above. Visual acuity was done on every participant whereas slit-lamp examination and ophthalmoscopy were done on selected individuals when indicated. The overall prevalence of monocular and bilateral blindness was 6.9% and 3.6% respectively. Cataracts and corneal opacities were the most common causes of visual loss in those aged 50 years and above. We conclude that blindness is an important public health problem in this valley and that this data provides a background that can be used to evaluate blindness prevention programmes that will be implemented in the future.

A three year follow-up of chemotherapy with praziquantel in a rural Zambian community endemic for schistosomiasis mansoni.

A resurvey for schistosomiasis mansoni was carried out in a community 2 years after chemotherapy with praziquantel was stopped. Data on infection status, morbidity, subjective symptoms, and liver and spleen enlargement were collected from participants. Results show that prevalence of Schistosoma mansoni infection and subjective symptoms of morbidity have returned to pretreatment levels. However, the population mean egg output remained low. Liver and spleen sizes in individuals who received treatment have shown a further decline compared to 2 years before. We conclude that selective mass chemotherapy with praziquantel can give the community as a whole a respite from schistosomiasis morbidity for at least 2 years despite an increase in prevalence.

Reduction in prevalence, intensity of infection and morbidity due to Schistosoma mansoni infection in a community following treatment with praziquantel.

Five hundred and twenty-three individuals from an area endemic for Schistosoma mansoni infection were followed for a 16 month period in a population-based study in rural Zambia. Those found infected in each of five surveys were treated with praziquantel (40 mg kg-1 body weight). Data on prevalence, intensity of infection and morbidity (intestinal symptoms and liver and spleen enlargements) were also gathered. At the end of the study, prevalence had fallen from 64.8% to 11.5%, intensity of infection had dropped from 28.2 to 0.5 eggs per gram of stool (geometric means) and morbidity showed marked reduction.

The relationship between morbidity and intensity of Schistosoma mansoni infection in a rural Zambian community.

Six hundred and ninety-three individuals from an area endemic for S. mansoni infection had parasitological and physical examinations done. A morbidity questionnaire was also administered to each participant. Among those with S. mansoni infection, there was significant increase in watery diarrhoea, bloody diarrhoea, blood in stool and hepatomegaly. The severity of the disease appears to be directly related to the egg load and therefore these results give further justification for treatment of high intensity age groups in community based chemotherapy programmes designed to reduce morbidity in endemic areas.

Evaluation of selected symptoms in the diagnosis of Schistosoma mansoni infection.

Data on morbidity associated with S. mansoni infection was gathered using a questionnaire before parasitological screening was done in a rural Zambian community. Blood in stool, bloody diarrhoea and watery diarrhoea were found to be significantly associated with S. mansoni infection. Levels of sensitivity, specificity and predictive values were calculated for each symptom. On the basis of results obtained we speculate that these symptoms could be used by peripheral health workers in making early diagnosis of the disease in the absence of laboratory diagnostic tests.

Risks of liver and spleen enlargement in schistosomiasis mansoni infection in a rural Zambian community.

At the Tropical Diseases Research Centre, Ndola, Zambia, we have used "relative risks" to demonstrate the relationship between intensity of Schistosoma mansoni infection and liver and spleen enlargement. There was a significant trend in risk for both right and left lobe liver enlargement across the intensity strata. However the risk for spleen enlargement showed no significant trend.

Guidelines for the control of malaria in Zambia with emphasis on curative and prophylactic aspects

Malaria is endemic in all of Zambia and is a leading cause of morbidity and mortality. It is the most common cause of hospital admissions for all age groups. During the period 1976-1986; there has been a four-fold increase in the number of hospital deaths due to malaria and more than doubling of new cases. The incidence (new cases per year per 1000 population) has steadly increased from 137.8 in 1978 to 287.9 in 1988. The hospital case fatality rate has sharply increased; more than doubling from 13.9 per 1000 in 1978 to 74.8 per 1000 1988. The figures are an underestimate of the true epidemiological picture of malaria in the country as they represent only reported cases from public health institutions excluding information from the private practitioners and people who self treat their malaria when they fall ill. Factors influencing these trends include increasing disease virulence; increase in chloroquine resistant strains; loss herd immunity and changes in community prophylaxis