Randomised placebo-controlled study of atovaquone plus proguanil for malaria prophylaxis in children

BACKGROUND: The combination of atovaquone and proguanil is highly effective and safe for the treatment of Plasmodium falciparum malaria. We aimed in this randomised, double-blind, placebo-controlled study to assess the efficacy and safety of this combination for malaria prophylaxis. METHODS: 320 children who lived in a hyperendemic area for P falciparum malaria were stratified by weight and randomly assigned atovaquone plus proguanil or placebo once daily for 12 weeks. All children received initial curative treatment with atovaquone and proguanil before the start of chemosuppression. We recorded adverse events daily and collected thick blood smears once a week. The primary endpoint was a positive blood smear. FINDINGS: 25 of 140 children in the placebo group and none of the 125 children in the atovaquone plus proguanil group had positive smears during chemosuppression (p<0.001). Adverse events during the chemosuppression phase did not differ between the groups. INTERPRETATION: The combination of atovaquone plus proguanil is a highly effective and well-tolerated chemosuppressive antimalarial in children. This drug combination could replace current regimens.     

Effects of malaria infection in human immunodeficiency virus type 1-infected Ugandan children

BACKGROUND: Malaria causes severe morbidity and mortality in many areas of Africa where HIV-1 infection is also prevalent. Immunosuppression is associated with both diseases but most reports do not find significant interactions between them. METHODS: A collaborative study of HIV-1 infection in Ugandan women and their infants was established between the Ministry of Health, Makerere University, Kampala, and Case Western Reserve University in 1988. Four hundred fifty-eight infants, including 77 HIV-1-infected, 232 seroreverter and 125 control children born to HIV-1-negative mothers and 24 of indeterminate status were followed closely from birth for 4 years. Data on these infants were reviewed with respect to episodes of general illness and infections, suspected and confirmed episodes of malaria, onset and frequency of malaria, use of chloroquine and occurrence of selected illnesses after episodes of febrile illnesses. Thick and thin blood smears for malaria were obtained from children with fever. RESULTS: There was no association between occurrence of febrile illnesses and childrens' HIV-1 category. The relative rates of occurrence were 1.0 (95% confidence interval (CI), 0.8 to 1.2) and 1.1 (95% CI 0.9 to 1.4) for the HIV seroreverter and control children compared with the HIV-infected children. Although there was no association (P = 0.83) between HIV-1 status and a smear being taken during a febrile episode, there was an increase in smears positive for malaria parasitemia among seroreverter (risk ratio, 1.5; 95% CI 1.1 to 1.9) and control infants (risk ratio, 1.6; 95% CI 1.2 to 2.2) compared with HIV-1-infected infants. The level of parasitemia was similar in each group. A greater proportion of malaria episodes among the HIV-infected group than among the control groups resulted in hospitalizations (P = 0.001) and blood transfusions (P = 0.02). There was a positive association between time to clinical AIDS and absence of malaria (adjusted for follow-up age) in infected children (P = 0.02). Use of chloroquine was similarly high in each HIV-1 category (80%). CONCLUSIONS: In this group of HIV-infected children there was no significant increase in malarial episodes as compared with their HIV-negative controls. The results suggest a possibility that malaria may offer some protection against HIV-1 progression or that chloroquine used to treat malaria may have a direct effect against the HIV-1 virus.     

The role of nitric oxide in mechanisms of the nephrotoxic effect of verografin

A clinic based cross-sectional study was conducted at Immunoprophylaxis Clinic at Govt. Medical College, Nagpur. Mothers of 217 children were interviewed for infant feeding practices. In 62.67% of children, breast-feeding was initiated within 24 hrs. after birth. About 22% mother used prelacteal feed and 70% mothers preferred demand feeding. Prominent area of concern includes discarding of colostrum, low exclusive breast feeding rate, delayed weaning and early termination of breast feeding. Further improvement in present day infant feeding practices is possible by emphasising on the health education component of existing nutritional programmes.     

Chronic salicylate poisoning and severe malaria

BACKGROUND Salicylates continue to be marketed and to be used in developing countries as over-the-counter (OTC) antipyretics in children, whereas in developed countries they are no longer used in children because of safety concerns. The presenting signs of salicylate poisoning, especially chronic (repeated administration of therapeutic or excessive doses for longer than 12 h), can include metabolic acidosis, hypoglycaemia, lethargy, and coma and fits. These signs are also common in severe malaria in African children. Admission of two probable cases of chronic salicylate poisoning prompted us to look for other cases among children presenting to our hospital in Kenya, apparently with severe malaria. METHODS All children admitted to Kilifi District Hospital between July and September, 1994, who had a positive blood film for Plasmodium falciparum, and one or more of coma, prostration, or respiratory distress were eligible. As well as routine tests for malaria and routine biochemistry, salicylate concentrations were measured. Management of children (aged 6 months to 10 years) in the community was assessed by a cross-sectional survey of 463 households and by interviews with mothers 2 days after they had bought OTC drugs for a child with fever. FINDINGS Data were available for 143 of 154 children with initial primary diagnoses of severe malaria. 129 (90 percent) had detectable (>l mg/dL) salicylate. Six of these had salicylate concentrations of 20 mg/dL or higher. All six had neurological impairment and metabolic acidosis and four were, or became, hypoglycaemic. OTC drugs were the first-line treatment in 188 (74 percent) of 254 fever episodes during the 2 weeks before the cross-sectional survey. Of 250 mothers who bought drugs for a febrile child, 236 (94 percent) bought a preparation containing salicylates and 50 (21 percent) gave a dose higher than the manufacturer's recommended maximum. INTERPRETATION These cases suggest that in some children salicylate poisoning may cause or contribute to the development of metabolic acidosis and hypoglycaemia, complications of severe malaria associated with high mortality.     

Identification of a subpopulation of immune Nigerian adult volunteers by antibodies to the circumsporozoite protein of Plasmodium falciparum

Collections of human sera from malaria-endemic areas would be valuable for identifying and characterizing antigens as malaria vaccine candidates if the contributing serum donors' ability to resist infection were fully characterized. We prepared such a serum collection from 26 apparently immune Nigerian adults who failed to develop patent parasitemia for at least 20 weeks following a documented increase in antibodies to the circumsporozoite protein (CSP) from Plasmodium falciparum. Volunteers were evaluated five times per week for malaria symptoms and bimonthly for parasites by examining thick blood smears. The incidence rate over 13 months for the cohort was 42% (47 malaria-confirmed volunteers) and the risk of infection was 1.3 infections/year. Responses to CSP did not correlate with protection. Because antibody responses to antigens other than CSP may be associated with protection, the sera from these immune individuals may be useful for identifying and characterizing other potential malaria vaccine candidates.     

The analysis of methamphetamine hydrochloride by thermal desorption ion mobility spectrometry and SIMPLISMA

The treatment of malaria tropica is becoming difficult because of the increasing drug resistance rates of Plasmodium falciparum against several of the currently available antimalarias. A fixed combination of rifampicin, co-trimoxazole and isoniazid (CotrifazidTM, CF) was found to be highly effective for the treatment of malaria tropica. The aim of the present study in Kenya was to scrutinize this finding in a 14-day trial. Patients with malaria tropica were given in an open, double-arm randomized study CF for 5 days, or chloroquine or pyrimethamine/sulphadoxine as the control. Because of an apparently better activity and tolerance of CF, the randomization had to be stopped after the enrollment of 50 patients. A total of 61 patients in both groups (35 of them between 2 months and 6 years of age) were available for final analysis. All 41 patients treated with CF, originally positive in their blood smears, turned negative; in 2 cases blood smear positivity reappeared on day 14. There were 7 failures in the control group, 4 of them a primary one. Four of those failures were turned negative with CF, 2 failed with CF also, and 1 disappeared. The tolerance of CF was excellent even in infants. In our experience, CF is very well suited for the treatment of malaria tropica, also in cases of apparent drug resistance of P. falciparum against other antimalarials, and even in severe cases of the disease.     

Perianal disease, growth failure, and quality of life

The micro-wave oven permits a rapid drying of thick blood smears classically used for parasitological malaria diagnosis. In order to evaluate this type of drying on the microscopic reading, a study was carried out in an hyperendemic area of malaria with 382 asymptomatic volunteers of all ages. Two thick smears were made for each volunteer, one immediately dried with a micro-wave oven for one minute, the second dried in the open air without any intervention. A single microscopist examined all the thick smears. The observation of Plasmodium falciparum trophozoites differed significantly between the two methods, the prevalence was 50% by normal drying versus 41% by the micro-wave oven. The geometric mean of the trophozoite number for positive thick smears was significantly lower with the micro-wave oven. When the parasitological density with normal drying was lower than 200 trophozoites/microliter of blood, 54% of results were wrongly negative with the micro-wave oven. On the other hand, the observation of P. falciparum gametocytes was significantly facilitated after drying with the micro-wave oven; the prevalence was 8% with normal drying versus 12% by micro-wave oven. In conclusion, the use of the micro-wave oven for the drying of thick smears is not recommended for malaria diagnosis although it improves the observation and counting of P. falciparum gametocytes.     

Parenting behavior and emotional status of physically abusive mothers.

Administered the Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), and Cornell Medical Index (CMI) to 8 physically abusive mothers (mean age 27.5 yrs) from low-SES families, 8 matched low-SES control mothers (mean age 26.5 yrs), and 8 matched middle-SES control mothers (mean age 32.9 yrs). Results show that abusive Ss differed from both control groups on the BDI and the Emotional Distress and Physical Symptoms scales of the CMI. Marginally significant differences were found on the Trait Anxiety scale of the STAI. No significant differences were found between control groups. Although direct observation in the home revealed no significant differences among the 3 groups on any measure of child behavior, the abusive Ss engaged in a far higher percentage of negative physical behaviors and a lower percentage of positive behaviors toward their children than did either of the control groups. A model of child abuse is suggested that proposes that parents who are in greater emotional and somatic distress may have a lower threshold for child misbehavior and may react more punitively to it. (37 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A randomized controlled trial of artemether/benflumetol, a new antimalarial and pyrimethamine/sulfadoxine in the treatment of uncomplicated falciparum malaria in African children

We report here the results of a randomized double blind trial comparing coartemether (CGP56697), a combination of artemether and benflumetol, with pyrimethamine/sulfadoxine (P/S). Two hundred eighty-seven children 1-5 years of age with uncomplicated falciparum malaria were enrolled at two centers in The Gambia between July 1996 and December 1996. Following treatment, children were visited at home every 24 hr until a blood film free of asexual parasites was obtained. Genotyping of parasites was used to distinguish recrudescence from new infections. Three days after the start of treatment, 133 (100%) of the CGP56697-treated children compared with 128 (93.4%) of children treated with P/S had cleared their parasites (P = 0.003). The day 15 cure rate was 93.3% for CGP56697 and 97.7% for P/S (P = 0.13). Within the third and fourth week after initiation of therapy, 20 children treated with CGP56697 and one of the P/S-treated children returned with second malaria episodes (P < 0.0001). Genotyping suggested that the majority (19 of 23 [82.6%]) of these second episodes were due to new infections, supporting the World Health Organization recommendation that longer follow-up is not relevant for the assessment of drug efficacy. At the two-week follow-up, 28.9% of the P/S treated children but none of the CGP56697-treated children carried gametocytes (P < 0.0001). This study showed that CGP56697 is safe in African children with acute uncomplicated falciparum malaria, clears parasites more rapidly than P/S, and results in fewer gametocyte carriers. More frequent new infections within the third and fourth week following treatment with CGP56697 than treatment with P/S are likely to be due to the short prophylactic effect of CGP56697.     

Lack of association between falciparum malaria parasitemia and acute diarrhea in Nigerian children

It is widely believed that malaria causes diarrhea. Yet, national and international diarrheal diseases control programs are silent about the overlap between these two major public health problems that coexist in most tropical countries. To test the hypothesis that malaria is associated with diarrhea and to define the role of malaria in morbidity due to diarrhea, 522 children 6-60 months of age presenting with acute diarrhea to the Children's Emergency Ward of the University College Hospital in Ibadan, Nigeria were routinely screened by means of thin and thick blood films for malaria parasitemia. Controls, without diarrhea, were studied in parallel. Detailed clinical features were recorded for every patient. Sixty-eight (13%) of the 522 diarrhea patients screened had malaria parasitemia. Among the controls (who had similar distributions of admission temperature, hemoglobin types, glucose-6-phosphate dehydrogenase deficiency, and prior treatment with antimalarial drugs), parasitemia was not significantly different, occurring in 56 (17.9%) of 313. In the dry season, however, a significantly higher prevalence of parasitemia was observed among the control group (15.5%) than in the diarrhea group (7.0%) (P = 0.004). Parasitemia was significantly more common in the dehydrated diarrhea patients than their well-hydrated counterparts (25% of 56 versus 11% of 466; P < 0.005). There were no significant differences in admission temperature, the presence of vomiting, or the home use of oral rehydration fluids between the dehydrated and the well-hydrated subsets of diarrhea patients. Consideration of parasite densities did not alter any of the foregoing relationships. These data contradict the widely held view that diarrhea is a symptom of malaria or that malaria causes diarrhea. They do, however, provide support for examining blood smears at least in dehydrated children with diarrhea in malaria-endemic areas and giving immediate antimalarial therapy to those who have malaria parasitemia.     

Cefotaxime prophylaxis in major non-contaminated head and neck surgery: one-day vs. seven-day therapy

Exfoliated cervical epithelial cells from women 6 weeks postpartum were analyzed for human papillomavirus (HPV) DNA using the polymerase chain reaction, and results were compared with those from buccal mucosal smears from their babies. Eleven mothers had genital genotypes of HPV in their cervical smears, and the children of 8 of these had HPV of the same genotype in buccal mucosal cell samples. Nineteen mothers had no HPV DNA detected in their cervical smears, and 1 of the buccal mucosal cell samples from their children was positive for HPV DNA (p < 0.0001). Contamination of a child's mouth with 'genital' HPV from a mother's cervix appears to occur commonly at birth or in the perinatal period, and to persist for at least 6 weeks. This observation has implications for the epidemiology and management of HPV associated cancer and precancerous conditions in the cervix and the mouth.     

Passive smoking in children up to 5 years of age

Passive smoking is a major health risk in young children. We investigated the percentage of children with mothers and/or fathers who reported regular smoking. Data are the national and regional health surveys of the German Cardiovascular Prevention Study (GCP) conducted from 1984 to 1992 in West Germany. 2538 mothers aged 25-40 years were included. The prevalence of passive smoking in children due to smoking mothers was 33.6% 55.4% of the children up to 5 years lived in households with at least one smoking parent member. In 23.4% of these households both parents were smokers. If only one member of the parents smoked this was in two out of three cases the father. 28.2% of mothers with a child younger than one year were current smokers. This prevalence rate increased with the age of the youngest child up to 35.6% for mothers, whose youngest child was 5 years old. Multiple logistic regression analysis was performed to investigate the association between smoking behaviour and the following variables: mother's age, social class, family status, community size and year of the survey. It was found that lower social class members, unmarried or divorced mothers and inhabitants of large cities reported significantly more often regular current smoking. These results underscore the importance of special intervention programs to reduce smoking in parents with young children.     

Child weighing by the unschooled: a report of a controlled study of growth monitoring over 12 months of Maasai children using direct recording scales

Growth monitoring was developed as a clinic-based programme in the early 1960s, and has spread widely in many countries. The results of weighing children are usually presented in a graphic form, unintelligible to most mothers and difficult for many health workers to interpret. This study suggests that the TALC Direct Recording Scale will allow growth monitoring to be undertaken even by illiterate mothers in the community and reports the results of a trial with a group of illiterate mothers amongst the Maasai of Kenya.     

Congenital malaria: an African survey

Even in malaria-endemic areas, congenital malaria has been considered to be rare. Some recent reports suggest, however, that up to one fourth of newborns in some areas may be parasitemic. In an effort to determine current prevalence rates of congenital malaria, malaria smears were done on peripheral blood from 100 peripartum mothers and on cord blood from their offspring at each of seven sites spanning sub-Saharan Africa. The prevalence rate of maternal parasitemia was 15% overall and varied from 4% to 30% at the different sites. Congenital malarial infection was found in 7% of newborns, the prevalence rate varying from 0% to 23% at the different sites. There was no apparent relationship between the season of sampling and either the prevalence rates of parasitemia or the penetrance of malaria from mother to offspring. In summary, congenital malarial infection is not rare in sub-Saharan Africa, but the prevalence rate of neonatal parasitemia varies from site to site.     

Identification of evolutionarily invariant sequences in the protein C gene promoter

To identify a marker associated with poor outcome in severe malaria that requires no technology, the relationship between the presence of pallor and mortality was reviewed retrospectively in 291 Zambian children with cerebral malaria. The mean (S.D.) haemoglobin concentration among the 222 children assessed as having pallor on admission was significantly lower than that among the 69 children not considered to have pallor [6.0 (1.9) v. 9.2 (1.6) g/dl; P < 0.0005]. Thirty-nine (17.6%) of the children presenting with pallor died, compared with only five (7.2%) of those without pallor (P = 0.036). The adjusted odds of death in children with pallor on admission was 2.8 times higher than that in children without pallor (95% confidence interval = 1.03-7.7; P = 0.044). The clinical observation of pallor may therefore identify children with low haemoglobin concentrations and a high risk of mortality. Whether mothers and village health workers can be taught to recognize pallor in a child with malaria and then to seek early medical attention will need to be determined in further studies.     

Time utilisation pattern of staff of two primary health centres in Ballavgarh, Haryana

BACKGROUND: All National health programmes are implemented through the Primary Health Centre staff. Targets for the year 2000 A.D. have been fixed for different programmes. Some programmes are getting more emphasis, perhaps at the cost of others. The study area has already achieved most of the targets set for 2000 A.D. Studying the time utilisation pattern of the workers of these PHCs can give valuable information for planning of working of other PHCs. OBJECTIVE: To study the time utilisation pattern of the staff of the two PHCs run by Centre for Community Medicine, AIIMS. METHODS: The multipurpose workers (MPWs) and the health assistants (HAs) were accompanied by investigators and information collected regarding their utilisation of time in the field. The Medical Officers were asked to maintain a diary from which this information was collected RESULTS: The MPWs spend about 3.3 minutes in each house. Child care (immunisation, Vit. A and folifer distribution) is the main activity being carried out by both male as well as female worker. Other important activities for male worker are: family welfare (18%), malaria work (11%) and collection of vital statistics (10%). For the female worker Antenatal care (25%) and family welfare (20%) were other important activities. For the HAs also child care was an important activity. However for the male HA malaria related work was the most important. The Medical Officer spends about 60% of this time in administrative and supervisory work. CONCLUSIONS: Immunisation programme is getting the maximum input from workers, which is reflected in > 90% coverage of all vaccines. Family Welfare and Tuberculosis activity are not getting the emphasis which they deserve. Some rethinking about the strategy is essential if all round progress in achieving the targets for the year 2000 A.D. is to be made.     

Comparison of morbidity interviews with a health examination survey in rural Africa

This paper describes a study of the Danfa Comprehensive Rural Health and Family Planning Project, Ghana. The report compares information obtained from morbidity interviews with information obtained during subsequent health examinations. One to 4 days prior to examination by a team of physicians, 3,653 rural Ghanaians were interviewed by a team of auxiliary workers. Information obtained from the interview survey was noticeably different from examination diagnoses. Significant health problems such as malaria, intestinal parasites and diarrhea, as well as minor and chronic conditions were seriously under-reported. Interview findings were more accurate for children, women in the reproductive age group, and in cases in which the disease caused considerable discomfort or diability. Although individual examination was eight times as costly as an interview, small scale rural health examination surveys of a representative sample of the population are recommended to provide accurate morbidity information for health planners.     

Rhabdoid tumours of the central nervous system. Report of three cases with immunocytochemical and ultrastructural findings

Blood samples from malaria-infected patients and from in vitro culture were analyzed using the H*1 hematology analyzer. An attempt to find a hematologic parameter for detecting the malaria infection and to characterize the pathophysiological changes of red cells was made. The study included 18 malaria-infected patients (10 with Plasmodium falciparum and 8 with Plasmodium vivax) and 52 normal, healthy volunteers. Increased young large lymphocyte or large unstained cell count (LUC over 3%) in the peripheral blood of malaria-infected patients was evidence for malaria infection. Increased population dispersions of red cell volume (red cell distribution width: RDW) and intraerythrocytic hemoglobin concentration (hemoglobin distribution width: HDW) were demonstrated both in clinical samples and cultured blood. The increased RDW correlated with an increased percentage of macrocytes (r = 0.64, P = 0.004). Comparison of HDW and percentage of hypochromic red cells between the clinical specimen and the cultured blood supports the finding that changes in red cell hemoglobin concentration were mainly due to the response of the patient to malaria infection and partly due to the effect of malaria parasites on the red cells.     

The effect of distance from home on attendance at a small rural health centre in Papua New Guinea

BACKGROUND: The willingness of patients in the rural tropics to seek medical care at primary health care facilities is influenced by the distance they have to travel, but few studies have tried to estimate these distance effects. METHODS: Distance decay effects in attendance rates were estimated from a database of 4348 attendances at a rural health centre in Papua New Guinea, linked to demographic and house position data for the catchment population. Small-scale spatial patterns and differences between diagnoses, age groups and gender are described. RESULTS: Attendance decreased markedly with distance both overall (50% decrease at 3.5 km) and for patients with malaria or acute respiratory infections. This decrease was non-linear (on log scale) with distance. Although constant over time, there were big differences in this distance effect among age and gender groups: Female patients showed less distance decay in adolescents and adults, but higher in the infant group. Spatial patterns accounted for 32% of the variation in age- and gender-specific attendance rates. Of the spatial effects more than 50% were due to distance effects. CONCLUSIONS: Distance effects were similar in magnitude to those reported elsewhere, suggesting that distance effects may be generalizable to many parts of the rural tropics. The non-linearity of distance decay implies that a bell-shaped demand function should be used in health planning.     

Effects of treatment for intestinal parasites and malaria on the cognitive abilities of schoolchildren in Zaire, Africa.

97 Zairian school children were evaluated for cognitive ability, health status, and quality of home environment. Children successfully treated for serious types of chronic intestinal parasites demonstrated significant improvements in Kaufman Assessment Battery for Children—Spatial Memory, supporting this task as one of the more sensitive measures to changes in general health and neurological integrity. These findings were not obtained for successful treatment of low-grade malaria infection. Children initially negative for intestinal parasites tended to come from more economically and socially favorable home environments. They also demonstrated more dramatic improvements in visual–spatial analysis tasks. The implication is that home environment factors conducive to chronic infestation with intestinal parasites are markers for favorability of the developmental milieu affecting long-term intellectual development. (PsycINFO Database Record (c) 2010 APA, all rights reserved)