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Showing papers in "American Journal of Tropical Medicine and Hygiene in 2003"


Journal ArticleDOI
TL;DR: In areas with intense malaria transmission with high ITN coverage, the primary effect of insecticide-treated nets is via area-wide effects on the mosquito population and not, as commonly supposed, by simple imposition of a physical barrier protecting individuals from biting.
Abstract: Spatial analyses of the effect of insecticide (permethrin)-treated bed nets (ITNs) on nearby households both with and without ITNs was performed in the context of a large-scale, group-randomized, controlled mortality trial in Asembo, western Kenya. Results illustrate a protective effect of ITNs on compounds lacking ITNs located within 300 meters of compounds with ITNs for child mortality, moderate anemia, high-density parasitemia, and hemoglobin levels. This community effect on nearby compounds without nets is approximately as strong as the effect observed within villages with ITNs. This implies that in areas with intense malaria transmission with high ITN coverage, the primary effect of insecticide-treated nets is via area-wide effects on the mosquito population and not, as commonly supposed, by simple imposition of a physical barrier protecting individuals from biting. The strength of the community effect depended upon the proportion of nearby compounds with treated nets. To maximize their public health impact, high coverage with treated nets is essential.

575 citations


Journal ArticleDOI
TL;DR: Evidence from past literature is presented to build a conceptual framework to begin to explain this heterogeneity in malaria transmission and the potential for malaria epidemics owing to decreasing levels of natural immunity being offset by negative impacts of urbanization on the larval ecology of anopheline mosquitoes.
Abstract: The rapid increase in the world's urban population has major implications for the epidemiology of malaria. A review of malaria transmission in sub-Saharan African cities shows the strong likelihood of transmission occurring within these sprawling cities, whatever the size or characteristics of their bioecologic environment. A meta-analysis of results from studies of malaria transmission in sub-Saharan Africa shows a loose linear negative relationship between mean annual entomologic inoculation rates (EIR) and the level of urbanicity. Few studies have failed to find entomologic evidence of some transmission. Our results show mean annual EIRs of 7.1 in the city centers, 45.8 in periurban areas, and 167.7 in rural areas. The impact of urbanization in reducing transmission is more marked in areas where the mean rainfall is low and seasonal. Considerable variation in the level of transmission exists among cities and within different districts in the same city. This article presents evidence from past literature to build a conceptual framework to begin to explain this heterogeneity. The potential for malaria epidemics owing to decreasing levels of natural immunity may be offset by negative impacts of urbanization on the larval ecology of anopheline mosquitoes. Malaria control in urban environments may be simpler as a result of urbanization; however, much of what we know about malaria transmission in rural environments might not hold in the urban context.

446 citations


Journal ArticleDOI
TL;DR: The findings illustrate the uniqueness of each serotype in producing epidemics and severe disease and underscore the importance of long-term surveillance of dengue serotypes in understanding the epidemiology of these viruses.
Abstract: Dengue virus circulation and association with epidemics and severe dengue disease were studied in hospitalized children with suspected dengue at the Queen Sirikit National Institute of Child Health in Bangkok, Thailand, from 1973 to 1999. Dengue serology was performed on all patients and viral isolation attempted on laboratory-confirmed patients. Acute dengue was diagnosed in 15,569 children and virus isolated from 4,846. DEN-3 was the most frequent serotype in primary dengue (49% of all isolates), DEN-2 in secondary and in dengue hemorrhagic fever (37% and 35%, respectively). The predominant dengue serotype varied by year: DEN-1 from 1990-92, DEN-2 from 1973-86 and 1988-89; DEN-3 in 1987 and 1995-99; and DEN-4 from 1993-94. Only DEN-3 was associated with severe outbreak years. Our findings illustrate the uniqueness of each serotype in producing epidemics and severe disease and underscore the importance of long-term surveillance of dengue serotypes in understanding the epidemiology of these viruses.

371 citations


Book ChapterDOI
TL;DR: It is concluded that entomologic risk of human dengue infection should be assessed at the household level at frequent time intervals.
Abstract: We determine the spatial pattern of Aedes aegypti and the containers in which they develop in two neighborhoods of the Amazonian city of Iquitos, Peru. Four variables were examined: adult Ae. aegypti, pupae, containers positive for larvae or pupae, and all water-holding containers. Adults clustered strongly within houses and weakly to a distance of 30 meters beyond the household; clustering was not detected beyond 10 meters for positive containers or pupae. Over short periods of time restricted flight range and frequent blood-feeding behavior of Ae. aegypti appear to be underlying factors in the clustering patterns of human dengue infections. Permanent, consistently infested containers (key premises) were not major producers of Ae. aegypti, indicating that larvaciding strategies by themselves may be less effective than reduction of mosquito development sites by source reduction and education campaigns. We conclude that entomologic risk of human dengue infection should be assessed at the household level at frequent time intervals.

344 citations


Journal ArticleDOI
TL;DR: The highly non-linear relationship between EIRs and prevalence indicates that the consistent pattern of high prevalence might be governed by substantial variation in transmission intensity measured by entomologic surveys.
Abstract: The seasonal dynamics and spatial distributions of Anopheles mosquitoes and Plasmodium falciparum parasites were studied for one year at 30 villages in Malindi, Kilifi, and Kwale Districts along the coast of Kenya. Anopheline mosquitoes were sampled inside houses at each site once every two months and malaria parasite prevalence in local school children was determined at the end of the entomologic survey. A total of 5,476 Anopheles gambiae s.l. and 3,461 An. funestus were collected. Species in the An. gambiae complex, identified by a polymerase chain reaction, included 81.9% An. gambiae s.s., 12.8% An. arabiensis, and 5.3% An. merus. Anopheles gambiae s.s. contributed most to the transmission of P. falciparum along the coast as a whole, while An. funestus accounted for more than 50% of all transmission in Kwale District. Large spatial heterogeneity of transmission intensity (< 1 up to 120 infective bites per person per year) resulted in correspondingly large and significantly related variations in parasite prevalence (range = 38-83%). Thirty-two percent of the sites (7 of 22 sites) with malaria prevalences ranging from 38% to 70% had annual entomologic inoculation rates (EIR) less than five infective bites per person per year. Anopheles gambiae s.l. and An. funestus densities in Kwale were not significantly influenced by rainfall. However, both were positively correlated with rainfall one and three months previously in Malindi and Kilifi Districts, respectively. These unexpected variations in the relationship between mosquito populations and rainfall suggest environmental heterogeneity in the predominant aquatic habitats in each district. One important conclusion is that the highly non-linear relationship between EIRs and prevalence indicates that the consistent pattern of high prevalence might be governed by substantial variation in transmission intensity measured by entomologic surveys. The field-based estimate of entomologic parameters on a district level does not provide a sensitive indicator of transmission intensity in this study.

290 citations


Journal ArticleDOI
TL;DR: Fear of injections was common in this cohort and was highly associated with past fainting after vaccination, and perceived empathy, on the other hand, was a significant protective factor.
Abstract: Fear of injections may interfere with receipt of vaccines. The frequency, associations, and precipitators of fear-provoking factors of 400 travelers visiting a travel health clinic were evaluated. The median age of this group was 25, 7% were medical staff members, and 2.8% were regular injectors (insulin). Eighty-five (21.7%; 95% confidence interval, 17.3-25.6%) of the travelers indicated that they were afraid of injections, and in 8.2%, the fear was unreasonably intense. Multivariate analysis revealed that watching other people being vaccinated, fear of pain, needle size, and a history of fainting were highly and independently associated with injection phobia. The sensitivity, specificity, and discrimination accuracy of this model were 79.5%, 78.0%, and 78.3%, respectively. Injection phobia and a bad past vaccination experience were significantly associated with fainting. Perceived empathy, on the other hand, was a significant protective factor. Fear of injections was common in this cohort and was highly associated with past fainting after vaccination.

284 citations


Journal ArticleDOI
TL;DR: Dense monocyte infiltrates and presence of intramonocytic malaria pigment were associated with anemia and LBW, and pigment-containing placental monocytes may have a causative role in their development.
Abstract: Maternal anemia and low birth weight (LBW) may complicate malaria in pregnancy, and placental monocyte infiltrates have been associated with LBW, and anecdotally with anemia We examined placental pathology from 357 Malawian women Intervillous monocyte infiltrates were frequent in placental malaria and were not seen in uninfected placentas Histology was grouped according to a 5-point scale Dense monocyte infiltrates and presence of intramonocytic malaria pigment were associated with anemia and LBW Of factors associated with LBW and/or anemia in univariate analysis, gravidity (P = 0002), number of antenatal clinic (ANC) visits (P < 0001), malaria pigment in fibrin (P = 003), and monocyte malaria pigment (P = 00001) remained associated with lower birth weight by multivariate analysis Associated with maternal anemia were HIV infection (P < 00001), intervillous monocyte numbers (P < 00001), number of ANC visits (P = 0002), and recent febrile symptoms (P = 00001) Pigment-containing placental monocytes are associated with anemia and LBW due to malaria, and may have a causative role in their development

268 citations


Journal ArticleDOI
TL;DR: A group-randomized controlled trial of insecticide (permethrin)-treated bed nets (ITNs) was conducted in an area of high perennial malaria transmission in western Kenya to test the effect of ITNs on all-cause mortality in children 1-59 months of age as mentioned in this paper.
Abstract: A group-randomized controlled trial of insecticide (permethrin)-treated bed nets (ITNs) was conducted in an area of high perennial malaria transmission in western Kenya to test the effect of ITNs on all-cause mortality in children 1-59 months of age. Child deaths were monitored over a two-year period by biannual household census in Asembo (1997-1998) and in Gem (1998-1999). Overall, 1,722 deaths occurred in children 1-59 months followed for 35,932 child-years. Crude mortality rates/1,000 child-years were 51.9 versus 43.9 in control and ITN villages in children 1-59 months old. The protective efficacy (PE) (95% confidence interval) adjusted for age, study year, study site, and season was 16% (6-25%). Corresponding figures in 1-11- and 12-59-month-old children in control and ITN villages were 133.3 versus 102.3, PE = 23% (11-34%) and 31.1 versus 28.7, PE = 7% (-6-19%). The numbers of lives saved/1,000 child-years were 8, 31, and 2 for the groups 1-59, 1-11, and 12-59 months old, respectively. Stratified analysis by time to insecticide re-treatment showed that the PE of ITNs re-treated per study protocol (every six months) was 20% (10-29%), overall and 26% (12-37%) and 14% (-1-26%) in 1-11- and 12-59-month-old children, respectively. ITNs prevent approximately one in four infant deaths in areas of intense perennial malaria transmission, but their efficacy is compromised if re-treatment is delayed beyond six months.

248 citations


Journal ArticleDOI
TL;DR: Exposure of larvae to a diagnostic dose of temephos showed in alterations in susceptibility in all populations, and adults from only one municipality remained susceptible to both fenitrothion and malathion.
Abstract: Chemical insecticides have been widely used in Brazil for several years. This exposes mosquito populations to an intense selection pressure for resistance to insecticides. In 1999, the Brazilian National Health Foundation started the first program designed to monitor the resistance of Aedes aegypti to insecticides. We analyzed populations from 10 municipalities (from 84 selected in Brazil) in the states of Rio de Janeiro and Espirito Santo. Exposure of larvae to a diagnostic dose of temephos showed in alterations in susceptibility in all populations. Mosquitoes from eight municipalities exhibited resistance, with mortality levels ranging from 74% (Campos dos Goytacazes, Rio de Janeiro) to 23.5% (Sao Goncalo, Rio de Janeiro). The resistance ratios of mosquitoes from three municipalities ranged from 3.59 to 12.41. Adults from only one municipality (Nova Iguacu, Rio de Janeiro) remained susceptible to both fenitrothion and malathion. These results are being used to define new local vector control strategies.

234 citations


Journal ArticleDOI
TL;DR: Sequestration of parasitized red blood cells in cerebral microvessels was significantly higher in the brains of patients with CM compared with those with non-cerebral malaria (NCM) in all parts of the brain and the degree of sequestration of P. falciparum-infected erythrocytes in cortex is quantitatively associated with pre-mortem coma.
Abstract: Cerebral malaria (CM) is a major cause of death in severe Plasmodium falciparum malaria. We present quantitative electron microscopic findings of the neuropathologic features in a prospective clinicopathologic study of 65 patients who died of severe malaria in Thailand and Vietnam. Sequestration of parasitized red blood cells (PRBCs) in cerebral microvessels was significantly higher in the brains of patients with CM compared with those with non-cerebral malaria (NCM) in all parts of the brain (cerebrum, cerebellum, and medulla oblongata). There was a hierarchy of sequestration with more in the cerebrum and cerebellum than the brain stem. When cerebral sequestration was compared with the peripheral parasitemia pre mortem, there were 26.6 times more PRBCs in the brain microvasculature than in the peripheral blood. The sequestration index was significantly higher in CM patients (median = 50.7) than in NCM patients (median = 6.9) (P = 0.042). The degree of sequestration of P. falciparum-infected erythrocytes in cerebral microvessels is quantitatively associated with pre-mortem coma.

234 citations


Journal ArticleDOI
TL;DR: The most important reason for non-adherence was disruption of sleeping arrangements, indicating that ITNs were not readily redeployed in the face of shifting sleeping patterns due to visitors, funerals, house construction, and other events.
Abstract: Adherence with permethrin-treated bed net (ITN) use and their proper deployment was directly observed in 2,178 individuals (784 households) participating in a large-scale trial of ITNs onchild mortality inwesternKenya. The ITNs were distributed free of charge to ensure high coverage, resulting in a ratio of 1.46 persons per ITN. Approximately 30% of ITNs present were unused. The overall percentage adherence was 72.3%. The probability of adherence by individuals depended strongly on age (relative risk (RR) 0.86, 95% confidence limit (CL) − 0.78-0.94), in which childrenless thanfive years of age were less likely to use ITNs thanolder i ndividuals, and temperature, in which ITNs were more likely to be used in periods of cooler weather. A marginally significant diminution in adherence during the second year of the project was also observed (RR 0.83, 95% CL 0.68-1.01). Mosquito numbers, relative wealth, number of house occupants, and the educational level of the head of the household had no effect on adherence. In unstructured questioning of house residents, excessive heat was often cited as a reason for not deploying the child's ITN. The most important reason for non-adherence was disruption of sleeping arrangements, indicating that ITNs were not readily redeployed in the face of shifting sleeping patterns due to visitors, funerals, house construction, and other events. Challenges faced by health education programs to maximize adherence with ITN use are discussed.

Journal ArticleDOI
TL;DR: Analysis of the use of improved diagnostic tests for amebiasis demonstrated that E. histolytica contributed to overall morbidity from diarrheal illness in Bangladeshi children, consistent with the development of species-specific acquired immunity.
Abstract: The epidemiology, clinical features, nutritional status, and causative agents of diarrhea were studied in 289 Bangladeshi children (147 boys and 142 girls) 2-5 years old. The use of improved diagnostic tests for amebiasis enabled for the first time analysis of the contribution of Entamoeba histolytica to total diarrheal illness in this community setting. The average incidence rate of diarrhea was 1.8/child-year, and the average number of diarrheal days was 3.7 days/child-year over an average observation period of 2.8 years/child. Seventy-five percent of the diarrheal episodes were < or = 2 days in duration. Persistent diarrhea was relatively uncommon (0.2% of the children) and chronic diarrhea was observed in only one episode. Compared with malnourished and/or stunted children, better-nourished children experienced significantly fewer diarrheal episodes. The diarrheal incidence rate for children with blood group A was significantly less that that of the children with blood groups O and AB. The most frequent bacterial enteropathogens isolated from diarrheal stool specimens were enterotoxigenic Escherichia coli (9%) and Aeromonas species (9%), followed by Plesimonas shigelloides (4%) and Shigella flexneri (3.8%). Rotavirus was the most common viral agent isolated from diarrheal stool samples (5%). Giardia lamblia, Cryptosporidium parvum, and E. histolytica were identified in 11%, 8.4%, and 8%, respectively, of the diarrheal stool specimens. Dysentery was observed in 7.7% of all diarrheal episodes. The most common pathogens isolated from dysenteric stool were S. flexneri (11.6%), Aeromonas sp. (10%), E. histolytica (8.7%), Campylobacter jejunii (5.8%), P. shigelloides (4.3%), and A. caviae (4.3%). The overall incidence rate of E. histolytica-associated diarrhea was 0.08/child-year. Visible blood and hemoccult test-detected blood loss was found in 7% and 25%, respectively, of cases of E. histolytica-associated diarrhea. Children who had recovered from a diarrheal episode with E. histolytica, but not E. dispar, had half the chance of developing subsequent E. histolytica-associated diarrhea, consistent with the development of species-specific acquired immunity. In conclusion, the use of modern diagnostic tests demonstrated that E. histolytica contributed to overall morbidity from diarrheal illness. Understanding the etiology, frequency, and consequences of acute diarrhea in children from a developing country should aid in the design of interventions to improve child health.

Journal ArticleDOI
TL;DR: Mortality rates were higher among children with severe dehydration and persistent diarrhea, and in stunted or underweight children infected with C. parvum, which remains untreatable among Ugandan children.
Abstract: A cross-sectional case-control study (ratio = 3:1) was conducted over a 15-month period to determine the prevalence and consequences of cryptosporidiosis in hospitalized diarrheic children (0–5 years old) at Mulago Hospital in Kampala, Uganda. Cryptosporidium parvum was detected and genotyped among 2,446 children of whom 1,779 (72.7%) had diarrhea, and 667 (27.3%) were age- and sex-matched controls. Of the 1,779 children with diarrhea, 532 (29.9%) had persistent (> 14 days) diarrhea and 1,247 (70.1%) had acute diarrhea. Overall, 444 (25.0%) of the 1,779 children with diarrhea had C. parvum, compared with only 57 (8.5%) of the 667 children without diarrhea (χ2 = 80.2, P ≤ 0.0001). Within this group of infected children, 72.8% were infected with genotype 1, 18.4% with genotype 2, and 4.1% with a mixture of both genotypes, and 4.1% isolates were either unclassified or C. meleagridis. The prevalence was highest during the rainy months of April to June. Of the 532 children with persistent diarrhea, 166 (31.2%) had C. parvum compared with 278 (22.3%) of the 1,247 children with acute diarrhea (χ2 = 15.8, P ≤ 0.0001). There was a significant association between C. parvum and malnutrition including stunting, being underweight, and wasting. Unfavorable outcome (death or failure to resolve within 14 days) occurred in 139 (72.8%) of the 191 children with C. parvum, and in only 65.1% of the 545 without (odds ratio = 1.117, 95% confidence interval = 1.005–1.243, P = 0.05), Of the 191 children with C. parvum, 24 (12.6%) died, compared with 34 (6.2%) of the 545 without C. parvum (P = 0.005). Mortality rates were higher among children with severe dehydration and persistent diarrhea, and in stunted or underweight children infected with C. parvum. Among Ugandan children, cryptosporidiosis, which remains untreatable, is frequently associated with diarrhea and other serious and unfavorable consequences.

Journal ArticleDOI
TL;DR: Age-adjusted comparison of subjects able to clear resistant parasites and those unable to do so provides a new phenotype for identifying host immune and genetic factors responsible for protective immunity against malaria.
Abstract: Residents of malaria-endemic areas sometimes spontaneously clear Plasmodium falciparum infection without drug treatment, implying an important role for host factors such as immunity in this clearance. Host factors may also contribute to clearance of parasites resistant to a treatment drug. Chloroquine resistance is caused by point mutations in P. falciparum chloroquine resistance transporter (pfcrt) gene. We investigated the clearance of malaria parasites carrying the key chloroquine resistance-conferring PfCRT mutation K76T in patients treated with chloroquine. We found that the ability to clear these resistant parasites is strongly dependent on age (the best surrogate for protective immunity in endemic areas), suggesting that host immunity plays a critical role in the clearance of resistant P. falciparum infections. Age-adjusted comparison of subjects able to clear resistant parasites and those unable to do so provides a new phenotype for identifying host immune and genetic factors responsible for protective immunity against malaria.

Journal ArticleDOI
Abstract: The effect of permethrin-treated bed nets (ITNs) on malaria vectors was studied as part of a large-scale, randomized, controlled trial in western Kenya. Indoor resting densities of fed Anopheles gambiae s.l. and An. funestus in intervention houses were 58.5% (P 0.010) and 94.5% (P 0.001) lower, respectively, compared with control houses. The sporozoite infection rate in An. gambiae s.l. was 0.8% in intervention areas compared with 3.4% (P 0.026) in control areas, while the sporozoite infection rates in An. funestus were not significantly different between the two areas. We estimated the overall transmission of Plasmodium falciparum in intervention areas to be 90% lower than in control areas. Permethrin resistance was not detected during the study period. As measured by densities of An. gambiae s.l., the efficacy of bed nets decreased if one or more residents did not sleep under a net or if bed nets had not been re-treated within six months. These results indicate that ITNs are optimally effective if used every night and if per- methrin is reapplied at least biannually. As part of the efficacy trial, we assessed some standard entomologicparameters: the number of indoor resting mos- quitoes, house exiting behavior, the proportion of mosquitoes infected with Plasmodium falciparum sporozoites, and insec- ticide resistance. We also assessed the effect of several human factors on the number of blood fed mosquitoes found resting indoors. The most important of these is adherence, which is whether the individual owning the net actually slept under a properly deployed net during the night before resting mos- quitoes were collected. We also measured the impact of the number of bed nets in houses and the time since re-treatment of nets with insecticide on numbers of fed mosquitoes.

Journal ArticleDOI
TL;DR: In areas of intense perennial malaria transmission, permethrin-treated bed nets reduce the adverse effect of malaria during the first four pregnancies, and in gravidae 1-4, no beneficial impact was observed.
Abstract: The impact of insecticide (permethrin)-treated bed nets (ITNs) on malaria in pregnancy was studied in a rural area in western Kenya with intense perennial malaria transmission. All households in 40 of 79 villages were randomized to receive ITNs by January 1997. The ITNs were distributed in control villages two years later. Complete data on birth outcome were available on 2,754 (89.6%) of 3,072 deliveries. Women (n = 780) were followed monthly throughout pregnancy in 19 of 79 villages. Among gravidae 1-4, ITNs were associated with reductions of 38% (95% confidence interval [CI] = 17-54%) in the incidence of malaria parasitemia and 47% (95% CI = 6-71%) in the incidence of severe malarial anemia (hemoglobin level < 8 g/dL with parasitemia) during pregnancy. At the time of delivery, mean hemoglobin levels were 0.6 g/dL (95% CI = 0.01-1.2 g/dL) higher, the prevalence of placental or maternal malaria was reduced by 35% (95% CI = 20-47%), and the prevalence of low birth weight was reduced by 28% (95% CI = 2-47%) in gravidae 1-4 from ITN villages. No beneficial impact was observed in gravidae five or higher. In areas of intense perennial malaria transmission, permethrin-treated bed nets reduce the adverse effect of malaria during the first four pregnancies.

Journal ArticleDOI
TL;DR: Seven formulations met the serologic criteria required for an expanded trial, and three were sufficiently attenuated clinically to justify further testing and would be considered for an expand Phase II trial in the future.
Abstract: Laboratory-attenuated strains of each of the four dengue serotypes previously tested as monovalent vaccines in volunteers were combined and tested for immunogenicity, safety, and reactogenicity in 16 dosage combinations. Tetravalent vaccines made using combinations of high (105–6 plaque-forming units [PFU]/dose) or low (103.5–4.5 PFU/dose) dosage formulations of each of the four viruses were inoculated in 64 flavivirus non-immune adult volunteers to determine which, if any, formulation raised neutralizing antibodies in at least 75% of volunteers to at least three of four dengue serotypes following one or two inoculations. Such formulations, if safe and sufficiently non-reactogenic, would be considered for an expanded Phase II trial in the future. Formulations 1–15 were each inoculated into three or four volunteers (total = 54) on days 0 and 28. Formulation 16 was tested in 10 volunteers, five volunteers inoculated on days 0 and 30, one volunteer on days 0 and 120, and four volunteers on days 0, 30, and 120. Blood was drawn for serologic assays immediately before and one month after each vaccination, and for viremia assay on day 10 after each vaccination. The 16 formulations were safe, but variably reactogenic after the first vaccination, and nearly non-reactogenic after the second and third vaccinations. Reactogenicity was positively correlated with immunogenicity. Similar proportions of volunteers seroconverted to dengue-1 (69%), dengue-2 (78%), and dengue-3 (69%), but significantly fewer volunteers seroconverted to dengue-4 (38%). The geometric mean 50% plaque reduction neutralization test titers in persons who seroconverted were significantly higher to dengue-1 (1:94) than to dengue-2 (1:15), dengue-3 (1:10), and dengue-4 (1:2). Seven formulations met the serologic criteria required for an expanded trial, and three of these were sufficiently attenuated clinically to justify further testing.

Journal ArticleDOI
TL;DR: In areas of intense perennial malaria transmission, ITNs substantially reduce exposure to malaria and subsequent malaria-associated morbidity in children less than 24 months old, and Protective efficacy was greatest in infants less than three months old and similar in older infants and one-year-old children.
Abstract: As part of a community-based, group-randomized, controlled trial of insecticide-treated bed nets (ITNs) in an area with intense malaria transmission in western Kenya, a birth cohort (n = 833) was followed monthly until the age of 24 months to determine the potential beneficial and adverse effects of reduced malaria exposure during pregnancy and infancy. Malaria transmission and morbidity were comparable pre-intervention. The ITNs reduced malaria attack rates (force of infection) in infancy by 74%, and delayed the median time-to-first parasitemia (4.5 to 10.7 months; P < 0.0001). The incidence of both clinical malaria and moderate-severe anemia (hemoglobin level <7 g/dL) were reduced by 60% (P < 0.001 for both). Protective efficacy was greatest in infants less than three months old and similar in older infants and one-year-old children. Efficacy was lowest in the dry season. Infants from ITN villages experienced better height and weight gain. In areas of intense perennial malaria transmission, ITNs substantially reduce exposure to malaria and subsequent malaria-associated morbidity in children less than 24 months old. Reduced malaria exposure during infancy did not result, with continued ITN use, in increased malaria morbidity in one-year-old children.

Journal ArticleDOI
TL;DR: Comparing the 3 studied genes, msp-2 results were most accurate, and analysis of this single gene effectively distinguished recrudescence from reinfection in the study population.
Abstract: Genotyping frequently is used to distinguish recrudescent from new infections in antimalarial drug efficacy trials, but methodology and interpretation of results have not been standardized. We compared the utility of polymorphisms within 3 Plasmodium falciparum genes during a longitudinal trial in Kampala, Uganda. Merozoite surface protein-1 (msp-1) and merozoite surface protein-2 (msp-2) revealed greater diversity than glutamate-rich protein. Genotypes based on msp-1, msp-2, and all 3 genes combined were compared for 394 initial and subsequent isolates. Classification of most episodes as due to recrudescence or reinfection was straightforward. In 24% (msp-1), 16% (msp-2), and 62% (3 genes combined) of samples, subsequent episodes contained identical and new alleles, however. Our analysis suggested that such episodes should be classified as reinfections and not recrudescence. Comparing the 3 studied genes, msp-2 results were most accurate, and analysis of this single gene effectively distinguished recrudescence from reinfection in our study population.

Journal ArticleDOI
TL;DR: Withdrawal of the use ofchloroquine appears to have resulted in the recovery of chloroquine efficacy and a reduction in the prevalence of K76T, however, other polymorphisms are also expected to contribute to resistance.
Abstract: In 1993, Malawi stopped treating patients with chloroquine for Plasmodium falciparum malaria because of a high treatment failure rate (58%). In 1998, the in vitro resistance rate to chloroquine was 3% in the Salima District of Malawi; in 2000, the in vivo resistance rate was 9%. We assayed two genetic mutations implicated in chloroquine resistance (N86Y in the P. falciparum multiple drug resistance gene 1 and K76T in the P. falciparum chloroquine resistance transporter gene) in 82 P. falciparum isolates collected during studies in 1998 and 2000. The prevalence of N86Y remained similar to that in neighboring African countries that continued to use chloroquine. In contrast, the prevalence of K76T was substantially lower than in neighboring countries, decreasing significantly from 17% in 1998 to 2% in 2000 (P 0.29). Withdrawal of the use of chloroquine appears to have resulted in the recovery of chloroquine efficacy and a reduction in the prevalence of K76T. However, other polymorphisms are also expected to contribute to resistance.

Journal ArticleDOI
TL;DR: This large-scale field study demonstrated early age of tapeworm and cysticercosis infections in humans, and short duration of taeniasis infections.
Abstract: The prevalence and characteristics of human taeniasis/cysticercosis and porcine cysticercosis were assessed in an endemic area of the Peruvian highlands. Individuals from 10 communities had stool examinations (N = 2,951) and serologic testing for Taenia solium antibodies (N = 2,583). The total porcine population present (N = 703) was also examined by serology. Cysticercosis is hyperendemic in this area and is associated with an important number of seizure cases. Human seroprevalence by village ranged from 7.1-26.9% (mean, 13.9%). Seroprevalence was higher among individuals with a history of seizures but not in those reporting a history of headache or intestinal taeniasis. Prevalence of taeniasis ranged from 0-6.7% (median, 2.5%). Coproantigen detection found 2.4 times more taeniasis cases than did microscopy (direct and after concentration). Age distribution for taeniasis showed a peak at younger ages than for seroprevalence. Porcine seroprevalence ranged from 42-75%. Random effects logistic regression models for human seropositivity demonstrated both in-house clustering of cases and a large increase in risk associated with a tapeworm carrier in the house. Besides confirming the close relationship between taeniasis and cysticercosis cases, this large-scale field study demonstrated early age of tapeworm and cysticercosis infections in humans, and short duration of taeniasis infections.

Journal ArticleDOI
TL;DR: In this article, the effect of insecticide (permethrin)-treated bed nets (ITNs) on the spatial distribution of malaria vectors in neighboring villages lacking ITNs was studied during a randomized controlled trial of ITNs in western Kenya.
Abstract: The effect of insecticide (permethrin)-treated bed nets (ITNs) on the spatial distribution of malaria vectors in neighboring villages lacking ITNs was studied during a randomized controlled trial of ITNs in western Kenya. There was a trend of decreased abundance of Anopheles gambiae with decreasing distance from intervention villages both before (P = 0.027) and after (P = 0.002) introduction of ITNs, but this trend was significantly stronger after ITNs were introduced (P = 0.05). For An. funestus, no pre-intervention trend was observed (P = 0.373), but after the intervention, a trend of decreased abundance with closer proximity to intervention compounds developed (P = 0.027). Reduction in mosquito populations in villages lacking ITNs was most apparent in compounds located within 600 meters of intervention villages. Sporozoite infection rates decreased in control areas following the introduction of ITNs (P < 0.001 for both species), but no spatial association was detected between sporozoite rates and distance to nearest intervention village. We conclude that high coverage of ITNs is associated with a community-wide suppression of mosquito populations that is detectable in neighboring villages lacking ITNs, thereby affording individuals residing in these villages some protection against malaria.

Journal ArticleDOI
TL;DR: It was found that average rainfall and the altitude were the best predictors of VL incidence, which is a vector-borne disease highly influenced by environmental factors.
Abstract: Visceral leishmaniasis (VL) is a vector-borne disease highly influenced by environmental factors. A model was developed for mapping the distribution and incidence of VL in Gedaref State, eastern Sudan, in relation to different environmental factors. Geographical information systems (GIS) were used to extract and map regression results for environmental variables of 190 villages in Gedaref State, including rainfall, vegetation status, soil type, altitude, distance from river, topography, wetness indexes, and average rainfall estimates. VL incidence in each village was calculated from hospital records. By use of logistic and linear multivariate regression analyses, models were developed to determine which environmental factors explain variability in VL presence and incidence. We found that average rainfall and the altitude were the best predictors of VL incidence. The resulting models were mapped by GIS software predicting both VL presence or absence and incidence at any locality in Gedaref State. The results are discussed in relation to VL control.

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TL;DR: Molecular and morphologic observations of specimens identified as An.
Abstract: Anopheles funestus is a major vector of malaria in Africa. It belongs to a group of sibling species that can be identified morphologically only at certain stages of their development. A diagnostic polymerase chain reaction (PCR)-based tool made it possible to differentiate five species of the group. The assay seems to be applicable over all their distribution area for four of these species: An. funestus, An. leesoni, An. parensis, and An. vaneedenip. The fifth species, An. rivulorum, is the second most abundant species of the group and can be mistaken at its adult stage for the major vector of malaria An. funestus. Molecular and morphologic observations of specimens identified as An. rivulorum from Cameroon and South Africa showed that they belong to two different taxa. The species identified in Cameroon, and named here An. rivulorum-like, might extend to western Africa and central Africa. The species-specific PCR assay is supplemented by a primer specific to An. rivulorum-like and thus makes it possible to differentiate the five species of the An. funestus group and the newly defined taxon.

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TL;DR: In a setting where diarrhea was a leading cause of death, intermittent use of home water treatment with flocculant-disinfectant decreased the incidence of diarrhea.
Abstract: We conducted a study to determine if use of a new flocculant-disinfectant home water treatment reduced diarrhea. We randomly assigned 492 rural Guatemalan households to five different water treatment groups: flocculant-disinfectant, flocculant-disinfectant plus a customized vessel, bleach, bleach plus a vessel, and control. During one year of observation, residents of control households had 4.31 episodes of diarrhea per 100 person-weeks, whereas the incidence of diarrhea was 24% lower among residents of households receiving flocculant-disinfectant, 29% lower among those receiving flocculant-disinfectant plus vessel, 25% lower among those receiving bleach, and 12% lower among households receiving bleach plus vessel. In unannounced evaluations of home drinking water, free chlorine was detected in samples from 27% of flocculant-disinfectant households, 35% of flocculant-disinfectant plus vessel households, 35% of bleach households, and 43% of bleach plus vessel households. In a setting where diarrhea was a leading cause of death, intermittent use of home water treatment with flocculant-disinfectant decreased the incidence of diarrhea.

Journal ArticleDOI
TL;DR: Proximity to the lake and contact with lake water were associated with infection, as were specific water-related activities including swimming, fishing, and collecting water.
Abstract: A survey of 1,246 children 10-12 years old in 32 primary schools in Kenya near Lake Victoria was conducted to determine prevalence and distribution of schistosome and geohelminth infections. Stool and urine samples were collected and examined for eggs of Schistosoma mansoni, S. haematobium, and intestinal helminths. A questionnaire was used to obtain demographic information and to quantify exposure to surface waters. Houses, schools, and water sources were mapped using a geographic information system. The mean school prevalence of S. mansoni infection was 16.3% (range = 0-80%). Proximity to the lake (r = 0.89, P < 0.001) and contact with lake water were associated with infection, as were specific water-related activities including swimming, fishing, and collecting water. Sixty-three percent of students were infected with one or more other geohelminths and these infections were more homogenously distributed. The separate distributions of schistosome and geohelminth infections have important implications for combined mass-treatment programs.

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TL;DR: The ITNs substantially reduced malaria-associated morbidity and improved weight gain in young children in this area of intense perennial malaria transmission and was associated with significantly higher mean weight-for-age Z-scores and mid-upper arm circumferences.
Abstract: Information on the impact of insecticide (permethrin)-treated bed nets (ITNs) from randomized controlled trials in areas of intense perennial malaria transmission is limited. As part of a large-scale, community-based, group-randomized controlled trial of the effect of ITNs on childhood mortality in a holoendemic area in western Kenya, we conducted three cross-sectional surveys in 60 villages to assess the impact of ITNs on morbidity in 1,890 children less than three years old. Children in ITN and control villages were comparable pre-intervention, but after the introduction of ITNs, children in intervention villages were less likely to have recently experienced illness requiring treatment (protective efficacy [95% confidence intervals] = 15% [1-26%]), have an enlarged spleen (32% [20-43%]), be parasitemic (19% [11-27%]), have clinical malaria (44% [6-66%]), have moderately severe anemia (hemoglobin level < 7.0 g/dL; 39% [18-54%]), or have a pruritic body rash, presumably from reduced nuisance insect bites (38% [24-50%]). Use of ITNs was also associated with significantly higher mean weight-for-age Z-scores and mid-upper arm circumferences. There was no evidence, however, that ITNs reduced the risk of helminth infections, diarrhea, or upper or lower respiratory tract infections. The ITNs substantially reduced malaria-associated morbidity and improved weight gain in young children in this area of intense perennial malaria transmission.

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TL;DR: Babiesial incidence at endemic sites in southern New England appears to have risen during the 1990s to a level approaching that due to borreliosis, and more older adults were admitted to hospital than younger adults.
Abstract: Human infection due to Babesia microti has been regarded as infrequent and a condition primarily affecting the elderly or immunocompromised. To determine whether risk in endemic sites may be increasing relative to that of Borrelia burgdorferi and to define its age-related clinical spectrum, we carried out a 10-year community-based serosurvey and case finding study on Block Island, Rhode Island. Less intensive observations were conducted in nearby sites. Incidence of babesial infection on Block Island increased during the early 1990s, reaching a level about three-fourths that of borrelial infection. The sera of approximately one-tenth of Block Island residents reacted against babesial antigen, a seroprevalence similar to those on Prudence Island and in southeastern Connecticut. Although the number and duration of babesial symptoms in people older than 50 years of age approximated those in people 20 to 49 years of age, more older adults were admitted to hospital than younger adults. Few Babesia-infected children were hospitalized. Babesial incidence at endemic sites in southern New England appears to have risen during the 1990s to a level approaching that due to borreliosis.

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TL;DR: The reliability of the PCR test was demonstrated, since all the 18 blood samples from newborns with congenital T. cruzi infection were positive, whereas the remaining samples (30 from control newborns of uninfected mothers and 262 of 263 from babies born to infected mothers) were negative.
Abstract: The polymerase chain reaction (PCR) is a potentially interesting diagnostic tool for detecting congenital Trypanosoma cruzi infection at birth. We have compared the sensitivity and capacity of a group of T. cruzi PCR primers in detecting the complete spectrum of known T. cruzi lineages, and to improve and simplify the detection of infection in neonatal blood. We found that the two primers, Tcz1/Tcz2 and Diaz1/Diaz2, which target the 195-basepair satellite repeat, detected all parasitic lineages with the same sensitivity. However, the intensity of the amplicon was somewhat higher with Tcz1/Tcz2. For other tested primers (nuclear DNA primers BP1/BP2, O1/O2, Pon1/Pon2, and Tca1/Tca2 and kinetoplast DNA primers S35'/S36' and 121/122), either the intensity of amplicons varied according to T. cruzi lineages or the PCR assay was less sensitive. The use of the Tcz1/Tcz2 primers, which target a tandem repetitive sequence, requires a careful determination of the appropriate amount of Taq polymerase to avoid the formation of smears and multiple amplicon bands. The Tcz1/Tcz2 primers resulted in an intense 200-basepair amplicon with DNA extracted from blood equivalent to 0.02 parasites per assay when used with a simple DNA extraction method and of a low amount of Taq polymerase from a standard PCR kit. To better assess such PCR protocol, we assayed 311 samples of neonatal blood previously tested by parasitologic methods. The reliability of our PCR test was demonstrated, since all the 18 blood samples from newborns with congenital T. cruzi infection were positive, whereas the remaining samples (30 from control newborns of uninfected mothers and 262 of 263 from babies born to infected mothers) were negative. Since our PCR method is simple, reliable, robust, and inexpensive, it appears suitable for the detection of T. cruzi infection in neonatal blood, even in laboratories that are not equipped for performing the PCR.

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TL;DR: Fecal samples from 194 individuals living in an area of Brazil endemic for Schistosoma mansoni were analyzed by a polymerase chain reaction (PCR) and the Kato-Katz parasitologic examination, demonstrating that the PCR assay might be a valuable alternative for diagnosing Schistsoma infections.
Abstract: Fecal samples from 194 individuals living in an area of Brazil endemic for Schistosoma mansoni were analyzed by a polymerase chain reaction (PCR) and the Kato-Katz parasitologic examination. Statistical analysis of the results showed a kappa index of 0.8 between the two methods. The prevalence of infection was 30.9% in three fecal samples examined by the Kato-Katz method, but 38.1% in one fecal sample examined by the PCR technique. Repeated survey of discordant results showed that five (41.6%) of 12 parasitologically negative cases for which PCR gave positive results were misdiagnosed by Kato-Katz examinations. The PCR technique showed a sensitivity of 96.7% and a specificity of 88% when the parasitologic examination was used as the reference test. The efficacy of cure with praziquantel was 87.8% in three parasitologic stool examinations and 75.6% in one PCR survey. These results demonstrate that the PCR assay might be a valuable alternative for diagnosing Schistosoma infections.