An overview of parasitic diseases in children in the United States: what's old? What's new? Where's help?
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Biomedical subjects
F O Richards
Publications and source records attributed to F O Richards.
Effects of permethrin-impregnated bed nets on malaria vectors of northern Guatemala.
The authors evaluated the effects on malaria vectors of bed nets impregnated with permethrin over the course of a 16-month controlled study in four communities of Northern Guatemala. Anopheles albimanus and An. vestitipennis were the known malaria vectors in the area. Households were allocated to one of three experimental groups: those receiving bed nets impregnated with 500 mg/m2 of permethrin, those receiving untreated bed nets, and those where no intervention measures were taken. The impact of the treated and untreated bed nets on mosquito abundance, behavior, and mortality was determined by indoor/outdoor night-bite mosquito collections, morning pyrethrum spray collections, inspection of bed net surfaces for dead mosquitoes, and capture-release-recapture studies. The duration of the treated nets' residual insecticide effect was assessed by modified WHO cone field bioassays, and their pyrethrin content was estimated by gas-liquid chromatography analysis. The most important observation was that fewer mosquitoes were found to be resting in the households with treated bed nets. The treated nets probably functioned by both repelling and killing vector mosquitoes. Capture-release-recapture studies showed exit rates from houses with treated nets were higher (94%) than those from control houses (72%), a finding that suggests repellency. However, no significant differences were noted between the indoor night-bite mosquito collections at houses with and without treated nets. The horizontal surfaces of treated bed nets were nearly 20 times more likely to contain dead anopheline mosquitoes than were the comparable surfaces of untreated nets. the bioassays indicated that unwashed permethrin-impregnated bed nets retained their insecticidal activity for 6 months after treatment.
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Permethrin-impregnated bed nets for malaria control in northern Guatemala: epidemiologic impact and community acceptance.
Permethrin-impregnated bed nets were evaluated as a control measure for malaria in northern Guatemala. Twelve hundred forty participants were allocated to one of three experimental groups (impregnated bed nets [IBN], untreated bed nets [UBN], and controls) and followed up for a period of 13 months. The incidence density of malaria was significantly lower in both IBN (86 cases/1,000 person-years) and UBN groups (106/1,000) compared with that in controls (200/1,000). No difference in malaria incidence was noted between the IBN and UBN groups. Complaints of fever and chills were less frequent in the IBN group compared with controls. The participants were enthusiastic about the nets, which they saw as a means for avoiding nuisance insects more than for preventing malaria. Most (85%) wanted to wash their nets every 4-12 weeks, a practice known to shorten the duration of residual insecticide action. Larger studies are needed to determine whether or not impregnated bed nets offer an advantage over untreated nets in this setting.
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Recent trends in the prevalence and distribution of schistosomiasis in the Nile delta region.
In 1983, a survey of 71 villages in the Nile delta demonstrated that the overall prevalence of Schistosoma mansoni and S. haematobium infections was 39% and 5%, respectively. Recent increased availability of praziquantel, combined with Egyptian Ministry of Health-sponsored media efforts to educate the public about schistosomiasis, prompted us to determine the current status of S. mansoni and S. haematobium infections in the delta and evaluate any changes that may have occurred since the previous survey. The same villages that participated in the 1983 survey were resampled in 1990. Stool and urine samples were requested from all occupants over the age of two years in a 5% sample of houses within each village. Stool (Kato) thick smears and urine sediments were read qualitatively at the rural health station. Field-prepared Kato smears and a 20% sample of urine specimens were forwarded to the Ministry of Health Laboratory, where quantitative readings were also performed. Analysis of samples obtained from 17,310 persons revealed that S. mansoni prevalence had decreased to 23% and that S. haematobium prevalence had decreased to 3% (P < 0.001). The highest levels of schistosome infection were found in governates located in the eastern section of the delta. The observed changes in the prevalence of S. mansoni and S. haematobium suggest that control measures are having a favorable impact on schistosomiasis transmission in this region.
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Use of geographic information systems in control programs for onchocerciasis in Guatemala.
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Alterations in filarial antigen-specific immunologic reactivity following treatment with ivermectin and diethylcarbamazine.
The presence of circulating microfilariae has been associated with alterations in B and T cell functions. In this study, we compared the influence of diethylcarbamazine (DEC) and ivermectin on filarial antigen-specific immune responses in a Haitian population. Both drugs were effective at reducing microfilaremia levels to less than 10% of pretreatment levels for up to one year. This reduction in microfilaremia was associated with two phases of altered cellular responsiveness monitored with in vitro assays. Five days post-treatment, cellular proliferation in response to both filarial and nonfilarial antigens was significantly increased, as was the background response in the absence of any antigen. At both nine months and one year post-treatment, the filarial antigen-specific reactivity of both DEC- and ivermectin-treated patients was significantly increased over baseline levels. No differences were observed between the two treatment groups in terms of humoral or cellular reactivity to filarial antigens, despite evidence suggesting a role for DEC in adult worm killing. These results provide additional evidence that microfilariae modulate antifilarial immune reactivity.
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Ivermectin: reduction in prevalence and infection intensity of Onchocerca volvulus following biannual treatments in five Guatemalan communities.
Residents of five hyperendemic communities located in the central focus of onchocerciasis in Guatemala were treated with ivermectin (Mectizan) or placebo every six months for 30 months. The effects of treatment on prevalence and the intensity of skin infection (microfilarial skin density [MFD]) were evaluated. Significant and persistent reductions in both of these indices were achieved by coverage of 80.7% of the eligible populations. The highest proportionate reductions in both indicators of infection occurred after the first treatment, followed by more gradual decreases through the fourth treatment. In one community in which the mean coverage was 92.7%, prevalence decreased from 74.0% at pretreatment to 34.9% after four treatments, while the MFD decreased from 7.8 to 2.0; reductions of 52.8% and 74.3% from pretreatment values, respectively. In every ivermectin-treated community except one, in which drug acceptance was low, the mean community MFD values were reduced to the level associated with low infectiousness for the vector, Simulium ochraceum. Moreover, the category of MFD associated with high vector infectiousness was reduced at least ten-fold over the pretreatment level. One community had low participation during the first two treatments (32.8% and 22.7% of those eligible). This increased to 55.2% at the third treatment because of implementation of an educational program describing both the disease and the beneficial effects of ivermectin and because skin biopsies and nodulectomies were not performed. Secondary reaction rates for all communities were 29.5%, 9.9%, 10.3%, 8.2%, and 7.1% for the first through fifth treatments, respectively. Pruritus was the most common (34.0%) secondary reaction, followed by facial edema (31.8%). All reactions were classified as mild to moderate. Recommendations for mass distribution of ivermectin in Guatemala are given.
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Cysticercosis surveillance: locally acquired and travel-related infections and detection of intestinal tapeworm carriers in Los Angeles County.
A surveillance system for cysticercosis was initiated in January 1988 in Los Angeles County to measure the incidence of the disease, to more accurately assess the level of locally acquired and travel-related infection, and to evaluate household contacts for intestinal tapeworm infection. In three years of surveillance (1988-1990), 138 incident cases were reported for an average crude annual incidence rate of 0.6 per 100,000 population. The highest rates were among Hispanics (1.6/100,000), most of whom were Mexican immigrants. Eight (5.8%) cases were fatal. Nine (6.5%) probable travel-associated cases occurred among persons born in the United States who had traveled to Mexico. Ten (7.2%) autochthonous cases of cysticercosis were documented. Taenia eggs were recovered more commonly in specimens from contacts with cysticercosis cases (1.1%) than in specimens from noncontact patients (0.2%). At least one Taenia tapeworm carrier was found among contacts of five (6.9%) of 72 cysticercosis patients. Carriers were more likely to be found among contacts of patients born in the United States (22.2%) than among those of foreign-born (4.8%) patients (odds ratio = 5.4) Cysticercosis causes appreciable morbidity and mortality in Los Angeles County, principally among Hispanic immigrants. However, these results indicate that both travel-acquired and locally acquired cysticercosis may be more common than previously recognized. Public health followup of cysticercosis cases, including screening of household contacts, can identify tapeworm carriers, who can be treated and removed as potential sources of further infection.
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Guatemalan human onchocerciasis. I. Systematic analysis of patient populations, nodular antigens, and specific isotypic reactions.
The population from five Guatemalan plantations in areas endemic for onchocerciasis was surveyed, and 1032 individuals were recruited to participate in our study. From physical examination, past clinical history (5 to 8 yr), laboratory evidence and sample availability, a group of 778 long term residents with confirmed disease status were selected for detailed examination. We were able to identify 268 long term residents of endemic areas who had never been infected, 44 of these are from hyper- and mesoendemic areas. The 44 uninfected individuals from the hyper- and mesoendemic areas, because of their considerable exposure to this disease, were classified as "putatively immune." Intact nodules containing adult worms of Onchocerca volvulus were homogenized in the presence of protease inhibitors and fractionated into particulate and aqueous isotonic soluble antigens. Systematic analysis of these Ag fractions showed considerable amounts of Ig, presumably associated with Ag in the form of immune complexes. Individual specific antibody reactions from all 778 patients to nodule Ag were examined. Reactions to O. volvulus antigens by antibodies from patients with confirmed parasitic infections were almost exclusively restricted to IgG1 and IgG4 isotypes. Antigenic activity appeared to be primarily associated with low molecular mass (14 to 29 kDa) components. Some competitive blocking of antibody activities of other isotypes by IgG1 was observed, most notable was that of IgG3 and IgA. IgG4 and IgM activities were not significantly blocked.
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Changes in circulating parasite antigen levels after treatment of bancroftian filariasis with diethylcarbamazine and ivermectin.
This study assessed changes in circulating parasite antigen levels after diethylcarbamazine (DEC) and ivermectin treatment of bancroftian filariasis to determine effects of these drugs on adult Wuchereria bancrofti in vivo. Thirty adult Haitians with microfilaremia were treated with 1 mg of ivermectin to reduce counts of microfilariae. Later, subjects were treated with either one or two 200 micrograms/kg doses of ivermectin or with 12 daily 6 mg/kg doses of DEC. Macrofilaricidal activity of these drugs was indirectly monitored by measuring circulating W. bancrofti antigen by EIA. Antigen levels fell by 75% after DEC and by 34% after ivermectin. These results suggest that low-dose ivermectin treatment followed by a standard course of DEC is a more effective macrofilaricidal regimen for W. bancrofti than either of the multidose ivermectin regimens used in this study.
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Molecular cloning and characterization of recombinant parasite antigens for immunodiagnosis of onchocerciasis.
Immunological cross-reactivity among nematodes has hampered the development of specific serodiagnostic assays for onchocerciasis. In the present study, an Onchocerca volvulus adult worm complementary DNA expression library was differentially screened with human sera from patients infected with O. volvulus and with an omnibus anti-nematode serum pool comprised of sera from patients infected with Brugia malayi, Loa loa, Wuchereria bancrofti, Mansonella perstans, Strongyloides stercoralis, Ancylostoma duodenale, Ascaris lumbricoides, and Dracunculus medinensis. Seven Onchocerca-specific clones were identified and screened with individual onchocerciasis patient sera. Additional studies were performed to characterize the most immunoreactive clones, OC 3.6 and OC 9.3. OC 3.6 produced a 152-kD beta-galactosidase fusion protein that was recognized in dot-immunoblots by 54 of 55 sera from onchocerciasis patients (98%). The OC 3.6 DNA insert is 996 bp long with an open reading frame of 627 bp and a 369-bp untranslated 3' end. OC 3.6 is closely related to a previously reported clone (OV 33-3), but it differs from that clone at both the 5' and 3' ends. OC 9.3 contained a novel 565-bp insert and produced a 138-kD fusion protein that was recognized by 46 of 55 sera from onchocerciasis patients (83%). Additional studies are in progress to develop and evaluate immunodiagnostic tests for onchocerciasis based on measurement of antibodies to these promising recombinant antigens.
Amino Acid Sequence↗
Experimental Onchocerca volvulus infections in mangabey monkeys (Cercocebus atys) compared to infections in humans and chimpanzees (Pan troglodytes).
Three chimpanzees, three mangabey monkeys (Cercocebus atys), and 14 patas monkeys (Erythrocebus patas) were inoculated with L3 Onchocerca volvulus of Guatemalan origin. One chimpanzee and two mangabey monkeys developed antibody activity to at least three different antigens. Both mangabey monkeys recognized a 20 kDa antigen 3.5-5 months post-inoculation, and the monkeys and the chimpanzee developed antibody activity to 14 and 22 kDa antigens 7.5-13 months post-inoculation. One mangabey monkey and the chimpanzee became microfilaria-positive in skin snips at 16 and 21 months post-inoculation, respectively. Antibody activity to the 20 kDa antigen in the mangabey monkeys is noteworthy because of the prominence of this antigen among putatively immune persons living in onchocerciasis-endemic areas. The two mangabey monkeys responded parasitologically in a manner comparable to immune humans. No microfilariae were detected in one monkey and only scant numbers of microfilariae were observed in the second. The mangabey monkey may be a good animal model for the study of onchocerciasis.
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Comparison of high dose ivermectin and diethylcarbamazine for activity against bancroftian filariasis in Haiti.
This three-phase study was designed to compare high dose ivermectin with a standard diethylcarbamazine (DEC) regimen for patient tolerability, potential to kill adult filaria, and duration of microfilarial suppression in 30 Haitian subjects with Wuchereria bancrofti microfilaremia. All were first given a 1-mg oral dose of ivermectin (phase 1) to reduce microfilaria densities. Participants were randomized into three groups: Group 1 received DEC (6mg/kg per day for 12 days), Group 2 received 200 mcg/kg of ivermectin, and Group 3 received 400 mcg/kg of ivermectin (200 mcg/kg per day for 2 days). All drug regimens were well tolerated with few adverse reactions. Most reactions occurred during phase I and consisted primarily of headache, fever, and myalgia. At the end of phase 1, 27 of 30 (90%) patients were microfilaria negative. During phase 2, four of the six men receiving DEC developed scrotal reactions suggesting killing adult worms; no such reactions were noted in 10 men receiving ivermectin (p less than 0.05). At one-year follow up (phase 3), all treatment groups had less than 10% return to pretreatment microfilaria levels. The mean percent of baseline microfilaria counts were for Group 1, 0.9% (range 0-5%); Group 2, 8.2% (range 0-31%); and Group 3, 3.8% (range 0-25%). Seven individuals in Group 1 were microfilaria-negative, while only one and three individuals were microfilaria-negative in Groups 2 and 3, respectively. These results suggest that DEC causes more damage to the adult worms and greater reduction in microfilaria densities than ivermectin, but that high doses of ivermectin may suppress microfilaremia in lymphatic filariasis for periods much longer than previously reported.
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1983 Nile Delta schistosomiasis survey: 48 years after Scott.
To determine whether the sharply declining Schistosoma haematobium infection rates in parts of the Nile Delta could be generalized to the entire region, and to update the status of S. mansoni infection rates, a large scale survey was undertaken in 1983 in 70 of the 71 districts of the Nile Delta. In a house-to-house survey, greater than 91% of the sample population of 16,675 participated by providing stool and/or urine specimens which were examined qualitatively by Kato thick smear and sedimentation techniques, respectively. After the 1935 survey by Scott, the prevalence of S. mansoni appeared to change little, from 33% in 1935 to 39% in 1983, but a more sensitive diagnostic technique in 1983 strongly suggested that the actual prevalence had decreased between the 2 surveys. In contrast, the prevalence of S. haematobium infection decreased from 56% to 5%, with a similar decline in all 8 governorates. The dramatic decline in S. haematobium prevalence has been accompanied temporally with a sharp decrease in the population density of Bulinus truncatus. S. mansoni has become the predominant human schistosome species in the Nile Delta.
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Modification of the FAST-ELISA for field diagnosis of schistosomiasis mansoni with serum or blood samples.
Using well-characterized serum pools from patients (with schistosomiasis mansoni), we modified the FAST-ELISA system for detecting serum antibodies to Schistosoma mansoni for field use. We found little or no change in test function or results when the test was run 1) with blood instead of serum, 2) after addition of sodium azide preservation to diluted and lysed blood specimens, 3) using impure water in wash steps, and 4) without a spectrophotometer (i.e., read with the naked eye). Our evaluation of the modified FAST-ELISA showed that it can be successfully used under the restraints of minimally equipped field laboratories.
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Dynamics of microfilariae of Onchocerca volvulus over the first 72 hours after treatment with ivermectin.
Changes in microfilaria (mf) densities in skin, blood and urine were followed over 72 hours in 8 Guatemalan patients who received invermectin (150 mcg/kg po in a single dose). After an initial increase at 6 hours, the significance of which is not clear, mf densities in skin snips decreased rapidly to reach 13% of their pre-treatment level by 48 hours and then fell much more slowly over the next 24-hour period. The fall in mf concentrations is thought to be mainly a result of movement away from the subepidermal layer. In contrast to what happens after DEC, it was not accompanied by any marked wave of microfilaraemia or microfilaruria, nor by the appearance of a papular rash, although brawny oedema of the skin sometimes developed. Reactions that occurred after ivermectin could not be correlated with the initial density of microfiladermia. It is hypothesized that the movement of mfs may be 1) into the deeper layers of the dermal collagen, 2) the subcutaneous fat, or 3) the lymphatic system.
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Cysticercosis in Los Angeles County.
Four hundred ninety-seven patients were identified as having been treated for cysticercosis at four hospitals in Los Angeles during the 11-year period 1973 through 1983. Eleven deaths were recorded. Over 90% of these patients were Hispanics in productive age groups; the majority were Mexican by nationality. Hospitalizations were generally short, and readmissions for recurrence of symptoms or complications of therapy occurred in only 14% of patients. Cysticercosis was diagnosed in 12 US citizens who had no history of travel to countries considered traditionally endemic for Taenia solium taeniasis/cysticercosis. A dramatic rise in numbers of cases was observed after 1977, appearing to plateau at approximately 80 cases per year in 1981. The increase in cases beginning in 1977 coincided with the introduction of the computed tomographic scan.
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An evaluation of quantitative techniques for Schistosoma haematobium eggs in urine preserved with carbolfuchsin.
The objective of this study was to determine a suitable method for quantitating Schistosoma haematobium eggs in urine specimens preserved in carbolfuchsin. Using a 0.002% carbolfuchsin-phenol-alcohol solution as a stain/preservative for urine obtained from 30 patients infected with S. haematobium, we compared egg counts obtained with four quantitative techniques: Nytrel filtration, Nuclepore filtration, suction filtration and centrifugation. Centrifugation gave statistically higher values than all other techniques for absolute number of eggs recovered in the preserved urine. We also measure a statistical difference between the counts obtained from Nuclepore filtration of fresh urine and those established on an equivalent volume of preserved urine by Nuclepore and Nytrel filtration. The preserved urine frequently caused obstruction of both Nuclepore filters and Whatman No. 1 filters (used in suction filtration), rendering them technically difficult to use and less satisfactory than other methods. From the techniques we examined, we conclude that in field studies where preservation of urine is necessary, preparation of Nuclepore filters with fresh urine, or centrifugation of a carbolfuchsin-preserved urine, are the methods of choice for quantitation of specimens.
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