Mass treatment to eliminate filariasis in Papua New Guinea.
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BACKGROUND: The global initiative to eradicate bancroftian filariasis currently relies on mass treatment with four to six annual doses of antifilarial drugs. The goal is to reduce the reservoir of microfilariae in the blood to a level that is insufficient to maintain transmission by the mosquito vector. METHODS: In nearly 2500 residents of Papua New Guinea, we prospectively assessed the effects of four annual treatments with a single dose of diethylcarbamazine plus ivermectin or diethylcarbamazine alone on the incidence of microfilariae-positive infections, the severity of lymphatic disease, and the rate of transmission of Wuchereria bancrofti by mosquitoes. Random assignment to treatment regimens was carried out according to the village of residence, and villages were categorized as having moderate or high rates of transmission. RESULTS: The four annual treatments with either drug regimen were taken by 77 to 86 percent of the members of the population who were at least five years old; treatments were well tolerated. The proportion with microfilariae-positive infections decreased by 86 to 98 percent, with a greater reduction in areas with a moderate rate of transmission than in those with a high rate. The respective aggregate frequencies of hydrocele and leg lymphedema were 15 percent and 5 percent before the trial began, and 5 percent (P<0.001) and 4 percent (P=0.04) after five years. Hydrocele and leg lymphedema were eliminated in 87 percent and 69 percent, respectively, of those who had these conditions at the outset. The rate of transmission by mosquitoes decreased substantially, and new microfilariae-positive infections in children were almost completely prevented over the five-year study period. CONCLUSIONS: Annual mass treatment with drugs such as diethylcarbamazine can virtually eliminate the reservoir of microfilariae and greatly reduce the frequency of clinical lymphatic abnormalities due to bancroftian filariasis. Eradication may be possible in areas with moderate rates of transmission, but longer periods of treatment or additional control measures may be necessary in areas with high rates of transmission. (+info)
Rapid assessment method for prevalence and intensity of Loa loa infection.
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OBJECTIVE: To assess the validity of observations on eye worm and Calabar swellings for the rapid assessment of the prevalence and intensity of loiasis at the community level. METHOD: A total of 12895 individuals over the age of 15 years living in 102 communities in Cameroon and Nigeria took part in the study. A standardized questionnaire was administered to participants from whom finger-prick blood samples were collected and examined for Loa loa microfilariae. Rapid assessments of the prevalence and intensity of loiasis were made on the basis of a history of eye worm or Calabar swellings. FINDINGS: There was a strong correlation between the indices of the rapid assessment procedures and the parasitological indices of L. loa endemicity. The rapid assessment indices were effective in diagnosing high-risk communities (sensitivity 94-100%; specificity 66-92%). The highest sensitivity (100%) and specificity (92%) were obtained with a rapid assessment procedure based on a history of eye worm lasting 1-7 days together with confirmation by the guided recognition of a photograph of adult L. loa in the eye. CONCLUSION: Rapid assessment of the prevalence and intensity of loiasis at the community level can be achieved using a procedure based on the history of eye worm lasting 1-7 days together with confirmation by the guided recognition of a photograph of an adult L. loa in the eye. (+info)
Streptomyces avermitilis sp. nov., nom. rev., a taxonomic home for the avermectin-producing streptomycetes.
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The taxonomic status of 'Streptomyces avermitilis' strain MA-4680 was established using a polyphasic approach. Strain MA-4680 formed a distinct phyletic line in the 16S rDNA streptomycete tree, and it was evident from the almost complete 16S rDNA sequence data that it was most closely related to Streptomyces cinnabarinus, Streptomyces griseochromogenes, Streptomyces resistomycificus and Streptomyces viridochromogenes. However, strain MA-4680 was readily distinguished from the type strains of these species by using a range of phenotypic properties, notably morphological and pigmentation features. The combined genotypic and phenotypic datasets indicate that the organism forms a recognizable centre of variation within the genus Streptomyces. It is proposed that 'Streptomyces avermitilis' be formally recognized as a species of Streptomyces. The type strain is MA-4680(T) (ATCC 31267(T) = NCIMB 12804(T0 = NRRL 8165(T)). (+info)
Streptomyces avermectinius sp. nov., an avermectin-producing strain.
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We propose the establishment of a new species, Streptomyces avermectinius, based on characterization of strain MA-4680(T) and morphological and phylogenetic comparisons with closely related members of the genus Streptomyces. The 16S rDNA sequence was obtained from this strain and used to place it among Streptomyces species using the variable alpha region and the nearly complete 16S rDNA sequence. Four Streptomyces species were selected as related species from phenotypic data, three species from phylogenetic databases on alpha region sequences and two species from phylogenetic data using nearly complete 16S rDNA sequences. Analysis of DNA-DNA hybridization tests distinguished strain MA-4680(T) from these eight Streptomyces species. The type strain is strain MA-4680(T) (= ATCC 31267(T) = NRRL 8165(T)). (+info)
Toxicity and pathological effects of orally and intraperitoneally administered ivermectin on sea bass Dicentrarchus labrax.
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The toxicity and histopathology of ivermectin was studied in 3 and 35 g sea bass Dicentrarchus labrax L. following in-feed, oral intubation and injection administration at dose rates ranging from 0.5 to 3.5 mg kg(-1). Estimated LD50 values for 3 g fish were 0.335 and 0.106 mg kg(-1) following oral intubation and injection administration respectively, for fish reared at 11 degrees C; and 0.839 and 1.023 mg kg(-1) following oral intubation and injection administration, respectively for fish reared at 20 degrees C. For 35 g fish reared at 11 degrees C, the estimated LD50 was 0.523 and 0.361 mg kg(-1) following oral intubation and injection administration respectively. No signs of toxicity were observed when the compound was administered via the feed at 0.5 and 0.7 mg kg(-1). However, toxicity (> 10%) was observed at dose rates of 0.2 mg kg(-1) and higher when the compound was administered via oral intubation and at 0.5 mg kg(-1) when administered via injection. The compound was significantly more toxic to fish reared at 11 degrees C than at 20 degrees C. Further, ivermectin was more toxic to 3 g than to 35 g sea bass when administered via injection. Histopathological examination of the major organs revealed pathology was largely restricted to gills and intestinal tissue. In 3 g sea bass, lesions were also found in the kidneys. (+info)
Cloning and analysis of a DNA fragment stimulating avermectin production in various Streptomyces avermitilis strains.
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To isolate a gene for stimulating avermectin production, a genomic library of Streptomyces avermitilis ATCC 31267 was constructed in Streptomyces lividans TK21 as the host strain. An 8.0-kb DNA fragment that significantly stimulated actinorhodin and undecylprodigiosin production was isolated. When wild-type S. avermitilis was transformed with the cloned fragment, avermectin production increased approximately 3.5-fold. The introduction of this fragment into high-producer (ATCC 31780) and semi-industrial (L-9) strains also resulted in an increase of avermectin production by more than 2.0- and 1.4-fold, respectively. Subclones were studied to locate the minimal region involved in stimulation of pigmented-antibiotic and avermectin production. An analysis of the nucleotide sequence of the entire DNA fragment identified eight complete and one incomplete open reading frame. All but one of the deduced proteins exhibited strong homology (68 to 84% identity) to the hypothetical proteins of Streptomyces coelicolor A3(2). The orfX gene product showed no significant similarity to any other protein in the databases, and an analysis of its sequence suggested that it was a putative membrane protein. Although the nature of the stimulatory effect is still unclear, the disruption of orfX revealed that this gene was intrinsically involved in the stimulation of avermectin production in S. avermitilis. (+info)
Immune responses directed against microfilariae correlate with severity of clinical onchodermatitis and treatment history.
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The induction of pathological changes in Onchocerca volvulus infections is directly related to the presence of the microfilarial stage of this filarial nematode. Patients with either of the 2 major forms of the clinical disease (i.e., asymptomatic/mild [n=12] and severe [n=16] dermatopathology) were studied. The cellular immune responses (cell proliferation) of those with severe disease were stronger (stimulation index [SI], 12.3+/-1.9) than those with mild dermatopathological effects (SI, 2.9+/-0.6) or control patients (SI, 4.5+/-0.4). Cytoadherence antibody responses were greatest (grade 4) in the clinically severe group and only weak (grades < or = 1) in the mild group or the control patients. Ivermectin treatment was followed by an increase in immune responsiveness in those with initially poor responses. Thus, the degree of dermatopathological effect is related to the host's immune response against microfilariae, and ivermectin augments such responses. (+info)
A comparison of the efficacy of single doses of albendazole, ivermectin, and diethylcarbamazine alone or in combinations against Ascaris and Trichuris spp.
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OBJECTIVE: To determine the efficacy of single doses of albendazole, ivermectin and diethylcarbamazine, and of the combinations albendazole + ivermectin and albendazole + diethylcarbamazine against common intestinal helminthiases caused by Ascaris and Trichuris spp. METHODS: In a randomized, placebo-controlled trial, infected children were randomly assigned to treatment with albendazole + placebo, ivermectin + placebo, diethylcarbamazine + placebo, albendazole + ivermectin, or albendazole + diethylcarbamazine. The Kato-Katz method was used for qualitative and quantitative parasitological diagnosis. The chi2 test was used to determine the significance of cure rates, repeated measures analysis of variance for the comparison of mean log egg counts, the Newman-Keuls procedure for multiple comparison tests, and logistic regression for the comparison of infection rates at days 180 and 360 after treatment. FINDINGS: Albendazole, ivermectin and the drug combinations gave significantly higher cure and egg reduction rates for ascariasis than diethylcarbamazine. For trichuriasis, albendazole + ivermectin gave significantly higher cure and egg reduction rates than the other treatments: the infection rates were lower 180 and 360 days after treatment. CONCLUSION: Because of the superiority of albendazole + ivermectin against both lymphatic filariasis and trichuriasis, this combination appears to be a suitable tool for the integrated or combined control of both public health problems. (+info)