Comparative insecticidal power of three pyrethroids on netting.

Adult mosquitoes, Anopheles gambiae Giles and Culex quinquefasciatus Say (Diptera: Culicidae), were exposed for 3 min to replicate samples of polyester netting cut from replicate bednets treated with pyrethroid insecticide formulations at the recommended concentration (alphacypermethrin SC at 40mg ai/m2; cyfluthrin EW at 50 mg ai/m2; deltamethrin WT at 25 mg ai/m2), or treated with only a quarter of those dosages. After 4 months domestic use of the bednets in Malawi, chemical assays showed that pyrethroid deposits on the netting were somewhat less than the target concentrations. Comparing the pyrethroid bioassay results with Anopheles at both treatment concentrations, deltamethrin gave significantly higher mortality (99.7-100%) than the other compounds (alphacypermethrin 94-96%, cyfluthrin 80-89%). Culex bioassay mortality was lower (alphacypermethrin 56-74%; cyfluthrin 63-65%; deltamethrin 50-81 %) and results with the three pyrethroid insecticides at their recommended doses did not differ significantly.

Impact of fly control on childhood diarrhoea in Pakistan: community-randomised trial.

BACKGROUND: Several million children are killed each year by diarrhoeal diseases; preventive strategies appropriate for developing countries are vital. Despite strong circumstantial evidence that flies are vectors of diarrhoeal diseases, no convincing studies of the impact of fly control on diarrhoea incidence in developing countries have been reported. We undertook a randomised study of the effect of insecticide spraying on diarrhoea incidence. METHODS: Six study villages were randomly assigned to two groups. Flies were controlled through insecticide application in group A in 1995 and in group B in 1996. In 1997 the effectiveness of baited fly traps was tested in group A villages. Diarrhoea episodes were monitored in children under 5 years through mothers' reports during weekly visits by a health visitor. Fly density was monitored by use of sticky fly-papers hung in sentinel compounds. FINDINGS: During the fly seasons (March-June) of both 1995 and 1996, insecticide application practically eliminated the fly population in the treated villages. The incidence of diarrhoea was lower in the sprayed villages than in the unsprayed villages in both 1995 (mean episodes per child-year 6.3 vs 7.1) and 1996 (4.4 vs 6.5); the reduction in incidence was 23% (95% CI 11-33, p=0.007). At times other than the fly season there was no evidence of a difference, in diarrhoea morbidity between sprayed and unsprayed villages. Fly density data for 1997 indicate the ineffectiveness of baited traps in this setting. INTERPRETATION: Fly control can have an impact on diarrhoea incidence similar to, or greater than, that of the interventions currently recommended by WHO for inclusion in diarrhoeal disease control programmes in developing countries. This important finding needs confirmation in other settings in developing countries. Technologies and practices that interrupt disease transmission by flies need to be developed and promoted.

PIP: Since circumstantial evidence suggests that flies are vectors of diarrheal diseases, a randomized study of the effect of insecticide spraying upon the incidence of diarrhea was conducted near the town of Peshawar, North West Frontier Province, Pakistan. 6 study villages were randomly assigned to 2 groups, with flies controlled through the twice weekly application of ultra low volume space spraying with insecticide in group A in 1995 and in group B in 1996. The insecticide used was Aqua K-Othrine, a water-based formulation of deltamethrin, applied at a dose of 0.5-1.0 g of active ingredient per hectare by Porta-Pak sprayers. In 1997, the effectiveness of baited fly traps was tested in group A villages. The incidence of diarrhea episodes was monitored in children under age 5 years through mothers' reports during weekly visits by a health worker, and fly density was monitored using sticky fly-papers hung in sentinel compounds. During the fly seasons of March-June in 1995 and 1996, the application of insecticide almost eliminated the fly population in the treated villages. The incidence of diarrhea was lower in the sprayed villages than in the unsprayed villages in both 1995 and 1996, for an overall 23% reduction in incidence. At times other than the fly season, no evidence was observed of a difference in diarrhea morbidity between sprayed and unsprayed villages. Fly density data for 1997 found the baited traps to be ineffective.

Onchocerciasis in the Amazonian focus of southern Venezuela: altitude and blackfly species composition as predictors of endemicity to select communities for ivermectin control programmes.

In preparation for an ivermectin distribution programme, the prevalence and intensity of infection due to Onchocerca volvulus as well as the species composition and abundance of Simulium vectors were investigated in 22 Yanomami communities situated along 2 altitudinal transects in the southern Venezuelan onchocerciasis focus. These transects corresponded to the Ocamo-Putaco and Orinoco-Orinoquito river systems, covering a range of elevation between 50 m and 740 m above sea level (asl). A total of 831 people underwent parasitological examination in this survey and an additional 196 patients from a previous study, at an altitude of 950 m, were included in the analysis. A total of 92,659 man-biting blackflies were collected and identified to morphospecies. S. oyapockense s.l. was the predominant simuliid up to 150 m asl, whereas S. guianense s.l. and S. incrustatum s.l. prevailed above 150 m. Communities located below 150 m were found to range from hypo- to mesoendemic; all villages above 150 m proved to be hyperendemic (> 60% microfilarial prevalence) and mass ivermectin treatment should be implemented. Age above 10-14 years, altitude of the village and biting rate of S. guianense s.l. up to 200 m asl were found to be statistically significant independent predictors of infection by multivariate logistic regression using a spline model. There were no differences in infection status according to sex. Above 200 m, microfilarial rate and density remained approximately constant, prevalence averaging 79% regardless of blackfly abundance. For the implementation of ivermectin-based onchocerciasis control programmes in the Amazonian focus, altitude and species composition of the blackfly population might be adopted as useful indicators aiding selection of the most affected communities. However, below 200 m additional parasitological indicators may also be necessary. As a direct result of this study, regular mass-ivermectin delivery to meso- and hyperendemic communities is now in progress.

Low level ivermectin coverage and the transmission of onchocerciasis.

Regular collections of biting Simulium damnosum s.l. were carried out during a community-based trial of doses of ivermectin every 6 months for onchocerciasis in Sierra Leone. Over 64,000 blackflies were caught at 4 sites close to treated villages and one site near an untreated village. More than 17,000 of these blackflies were dissected during the 31 months of the study and 5 doses of ivermectin were distributed to about 30% of the human population in the treated villages. High annual biting rates (about 100,000 bites per year) and transmission potentials (about 5000 larvae per year) were found at all catching sites. Approximately 30% of parous blackflies carried Onchocerca volvulus larvae, and 8% had infective stage larvae. None of these indices appeared to be affected by the distribution of ivermectin. However, the mean number of larvae per infected blackfly fell from 8.7 to 5.8 during the study period in the treated villages, equivalent to a 21% decrease per year. No such reduction was seen in the control village. This study demonstrates that in areas where high capacity vectors predominate, the effect on transmission of even a low coverage of the human population with repeated doses of ivermectin may be detectable using the sensitive entomological index of intensity of infection in infected flies. Statistical analysis of onchocerciasis transmission data is a complex issue and ways of improving the design of trials and applying appropriate statistical methods are discussed.

Mosquito control in Dar es Salaam. I. Assessment of Culex quinquefasciatus breeding sites prior to intervention.

In preparation for a trial polystyrene beads and pyriproxyfen for the control of Culex quinquefasciatus mosquitoes, surveys of their breeding were carried out in two contrasting areas of Dar es Salaam, Mikocheni and Ilala, during the dry season. Sanitation structures (latrines, soakage pits, septic tanks and cess pits) were the most profilic breeding places, totalling 780 in Mikocheni and 1544 in Ilala. Those in Mikocheni were estimated to contain about 1.4 times more mosquito pupae, per site, than in such structures in Ilala. This was both because a higher proportion of sites contained visible water and because sites with water were more likely to contain pupae in Mikocheni. The relative importance of the different types of structure, in terms of productivity, was the same in both areas. Although septic tanks and cess pits made up only 10.5% of the on-site sanitation structures in Ilala, they contained 53% of the total number of pupae in enclosed sites; they were therefore particularly important targets for treatment with polystyrene beads. A survey during the rainy season of sites in Ilala revealed little change in the proportion that were wet, or in the frequency of breeding in those with visible water. The number, type and area of open breeding sites varied greatly between the two study areas. In Mikocheni the area of open breeding sites was 100 times greater than in Ilala, with 97% of the 13,000 m2 being flooded grassland. In Ilala all but four of the sixty-six open breeding sites were puddles of sullage water derived from bathrooms.(ABSTRACT TRUNCATED AT 250 WORDS)

Mosquito control in Dar es Salaam. II. Impact of expanded polystyrene beads and pyriproxyfen treatment of breeding sites on Culex quinquefasciatus densities.

In two contrasting areas of Dar es Salaam (Ilala and Mikocheni) all enclosed breeding sites of Culex quinquefasciatus, such as latrines and septic tanks, were treated with a floating layer of expanded polystyrene beads. 7 months later checks in both study areas revealed only one site (from which the polystyrene had been removed during emptying) containing immature stages of Cx quinquefasciatus. Open breeding sites such as areas of flooded land and blocked drains were treated with pyriproxyfen (an insect growth regulator) at a concentration of 0.1 ppm. Emergence of Cx quinquefasciatus adults from these sites was inhibited for 4 weeks during the rainy season and for up to 11 weeks during the dry season. The problem of mosquito breeding sites caused by bathroom sullage water was addressed through a combination of health education and indirect pressure from the Urban Malaria Control Project (UMCP) via local community leaders. Households responsible for these sites were encouraged to eliminate them by diverting the water into an enclosed drainage structure, usually a pit latrine. After two weekly visits 64.7% of households had complied and 93.4% had complied after five visits. 5 months later, only 15.7% had reverted to allowing sullage water to collect into puddles. Densities of Cx quinquefasciatus adults dropped by 76.7% in Mikocheni and by 46.2% in Ilala following intervention, but increased by 84.9% and 25.6% in two untreated comparison areas. The reasons for differential success of the combined interventions in the two treated areas are discussed.

How long do the effects of ivermectin on adult Onchocerca volvulus persist?

The persistence of the effects of ivermectin on the viability, morphology and reproductivity of adult Onchocerca volvulus was examined eighteen months after treatment with a single or five six-monthly doses of ivermectin and compared with untreated controls. Treated nodules were removed from patients participating in a randomised controlled trial of ivermectin in Sierra Leone. Adult filariae, 545 females and 348 males, were isolated by collagenase digestion. The nodules were significantly smaller, contained fewer young worms and supported lower microfilarial production in those treated with five doses of ivermectin. The productivity index, a measure of the reproductive potential of a worm population, was still reduced by 83% eighteen months after five doses and by 63% after a single dose compared to controls. These results show that worms recover their fertility even after multiple doses of ivermectin, but do so slowly compared to standard dosage intervals. In addition ivermectin may have a partial chemoprophylactic effect which contributes to the maintenance of low microfilarial production in conditions of on-going transmission.

Absence of sperm from the seminal receptacle of female Onchocerca volvulus following multiple doses of ivermectin.

It is already known that multiple doses of ivermectin have a profound effect on embryonic development in Onchocerca volvulus and that this appears to operate mainly at the single cell stage. To investigate this further, we examined adult female O. volvulus originating from patients treated either with placebo or one, four or five doses of ivermectin. The reproductive organs were dissected out of the worm and examined for evidence of oogenesis and for the quantity of sperm and oocytes in the seminal receptacles. A single dose of ivermectin had no measurable effect on oogenesis or on the amount of sperm and oocytes compared to placebo. However after multiple doses of ivermectin a significantly lower proportion of seminal receptacles contained sperm and there was a significantly higher proportion of ovaries with impaired oogenesis compared to placebo. It is concluded that the reduction in the number of multicellular embryonic stages from worms exposed to multiple doses of ivermectin is due, at least in part, to a major reduction in the effective insemination of female worms and to a minor impairment of oogenesis.

The effect of repeated doses of ivermectin on adult female Onchocerca volvulus in Sierra Leone.

The effects of single and multiple doses of ivermectin on mortality and morphology were assessed in over 700 female Onchocerca volvulus worms and the effects on embryogenesis were assessed in 490. Nodules were surgically removed from Sierra Leoneans recruited from a double-blind placebo controlled study of ivermectin given at six-monthly intervals. Nodules were digested in collagenase to isolate whole adult worms. After four or five doses of ivermectin there were significant increases in the numbers of discoloured and calcified worms and possibly a trend towards increased mortality, but this was not seen consistently. There was no evidence of a prophylactic effect of the drug. Worms were then homogenised and embryograms constructed. A single dose of ivermectin produced large numbers of degenerating intrauterine microfilariae, but embryonic development occurred normally. After multiple doses we observed almost complete cessation of embryogenesis, with a highly significant decrease in the numbers of viable multicellular embryonic stages, while oocytes appeared to be produced normally. Development is probably impeded at the single cell stage, possibly because of reduced fertilization. In planning the future role of ivermectin as a control measure for onchocerciasis it is crucial to determine if these effects on embryogenesis are reversible.