Effectiveness of a long-lasting piperonyl butoxide-treated insecticidal net and indoor residual spray interventions, separately and together, against malaria transmitted by pyrethroid-resistant mosquitoes: a cluster, randomised controlled, two-by-two factorial design trial.

BACKGROUND: Progress in malaria control is under threat by wide-scale insecticide resistance in malaria vectors. Two recent vector control products have been developed: a long-lasting insecticidal net that incorporates a synergist piperonyl butoxide (PBO) and a long-lasting indoor residual spraying formulation of the insecticide pirimiphos-methyl. We evaluated the effectiveness of PBO long-lasting insecticidal nets versus standard long-lasting insecticidal nets as single interventions and in combination with the indoor residual spraying of pirimiphos-methyl. METHODS: We did a four-group cluster randomised controlled trial using a two-by-two factorial design of 48 clusters derived from 40 villages in Muleba (Kagera, Tanzania). We randomly assigned these clusters using restricted randomisation to four groups: standard long-lasting insecticidal nets, PBO long-lasting insecticidal nets, standard long-lasting insecticidal nets plus indoor residual spraying, or PBO long-lasting insecticidal nets plus indoor residual spraying. Both standard and PBO nets were distributed in 2015. Indoor residual spraying was applied only once in 2015. We masked the inhabitants of each cluster to the type of nets received, as well as field staff who took blood samples. Neither the investigators nor the participants were masked to indoor residual spraying. The primary outcome was the prevalence of malaria infection in children aged 6 months to 14 years assessed by cross-sectional surveys at 4, 9, 16, and 21 months after intervention. The endpoint for assessment of indoor residual spraying was 9 months and PBO long-lasting insecticidal nets was 21 months. This trial is registered with ClinicalTrials.gov, number NCT02288637. FINDINGS: 7184 (68·0%) of 10 560 households were selected for post-intervention survey, and 15 469 (89·0%) of 17 377 eligible children from the four surveys were included in the intention-to-treat analysis. Of the 878 households visited in the two indoor residual spraying groups, 827 (94%) had been sprayed. Reported use of long-lasting insecticidal nets, across all groups, was 15 341 (77·3%) of 19 852 residents after 1 year, decreasing to 12 503 (59·2%) of 21 105 in the second year. Malaria infection prevalence after 9 months was lower in the two groups that received PBO long-lasting insecticidal nets than in the two groups that received standard long-lasting insecticidal nets (531 [29%] of 1852 children vs 767 [42%] of 1809; odds ratio [OR] 0·37, 95% CI 0·21-0·65; p=0·0011). At the same timepoint, malaria prevalence in the two groups that received indoor residual spraying was lower than in groups that did not receive indoor residual spraying (508 [28%] of 1846 children vs 790 [44%] of 1815; OR 0·33, 95% CI 0·19-0·55; p<0·0001) and there was evidence of an interaction between PBO long-lasting insecticidal nets and indoor residual spraying (OR 2·43, 95% CI 1·19-4·97; p=0·0158), indicating redundancy when combined. The PBO long-lasting insecticidal net effect was sustained after 21 months with a lower malaria prevalence than the standard long-lasting insecticidal net (865 [45%] of 1930 children vs 1255 [62%] of 2034; OR 0·40, 0·20-0·81; p=0·0122). INTERPRETATION: The PBO long-lasting insecticidal net and non-pyrethroid indoor residual spraying interventions showed improved control of malaria transmission compared with standard long-lasting insecticidal nets where pyrethroid resistance is prevalent and either intervention could be deployed to good effect. As a result, WHO has since recommended to increase coverage of PBO long-lasting insecticidal nets. Combining indoor residual spraying with pirimiphos-methyl and PBO long-lasting insecticidal nets provided no additional benefit compared with PBO long-lasting insecticidal nets alone or standard long-lasting insecticidal nets plus indoor residual spraying. FUNDING: UK Department for International Development, Medical Research Council, and Wellcome Trust.

The efficacy of Australian essential oils for the treatment of head lice infestation in children: A randomised controlled trial.

BACKGROUND: The increase in resistance of head lice to neurotoxic pediculicides and public concern over their safety has led to an increase in alternative treatments, many of which are poorly researched or even untested. METHODS: A multicentre, randomised, assessor-blind, parallel-group trial (Trial 1) was conducted to compare the safety and efficacy of a head lice treatment containing Australian eucalyptus oil and Leptospermum petersonii (EO/LP solution; applied thrice with 7-day intervals between applications) with a neurotoxic treatment containing pyrethrins and piperonyl butoxide (P/PB mousse; applied twice with a 7-day interval) in children. A single-blind, open trial (Trial 2) was conducted to assess the efficacy of EO/LP solution following a single application. In addition, skin irritancy and sensitisation tests using EO/LP solution were performed in adults and children. In vitro tests were performed to further assess the ovicidal and pediculicidal efficacy of EO/LP solution. RESULTS: EO/LP solution was found to be more than twice as effective in curing head lice infestation as P/PB mousse in per-protocol participants (Trial 1; 83% vs 36%, P < 0.0001), and was also found to be 100% pediculicidal following a single application (Trial 2). Adverse events were limited to transient itching, burning or stinging. Further skin testing with the EO/LP solution reported no irritation or sensitisation in adults, or irritation in children. In vitro exposure of lice and eggs to the EO/LP solution resulted in 100% mortality. CONCLUSION: The efficacy, safety and relative ease of use of the EO/LP solution make it a viable alternative in treating head lice.

[Investigation of pediculosis carried out as the special study module No. 74, a part of Ege University Medical Faculty's educational program]. / Ege Universitesi Tip Fakültesi egitim programi kapsamindaki 74 no'lu özel çalisma modülünde gerçeklestirilen pediculosis taramasi.

In this study, in the program of the special study module No: 74, 68 students, who attended the Izmir Konak Yüzbasi Serafettin Primary School were examined for Pediculus humanus capitis in March 2005. Twenty female students had pediculosis capitis, but no male students were infested. The infestation rate in the girls was 55.5%. Positive cases were treated and 35.0% were found to be cured during a control performed one week later.

Changes to oxfendazole chiral kinetics and anthelmintic efficacy induced by piperonyl butoxide in horses.

REASONS FOR PERFORMING THE STUDY: The study of novel pharmacological strategies to control parasitism in horses is required since many parasite species have developed resistance to anthelmintic drugs. OBJECTIVES: To evaluate the effects of piperonyl butoxide (PB) (a metabolic inhibitor) on the plasma availability and enantiomeric behaviour of oxfendazole (OFZ) given orally to horses, and to compare the clinical efficacy of OFZ given either alone or co-administered with PB in naturally parasitised horses. METHODS: Fifteen naturally parasitised crossbred male ponies were allocated into 3 groups (n = 5) and treated orally as follows: Group I (control) received distilled water as placebo; Group II was dosed with OFZ (10 mg/kg bwt); and Group III was treated with OFZ (10 mg/kg bwt) co-administered with PB (63 mg/kg bwt). Jugular blood samples were obtained over 120 h post treatment. Three weeks after treatments, all experimental horses were subjected to euthanasia. RESULTS: The observed maximum plasma concentration (Cmax) and area under the concentration vs. time curve (AUC) values for OFZ increased 3- and 5-fold, respectively, in the presence of PB. The plasma concentration profiles of fenbendazole (FBZ), a metabolite generated from OFZ, were significantly lower after the treatment with OFZ alone (AUC = 0.8 microg x h/ml) compared to those obtained after the OFZ + PB treatment (AUC = 2.7 microg x h/ml). The enhanced pharmacokinetic profiles correlated with increased anthelmintic efficacy. The combination OFZ + PB showed 100% efficacy against mature nematode parasites. The efficacy against cyathostome L3 larvae increased from 94% (Group II) to 98.7% (Group III). Consistently, the number of L4 larvae recovered from OFZ + PB treated horses (Group III) (n = 146) was significantly lower (P<0.05) than that recovered from Group II (n = 1397). CONCLUSIONS: The use of PB as a metabolic inhibitor may be useful to enhance OFZ activity against mature and migrating larvae of different parasite species in horses. POTENTIAL RELEVANCE: Metabolic inhibitors may be used to enhance the activity of benzimidazole anthelmintics and extend the effective lifespan of benzimidazole drugs in the face of increasing resistance.

Eficacia de los pediculicidas en la pediculosis capitis / Efficacy of pediculicidal drugs in pediculosis capitis

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The in vivo pediculicidal efficacy of a natural remedy.

BACKGROUND: Head louse infestations are prevalent worldwide. Over the past 20-25 years, 15-20% of all children in Israel between 4 and 13 years of age have been infested with head lice. This is mainly due to the existence of ineffective pediculicides on the market. OBJECTIVE: To examine the pediculicidal efficacy and safety of a natural remedy ("Chick-Chack") and to compare it in an open clinical study with a known pesticide spray. METHODS: The natural remedy, which contains coconut oil, anise oil and ylang ylang oil, was applied to the hair of infested children three times at 5 day intervals. Each treatment lasted for 15 minutes. The control pediculicide was a spray formulation containing permethrin, malathion, piperonyl butoxide, isododecane and propellant gas, which was applied twice for 10 minutes with a 10 day interval between applications. RESULTS: Of 940 children, aged 6-14 years, from six schools in Jerusalem who were examined for head louse infestation, 199 (21.2%) were infested with lice and eggs, while 164 (17.4%) were infested only with nits. Altogether, 119 children were randomly treated with either the natural remedy or the control product. Treatment was successful with the natural remedy in 60 children (92.3%) and with the control pediculicide in 59 children (92.2%). There were no significant side effects associated with either formulation. CONCLUSIONS: The natural remedy was very effective in controlling louse infestations under clinical conditions and caused no serious side effects.

Cypermethrin pour-on synergized with piperonyl butoxide: effects on Haematobia irritans (Diptera: Muscidae) natural populations resistant to cypermethrin.

Development of pyrethroid resistance in Haematobia irritans in Santa Fe province, Argentina, resulted in an increased use of pyrethroid insecticides, probably due to lack of suitable alternative treatments. We explored the efficacy of mixtures of cypermethrin and piperonyl butoxide (PBO) against pyrethroid-resistant H. irritans. Groups of 25 Holstein cows each, naturally infested with cypermethrin resistant H. irritans were assigned to treated or control groups in April, September, October and December 1997. Cattle in treated groups were medicated with pour-on oil formulations of 5% cypermethrin (dose = 4 mg per kg of body weight) with 5% or 10% PBO in April, and with a mixture containing 5% of both components thereafter. Efficacy was tested for 21 days after treatment. A treatment of 5% cypermethrin pour-on without PBO was evaluated in October 1997. Samples of horn flies were obtained before September, October and December treatments and exposed for 2 h to filter papers impregnated with different cypermethrin concentrations to determine the 50% lethal concentration (LC50). No difference in efficacy was found between cypermethrin pour-on formulations with 5% or 10% of PBO (more than 94% efficacy on day 21 after treatment). Efficacy of 5 % cypermethrin-5% PBO mixture decreased rapidly in the successive treatments (less than 40% efficacy was observed on day 21 after the December treatment), and the period after treatment with an efficacy higher than 95% was 14 days for the treatment carried out in April, 10 days in September; 7 days for the treatment performed in October and 4 days for the December treatment. The LC50 of cypermethrin was 36.6 microg per cm2 in September and increased to 116.6 and 226.1 microg per cm2 in October and December, respectively. It is concluded that the addition of PBO to cypermethrin did not provide a treatment that would give a long term control of pyrethroid resistant-horn flies.