Social acceptance of livestock-administered endectocides for malaria control in Vhembe District, Limpopo Province, South Africa.

BACKGROUND: Malaria continues to be a leading cause of morbidity and mortality in Africa and conventional malaria control strategies, such as indoor residual spraying and insecticide-treated bed nets, have limited effectiveness for some malarial vectors. Consequently, the development of alternative or supplementary strategies is required. One potential strategy is the use of livestock-administered endectocides to control vector mosquitoes that feed outdoors on livestock. However, since this strategy requires support from local communities and livestock owners consenting for their animals to be treated, it can only be implemented if agreed to by affected communities. The aim of this study was to assess the social acceptance of the use of livestock-administered endectocides in the malaria endemic villages of Vhembe District, Limpopo Province, South Africa, where malaria incidence is high. METHODS: Questionnaires were administered to 103 livestock-owning households from four villages, namely, Gumbu, Malale, Manenzhe and Bale. The assessment included questions on the acceptability of the strategy, the type and number of livestock owned, distances between houses and kraals (overnight pens) as well as previous use and awareness of endectocides. The results were analysed using descriptive statistics and multinomial logistic regression. RESULTS: The types of livestock owned by the participants comprised, cattle, goats, sheep and donkeys, with the most dominant being goats (n = 1040) and cattle (n = 964). The majority of kraals were less than 10 m from homesteads. Most participants (72.5%) were already using chemicals to treat their livestock for parasites. All participants were amenable to the implementation of the strategy, and would give consent for their animals to be treated by endectocides. CONCLUSIONS: The use of livestock-administered endectocides appears to be a feasible and acceptable approach for control of animal-feeding malaria vector species in the malaria endemic villages of Vhembe District. This is based on a high percentage of rural residents keeping suitable livestock close to their homes and expressing willingness to use endectocides for mosquito control.

The effect of cattle-administered ivermectin and fipronil on the mortality and fecundity of Anopheles arabiensis Patton.

BACKGROUND: Malaria control primarily depends on two vector control strategies: indoor residual spraying (IRS) and long-lasting insecticide-treated nets (LLINs). Both IRS and LLIN target indoor-biting mosquitoes. However, some of the most important malaria vectors have developed resistance against the chemical compounds used in IRS and LLINs. Insecticide-induced behavioural changes in vectors, such as increased outdoor feeding on cattle and other animals, also limit the effectiveness of these strategies. Novel vector control strategies must therefore be found to complement IRS and LLINs. A promising tool is the use of cattle-applied endectocides. Endectocides are broad-spectrum systemic drugs that are effective against a range of internal nematodes parasites and blood-feeding arthropods. The aim of this study was to investigate the effect of two endectocide drugs, injectable ivermectin and topical fipronil, on the survival and fecundity of zoophilic Anopheles arabiensis. METHODS: Laboratory-reared mosquitoes were allowed to feed on cattle treated with either injectable ivermectin (0.2 mg/kg), topical fipronil (1.0 mg/kg) or saline (control) on days 0, 1, 4, 7, 13, 21 and 25 post-treatment, and mortality and egg production were recorded daily. RESULTS: Compared to controls, the mortality of An. arabiensis increased by 3.52- and 2.43-fold with injectable ivermectin and topical fipronil, respectively. The overall fecundity of mosquitoes that fed on both ivermectin- and fipronil-treated cattle was significantly reduced by up to 90 and 60%, respectively, compared to the control group. The effects of both drugs attenuated over a period of 3 weeks. Injectable ivermectin was more effective than topical fipronil and increased mosquito mortality by a risk factor of 1.51 higher than fipronil. Similarly, both drugs significantly reduced the fecundity of An. arabiensis. CONCLUSIONS: This study demonstrates that injectable ivermectin and topical fipronil are able to suppress An. arabiensis density and could help to reduce outdoor malaria transmission. Data from the present study as well as from other similar studies suggest that current-generation endectocides have a limited duration of action and are expensive. However, new-generation, sustained-release formulations of ivermectin have a multi-week, high mortality impact on vector populations, thus holding promise of an effective reduction of outdoor malaria transmission.

Understanding human genetic factors influencing primaquine safety and efficacy to guide primaquine roll-out in a pre-elimination setting in southern Africa.

BACKGROUND: Primaquine (PQ) is recommended as an addition to standard malaria treatments in pre-elimination settings due to its pronounced activity against mature Plasmodium falciparum gametocytes, the parasite stage responsible for onward transmission to mosquitoes. However, PQ may trigger haemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. Additional human genetic factors, including polymorphisms in the human cytochrome P450 2D6 (CYP2D6) complex, may negatively influence the efficacy of PQ. This study assessed the prevalence of G6PD deficiency and two important CYP2D6 variants in representative pre-elimination settings in South Africa, to inform malaria elimination strategies. METHODS: Volunteers (n = 248) attending six primary health care facilities in a malaria-endemic region of South Africa were enrolled between October and November 2015. G6PD status was determined phenotypically, using a CareStart™ G6PD rapid diagnostic test (RDT), and genotypically for two common African G6PD variants, namely A+ (A376G) and A- (G202A, A542T, G680T & T968C) by PCR, restriction fragment length polymorphisms (RFLP) and DNA sequencing. CYP2D6*4 and CYP2D6*17 variants were determined with PCR and RFLP. RESULTS: A prevalence of 13% (33/248) G6PD deficiency was observed in the cohort by G6PD RDT whilst by genotypic assessment, 32% (79/248) were A+ and 3.2% were A-, respectively. Among the male participants, 11% (6/55) were G6PD A- hemizygous; among females 1% (2/193) were G6PD A- homozygous and 16% (32/193) G6PD A- heterozygous. The strength of agreement between phenotyping and genotyping result was fair (Cohens Kappa κ = 0.310). The negative predictive value for the G6PD RDT for detecting hemizygous, homozygous and heterozygous individuals was 0.88 (95% CI 0.85-0.91), compared to the more sensitive genotyping. The CYP2D6*4 allele frequencies for CYP2D6*4 (inferred poor metabolizer phenotype) and CYP2D6*17 (inferred intermediate metabolizer phenotype) were 3.2 and 19.5%, respectively. CONCLUSIONS: Phenotypic and genotypic analyses both detected low prevalence of G6PD deficiency and the CYP2D6*4 variants. These findings, combined with increasing data confirming safety of single low-dose PQ in individuals with African variants of G6PD deficiency, supports the deployment of single low-dose PQ as a gametocytocidal drug. PQ would pose minimal risks to the study populations and could be a useful elimination strategy in the study area.