Aberrant use and poor quality of trypanocides: a risk for drug resistance in south western Ethiopia.

BACKGROUND: Trypanocidal drugs have been used to control African animal trypanosomosis for several decades. In Ethiopia, these drugs are available from both authorized (legal) and unauthorized (illegal) sources but documentation on utilization practices and quality of circulating products is scanty. This study looked at the practices of trypanocidal drug utilization by farmers and the integrity of active ingredient in trypanocides sold in Gurage zone, south western Ethiopia. The surveys were based on a structured questionnaire and drug quality determination of commonly used brands originating from European and Asian companies and sold at both authorized and unauthorized markets. One hundred farmers were interviewed and 50 drug samples were collected in 2013 (Diminazene aceturate = 33 and Isometamidium chloride = 17; 25 from authorized and 25 from unauthorized sources). Samples were tested at the OIE-certified Veterinary Drug Control Laboratory (LACOMEV) in Dakar, Senegal, by using galenic standards and high performance liquid chromatography. RESULTS: Trypanosomosis was found to be a major threat according to all interviewed livestock keepers in the study area. Diminazene aceturate and isometamidium chloride were preferred by 79% and 21% of the respondents respectively, and 85% of them indicated that an animal receives more than six treatments per year. About 60% of these treatments were reported to be administered by untrained farmers. Trypanocidal drug sources included both unauthorized outlets (56%) and authorized government and private sources (44%). A wide availability and usage of substandard quality drugs was revealed. Twenty eight percent of trypanocidal drugs tested failed to comply with quality requirements. There was no significant difference in the frequency of non-compliance between diminazene-based and isometamidium chloride products (P = 0.87) irrespective of the marketing channel (official and unofficial). However, higher rates of non-compliant trypanocides were detected for drugs originating from Asia than from Europe (P = 0.029). CONCLUSION: The findings revealed the presence of risk factors for the development of drug resistance, i.e. wide distribution of poor quality drugs as well as substandard administration practices. Therefore, it is strongly recommended to enforce regulatory measures for quality control of veterinary drugs, to expand and strengthen veterinary services and to undertake trypanocidal drug efficacy studies of wider coverage.

Inter-epidemic Rift Valley fever virus seroconversions in an irrigation scheme in Bura, south-east Kenya.

Rift Valley fever (RVF) is an acute mosquito-borne viral zoonosis whose outbreaks are often associated with prolonged rainfall and flooding, during which large numbers of vectors emerge. Recent studies into the inter-epidemic maintenance of RVF virus (RVFV) suggest that both vertical transmission in vectors and direct transmission between hosts act in combination with predisposing factors for persistence of the virus. A comparative longitudinal survey was carried out in Tana River County, Kenya, in irrigated, riverine and pastoral ecosystems from September 2014-June 2015. The objectives were to investigate the possibility of low-level RVFV transmission in these ecosystems during an inter-epidemic period (IEP), examine variations in RVFV seroprevalence in sheep and goats and determine the risk factors for transmission. Three hundred and sixteen small ruminants were selected and tested for immunoglobulin G antibodies against RVFV nucleoprotein using a competitive ELISA during six visits. Data on potential risk factors were also captured. Inter-epidemic RVFV transmission was evidenced by 15 seroconversions within the irrigated and riverine villages. The number of seroconversions was not significantly different (OR = 0.66, CI = 0.19-2.17, p = .59) between irrigated and riverine areas. No seroconversions were detected in the pastoral ecosystem. This study highlights the increased risk of inter-epidemic RVFV transmission posed by irrigation, through provision of necessary environmental conditions that enable vectors access to more breeding grounds, resting places and shade, which favour their breeding and survival.

Cattle breeding, trypanosomosis prevalence and drug resistance in Northern Togo.

African Animal Trypanosomosis (AAT) is a major disease of cattle in Togo and its control is essentially based on chemotherapy. However, because of excessive use of trypanocides during the past decades, chemo-resistance in the parasites has developed. In order to assess the current situation of AAT and resistance to trypanocidal drugs in Northern Togo, a study was conducted on cattle from December 2012 to August 2013 in the regions of Kara and Savanes. An initial cross-sectional survey was carried out in 40 villages using the Haematocrit Centrifugation Technique (HCT). Out of these, 5 villages with a trypanosome prevalence of >10% were selected for a block treatment study (BT) with diminazene diaceturate (DA: 3.5mg/kg for a 14-day follow-up) and isometamidium chloride (ISM: 0.5mg/kg for a 28-day follow-up). Positive blood samples collected during the parasitological surveys and an equivalent number of negatives were further analyzed by PCR-RFLP for trypanosome species confirmation and molecular diagnosis of resistance to DA in Trypanosoma congolense. The results from 1883 bovine blood samples confirmed a high overall trypanosome prevalence of 10.8% in Northern Togo. PCR-RFLP revealed that T. congolense is the dominant pathogenic trypanosome species (50.5%) followed by T. vivax (27.3%), and T. brucei (16.2%). The BT showed varying levels of treatment failures ranging from 0 to 30% and from 0 to 50% for DA and for ISM respectively, suggesting the existence of resistant trypanosome populations in the study area. Our results show that AAT still represents a major obstacle to the development of cattle husbandry in Northern Togo. In areas of high AAT risk, a community-based integrated strategy combining vector control, rational use of trypanocidal drugs and improving the general condition of the animals is recommended to decision makers.

Drug quality analysis through high performance liquid chromatography of isometamidium chloride hydrochloride and diminazene diaceturate purchased from official and unofficial sources in Northern Togo.

Trypanocidal drugs remain the most accessible and thus commonly used means of controlling tsetse transmitted animal African trypanosomosis. In Togo, trypanocides are sold on official as well as unofficial markets, but the quality of these trypanocides is undocumented so a drug quality assessment study was conducted from May 2013 to June 2014. Trypanocides supplied by European, Indian and Chinese pharmaceutical companies and sold on official and unofficial markets in Togo were purchased. In total fifty-two trypanocides were obtained, 24 of these samples from official markets and 28 from unofficial markets made up of a total of 36 diminazene diaceturate and 16 isometamidium chloride hydrochloride samples. The samples were analysed in the reference laboratory of the OIE (World Organisation for Animal Health), Laboratory for the Control of Veterinary Medicines (LACOMEV) in Dakar which uses galenic testing and high performance liquid chromatography (HPLC) testing as standard reference analysis methods. The results revealed a high proportion of trypanocides of sub-standard quality on the Togolese market: 40% were non-compliant to these quality reference standards. All of the HPLC non-compliant samples contained lower amounts of active ingredient compared to the concentration specified on the packaging. Non-compliance was higher in samples from the unofficial (53.57%) than from the official markets (25%; p=0.04).The main drug manufacturers, mostly of French origin in the study area, supply quality drugs through the official legal distribution circuit. Products of other origins mostly found on illegal markets present a significantly lower quality.

Multiple host feeding in Glossina palpalis gambiensis and Glossina tachinoides in southeast Mali.

Changes in agricultural practices and the resulting extinction of wildlife have led to the reduction or disappearance of savannah tsetse species. Riparian tsetse such as Glossina palpalis gambiensis Vanderplank 1949 and Glossina tachinoides Westwood 1850 (Diptera: Glossinidae) continue to persist in peridomestic sites, transmitting trypanosomiasis. At present, little is known about interspecies differences in feeding behaviour in these two species in southeast Mali, or of the phenomenon of multiple bloodmeals. To study these topics, 279 samples of G. p. gambiensis and G. tachinoides containing host DNA, caught in the Sikasso region between November 2008 and April 2009, were analysed by applying host species-specific primers and sequencing. Human accounted for > 66% of G. p. gambiensis bloodmeals, whereas G. tachinoides contained in equal parts DNA of human, cattle or both, showing a significantly higher proportion of multiple host use. Further, the trypanosome infection rate was found to be three-fold higher in G. tachinoides. Logistic regression analysis revealed double-feeding and infection to be independent of one another, but showed infection to be correlated with engorgement in G. p. gambiensis and female sex in G. tachinoides. Enhanced host-seeking activities paired with the high trypanosome infection rate found in G. tachinoides would indicate that this species has a higher vectorial capacity than G. p. gambiensis.