Antiprotozoal Drug Handling and Management Practices in Asella District, Central Oromia, Ethiopia

Results The preliminary survey comprising 70 animal health professionals and animal owners was undertaken through observation, interview using a structured questionnaire, and discussion with key informants to evaluate their handling and management practices of antiprotozoal drugs. According to the finding of this preliminary survey, there was inadequate antiprotozoal drug distribution and only few drugs, namely, diminazene diaceturate, amprolium, and sulfa drugs, were available with different trade names being imported from different manufacturing countries. Among the current available antiprotozoal drugs circulating in the area, those manufactured and imported from China were highly distributed in the majority of veterinary drug shops. The assessment showed that there was a gap in achieving the required knowledge and practice of proper handling and management issues in the professionals and awareness problems in the community. The study indicated that there were inappropriate transportation and storage practices. Moreover, selling drugs without prescription, ignoring farmers without properly informing the drug withdrawal period, and administration of drugs by nonprofessionals were the other most critical and unethical practices in the area. It is emphasized that this inappropriate handling and management practice, scarcity of antiprotozoal drugs, easy accessibility, and distribution by nonprofessionals could potentially affect the quality, safety, and effectiveness of antiprotozoal drugs which may lead to drug resistance development. Conclusion Hence, continuous awareness creation in the community, capacity building, training, and upgrading programs to the professionals, as well as strict enforcement of drug control and administration regulation of the country, are essential in the overall effort of improving animal health and productivity through the control of protozoan diseases in and around Asella.


Background
Protozoa are ubiquitous single-celled organisms, of which over 65,000 species have been described.
Many occur as either free-living forms or harmless commensals, but their numbers include some of the most signi cant causes of disease in domesticated animals and humans [1]. Protozoal infections are common in tropical and subtropical countries where sanitary conditions, hygiene practices, and control of the vectors of transmission are inadequate. Two types of infections caused by the major types of protozoa of veterinary importance are the haemoparasitic such as Trypanosome, Babesia, Theileria, and the common enteric Coccidian, Toxoplasma, and Giardia [2]. Among protozoan diseases caused by trypanosomes, dourine which is restricted to the Arsi-Bale zone of Ethiopian highland areas has been recognized by local farmers for many years as 'Lappessa' and found to be a threat to the life and productivity of the equine population [3].
Antiprotozoal drugs are used to treat infections caused by protozoa which either destroy or inhibit their growth and the ability to reproduce. Antiprotozoal drugs destroy or inhibit protozoa by interfering with metabolic processes; drugs interfering with reproduction and larval physiology, and drugs interfering with neuromuscular physiology of parasites [4]. The control of trypanosomosis in Ethiopia relies on either curative or prophylactic treatment of animals with Diminazine aceturate or Isometamidium chloride [5]. Whereas, the treatment of Babesiosis is dependent upon the availability of a particular drug in the market.
Although Imidocarb is the rst drug of choice [6], Diminazine aceturate is widely used in the tropics [7].
Remedy for Theileriosis is best observed by Buparvaquone, which is a more effective and reliable drug than any other eld condition [8]. Diminazine aceturate is a currently available drug for the treatment of dourine, although not fully effective in curing [3]. But, it was found that Cymelarsan was quite effective in curing acutely or chronically infected horses at both 0.25 mg/kg and 0.5 mg/kg, and relapses were not observed up to a year after treatment [9, 10]. Some antibacterial and antihelmintic drugs also have antiprotozoal activity. In vitro activity of antiprotozoal drugs, and monitoring of resistance is more di cult for antiprotozoal drugs because standardized susceptibility testing is not routinely performed for these pathogens. Besides, many antiprotozoal drugs are designed to be active in the lumen of the intestine for treatment of intestinal protozoal infections, and the concentration of active drug in the intestinal lumen after oral administration is di cult to measure. Therefore, the concentration of drug to which these pathogens are exposed is often not known. The activity and dosage regimens of antiprotozoal drugs are often based on the results of clinical trials, rather than concentration-exposure relationships between antiprotozoal drugs and the organism of interest [11].
Drug use is a complex subject involving the prescriber, the dispenser, the patient, and pharmaceutical institutions. It is in uenced by factors such as drug availability, prescriber's experience, knowledge of dispensers, and many more. Inappropriate drug use is a problem of the whole world; however, the degree of the problem is higher in developing countries like Ethiopia [12,13]. Improper use of drugs may cause ineffective treatment, unnecessary wastage of resources, and may harm the patient [14]. Medicinal products, and starting materials used in the manufacture of medicinal products, should be stored and transported under conditions that ensure that their quality is maintained. Manufacturers' recommendations concerning storage temperatures should be observed and this may involve the use of specialized storage and transport facilities [15].
Even though the effectiveness of drugs is damaged due to problems such as lack of awareness on how to handle and manage the drugs, lack of understanding of the potential effects of drug misuse and abuse, and lack of required facilities; Veterinary drugs handling and management problems, illegal drug smuggling, and free charge drug supply are widely occurring events in Ethiopia [4]. Therefore, the study was conducted to assess the current circulating antiprotozoal drugs, their handling, and management practice in and around Asella.

Study area
The study was conducted in and around Asella town of Arsi zone, Oromia region, which is situated in central Ethiopia within 6°59'-8°49' North latitude and 38°41'-40°44' East longitude in central Ethiopia at 175 km southeast of Addis Ababa. The area has an elevation ranges from 1780-3100 m.a.s.l and is characterized by mild subtropical weather ranging from 5 to 28°C. Livestock is a major agricultural resource in the area with 2, 249, 479 cattle, 1,395,824 small ruminants, 388, 082 equines, and 11, 716 camels [16]. The annual temperature range is 10 to 22.6°C. It has a daily maximum temperature that can reach up to 28°C and a minimum temperature of 10°C [17].

Study subjects
The study subjects included in this study are government-owned veterinary clinics, private drug shops, animal health professionals, and animal owners (farmers) found in and around Asella.

Study methods
A cross-sectional study was conducted from December 2017 to May 2018 to assess the current circulating antiprotozoal drugs, their handling, and management practice in and around Asella, Oromia, Ethiopia. Brie y, the study was conducted by collecting data through participant observation, by interviewing professionals who work in veterinary clinics or private drug shops and animal owners/clients who come to the clinic for treatment of their animals or pharmacy to buy drugs using a structured questionnaire and discussion with key informants. The questionnaire was with a target of assessing the current management practice of antiprotozoal drugs used for prophylaxis and treatment of protozoal infections in the study area.

Sampling methods
The study sites (government clinics and private pharmacies) were selected purposively due to ease of access and willingness to provide information. The total sample size considered during the questionnaire survey were 20 animal health professionals who were actively working with veterinary drugs in which nine of them were working in private veterinary drug shops and the other eleven were veterinary pharmacy attendants who work on public veterinary clinics. Moreover, 50 animal owners or attendants coming for animal treatment in veterinary clinics and clients coming to a private pharmacy to buy drugs were also included.

Data collection methods
A total of 20 animal health professionals and 50 animal owners (farmers) were interviewed using a structured questionnaire to assess their knowledge, awareness, and practices towards safe handling and management of antiprotozoal drugs. A complete data collecting format was prepared and used to collect data from each veterinary clinics and drug shops during close observation. During observation key informant discussion with working professionals and some animals, owners were also carried out.
A separate and structured questionnaire was prepared to the government veterinary clinicians, private drug shop owners, and attendants to assess the knowledge, attitude, and practice of the professionals towards veterinary drug handling and management practice issues. The relevant issues were incorporated in an open-ended form. Verbal consent was obtained from the respondents after the objective of the study was explained to them before starting the interview. The questionnaire was focused on antiprotozoal drug handling and management practices during acquisition, transportation, storage, dispensing, administration, and disposal of expired drugs.

Data management and Statistical analysis
The collected data were entered into Microsoft excels spreadsheet and summarized using STATA version 13 for descriptive statistics. The output of the analyzed data were presented and summarized using tabulation, charts, and frequencies (percentage) to describe the data.

Assessment of available antiprotozoal drugs in and around Asella
Information was collected from four (Asella, Bilalo, Gonde, and Golgia) government-owned veterinary clinics and 9 private veterinary drug pharmacies that found in Asella, Gonde, and Golgia during close visual observation. Accordingly, only three types of antiprotozoal drugs namely; Diminazine diacetate, Amprolium, and sulfa were available in the area. These drugs are imported from different countries with different trade names given by their manufacturing company (Table 1).

Sources of antiprotozoal drugs in and around Asella
The questionnaire survey showed that the sources of antiprotozoal drug supply in and around Asella were the governmental sources, private legal traders, and illegal drug sellers. According to the result of the questionnaire, above 50% of animal health professionals indicated that the source of antiprotozoal drugs are governmental, about 45% from the legal trader, and the remaining 5% from illegal drug sellers ( Figure  1). Also, the questionnaire survey from animal owners revealed that out of 50 animal owner respondents 7(14%) individuals were buying drugs from open markets supplied by illegal drug smugglers. However, these drug smugglers were not visually observed in the market during the study time.

Knowledge and practices of animal health professionals
Out of the 20 respondents, in which 9 individuals from private veterinary drug dispensers or owners and 11 from government-owned veterinary clinic workers 18(90%) were male, 2(10%) were female and again 12(60%) of them were animal health assistants, 3(15%) were animal health technicians, 2(10%) were animal science and 3(15%) were veterinary doctors with 55% greater than ve years, 35% between 1-5 year and 10% less than a year of working experience.
The vast majority of the respondents (90%) use public vehicles to transport drugs, 85% do not store drugs according to the manufacturer's direction and about 90% of the respondents sell drugs without prescription. Out of 20 respondents, 18(90%) professionals did not properly inform the drug withdrawal period to end-users while giving treatment. The assessment indicated that 70% of the professionals had no enough knowledge of safe handling and management of drugs starting from acquisition to end-users (Table 3).

Awareness and practice of farmers
Out of 50 farmers interviewed 58% were come to buy veterinary drugs and 42% to treat their animals. Of the total respondents, 62% replied as they do not have formal education. When their animals became suffering from protozoan diseases 64% of the farmers administer drugs bought from nearby veterinary pharmacies and 14% from open markets. It was noted that 62% of farmers replied as they were not satis ed with the response of therapy as the drug gives only some relief and 18% of them answered as the drug has no effect (Table 4).

Drug administration practices in the area
The questionnaire survey of both animal health professionals and farmers revealed that 50% of professionals and 34% of farmers replied that drugs were administered by veterinary personnels whereas, 50% of professionals and 66% of farmers replied as drugs were administered by nonprofessionals (experienced local farmers and farmers themselves) (Figure 2).

Discussion
Since the livelihood of the community is mainly depending on mixed crop and livestock production, livestock is the major agricultural resource in the area [16]. The questionnaire survey and discussion with key informants indicated that there are different types of protozoan diseases in this area such as dourine, coccidiosis, and babesiosis which hinder the productivity of animals and cause economic loss to the community. In addition to this nding, it was reported that both animal owners and professionals interviewed in the area stated that dourine is a major health problem of horses causing high mortality and economic loss [10].
However, the present study disclosed that the presence of veterinary services and the amount of veterinary inputs particularly antiprotozoal drugs is not su ciently available in the area because, the assessment revealed only three types of antiprotozoal drugs namely; Diminazine diaceturate, Amprolium, and sulfa drugs. These drugs are imported from different countries with different trade names. Among the current available antiprotozoal drugs in the area, those manufactured and imported from China were highly distributed in the majority of veterinary drug shops.
According to the result and discussion with key informants, Diminazine diaceturate is one of the known and relatively highly purchased drugs by local farmers which is mainly used to treat dourine contracted horses. It can be indicated against several species of trypanosomes and piroplasms for cattle, camels, sheep, goats, and pigs. Although it is found with different trade names, DIMAZNC originated from China was distributed among 69.2% of the total drug stores assessed in the area. It was available in the form of powder (sachet) containing 2.36 grams of active hydrosoluble granules to be dissolved in 15ml of water for one intramuscular injection at a dosage of 3.5mg/kg (1ml/20kg). Diminazine diaceturate is not an effective treatment to cure clinical cases of dourine [18]. However, the absence of other quali ed and curative therapeutic agents in the area against diseases like dourine makes Diminazine diaceturate as a sole treatment option by animal health professionals and the local farmers.
Amprolium is an anticoccidial drug used as therapeutic, prophylactic, and growth promotion especially in poultry. Chinese imported Amprolium present as AMPROLIUM 20% was found distributed among 76.9% of the total observed drug stores in the area. Amprolium imported from Jordan was also available as JOPROX ® (Amprolium HCL, Sulphaquinoxaline sodium, and vitamin K3) and JOPROL 20% ® (Amprolium HCl). This drug is available in powder form and can be given in drinking water for poultry and ruminants mainly calves.
Sulfa drugs are broad-spectrum drugs that are used against bacteria and coccidian parasites. It is found in the form of Sulphadimidine sodium imported from China and Trisulpha forte ® (Sulphadimidine sodium, Sulphadiazine sodium, and Sulphathiazole sodium) imported from Jordan which were found distributed in 61.5% and 15% of observed drug stores respectively. Sulphadimidine sodium was found in 100ml veal to be injected parenterally whereas Trisulpha forte ® was found as a 100gram powder form to be given in drinking water for 3 days at a dosage of 4-5gram/50kg for large animals and 5gram/20liter for poultry.
Governmental sources, private legal traders, and illegal drug sellers are the sources of antiprotozoal drugs supply in the Asella district. The result of the questionnaire and discussion with key informants indicated that about 50% of antiprotozoal drugs are sourced from governmental drug stores, about 45% from private legal traders, and the remaining 5% from illegal drug sellers. The drugs from these sources reach end-users through distribution via veterinary clinics and pharmacies as well as illegal black markets found in the area.
The governmental and private sources get the drugs from distributors in the capital city of the country, Addis Ababa, and other nearby cities such as Adama whereas illegal drug smugglers get the drugs from retailers without any legal license and from the black market inside and outside the country. Also, the questionnaire survey from animal owners revealed that out of 50 respondents 7(14%) were buying drugs from open markets supplied by illegal drug smugglers. Discussion with key informants showed that there are illegal drug smugglers who sell drugs in open markets and other shops in the area. However, these drug smugglers were not visually observed in the market during the study time.
Assessment of the knowledge, awareness, and practices of animal health professionals and farmers towards safe handling and management of antiprotozoal drugs using a structured questionnaire showed that there are many awareness problems and inappropriate practices. The result indicated 70% of the professionals had no enough knowledge and awareness on safe handling and management of drugs starting from acquisition to end-user. All the professionals diagnose animals suffering from protozoan diseases tentatively and determine the dose of the drugs by estimating animal's age and body weight. 80% of the professionals did not follow up and complete the treatment of animals. On the other hand, 64% of the farmers administer drugs that were bought from nearby veterinary pharmacies and 14% from open markets when their animals became suffering from protozoan diseases.
It is noted that public transport and storing drugs without referring the manufacturer's direction can expose the drugs to sunlight, unadjusted temperature, humidity, and other conditions including physical damage to the containers which disturbs the stability of the drugs. However, the vast majority of the respondents (90%) use a public vehicle to transport drugs and 85% do not store drugs according to the manufacturer's direction. The other most critical and unethical practices in the area were selling drugs without the prescription, not informing the drug withdrawal period, and allowing nonprofessionals to administer drugs by themselves. However, 90% of the professionals were found selling drugs without a prescription and did not properly inform the drug's withdrawal period in which they did not advise end users about the potential effect of drug residue on public health. Moreover, the questionnaire survey revealed that 50% of professionals and 66% of farmers replied as drugs were administered by nonprofessionals (experienced local farmers and farmers themselves). But, 62% of the interviewed animal owners did not have formal education which indicated that they could not read and understand the information on the lea ets of the drugs and unable to get the dose rate and expiry date indicated on the lea ets. These conditions facilitate drug misuse and abuse, drug resistance, and unexpected outcome in both animal and human health.
Even though the purpose, dosage, method of administration, contraindication, and other conditions of the drugs is not clear to the sellers and users if it is not accompanied through prescription. Desta, [4] discussion with the key informants showed that farmers buy drugs without prescription from pharmacies and also open markets easily and they put it in their house for a long period and have been practicing drug administration by themselves for treating their animals. Most of the farmers' treatment practice didn't follow the proper dosage and site of injection and they give under dosage of drugs on the basis to treat numerous animals at a time with the available amount of drug and on the other hand, they give overdosage on the basis to relieve animal pain within a short period. They believe that all drugs are functional for long period and used at any time.
Generally, the above conditions collectively showed that there were deep-rooted problems in the proper handling and management of veterinary drugs in general and antiprotozoal drugs in particular. This all are due to the knowledge gap in professionals and awareness problems in the community that can potentially affect the drug's quality, safety, and effectiveness. If the drugs are not handled and administered properly, there will be drug ineffectiveness that leads to high morbidity and mortality of animals that directly affects the life of the community [4]. The other potential threat of this improper drug handling and administration by nonprofessionals is drug-resistance development in which nally no drug will be left for treatment in the area because of the variety of antiprotozoal drugs commonly used in the area are very few.