4 DISCUSSION
This survey investigates AMU in comparable beef cattle production systems and associated drivers for misuse and resistance emergence in Nigeria. We found overall low level of practices towards AMU amongst beef farmers. This can predispose MAR emergence. The low levels of practices could be due to lack of sensitization of farmers on the impacts of AMR and consequent public health implications. Antimicrobials sales are supposed to be restricted and sold only by trained animal health authorities. However, we found high practices of over-the-counter purchase of antimicrobials from human pharmacy stores and drug hawkers for use in beef farms. This could be due to lack of stringent government regulations guiding antimicrobials sales for animal use in Nigeria.
The study found high practices of self administration of antimicrobials among intensive beef farmers (68.4%) and semi-intensive farmers (58.2%). This can lead to under-dosing or over-dosing on animals, a characteristic of antimicrobials misuse (Maron et al., 2013). We observed practices of giving only a single dose of antimicrobials once on sick animals. The use of appropriate dose is as important as the completion of the antimicrobial course (Maron et al., 2013). It is noteworthy that a single dose of antimicrobials administered to an animal has the propensity to generate AMR within pathogens populations resident in that animal, and the repeated and continued AMU compounds this risk (Harada & Asai, 2010). Inappropriate AMU on animals exposes the pathogens to sub-inhibitory concentrations of the antimicrobials (Davies & Davies, 2010), which can result as in the development of AMR. High practices of inappropriate dosing could be due to inadequate veterinary services (Garforth, 2015).
We also found non compliance with antimicrobials withdrawal periods among intensive (72.4%) and semi-intensive (83.9%) farmers. Lack of compliance with antimicrobials withdrawal periods could create low therapeutic doses and high concentration of residues in tissues, which in turn, could result in new pathogens with antimicrobial resistant genes emergence (Alhaji & Isola, 2018). Additionally, this identified antimicrobials to be used for therapeutic, prophylaxis and growth promotion purposes in the two beef production systems. The likelihood of AMR emergence from these purposes is dependent factors that are mainly associated with quantity, dosage, frequency and duration of application (McEwen, 2006). The most striking concern was the use by high proportions of intensive and semi-extensive farmers (71.5% and 53.2%, respectively) for promotion of growths in beef farms. AMU for growth promotion and infection prevention in food animals significantly contributes to AMR emergence, an escalating global public health threat (Pokharel et al., 2020). When antimicrobials are used for growth promotion, selective pressure is created among the pathogens, and possibly forcing the exposed pathogens to mutate or acquire DNA pieces to become antimicrobial resistant (Zowawi et al., 2015).
Tetracyclines, sulfonamides and penicillin, amongst others, were observed to be significantly used in very high proportions in the farms. This is consistent with findings that reported high level of AMU, especially tetracycline, aminoglycoside and penicillin in food animals in Africa (Kimera et al., 2020). The high levels usage may be due to poor sanitation and low biosecurity practices. Most of the observed frequently used antimicrobials are considered by WHO to be critically important (neomycin) or highly important (oxytetracycline and sulphonamides) for humans (WHO, 2012). Their residues in beef products can be transferred to humans with consequent reactions.
The study identified risk routes for dissemination of antimicrobial residues and resistance, creating potential One Health challenge. The most probable ways are through: consumption of contaminated beef and beef products; direct or indirect contacts with contaminated beef animals, beef and fomites; and contaminated faeces and urine, aerosols, as well as flies and rodents in farm environment. These are in consonant with reports of a study that found AMR, especially resistant pathogens, to be transmitted from food animals to humans through consumption of food, contacts with contaminated animals and their waste products in the environment (Marshall & Levy, 2011). Most of the farmers in Africa are often in close contacts with animals, which facilitate resistant pathogens transmission (Doyle, 2015). Studies have shown that food animal products contaminated with resistant pathogens are direct pathways to human colonization (Hong et al., 2011; Marti et al., 2013). Food animals have been shown to be most important known pathway for the spread of AMR to humans (Capita and Alonso-Calleja, 2013).
The findings on environmental pathway through contaminated faces and urine, and aerosols are extremely important. It has been reported that antimicrobial residues, resistant genes and pathogens can be disseminated through airborne particulate matter from large cattle feedlots (McEachran et al., 2015). Rapid and ceaseless transportation of people and animals as well as aerosols from one place to another make transmission of resistant pathogens easy, thereby threatening global health, food safety, and food security (Zhao et al., 2010; Hong et al., 2011; Li et al., 2012; Woolridge, 2012; FAO, 2016). This means that there is higher propensity for transboundary spread of resistant pathogens propagated in food animals in the environment via aerosols.
Some factors that include inappropriate dosage of antimicrobials, non enforcement of laws regulating AMU, weak economic status of beef farmers, low education and expertise of the farmers, husbandry management systems, and poor sanitation and biosecurity at farm sites were observed to significantly drive antimicrobials misuse in farms. Excessive use and misuse of antimicrobials are widely identified as major drivers for AMR as a result of the selection pressure imposed on food animal microbiota abd consequent emergence, persistence, and dissemination of resistant pathogens to humans (Morgan et al., 2011; Larissa et al., 2013; Novo et al., 2013; WHO, 2014). Absence of adequate regulations promotes misuse, residues and resistant pathogens emergence and spread (Mtenga et al., 2011). Poverty has been reported to be a major driver of antimicrobial misuse in developing countries (Okeke et al., 2005).
In the present survey, Traffic Light model findings indicate that very high proportions intensive (63.6%) and semi-intensive (57.6%) farms are at Red risk status (Class 3) due to frequent AMU without veterinarians’ consultations, a common practice by farmers in developing countries, just to save costs. The predisposition to rely on personal experience without patronizing veterinary services drives farmers to indiscriminately use antimicrobials through unregulated supply chains. They only consult professionals when there are complications after all available options of therapy have been tried with no response, a common practice found in developing countries (Kunin, 1993; Byarugaba, 2004). In many countries such as the Netherlands, Denmark, Norway and Sweden, the use of antimicrobials on food animals are strictly under the veterinarians’ supervision (Cogliani et al., 2011), and such practices are very much needed in beef farms in developing countries, especially Nigeria.
Significant antimicrobial residues were identified in the urine of intensively managed farms (48.4%) and semi-intensive herds (34.4%). Food animals are estimated to excrete between 10% and 90% of the antimicrobials ingested, either as bioactive compounds or unchanged, and these can potentiate resistant pathogens emergence in the environment (Li et al., 2018). As food animal production and associated consumption of animal protein is forecast to markedly increase over the years to come in LMICs, systematic surveillance of AMU on animals has become imperative so as to mitigate AMR ( Cuong et al., 2018). Best practices of biosecurity measures are also required to control and prevent high level of infectious diseases in farms and avoid frequent use of antimicrobials in farms.
The study was limited by use of relatively small sample size (660) for the farmer when compared to the size of the study area. This might have underestimated the effects of determinants on the outcomes. Lack of full adjustments for clustering in the designed random sampling is a further limitation. Application of central tendency measures, however, was valuable enough to tolerate the likely imperfections in the confidence intervals. Being a cross-sectional study, the survey did not demonstrate causal relationship but does show associations of dependent and independent variables.