Introduction

Substandard medicines are authorised medical products that fail to meet the quality standards or specifications set out by regulatory bodies [1,2]. They may contain insufficient quantities of active ingredients or incorrect formulations, typically due to deficiencies in the manufacturing, distribution and/or storage processes [1,2]. For example, the quality of a medicine can deteriorate over time if it is stored incorrectly, leading to inadequate dosing. Falsified medicines deliberately misrepresent their identity, composition, and/or source. These products may intentionally contain no active ingredients, wrong ingredients, or incorrect quantities of the ingredients [1,2]. Between 2017 and 2021, the global incidence of Substandard and Falsified medicines (SFMs) increased by 36.3% [3]. SFMs have been identified as potential drivers of antimicrobial resistance (AMR) [4–9], undermining antimicrobial stewardship (AMS) efforts. As such, action plans, including the Uganda AMR National Action Plan, have a strong emphasis on strengthening detection mechanisms to identify and address SFMs [10,11].

Despite SFMs being a global problem, counterfeit pharmaceuticals have an estimated global trade value of 4.4 billion USD per year [12], driven in part by online availability [13,14], and limited access to quality health care services, especially in low- and middle-income countries (LMICs) [3]. The World Health Organization (WHO) estimates that one in ten medical products in LMICs is substandard or falsified [1] hence, the African continent bears the largest burden (>75%) of SFMs alerts [15]. Recent systematic reviews estimated that 18.7–22.6% of medicines in Africa [16,17], 26.9% in West and Central Africa [18], and 22.6% in East Africa [7] are SFMs. SFMs were responsible for approximately 122,350 under‑5 deaths across 39 sub‑Saharan countries [19], 693 under‑5 in Benin [20] and 12,300 in Nigeria [21] annually.

Through the support of the African Union, the African Medicines Regulatory Harmonization Initiative (AMRH) was established to increase access to safe and effective medicines in 2009 [22,23]. The AMRH initiative led to the establishment of the African Medicines Agency (AMA) in 2019, which aims to ensure that all Africans have access to affordable medical products for priority diseases/conditions that meet internationally recognized standards of quality, safety and efficacy [22–24]. In East Africa, the regulation of medical products is through the respective national medicines regulatory authorities supported by East African Community regulatory harmonisation initiative, which has contributed to better control of SFMs [25]. Furthermore, Uganda is part of the Lomé Initiative, which was signed amongst 7 countries to criminalise the trafficking of SFMs in Africa [15,26]. Within Uganda, National Drug Authority (NDA) is the country’s National Medicines Regulatory Authority (NMRA) and is therefore responsible for the regulation (quality, safety and efficacy) of all pharmaceutical products in human and animal health [27,28]. Despite the availability of these agencies, identification, monitoring and reporting of SFM remains a major challenge in most LMICs, including Uganda [24,29,30].

The structure of Uganda’s pharmaceutical sector and health supply chain has been described elsewhere [31–34]. This sector in the country is allocated 14% of the health budget, which is only 7.8% of the national budget [35]. Additionally, 96% of its pharmaceutical products are imported [36]. The government has made strides to expand local pharmaceutical production (LPP) by imposing import tariffs on imported pharmaceuticals, which has increased 8.2% of LPP [37]. Despite a 15.9% increase in essential medicines and health supplies, the overall allocation of resources remains low to meet both public and private health needs [38]. In Uganda, the most commonly available SFMs are for lifestyle conditions (such as diabetes and hypertension), impotence, malaria and bacterial infections [39–42]. Poor quality antimalarial drugs have been estimated to cost Ugandan patients $26 million each year, with the health and economic burden mainly on poor and rural populations, furthering health inequities [41]. Application of the Substandard and Falsified Antimalarial Research Impact (SAFARI) model in Uganda found that 9% of malaria deaths in people who had sought treatment were attributable to poor quality antimalarial drugs [43]. A recent study in Ghana, Nigeria, Sierra Leone and Uganda found that less privileged groups were disproportionately exposed to SFMs and had lower awareness of them [44]. Over 30% of respondents in Uganda reported having obtained medicines from unofficial sources, most commonly, street hawkers and family/friend [44]. A recent assessment of the pharmacopeial quality of artemether-lumefantrine antimalarials in Uganda found that all samples passed visual inspection but 18.9% of the samples were of substandard quality in terms of their drug content [45].

The drivers, prevalence and impacts of substandard medicines have been relatively well-studied. These drivers include limited access to affordable, safe and high quality medicines, limited in-country manufacturing capacity with quality assurance systems, weak regulatory systems, poor governance and enforcement including weak reporting mechanisms, poor drug distribution practices, poor drug supply chain management leading to drug stock outs, presence of crime entities, and limited public awareness [3,15,46]. The impacts of SFMs can be summarised into three categories: health (increased morbidity and mortality, progression of AMR, higher disease prevalence, loss of consumer trust in modern medicines, health workers and health systems, increased risk of side effects, and adverse reactions); socioeconomic (loss of income and productivity, increased poverty, and lack of social mobility); and economic impact (economic loss, increase out of pocket spending, and wastage of resources) [15,31,47]. Qualitative studies have been employed to understand the problem of SFMs with views from multiple stakeholders in sub-Saharan Africa [48–54]. However, most of these studies have a focus on human health [55], which creates a knowledge gap for understanding SFMs and the implications of this for AMR using One Health approaches [56]. To fill in this gap, we undertook an in-depth exploration of experiences and perceptions of stakeholders from a One Health perspective on SFMs in the Ugandan context. These stakeholders included representatives from the human health, animal health, and environment sectors. This study, therefore, qualitatively assessed the perceptions and practices on SFMs for use in humans and animals in Wakiso District, Uganda.

Methodology

Sampling

A total of 12 FGDs and 11 KIIs were conducted. This sample size was arrived at when data saturation was reached during data collection. The 12 FGDs were conducted in the selected rural, peri-urban and urban villages of Namayumba Subcounty and Kakiri Town. These areas were purposively selected because of being remote yet they had a reasonable number of veterinary drug shops and private pharmacies. CHWs who were actively involved in health promotion, and farmers who were practicing animal husbandry were purposively selected to participate in the FGDs after consultations with village leaders and mobilisers. Each FGD comprised of 8–12 participants, and a variety of male only, female only, mixed sex, and youth groups were constituted. This strategy was employed because mixing respondents could have affected the quality of the discussions considering some cultural, gender-related beliefs in the society. Some FGDs combined CHWs and farmers to explore how health and agricultural practices and knowledge on SFMs can influence each other in rural communities. The FGDs were carried out in four different categories (Table 1).

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Table 1. Focus Group Discussion categories.

https://doi.org/10.1371/journal.pone.0339569.t001

Results

Findings from the study are presented under 4 themes: definition of substandard and falsified medicines (SFMs); identification of SFMs; drivers of SFMs; and challenges in reporting SFMs.

Discussion

This study assessed perceptions and practices on SFMs for use in humans and animals and the potential impacts of this from a One-Health perspective in Wakiso district, Uganda. The availability of SFMs in human and animal communities is evident and the acceptance of this should not be taken lightly due to the ramifications for human, animal and environmental health [2,8,40,56]. Despite limited formal education or public health awareness campaigns, participants were able to recognise and discuss the existence of SFMs in their communities and the compounding factors of this health threat. Defining SFMs in relation to identifying their effects and appearance in both human and animal health was well described by the study participants. Studies in Sudan, Nigeria, Ethiopia, Tanzania, Lebanon and various continents have also shown that the public identifies SFMs through their side effects, appearance and packaging [49,52,59–64].

Despite being aware that SFMs could lack a quality mark, seal, batch number, label, packaging, or have a broken seal or a difference in the spelling of words on the packaging/ colour/ texture from the original, the FGD participants unanimously agreed that actual identification of SFMs was difficult without using them, as described elsewhere [52,53]. Difficulties in the identification of SFMs have also been raised in the recent WHO global report [30]. Furthermore, having knowledge about how to identify SFMs did not necessarily guarantee that community members would actually check their medicines before use, as found elsewhere [63,65]. In Nigeria, failure to verify medicines was attributed to time constraints [63]. However, in a study carried out in Tanzania, participants with knowledge of the health effects of falsified drugs better identified genuine and falsified drugs than their counterparts [64]. Our finding could be explained by the fact that participants stated that they had not been educated or trained on how to identify SFMs nor did they have the knowledge about the potential consequences on their health. Health campaigns to increase knowledge on identification of SFMs through investment in regular awareness programmes should ensure that the messages are understandable for all community members [66]. This can be achieved through using lay language without technical terminologies for the public to easily understand [67]. Use of visuals such as pictures during public health campaigns among communities with high illiteracy rates, as well as the provision of information on SFMs in local languages should also be explored.

In our study, it was reported that neither community members nor health workers knew where to report suspected SFMs. Similar findings have been found among the public [49] and health workers [68]. Enhancement of knowledge on the identification and reporting of SFMs is therefore needed, not only for the general public, but also health workers [67]. Such campaigns in Uganda should take a multisectoral approach involving various stakeholders including MOH, MAAIF, NDA, National Medical Stores (NMS), and the Pharmaceutical Society of Uganda (PSU). It is important to highlight that consumer attempts to directly report SFMs to manufacturers or question medical staff about SFMs at the point of purchase have been refuted as they are likely not to yield positive results [69], possibly due to power dynamics.

Our study showed a strong reliance on observation of the effects of SFMs after their use in humans and animals to distinguish them from genuine ones. However, this is a high-risk practice as harm caused by toxic ingredients cannot always be mitigated and may result in morbidity or death [49,70]. Whilst participants expressed safety concerns related to ineffective treatment and toxicities from SFMs, it should be noted that the public may continue to use these medicines if they fully or partially alleviate their symptoms due to their availability and affordability [52,71]. Our study participants believed it was the role of human and animal health workers to identify SFMs and stop the public from using them. In many peri-urban and rural communities, as shown by the study findings, access to medicines is usually through health and veterinary professionals, especially among farmers for their animals. Accessing medicines through trusted professionals was seen as a way to avoid SFMs, with participants placing confidence in the relationships they had cultivated with these providers, as reported in earlier studies [53,65,72,73]. However, sometimes these professionals may distribute SFMs intentionally (due to a desire to make profits/ supplement income) or unknowingly (due to a lack of knowledge on identification and reporting of SFMs) [17,30,52,53,74–76]. Additionally, a study conducted in Qatar revealed that there were few differences in levels of knowledge of SFMs between health workers and community members which is concerning [77]. Education of the public on SFMs should adopt a One Health perspective, addressing their impact across human and animal health systems, and supported by policies that encourage cross-sector collaboration. This is particularly important to reduce the risks of emergence of AMR as consumption of inadequate quantities of antimicrobials can increase the evolution of resistant micro-organisms which can be spread through the food-chain and environment. Such education should emphasize the need for animal and human medicines to be bought from their respective registered pharmacies, clinics and drug outlets.

Drivers of SFMs established in our study were divided into customer and supplier-led. Customer drivers included lack of knowledge, lack of finances, and inaccessibility of licensed drug shops/ pharmacies, which are interlinked. Recent multi-country studies in Ghana, Nigeria, Sierra Leone, and Uganda highlighted similar drivers of use of SFMs [44,66]. Our study participants believed that cheaper medicine which was thought to be substandard or falsified was more likely to reach them since the majority were residing in remote and inaccessible communities as described elsewhere [5]. Additionally, participants mentioned that their limited finances exposed them to buying cheap medicines for both humans and animals. According to the participants, their low purchasing power was linked to the likelihood of buying SFMs in the community. Similar perceptions of the cost of medicines having an impact on efficacy have been expressed in Ghana [53], Nigeria [78], Benin [79], Lebanon [65], Sudan [80] and globally [81,82]. Less privileged groups such as persons living in rural areas are likely to be disproportionally exposed to SFMs due to unaffordability of genuine medicines as shown in earlier studies [7,44,49,65] including Uganda where 97.9% of the deaths attributable to poor-quality antimalarials were among rural populations who also paid 10.7 times as much annually in out-of-pocket expenses compared with urban populations [41]. The same rural populations are more likely to be less educated, hence having limited knowledge of SFMs [44,83]. Earlier studies have raised concerns that SFMs disproportionately affect vulnerable communities, noting that their circulation is largely driven by the inaccessibility and unavailability of quality essential medicines, which in turn creates demand for cheaper alternatives exploited by SFM criminal supplier entities [18,46,71,83]. Additionally, the fear of agricultural modernisation may also expose rural veterinary communities to SFMs [84]. Such disadvantaged populations need to be prioritised while designing and implementing interventions to reduce access to and use of SFMs among the population. More importantly, the Ugandan government needs to increase household income through economic development, which would address the affordability constraints that drive poor families towards informal medicine markets. Additionally, a mechanism to subsidise the price of quality medicines could be developed so that they are more affordable to poor communities. Deploying mobile human and animal healthcare access points in remote areas would also take quality medicines closer to the population.

Our study identified poor regulation and enforcement as a supplier-led driver of SFMs which was closely linked with fear of reporting suspected cases and lack of trust in government systems. In many African countries, policy, regulation and implementation plans with respect to SFMs in human and animal health are inadequate [18,48,75,85–87]. Poor law enforcement has previously been seen to lead to corruption resulting in mistrust in government authorities and health workers [52,88]. These findings are consistent with a World Bank report that linked poor regulation and surveillance of SFMs to bribery and corruption [40]. As an example, cases of SFMs were found to have disappeared before courts of law in Uganda [40]. Studies in Ethiopia, Nigeria and Lebanon have also mentioned corruption within government and regulatory bodies to manipulate sales of SFMs for their private gain [52,89,90]. In our study, participants mentioned several incidences in which regulatory authorities were bribed by those selling SFMs to continue their businesses. Such bribery has also been described to happen among district drug inspectors in Uganda [91]. This occurrence of SFMs distributors and other personnel evading regulatory procedures has been observed in Lebanon as well [89].

Business orientation of medicine markets with the desire to make high profits has been documented in drug shops and pharmacies in Uganda [92–94]. Acts of tampering with expiry dates and alternations in medicine quantities and compositions in Uganda have also been reported for both human and animal health [39,95]. The lack of transparency and professional misconduct among medicines suppliers and government regulatory bodies regarding SFMs may be a major driver of mistrust in communities for both human and animal health [73,75,89]. While there is progress on dismantling the supply chain of SFMs through policing bodies as AFRIPOL-Interpol [96], Ugandan, government regulatory bodies, particularly the NDA, need to be more intentional in apprehending SFMs and their sellers [34]. Although pertinent recommendations for enforcing regulatory standards for quality in the production and supply of pharmaceutical products have been made [46], it is also important to note that without adequate political will and leadership, the regulation of SFMs will derail [97]. Additionally, more strict regulations and punishment for individuals or companies involved in the making, selling and distribution of SFMs is needed. For example, substantive fines for manufacturers, suspension or loss of licenses for pharmacies, clinics and drug shops, and imprisonment for fake veterinary/ human health care providers could be enforced.

Not knowing where to report suspected cases of SFMs was a recurring finding in our study as also found in Lebanon and Tanzania where the official reporting channels were unknown [89,98]. The NDA website stipulates that the public is expected to remain vigilant and report any suspected substandard products including medicines by email (druginfo@nda.or.ug) phone or text on 0800101999 (toll-free line) and +256417788100 or WhatsApp (+256740002070). Having no evidence to prove the purchase of SFMs emerged as a concern regarding reporting of SFMs. However, NDA does not require proof of purchase for one to report suspected SFMs as the post marketing surveillance team only requires specifics about the product and where it was bought, then samples are picked for quality control tests. Many participants also expressed concerns about the aftermath of exposure of their personal information upon reporting suspected SFM sellers which could lead to threats to their lives, family, friends and livelihood. This should not be the case as Uganda’s Whistleblowers Protection Act 2010 forbids the disclosure of the whistle-blowers identifying information [99]. Additionally, suspicion of SFMs can be reported anonymously to NDA using the various available channels including telephone and standard forms. To encourage reporting of suspected SFMs without fear of the consequences among the public including CHWs and farmers, increasing awareness on the anonymous channels such as phone hotlines and websites that can be used is needed. Establishment of a drug tracking code system based on barcode or two-dimensional code so that each drug could be traced throughout its supply chain to its end user may also be explored. Mandatory transaction receipts for pharmaceutical products during pharmacy and drug shop sales would provide a good starting point as proof for investigating SFM cases.

The study was undertaken in Wakiso district which might limit the generalizability of findings to other regions of Uganda with different demographics, healthcare access, or agricultural practices. Since self-reported data was collected, some participants especially human and animal health practitioners could have provided some information with a bias to appear correct since it is assumed that health professionals exhibit appropriate practices regarding SFMs. A strength of this study is that it was conducted among various stakeholders beyond health practitioners including policy makers, CHWs, farmers, and local leaders through both FGDs and KIIs. To gather diverse perspectives on SFMs, we carefully selected study participants including the separation of FGDs by gender, age and role, thereby incorporating gender, cultural and social considerations. While consistent with previous suggestions [8,29,30,46,78,83,86], our recommendations extend these by emphasising community-level and One health perspectives.

Conclusions

Several drivers of SFMs in the community among both humans and animals were established related to individuals such as a lack of knowledge, sources of medicines particularly drug shops and pharmacies, and weak regulatory frameworks including limited enforcement by the authorities. The use of the One Health approach showed the need of a unified approach to address SFMs as the experiences and challenges in human and animal health were similar. Increased awareness and better enforcement of regulations are needed to reduce the use and risks of SFMs in the community. Campaigns on visual identification and clear reporting channels for SFMs should be strengthened to protect public health and improve patient outcomes.

Supporting information

Acknowledgments

Our appreciation goes to the Research Assistants, Ministry of Health, Wakiso District Health Office, and local leaders for supporting the study. The contribution to the study by other members of the partnership between Nottingham Trent University (UK), Makerere University (Uganda), and Buckinghamshire Healthcare NHS Trust (UK) is also acknowledged.