Emerging and Re-Emerging Bacterial Zoonoses: A Nigerian Perspective on Control, Prevention and Intervention

Abstract

A propensity to re-emerge is a characteristic of bacterial zoonoses, diseases caused by bacteria that can be transmitted to humans from animals. Research shows that their transmission occurs in Nigeria, the most populated nation in Africa. However, due to insufficient epidemiological surveillance of bacterial zoonoses, the magnitude and burden of these infectious diseases is not fully acknowledged. They are therefore not a priority target of the national public health policy. This lesser concern is regardless of their likely role in the extensive prevalence of non-malarial undifferentiated fever in Nigeria. Several animal reservoirs and arthropod vectors of transmission have been identified for these diseases, Yet, the increase in cases of undiagnosed febrile illness emphasizes the imperative to undertake an extensive evaluation of other possible reservoirs, vectors and transmission cycles that may raise the local risk of zoonotic bacterial infections. Animal health interventions have been advanced as an economically viable and practical approach. Further, facilitating the operation of a community-based One Health program is essential to providing the comprehensive epidemiological information that is required in order to improve prioritization of bacterial zoonoses. This would generate impetus for much-needed investment in relevant public health interventions.

1. Introduction

Diseases that are transmitted directly or indirectly from wildlife to humans are a major cause of morbidity and mortality globally, including in Nigeria, which has the largest population and economy in Africa [1]. Around 60% of the 1500 or more infectious microorganisms known to be human pathogens are recognized as zoonotic, i.e. they normally exist in animals but they can also infect humans [2, 3]. While approximately 73% of emerging and re-emerging pathogens cause zoonotic diseases [2, 3], even more prevalent infectious diseases of major public health importance worldwide, notably malaria and HIV/AIDS, are known to be of zoonotic origin [2]. It is therefore speculated that future generations may face a higher risk of exposure to zoonotic diseases, requiring us to acknowledge the potential impact of this on life expectancy and quality of health [2, 3].

Zoonotic bacterial diseases such as bubonic plague and bovine tuberculosis inflicted enormous damage on mankind during the medieval period, an age in which sanitary measures, vaccines and antibiotics did not exist. In this context, the increasing occurrence and spread of zoonotic bacteria is of concern worldwide, with animals frequently identified as the reservoir host of a wide variety of potential pathogens [3]. The livelihoods of more than 600 million people globally are thought to depend directly on livestock. These communities represent 70% of the poor and marginalized population who are most at risk of zoonotic diseases but are often isolated from adequate health care provision [4].

Bacterial zoonoses are a category of much neglected human infections that may account for a substantial proportion of febrile illnesses without focal features, especially in malaria-endemic hotspots of sub-Saharan Africa, where they are often misdiagnosed as the more familiar protozoan infection [5]. While there are no reported estimates of the prevalence of fever of unknown origin (FUO) in Nigeria records suggest both its common occurrence and incorrect determination of the etiology [6, 7]. Despite the incidence of FUO and although humans have obvious contact with animal reservoirs and vectors of zoonotic disease, potentially important pyrogenic pathogens have not been rigorously investigated in many low- and middle-income countries, particularly in rural areas [8]. A deeper knowledge of the preventable and treatable infectious causes of severe febrile illness is critical to achieving a high level of disease control in developing countries and improving outcomes of affected patients [8].

This chapter discusses the neglected zoonotic bacterial pathogens of Nigeria, West Africa [9]. The focus is on commonly occurring emerging and re-emerging zoonotic diseases, presenting key developments in the field from recent worldwide research, highlighting findings from Nigerian investigations to date and identifying pivotal epidemiological features that have not been described in local studies. Adopting the One Health concept to combat bacterial zoonoses in Nigeria invokes a collaborative, interdisciplinary and multi-sectorial strategy to human and animal health management and interventions. The knowledge gleaned from implementing these principles can be applied in similar West African settings as well as low-income contexts elsewhere.

2. Bacterial zoonoses of public health relevance to Nigeria

As they are frequently associated with high case fatality rates, zoonoses dominate Nigeria’s register of notifiable infectious diseases for which emergency declaration is required [10]. Notable zoonotic diseases in Nigeria include Lassa fever, Ebola virus disease, rabies, influenza, yellow fever, anthrax, plague, tuberculosis, salmonellosis and trypanosomiasis, most of which are endemic [1, 10, 11]. Cryptosporidiosis and food-borne Campylobacter and Escherichia coli O157:H7 infections also constitute important national zoonotic diseases [1]. Leptospirosis, scabies, pentastomiasis and African histoplasmosis occur sporadically [1]. Considered endemic throughout the developing world, neglected zoonoses are inherently capable of causing local outbreaks and larger epidemics [12].

Zoonotic bacterial infections show tremendous potential to re-emerge once they are considered eradicated or under control, and therefore pose grievous, enduring threats to public health [3]. Although re-emerging across sub-Saharan Africa bacterial zoonoses are mostly neglected and under-reported in low-income nations [12]. However, they are acknowledged to be common and widely distributed in Nigeria [13]. Their emergence and re-emergence have been attributed to a combination of climatic, ecological, agricultural and socio-economic factors that create an uncertain public health situation [1].

In a recent investigation, a trend towards disease outbreak in Nigeria was reported for zoonoses of Leptospira, a Gram-negative, obligate aerobe spirochete [14]. Leptospirosis is an important bacterial zoonosis, especially in northern Nigeria, with a significant level of sporadic occurrences [1]. A national average incidence of six clinical cases of leptospirosis is reported annually, which is considered to be an underestimate [15]. Research during the past two decades in different regions of Nigeria have detected by serology and urinalysis various serovars of Leptospira interrogans, including Canicola and Hardjo, which are considered pathogenic in other continents [14, 16, 17, 18, 19].

Possibly the first report of the Gram-negative coccobacillus Yersinia pseudotuberculosis in the tropics was from Plateau State, Nigeria, and gastrointestinal yersiniosis due to infection with the pathogenic Yersinia enterocolitica is also known [20, 21]. Various serotypes of the Gram-negative, motile bacillus Campylobacter jejuni emerged in Nigeria decades ago as prominent causes of human gastroenteritis, inflammation of the stomach and small intestine [1]. Infection due to C. jejuni and the other primary zoonotic agent of campylobacteriosis, Campylobacter coli, have been on the increase worldwide and often exceed salmonellosis and shigellosis in national notifications [22]. Although comprehensive information on zoonotic campylobacteriosis in Nigeria is limited, both C. jejuni and C. coli have been isolated [22, 23, 24]. Globally, campylobacteriosis and non-typhoidal salmonellosis constitute the most prominent and significant enteric zoonoses [24].

Salmonella enterica serovars Typhimurium and Enteritidis are the main causative agents of sporadic outbreaks of salmonellosis among Africans, with which observations in Ibadan, the capital city of Oyo State, Nigeria, are consistent [25, 26, 27]. However, other less common serovars of the Gram-negative, flagellate, facultatively aerobic bacillus have a more geographically restricted distribution. For instance, the rare S. enterica Hidudiffy was the predominantly detected serovar in a study in northern Nigeria but was absent in a similar investigation in the southern region [25, 27]. This was attributable to factors like variation in climate or farming systems between the two regions and may need verification [25]. Other rare serovars that have been detected in Nigeria include S. enterica Apapa, Mouschaui and Vinohrady [25, 28]. In a recent large-scale surveillance program in Nigeria, S. enterica Eko was identified as a major serovar, one of 17 different serotypes that are potentially being transmitted locally within the country [27].

Brucellosis also remains a major neglected zoonotic disease of low-income nations. While assessment of existing data suggests ongoing transmission of human brucellosis in Nigeria, information on the causative Brucella spp. Gram-negative, facultative coccobacilli is not sufficiently clear from the limited bacteriological studies [12, 29]. Other common zoonotic bacterial infections, such as bartonellosis, borreliosis, Q fever and rickettsiosis, are also on the rise globally, especially in developing countries like Nigeria [3, 8]. Another Gram-negative coccobacillus, Coxiella burnetii, which causes Q fever in humans, has been reported at high serological prevalence in West African countries and has also been detected in veterinary studies in Nigeria [30]. Species of the Gram-negative Bartonella such as B. elizabethae, B. grahamii, known to cause human diseases in Peru and Thailand [31, 32], were recorded in a Nigerian study [33]. Another investigation identified Bartonella spp. in Nigeria similar to those detected in Ghana and Kenya [7]. Several studies have also detected rickettsiae, Gram-negative, intracellular coccobacilli, as potential agents of zoonoses in the country [34, 35]. Rickettsia massiliae, Rickettsia conorii israelensis and Rickettsia africae-like species have been identified as agents of bacterial zoonoses with possible ongoing transmission in Nigeria while Rickettsia felis, a prominent emerging rickettsial pathogen that is common in Senegal and Kenya [36], has a largely unknown epidemiology in the rest of the Africa, including Nigeria [30, 34, 35, 36].

Together with the isolation of other Gram-negative bacterial zoonotic agents in Nigeria, such as Anaplasma platys and Candidatus Neoehrlichia mikurensis, its first known description in Africa [34, 35], the scenario presented is of an increasing threat of bacterial zoonotic infections to Nigerian public health. However, fewer studies are conducted to investigate this class of zoonosis than most other infectious agents across a large geographic footprint of the developing world [8]. Plague is an important re-emergent bacterial zoonosis caused by Yersinia pestis, one of the most extensively studied pathogenic bacteria. Yet, with current case reports restricted to Africa, there is no known incidence in Nigeria [37, 38]. It is recognized that most zoonotic infections in the country are documented either poorly or not at all, comprehensive efforts to characterize the zoonotic agents are insufficient, and data on important aspects of their epidemiology are also limited [1, 13].

2.1 Infection risks associated with common transmission routes of zoonoses

Close contact with animals due to a person’s lifestyle choices or occupation is often associated with the re-emergence and heightened risk of zoonotic bacterial infections. Among others, this subjects farmers, hunters, wildlife workers, veterinarians, pet traders, families with pets, butchers and slaughterhouse workers to an increased risk of transfer of infection from animals [3, 10]. Therefore, bacterial zoonoses are generally considered occupational diseases in Nigeria [10, 14], where intimate proximity to animals as well as exposure to their tissues and body fluids are principal risk factors for zoonotic disease transmission. A prime example is that of leptospirosis during livestock slaughter and processing in abattoirs [14].

Infections with Brucella and Leptospira have been associated with handling of wild and domestic animals, through which direct transmission may occur [29, 39]. Association with livestock and pets in northern Nigeria increases the risk of Leptospira infection acquired through abraded skin when carelessly handling infected animals and their fluids or tissues [14, 15]. However, a significant link between a person’s intimate proximity to livestock or other animals and their contracting leptospirosis is not corroborated by inconsistent observations from other countries, thereby suggesting a complexity of region- and context-specific factors in infection risk [40]. Since studies of leptospirosis in Nigeria are limited [40], concentrated in the north and performed on standard risk groups [14, 15], whether such disparity occurs across varied settings in all regions of the country requires further investigation.

Indirect transmission routes for leptospirosis include soil and water contaminated with urine or other body fluids from infected animals via which L. interrogans may enter the human body through mucous membranes of the eyes and nose during activities such as bathing [14, 41]. Globally, heavy rainfall and flooding are associated with leptospirosis outbreaks in overcrowded locations with deficient waste disposal and poor sanitation [41, 42]. These conditions prevail in Nigeria among socioeconomically disadvantaged communities living in shanty towns, squatter settlements and relief camps [43]. Zoonotic bacterial agents like Salmonella, Campylobacter, Shigella, Yersinia and Listeria may also be acquired from contact with animals, their dung and droppings, as well as via indirect transmission by ingesting contaminated food [3]. Although known to occur predominantly in temperate zones, sporadic infections with pathogenic serotypes of food-borne Yersinia enterolitica as well as the rare Y. pseudotuberculosis have been reported in Nigeria [20]. However, aspects of the epidemiology of food-borne yersiniosis in developing countries, such as contamination routes in food, remain poorly understood and require clarification [21].

While leptospirosis may also be acquired through food [14] Salmonella and Campylobacter are regarded as the leading and most frequent zoonotic agents of human food-borne bacterial gastroenteritis in both developing and developed regions globally. Research performed on food products from markets in the Nigerian States of Sokoto, Plateau and Oyo identified bacteria of both genera to be associated with, and commonly transmitted via, contamination of poultry meat and eggs [3, 22, 24, 44]. A recent investigation in the north-east of the country also identified vegetables as a potential source of salmonellosis transmission, corroborating reports of increasing frequency of Salmonella outbreaks elsewhere in the world [28].

Consumption of raw or unpasteurized milk constitutes an important transmission route for Campylobacter spp., C. burnetii and Brucella spp. [3, 24, 29]. In Nigeria, C. jejuni was quite recently isolated from raw cow’s milk in Sokoto [45], while shedding of C. burnetii was detected in milk from cattle in Zaria in the 1980s [46, 47, 48]. Q fever is a devastating zoonotic disease that is associated with dairy farming, especially of goats, even in industrialized nations like the Netherlands, where it was epidemic between 2007 and 2010 [3, 49]. Among Fulani pastoralists in Nigeria it is important to assess the risk of C. burnetii infection due to Q fever outbreaks [50, 51, 52].

Inhalation of aerosolized organisms, one of the ways to contract the plague-causing Y. pestis that is endemic to Africa, is also regarded as the most important transmission route for C. burnetii infection in humans [53, 54]. Aerosols containing C. burnetii result from infected animals shedding bacteria, usually during parturition and lactation, which are inhaled from placental fluid, vaginal mucus, milk, urine and environmental dust [48, 49]. Q fever contracted by humans inhaling contaminated aerosols or ingesting raw milk or raw milk products has been reported elsewhere but not yet in Nigeria [54, 55]. A nationwide assessment of the risk of C. burnetii contamination of aerosols and dairy products may be justified in light of the fact that 90% of milk produced in rural areas is consumed raw [13].

Q fever poses a chronic health risk to immunocompromised individuals [48]. Immunosuppression from such varied causes as cancer treatment, pregnancy, organ transplant, diabetes, alcoholism and even infancy is also an important risk factor for other bacterial zoonoses including salmonellosis, bovine tuberculosis and bartonellosis, with Salmonella being a leading cause of bacteremia in this at-risk population across sub-Saharan Africa [3, 10, 26, 33, 56].

2.2 Animal reservoirs and the potential role of arthropods as transmission vectors

Livestock and animal reservoirs are recognized to contribute substantially to the continued transmission of bacterial zoonoses. This involvement ranges from passive to active roles including passive transmission of infection through bites and scratches, contamination of the environment and active transmission as vectors [3, 41, 57, 58]. The widespread distribution of zoonotic pathogens in domestic and wild animal populations represents a large reservoir of these disease-causing agents. Consequently, there is a perpetually high risk of infection between infected and susceptible animals with the potential for spread to human hosts [13].

It is estimated that approximately 20% of animal bites or scratches become infected, which is an important transmission route to humans for Bartonella henselae, the causative agent of cat-scratch disease. This is also transmitted by cat fleas (Ctenocephalides felis) that are found on both cats and dogs [3, 53, 59]. Cats are under-studied as potential reservoirs of locally acquired Bartonella infection despite their relative popularity as companion animals and the frequent occurrence of strays [60, 61] even in hospital premises in northern Nigeria [62]. However, a first report of bats as reservoirs of Bartonella in Nigeria identified four species as well as blood-feeding bat flies as possible contributors to local transmission of bartonellosis [7], similar to findings from Kenya, Ghana and Algeria [63, 64, 65]. While bats are thought to host numerous pathogens, most research has focused on viral zoonotic agents. Accordingly, the main aim of the recent survey overseen by the Nigerian Ministry of Health was to catalog new and existing viruses in the bat population [7, 66]. These flying mammals live near humans in many communities in Nigeria, where they are used for food, cultural practices and rituals. They may therefore play hitherto unrecognized roles in transmission of Bartonella and other zoonotic bacterial agents [7].

The past decade has seen reports of fleas, which are commonly known to transmit Y. pestis plague and likely contribute to the transmission of zoonotic pathogens such as Rickettsia typhi, R. felis and B. henselae [53, 67]. Therefore, it is necessary to investigate this hematophagous insect vector in Nigeria, a location where information about the possible role of fleas in zoonotic transmission is scarce. Conducted in 2011, the first known examination of rodents and their ectoparasites for Bartonella in Nigeria detected species in fleas, ticks and earwigs; some isolates represent known strains while others are of uncertain identity and require further characterization and evaluation for possible pathogenicity [34]. Meanwhile, human fleas (Pulex irritans), which have been found to infest Nigerian pets [68], and cat fleas have each been linked with recently re-emerged Bartonella quintana infections in some developed countries [53]. Cat fleas and several other flea species are also considered to be major reservoirs and biological vectors of R. felis, capable of transmitting this pathogen horizontally and vertically. However, conflicting reports from Senegal suggest that, despite the high prevalence of human infection, cat fleas do not contribute to local transmission of R. felis [53, 69]. Canine fleas such as Ctenocephalides canis, associated with transmission of B. henselae in other global regions, have a high prevalence in Nigeria where pet dogs are ubiquitous and in close contact with humans, yet the potential role of this flea in transmitting zoonoses locally is not well understood [68, 70, 71]. It is also thought that any species of flea is capable of transmitting Y. pestis under suitable conditions, and that P. irritans may play a crucial role in the transmission of plague from person to person [53]. Often considered a mere nuisance because of prior reports of vector incompetence for Y. pestis, cat fleas are suspected of causing an outbreak of plague in Uganda [53]. However, although human and other flea species are found on Nigerian pets there is currently no documented association between cat fleas and local transmission of Y. pestis [38].

In addition to hosting Y. pestis, rodents are reservoirs of R. typhi, the causative agent of murine typhus, as well as other zoonotic bacteria like Bartonella [32, 53]. Y. pestis has been detected in over 200 species of wild rodent in natural plague foci in Africa and across the globe [32, 53]. Small mammals such as rodents are common natural Bartonella reservoirs and close associations with humans due to conditions like overcrowding in rural communities enhance infection transmission [31, 33]. Rodents, particularly rats, are also widely recognized as prominent reservoirs of L. interrogans, typically spreading leptospirosis via their infected urine [42]. A variety of wild and domestic animals that are considered reservoirs of Leptospira have been extensively studied for leptospirosis in Nigeria. Dogs, cattle, pigs, sheep and goats are recognized to excrete leptospirochetes in their urine, thereby contaminating the environment for many months or even years after infection [19, 39, 42]. Yet, in Nigeria very little effort has been made to investigate the contribution of rodents to the epidemiology of this disease, with the last known report being published in 1990 [42, 72].

Livestock are principal reservoirs of zoonotic infections such as brucellosis and Q fever, with ruminants being the main source for transmission to humans [29, 48, 55]. For food-borne zoonotic pathogens like Y. pseudotuberculosis and Y. enterocolitica, pigs, sheep, goats and cattle are the main reservoirs of the pathogenic serotypes causing human infection in Nigeria [20]. C. jejuni and other human campylobacteriosis agents are also food-borne bacteria for which chicken has frequently been identified in Nigeria and elsewhere as a common reservoir [23, 24]. A higher prevalence of C. burnetii was observed in feeding Rhipicephalus evertsi ticks than in questing ticks collected from cattle in Oyo State, indicating that cows may be reservoirs of Q fever in Nigeria [30]. Wild birds, dogs, cats and monkeys are also natural reservoirs of Campylobacter, with certain species showing association with specific animal hosts [23]. The increasing consumption of camel meat and its other products in northern Nigeria prompted investigation that identified camels as potential reservoirs of Campylobacter zoonosis [23]. Genomic analysis of S. enterica Eko isolates collected from various sources in Nigeria also demonstrated an association between camels and non-typhoidal Salmonella zoonoses, implicating camels, together with cattle, as a principal reservoir for infection of humans [27]. In low-income nations, where sources and routes of transmission of salmonellosis are poorly defined, common food-producing animals are considered to be major reservoirs of Salmonella. An example is that of poultry in Nigeria, the studies on which corroborated research performed elsewhere in identifying chickens as a major reservoir of a broad range of Salmonella serotypes such as Hadar known to colonize flocks [26, 28]. However, transmission of Salmonella has also been linked to pet and indoor-dwelling reptiles such as wall geckos in Nigeria and worldwide, pointing to a potential role for captive reptiles as reservoirs of disease [25]. A pet lizard was implicated as the source in the first report of human infection with S. enterica Apapa [73]. Infections of Apapa and other rare serotypes such as Jukestown, Mouschaui and Oritamerin were identified in Ibadan, where these bacteria were not detected in chickens screened for salmonellosis. This suggests local transmission via unverified sources of infection such as household lizards, as these serovars have previously been associated with reptiles and amphibians [25].

The number of known animal reservoirs and vectors of Bartonella also continues to increase; as with fleas, other hematophagous arthropods such as sand flies, lice, mites and ticks transmit bartonelloses between the reservoir and final mammalian host, including humans [3, 34]. Tick-borne bacteria and other pathogens are recognized as significant causative agents of human and animal disease [33]. Considered a carrier of infectious disease second only to mosquitoes [33, 74], ticks were identified as a potential vector of Q fever in the 1930s following the first isolation of C. burnetii from Dermacentor andersoni, the Rocky Mountain wood tick [55]. Because of the frequent detection of C. burnetii in ticks collected from the wild as well as experimental evidence of their vectorial capacity, ticks are now considered to act as vectors of Q fever transmission [55]. The tropical bont tick, Amblyomma variegatum, is adept at supporting transmission of C. burnetii, for which it is considered a reservoir, as well as of R. africae, in Nigeria and Uganda [54, 75]. The largest tick species in Nigeria, A. variegatum, is the most common, providing a significant risk of Q fever transmission in Nassarawa, Oyo and Plateau States, where C. burnetii has been isolated from field-sampled ticks [54]. Detection of C. burnetii in ticks should be carefully interpreted until a method to directly distinguish between C. burnetii and Coxiella-like bacteria is developed. However, while following currently recommended procedures for screening for C. burnetii, these findings point to a role for tick reservoirs in transmitting Q fever in Nigeria [55].

Tick-borne rickettsiosis also occurs frequently in West Africa and R. conorii israelensis, the etiological agent of Mediterranean Spotted Fever which has been reported in Senegal [76], was first detected in Nigeria in the brown dog tick, Rhipicephalus sanguineus [34]. R. africae, the cause of African tick-bite fever, was identified in the cattle tick, Rhipicephalus microplus, from Nigeria in a study screening fed and questing ticks [30]. This rickettsial species is often associated with Amblyomma ticks and less commonly with other possible vectors including Rhipicephalus annulatus [77]. R. africae was isolated from feeding ticks only, so was likely acquired by ingesting blood from an infected host [30, 77, 78, 79]. From these reports it is unclear which tick species are potential vectors and thus further elucidation of their vector competence is required. A further Nigerian study in which dogs and brown dog ticks were free of R. africae may indicate a specific association between zoonotic bacteria and ticks of cattle and game animals [33], as reported in South Africa [80]. Detection of Rickettsia massilae in unfed ticks but not in their cattle hosts implies that ticks serve as both an important vector and reservoir of this pathogen in Nigeria [30]. Similarly, in Plateau State, Bartonella spp. was identified in R. sanguineus but not in rodent hosts, suggesting that the brown dog tick, whose role in transmission of Bartonella has not been previously shown, may be a local reservoir [33].

Other agents of bacterial zoonoses that have been associated with ticks in Nigeria include Candidatus N. mikurensis and A. platys, which were first detected in dogs, Ehrlichia spp., and a possibly novel form of the Borrelia burgdorferi sensu lato group that differs from known forms and which is associated with the Rhipicephalus ticks that can parasitize humans [30, 34, 68]. Comparing prevalence of pathogen bacteria in Nigerian ticks reiterates that detection in feeding ticks does not establish vectorial competence, i.e., the capacity of a tick to acquire, maintain, and transmit a bacterial species [30]. This highlights the need to demonstrate experimentally the vector capacity of ticks to sustain transstadial transmissibility of major zoonotic bacterial pathogens [30].

While the in vitro vector capacity of ticks, from which Leptospira spp. were isolated, was demonstrated several years ago, a link between arthropods and transmission of leptospirosis is not widely acknowledged [39, 81]. However, Leptospira was detected recently in Ixodes ticks from a wetland in Poland, eastern Europe [81]. This hints at a switch of Leptospira, aided by environmental fluxes, to adapt to novel hosts and maintain transmission through them, as previously documented for L. interrogans Hardjo serovar [41]. This finding requires confirmation from other global locations where ticks are recognized to contribute to transmission of bacterial zoonoses. However, Ixodes ticks of medical and veterinary importance are not a common presence in those regions of Nigeria that are prone to flooding [33].

Recent research suggests that mosquito species have emerged as transmission vectors for R. felis in West Africa. R. felis was detected in the tiger mosquito, Aedes albopictus, in Gabon, which lies to the south of Nigeria, at a similar infection load as found in the cat flea, Ctenocephalides felis, currently considered as the primary vector [82]. An invasive species to Nigeria, Ae. albopictus is now dominant over the native yellow fever mosquito, Ae. aegypti; first discovered in Delta State, analysis suggests a broader distribution across the southern part of the country [83]. Although originally identified in Nigeria in 1991 and first reported in Gabon as recently as 2006, the role of Ae. albopictus in arbovirus transmission is a major focus of investigation in Nigeria [83], yet its possible association with R. felis is less of a research priority. In Cote d’Ivoire, Gabon and Senegal, West African countries in which Ae. albopictus is not known to occur, the major malaria vector in Africa, Anopheles gambiae, presents a threat of rickettsial infection as R. felis and a new Rickettsia species were detected in An. gambiae and also An. melas [84].

Mosquito transmission may be implicated in the high risk of R. felis infection that has been reported in Senegal, where fleas are not involved [36, 69]. However, the possible role of mosquito species in transmitting rickettsial zoonoses in Nigeria remains poorly understood or not described. This also applies to other arthropods, particularly the housefly, Musca domestica, which has been identified as a potential mechanical vector able to transmit zoonotic infectious agents such as C. burnetii and Campylobacter in other parts of the world [58, 85].

2.3 Zoonosis surveillance and public health interventions

Infection rates in surveillance indicators such as arthropods and other host animals are commonly used to determine the risk of local transmission of pathogens to humans. Thus, within a defined area, the abundance and distribution of ticks and other hematophagous vectors are considered determinants of the epidemiology of vector-borne infections [33, 86]. Nigerian investigations showed that ongoing transmission of emerging and re-emerging bacterial zoonoses is associated with several animal reservoirs and vectors, while preliminary assessment of the risk of infection has also been made [13]. Human infection data are also a valuable surveillance indicator of infection risk [86]. However, in Nigeria this information is vanishingly scarce for bacterial zoonoses such as brucellosis, of which little is known about its prevalence. Further studies are needed to provide comprehensive profiling of clinical cases [13, 29]. Serological evidence of human brucellosis has been recorded but no details are available on the isolation of Brucella from patients in Nigeria [29].

Estimates of vector-borne infectious disease burden in low- and middle-income countries focus primarily on malaria and dengue, while zoonotic bacterial infections are largely ignored [8]. This is irrespective of reports from Nigeria justifying an assessment of the human disease burden imposed by C. burnetii, R. conorii israelensis and other zoonotic pathogens, plus a lack of attention to the public health impacts related to different vectors and animal reservoirs [30, 33]. This neglect of zoonotic bacterial infections is explained partly by under-reporting resulting in a reduced estimation of their disease burden and health impacts, which downgrades their relevance to politicians, policymakers and other interested parties [12]. In Nigeria, brucellosis is often confused with malaria [29], which frequently occurs in the reporting of bacterial zoonoses in other malaria-endemic areas [87]. Recent research conducted in malaria-endemic northern Tanzania showed that leptospirosis, brucellosis, rickettsioses and Q fever are often excluded or misdiagnosed as the parasitic disease [5]. After the gradual reduction of malaria incidence in sub-Saharan Africa this century, there is raised awareness of bacterial zoonoses as significant causes of FUO [5, 88, 89]. In the capital city of Nigeria, the centrally located Abuja, where historical overdiagnosis of malaria is suspected, non-typhoidal Salmonella infections were reported in the etiological diagnosis of febrile illnesses [90]. In contrast, for a case of FUO in southeast Nigeria, plausible causes were overlooked in favor of a presumptive malaria diagnosis, a practice common in this region that is also reported for management of febrile pediatric cases [91, 92]. Patients in Africa infected with bacterial zoonoses are likely to be discharged from hospital without receiving a correct diagnosis and thus the appropriate specific treatment. Focus on a wide range of potential causes of FUO, especially zoonotic infections, has been recommended for patient management and disease control in resource-limited settings [5].

While public health interventions for zoonotic infections in Nigeria have been proposed, prioritizing a disease for investment and funding will depend on impact assessments on both humans and animals [12, 13]. Initial reports identified how important joint efforts of medical and veterinary professionals are to controlling zoonoses that affect Nigerian public health and animal welfare [1]. Subsequently, the key role of the Ministries of Agriculture, Health and Information to promote the health of human and animal populations was emphasized [10, 13]. The complex interdependent relationships between human, animal and environmental health have given rise to the concept of ‘One Health’. This promotes collaboration of experts from diverse fields, such as physicians, veterinarians and environmentalists, working at state, national and international levels to achieve improved public health outcomes [2]. Despite growing global support for countries to embrace a One Health approach, in Nigeria the interdisciplinary similarities, especially between clinical and veterinary medicine, have not yet been recognized. This remains a major challenge to progress in addressing zoonotic diseases in the country despite increasing awareness of misdiagnosed undifferentiated fever [2, 13]. In 2009, the US Centers for Disease Control and Prevention launched the Animal-Human Interface Project (AHIP), providing technical training to facilitate progress on One Health in Nigeria [66]. Several collaborative projects have been promoted by AHIP together with partner agencies in Nigeria to investigate a wide range of zoonoses; however, attention has mainly focused on viral diseases. This may reflect the assertion that zoonotic viruses have the potential to influence stronger political and economic responses, as exemplified by recent Ebola outbreaks in Nigeria and the Democratic Republic of the Congo [93, 94].

A key recommendation of the One Health strategy for food-borne zoonoses is on-farm intervention. This includes routine vaccinations, immunostimulants and probiotic feed additives to manage animal health, as well as implementing animal welfare policies and measures to limit antibiotic resistance [3]. However, the successful adoption of these interventions in Nigeria is restricted by sustainability issues resulting from the discontinuation of disease control programs [13]. Furthermore, culling livestock and compensating farmers, a strategy that has helped to control zoonoses in industrialized nations, has not proved effective in Nigeria. This is because farmers, especially Fulani pastoralists, are unwilling to cooperate when infectious disease control involves the intentional loss of their herds [13]. However, changing lifestyles among settled Fulani communities, including healthcare attitudes and practices, may lead to greater receptivity of this influential group to interventions in future [51].

Among food-borne zoonoses such as salmonellosis conspicuous antimicrobial resistance of public health concern has been reported in Nigeria [25, 95]. Curbing the indiscriminate use of antibiotics as animal growth promoters that is commonly practiced requires the imposition of strict regulations. S. enterica Typhimurium isolates bearing close similarity to the multidrug-resistant ST313 strain that circulates in sub-Saharan Africa, as well as other strains resistant to tetracycline and sulfamethoxazole, have been identified in Ibadan [25]. This is attributed to the non-selective use of antibiotics at therapeutic and sub-therapeutic doses, which was observed in cattle examined in the same location where residual doses of oxytetracycline and penicillin-G were found [96]. Of associated concern, an alarming trend in the use of fluoroquinolones, tetracyclines, beta-lactams/aminoglycosides and macrolides for questionable purposes including disease management and growth promotion of livestock was recently highlighted for southwest Nigeria [95]. Meanwhile, other countries led by the United States have banned quinolones as a growth promoter in poultry feed due to the public health impact of pharmaceuticals used to treat both human and infections [3, 95]. In Nigeria, there are no strict laws governing antibiotic residues in animal tissues, while local food and drug regulatory authorities do not pay much attention to veterinary drug safety regulations [97].

Vector-borne diseases are also an important target of the One Health approach. It is expected that better national surveillance and reporting will improve disease control strategies, whereby clinicians play an important role in the effective management of vector-borne zoonoses with enhanced differential diagnoses [3]. The multiple causes of fever are difficult to distinguish clinically and hence many cases of FUO in low-resource contexts may be attributed to either lack of access to or limited provision of suitable medical microbiology laboratory services [8]. As an example, it was reported that Nigerian abattoir workers who eventually received a correct diagnosis of Brucella infection frequently complained of continued treatment for malaria despite their condition failing to improve [29]. It is evident that clinicians often lack information on the local epidemiology of causes of severe febrile illness. Consequently, internationally set management guidelines and disease control programs currently have insufficient data to set local priorities for prevention [8].

In sub-Sahara Africa, where hospitals and clinics typically are not readily accessible to affected people, accurate statistics on morbidity and mortality resulting from bacterial zoonoses are difficult to obtain [12]. Food-borne yersiniosis caused by the pathogenic Y. enterolitica that is commonly found in developed nations has been associated with chronic gastrointestinal illness, glomerulopathy and other disease symptoms in Nigerians [21, 98]. While Bartonella spp. are linked with endocarditis and neuroretinitis in Peru [32], for identical strains isolated in Nigeria a similar association to human disease has yet to be made [34]. In Senegal, where there are lower rates of detection of C. burnetii in reservoir cattle than those in Nigeria, seroprevalence rates in humans are as high as 51% [48], suggesting that these may be even surpassed in Nigeria [30]; however, this requires to be substantiated through further investigation. While a case of human leptospirosis recently occurred in Plateau State, no survey of leptospirosis as the cause of febrile illness has been conducted in Nigeria [42]. In 2006, the zoonotic bacterial infections leptospirosis, brucellosis, bovine tuberculosis, campylobacteriosis and salmonellosis were acknowledged as less recognized and under-reported [99]. The true extent to which these zoonoses exert an impact on health, especially at the population level, is unknown. In the following decade, the situation remained generally unchanged for most of these diseases, including brucellosis [29]. Therefore, the underestimation of zoonotic bacterial pathogens in Nigeria contributes to a dearth of integrated approaches to preventing morbidity and mortality from febrile illnesses. For example, this relative neglect stands in stark contrast to pneumonia and diarrhea, each of which is the focus of coordinated global control and prevention initiatives across most of its pathogen range [4, 5].

Determining the spatiotemporal distribution of an infectious disease is an important step in planning and implementing effective infection control and prevention measures [100]. However, in developing countries coordinated epidemiological systems for national surveillance of zoonotic infections are generally inadequate despite indications of a substantial burden of disease [22, 26]. The first comprehensive laboratory-based surveillance of human and animal salmonellosis in Nigeria was targeted at the north-east of the country [101], while another more recent attempt that employed whole genome sequencing to identify sources of Salmonella infection from isolates collected across Nigeria was focused solely on the S. enterica Eko serovar [27]. Reports from the country on human brucellosis similarly focus on standard at-risk populations and thus ignore other potentially susceptible groups. As a result, a century since its initial identification in Nigeria, little is still known about Brucella in regard to accurately assessing its zoonotic potential and hence informing establishment of appropriate control measures [29].

Many endemic diseases have increased in global incidence in the past two decades and a large number of vector-borne infections have also emerged in new regions [3]. For Nigeria, this growing public health concern underscores the need for up-to-date, accurate information on bacterial zoonoses, particularly with respect to arthropod-borne zoonotic pathogens that have recently emerged in novel vectors, such as R. felis in mosquitoes [68]. There is a correlation between the epidemiology of R. felis infection and increased risk of dengue in sub-Saharan Africa but not in other regions [78]. Mosquito species identified as potential vectors of R. felis in other West African countries, and which may be responsible for its transmission in Senegal [84], are known to be endemic to Nigeria [69, 82, 83, 84]. Although human rickettsial infections have yet to be confirmed in Nigeria, as a precautionary measure they are highlighted as a source of potential disease for travelers to the country [102]. Other pathogenic agents of bacterial zoonoses such as Candidatus N. mikurensis and Y. pseudotuberculosis were described recently for the first time in Nigeria [20, 33], which indicates an extension of their respective geographic ranges into the country.

The risk of contracting zoonotic bacterial infections is elevated among rural communities and for individuals who otherwise come into close contact with livestock or wild animals. Unfortunately, zoonoses that mainly affect subsistence farmers and low-income residents of regional and remote regions do not have a designated control or prevention scheme within Nigeria’s national healthcare program [12, 13]. Misreporting of cases and undervaluation of the clinical impact of a disease are factors for a lack of prioritized investment in tailored health interventions [12]. Applying a global burden of human disease methodology, Nigerian policymakers rely on unsubstantiated, incomplete data from other regions, an extrapolation that contributes to the systematic depreciation of zoonotic diseases nationwide [12]. The consequent paucity of resource commitment to public health issues by Nigeria and other developing countries poses a continuing challenge for One Health interdisciplinary collaborations and partnerships to enhance public health surveillance and disease control [13].

As an alternative criterion to total disease burden, appraising the cost-effectiveness of an intervention is a way to identify investment priorities for infection control [103]. The existence of multiple reservoir hosts is highlighted as a major hindrance to the elimination of zoonoses in Nigeria. Thus, interventions primarily targeting animal reservoirs and accompanied by promoting national public awareness are considered cost-effective strategies to constrain zoonotic bacterial and non-bacterial diseases [10, 13]. Investing funds in monitoring and treating animal populations is rarely supported strongly in most developing countries despite the potential benefits of improving food security and reducing poverty [12]. Interventions for zoonotic diseases may seem expensive in proportion to the public health benefits per se. Evidence of the burden to communities and the cost-effectiveness of integrated control would strengthen the case for a One Health approach to endemic zoonotic diseases [12]. It is argued that by investing in animal health interventions and veterinary care the exposure of a population to locally endemic zoonotic diseases is commensurately reduced [13, 104].

The rewards of a multidisciplinary analysis that covers health and economic factors will easily exceed the outlay and enable the health sector to present a case to policymakers based not on the impact on disability-adjusted life years but rather on the rate of return on public and private investment [12]. Hence, it is advocated that in Nigeria interventions against zoonotic infections should be viewed as a human capital asset and as integral to a poverty reduction plan [12].

3. Future directions

In order to enhance the security of human and animal health in Nigeria, cost-effective strategies are needed to raise the prioritization of bacterial zoonoses in health policies and to encourage investment in health interventions [9]. Current epidemiological surveillance of zoonotic bacterial infections across the country is incomplete, a situation that hinders development of a One Health program. This is an impediment to interdisciplinary collaboration between qualified professionals including environmentalists, veterinarians and clinicians. While different species and strains of common and rare pathogenic bacteria have been identified in vectors and reservoir animals in Nigeria, little is known about their potential impact on human health. Indeed, data on human infection do not exist for some zoonotic diseases. Recent research revealing the emergence of several zoonotic bacterial pathogens in previously unknown vectors and in new geographic locations demands a re-evaluation of their formally recognized national distributions. The knowledge gap regarding bacterial zoonoses in Nigeria is significant, closing of which is critical to the future success of control and preventive interventions. Implementing these public health measures will likely reduce local incidence of FUO.

Author contributions

Both authors contributed significantly to preparing and writing this chapter.

Funding statement

No specific funding was received for this work.

Competing interests

No conflicts of interest declared.