|Year : 2019 | Volume
| Issue : 4 | Page : 217-227
Challenges of bovine tuberculosis control and genetic distribution in Africa
Benjamin David Thumamo Pokam1, Prisca W Guemdjom2, D Yeboah-Manu3, Elroy P Weledji4, Jude E Enoh5, Patience G Tebid6, Anne E Asuquo7
1 Department of Medical Laboratory Science, Faculty of Health Sciences, University of Buea, Buea, Cameroon; Department of Bacteriology Department, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana
2 Department of Public Health, Faculty of Health Sciences, University of Buea, Buea, Cameroon
3 Department of Bacteriology Department, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana
4 Department of Surgery, Faculty of Health Sciences, University of Buea, Buea, Cameroon
5 Department of Medical Laboratory Science, Faculty of Health Sciences, University of Buea, Buea; Department of Laboratory of Endocrinology and Radioelements, Medical Research Centre, Institute of Medical Research and Studies on Medicinal Plants, Yaounde, Cameroon
6 Department of Medical Laboratory Science, Faculty of Health Sciences, University of Buea, Buea, Cameroon
7 Department of Medical Laboratory Science, College of Medicine, University of Calabar, Calabar, Nigeria
|Date of Submission||08-Feb-2019|
|Date of Acceptance||20-Sep-2019|
|Date of Web Publication||03-Dec-2019|
Dr. Benjamin David Thumamo Pokam
Department of Medical Laboratory Science, Faculty of Health Sciences, University of Buea, P.O.Box, 63 Buea
Source of Support: None, Conflict of Interest: None
Bovine tuberculosis (BTB), caused by Mycobacterium bovis(M. bovis); a member of the Mycobacterium tuberculosis complex (MTBC), is a well-known zoonotic disease, which affects mainly cattle. Control programs have either nearly or completely eliminated this disease from domesticated animals in many developed countries. Its persistence in developing countries results from interactions between people, livestock transhumance, and wildlife. In addition, deficiencies in preventive and/or control measures, poor sanitation, veterinary and slaughterhouse services, and lack of political measures have been blamed. The proportion of human TB cases caused by M. bovis is most likely underestimated since tests to distinguish between MTBC are seldom performed. Molecular techniques, especially spoligotyping, have helped to link human and animal transmission. Several challenges in the control of M. bovis TB in Africa have been identified, and its eradication efforts require a holistic approach. This review explores the challenges in the control efforts of BTB in Africa, as well as the impact of the genotyping evolution and distribution of M. bovis in the continent and strategies to improve its control.
Keywords: Africa, bovine tuberculosis, control, genetic diversity, human transmission
|How to cite this article:|
Pokam BD, Guemdjom PW, Yeboah-Manu D, Weledji EP, Enoh JE, Tebid PG, Asuquo AE. Challenges of bovine tuberculosis control and genetic distribution in Africa. Biomed Biotechnol Res J 2019;3:217-27
|How to cite this URL:|
Pokam BD, Guemdjom PW, Yeboah-Manu D, Weledji EP, Enoh JE, Tebid PG, Asuquo AE. Challenges of bovine tuberculosis control and genetic distribution in Africa. Biomed Biotechnol Res J [serial online] 2019 [cited 2019 Dec 9];3:217-27. Available from: http://www.bmbtrj.org/text.asp?2019/3/4/217/272181
| Introduction|| |
Bovine tuberculosis (BTB) is a well-known zoonotic disease resulting primarily from infection with Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex (MTBC) which consists of M. tuberculosis sensu stricto, Mycobacterium africanum, Mycobacterium caprae, Mycobacterium pinnipedii, Mycobacterium canettii, Mycobacterium microti, Mycobacterium mungi, Mycobacterium orygis, Mycobacterium suricattae, and the dassie bacillus., BTB was previously found worldwide; however, the introduction of control measures including test and slaughter and pasteurization has nearly eliminated this disease from domesticated animals in many countries. Several European, Asian, or American Nations are currently classified as BTB free or are underway of eradication with adopted programs. BTB, however, is still widespread in domestic animals or wildlife in parts of Africa, Asia, the Pacific, and some Middle Eastern countries, as well as some regions in the Americas and Europe. In 2017 and early 2018, the disease was declared present in 43% of reporting countries and territories and is distributed in every region of the world., Its persistence in developing countries results from deficiencies in preventive and/or control measures, poor sanitation, and health care. It is classified by the Food and Agriculture Organization of the United Nations (FAO) and the World Organization for Animal Health (OIE) as a “List B” disease; a category including “Transmissible diseases which are considered to be of socioeconomic and/or public health importance within countries and which are significant in the international trade of animals and animal products.” (http://www.fao.org/docrep/004/x3331e/X3331E01.htm).
The genetic characterization of tubercle bacillus isolates causing disease in humans has been extensively studied contrary to those causing disease among wild and domesticated mammals. Despite the fact that very closely related mycobacteria have adapted to causing TB disease in a specific host species (some exclusively human), for example, M. tuberculosis, M. africanum, M. canettii or rodent pathogens (e.g. M. microti), interspecies transmission can occur with a wide host spectrum as with M. bovis.,
| Mycobacterium Bovis Hosts and Transmission|| |
Among the MTBC, M. bovis has the widest host range; it infects mainly cattle, but cross-infection of humans and a wide range of both domestic and wild animals can occur. The pathogen can be transmitted by aerosol and ingestion of infected carcasses. The interactions between humans, livestock, wildlife, and the consumption of unpasteurized contaminated milk and other dairy products, especially in developing countries, puts people at a greater risk of exposure to the disease. BTB manifests as tubercles consisting of a necrotic caseous core surrounded by granulomatous inflammation. These tubercles can be found in any organ but are the most common in the lymph nodes, particularly of the mammary gland and lungs., Cattle shed M. bovis in various secretions including the respiratory, feces, milk, and urine, as well as vaginal secretions or semen. In most cases, M. bovis is transmitted between cattle in aerosols in close contact. Ingestion is the main route in calves that nurse from infected cows. Cutaneous, genital, and congenital infections have been seen but are rare. All infected cattle may not transmit the disease, however, asymptomatic and anergic carriers occur.
Eating meat from wildlife obtained by poaching/hunting which are likely not to undergo veterinary inspection is another potential source of infection to humans. While disease prevalence in cattle decreases, control efforts are sometimes impeded by the passage of M. bovis from wildlife to cattle. In epidemiological terms, the disease can persist in some wildlife species, creating disease reservoirs. Several animals have been reported to be spillover hosts. Although most mammals may be susceptible, little is known about the susceptibility of birds to M. bovis, as they are generally thought to be resistant based on the experimental infection.
| Bovine Tuberculosis Control in Africa|| |
Several control strategies such as tuberculin testing of livestock, removal of positive reactors and milk pasteurization have contributed to the very low risk of contracting zoonotic TB in developed countries. The lack of control measures among other factors contribute to the continued risk and difficult eradication and spread of BTB in Africa. The impact of noneradication will have global implications considering the current trends in international trade and globalization. In 2016, 35 and 27 countries between January–June and July–December, respectively, notified the disease in the African region. None of the countries had either official vaccination, treatment, or wildlife reservoir control policy, although 24 countries practiced some precautions at the borders. (www.oie.int/wahis_2/public/wahid.php/Diseasecontrol/measures).
Wildlife reservoirs have been shown to hinder greatly the control efforts of M. bovis., The role of these reservoirs in M. bovis disease dynamics has been established by various molecular methods and guiding to some level the control measures, especially in developed countries. It has also aided in tracing the sources of infections that result from within-herd transmission and movement of livestock. Once BTB is established in a herd, it spreads through aerosols, suckling, direct contact between animals, and sharing of water and feed. The BTB infection in maintenance hosts can persist through horizontal transfer in the absence of any other source of M. bovis and can be transmitted to other susceptible hosts. Moreover, the comparison of the clonal complex data from African regions indicates an intercountry transmission associated with a country-specific evolution, and the clusters suggest the current transmission that occurs mainly within cattle populations, less frequently between cattle and humans and possibly between humans, pointing out the difficulty to develop an efficient national control strategy of BTB in Africa.
| Challenges Associated With Bovine Tuberculosis Control in Africa|| |
Diagnostic challenges of human Mycobacterium bovis infection in Africa
Although studies in Africa have shown that a median of 2.8% (range 0%–37.7%) of all TB cases in humans is caused by M. bovis, these figures most likely underestimate the true number of cases since differential diagnosis of MTBC are seldom performed. Several African settings still rely on smear microscopy diagnosis of TB, with culture and differentiation of M. tuberculosis species remaining limited. The importance of the introduction of laboratory culture for the specific identification of the mycobacteria in Africa has been pointed out. Several other factors might be associated with the low prevalence of M. bovis in Africa; further contributing to its underestimation. These include the generalized use of glycerol in the culture media for tubercle bacilli isolation in available facilities with such diagnostic capacity. Human disease caused by M. bovis and other species of the MTBC are similar, although the anatomic site of M. bovis disease is more often extrapulmonary. Therefore, identifying M. bovis in extrapulmonary and respiratory samples would provide more accurate estimates of M. bovis infections of human TB.
It has been reported that approximately 13% of isolates were more likely to be M. africanum and M. bovis rather than M. tuberculosis. The need for molecular characterization of clinical isolates to ensure that correct estimates are made of the true burden of infection due to M. bovis and M. africanum in developing countries has been highlighted; M. africanum isolates have substantial phenotypic heterogeneity with some strains resembling M. bovis and others resembling M. tuberculosis.,,,, This has led several authors to question the validity of the species designation., In most cases, the available information indicates the mere presence or absence of the TB disease but does not provide any analysis of the spatial prevalence and proportion of M. bovis infection in a specific region. Data on human infection with M. bovis mainly stem from individual research on molecular epidemiology or genetic diversity studies of MTBC in Africa. Given the low-sample sizes and the lack of large-scale, population-based studies, available data are insufficient to identify specific risk groups associated with M. bovis infections. The link between the population of M. bovis strains causing human TB disease originating from a distant population has been shown through spoligotype patterns. As advanced as the newly introduced Genexpert molecular technique is, it is unable to differentiate the various species of the MTBC. Consequently, patients infected by M. bovis who are placed on standard treatment are likely to experience treatment failure as a result of intrinsic pyrazinamide resistance.
Transhumance control challenge
Several factors such as the variation in the ecological zones (arid, semiarid, subhumid, humid, and highlands), the differences in the production and movement of livestock within the continent (pastoralism, “agro-pastoralism,” mixed farming, and intensive dairy farming), as well as the macro- and micro-climates affecting the stability of the agent in the environment influence the distribution and transmission of animal TB and thus its control in Africa. This affects its prevalence between different areas. About two-thirds of the African continent comprises arid or semi-arid areas, and the majority of rural African drylands are inhabited by livestock keepers, who are either pastoralists or farmers; combining rainfed agriculture with pastoralism. Most of the pastoral communities (Bedouins, Berbers, Maasai, Somali, Boran, and Turkana) across the continent live in the semi-arid grasslands or arid deserts where rain-fed agriculture is difficult, and the effects of climate change observed in some subregions have led to intensification of these movements. Drought generally affects the life of pastoralists, and with the diminution of rains and dried pastures, they are forced to move in areas where the forage is available to avoid the starvation of cattle. The mobility of animals and their herders is not only motivated by the search for pasture and water but equally to avoid areas affected by livestock disease or to engage in livestock trade. The movements vary greatly in the distance and may take place within a country or into bordering countries. The diversity of the restriction fragment length polymorphism (RFLP) and/or spoligotype patterns has been shown to reflect the extensive internal movements of cattle belonging to pastoralists, and strains sharing common evolutionary origin have been described between countries with cattle trading links. Nomadic or seminomadic pastoralists predominate across the dryland Sahelian and Saharan belt that transects West, North and the Horn of Africa, where the belt of aridity turns southward to penetrate East Africa. With cross-border mobility commonly practiced with some resultant occurrence of friction and conflicts between pastoralists and local communities, countries such as Benin, Togo, Ghana, and Côte d'Ivoire, like countries in the Sahel region, have become host or transit countries, and initiatives have been recorded in the horn of Africa seeking to promote and document cross-border trade to stimulate regional growth, food security, and allow the effective vaccination of livestock.
Large variations in disease occurrence within different regions of the same country have been reported in Africa. High prevalence rates of BTB have been described in areas where cattle shared grazing and water as well as in areas where the traditional management of livestock in transhumant herds prevailed., Under these often nomadic conditions, the risk of exposure to M. bovis is increased significantly by creating multiple herd contacts and increasing the total herd size. The latter has also been suggested as a driver of the disease prevalence. Isolation of M. bovis from humans and M. tuberculosis from livestock has pointed out transmission between livestock and humans in the pastoral areas. Although some countries within the Economic Community of the West African States have formulated and passed legislation, these legal texts have not been put into practice. Moreover, pastoralist development projects and programs helping to improve transhumance practices by establishing infrastructure along the livestock corridors (a strip of land reserved for livestock passage to access pasture, a source of water or other herd infrastructures such as a livestock market, vaccination area, or livestock-holding area) are still insufficient.
There have been initiatives seeking to promote cross-border trade and also document it, to stimulate regional growth and food security and allow the effective vaccination of livestock. Initiatives include Regional Resilience Enhancement Against Drought, the Enhanced Livelihoods in Mandera Triangle/Enhanced Livelihoods in Southern Ethiopia as part of the Regional Enhanced Livelihoods in Pastoral Areas program in East Africa, and the Regional Livelihoods Advocacy Project.
Slaughterhouse to consumers and environmental security challenge
Although postmortem inspection of carcasses is carried out at the structured available slaughterhouse in Africa, low standard of hygienic practices within its setting as well as unreliable and inadequate meat inspection record have been reported. This points out to the lack of thoroughness of the veterinary staff incriminated with downstream consumers risk of BTB infection., Within the slaughterhouse, the diagnosis of BTB can be made following the macroscopic detection at necropsy of typical lesions, and postmortem inspection of carcasses has been found to be insensitive for the detection of lesions. To determine the significance of cattle that give a positive reaction in diagnostic tests but do not have visible lesions due to early infection, a bacteriological examination is necessary. Although methods employing monoclonal antibodies and DNA probes may be used to obtain a rapid identification, this is impractical in Africa due to lack of basic infrastructure.
Risky behavior and poor attitudes and practices within African slaughterhouse constitute itself the point of dissemination of the disease, not only to workers but equally to the population and environment. It has been observed that there are many risks for those working within its vicinity that can create accidents likely to promote zoonosis as BTB infection especially because of lack of safety procedures observance (e.g. no use of Personal Protective Equipment) leading to accidents works such as injuries caused by the different sharp objects, falls on wet, greasy, and slippery floor from handling raw meat. Furthermore, good hygiene and sanitation are not fully observed in slaughterhouse added to the lack of potable water (the use of untreated water drawn from well polluted with drain) put at-risk workers to M. bovis infection. The lack of proper sewage system leading to stagnant water, environmental pollution, poor waste management, and disposal contributing to pollution in slaughterhouse itself, air, water, land in the vicinity [Figure 1], as well as delayed disposal of animal carcasses such as abandoned horns often heaped awaiting its sales and/or incineration have been observed [Figure 2]. Slaughterhouses are a major source of water and air pollution worldwide, and the environmental and public health implications of unhygienic waste disposal has been pointed out in Africa with recommendations for a safe disposal following the international norms.
|Figure 1: Wastewater disposal from a slaughterhouse to close inhabited environment|
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|Figure 2: Unsanitary environment and disposal of animal carcasses and horns within an African slaughterhouse|
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Movement of people in and out of the slaughterhouse is not controlled, and the lack of knowledge by the workers eating in the slaughter hall and not respectful of personal hygiene and sanitation all contribute to put at risk all those having access to the slaughterhouse. Moreover, there are usually no medical facilities to take care of any emergencies that may occur while they are working. Interrupted power supply, inadequate temperature checks and close monitoring of cold chambers for proper meat preservation, as well as transportation of meat in dirty car trunks or other available local transport systems, constitute the poor system management of slaughterhouse in Africa. Moreover, the deficiencies of veterinary services in the rural and remote areas in developing countries constitute a setback and thus likely to promote the spread of the infection. Sometimes, animals are slaughtered outside approved facilities, especially during transhumance, where some sick animal can be sold to avoid the economic loss of herders. Furthermore, socioeconomic challenges faced by herders, religious and various cultural practices as well as the inability of the governments in Africa to compensate herders hinder the test and slaughter policy, leading to the perpetuation of disease transmission.
| Molecular Epidemiology as a Contribution in Bovine Tuberculosis Control in Africa|| |
Host tropism and genetic evolution of Mycobacterium bovis
The MTBC is characterized by 99.9% similarity at the nucleotide level and identical 16S rRNA sequences but differs widely in terms of their host tropisms, phenotypes, and pathogenicity.,, Gene expression differences between the sequenced M. tuberculosis and M. bovis have been defined, and comparative analyses of the M. tuberculosis and M. bovis genomes have revealed the basis for distinguishing phenotypes such as the pyruvate requirement of M. bovis in glycerol-based media, or the reason for eugonic/dysgonic colony morphology. Contrary to earlier assumptions that human TB evolved from the bovine disease by adaptation of an animal pathogen to the human host, new findings in the light of genome sequencing indicate that TB first emerged in humans and was subsequently transmitted to animals. The common ancestor of the MTBC is suggested to have emerged from its progenitor perhaps 40,000 years ago in East Africa. Some 10,000–20,000 years later, two independent clades evolved, one resulting in M. tuberculosis lineages in humans, while the other spread from humans to animals, resulting in the diversification of its host spectrum and formation of other MTBC members, including M. bovis. Based on the high sequence conservation in housekeeping genes, it has been hypothesized that the tubercle bacilli encountered a major bottleneck 15,000–20,000 years ago. As the conservation of the TbD1 junction sequence in all tested TbD1-deleted strains suggests a descent from a single clone, the TbD1 deletion is a perfect indicator that modern M. tuberculosis strains that account for the vast majority of today's TB cases definitely underwent such a bottleneck and then spread around the world, and the adaptation to animal hosts probably coincided with the domestication of livestock approximately 13,000 years ago.
M. bovis has undergone numerous deletions compared to M. tuberculosis. The genome sequence analysis of M. bovis AF2122/97, isolated from cattle, revealed no new gene clusters that were confined specifically to M. bovis, indicating that the genome of M. bovis is smaller than that of M. tuberculosis.M. bovis seems, therefore, the final member of a separate lineage represented by M. africanum, M. microti and M. bovis that branched from the progenitor of M. tuberculosis isolates. Successive loss of DNA may have contributed to clonal expansion and the appearance of more successful pathogens in certain new hosts. Whole-genome sequencing (WGS) and comparative genomics have generated information on the evolution and molecular basis of pathogenicity and transmissibility. Although genomic information is more available for M. tuberculosis infecting humans, little is known about M. bovis, probably because of the limited human-to-human transmission. Widespread application of WGS using approaches that more directly integrate it as an additional epidemiological data to M. bovis will bring novel and important insights into the dynamics of its spread and persistence.
Genotyping utilities and techniques for Mycobacterium bovis detection
Different techniques have been developed for the genotyping of M. bovis. Although the IS6110- RFLP (classified with variable number tandem repeat [VNTR] typing as the Tandem Repeated Sequences) has been used as the gold standard for both human and BTB over many years, its use in BTB is less common due to the lower copy number of IS6110 in M. bovis. Another technique includes the spacer oligonucleotide typing (spoligotyping – a nontandem-repeated sequences) that identifies polymorphism in the presence or absence of 43 specific DNA spacer units in the direct-repeat (DR) region in strains of the MTBC, with M. bovis showing a characteristic absence of five spacers in the 30 DR region (39–43).
The whole-genome techniques include the restriction endonuclease analysis (REA) typing, the pulsed-field gel electrophoresis, the RFLP, WGS, and whole-genome microarray. REA typing has helped in tracing the source of infections that resulted from within-herd transmission and movement of livestock, thus allowing for outbreak source differentiation among wildlife reservoirs in different regions or reinfection from herd movement.,,
Other techniques termed the partial genome techniques with specific repeated sequences include the tandem-repeated sequences and non-tandem repeated sequences; random sequences as the random amplified polymorphic deoxyribonucleic acid analysis; rarely used now due to its lack of reproducibility and poor discrimination. Others including house-keeping genes as the multilocus sequence typing, typing, and regions of difference and single nucleotide polymorphism (SNP). SNP typing has a clear discriminatory power though there is a need to test a large set of genes to achieve a satisfactory resolution. It has been used to show some phylogenetic distribution., It is not used too commonly because it is a two-step technique which makes it expensive and time-consuming. SNP-based analyses have demonstrated the genotypic differences within M. bovis strains and differentiated these strains from M. tuberculosis strains representing diversity in time and space. It has equally provided population genetic frameworks that may aid in identifying factors responsible for the wide host range and disease phenotypes of M. bovis.
Although the various molecular epidemiological studies enable the traceability of M. bovis infections and help in the detection of the outbreaks source,M. bovis genotyping systems still need to be standardized. VNTR typing (that provides better discrimination than all other methods except for REA), and spoligotyping, either alone or together, have now become the preferred approaches as they are robust and amenable to electronic analysis and comparison. Spoligotyping though only moderately discriminatory can be easily applied to large numbers of isolates. It is the most common epidemiological molecular-typing method applied to strains of M. bovis [Table 1].
|Table 1: Mycobacterium bovis prevalence and typing techniques from livestock and human in Africa|
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Molecular studies of Mycobacterium bovis infection in human in Africa
Spoligotyping and VNTR have aided the survey of isolates, and clearly illustrated the geospatial localization of epidemiologically distinct group of M. bovis types across wildlife populations and cattle. Although the discriminatory power of the different typing techniques for M. bovis varies by country, M. bovis genotypes of human origin (with rare exception of M. bovis recovered from humans not matching the molecular type of the cattle strains) generally parallel those of livestock within the same country, which supports the presence of an epidemiological link between human and animal M. bovis TB cases., Three clonal lineages of M. bovis: African 1, African 2, and European 1, with a distinct spoligotype signature, have been characterized with the African 1 and African 2 groups shown to be restricted to Central-west Africa and East Africa, respectively, while the European 1 members being globally distributed.
The African 1 (Af1) clonal complex of M. bovis defined by a specific chromosomal deletion (RDAf1) and the absence of spacer 30 in the standard spoligotype has been shown to be present at high frequency in cattle samples from several sub-Saharan west/central African countries such as Mali, Cameroon, Nigeria, and Chad, suggesting that the recent mixing of strains between countries is not common in this area of Africa. However, two groups of M. bovis have been shown to circulate in Burkina Faso: a major group (Af1) and a minor group belonging to the putative Af5 clonal complex. The Af1-specific deletion has not been identified in M. bovis isolates in several other African countries such as Algeria, Burundi, Ethiopia, Madagascar, Mozambique, South Africa, Tanzania, and Uganda, as well as from Europe and South America pointing out its geographic localization to several African countries.
Molecular studies have shown that the isolation rate of M. bovis from human patients is highly variable in Africa,,,,, and despite limited human-to-human transmission of zoonotic TB, the infection often causes extrapulmonary disease in humans, with severe effects on livelihoods. Higher prevalence (up to 30%) of M. bovis is usually recorded in rural settings where the population is more closely associated with livestock compared to urban areas. Some studies have shown that the mutations on the PhoPR regulation system in the MTBC lead to a decreased affinity of M. bovis to humans., In Africa, M. bovis bacillus Calmette–Guérin (BCG) vaccination generalized in several countries is hypothesized to have lead in M. bovis strain suppression with the emergence and dissemination of a different lineage. BCG vaccination has been implicated in the decrease of M. africanum which is less virulent in experimental animal models than M. tuberculosis, and equally its possible role in the selection of resistant strains with BCG-induced immunity has been suggested to explain the expansion of Beijing family strains and the predominance of other families in certain geographic settings.,
| Strategies to Improve Bovine Tuberculosis Control in Africa|| |
Roadmap for zoonotic tuberculosis and one heath strategy
The strategies required for the control and elimination of BTB are defined, though several challenges including among others financial constraints, scarcity of trained professionals, lack of political will, and the underestimation of the importance of zoonotic TB in both the animal and public health sectors by national governments and donor agencies hinder the applications of the control measures, especially in Africa. There is an initiative to combat BTB in humans, alongside other zoonotic diseases in an integrated approach to improve human and animal health. A multi-sectorial collaboration pioneered by the World Health Organization (WHO), OIE, and FAO under a tripartite partnership and providing guidance on how to reduce zoonoses risks at the human-animal-environment interface has been developed to jointly pursue the One Health approach and working in close partnership with research institutions, academia, intergovernmental organizations, the private sector, nongovernmental organizations, civil societies, and all stakeholders.
The roadmap calling for concerted action through broad engagement across political, financial, and technical levels lays down ten priorities grouped into three core themes (improve the scientific evidence base, reduce transmission at the animal-human interface, strengthen intersectoral, and collaborative approaches) with milestones defined for the short-term, by 2020, and medium-term, by 2025, in a WHO's End TB Strategyby 2030. This initiative, however, will require a strong political will (still absent in Africa) to address the basic utilities and focus first on appropriate human and infrastructure capacities building to ensure its applications. It has to take into account the economic, cultural, technological, and logistical issues encountered in Africa. The success of the “One Health” approach has shown the potential benefit of human and veterinary medical health professionals working cooperatively to identify “shared risks” to humans and animals. This synergism will advance health care, improve biomedical research discoveries, and enhance public health efficacy (http://www.onehealthinitiative.com/about.php).
Surveillance, capacity building, and innovation strategies
The complex nature of zoonotic diseases and the limited resources is a reminder of the importance of disease surveillance in the most affected countries. The human burden of disease cannot be reduced without improving standards of food safety and controlling bovine TB in the animal reservoir. Low prevalence of BTB has been attributed to effective surveillance activities which included both active surveillance with detection during meat inspection, targeted screening of cattle, laboratory testing, restriction of movement from infected herds, and awareness creation on its economic and health implications, as well as passive surveillance with reporting from dairy farms and cattle herdsmen to veterinary staff. BTB surveillance in Africa is either weak or nonexistent and will require an enforcement of known regulations which has shown to lead to a reduction of human TB infections due to M. bovis. Building capacity for surveillance of BTB will include building technical capacity for quality control of tuberculin and tuberculin testing and designing epidemiological surveys; strengthening capacity for epidemiological data analysis; improving the capacity of meat inspectors to recognize and to report TB on carcasses; building and strengthening existing capacities of laboratory diagnosis of animal TB; and building leadership of veterinarians and farmer/nomadic population awareness, trust, and advocacy. Emphasis has to be laid on the capacity building for physicians, veterinarians, scientists, and technicians trained for an adequate surveillance system, including a strong laboratory network, which is a key component of a meaningful prevention and control of BTB diseases. The development of capable diagnostic facilities is paramount for dealing with BTB surveillance for differentiation from other mycobacteria for effective treatment and control. Although some progress has been made, there is a need for continued investment and political commitment to meet the enormous persisting challenge of BTB in Africa.
The increasing use of bioinformatics tools and linkage of epidemiological and molecular surveillance data on animal and human health to understand better the evolution of pathogens crossing between animal and human populations, and the factors driving pathogen adaptation, as well as the introduction of routine molecular information within the African public health and veterinary systems coupled with proper capacity building will help to improve zoonotic TB surveillance. The progress on genomic sequencing of nonhuman animals will open up opportunities for comparative genomic approaches to understanding differential susceptibility between species, and the genomic development in Africa could result in significant progress to monitor and improve the environmental conditions that are critical to both human and animal health. The molecular and biodiversity information introduced into public health practice in Africa will enable epidemiologists to target their population-level surveillance of zoonotic TB to the most susceptible at-risk animals.
The linkages between the types of data streams to identify key environmental factors driving disease emergence in animal and human populations can be established and analyzed using the on-time and real-time strengthening communication and awareness creation of FAO established systems as the Global Early Warning System for transboundary animal diseases and major zoonoses. Biosurveillance system such as the real-time outbreak and disease surveillance system at the Automated Epidemiologic Geotemporal Integrated Surveillance could be modified to support the linkage of animal and human data for monitoring of zoonotic diseases in Africa.,
Mycobacterium bovisvaccination as control strategy in Africa
A long-lasting solution such as the protection of cattle against BTB by vaccination could be an important control strategy in countries where there is the persistence of M. bovis infection in wildlife and in developing countries where it is not economical to implement a “test and slaughter” control program. Vaccination of cattle represents an alternative intervention strategy to reduce the impact of BTB on livestock productivity and human health in developing countries. The only currently available vaccine against TB is the human vaccine - M. bovis BCG. Although early field trials with BCG M. bovis vaccine in cattle have been shown to produce disappointing results, with the induction of tuberculin skin-test reactivity following vaccination and low levels of protection, an encouraging protective effect of BCG against BTB in a natural transmission setting in Africa has been demonstrated. However, a large number of experiments and trials have shown variable efficacies, and the variation in the level of protection is explained with the increased in the understanding of immunity to TB. This includes the use of different BCG strains, very high doses of BCG administered, pre-existing exposure to environmental mycobacteria, lack of long-term protection, very high levels of natural challenge, and M. bovis exposure from milk of infected cows prior to vaccination. This variable levels of protection observed in field trials mirror the situation in humans where BCG vaccine efficacy against pulmonary TB in children and adults is highly variable. Moreover, a complementary diagnostic test to differentiate between vaccinated animals and those infected with M. bovis is required so that test- and slaughter-based control strategies can continue alongside vaccination.
Peptide and protein cocktails has been suggested to discriminate between M. bovis infection and BCG vaccination in animals, and a prototype differential diagnosis of infected and vaccinated animals reagents based on the early secreted antigen target 6 kDa protein and culture filtrate protein 10 present in M. bovis but absent from BCG in the bovine interferon-gamma (Bovigam) test assay has been shown to be able to distinguish between vaccinated animals that were protected against BTB and those animals that were not in Africa. In the past two decades, considerable progress has been made in the development and evaluation of TB vaccines for cattle, with new attenuated mycobacterial vaccines providing an alternative to the use of BCG vaccine and subunit vaccines to boost protection induced by BCG. With the development of tests to differentiate infected from vaccinated animals, it is now feasible to use vaccines to assist in the control of this disease.
| Conclusion|| |
Understanding the epidemiology of the infection within and between species is crucial to the control of BTB in both domestic and wild animals. The transmission is highest from infected domestic animals to susceptible wildlife (and vice versa) when they share pasture or territory. BTB prevention and control need to be step up in the African region and will require a constant effort to be eradicated. As the trade of animal products, the urbanization and the movements of people intensify; the risk of its introduction/reintroduction in different areas is challenging and thus will require a country level as well as regional or subregional surveillance scheme to tackle its spread. Improving laboratory capacities for rapid and appropriate diagnosis of strain involved in human transmission will improve treatment and limit haphazard management of acid-fast bacilli in patients with the direct consequence of increased drug resistance. The evidence of genomic overlap of M. bovis between cattle and man points out the need for synergy of veterinary and medical policies in the control of TB for its eradication.
The authors are grateful to Dr. Afutendem Lucas of the University of Dschang (English Language - Applied Linguistics, Phonology) for English language editing and proofreading.
Financial support and sponsorship
This work was supported by the Bill and Melinda Gates Foundation to B.D.T.P, under the Postdoctoral and Postgraduate Training in Infectious Diseases Research awarded to the Noguchi Memorial Institute for Medical Research (Global Health Grant number OPP52155). The funding body has no role in the design and writing of the manuscript.
Conflicts of interest
There are no conflicts of interest.
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