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From my basic understanding: The viruses causing Ebola, Sars and Covid-19 are all the result of a zoonosis, meanings that the viruses have passed from animals to humans.
So my question is: Are all recently (let's say 100 years) emerged viral diseases, with potential for a global epidemic, the result of a zoonosis?
To my knowledge, yes. A partial list of recently emerged/emerging viral diseases (I certainly could have missed some), with probable reservoir hosts:
- Chikungunya* (birds, rodents)
- coronaviruses (SARS [bats], MERS [camels], COVID-19 [?? bats ?? pangolins ??])
- Ebola and other filoviruses (Marburg): (bats?)
- Hendra, Nipah (bats)
- Ross river virus* (various mammals)
- HIV (primates)
- influenza (H1N1, avian) (birds/pigs)
- monkeypox (monkeys, duh; also rodents)
- West Nile virus* (birds)
- Zika* (? "a wide range of animals in West Africa")
Starred examples are vector-borne (so perhaps of slightly lower concern - might not fit your criterion of "capable of causing a global pandemic").
- older zoonotic viruses (rabies, dengue, hepatitis,… )
- non-viral zoonoses (malaria, plague, anthrax)
A list of zoonoses; another from US CDC
More generally, the only other place an emerging virus could come from would be from mutation or recombination of existing human viruses. I'm not aware of such an example.
Hepatitis D emerged in the past 100 years, without being a zoonosis
Hepatitis D is a virus which is able to replicate only in the presence of a hepatitis B co-infection. It causes the same symptoms as the hepatitis B virus, but with greater severity and lethality. In developed countries, it is rare except among intravenous drug users.
It was discovered in 1977, although epidemics of Lábrea fever in the 1950s were later determined to be caused by the virus. Comparisons of known strains and the mutation rate suggest a common ancestor around the year 1930.
Hepatitis D is the smallest known animal virus (less than 1700 nucleotides), and is the only species in the Deltavirus genus. There is no known animal reservoir. The most similar known animal virus shares only 32% of the nucleotides of hepatitis D.
According to its Wikipedia page,
It has been proposed that HDV may have originated from a class of plant pathogens called viroids, which are much smaller than viruses.
Transmissibility of emerging viral zoonoses
Affiliations Odum School of Ecology, University of Georgia, Athens, Georgia, United States of America, Center for the Ecology of Infectious Diseases, University of Georgia, Athens, Georgia, United States of America
Roles Conceptualization, Methodology, Supervision, Writing – review & editing
Affiliation Cary Institute for Ecosystem Studies, Millbrook, New York, United States of America
Roles Investigation, Methodology, Writing – review & editing
Affiliation Southeastern Cooperative Wildlife Disease Study, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America
Roles Conceptualization, Methodology, Project administration, Resources, Supervision, Writing – review & editing
Affiliations Odum School of Ecology, University of Georgia, Athens, Georgia, United States of America, Center for the Ecology of Infectious Diseases, University of Georgia, Athens, Georgia, United States of America
Self-disseminating vaccine vectors
Even with programs such as EPT, prediction of which animal pathogens will become established as globally significant EIDs within the human population still remains beyond our capability. However, pathogens emerging from an animal source are often initially poorly adapted to their new human host in terms of sustained human to human transmission. Mechanisms involved in adaptation are unclear and will presumably be idiosyncratic to the particular emerging pathogen, but have been suggested to impart a requirement for repeated introductions into the human population before a successful adaptation event results in full human adaptation. This requirement may provide a potential ‘window of opportunity’ for immunological targeting of the pathogen within the animal transmission species, thereby stemming its continued zoonotic flow prior to acquisition of full adaptation to humans. Self-disseminating vaccines are a vaccine strategy that may in some instances be better suited than conventional vaccines to immunologically contain emerging pathogens within their non-human host in challenging under-resourced ‘hotspots’. Disseminating vaccines are designed to exploit the ability of replicating virus-based vectors to spread through their animal host populations without the need for direct inoculation of every animal. In this strategy, vaccination of a limited number of 𠆏ounder’ animals is used for initial introduction of the vaccine into the target population. As the vaccine is engineered to express target antigens from the EID pathogen of interest, its spread from vaccinated to non-vaccinated animals will result in coordinated spread of EID-specific immunity throughout the targeted animal population.
Myxoma virus-based vaccines for myxomatosis and rabbit hemorrhagic disease virus
The earliest disseminating vaccine for animals was designed to target two highly lethal rabbit-specific EIDs in the European rabbit population, myxoma virus (MV) and rabbit hemorrhagic disease virus (RHDV). The vaccine was based on a naturally attenuated MV strain (strain 6918) selected for low virulence (non-lethality), high immunogenicity, and maintenance of horizontal transmission. MV6918 is essentially identical to the highly pathogenic wild-type strain except for disruption of four genes, two of which are known virulence factors. MV6918 was able to protect against lethal MV challenge following vaccination using direct inoculation. Importantly, MV6918 was transmitted to 㹐% of co-housed rabbits (assessed by sero-conversion), and immunity conferred by transmission was protective. Onward transmission was less efficient (approx. 12%) and was no longer protective. MV1698 was subsequently engineered to express RHDV capsid protein as a transmissible bi-valent vaccine against both RHD and myxomatosis.[21,22] Under laboratory conditions, the MV6918VP60-T2 bivalent vaccine was shown to exhibit similar characteristics to MV6918. Direct inoculation was immunogenic and protective in essentially all animals with 㹐% transmission from directly inoculated to co-housed rabbits and a substantial drop in onward transmission. MV6918VP60-T2 was shown to perform in a remarkably comparable fashion in a limited field trial performed on an island with an estimated population of 300 wild European rabbits with the vaccine showing maintained avirulence, high immunogenicity following direct inoculation and 㹐% transmission rate.
In the above studies, MV was selected as the genetic basis for the disseminating vaccine due its ability to spread through rabbit populations. High species specificity of MV for rabbits also decreased the potential for spread to ‘off-species’ targets within the environment. However, use of a normally virulent pathogen for the host species being targeted as the self-disseminating vaccine platform necessarily required use of an attenuated MV strain. This requirement had a clear impact on the disseminating capacity of the MV6918-based vaccine. More recent self-disseminating vaccine approaches have used cytomegalovirus (CMV), which is a beta-herpesvirus, as the disseminating vaccine platform. Similar to MV, CMVs are immunogenic and spread efficiently through their host species. However, CMV infection is normally benign in the healthy host. This important difference removes the need to use attenuated strains, thereby potentially enabling use of wild-type CMVs with preserved animal-to-animal transmission characteristics. Similar to MV, CMVs are also highly species-restricted with each mammalian host species studied carrying its own CMV. The species barrier for CMV appears remarkably robust, with direct experimental inoculation being unable to establish off-species infection even between closely related rhesus and cynomolgous macaque CMVs (90% identical at the nucleotide level). A recent study showed this strict species restriction to extend to CMVs in the wild, with the absence of cross-species CMV transmission even between chimpanzees and monkey prey species involved in an intimate NHP predator–prey relationship in the Tai Forest National Park, Cote d’Ivore. CMVs are also ubiquitous within their host species, which allows vaccines to be engineered from CMV strains already endemic within the target species. This helps remove concerns associated with introduction of new viruses into animal populations with which there is no long established biological relationship.
Murine cytomegalovirus-based immunocontraceptive vaccine for domestic mouse (Mus domesticus) plagues
Although not targeting an EID, over a decade of work toward the use of a murine CMV (MCMV) as a viral vectored immunocontraceptive vaccine to control mouse plagues in Australia gives some insight into the application of disseminating vaccines to target high risk pathogens for EID control. Mice directly infected with MCMV strains expressing female mouse fertility antigens develop prolonged – essentially life-long – infertility. Immunocontraception was dependent on antibody production and led to the ablation of ovarian follicles.[31,32] Despite the success of MCMV as an injectable vaccine, lack of direct transmission to uninfected mice under laboratory conditions has been a hurdle to its further development. Transgene expression by MCMV is frequently associated with salivary gland attenuation (a major organ involved in animal-to-animal transmission of CMV). However, even low passaged, non-genetically manipulated wild-type strains of MCMV transmit poorly under laboratory conditions. Therefore, it is not clear if poor transmission of vaccine strains is due to genetic manipulation of the virus and/or reflects a general lack of viral transmission under laboratory conditions. It is possible that the inability to transmit under laboratory conditions may be due to transmission characteristics unique to rodent CMVs. Similar to the situation with MCMV in mice, transmission of Sin Nombre hantavirus (SNV) in deer mice could not be demonstrated under standard laboratory conditions. However, efficient transmission was observed following co-housing in outdoor enclosures and correlated with the number of aggressive encounters enumerated by the number of biting wounds.
Deer mouse CMV-based vaccine to interrupt Sin Nombre hantavirus zoonotic transmission
The first studies using CMV as a disseminating vaccine targeting a human EID used CMV from deer mice (Peromyscus CMV (PCMV)) to target SNV in the wild deer mouse SNV transmission species. Using a PCMV expressing the SNV envelope glycoprotein G1, the PCMV(ΔP33:G1EGFP) vaccine induced G1-specific antibodies following direct inoculation of deer mice. PCMV(ΔP33:G1EGFP)-induced immunity was durable, persisting over a 12-month period, but was associated with a lower level of PCMV-specific antibodies compared to the wild-type PCMV.[35,36] An observed delay in replication in vitro combined with the lower anti-PCMV antibody levels suggested a level of attenuation. However, PCMV(ΔP33:G1EGFP) was still able to induce G1-specific immunity in healthy deer mice previously infected with either PCMV(ΔP33:G1EGFP) or wild-type PCMV.[35,36] This ability of CMV to re-infect the CMV seropositive host is a characteristic shared by other CMVs, and is critical for use of this virus as a disseminating vaccine platform due to CMVs being ubiquitous within their mammalian hosts. The ability of PCMV(ΔP33:G1EGFP) to transmit G1-specific immunity in co-housed mice, or to protect against SNV challenge has not been determined. However, these studies further suggest the importance of using a non-attenuated virus-based vaccine platform with wild-type characteristics, which is possible with CMV given its benign nature in the healthy host.
CMV-based vaccine to interrupt Ebola virus zoonotic transmission
A disseminating CMV-based approach is also being developed toward the control of Ebola virus in wildlife reservoir and transmission species in Africa.[38,39] Approximately 30% of past human Ebola virus outbreaks are known to have resulted from the direct handling of infected ape carcasses, identifying apes as a critical wildlife Ebola virus transmission species. Ebola virus is also regarded as a major threat to the survival of African ape populations in the wild. Consequently, a disseminating CMV-based strategy is being developed as part of an ongoing multidisciplinary effort between human health scientists and the conservationists at the World Wildlife Fund to target Ebola virus infection in African great apes (bonobo, chimpanzee and gorilla) and potentially also fruit bats. Fruit bats (Rousettus aegyptiacus) are also a known reservoir of Marburg virus  a disseminating vaccine platform targeted at bat roosts may also therefore be suitable to interrupt transmission of this related filovirus. A recent series of studies have shown that a CMV-based vaccine is able to provide protection against Ebola virus challenge following direct inoculation.[38,39] In these studies, a MCMV vector expressing a CD8 + T cell epitope from nucleoprotein (NP) of Ebola virus fused to a non-essential MCMV protein (MCMV/ZEBOV-NPCTL) was shown to induce durable NP-specific immunity (㸔 months).[38,39] MCMV/ZEBOV-NPCTL vaccinated mice showed no evidence of Ebola virus disease (EVD) following lethal Ebola virus challenge. Impressively, 5/8 mice completely controlled Ebola virus infection, with no detectable viremia the remaining 3 mice showed a 2.8 log reduction in viremia relative to non-vaccinated controls. Protection was long-lived as mice vaccinated with a single dose of MCMV/ZEBOV-NPCTL were protected against EVD following lethal challenge 17 weeks post-vaccination – an attractive quality for a disseminating vaccine to be used in wildlife populations. Studies in the NHP Ebola virus challenge model were recently completed (manuscript under review). In this model, the key question of transmissibility of immunity in CMV seropositive animals (which cannot be assessed in the laboratory mouse model (see above)) can now be addressed in an experimental system more translatable to NHPs in the wild.
Substantial evidence supports the ability of primate CMVs, including human CMV (HCMV), to superinfect the seropositive host. A 2008 study examining HCMV seropositive women showed the frequent presence of multiple glycoprotein N (gN) and/or gB variants within HCMV positive urine and blood samples suggesting that most individuals are infected with multiple HCMV strains. A subsequent study monitoring development of HCMV strain-specific antibody responses in a cohort of healthy seropositive women reported 29% of participants developed new strain-specific antibodies with a mean time of 17.8 months (± 10.3 months) indicating that superinfection is a relatively common event. Superinfection of CMV seropositive NHPs has been demonstrated experimentally in the simian immunodeficiency virus (SIV):rhesus macaque AIDS model following direct inoculation of recombinant rhesus CMV (RhCMV) genetically modified to express SIV antigens. Following superinfection, recombinant RhCMVs were able to establish a persistent long-term infection and induced CD4+ and CD8+ T-cell responses against the expressed SIV antigen comparable to those observed in RhCMV seronegative animals. This ability to induce a robust T-cell response against the ‘new’ heterologous antigen encoded by the RhCMV vector in the presence of prior CMV immunity is notable  as it suggests that ‘original antigenic sin’ – a phenomenon first observed for influenza A-specific antibodies, and then for virus-specific T-cell responses in the lymphocytic choriomeningitis virus mouse model, whereby the presence of pre-existing immunity blunts the immune response against a new but cross-reactive antigen – may not apply in this situation. However, the effect on more closely antigenically related heterologous target antigens within the context of CMV infection will need to be determined.
The studies performed in the SIV:rhesus macaque model showed that the ability to superinfect was dependent on genes in the US2-11 region of the genome – a region which contains several genes involved in down-modulation of MHC class I antigen presentation. CD8+ T-cell depletion restored the ability of RhCMVs deleted for US2-11 to superinfect seropositive animals indicating that superinfection was due to viral subversion of the host CD8+ T-cell immune response. Interestingly, following recovery of the CD8+ T-cell response in these animals, the US2-11 deleted viruses were able to persist, which indicates that once established, the host CD8+ T-cell response is unable to clear virus infection. Outside of the MCMV mouse model (see above), the ability of recombinant CMVs to spread between animals has not been tested. However, a recent study investigating transmission of RhCMV in co-housed animals showed that non-recombinant, but tissue culture-passaged RhCMV strains maintain an ability to be shed into bodily fluids (saliva and urine) at levels comparable to those of wild-type RhCMV, provided that a region of the genome encoding several genes involved in tropism and immune evasion (called the UL/b’ region) is intact. CMV transmission is generally believed to involve mucosal exposure to such fluids (as well as genital secretions and breast milk). Consistent with their maintained shedding characteristics, the tissue culture-passaged viruses also retained the ability to spread between co-housed RhCMV-seropositive animals. This observation indicates that it is at least possible for laboratory manipulated CMV strains to maintain the ability for wild-type transmission.
Further studies are needed to ensure recombinant CMVs expressing heterologous target antigens can similarly maintain wild-type transmission and target-specific immune responses following transmission. Experience from studies exploring the use of disseminating vaccines targeting other pathogens (see above) are expected to prove invaluable for these studies, especially in regard to the importance of avoiding vaccine attenuation to maintain wild-type characteristics of CMV transmissibility. Where studied, frequencies of CMV infection from natural transmission in animal populations approach 100%. Consistent with epidemiological studies in humans, a major peak of infection occurs at an early host age, with essentially all US primate center rhesus macaques being RhCMV seropositive by the age of one year. Environmental stresses, such as SIV infection of chimpanzees, can result in immune suppression of animals in the wild. It will therefore also be important to ensure that any CMV-based vaccine presents no higher risk in immune-compromised animals than the wild-type CMV strains with which they are already infected.
Livestock infectious diseases and zoonoses
Infectious diseases of livestock are a major threat to global animal health and welfare and their effective control is crucial for agronomic health, for safeguarding and securing national and international food supplies and for alleviating rural poverty in developing countries. Some devastating livestock diseases are endemic in many parts of the world and threats from old and new pathogens continue to emerge, with changes to global climate, agricultural practices and demography presenting conditions that are especially favourable for the spread of arthropod-borne diseases into new geographical areas. Zoonotic infections that are transmissible either directly or indirectly between animals and humans are on the increase and pose significant additional threats to human health and the current pandemic status of new influenza A (H1N1) is a topical example of the challenge presented by zoonotic viruses. In this article, we provide a brief overview of some of the issues relating to infectious diseases of livestock, which will be discussed in more detail in the papers that follow.
1. Introduction and food security
At the beginning of the twenty-first century, the world is faced with a changing landscape of infectious diseases that affect man and animals, and that pose significant threats to health and welfare and to the international food security agenda. Livestock diseases that have devastating outcomes on animal health and that impact on national and international trade remain endemic in many parts of the world. Threats from old and new pathogens continue to emerge, fuelled by changes in the environment (climate, hydrology, disruption of ecosystems, etc.), in agriculture and food production (intensive systems of husbandry, farming monoculture, food processing, etc.) and in the demography and connectivity of the modern ‘global’ village (population growth, urbanization, international trading, world tourism and rapid transportation, etc. Gibbs 2005). The spread of new influenza A (H1N1) is illustrative: between February 2009 when the first cases of an influenza-like illness in people were reported in the Gulf coast state of Veracruz, Mexico, and 24 June 2009, it had spread to 91 countries with 55 867 cases reported (see http://www.who.int for daily updates).
The global human population is expected to increase from approximately 6.5 billion in 2008 to approximately 9.2 billion by 2050 (UNDP 2008), with around one billion of this increase occurring in Africa. Population growth on such a scale poses enormous challenges for food production in general, as an increased demand for 50 per cent more food is expected by 2030, and for livestock in particular, especially in developing countries where material increases in household incomes and accompanying urbanization drives demand for meat and dairy products (Delgado et al. 1999 Jones & Thornton 2009). The first year in which more than half the people on Earth (approx. 3.3 billion) inhabited urban areas was 2008, and by 2030, this number is expected to increase to approximately five billion, with the vast majority of urban growth occurring in Africa and Asia (UNFPA 2008). Alongside these unprecedented changes in the size and location of human populations and the demands for food, the impacts of environmental change are likely to be detrimental to agricultural production (Fresco 2009). These factors will therefore drive a requirement for a systematic application of science through the entire food chain in order that all food-producing sectors adapt to changing temperatures, nutrient and water conditions and exposure to harmful pathogens. The opportunities for scientific innovation are tremendous in number and scope and must be exploited if the world's population is to have enough to eat in the decades ahead. Control of livestock pathogens will continue to be a highly important component of efficient food production and become associated more overtly with the food security agenda.
The world cattle population is estimated currently to be approximately 1.3 billion head, with 30 per cent in Asia, 20 per cent in South America, 15 per cent in Africa, 14 per cent in North/Central America and 10 per cent in Europe (http://cattletoday.info). Estimates of the global number of smaller livestock vary considerably from source to source, but it is generally accepted that there are approximately one billion pigs, approximately two billion small ruminants and more than 50 billion poultry reared annually for food production. Methods of farm production are tremendously varied and bring with them their own particular risks in terms of the introduction and transmission of infectious diseases. At one extreme is the very low-intensity subsistence livestock farming, particularly of poultry, sheep and goats, that operates in the poorest of the world's rural households and that is critical to sustaining local food supplies, alleviating poverty through income generation and for nutritional status. These animals are often kept under scavenging conditions with little attention to disease control, housing or feed supplementation, suffer a high burden of endemic disease and are likely to be in close contact with other livestock species and humans, and potentially in contact with a variety of non-domestic animals. The impact of epidemic diseases on the livelihoods of these poor farmers, particularly if there is high mortality or the imposition of animal movement restrictions or culling, is severe (http://smallstock.info). In this issue, Perry & Grace (2009) consider in detail the impacts that livestock diseases, and control of these, can have on developing and promoting national and international policies that are pro-poor and that will reduce rural poverty. At the other end of the farming spectrum are the highly organized and intensive sectors of the poultry industry where the rapid growth rates of birds reared in stocking densities of up to 50 000 birds in a single shed give the most efficient feed-to-meat conversions of any farm system and provide cheap, high-quality products for the consumer. This intensity of husbandry can only be done by controlling many infectious diseases that would otherwise inflict severe losses or even prevent intensive poultry production completely, by the administration of vaccines at the start of the rearing period. For the poultry sector, the emergence of a new pathogen, or a new variant of an old pathogen has the potential to spread rapidly and devastate national flocks, as has happened on several occasions with strains of highly pathogenic avian influenza (Alexander 2000, 2007 Velkers et al. 2006). Indeed, some outbreaks of highly pathogenic avian influenza have resulted in the destruction of entire national flocks of poultry and complete restocking has been required from an international breeding company before poultry production could be resumed. Such vulnerability illustrates the importance of infectious livestock diseases within the context of global food security.
Some of the pathogens considered in this series of reviews present an actual or real risk to a serious shortage of food in many parts of the world. Within Europe, the recent incursions of bluetongue virus (BTV) and subsequent outbreaks of disease have provided a reminder that livestock can quickly become exposed to the ravages of a new disease that takes hold because of changing conditions. Across Northern Europe, BTV has become a very recent new threat to sheep and cattle and in 2008 the mortality rates of infected sheep were high (more than 10% in some countries). Only the introduction by the UK of a national plan for vaccination against BT in 2008 prevented establishment and spread of the disease, and the high susceptibility of most European breeds of sheep to BTV means that vaccination must continue. While the gradual northwardly spread of BTV from Northern Africa and the south Mediterranean regions had been observed for several years (Mellor et al. 2008), the abrupt introduction of BTV-8 in Northern Europe was unexpected and a further reminder that livestock diseases can appear rapidly and without apparent warning (Wilson & Mellor 2009). Bovine spongiform encephalopathy in the UK in the 1980s is arguably the best exemplar of a new and highly significant disease of livestock emerging as a consequence of change, in this case to feeding practices, with a profound impact on food supplies and security and public confidence.
2. Emerging and re-emerging diseases
Increases in the emergence or re-emergence of animal and human infectious diseases have been evident in many parts of the world for several years (Weiss & McMichael 2004 Gibbs 2005 Woolhouse et al. 2005). Over 1600 human pathogens are now described, an average of three new diseases is reported approximately every 2 years, and a new infecting organism is published every week (http:/www.gideononline.com). Some emerging diseases such as Lyme borreliosis, cat-scratch fever (bartonellosis), fifth disease (parvovirus B19), legionellosis and cryptosporidiosis are actually much older, but the causative agents were recognized only relatively recently similarly, several presumed non-infectious conditions such as peptic ulcer, Kaposi sarcoma and cervical cancer are now known to have infectious aetiologies. Nevertheless, there is no doubting the emergence of many genuinely new diseases and, whereas 60 per cent of all known infectious agents are zoonotic (Taylor et al. 2001 Jones et al. 2008), it is estimated that approximately 75 per cent of ‘new’ human pathogens reported in the past 25 years have originated in animals and the risk of zoonoses is predicted to continue to increase (King et al. 2006). RNA viruses pose particularly high zoonotic risks because they can emerge and spread rapidly and a recent statistical analysis of 146 viruses of livestock indicates that the ability of a virus to replicate in the cytoplasm (without nuclear entry) is the strongest single predictor of cross-species transmission and the ability to infect humans (Pulliam & Dushoff 2009).
Against the background of zoonoses accounting for around 60 per cent of new disease introductions (Taylor et al. 2001 Jones et al. 2008 Jones & Thornton 2009), the ‘megacities’ of the world provide an obvious focus of attention as they typically constitute melting-pot environments for the mixing of human and animal infectious diseases and their potential rapid spread, both locally and internationally. In 2000, there were 18 megacities with populations in excess of 10 million inhabitants, by 2025 Asia alone is expected to have at least 10 megacities and by 2030 over two billion people in the world will be living in slums associated with cities (http://en.wikipedia.org/wiki/Megacity). Mexico City, with a population of around 23 million people, was the focus of the early phase of the 2009 spread of influenza A/H1N1, and Ma et al. (2009) in this issue describe the emergence of zoonoses in the context of China, where it is forecast that cities will contain a total population of 800 million people by 2020. The emergence of the severe acute respiratory syndrome (SARS) virus and its rapid international spread provides another recent example of the transmission of a new disease from a megacity. Fortunately, the outbreak of SARS was ‘owned’ by the countries involved subsequently and a series of fast-acting global campaigns by medical practitioners and others proved adequate to stop the disease from becoming established. However, many diseases, including livestock diseases, are regarded as seemingly intractable problems and if the affected areas of the world straddle political or economic boundaries, especially involving countries in different national, regional and economic groupings, a lack of ownership of the disease may more typically define the need for containment and control.
The rate of introduction of vector-borne pathogens to previously ‘free’ areas of the world is increasing (Jones et al. 2008). It is estimated that almost half of the world's population is infected by vector-borne pathogens (http://sedac.ciesin.columbia.edu) with the greatest impact on developing countries within tropical and subtropical areas. The impacts of climate change and global warming are becoming more obvious and the survival and spread of BTV into Northern Europe provides a disturbing example of how an ‘exotic’ vector-borne livestock pathogen can quickly become established within new geographical regions to present new and significant risks to livestock production. Since the arrival of BTV-8 in The Netherlands in 2006, bluetongue (BT) has spread widely throughout Northern Europe with around 57 000 holdings in Europe affected by BTV in 2007 (with tens of thousands of animals killed) and around 33 000 holdings were affected in 2008. Significantly during the past 3 years, more serotypes have been introduced very recently within Northern Europe (including BTV-1, BTV-11 and BTV-16) and, with BTV-1 circulating, it is now clear that ongoing and sustained vaccination campaigns will be necessary for several years if the disease of BT is not to cause further welfare problems and high rates of mortality in sheep.
Other livestock diseases are also moving geographically and include African Swine Fever (ASF), the cause of a very serious haemorrhagic fever of pigs, which leads to mortality rates close to 100 per cent. Rather typically for diseases that are now emerging as serious pathogens on a potentially far larger scale than hitherto (and somewhat neglected for scientific study), there is no vaccine against ASF virus (ASFV) and control has to rely on other approaches, such as slaughter of infected herds. ASF had been previously been confined mainly to sub-Saharan Africa, with continued spread to previously uninfected countries on that continent, but the introduction of ASFV into Georgia in 2007 and its subsequent spread from the Caucasus has introduced a new risk to pig production in Europe. In this issue, Costard et al. (2009) review the mechanisms by which ASFV is maintained within wildlife and domestic pig populations, how it can be transmitted, the broader risks for global spread of ASFV and how disease might be mitigated. Wild boars have the potential to distribute ASFV widely and they are also known as reservoirs for a number of other important diseases and their growing importance in transmission of zoonotic diseases is the specific theme of Meng et al. (2009) in this issue. The roles of wildlife in transmission are being identified with increasing clarity and for avian influenza wild waterfowl have been shown to be capable of widely distributing the virus. Iqbal et al. (2009) in this issue set the scene for their work on investigating whether different avian influenza viruses show variation in the degree of diversity from the consensus sequence of the virus as they replicated in different hosts by broadly reviewing the maintenance of highly pathogenic H5N1 viruses in different avian host species. They note the prevalence of the virus in waterfowl such as ducks and swans, but also a variety of other wild bird species, including sparrows, crows, magpies and birds of prey.
Other wildlife seen as increasingly important in the transmission of zoonotic pathogens includes the fruit bat, which is known to be a reservoir of internationally important zoonotic pathogens such as Hendra virus and Nipah virus. Greater risks to human health from wildlife pathogens appear to be inevitable as a consequence of increasing human contact with wildlife through greater access to, and disturbance of, wildlife habitats. Deforestation and the taking of land for livestock farming can lead to the habitats of wildlife being disturbed, and the spread of Nipah virus to pigs (and thence to humans) in 1998 in Malaysia is associated with the movement of fruit bats from their forest environment to cultivated orchards and pig farms, driven by fruiting failure of forest trees during El Nino-related drought as more land was sought for farming (Chua et al. 2002 Looi & Chua 2007).
In general, much less is known about infectious agents of wildlife, livestock and even companion animals than of humans, and there are several examples where enzootic viruses of animals (SARS coronavirus, hantaviruses, Ebola and Marburg viruses, Nipah virus, Hendra virus and human immunodeficiency viruses) were completely unknown until they switched hosts to cause disease in humans (Parrish et al. 2008). However, emerging infectious diseases (EIDs) and zoonoses are not solely due to viruses and a recent detailed study of 335 EID events in man and animals between 1940 and 2004 concluded that more than 50 per cent were due to bacteria or rickettsia, more than 10 per cent to protozoa, 6 per cent to fungi and 3 per cent to helminths (Jones et al. 2008). A major concern is that vector-borne diseases have increased dramatically over the last decade adding support to hypotheses that climate change drives emergence of diseases where arthropod vectors are sensitive to environmental changes. Tropical areas have seen the highest increases in EIDs, and while those caused by zoonoses emanating from wildlife are correlated with wildlife biodiversity, those caused by emergence of new drug resistant strains are correlated with agronomic factors such as antibiotic use and population density.
In the spring of 2009, a new influenza A (H1N1) virus emerged and spread rapidly throughout the world, and was declared a pandemic by the World Health Organisation on 11 June. Epidemiological data indicate that the outbreak in humans started in mid-February in Veracruz, Mexico (Fraser et al. 2009), the virus is related to swine influenza A (H1N1) viruses recently circulating in pigs in North America and in Europe/Asia and carries a mixture of genes from viruses circulating in these two geographical regions (Garten et al. 2009 Trifonov et al. 2009). Six gene segments are most similar to those of swine H1N2 influenza A viruses isolated from North America in the late 1990s, whereas two gene segments are related to those of Eurasian strains of the early 1990s. Evolutionary phylogenetic analysis suggests that it is likely that initial transmission to humans occurred several months before recognition of the outbreak and that it is possible that reassortment of swine lineages to generate the direct precursor of the pandemic strain may have occurred years ago (Smith et al. 2009). However, the virus has not been previously detected in any animal or human populations and definitive scientific evidence to support its origin directly in pigs is not yet confirmed (Irvine & Brown 2009). It has been established experimentally that the virus can infect and transmit between pigs (Brookes et al. 2009), and it is highly probable that natural transmissions between humans and pigs will become a feature of the pandemic, although a complete picture of the potential host species range of these viruses has not yet emerged and many questions relating to disease severity in susceptible hosts, transmission dynamics within and between hosts and probable risks of selection for increased virulence due to zoonotic transmission remain to be determined.
Maudlin et al. (2009) in this issue make the point that, unlike newly emerging zoonoses that attract the attention of the developed world, many endemic zoonoses are neglected by comparison and this ‘in turn artificially downgrades their importance in the eyes of administrators and funding agencies’. This is a problem familiar to most scientists working on endemic livestock pathogens per se and presents many risks to the broader relevant scientific activity, not least the prospect that important basic and underpinning research data, tools and reagents are not in place. A good example of endemic zoonoses that continues to cause divergent clinical disease is toxoplasmosis, caused by the ubiquitous apicomplexan protozoan Toxoplasma gondii, which has high prevalence in many parts of the world associated with consumption of tissue cysts in undercooked meat, or exposure to oocysts derived from cat faeces (Sibley et al. 2009, this issue). As well as causing congenital infections with severe clinical sequealae, T. gondii establishes chronic, persistent infection in humans with a lifelong risk of reactivation, often associated with immunosuppression. Ocular toxoplasmosis is on the increase in immunocompetent people throughout the world, with an estimated incidence of 2 per cent in the USA (up to five million patients) and a much higher incidence in southern Brasil (Holland 2003) where it has been shown recently that clinical disease is associated with the emergence of newly described divergent parasite genotypes (Khan et al. 2006).
The changing incidence of pathogens and patterns of diseases over time requires the scientific community to review, develop and use different sets of skills. For example, climate change and the increasing spread of vector-borne diseases has driven a need for more entomologists and vector biologists and the re-emergence of helminth infections globally will, as Robinson & Dalton (2009) note in this issue, increase the need for basic laboratory research on zoonotic helminths. As the diseases change, so will the professional skills set required.
3. Past successes and future prospects
Infectious diseases are remarkably difficult to eliminate and only smallpox virus has formally been eradicated. However, a highly significant veterinary achievement is the expectation that, by 2010, the disease rinderpest (the cause of cattle plague) will also have been eliminated from the planet. This prospect was facilitated by the launch in 1994 of a Global Rinderpest Eradication Programme (GREP) both to consolidate gains in rinderpest control and to move towards disease eradication. While the biology of the virus was permissive to control by vaccination, the GREP was ultimately successful because it implemented a highly effective international coordination mechanism to promote the initiative, confirm freedom from rinderpest in affected areas and to deliver technical guidance and the means to achieve the goals. Thus, the expected eradication of rinderpest represents a triumph for a holistic approach to control, which integrates vaccination, robust diagnostic practices and, crucially, the political wills of many countries.
Unfortunately, for the prospects of further eradication successes, most pathogens are characterized by phenotypes presenting different antigenic forms that are stable with time (antigenic diversity) or that show antigenic variation during the course of infection. The presence of multiple serotypes or variants of a pathogen is a major hurdle for long-term control by vaccination and it seems that more complete successes such as the eradication of smallpox virus and rinderpest virus are aspirational rather than realistic. However, good progress continues to be made on the control of several important livestock pathogens and mechanisms are now in place to bring together the critical scientific expertise and political will to succeed. For example, to provide tools to endemically affected countries to help with control of foot and mouth disease (FMD) virus and to improve methods to better manage and reduce risk of outbreaks in FMD-free countries, a Global Foot-and-Mouth Disease Research Alliance (GFRA) was established in 2003 to bring together the relevant animal health research organizations worldwide. Thus, the GRFA is aligned conceptually to the GREP and is spearheading work to understand more about key issues of the biology of FMD virus, such as predictions of the virulence and spread of FMD virus under different circumstances, immunological mechanisms of protection against disease and virus replication and how to generate longer-lasting protective immunity after vaccination, the drivers of virus evolution and ways to improve vaccine stability and generate protection to multiple serotypes. Initiatives such as GFRA will help to share the burden of controlling burdensome diseases because, as Paton et al. (2009) point out for FMD in this issue, if the potential for disease control becomes too large for individual nations to tackle, responsibility for control may be seen to belong to a third party. This type of political dimension is clearly a significant factor in the prospects of better control of some very important diseases and any inertia in implementing plans at national government levels will make it easier for pathogens to persist and spread further.
The ability to control livestock diseases effectively is sometimes problematic because of the ‘carrier state’ in which a pathogen persists in the host for extended periods. Stevens et al. (2009) in this issue report that the bacterium Salmonella enterica may develop a carrier state in the host after primary challenge and such carriers typically excrete high levels of bacteria during recovery from enteric or systemic disease, often in the absence of clinical signs. In some cases, the carrier state may exist for the lifetime of the host, for example, with bacterial species such as S. enterica serovar Dublin.
FMD is also characterized by a carrier state in which FMD virus locates rapidly to, and is maintained in, the light zone of germinal centres (Juleff et al. 2009) and it remains a fundamental problem to be overcome before more effective control measures can be put in place. The tropism of pathogens and why some organisms translocate from one site of development to another remains generally poorly understood. Stevens et al. (2009), this issue, report an emerging theme among pathogens associated with enteric fevers, such as S. enterica serovar Typhi, Brucella spp. and enteropathogenic Yersinia spp.: they use ‘stealth strategies’ to evade detection by the innate immune system of the host and thus any control by the host at the level of mucosal surfaces.
In summary, considerable challenges are presented by livestock and zoonotic pathogens to the health and well being of animals and man. For some critically important diseases, the first line of defence will be the deployment of state-of-the art approaches to diagnosis and surveillance to provide a network of global intelligence on their spread and an assessment of risk presented. Combined with this, the delivery of effective vaccine strategies for the control of major pathogens of livestock will be especially testing and a continuum of new and better vaccines able to deliver more long-lasting and durable protective immunity and to be effective against multiple strains or variants will be essential.
Wild animals were implicated as a source of disease spillover to humans for the vast majority of zoonotic viruses, further substantiating the concept that the diversity of wildlife on our planet has provided a rich pool of viruses, a fraction of which have successfully adapted to infect humans. Our findings indicate that high viral host plasticity is an important trait that is predictive of pandemic potential of viruses in the zoonotic pool, not only because wide host range was common among viruses that have spilled over from animals to humans, but also because this trait was associated with increased human-to-human transmission and spread on a global scale. Reporting bias must be considered in the interpretation of any association based on data reported in the literature and the relationship between human-to-human transmissibility and host plasticity could be biased by increased research effort for viruses that have been shown to be transmissible among humans. However our analyses identified a strong linear relationship between host plasticity and likelihood of human-to-human transmissibility and we estimate zoonotic viruses found in 10 host orders are 12 times more likely to be human-to-human transmissible than zoonotic viruses found in only one animal host order. Human-to-human transmission of viruses with high host plasticity is consistent with the hypothesis that evolutionary selection for viruses with greater ability to adapt rapidly to new hosts co-selects for viruses capable of effective intraspecies transmission in the new host. Evolutionary selection of viruses capable of infecting a wide range of hosts has been a key hypothesis underpinning disease emergence theory 7,21 and we provide evidence for the importance of viral host plasticity as a synergistic trait aiding mechanisms of disease transmission, particularly at the high-risk human-animal interfaces reported here.
Human practices facilitating heightened contact between taxonomically diverse animal hosts has likely facilitated selection of viruses with high host plasticity and sharing of zoonotic diseases. Zoonotic viruses reported in domestic animals had a significantly wider host range than viruses not shared by domesticate species. Increased research effort targeting diseases in domesticated species could bias data towards this finding, but we also detected increased host range among viruses transmitted by wildlife kept in similarly confined circumstances. Increased host plasticity among viruses shared by domestic animals supports the concept that the breeding and keeping of taxonomically diverse domesticated species in regular close contact with people for centuries has enabled evolutionary adaptive selection for mutation-prone RNA viruses capable of cross-species transmission 2 . For the many viruses shared by wildlife and domestic animals, domesticated species play a critical role in facilitating direct contact with people, as well as amplification of disease transmission in intensive animal production facilities.
Our finding of significantly higher host plasticity among viruses transmitted by direct contact with wildlife kept as pets or in zoos and sanctuaries provides additional evidence to support the premise that confining taxonomically diverse species in close proximity selects for transmission of adaptable viruses with high host plasticity, even among wildlife. Diverse species of wild animals that are confined in zoos, sanctuaries, kept as pets and sold at markets are also subject to circumstances that facilitate cross-species virus transmission via intimate contact, particularly for zoonotic viruses already adapted to transmission among domesticated animals. Vectorborne transmission similarly enables opportunities for effective contact across diverse animal hosts, which is consistent with our finding of higher host plasticity among vectorborne viruses. Through this mechanism, vector-borne transmission has facilitated emergence of animal diseases in humans, particularly those from wildlife, and, for viruses with generalist vectors, this transmission route is an effective method for interspecific dispersal 6 .
Here we provide an epidemiologic picture of the animal-human transmission networks likely to perpetuate future disease emergence and our findings add to previous efforts to guide global health research geographically 3 . In addition to an emphasis on vector control, the myriad of other high-risk interfaces with human activities that have facilitated animal-to-human viral spillover should be a focus for education and interventions directed at disease prevention. More in depth investigation of the epidemiology of zoonoses at high risk human-animal interfaces is needed to assess risk of viral disease emergence and direct global, as well as local, disease prevention and control. Risk for a new human pandemic is likely highest at the high-risk interfaces facilitating disease threats in the past. Unfortunately, wild animal hosts and high-risk interfaces facilitating spillover of zoonotic viruses, particularly beyond their first emergence, remains vastly under-reported. Adequate data on circumstances at the point of disease spillover are lacking for many viruses because animal involvement in zoonotic disease exposure is very difficult to ascertain and this information is often not linked to diagnoses in published reports. Global animal disease data are largely incomplete due to inadequate livestock and wildlife health surveillance worldwide. Resulting ascertainment biases are especially problematic for spillover events that do not involve professions likely to self-report, as is likely the case for veterinarians, researchers and scientists working at laboratory facilities. Detailed patient histories that elucidate activities precipitating animal exposure will greatly assist in completing the epidemiologic picture underlying the emergence of many zoonotic viruses. This, together with heightened surveillance to gather data on human practices enabling contact with animals in settings with diverse host assemblages, particularly at high-risk interfaces under-reported to date, will direct us towards critical control points for disease control and behavior change interventions aimed at prevention.
Factors in the Emergence or Re-emergence of Infectious Diseases
There are many factors involved in the emergence of new infectious diseases or the re-emergence of “old” infectious diseases. Some result from natural processes such as the evolution of pathogens over time, but many are a result of human behavior and practices. Consider how the interaction between the human population and our environment has changed, especially in the last century. Factors that have contributed to these changes are population growth, migration from rural areas to cities, international air travel, poverty, wars, and destructive ecological changes due to economic development and land use.
For an emerging disease to become established at least two events have to occur – (1) the infectious agent has to be introduced into a vulnerable population and (2) the agent has to have the ability to spread readily from person-to-person and cause disease. The infection also has to be able to sustain itself within the population, that is more and more people continue to become infected.
Many emerging diseases arise when infectious agents in animals are passed to humans (referred to as zoonoses). As the human population expands in number and into new geographical regions, the possibility that humans will come into close contact with animal species that are potential hosts of an infectious agent increases. When that factor is combined with increases in human density and mobility, it is easy to see that this combination poses a serious threat to human health.
Climate change is increasingly becoming a concern as a factor in the emergence of infectious diseases. As Earth's climate warms and habitats are altered, diseases can spread into new geographic areas. For example, warming temperatures allow mosquitoes - and the diseases they transmit - to expand their range into regions where they previously have not been found.
A factor that is especially important in the re-emergence of diseases is antimicrobial resistance - the acquired resistance of pathogens to antimicrobial medications such as antibiotics. Bacteria, viruses, and other microorganisms can change over time and develop a resistance to the drugs used to treat diseases caused by the pathogens. Therefore, drugs that were effective in the past are no longer useful in controlling disease.
Another factor that can cause a disease to re-emerge is a decline in vaccine coverage, so that even when a safe and effective vaccine exists, a growing number of people choose not to become vaccinated. This has been a particular problem with the measles vaccine. Measles, a highly contagious and serious infection that was eliminated from the U.S. in 2000 and from the Western Hemisphere in 2016, has returned in certain areas due to an increase in the number of people opting to take nonmedical vaccine exemptions for reasons of personal and philosophical belief. This has been driven by an anti-vaccine movement that was founded largely on an invalid and discredited study that claimed a link between a vaccine against measles and autism. As a result of the decline in vaccine coverage, measles cases are highest by far this decade with more than 1,000 cases of measles reported in the U.S. in the first half of 2019.
Control of zoonoses in emergency situations: lessons learned during recent outbreaks (gaps and weaknesses of current zoonoses control programmes)
In emergency situations, domestic animals and wildlife are, like people, exposed to infectious diseases and environmental contaminants in the air, soil, water and food. They can suffer from acute and/or chronic diseases from such exposure. Often animals serve as disease reservoirs or early warning systems for the community in regard to the spread of zoonotic diseases. Over 100 years of experience have shown that animal and human health are closely related. During the past few years, emergent disease episodes have increased nearly all have involved zoonotic agents. As there is no way to predict when or where the next important new zoonotic pathogen will emerge or what its ultimate importance might be, investigation at the first sign of emergence of a new zoonotic disease is particularly important. Today, in many emerging situations, different activities involving zoonotic disease control are at risk because of failed investigative infrastructures or financial constraints. Considering that zoonotic diseases have their own characteristics, their prevention and control require unique strategies, based more on fundamental and applied research than on traditional approaches. Such strategies require cooperation and coordination between animal and public health sectors and the involvement of other disciplines and experts such as epidemiologists, entomologists, environmentalists and climatologists. Lessons learned from the avian influenza pandemic threat, the Crimean-Congo haemorrhagic fever and rabies outbreaks are presented and the gaps and weakness of current control programmes are discussed.
NH and RK: conceptualization and preparing the first draft manuscript. NH, RK, and PR-O: methodology and literature review. PR-O, RK, AYO, LBA, LE, MJT, DY-M, RA, NK, LM, JR, TDM, DLH, AZ, and LM-B: writing review and editing. NH, PR-O, RK, and LM-B: address the comments of reviewers and editors. All authors contributed to the article and approved the submitted version.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Bats are the only flying placental mammals that present all around the world except in Arctic, Antarctica and a few oceanic islands. They are the second largest order of mammals that evolved from one of the oldest fossil, Icaronycteris, during Eocene period (50 million years ago) and diverged into 925 known species which constitute 20% of > 4800 mammalian species . Although the bats attribute advantages in the diverse ecosystem as pest controller (insectivorous bats) and pollinators (frugivorous bats) the worrisome fact is they act as natural reservoirs for a large number of emerging as well as re-emerging pathogens that other animals and humans can contract. Moreover they gained a bad reputation in classical literatures, in which bats are associated with evils- Lucifer, darkness, Dracula- blood fed vampires and as omens and in modern scientific society they were obligatorily dangerous, as evolved as a super-mammal for harboring many of the newly identified deadly diseases without any signs and lesions. Recent database on bat viruses from 69 countries worldwide comprises more than 4100 bat-associated animal viruses belonging to 23 viridae detected in 196 bat species . Recently reported 43% of the emerging and reemerging pathogens included in bioterrorism list as category A, B, C were recognized in different bat species. The emergence of bat borne zoonotic viruses significantly arise a global public health impact.
Many of the emerging and reemerging viruses are formidable foes for the physicians putting them into confusion due to their mutagenic nature. Best example is the recent report of Zika virus in India, which doesn’t cause any developmental mutagenicity in children compared to the outbreak in Brazil in 2015. In Asia and Pacific regions, bats were demonstrated as natural reservoirs for a large number of this types of emerging as well as re-emerging pathogens such as SARS, Ebola, Marburg, Nipha, Hendra, Tioman, Menangle, Australian bat lyssa virus, Rabies and many encephalitis causing viruses in humans and animals . Sub Saharan Africa, where people hunt bats as bush meat is the biggest hot spot for viral spill over from bats to humans and other mammals. Southeast Asia is also been considered as another danger zone. A change in agent, host and environment is responsible for the emergence and re emergence of various diseases. From bats the pathogen get transmitted to humans via intermediate hosts like horses(hendra) and pigs(nipah) and different species of animals get infected by consumption of partially eaten fruits of bats and the chewed out materials of bats after extracting the juice. Studies suggest bats can travel a long distance (2000–3000 km) which also develops issues of introducing new disease to the place unknown earlier. Phylogenetic analysis suggests a co evolutionary relationship between viruses and the existing bats . All these facts arose international scientific attention for the study on bats and bat associated viruses and it suggests that a series of events happened to precipitate the emergence of the viruses which were ancient and circulating in the bats for a long time.
Recent applications of conventional PCR/RT PCR, metagenomics and next-generation sequencing (NGS) technologies revealed the complexity of the bat virome, which may impact upon its reservoir capacity and consequently affect vector–reservoir host interactions. Several studies showed bats as an important reservoirs for a number of RNA viruses (including, lyssa, corona, paramyxo, filo and astro viruses) and DNA viruses (including, parvo, circo, herpes and adeno) . Variation in the incidence and diversity of viruses in bats suggests that some species of bats are reservoir host and some others are incidental hosts . The bat virome in frugivorous bats are less compared to the insectivorous bats . More than 200 viruses were reported in bats wherein most are RNA viruses. Out of 60 viruses found to be associated with bats, 59 were RNA viruses due to high degree of mutations and recombination [28, 56]. The first report of a transmission of a viral disease from bats to humans was a rabies virus (RABV) belonging to the Lyssa virus genus . Rio Bravo virus was the first non rabies virus to be recognized as originating from bats in 1960s . Majority of viruses identified in bats were belonging to flavi virus group including West Nile virus and Kyasanur forest disease virus  and the application of metagenomics helped to identify Picorna viruses in bats.
Since a large number of different types of virus were identified in bats it is better to understand the spectrum and characteristics of viruses that bats carry. It may help to prevent and control potential emerging bat-borne diseases. Further as bats are acknowledged for emerging zoonoses, identification and characterization of novel viruses from bats is needed. Unlike other animals the detailed information regarding bat anatomy, ecology, importance in ecosystem and their ability to act as reservoirs for a large number of viruses which are potentially harmful for humans and animals have to be studied. Moreover, knowledge regarding the antibody and cytokine synthesis in bats, pathogenicity and the pathology associated with infections are lagging. Some of important pathogenic RNA viruses identified in bats so far with emphasis on Nipha virus transmission and few more bat borne viruses are discussed below.
Infectious diseases—past, present, and future
In 1962 Sir McFarland Burnett stated, ‘By the end of the Second World War it was possible to say that almost all of the major practical problems of dealing with infectious disease had been solved.’ At that time, his statement was logical. Control and prevention measures had decreased the incidence of many infectious diseases, and with the ability to continue to identify new antibiotics, to handle new problems, and the ongoing development of appropriate vaccines, his statement appeared to be appropriate.
In the US, similar feelings were expressed and funding for infectious disease fellowships began to decline with federal resources being directed elsewhere.
The history of the world is intertwined with the impact that infectious diseases have had on populations. Evidence of smallpox has been found in 3000-year-old Egyptian mummies. Egyptian papyrus paintings depict infectious diseases such as poliomyelitis. Hippocrates wrote about the spread of disease by means of airs, water, and places, and made an association between climate, diet, and living conditions. Investigators described miasmas as the source of infections. Fracastoro discussed the germ theory in the 1500s and three routes of contagion were proposed—direct contact, fomites, and contagion from a distance (airborne). Epidemics of leprosy, plague, syphilis, smallpox, cholera, yellow fever, typhoid fever, and other infectious diseases were the norm.
The development of the microscope by Leeuwenhoek in the 1600s allowed scientists to visualize micro-organisms for the first time. The 1800s brought knowledge of the cultivation and identification of micro-organisms. Vaccines were developed and used which introduced specific methods to our storehouse of measures for control and prevention. Pasteurization was another important contribution to disease control. An appreciation of the environment and its relationship to infectious diseases resulted in implementation of broad control measures such as community sanitation, personal hygiene, and public health education. The importance of nutrition was appreciated for its impact on infectious diseases.
The 20th century brought chemotherapy and antibiotics into our infectious disease armamentarium. Greater dependency upon vaccination programmes and health education became important allies in our efforts at reducing the occurrence of infectious disease. So Sir McFarland’s statement was not an off hand remark.
But we are now aware that emerging and re-emerging infections have become a significant worldwide problem. In 1991, the Institute of Medicine of the National Research Council in the US appointed a 19-member multidisciplinary expert committee to study the emergence of microbial threats to health. Their report published in 1992 was entitled, ‘Emerging Infections —Microbial Threats to Health in the United States’ but the concepts that they discussed certainly have worldwide application. 1 They concluded that six categories of factors could explain the emergence or re-emergence of infectious diseases. These factors are: Human demographics and behaviour Technology and industry Economic development and land use International travel and commerce Microbial adaptation and change and Breakdown of public health measures.
There have been other groupings of causative factors proposed related to re-emerging infections and in some instances we do not yet have a clue as to how new agents have appeared in animal and human populations. The problem of emerging infections is well exemplified by the many examples of new and emerging infectious diseases that have impacted upon localized populations and/or geographical areas over the past several decades. Human immunodeficiency virus (HIV)/AIDS, first identified in 1981, portrays the significant impact that an infectious disease can have on the world. Presently HIV/AIDS is the fourth leading cause of death in the world and it remains the leading cause of death in Africa. The economic havoc it has created worldwide is frightening and its impact upon all peoples will remain embedded on mankind for decades. More geographically localized, but still creating worldwide concern, have been the haemorrhagic fevers, Nipah virus, and monkeypox. And more recently sudden acute respiratory syndrome (SARS) exemplifies how the occurrence of a new and dangerous infectious disease can monopolize governmental activities, cause fear and hysteria, have a significant impact on the economy throughout the world and on the freedom of movement of people.
We are bold in our attempts to control infectious diseases. We have eradicated one disease (smallpox) and two other diseases are in the final stages of eradication (poliomyelitis and dracunculiasis). These eradication programmes demonstrate how international collaboration and co-operation can significantly benefit the world. However, our goals must be realistic, that is, initiation of an eradication programme must be limited to the few diseases for which this is a valid goal. Control and prevention should be our main emphasis as we plan our ongoing commitment in our approach to infectious diseases.
In this issue of the International Journal of Epidemiology, a number of articles are included that exemplify the continuing problems with infectious diseases. Modelling has become an important ally in our attempts to project future occurrence of infectious diseases and can have a significant impact on our distribution of resources for purposes of control and prevention. Murray et al. studied behavioural changes among intravenous drug users in Australia as to the occurrence of HIV and hepatitis C virus (HCV) and, using a mathematical model, have made projections as to what the future prevalence of these two diseases will be. 2 Law and colleagues modelled HCV incidence in Australia, being concerned about the impact of hepatitis C infection on the development of chronic liver disease and increased mortality. 3 These two papers demonstrate the relationships between an infectious agent and chronic disease and the authors discuss their concern about the burden that these infections will have on future populations.
Pappalardo and colleagues are concerned about the relationship between pregnant women simultaneously infected with HIV and HCV and the impact upon the newborn infant. 4 Accurate evaluation of this risk has been hampered by small numbers in individual observational investigations. They conducted a meta-analysis and included 10 studies in their investigations. In developing larger groupings of cases for analysis they have concluded that infants born to HIV co-infected mothers increases the risk of HCV infection in these infants.
de los Angeles and colleagues conducted an investigation of seroprevalence of HIV in men who have sex with men in Argentina in order to determine the risk factors related to HIV infection. 5 Their analyses indicate that age, employment status, previous sexually transmitted disease history, and an HIV positive partner were all risk factors. The outcome of their investigations should impact upon the direction of HIV control and prevention activities.
Lagarde and colleagues have reported on their investigations of HIV in West Africa, pointing out the differences in the epidemiology of this infection from other parts of Africa. 6 They describe the relationship of mobility to the spread into rural areas, with rural migrants temporarily located in urban areas becoming infected and carrying HIV back to the rural areas. This is not a new finding but emphasizes the importance of instituting prevention measures, including health education, that can play a significant role in curbing this form of transmission.
Todd and colleagues looked at the use of randomized clinical trials to evaluate control and prevention measures for HIV infection. 7 They looked at homogenicity, and the number and size of the communities, and concluded that the power of community-randomized trials can be improved by selecting homogeneous communities or stratifying the communities prior to randomization.
Pezzotti and colleagues were interested in developing a more accurate estimate of the prevalence of HIV infection than could be ascertained from a single data source. 8 They cross-linked prevalence data from four sources and by applying capture– recapture methodology conclude that these methods can improve the accuracy of estimates of the prevalence of HIV infection.
Inigo and colleagues were concerned about improving the knowledge of the timing of transmission of tuberculosis (TB) in populations. 9 By comparing the molecular analysis of Mycobacterium tuberculosis organisms and conventional epidemiological information and using the capture–recapture method of analysis they were able to develop a better estimate of the timing of transmission of TB. This technology improves our ability to define the parameters of the spread of TB, which can have an impact upon implementing control and prevention measures.
Hussain and colleagues investigated the prevalence of TB in prisoners in a province in Pakistan. 10 By use of skin tests and sputum smears they were able to define the extent of infection among the prisoners (prevalence of 48%) and determine the significance risk factors associated with infection. They recommend the following measures in order to control and prevent this problem: routine screening of prisoners on entry, using sputum smear and skin tests for diagnosis of active or latent TB respectively, clinical or prophylactic treatment as appropriate, reduction of overcrowding, education, and public health surveillance of long-term prisoners.
Lago and colleagues studied the detection of polioviruses in wastewater following a poliomyelitis immunization campaign in Cuba. 11 Their concern emanated from recent epidemics of poliovirus caused by the vaccine-derived virus and whether this virus could continue to circulate after ‘eradication’ of the wild virus. As a supplement to acute flaccid paralysis surveillance, the sampling of wastewaters may be an important ancillary method of surveillance. Their investigations reveal that virus detection from wastewater using PCR (polymerase chain reaction) was as sensitive for detection of poliovirus as the standard cell culture and neutralization methods. Poliovirus was identified in fecal specimens from children through the seventh week following vaccination and the same poliovirus was identified in wastewater up to 15 weeks after vaccination. Though this methodology needs to be evaluated for its sensitivity, it adds to our ability to evaluate the eradication of poliovirus from communities.
Cooper and Bird investigated the projected incidence of variant Creutzfeldt-Jakob disease (vCJD) associated with dietary exposure to bovine spongiform encephalopathy (BSE) in the UK for two birth cohorts (1942–1969 and post-1969). 12 They concluded that there is a greater risk of developing vCJD in the time period 2001–2005 for the post-1969 birth cohort than for the earlier cohort. However, very few onsets of vCJD are predicted to occur in the post-1969 birth cohort after 2010, whereas almost half of the onsets of vCJD are predicted to occur up to 2010 in the 1940–1969 birth cohort. The use of simulation models is well demonstrated in this paper and does allow for considering projections of the occurrence of this disease.
The events of the last several decades demonstrate that our infectious disease guard cannot be reduced. We are making progress in controlling and preventing infectious diseases but we must not become complacent. The infectious disease papers in this edition of the Journal amply portray the continuing impact that infectious disease has on the world. They also demonstrate how new research can be important in defining new methods of control and prevention.
As we focus on the problems of emerging and re-emerging infectious diseases, we must not underplay other diseases and health conditions that also significantly impact on all of us. With finite limits on our resources for disease control and prevention, we must learn how to better use these resources. Better planning, more attention to training, improved efficiency, and strengthening the collaboration and co-operation between countries will help in our efforts to reduce the burden of disease.