Researchers from Erasmus disease the key factors needed for successful human-to-human contact-transmission of zoonotic pathogens.
Many infectious diseases cross the species barrier, and most infectious diseases in humans are zoonotic. Once a zoonotic pathogen infects humans, its success in the human population depends on whether it becomes capable of efficient human-to-human (H2H) transmission.
In a review article published in Current Opinion in Virology, Mathilde Richard, PhD, from Erasmus Medical Centre, Rotterdam, the Netherlands, and colleagues discuss some key factors involved in H2H transmission of contact-transmitted zoonotic pathogens. They focus on four modes of transmission, using examples of zoonotic diseases to highlight these factors.
Yaws is an infection caused by Treponema pallidum subspecies pertenue (TPE). This neglected tropical disease is endemic in West Africa, South East Asia, and the Pacific. It is a chronic, relapsing disease that spreads by skin-to-skin contact, and is characterized by lesions that predominantly affect skin, bones, and cartilage.
However, in recent decades, increasing evidence has also shown high levels of TPE infection of monkey species in Africa. Studies have also indicated that, genetically, the organisms infecting monkeys closely resemble the agent that causes yaws in humans. This suggests the potential for zoonotic transmission, with monkey species in Africa serving as a reservoir for human infection.
According to the authors, several factors have contributed to efficient H2H transmission of TPE. For example, the organism uses antigenic variation, altering its antigens to evade immune surveillance and allow it to chronically infect the individual. Skin ulcers may contain high concentrations of organisms, and their infectious dose is low. In addition to infecting an individual via cuts or abrasions, TPE can also penetrate healthy mucous membranes. Host factors such as crowded living conditions also facilitate transmission of the organism. And environmental factors such as high humidity and high temperature allow TPE to better survive outside the host. In addition, “lack of surveillance and inadequate health care favor the persistence and spread of human yaws in affected countries,” the authors say.
Sexual transmission is the main mechanism for the continued spread of the HIV-1 epidemic, with more than two-thirds of HIV-1 infections worldwide resulting from heterosexual intercourse. Viral particles or infected cells are transmitted in genital fluids or blood from an infected person, and are deposited on the mucosal surface of a recipient.
HIV-1 is a lentivirus that gradually attacks the immune system, targeting white blood cells known as CD4+ T cells, eventually leading to immunodeficiency, progression to AIDS, and death due to opportunistic infections.
Research has shown that HIV-1 is genetically similar to simian immunodeficiency virus (SIV)—a lentivirus that attacks the immune system of monkey species in the same way HIV-1 attacks the human immune system. One strain of SIV, found in chimpanzees, has been shown to be almost identical to HIV-1. This suggests that HIV-1 probably originated in chimpanzees and crossed into humans.
M strains of HIV-1 are the most prevalent strains of the virus. Despite the relatively low infectivity of these strains, several factors have facilitated their sustained H2H transmission. For example, M strains can overcome restriction factors in cells of the humans they infect. Restriction factors are proteins that provide an early line of defense against infection by helping to prevent viral replication.
M strains can also undergo genetic recombination and low-fidelity replication, allowing HIV-1 to evade the immune system and treatments. This accounts for “the nature of its long, ‘latent’, often sub-clinical infection, during which patients can transmit the virus,” the authors say.
Other factors that also promote H2H transmission include coinfection of the host with other sexually transmitted diseases, as well as promiscuous sexual behavior.
Four human coronaviruses (HCoV-229E, -NL63, -OC43, -HKU1) are responsible for causing the common cold. Of these, HCoV-229E originated in bats, and HCoV-OC43 in cattle. The zoonotic origins of the other two remain unknown.
Although these coronaviruses have low pathogenicity, they are mainly transmitted via airborne droplets to the nasal mucosa, and thus efficiently transmit between humans. Virus replicates locally in the upper respiratory tract. In the case of HCoV-229E, this is facilitated by an abundant supply of its receptor on non-ciliated bronchial epithelial cells.
Several routes have been identified for transmission of Ebola virus, which causes Ebola virus disease (EVD)—a hemorrhagic fever with a high fatality rate.
Direct contact with infected patients or their bodily fluids, as well as with contaminated surfaces or materials, is the main mode of transmission of the virus. Indeed, Ebola virus has been isolated from blood, breast milk, and semen of infected patients. Studies have also detected Ebola virus RNA in sweat, tears, and stool, as well as in samples from the skin, vagina, and rectum. In particular, the 2014 EVD outbreak emphasized the potential for sexual transmission of the virus.
Although some researchers hypothesized about the possibility of airborne transmission of Ebola virus, this mode of transmission is now considered unlikely. However, Ebola virus may be spread to humans through handling infected bushmeat and via contact with infected bats.
The authors discuss several pathogen-associated factors that promote H2H transmission of Ebola virus, including the high concentration of virus in bodily fluids, as well as its very low infectious dose.
Human behaviors and societal factors also contribute to efficient transmission of the virus. For example, cultural traditions often involve mourners bathing in water from the washing of corpses. During the 2014 EVD outbreak in West Africa, inadequate health care systems in Guinea, Sierra Leone, and Liberia also contributed to disease spread, as did ease of travel between these countries. International travel-associated cases of EVD were also documented.
In their concluding remarks, the authors summarize that, while some factors were specific for a particular pathogen or mode of contact transmission, other factors (such as immune evasion, high viral load, and low infectious dose) were common to several modes of transmission.
“The identification of such factors will lead to a better understanding of the requirements for human-to-human spread of pathogens, as well as improving risk assessment of newly emerging pathogens,” they conclude.
Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.