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What Are the Key Drivers of Human-to-Human Transmission of Arthropod-Borne Pathogens?

With an increase in attention on arthropod-borne diseases this year, scientists from Erasmus discuss the key factors involved in human-to-human transmission of these pathogens.

Arthropod-borne diseases are infections transmitted by the bite of infected arthropods, such as ticks and mosquitoes. These diseases are a major concern worldwide, and viruses, in particular, pose a serious public health problem.

In a review article published in Current Opinion in Virology, Byron E. Martina, PhD, from Erasmus Medical Centre, Rotterdam, the Netherlands, and colleagues discuss key factors involved in human-to-human (H2H) transmission of arthropod-borne pathogens.

“The ability of vectors to get infected by humans during a blood meal to further propel an epidemic depends on complex interactions between pathogens, vectors, and humans, in which human interventions and demographic and environmental conditions play a significant role,” the authors write.

Pathogens

For efficient H2H transmission, a pathogen must be able to infect the human host and replicate adequately to produce a pathogenic load in the host’s bloodstream that allows direct transmission of the pathogen to the arthropod vector. Several factors influence this, including the pathogen’s host range and affinity for specific tissues and cells, as well as its level and duration of circulation in the human donor and replication rate in the vector. The pathogen’s infective dose and pathogenicity of its strains are also important.

In the case of arthropod-borne viruses (arboviruses), genetic variations can also affect their risk of transmission. For example, during the 2005-2006 epidemic of chikungunya virus (CHIKV) disease in the Indian Ocean region, the strain of the virus that is transmitted by the Aedes aegypti mosquito vector acquired a mutation in the E1 envelope glycoprotein which allowed the virus to be better transmitted by Ae. albopictus. Another mutation in the viral E2 glycoprotein has also been shown to improve cell-to-cell transmission of CHIKV, allowing the virus to avoid the host’s neutralizing antibodies. This subsequently leads to persistent infection in the host, which may be key for H2H transmission, the authors say.

Vectors

According to Dr. Martina and colleagues, anthropophilic (primarily human-biting) vectors are also important for efficient H2H transmission. Vector-associated factors that affect H2H transmission include vector feeding preferences and activity patterns, as well as changes in vector behavior with changes in host availability. Reproduction rates of pathogens within vectors, and pathogen load in vector saliva are also important.

Pathogens must also survive the vector’s salivary gland and midgut barriers, as well as its immune system responses. The authors discuss the RNA interference (RNAi) pathway as an important antiviral defense mechanism in arthropods, emphasizing that the ability of an arbovirus to replicate efficiently in certain mosquitoes depends on how well the virus can counteract this RNA-based immune response.

A delicate balance also exists between a mosquito and its commensal gut microbiota “to limit bacterial over-proliferation and the subsequent immune response that may negatively affect mosquito fitness,” the authors add.

Humans

Various human-associated factors are also important in H2H transmission of arthropod-borne infections. The human donor’s ability to control pathogen replication and hence the amount of pathogen in the bloodstream affects transmission of the pathogen from the donor to the vector. Subsequently, the human recipient’s immune status influences transmission of the pathogen from the vector to the human recipient.

Humans are dead-end hosts for many arboviruses, such as eastern equine encephalitis (EEE)—although infected mosquitoes may feed on humans, EEE cannot be transmitted from humans because the viremia presented in the disease is not sufficient to allow H2H. However, for other arboviruses, such as CHIKV, humans serve as amplifying hosts to sustain H2H transmission of the virus because levels of viremia are sufficient to allow infected humans to transmit the virus directly to the mosquitoes.

Genetic factors also influence susceptibility of humans to vector-borne pathogens, of which malaria resistance genes are among the most well-known example. Although the genetic basis of resistance to malaria is complex at several levels, it represents a strong force for evolutionary selection that has allowed different populations to evolve different genetic variants to protect against malaria.

Environmental elements also play a role in H2H transmission, the authors add. These include factors such as temperature, humidity, rainfall, and socioeconomic changes, as well as people’s travel and migration patterns.

Moving forward, the authors stress the need for research into the drivers of H2H transmission of vector-borne diseases to become a fundamental component of risk-assessment and surveillance studies.

“Elucidating the factors playing a role in urban transmission cycles will allow predictive epidemiological risk models that integrate knowledge on vector ecology and vector—pathogen–host interactions,” 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.