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Most people have heard of the bacteria genus Rickettsia even if they don’t know it by that name. Rickettsiosis in humans presents as spotted fever, well known in the US as Rocky Mountain spotted fever, and as typhus fever. While most people know something about rickettsial infections, research in 2022 has advanced knowledge about both Rickettsia and what it can tell us about other kinds of infectious disease and genetic diversity.
Rickettsia and Its Relatives
The genus Rickettsia comes under the order Rickettsiales, which also includes Anaplasma, Ehrlichia, Neorickettsia, Neoehrlichia, and Orientia. (Find out more about the diseases caused by these species from the US CDC.) When someone refers to “rickettsial infections” they may be referring to any infections in the order Rickettsiales, but when someone says “rickettsiosis” they usually mean an infection from the genus Rickettsia.
Rickettsiales cause serious intracellular infections that can result in death. Much is still being learned about them. Recently, scientists discovered Neorickettsia risticii in bats in urban areas in South America this year, but the zoonotic disease risk is not fully understood.
Spotted fever rickettsiosis exists around the world and is caused by a variety of Rickettsia species. In the United States, the most well-known spotted fever rickettsiosis is Rocky Mountain spotted fever, caused by R. rickettsia. The bacteria responsible for spotted fever rickettsiosis are usually spread by ticks, but R. felis, a species found globally, is spread by fleas. Its most common animal hosts are mice, but dogs and cats can also be infected. A species in Africa and the West Indies can be carried by ruminants like cattle or goats.
Typhus fever is caused by two species of Orientia spread by chiggers andan unknown vector: Rickettsia prowazekii, and R. typhi. R. prowazekii is carried by humans and flying squirrels and spread by body lice and flying squirrel parasites. R. typhi is carried by rodents and spread by fleas.
2022 Rickettsial Research – One Health and Health Care
What follows is a round-up of 2022 publications on Rickettsial research. Publications on Rickettsial bacteria and on Rickettsia species in particular are not as numerous as publications on other tick-borne diseases like Lyme disease. The publications noted are not necessarily a “best of” list or even a full survey of research from the year, but have been selected for themes that help illustrate where the research on Rickettsia species can take us.
One Health
We live closely with our pets, so research with one health in mind helps us create and maintain healthy living environments. Unfortunately, one health research and treatment continue to be hindered by educational and health care systems that draw a sharp line between human and animal health. However, researchers from Serbia, France and Canada were able to study the household pets of 85 people in the Balkans who had tested positive for Rickettsial infections. They were wondering, was it possible they had been infected by their pets, or at least shared their infections with their pets? In this study group, none of the pets were infected with Rickettsial species that had infected people from their household.
A study of ticks and their hosts in eastern China found Rickettsia japonica in goats for the first time when 30% of a herd tested positive. This may be an occupational risk for people who work with goats, and it was only identified because of this tick survey study. This kind of survey research supports one health approaches to occupational risk for people who work with animals.
Another study in the US looked at cats from a trap-neuter-release program. This study was a multi-institution partnership between researchers who met while working in Galaxy Diagnostics’ co-founder Ed Breitschwerdt’s academic lab at NCSU. This study found that Bartonella, Rickettsia, and Wolbachia species were present together in fleas collected from the cats. These species are a risk to cats as well as to people, and flea control will protect both.
Coinfections
Coinfections are common with tick-borne diseases, as well as with respiratory and other diseases (we wrote more about coinfections here). This year, researchers published the results of a 2021 incident in which a group of children in Mexico contracted Rocky Mountain spotted fever and/or Ehrlichia canis. The symptoms of each of the three groups of children were evaluated against each other for commonalities and differences.
Unusual Dermatological Manifestations
Rickettsia coronii is a common cause of spotted fever rickettsiosis in India and can have unusual dermatological manifestations (link contains graphic medical images). An issue in the diagnosis of many diseases, including vector-borne diseases, is that dermatological manifestations can vary and rarely look like the pictures in a textbook. This issue is further exacerbated in North America since textbooks often show dermatologic signs on lighter skin. Publications such as this one from India are incredibly important.
Intracellular Infection
Rickettsia species and certain other vector-borne diseases infect endothelial cells. Disruption of the endothelium is associated with diseases that have long-term effects after the initial illness is over. A study of Rickettsia japonica in 11 patients found that those with severe disease had disseminated intravascular coagulation. Endothelial cell disruption has gotten a lot of attention as it is also caused by SARS-CoV-2, the virus that causes COVID-19. Earlier this year, we published a blog post describing the function of the endothelium and the effects of diseases that disrupt it.
2022 Rickettsial Research – Genetics
We can learn a lot about genetics from Rickettsiales. Rickettsiales have a small genome, requiring proteins to perform multiple functions. These are called “moonlight” proteins. Even though humans have a much larger genome, we still have moonlight proteins, and problems with these proteins are linked to certain diseases. These diseases in people can be better understood by studying this tiny bacteria model.
The genetic history of Rickettsia likely included adaptation to a series of vectors and co-evolved with other microbes that included genetic exchange. In this paper, the authors use numerous graphics to display the genetic diversity and relatedness of different Rickettsia species.
Other genetic pressures exist today. In Mongolia, Rickettsia species were found to have a flat genetic diversity across regions rather than changing across regions in genetic groupings. This is probably because of the movement of domestic animals.
Rickettsia have evolved to coexist with their microbiome, and this may have caused possible weak spots. Researchers from France, Canada and Serbia found that manipulating the tick microbiome can reduce Rickettsia helvetica. It’s unclear how this knowledge could be applied to reduce infections, but microbiome research is an exciting area of discovery in the potential control of pathogens.
And as is a perennial subject in taxonomy, researchers suggested that parts of Rickettsia should perhaps be their own genus. These species directly impact arthropods for good and ill, including one that kills ladybirds.
2022 Rickettsial Research – Vectors and Novel Species
Fleas
Despite being responsible for plagues, fleas are an underappreciated vector for zoonotic pathogens. At conferences, it is not uncommon for our scientists to ask for someone to name a disease spread by fleas and find that the audience has a difficult time coming up with an answer. Despite their impact on history and on families, fleas just can’t get any respect!
In places like India, other pathogens may be less well known, especially when dealing with plague outbreaks. This year a paper on flea-borne Rickettsia in India reminded readers that R. felis is found in fleas and has cats as a host, but R. conorii and R. typhi have also been found in fleas and cats in India.
Meanwhile, in the United States, a study of fleas from cats in southeastern Georgia found 17% positive for Rickettsia species (R. typhi was excluded as among those species).
Chiggers
Chiggers are potential zoonotic disease vectors which have not been well studied. Chiggers are known to spread Orientia species in the Asia-Pacific region, including Australia. This year, in a study of 46 chiggers collected in North Carolina, 48% tested positive for Rickettsia species that included a novel (previously unknown) species. North Carolina has a high rate of Rickettia species infections compared to the rest of the country (despite the name, Rocky Mountain spotted fever is most common in the US Southeast), and it is a question worth studying whether chiggers contribute to that infection rate.
Ticks
Ticks continue to increase their ranges around the world. The Gulf Coast tick is developing a population on Staten Island, NY, and the surrounding areas. Tests of these ticks found Rickettisa parkeri and R. felis. Recall that the latter is more commonly found in fleas. Consequently, both human and animal healthcare providers in this area should be aware that these pathogens may be acquired from tick bites.
Soft ticks have not been well-studied for their zoonotic disease risk. One reason is that they often parasitize reptiles and the risk from zoonotic vector-borne disease in reptiles was underappreciated until recently. This year, soft ticks collected from bats in Columbia were found to carry known zoonotic pathogens as well as an unidentified Rickettsia-like species, and a survey of four species of soft ticks by researchers in Egypt, Japan and Malawi found Rickettsia and other common tick-borne pathogens.
Conclusion
Spotted fever group and typhoid Rickettsia species cause disease around the globe. Their risk is sometimes underappreciated in conjunction with underappreciation of fleas as a risk for zoonotic disease. Research into Rickettsia highlights risk from a variety of vectors, some of which have not received the attention needed to protect human and animal health. Research into Rickettsia also shines a light on medical and scientific issues that extend beyond the genus and even beyond vector-borne disease.
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