ИНФЕКЦИОННЫЕ БОЛЕЗНИ INFECTIOUS DISEASES IXODID TICKS AND TICK-BORNE INFECTIONS IN THE REPUBLIC OF CUBA – LITERATURE REVIEW AND RATIONALE FOR RISK ASSESSMENT

The Republic of Cuba is a popular destination for Russian tourists and about 30-50 thousands of Russian citizens visit Cuba annually. However, the recreational activity is often associated with the risk of Ixodid ticks bites and infection with tick-borne pathogens. According to published literature, the fauna of the hard tick in Cuba is represented by nine species including Ixodes capromydis, Amblyomma albopictum, A. cajennense, A. dissimile, A. quadricavum, A. torrei, Dermacentor nitens, Rhipicephalus sanguineus and R. (Boophilus) microplus. Five of these species, i.e. A. cajennense, A. dissimile, D. nitens, R. sanguineus and R. (Boophilus) microplus, were reported as human parasites. Ticks are spread over the most part of the island territory. Several tick-borne pathogens should be considered as a potential threat for the bitten humans in Cuba, including Borrelia burgdorferi sensu lato, Rickettsia sp., Anaplasma sp., Ehrlichia sp., Coxiella sp., thogotovirus and Crimean-Congo hemorrhagic fever virus. Implications for the epidemiology of tick-borne infections in the Russian Federation are discussed.

С каждым годом растёт привлекательность Республики Куба в качестве места отдыха граждан Российской Федерации. Ежегодно эту страну посещают с туристическими целями порядка 30- In the modern world, the international journeys are a significant part of the global economy. Millions of people travel worldwide annually. In recent years, it became usual for tourists from the Russian Federation to travel to remote countries with a warm tropical and subtropical climate. However, the recreational activity is often associated with a risk of infection with vector-borne pathogens. Ixodid ticks that are very important disease vectors can bite both locals and travelers. Thus, according to our observations, up to 10 residents of the Irkutsk Region get a tick bite while traveling abroad annually. Tick bites were reported in 18 countries including such remote ones as Thailand, Japan, United Kingdom and USA [6]. The aim of this review is to summarize briefly the published information about the fauna of ixodid ticks in the Republic of Cuba and evaluate its implications for epidemiology of tick-borne diseases in Russia. The publications were selected from the PubMed database (https:// www.ncbi.nlm.nih.gov/pubmed) using key phrases "tick+Cuba", "Ixod+Cuba", "Dermacentor+Cuba", "Haema-physalis+Cuba", "Amblyomma+Cuba", "Tick-borne+Cuba", "Borrelia+Cuba", and "Anaplasm+cuba". The results were manually filtered according to the relevance. Taxonomy of Ixodidae family is used according to Filippova, 1997 [12]. . These ticks are considered as a group of closely related groups with yet unresolved taxonomic status and are proposed to be designated as R. sanguineus sensu lato [8]. Ticks identified as R. sanguineus s.l. were exclusively found on dogs, however occasionally, R. sanguineus can infest a wide range of domestic and wild hosts, including cats, rodents and birds. [7,8]. R. sanguineus is a recognized parasite biting humans both at imago and nymphal stages and is able to infest densely populated urban areas [15,35]

TICK-BORNE INFECTIONS
To date, several tick-borne infections of humans and domestic animals were shown to circulate in the Cuban ecosystems. The agents of human granulocytic anaplasmosis (HGA), Anaplasma spp., were detected in R. sanguineus [31]. Besides this, the antibodies against Lyme disease (LD) agent Borrelia burgdorferi sensu lato [30], Babesia bovis and B. bigemina [35] were detected in the blood of the local residents. The Anaplasma marginale that is a significant cattle pathogen was isolated both in western and in eastern parts of the country [4]. Authors emphasize that ixodid ticks pose the serious threat for human health and stock rising in developing countries [31]. Recently, it has been shown that D. nitens ticks can harbour the Borrelia burgdorferi sensu stricto [13], that suggest the vector capacity of these ticks for Lyme disease in Cuba.
A. cajanense was demonstrated as a biological vector for Theileria (Babesia) equi -an important haemoparasite of equines [33]. R. sanguineus have been regarded as a vector for a number of pathogenic microorganisms, including significant human pathogens such as Crimean-Congo hemorrhagic fever virus (CCHFV), Thogotovirus Thogoto (THOV), Coxiella burnetii (agent of Q-fever), E. canis, E. chaffeensis, R. conorii (agent of Mediterranean spotted fever), R. massiliae (agent of spotted-fever) and R. rickettsii (agent of Rocky Mountain spotted fever) [7,19,20]. R. microplus can transmit the Babesia spp. and Anaplasma marginale, agents that can cause a severe disease in cattle and often have major impacts on livestock production [2].

IMPLICATIONS FOR EPIDEMIOLOGY OF TICK-BORNE INFECTIONS IN RUSSIA
The official registration indicates about 15 000 reported tick bites annually in the Irkutsk region. There are six species of ixodid ticks inhabiting the Pribaikalye  Filippova, 1957 were reported from the Eastern Siberia and neighbor territories [5,11,23,24,25]. To reduce the risk of human infection, the technology of urgent detection and prevention of tick-borne diseases was developed and implemented at the Federal Budgetary Scientific Center for Family Health and Human Reproduction Problems (FBSC FHHRP) in Irkutsk. Each tick is routinely tested for infection with TBEV, B. burgdorferi sensu lato, A. phagocytophilum and E. muris/E. chaffeensis. In case when any pathogen is detected in the tick, the patient receives the treatment with anti-TBEV immunoglobulins and/or antibiotics to prevent the disease according to modern Russian healthcare regulations. However, the analyzed literature data indicate that people bitten by the Cuban ticks can be infected with other pathogens, those will be not detected by the currently used tests. Thus, in case when residents of Russia report a tick bite while being in Cuba, the infection with Rickettsia sp., Anaplasma sp., Coxiella sp., THOV, CCHFV should be considered as possible in addition to usual tick-borne pathogens.
Besides this, during the last decade several people were attacked by ticks that are exotic for the Eastern Siberia. In 2008, we revealed the unique case of sucking of Amblyomma americanum in the suburban area of Irkutsk city. Epidemiological investigation excluded the import of tick from abroad either by the bitten patient or by domestic pets. It was revealed that the causative tick was indeed molted and questing in the Siberian ecosystem [22,26]. In 2013 and 2014, there were local cases of tick bites caused by Rhipicephalus sanguineus Latreille, 1806. The detailed study confirmed the local origin of all these exotic ticks and revealed the existence of at least three independent migration routes of A. americanum and R. sanguineus into the Eastern Siberia from genetically divergent populations. All these ticks were able to migrate several thousands kilometers from their convenient ecosystems and survive at least for some time in continental climate [22]. It can not be excluded that exotic ticks may migrate from Cuba as well and any inconvenient tick need to be carefully studied to identify its species.

CONCLUSION
Published data clearly demonstrate that there could be a significant risk of tick attacks on human population in Cuban ecosystems and tourists from Russia definitely share this risk. Indeed, there are numerous species of hard ticks inhabiting various biotopes, including urban and suburban areas and, probably, places of historical and recreational interest. However, in spite of the significant advance in current research, the information on tick and tick-borne infections in Cuba is still incomplete. Thus, the data on modern geographical distribution, population density and structure and ecological characteristics of Cuban Ixodid ticks are very limited. For example, the spatial distribution and abundance of endemic tick I. capromydis was described for the last time about 50 years ago [3]. There are no data available on attack rate of ticks on human hosts and the associated risk of tick-borne infections. The Lyme disease is still not confirmed for Cuba and no data about clinical cases of this disease are published [9], though there are serological findings that indicate the presence of this pathogen in Cuban ecosystems. The diversity and prevalence of tick-borne pathogens in Cuban ticks are also not fully described. Even for confirmed microorganisms like A. marginale, B. bovis and B. bigemina the additional studies are recommended [34]. All this information is critical to evaluate the threat of the tick for human health. Thus, extended ecological and epidemiological research will improve our knowledge

Infectious diseases
about tick-borne infections in Cuba and will provide the proper urgent diagnostics and prevention of tick-borne diseases in the bitten humans. Such research will also be a significant contribution to further improvement of the healthcare in the Republic of Cuba.