Talgat Nurmakhanov’s research while affiliated with M. Aikimbayev’s National Scientific Center of Especially Dangerous Infections and other places

Crimean-Congo hemorrhagic fever (CCHF) is an acute tick-borne viral infection with a high fatality rate. The main vector of the CCHF virus is ticks of the genus Hyalomma. Humans get infected through tick bites or by direct contact with the blood of infected humans or domestic animals. The endemic regions of CCHF in Kazakhstan are Kyzylorda, Turkestan, and Zhambyl. In the Zhambyl region, the first evidence of human cases was reported in 1982. In the following years, cases of CCHF were annually registered in two districts (Sarysu and Moiynkum) of the Zhambyl region. The study goal is twofold: 1) to provide a retrospective review of CCHF cases reported through the surveillance system in the Zhambyl region from 1991 to 2023 and 2) to analyze epidemiological features of CCHF cases in the Zhambyl region in 2023. Surveillance data on CCHF during the 1991–2023 period in the Zhambyl region were extracted from the “Report on selected infectious and parasitic diseases”. Incidence (per 100,000 population) was defined as the number of annual new cases divided by the total population each year. Descriptive analysis was performed on case characteristics, time, and place of CCHF cases in the Zhambyl region in 2023. In total, 216 cases of CCHF were reported from 1991 to 2023. The incidence increased sharply with peak activity in 1995 and has declined since 2002. The natural foci of the disease have shifted from the Sarysu and Moiynkum districts to the Shu, Bayzak, and Zhambyl districts. Overall, 12 cases of CCHF were reported in the Zhambyl region in 2023, mainly in nonendemic (Shu, Bayzak, Zhambyl) districts. An analysis of epidemiological data for 2023 showed that the first peak of CCHF incidence was in March-June, with another peak from October to November. We observed dynamic distribution of CCHF in the Zhambyl region from 1991 to 2023, wherein Sarysu and Moiynkum endemic districts foci tended to increase by expanding to the Shu, Bayzak, Zhambyl districts. The disease trend is seasonal, and the life cycle of ticks can indirectly influence morbidity rates. Additional research is needed to elucidate the environmental, meteorological, and social factors associated with CCHF incidence in different decades.

The natural foci of Crimean-Congo haemorrhagic fever (CCHF) in Kazakhstan are geographically located in the southern regions of the country (Kyzylorda, Turkestan and Zhambyl regions), where the infection of ticks with the CCHF virus predominantly reside, tick species composition and the number of vectors are monitored annually. The objective of our research was to investigate the genetic variants of the CCHF virus in the southern endemic regions, as well as to monitor the spread of the CCHF virus in the western regions of the country (Aktobe, Atyrau and Mangystau regions). In total, 974 (216 pools) ticks from the western regions and 3527 (583 pools) ticks from the southern regions collected during 2021–2022 were investigated. The presence of CCHF virus was detected by real-time reverse transcription PCR (qRT- PCR) in 1 pool out of 799 pools (0.12%) with Hyalomma scupense ticks captured in the CCHF-endemic Kyzylorda region. In the western regions, CCHF virus was not detected in ticks. The sequencing of incomplete fragments of the S, M and L segments of the CCHF virus in the detected virus was identified as genotype Asia - I. Phylogenetic analysis showed that the isolate obtained in this study is grouped with the isolate from a patient with CCHF, which we reported in 2015 (KX129738 Genbank). Our findings highlight the importance of including sequencing in the annual monitoring system for better understanding the evolution of the CCHF virus in the study areas of our country.

Records on the distribution of Rickettsia spp. in their natural hosts in Central Asia are incomplete. Rodents and small mammals are potential natural reservoirs for Rickettsiae in their natural lifecycle. Studies about the maintenance of Rickettsia in wild animals are available for Western nations, but—to our knowledge—no studies and data are available in the Republic of Kazakhstan so far. The first case description of Rickettsioses in Kazakhstan was made in the 1950ies in the Almaty region and now Kyzylorda, East Kazakhstan, Pavlodar and North Kazakhstan are endemic areas. The existence of murine and endemic typhus was proven in arthropod vectors in the regions Kyzylorda and Almaty. Here we show for the first time investigations on tick-borne Rickettsia species detected by a pan-rickettsial citrate synthase gene ( gltA ) real-time PCR in ear lobes of small mammals (n = 624) in Kazakhstan. From all analysed small mammals 2.72% were positive for Rickettsia raoultii, R. slovaca or R. conorii. Sequencing of the rickettsial gene OmpAIV and the 23S–5S interspacer region revealed a similar heritage of identified Rickettsia species that was observed in ticks in previous studies from the region. In summary, this study proves that rodents in Kazakhstan serve as a natural reservoir of Rickettsia spp.

Orthohantaviruses are zoonotic pathogens that play a significant role in public health. These viruses can cause haemorrhagic fever with renal syndrome in Eurasia. In the Republic of Kazakhstan, the first human cases were registered in the year 2000 in the West Kazakhstan region. Small mammals can be reservoirs of orthohantaviruses. Previous studies showed orthohantavirus antigens in wild-living small mammals in four districts of West Kazakhstan. Clinical studies suggested that there might be further regions with human orthohantavirus infections in Kazakhstan, but genetic data of orthohantaviruses in natural foci are limited. The aim of this study was to investigate small mammals for the presence of orthohantaviruses by molecular biological methods and to provide a phylogenetic characterization of the circulating strains in Kazakhstan. Small mammals were trapped at 19 sites in West Kazakhstan, four in Almaty region and at seven sites around Almaty city during all seasons of 2018 and 2019. Lung tissues of small mammals were homogenized and RNA was extracted. Orthohantavirus RT-PCR assays were applied for detection of partial S and L segment sequences. Results were compared to published fragments. In total, 621 small mammals from 11 species were analysed. Among the collected small mammals, 2.4% tested positive for orthohantavirus RNA, one sample from West Kazakhstan and 14 samples from Almaty region. None of the rodents caught in Almaty city were infected. Sequencing parts of the small (S) and large (L) segments specified Tula virus (TULV) in these two regions. Our data show that geographical distribution of TULV is more extended as previously thought. The detected sequences were found to be split in two distinct genetic clusters of TULV in West Kazakhstan and Almaty region. TULV was detected in the common vole (Microtus arvalis) and for the first time in two individuals of the forest dormouse (Dryomys nitedula), interpreted as a spill-over infection in Kazakhstan.

Omsk haemorrhagic fever virus (OHFV) is the agent leading to Omsk haemorrhagic fever (OHF), a viral disease currently only known in Western Siberia in Russia. The symptoms include fever, headache, nausea, muscle pain, cough and haemorrhages. The transmission cycle of OHFV is complex. Tick bites or contact with infected small mammals are the main source of infection. The Republic of Kazakhstan is adjacent to the endemic areas of OHFV in Russia and febrile diseases with haemorrhages occur throughout the country—often with unclear aetiology. In this study, we examined human cerebrospinal fluid samples of patients with suspected meningitis or meningoencephalitis with unknown origins for the presence of OHFV RNA. Further, reservoir hosts such as rodents and ticks from four Kazakhstan regions were screened for OHFV RNA to clarify if this virus could be the causative agent for many undiagnosed cases of febrile diseases in humans in Kazakhstan. Out of 130 cerebrospinal fluid samples, two patients (1.53%) originating from Almaty city were positive for OHFV RNA. Screening of tick samples revealed positive pools from different areas in the Akmola region. Of the caught rodents, 1.1% out of 621 were positive for OHFV at four trapping areas from the West Kazakhstan region. In this paper, we present a broad investigation of the spread of OHFV in Kazakhstan in human cerebrospinal fluid samples, rodents and ticks. Our study shows for the first time that OHFV can not only be found in the area of Western Siberia in Russia, but can also be detected up to 1.600 km away in the Almaty region in patients and natural foci.

Flaviviruses are a family of viruses that cause many diseases in humans. Their similarity in the antigenic structure causes a cross-reaction, which complicates the precise diagnostic of disease causing agents. Tick-borne encephalitis virus (TBEV), a member of the flavivirus family, is the cause of tick-borne encephalitis (TBE). Worldwide the awareness of this disease is raising, however, in many countries such as the Republic of Kazakhstan (KZ) there is a lack of serological investigation of flaviviruses in humans. In our study, we focused on two TBE endemic regions of KZ (East Kazakhstan Oblast (EKO) and Almaty (AO)) and a region where TBE cases were registered only since 2010 (Akmola Oblast (AkO)). In KZ, up to 400 cases of serous meningitis of unknown origin were registered annually in the period from 2017 to 2019. Our goals were to calculate the prevalence of antibodies against TBEV in patients with suspected meningitis. We collected 179 sera and 130 cerebrospinal fluid (CSF) samples from patients and included a questionnaire with focus on socio-demographical factors and observed tick bites. The human samples were tested with TBEV and West-Nile fever virus (WNFV) IgM and IgG ELISA, by immunofluorescence assay using a flavivirus biochip, and TBEV-specific real-time RT-PCR. We found TBEV and WNFV antibodies in 31 samples by serological and molecular techniques. Seven serum samples out of 31 showed TBEV-specific antibodies, and three serum pairs had WNFV antibodies. Correlating the serological results with the information gained from the questionnaires it becomes apparent that the number of tick bites is a significant factor for a TBEV infection. This result has an impact on diagnostic in KZ and physicians should be aware that both flaviviruses play a role for serous meningitis of unknown origin in KZ.

In Kazakhstan natural foci of Crimea-Congo hemorrhagic fever is located on the territory of Turkestan, Kyzylorda and Zhambyl regions. Whereas preventive measures are taken, this disease is diagnosed annually among people, but there is a group of viruses such as Karshi, Tamdy, the Issyk-Kul fever virus and Syr Darya valley fever which are less known. In this regard the goal was set to identify the prevalence of viruses of Karshi, Tamdy, Issyk-Kul fever and fever of the Syr Darya valley in hemorrhagic fever endemic in the Crimea-Congo hemorrhagic fever to determine the main hosts and vectors of infection. Ticks captured in areas natural foci of the Crimean-Congo hemorrhagic fever virus. The species composition of captured ticks was represented by 9 species: Hyalomma scupense, Hyalomma asiaticum, Hyalomma turanicum, Hyalomma anatolicum, Haemaphysalis sucata, Haemaphysalis punctata, Dermacentor niveus, Rhipicephalus pumilio, Rhipicephalus schulzei. Preliminary work was carried out on the selection and design of oligonucleotide primers for the identification of viruses by molecular genetic analysis. As a result of the studies, positive samples were found for viruses of Tamdy and Syr Darya valley fever in ticks H. asiaticum, H. scupense from the Turkestan region. The Crimean-Congo hemorrhagic fever virus was detected in H. asiaticum and H. scupense ticks from Zhambyl and Turkestan regions.

West Nile virus is widespread in southern Russia, where the fever appears annually. Since Western Kazakhstan borders on southern Russia, we examined mosquitoes in this region for the presence of West Nile virus. Virus was detected in a small proportion of Culex modestus mosquitoes (3/239 pools) and isolates are related to strains from Volgograd, Russia. A screen for West Nile virus IgG was conducted and ~5% of the local human population tested positive.

Background: In the South of Kazakhstan, Almaty Oblast' (region) is endemic for tick-borne encephalitis, with 0.16-0.32 cases/100,000 population between 2016-2018. The purpose of this study was to determine the prevalence and circulating subtypes of tick-borne encephalitis virus (TBEV) in Almaty Oblast' and Kyzylorda Oblast'. Methods: In 2015 we investigated 2341 ticks from 7 sampling sites for the presence of TBEV. Ticks were pooled in 501 pools and isolated RNA was tested for the presence of TBEV by RT-qPCR. For the positive samples, the E gene was amplified, sequenced and a phylogenetic analysis was carried out. Results: A total of 48 pools were TBEV-positive by the RT-qPCR. TBEV-positive ticks were only detected in three districts of Almaty Oblast' and not in Kyzylorda Oblast'. The positive TBEV pools were found within Ixodes persulcatus, Haemaphysalis punctata and Dermacentor marginatus. These tick species prevailed only in Almaty Oblast' whereas in Kyzylorda Oblast' Hyalomma asiaticum and D. marginatus are endemic. The minimum infection rates (MIR) in the sampling sites were 4.4% in Talgar, 2.8% in Tekeli and 1.1% in Yenbekshikazakh, respectively. The phylogenetic analysis of the generated sequences indicates that TBEV strains found in Almaty Oblast' clusters in the Siberian subtype within two different clades. Conclusions: We provided new data about the TBEV MIR in ticks in Almaty Oblast' and showed that TBEV clusters in the Siberian Subtype in two different clusters at the nucleotide level. These results indicate that there are different influences on the circulating TBEV strains in south-eastern Kazakhstan. These influences might be caused by different routes of the virus spread in ticks which might bring different genetic TBEV lineages to Kazakhstan. The new data about the virus distribution and vectors provided here will contribute to an improvement of monitoring of tick-borne infections and timely anti-epidemic measures in Kazakhstan.

Little is known of the endemicity of flea-borne rickettsiae in Kazakhstan. Thus, a survey for rickettsiae within great gerbil fleas was conducted in Almaty oblast. High prevalence of Rickettsia asembonensis was detected among Xenopsylla gerbilli, demonstrating that flea-borne rickettsiae are endemic to southeastern Kazakhstan. Interestingly, no Rickettsia typhi were detected in these same fleas.