Displaying publications 21 - 40 of 42 in total

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  1. Kernif T, Socolovschi C, Wells K, Lakim MB, Inthalad S, Slesak G, et al.
    Comp Immunol Microbiol Infect Dis, 2012 Jan;35(1):51-7.
    PMID: 22153360 DOI: 10.1016/j.cimid.2011.10.003
    Rickettsioses and bartonelloses are arthropod-borne diseases of mammals with widespread geographical distributions. Yet their occurrence in specific regions, their association with different vectors and hosts and the infection rate of arthropod-vectors with these agents remain poorly studied in South-east Asia. We conducted entomological field surveys in the Lao PDR (Laos) and Borneo, Malaysia by surveying fleas, ticks, and lice from domestic dogs and collected additional samples from domestic cows and pigs in Laos. Rickettsia felis was detected by real-time PCR with similar overall flea infection rate in Laos (76.6%, 69/90) and Borneo (74.4%, 268/360). Both of the encountered flea vectors Ctenocephalides orientis and Ctenocephalides felis felis were infected with R. felis. The degrees of similarity of partial gltA and ompA genes with recognized species indicate the rickettsia detected in two Boophilus spp. ticks collected from a cow in Laos may be a new species. Isolation and further characterization will be necessary to specify it as a new species. Bartonella clarridgeiae was detected in 3/90 (3.3%) and 2/360 (0.6%) of examined fleas from Laos and Borneo, respectively. Two fleas collected in Laos and one flea collected in Borneo were co-infected with both R. felis and B. clarridgeiae. Further investigations are needed in order to isolate these agents and to determine their epidemiology and aetiological role in unknown fever in patients from these areas.
    Matched MeSH terms: Rickettsia Infections/epidemiology; Rickettsia Infections/transmission; Rickettsia Infections/veterinary*; Rickettsia felis/genetics*; Rickettsia felis/isolation & purification
  2. Tay ST, Ho TM, Rohani MY, Devi S
    Trans R Soc Trop Med Hyg, 2000 9 7;94(3):280-4.
    PMID: 10974999
    A serosurvey was conducted in 1995-97 among 1596 febrile patients from 8 health centres in Malaysia for antibodies against Orientia tsutsugamushi (OT), Rickettsia typhi (RT) and TT118 spotted fever group rickettsiae (SFGR) by using an indirect immunoperoxidase assay. A total of 51.4% patients had antibody against at least 1 of those rickettsiae. Antibody to SFGR was most prevalent (42.5%), followed by RT (28.1%) and OT (24.9%). The seroprevalences of antibodies to SFGR, RT or OT alone were 12.4, 3.6 and 4.3%, respectively. Antibodies against more than 1 species of rickettsiae were presence in 31.1% of the patients, suggesting the possibility of co-infection, previous exposures or serological cross-reactivities. Seroprevalence of the various rickettsiae varied according to locality, with SFGR antibodies being the most prevalent in most areas. There was no significant association of prevalence of rickettsial antibody with gender. The seroprevalence of OT, SFGR and RT increased with patient age but an increase of antibody titre with age was not significant. Those working in the agricultural sectors had significantly higher seroprevalence of OT, SFGR and RT than those not related with agricultural activities. Scrub typhus remains a public health problem with an estimated annual attack rate of 18.5%. Tick typhus and murine typhus as shown in this serosurvey appear much more widespread than scrub typhus in this country.
    Matched MeSH terms: Rickettsia Infections/diagnosis; Rickettsia Infections/immunology; Rickettsia Infections/epidemiology*; Rickettsia typhi/immunology*
  3. Tay ST, Kamalanathan M, Rohani MY
    PMID: 12971530
    The seroprevalence of Orientia tsutsugamushi (OT), Rickettsia typhi (RT) and TT118 spotted fever group rickettsiae (SFGR) among blood donors and febrile Malaysian patients in the urban areas was determined. Of the 240 blood donors, 5.4%, 9.2% and 1.7% had either present or previous exposure to OT, RT and SFG rickettsiae, respectively. Patients admitted to an urban hospital had high seroprevalences of OT (43.5%) and RT (22.9%), as compared to SFGR (11.6%). Antibody levels suggestive of recent infections of scrub typhus, murine typhus and tick typhus were detected in 16.8%, 12.7% and 8.2% of patients respectively. No significant difference was noted in the distribution of rickettsial antibodies among urban patients from 2 geographical locations. However, the serologic patterns of rickettsial infection in the urban areas were different form those of rural areas.
    Matched MeSH terms: Rickettsia Infections/diagnosis; Rickettsia Infections/immunology; Rickettsia Infections/epidemiology*; Rickettsia typhi/immunology*
  4. Norazah A, Mazlah A, Cheong YM, Kamel AG
    Med J Malaysia, 1995 Jun;50(2):177-9.
    PMID: 7565191
    A 34-year-old laboratory worker developed murine typhus after an accidental splashing of Rickettsia typhi over her right eye and lips. Indirect immunoperoxidase test showed a four-fold increase in titre to Rickettsia typhi. She responded well to doxycycline.
    Matched MeSH terms: Rickettsia typhi/immunology
  5. Azrizal-Wahid N, Sofian-Azirun M, Low VL
    PMID: 33609991 DOI: 10.1016/j.cimid.2021.101621
    Flea-borne pathogens were screened from 100 individual cat fleas using a PCR approach, of which 38 % were infected with at least one bacterium. Overall, 28 % of the flea samples were positive for Bartonella as inferred from ITS DNA region. Of these, 25 % (7/28) were identified as Bartonella clarridgeiae, 42.9 % (12/28) as Bartonella henselae consisted of two different strains, and 32.1 % (9/28) as Bartonella koehlerae, which was detected for the first time in Malaysia. Sequencing of gltA amplicons detected Rickettsia DNA in 14 % of cat flea samples, all of them identified as Rickettsia asembonensis (100 %). None of the flea samples were positive for Mycoplasma DNA in 16S rRNA gene detection. Four fleas were co-infected with Bartonella and Rickettsia DNAs. Statistical analyses reveal no significant association between bacterial infection and mtDNA diversity of the cat flea. Nevertheless, in all types of pathogen infections, infected populations demonstrated lower nucleotide and haplotype diversities compared to uninfected populations. Moreover, lower haplotype numbers were observed in infected populations.
    Matched MeSH terms: Rickettsia/classification
  6. Lewthwaite R, Savoor SR
    Br J Exp Pathol, 1936;17:448-60.
    1. Cross-immunity tests between strains of rural typhus and tsutsugamushi in the guinea-pig, rabbit and monkey were made. Complete cross-immunity between the strains was demonstrated.
    2. The problem of the absence of a primary ulcer in rural typhus and its presence in tsutsugamushi is discussed. Experimental findings are recorded; from consideration of these and certain clinical and epidemiological observations, the conclusion is drawn that one and the same virus may cause gradations of dermal lesion that vary greatly in extent and duration.
    3. Correlation of the results of cross-immunity tests and experimental infections with clinical, aetiological, epidemiological and serological findings indicates that the two diseases are identical. Rural typhus is not a disease sui generis, and the term should be discarded, the older designation, "tsutsugamushi disease ", being retained.
    Matched MeSH terms: Rickettsia Infections
  7. Lewthwaite R, Savoor SR
    Br J Exp Pathol, 1936;17:461-72.
    Part VIII.
    1. Cross-immunity experiments in the guinea-pig, rabbit and monkey were carried out with the viruses of the tsutsugamushi disease (including rural typhus) and the urban typhus of Malaya; they showed that immunogenically the two viruses are distinct.
    2. The characteristics of setiology, epidemiology, serology and experimental infections are compared, and the conclusion drawn that the two diseases belong to entirely separate groups of rickettsial disease.
    Part IX.
    1. Cross-immunity experiments in the guinea-pig and rabbit were carried out with the viruses of Rocky Mountain spotted fever, tsutsugamushi (including rural typhus) and urban typhus. They showed that, immunologically, tsutsugamushi
    and spotted fever are entirely distinct; whereas urban typhus and spotted fever, though more distinct than alike immunologically, do possess a minor degree of reciprocal cross-immunity.
    2. Spotted-fever vaccine was found to have no protective value against the viruses of tsutsugamushi and urban typhus.
    Matched MeSH terms: Rickettsia Infections
  8. Lewthwaite R, Hodgkin EP, Savoor SR
    Br J Exp Pathol, 1936;17:309-17.
    1. Transmission of the virus of urban typhus under experimental conditions from rat to rat by the rat flea (X. cheopis) by feeding has been effected. Collateral attempts to transmit the virus of rural typhus by precisely the same procedure failed.
    2. Transmission of the virus of urban typhus was also achieved by the inoculation of faeces or crushed tissue of infected fleas into the scarified skin of guinea-pigs.
    3. Multiplication of the virus of urban typhus occurs within the rat flea.
    4. Infection with the virus of urban typhus is not hereditary in the rat flea.
    5. Attempts to transmit the virus of urban or rural typhus by two species of ticks failed. In the case of rural typhus a lessened mortality in the experimental guinea-pigs following test inoculation with passage virus makes it, however, difficult to exclude ticks entirely as a minor factor in the epidemiology of rural typhus.
    Matched MeSH terms: Rickettsia Infections
  9. Tay ST, Rohani MY
    PMID: 12236431
    The indirect immunoperoxidase (HP) test has been used extensively in most government hospitals in Malaysia for the serodiagnosis of scrub typhus, murine typhus and tick typhus during the 1990s. The test was used to determine the IgG and IgM antibody titers in patients' sera for three rickettsial species, ie Orientia tsutsugamushi OT; the causative agent of scrub typhus), Rickettsia typhi (RT; the causative agent of murine typhus), and TT118 spotted fever group rickettsiae (TT; the causative agent of tick typhus). The serological findings obtained from Malaysian hospitals using the IIP test (1994-1999) were analyzed. During the six-year period, a total of 61,501 patients' sera were tested, of which 9.6%, 10.5%, and 12.9% had antibody (IgG and/or IgM of > or = 1:50) for OT, RT and TT respectively. A total of 8.6%, 9.8%, and 9.7% of sera had IgG antibody of > or = 1:50 for OT, RT, and TT respectively, indicating past infection. A total of 3.4%, 3.8%, and 6.4 % of sera had IgM antibody of > or = 1:50 for OT, RT, and TT respectively, indicating recent infection. A total of 2,986 (4.9%), 1,882 (3.1%), and 1,574 (2.6%) of sera had IgG and/or IgM antibody titers of > or = 1:400 for OT, RT, and TT respectively, suggesting active rickettsial infection. The seropositivity rates of OT, RT and TT varied according to geographical locations. While the seropositivity of OT remained constant during the six-year period, a reduction in the seropositivity of both RT and TT was noted during recent years. The serological findings reflect the endemicity of rickettsial diseases, including tick typhus, and endemic typhus in various parts of Malaysia. Awareness of these diseases by health and medical staff and by the general public is important if the mortality and morbidity associated with scrub typhus, tick typhus, and murine typhus in Malaysia, are to be reduced.
    Matched MeSH terms: Rickettsia Infections/diagnosis*; Rickettsia Infections/epidemiology
  10. Mokhtar AS, Tay ST
    Am J Trop Med Hyg, 2011 Nov;85(5):931-3.
    PMID: 22049052 DOI: 10.4269/ajtmh.2011.10-0634
    The presence of Rickettsia felis, Bartonella henselae and B. clarridgeiae in 209 fleas (Ctenocephalides felis) obtained from domestic cats and dogs in several locations in Malaysia was investigated in this study. Using a polymerase chain reaction specific for the citrate synthase (gltA) and 17-kD antigenic protein (17kD) genes of rickettsiae, we detected R. felis DNA in 6 (2.9%) fleas. For detection of bartonellae, amplification of the heme-binding protein (pap31) and riboflavin synthase (ribC) genes identified B. henselae and B. clarridgeiae DNA in 24 (11.5%) and 40 (19.1%) fleas, respectively. The DNA of B. henselae and B. clarridgeiae was detected in 10 (4.8%) fleas. Two B. henselae genogroups (Marseille and Houston-1) were detected in this study; genogroup Marseille (genotype Fizz) was found more often in the fleas. The findings in this study suggest fleas as potential vectors of rickettsioses and cat-scratch disease in this country.
    Matched MeSH terms: Rickettsia Infections/microbiology; Rickettsia Infections/epidemiology; Rickettsia Infections/transmission; Rickettsia felis/genetics; Rickettsia felis/isolation & purification*
  11. Kho KL, Koh FX, Tay ST
    Parasit Vectors, 2015;8:112.
    PMID: 25889376 DOI: 10.1186/s13071-015-0719-3
    Amblyomma ticks parasitize a wide range of animals in tropical regions. This study describes the identification of Amblyomma ticks from wild snakes in Malaysia and the detection of potential human pathogens such as Rickettsia, Anaplasma, Ehrlichia and bartonellae in the ticks.
    Matched MeSH terms: Rickettsia/genetics; Rickettsia/isolation & purification*
  12. Kho KL, Koh FX, Hasan LI, Wong LP, Kisomi MG, Bulgiba A, et al.
    Emerg Microbes Infect, 2017 Apr 12;6(4):e18.
    PMID: 28400593 DOI: 10.1038/emi.2017.4
    Rickettsioses are emerging zoonotic diseases that are often neglected in many countries in Southeast Asia. Rickettsial agents are transmitted to humans through exposure to infected arthropods. Limited data are available on the exposure of indigenous community and animal farm workers to the aetiological agents and arthropod vectors of rickettsioses in Peninsular Malaysia. Serological analysis of Rickettsia conorii and Rickettsia felis was performed for 102 individuals from the indigenous community at six rural villages and 87 workers from eight animal farms in Peninsular Malaysia in a cross-sectional study. The indigenous community had significantly higher seropositivity rates for R. conorii (P<0.001) and R. felis (P<0.001), as compared to blood donors from urban (n=61). Similarly, higher seropositivity rates for R. conorii (P=0.046) and R. felis (P<0.001) were noted for animal farm workers, as compared to urban blood donors. On the basis of the sequence analysis of gltA, ompA and ompB, various spotted fever group rickettsiae closely related to R. raoultii, R. heilongjiangensis, R. felis-like organisms, R. tamurae, Rickettsia sp. TCM1, R. felis, Rickettsia sp. LON13 and R. hulinensis were identified from tick/flea samples in animal farms, indigenous villages and urban areas. This study describes rickettsial seropositivity of the Malaysian indigenous community and animal farm workers, and provides molecular evidence regarding the presence of rickettsial agents in ticks/fleas infesting domestic animals in Peninsular Malaysia.
    Matched MeSH terms: Rickettsia conorii/immunology*; Rickettsia felis/immunology*
  13. Taylor AC, Hii J, Kelly DJ, Davis DR, Lewis GE
    PMID: 3107139
    A seroepidemiological survey of 837 people and 383 febrile patients was performed in rural areas of Sabah. We determined that the rickettsial diseases scrub typhus and endemic typhus were uncommon causes of febrile illness, as was tick typhus, except in forest dwelling peoples. The rate of occurrence of SFGR specific antibody was 16.5% among 412 forest dwellers, indicating that tick typhus may be a frequent cause of illness in this population.
    Matched MeSH terms: Rickettsia rickettsii/immunology; Rickettsia typhi/immunology
  14. Koay AS, Cheong YM
    Malays J Pathol, 1993 Jun;15(1):69-73.
    PMID: 8277794
    Forty-four serum samples of various reactivities to rickettsial antigens demonstrated by the indirect immunoperoxidase technique were tested with INDX Dip-S-Ticks (INDX Integrated Diagnostics Inc., USA) Kit for the detection of tick borne diseases. The kit utilised Rickettsia rickettsii the causative agent of Rocky Mountain spotted fever (RMSF) as antigens. The samples positive for endemic typhus were also tested against R. typhi, the agent for endemic typhus by the same method. The aim of this study was to determine the extent of cross-reactivity of R. rickettsii with rickettsial infections in Malaysia. Nine out of 12 tick typhus, 4 out of 10 scrub typhus and 4 out of 12 endemic typhus samples cross reacted with R. rickettsii. Ten out of 12 endemic samples were positive with R. typhi by the same method. From the study, we concluded that the INDX Dip-S-Ticks Kit can be used as a rapid screening test to detect endemic and tick-borne rickettsial infections in Malaysia but a second serological test is strongly recommended on all weakly reactive cases.
    Matched MeSH terms: Rickettsia/immunology*
  15. Tappe D, Gross Y, Ngui R, Rauch J, Tay ST, Lim YAL
    Vector Borne Zoonotic Dis, 2019 05;19(5):323-327.
    PMID: 30540546 DOI: 10.1089/vbz.2018.2391
    Rickettsioses of the typhus group (TG) and spotted fever group (SFG) are emerging bacterial infections worldwide, especially in the tropics. Only a few studies on these pathogens and their respective clinical diseases have been conducted in Malaysia. Here, we performed a seroprevalence study among 544 healthy, afebrile indigenous people (Orang Asli) from peninsular Malaysia for TG and SFG rickettsioses in nine rural and peri-urban settlements. The study population encompassed children, adolescents, and adults. The overall seroprevalence of rickettsiosis in the Orang Asli was 48.5%, with 27.9% seroprevalence against TG rickettsiae and 20.6% seroprevalence against SFG rickettsiae. In 7.9% of the study participants, antibodies against both rickettsial groups were found. The highest seropositivity rates against TG and SRG rickettsiae were detected in young children and adults. Overall, there were no gender differences. Seroprevalences were similar among inhabitants of different settlements, except for two localities. More studies are needed to shed more light on the ecology and risk factors for TG and SFG rickettsioses in Malaysia.
    Matched MeSH terms: Rickettsia/immunology*
  16. Sekhar WY, Devi S
    Singapore Med J, 2000 May;41(5):226-31.
    PMID: 11063173
    A seroepidemiology study was done in response to the recent increase of Endemic Typhus cases diagnosed at University Hospital. The serosurvey was based on doctors' request for the Weil Felix (WF) or the Indirect Immunoperoxidase (IIP) test in Pyrexia of Unknown Origin (PUO) patients for the years 1991 to 1997. Over the 7 years, we found that the incidence of Endemic typhus is increasing with gender (male:female = 2:1), age (20-40 years) and race distribution (Indians > Malay > Chinese) that reflects socioeconomic circumstances. A commercially available ELISA dot assay [INDX (E2R3) Dip-S-Ticks], for the detection of antibodies against R. typhi was compared with the indirect immunoperoxidase test (IIP). The ELISA assay was done against 219 IIP tested sera. The Dip-S-Ticks was found to be comparable to the IIP with a sensitivity of 91.7% and specificity of 92.8% at cut-off titres of > 1:80 IIP.
    Matched MeSH terms: Rickettsia typhi/immunology*
  17. Tee TS, Kamalanathan M, Suan KA, Chun SS, Ming HT, Yasin RM, et al.
    Am J Trop Med Hyg, 1999 Jul;61(1):73-7.
    PMID: 10432060
    The seroprevalence of Orientia tsutsugamushi, Rickettsia typhi, and TT118 spotted fever group (SFG) rickettsiae in 300 rubber estate workers in Slim River, Malaysia was determined in December 1996 and March 1997. In December, which was the wet season, 23.3%, 3.0%, and 57.3% of the population had antibodies detected against the three rickettsiae, respectively. The highest seropositive rate of 40% was detected for single infection with SFG rickettsiae, followed by a rate of 15.3% for both O. tsutsugamushi and SFG rickettsiae among the rubber estate workers. Subjects less than 21 years old had a lower seroprevalence of SFG rickettsiae compared with the other age groups. Indians had a higher seroprevalence of O. tsutsugamushi compared with other ethnic groups. Rubber tappers had a higher seroprevalence of SFG rickettsiae compared with other occupational groups. During the dry season in March 1997, there was a significant increase in the seroprevalence of R. typhi. The seroconversion rates for IgM against O. tsutsugamushi, R. typhi, and SFG rickettsiae were 5.7%, 12.3%, and 15.1%, respectively, during the four-month period. Significant variations of antibody titers towards the three rickettsiae was noted among subjects who were bled twice. This suggests a significant and continual exposure of rubber estate workers to the three rickettsiae.
    Matched MeSH terms: Rickettsia typhi/immunology; Rickettsia typhi/pathogenicity*
  18. Nguyen VL, Colella V, Greco G, Fang F, Nurcahyo W, Hadi UK, et al.
    Parasit Vectors, 2020 Aug 15;13(1):420.
    PMID: 32799914 DOI: 10.1186/s13071-020-04288-8
    BACKGROUND: Ticks and fleas are considered amongst the most important arthropod vectors of medical and veterinary concern due to their ability to transmit pathogens to a range of animal species including dogs, cats and humans. By sharing a common environment with humans, companion animal-associated parasitic arthropods may potentially transmit zoonotic vector-borne pathogens (VBPs). This study aimed to molecularly detect pathogens from ticks and fleas from companion dogs and cats in East and Southeast Asia.

    METHODS: A total of 392 ticks and 248 fleas were collected from 401 infested animals (i.e. 271 dogs and 130 cats) from China, Taiwan, Indonesia, Malaysia, Singapore, Thailand, the Philippines and Vietnam, and molecularly screened for the presence of pathogens. Ticks were tested for Rickettsia spp., Anaplasma spp., Ehrlichia spp., Babesia spp. and Hepatozoon spp. while fleas were screened for the presence of Rickettsia spp. and Bartonella spp.

    RESULT: Of the 392 ticks tested, 37 (9.4%) scored positive for at least one pathogen with Hepatozoon canis being the most prevalent (5.4%), followed by Ehrlichia canis (1.8%), Babesia vogeli (1%), Anaplasma platys (0.8%) and Rickettsia spp. (1%) [including Rickettsia sp. (0.5%), Rickettsia asembonensis (0.3%) and Rickettsia felis (0.3%)]. Out of 248 fleas tested, 106 (42.7%) were harboring at least one pathogen with R. felis being the most common (19.4%), followed by Bartonella spp. (16.5%), Rickettsia asembonensis (10.9%) and "Candidatus Rickettsia senegalensis" (0.4%). Furthermore, 35 Rhipicephalus sanguineus ticks were subjected to phylogenetic analysis, of which 34 ticks belonged to the tropical and only one belonged to the temperate lineage (Rh. sanguineus (sensu stricto)).

    CONCLUSION: Our data reveals the circulation of different VBPs in ticks and fleas of dogs and cats from Asia, including zoonotic agents, which may represent a potential risk to animal and human health.

    Matched MeSH terms: Rickettsia/classification; Rickettsia/genetics; Rickettsia/isolation & purification
  19. Watanabe M, Nakao R, Amin-Babjee SM, Maizatul AM, Youn JH, Qiu Y, et al.
    Trop Biomed, 2015 Jun;32(2):390-8.
    PMID: 26691268 MyJurnal
    A total of 44 Rhipicephalus sanguineus ticks collected from 23 dogs from Malaysia were screened for Rickettsia, Anaplasmataceae and Coxiella burnetii. Coxiella burnetii was detected in 59% (26/44) of ticks however Rickettsia and Anaplasmataceae were not detected in any of the ticks. In order to genotype the strains of C. burnetii, multispacer sequence typing (MST) was carried out using three different spacers. One of the spacers; Cox2 successfully amplified a fragment for which the full length sequence of 397 bp was obtained. The sequenced product revealed only a single nucleotide difference with the Cox2.3 type sequence.
    Matched MeSH terms: Rickettsia/isolation & purification*
  20. Alajmi RA, Ayaad TH, Al-Harbi HT, Shaurub EH, Al-Musawi ZM
    Trop Biomed, 2019 Sep 01;36(3):758-765.
    PMID: 33597497
    The present work aimed to identify camel ticks Hyalomma dromedarii and Hyalomma marginatum using direct sequence of the mitochondrial 16S rRNA gene and the detection of their natural infection rate with Rickettsia and Borrelia using the PCR/ hybridization method for amplification of the citrate synthase (gltA) gene. The phylogenetic analysis showed 99% similarity between Hyalomma dromedarii and its reference with accession # L34306.1, as well as between Hyalomma marginatum and its reference with accession # KT391060.1 obtained from GenBank data base. The prevalence of H. dromedarii and H. marginatum was about 99% and 1%, respectively. The intraspecific variation among H. dromedarii ranged between 0.2-6.6%. The interspecific variation between H. dromedarii and H. marginatum was 18.3%. PCR/hybridization of the sampled H. dromedarii detected about 31%, 37% and 18% natural infection with Rickettsia, Borrelia and co-infection with both pathogens, respectively. In contrast, none of Rickettsia or Borrelia was detected in H. marginatum. The present study emphasizes the accuracy of the identification of camel ticks based on molecular techniques. The ability of H. dromedarii to spread more than one disease is an important issue from the epidemiological standpoint. Future epidemiological research should be carried out in Saudi Arabia to monitor the distribution of tick species and suggest effective control strategies.
    Matched MeSH terms: Rickettsia/isolation & purification*
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