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Volume 21, Number 6—June 2015
Letter

Tickborne Relapsing Fever in Southern Iran, 2011–2013

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To the Editor: Tickborne relapsing fever (TBRF) is endemic in Iran; >1,400 cases were confirmed in 19 provinces during 1997–2006 (1). In the western, northwestern, and foothill regions of the Alborz Mountains, the Argasid soft tick Ornithodoros tholozani is commonplace and accounts for ≈60% of TBRF cases attributed to Borrelia persica. However, in central and western Iran, O. tholozani and B. microti–infected O. erraticus ticks coexist (1,2). Two other Borrelia species, B. latyschewii and B. baltazardi, have also been described in northeastern and northwestern Iran (3,4), but no recent human infections with these species have been documented. Cases of TBRF occurring in southern Iran have presumably been caused by B. microti because its tick vector, O. erraticus, predominates in this region.

Relapsing fever infections in Hormozgan Province in southern Iran are commonly identified during routine checks for malaria. During 2011–2013, blood samples were obtained from 14 febrile patients referred to medical centers in Jask and Rodan in Hormozgan Province (Technical Appendix Figure). Informed verbal consent was obtained from all participants, and the ethical committee of Pasteur Institute of Iran approved the project. Patients seeking care had fever and >1 sign or symptom, such as headache, chills, sweating, or fatigue. Six patients reported recurrent fever and generalized muscle and joint pain. Each patient lived in a local tent, called a kapar, or in a brick or concrete-block house.

Thick and thin blood smears were prepared from blood samples, stained with Giemsa, and examined. None showed malaria parasites; however, spirochetes were observed in thick or thin smears from 3 patients (Technical Appendix Table). Patients whose samples tested positive by microscopy were treated with 500 mg tetracycline every 6 hours for 10 days and became afebrile.

Figure

Thumbnail of Phylogenetic tree of Borrelia spp. strains isolated in Iran, 2014. Constructed on the basis of  intergenic spacer sequences, the tree is drawn to scale using evolutionary distance computed using the Jukes-Cantor method in which the units reflect substitutions per site. The final dataset used 587 bp. Numbers at nodes show the level of robustness in a bootstrap test performed with 2,000 replicates; numbers <85 were removed. Scale bar indicates nucleotide substitutions over length a

Figure. Phylogenetic tree of Borrelia spp. strains isolated in Iran, 2014. Constructed on the basis of intergenic spacer sequences, the tree is drawn to scale using evolutionary distance computed using the...

DNA was extracted from patients’ serum samples by using the Miniprep DNA kit (QIAGEN, Hilden, Germany) and screened for borrelia DNA by using real-time PCR; negative and positive control DNA from B. microti or B. persica was also screened. Borrelia spp. DNA was detected in 5 (36%) of 14 serum samples (Technical Appendix Table). Of these 5 samples, 2 were also positive by nested PCR that targeted the intergenic spacer (IGS) region (5). The 2 IGS regions were sequenced (ABI-3130XL sequencer; Applied Biosystems, Foster City, CA, USA) in both directions at the Pasteur Institute of Iran. The resulting 539- and 527-bp IGS sequences (GenBank accession nos. KM271987 and KM271988, respectively) were 97% homologous with B. recurrentis and B. duttonii from Africa (GenBank accession nos. CP000993 and DQ000280, respectively); 96% homologous with B. microti from Iran (GenBank accession no. JQ436580); and 92% homologous with B. crocidurae from Africa (GenBank accession no. GU350723). A neighbor-joining phylogenetic tree was constructed by using MEGA6 (http://www.megasoftware.net); the 2 IGS sequences clustered into a distinct group separate from B. microti, B. duttonii, and B. recurrentis genotypes (Figure).

B. microti was expected to be found because O. tholozani ticks that transmit B. persica are not seen in southern Iran, but B. microti–infected O. erraticus ticks have been frequently recovered from rodents’ burrows in the region (6). Current molecular data from TBRF borreliae from Iran are limited to 2 isolates of B. persica and B. microti from O. tholozani and O. erraticus ticks, respectively (5,7,8). In situ IGS analysis revealed that spirochetes in our analysis had highest homology (97%) with relapsing fever agents from eastern Africa, B. duttonii and B. recurrentis, followed by B. microti (96%) from Iran (8). B. microti clustered with 1 strain (B. duttonii; GenBank accession no. GU350721) and apart from other B. duttonii IGS strains, suggesting that this strain may not be B. duttonii. The phylogenetic tree separated B. duttonii into 4 clades, 2 of which also contained B. recurrentis, confirming previous observations (9) and providing further support that B. recurrentis represents an ecotype of B. duttonii rather than a species (10). Furthermore, the high level of phylogenetic similarity among borreliae from eastern Africa and Iran indicates that the borreliae in our study might represent ecotype-adapted strains. More sequencing of different genomic markers is required to substantiate or refute this possibility. Lack of GenBank data for the remaining borreliae from Iran, B. latyschewii and B. baltazardi, prevent exclusion of these species.

Although relapsing fever spirochetes from southern Iran and those from borreliae in Africa have a close phylogenetic similarity, they have different virulence levels and abilities to infect vector and host species. Consequently, deciphering the evolutionary links for these Borrelia spp. is of paramount importance and might provide valued insights into host–microbe interactions.

Our report confirms a novel Borrelia IGS sequence type detected in situ from 2 relapsing fever patients. This species showed greatest homology with the relapsing fever borreliae from Africa, B. recurrentis and B. duttonii, but not with B. microti, which is transmitted by O. erraticus ticks, previously believed to be the only soft tick species in this region. These findings challenge the assumption that TBRF in Iran is attributed to only B. persica or B. microti.

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Acknowledgments

We thank Gholam Mohseni, the late technical supervisor at Bandar Abbas Health Research Station, Tehran University of Medical Sciences, for his contributions to this study.

This study was partially funded by the Pasteur Institute of Iran and by the Center for Disease Control, Ministry of Health and Medical Education, Tehran, Iran (grant no. 749).

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Saied Reza Naddaf, Behnaz Ghazinezhad, Mohammad Mehdi Sedaghat, Hossein Masoumi Asl, and Sally Jane CutlerComments to Author 

Author affiliations: Pasteur Institute of Iran, Tehran, Iran (S.R. Naddaf, B. Ghazinezhad); Tehran University of Sciences, Tehran (M.M. Sedaghat); Ministry of Health and Medical Education, Tehran (H.M. Asl); University of East London, London, United Kingdom (S.J. Cutler)

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References

  1. Masoumi Asl  H, Goya  MM, Vatandoost  H, Zahraei  SM, Mafi  M, Asmar  M, The epidemiology of tick-borne relapsing fever in Iran during 1997–2006. Travel Med Infect Dis. 2009;7:1604. DOIPubMed
  2. Aghighi  Z, Assmar  M, Piazak  N, Javadian  E, Seyedi Rashti  MA, Kia  EB, Distribution of soft ticks and their natural infection with Borrelia in a focus of relapsing fever in Iran. Iran J Arthropod-Borne Dis. 2007;1:148.
  3. Karimi  U. Relapsing fever and its epidemiology [in Farsi]. Tehren (Iran): Pasteur Institute of Iran; 1981.
  4. Karimi  Y, Hovind-Hougen  K, Birch-Andersen  A, Asmar  M. Borrelia persica and B. baltazardi sp. nov.: experimental pathogenicity for some animals and comparison of the ultrastructure. Ann Microbiol (Paris). 1979;130B:15768.PubMed
  5. Oshaghi  MA, Rafinejad  J, Choubdar  N, Piazak  N, Vatandoost  H, Telmadarraiy  Z, Discrimination of relapsing fever Borrelia persica and Borrelia microtti by diagnostic species-specific primers and polymerase chain reaction-restriction fragment length polymorphism. Vector Borne Zoonotic Dis. 2011;11:2017. DOIPubMed
  6. Janbakhsh  B, Ardelan  A. The nature of sporadic cases of relapsing fever in Kazeroun area, southern Iran. Bull Soc Pathol Exot Filiales. 1977;70:5879.DOIPubMed
  7. Ras  NM, Lascola  B, Postic  D, Cutler  SJ, Rodhain  F, Baranton  G, Phylogenesis of relapsing fever Borrelia spp. Int J Syst Bacteriol. 1996;46:85965. DOIPubMed
  8. Naddaf  SR, Ghazinezhad  B, Bahramali  G, Cutler  SJ. Phylogenetic analysis of the spirochete Borrelia microti, a potential agent of relapsing fever in Iran. J Clin Microbiol. 2012;50:28736. DOIPubMed
  9. Cutler  SJ, Bonilla  EM, Singh  RJ. Population structure of East African relapsing fever Borrelia spp. Emerg Infect Dis. 2010;16:107680. DOIPubMed
  10. Lescot  M, Audic  S, Robert  C, Nguyen  TT, Blanc  G, Cutler  SJ, The genome of Borrelia recurrentis, the agent of deadly louse-borne relapsing fever, is a degraded subset of tick-borne Borrelia duttonii. PLoS Genet. 2008;4:e1000185. DOIPubMed

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Cite This Article

DOI: 10.3201/eid2106.141715

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Table of Contents – Volume 21, Number 6—June 2015

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Sally Jane Cutler, School of Health, Sport, and Bioscience, University of East London, Water Lane, Stratford, London E15 4LZ, UK

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Page created: May 18, 2015
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