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Ahead of Print -Rickettsia felis Infections and Comorbid Conditions, Laos, 2003–2011 - Volume 20, Number 8—August 2014 - Emerging Infectious Disease journal - CDC

Ahead of Print -Rickettsia felis Infections and Comorbid Conditions, Laos, 2003–2011 - Volume 20, Number 8—August 2014 - Emerging Infectious Disease journal - CDC



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Volume 20, Number 8—August 2014

Letter

Rickettsia felis Infections and Comorbid Conditions, Laos, 2003–2011

Tables

To the Editor: Fleaborne disease is highly prevalent in Laos, mainly attributed to murine typhus (Rickettsia typhi infection), transmitted by Xenopsylla cheopis fleas, but data on other fleaborne diseases are limited (1). We screened blood and cerebrospinal fluid (CSF) from participants in 2 large prospective studies in Laos forRickettsia spp. using a genus-specific 17-kDa-based Rickettsia real-time PCR assay, and positive results were confirmed by DNA sequencing (2,3). In samples from >2,500 patients (2,540 blood and 1,112 CSF), we detected 3 cases of sequence-confirmed R. felis infections.
A 50-year-old man, an official in Vientiane City, was admitted to a hospital with fever and headache in October, 2008. HIV infection and cryptococcal meningitis were diagnosed. Treatment with intravenous amphotericin B, then oral fluconazole, was successful; antiretroviral treatment was initiated 1 month after diagnosis. Among a panel of diagnostic PCRs, the CSF sample specimen tested positive for genus-specific 17-kDa-Rickettsiaquantitative PCR, but was negative for Orentia tsutsugamushi and R. typhi. DNA sequencing of 434 bp of the 17-kDa gene (Macrogen, Seoul, South Korea) revealed a 100% homology to the R. felis URRWXCal2 strain (Table).
R. felis positivity in CSF is rare; 4 incidents have been reported (3). The combined findings of R. felis infection and severe immunodeficiency in this case-patient led to a reevaluation of the 2 reported R. felis infections in Laos (2). Before this study, R. felis DNA or culture had not been handled in our facility. The interval between processing positive samples, dedicated separate areas for samples before and after PCR, and the low positivity rate make DNA contamination highly unlikely.
A 39-year-old housewife from Luang Namtha in northern Laos had a history of diabetes mellitus, which had been treated with glibenclamide. On arrival at the hospital in November, 2008, she had fever, headache, myalgia, and an eschar. She was empirically treated with doxycycline (Table). An eschar biopsy specimen was PCR-positive for Rickettsia spp. and O. tsutsugamushi; PCR of buffy coat detected O. tsutsugamushi DNA only (2). Molecular characterization included 17-kDa– and sca4- gene sequencing, which both revealed amplicons of 100% identity to the R. felis-URRWXCal2 strain. Serologic evidence for O. tsutsugamushi infection (scrub typhus) included a 4-fold rise in IgM and IgG titers, and IgM and IgG titers against typhus group rickettsiae, spotted fever group rickettsiae, and R. felis (isolate B377 in XTC-2 cells, Australian Rickettsial Reference Laboratory) were negative in admission and convalescent-phase samples (6-day interval) (Table).
A 13-year-old boy from Salavan, in southern Laos, had fever, headache, and nonspecific symptoms in July, 2009. P. falciparum malaria and dengue were diagnosed, both confirmed by PCR (Table). PCR results for the buffy coat specimen were positive for the 17-kDa gene; subsequent sequencing confirmed Rfelis with 100% identity to the URRWXCal2 strain. The fever resolved after treatment with antimalarial drugs and ceftriaxone; neither would be expected to be efficacious for R. felis infection.
These data suggest that R. felis occurs in Laos, and is possibly emerging, but whether it results in clinical disease or commonly causes subclinical infection is unknown. The screened cohorts of consecutively enrolled patients with febrile illnesses across 3 diverse geographic regions are representative of etiologic agents of fever across Laos. PCR has previously been used for detection of R. felis and resulted in the discovery of a new R. felis-like organism in fleas in Kenya, Candidatus Rickettsia asemboensis (4). Reports from Southeast Asia suggest that R. felis is not a common cause of febrile illness (1,2), which contrasts with findings in Kenya, where R. felis was found in ≈7% of febrile patients (4,5), and also in ≈% of afebrile patients (5).
The high R. felis carriage rate in fleas found in Laos (77% overall; 53% in Ctenocephalides felis felis, 89% in C. f. orientis) contrasts strongly with the apparent low incidence of R. felis human infections (6). Among febrile hospitalized patients in Vientiane, 1 case of R. felis infection was serologically diagnosed by using species-specific cross-absorption (1). Seroprevalence studies in the region could elucidate exposure to this pathogen and unmask subclinical infections missed in fever etiology studies.
The 3 patients from Laos described herein had comorbidities associated with variable degrees of immunodeficiency (HIV infection and malaria with cellular and humoral deficiencies, diabetes with functional neutrophil/macrophage impairment) (7,8). R. felis infections have not been associated with immunosuppression, but few investigations of this possible association have been published. Of the 3 patients, the woman and the boy had other vectorborne infections: scrub typhus, transmitted by Leptotrombidium mites, and P. falciparum malaria and dengue, transmitted by Anopheles andAedes mosquitoes, respectively. Recent reports described R. felis within a great diversity of vectors, including mites in South Korea and Anopheles andAedes mosquitoes in Africa (9,10).
More work is needed on the role of non-flea vectors in transmission of R. felis and the consequences this may have in terms of mixed infections of diverse vectorborne pathogens. The rare detection of R. felis in patients, combined with high flea carriage rates, unusual signs and symptoms linked to immunodeficiencies or multiple infections, and reports from Africa describing R. felis in asymptomatic patients, underscore the need for further investigations into the organism's natural history and its uncertain role as a pathogen.
Sabine Dittrich, Koukeo Phommasone, Tippawan Anantatat, Phonepasith Panyanivong, GA1/4nther Slesak, Stuart D. Blacksell, Audrey Dubot-PA(c)rA"s, JosA(c)e Castonguay-Vanier, John Stenos, Paul N. Newton, and Daniel H. ParisComments to Author 
Author affiliations: Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Mahosot Hospital, Vientiane, Laos (S. Dittrich, K. Phommasone, P. Panyanivong, S.D. Blacksell, A. Dubot-PA(c)rA"s, J. Castonguay-Vanier, P.N. Newton, D.H. Paris)Nuffield Department of Medicine, University of Oxford, Oxford, UK (S. Dittrich, S.D. Blacksell, A. Dubot-PA(c)rA"s, J. Castonguay-Vanier, P.N. Newton, D.H. Paris)Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand (T. Anantatat, S.D. Blacksell, D.H. Paris)Service Fraternel d�?(tm)Entraide�?"Laos Medical Projects, Luang Namtha, Laos (G. Slesak)Tropenklinik Paul-Lechler-Krankenhaus, TA1/4bingen, Germany (G. Slesak)Aix Marseille University, Medical University, Marseille, France (A. Dubot-PA(c)rA"s)The Geelong Hospital, Geelong, Victoria, Australia (J. Stenos)

Acknowledgments

We thank the patients and the families of those who participated in the studies. We also thank Rattanaphone Phetsouvanh, Mayfong Mayxay, and the staff of Mahosot Hospital, with special appreciation to the Microbiology Laboratory and Luang Nam Tha. We thank the Salavan Hospital directors and staff, especially Phouvieng Douangdala, Saythong Inthalath, and Phoutthalavanh Souvannasing. We also thank Ampai Tanganuchitcharnchai and Suthatip Jintawon for performing the IFAs.
Funding for this study was provided by the Wellcome Trust of Great Britain.

References

  1. Phongmany SRolain JMPhetsouvanh RBlacksell SDSoukkhaseum VRasachack BRickettsial infections and fever, Vientiane, Laos. Emerg Infect Dis2006;12:256–62DOIPubMed
  2. Mayxay MCastonguay-Vanier JChansamouth V. Dubot- PA(c)rA(c)s A, Paris DH, Phetsouvanh R, et al. Causes of non-malarial fever in Laos: a prospective study. Lancet Glob Health. 2013;1:e4654.
  3. Nilsson KWallmenius KHartwig SNorlander TPahlson CBell's palsy and sudden deafness associated with Rickettsia spp. infection in Sweden. A retrospective and prospective serological survey including PCR findings. Eur J Neurol2014;21:20614DOIPubMed
  4. Jiang JMaina ANKnobel DLCleaveland SLaudisoit AWamburu KMolecular detection of Rickettsia felis and Candidatus Rickettsia asemboensis in fleas from human habitats, Asembo, Kenya. Vector Borne Zoonotic Dis2013;13:5508DOIPubMed
  5. Maina ANKnobel DLJiang JHalliday JFeikin DRCleaveland SRickettsia felis infection in febrile patients, western Kenya, 20072010. Emerg Infect Dis2012;18:32831DOIPubMed
  6. Kernif TSocolovschi CWells KLakim MBInthalad SSlesak GBartonella and Rickettsia in arthropods from the Lao PDR and from Borneo, Malaysia. Comp Immunol Microbiol Infect Dis2012;35:517DOIPubMed
  7. Joshi NCaputo GMWeitekamp MRKarchmer AWInfections in patients with diabetes mellitus. N Engl J Med1999;341:190612.DOIPubMed
  8. Greenwood BMBradley-Moore AMBryceson ADPalit AImmunosuppression in children with malaria. Lancet1972;1:16972.DOIPubMed
  9. Socolovschi CPages FNdiath MORatmanov PRaoult DRickettsia species in African Anopheles mosquitoes. PLoS ONE2012;7:e48254.DOIPubMed
  10. Choi YJLee EMPark JMLee KMHan SHKim JKMolecular detection of various rickettsiae in mites (acari: trombiculidae) in southern Jeolla Province, Korea. Microbiol Immunol2007;51:30712DOIPubMed

Table

Suggested citation for this article: Dittrich S, Phommasone K, Anantatat T, Panyanivong P, Slesak G, Blacksell SD, et al. Rickettsia felis infections and comorbid conditions, Laos 20032011 [letter]. Emerg Infect Dis. 2014 Aug [date cited]. http://dx.doi.org/10.3201/eid2008.131308


DOI: 10.3201/eid2008.131308

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