Friday, July 19, 2019

Bejel, a Nonvenereal Treponematosis, among Men Who Have Sex with Men, Japan - Volume 25, Number 8—August 2019 - Emerging Infectious Diseases journal - CDC

Bejel, a Nonvenereal Treponematosis, among Men Who Have Sex with Men, Japan - Volume 25, Number 8—August 2019 - Emerging Infectious Diseases journal - CDC

Issue Cover for Volume 25, Number 8—August 2019

Volume 25, Number 8—August 2019
Research Letter

Bejel, a Nonvenereal Treponematosis, among Men Who Have Sex with Men, Japan

Takuya KawahataComments to Author , Yoko Kojima, Keiichi Furubayashi, Koh Shinohara, Tsunehiro Shimizu, Jun Komano, Haruyo Mori, and Kazushi Motomura
Author affiliations: Osaka Institute of Public Health, Osaka, Japan (T. Kawahata, Y. Kojima, H. Mori, K. Motomura)Sonezaki Furubayashi Clinic, Osaka (K. Furubayashi)Kyoto City Hospital, Kyoto, Japan (K. Shinohara, T. Shimizu)Nagoya Medical Center, Nagoya, Japan (J. Komano)Osaka University of Pharmaceutical Sciences, Takatsuki, Japan (J. Komano)

Abstract

Bejel, an endemic treponematosis caused by infection with Treponema pallidum subspecies endemicum, has not been reported in eastern Asia and the Pacific region. We report local spread of bejel among men who have sex with men in Japan. Spread was complicated by venereal syphilis.
Treponema pallidum subspecies pallidum is the causative agent of venereal syphilis. Globally, syphilis remains a disease of heterosexual persons in low-to-middle-income countries. Epidemics of syphilis among men who have sex with men (MSM) occur in high-income settings (1). Other Treponema species cause nonvenereal endemic treponematosis (also called bejel, nonvenereal syphilis, or endemic syphilis, caused by T. pallidum subsp. endemicum), yaws (T. pallidum subsp. pertenue), and pinta (T. carateum). These pathogens are morphologically and serologically indistinguishable (2). Clinically, there is little need to differentiate them. However, it is useful to differentiate them from a public health standpoint because their infection routes vary. For this purpose, a nucleic acid test is useful (3).
Bejel was eradicated in Europe in the 20th century but was prevalent there in the 16th century (4). Bejel is still prevalent in dry and hot areas, such as the Sahel region in western Africa, part of Botswana, Zimbabwe, and the Arabian Peninsula (5). The main route of transmission is direct skin-to-skin contact. Bejel can be transmitted sexually, but this route has not been studied because bejel affects mainly children. Only a few case reports of bejel have been reported in non-endemic areas since 1999, including France (3), Canada (6), and Cuba (7). Bejel in France was attributed to an imported case from Pakistan, and in Canada to an imported case from Senegal, whereas transmission in Cuba was regionalized. No patient with nonvenereal treponematosis has been reported in Japan.
In Japan, syphilis has been reemerging since 2010 (8). However, little attention has been paid to nonvenereal treponematosis. We thus conducted a molecular epidemiologic study to characterize the genotypes of T. pallidum subsp. pallidum among patients with venereal syphilis after 2011 (9).
The study protocol was approved by the Ethical Review Board of Osaka Institute of Public Health. We tested specimens from patients suspected of having or given a diagnosis of syphilis by using nucleic acid amplification tests for T. pallidum subsp. pallidum specific for the TpN47 and polA gene regions. We performed molecular genotyping of T. pallidum subsp. pallidum strains based on the nucleic acid sequences of the tp0548 and tp0856 gene regions (3,10).
Thumbnail of Phylogenetic tree for tp0548–tp0856 gene regions (1173–1233 bp) of clinical isolates of Treponema pallidum from Japan (bold) and reference isolates. The tree was constructed by using MEGA6 (https://www.megasoftware.net) with the bootstrapping maximum-likelihood algorithm and the Tamura–Nei model. Numbers along branches indicate bootstrap values. Scale bar indicates nucleotide substitutions per site. Strains from this study were submitted to GenBank under the following accession numb
Figure. Phylogenetic tree for tp0548–tp0856 gene regions (1173–1233 bp) of clinical isolates of Treponema pallidumfrom Japan (bold) and reference isolates. The tree was constructed by using MEGA6 (https://www.megasoftware.netExternal Link) with the...
Phylogenetic analysis showed that, of 58 isolates from nucleic acid test–positive specimens, 5 isolates (8.6%) were T. pallidum subsp. endemicum and different from T. pallidum subsp. pallidum and T. pallidum subsp. pertenue. We concluded that the 5 patients from whom these strains were isolated had bejel (Figure).
All 5 bejel patients were men from Japan 20–40 years of age; all were MSM. One patient was identified in 2014, another 3 in 2017, and 1 patient in 2018. Two of the patients identified in 2017 were in the secondary stage of the disease; the other 3 were in the primary stage. Clinical manifestations of the 3 patients in the primary stage were penile erosion or ulcer. The 2 patients in the secondary stage had systemic rashes and lymphadenopathy, in addition to pubic and perineal symptoms.
For serologic tests at admission, the 3 primary-stage patients showed negative results for the rapid plasma reagin test (<1.0 unit). Of these patients, 2 showed negative results of the T. pallidum latex agglutination test (<10 units) and 1 had a titer of 35.7 units. The 2 secondary-stage patients had positive results for the rapid plasma reagin test, and their T. pallidum latex agglutination test values were 2.4 × 103 and 20.8 × 103 units.
The first patient lived in Yamaguchi Prefecture. The other 4 patients lived in the Kansai area, including Osaka, Kyoto, and Hyogo Prefectures. Although the residential geographic areas were remote, the suspected locale of treponemal infection was the Kansai area, namely the city centers of Osaka and Kyoto. The 2018 patient was HIV positive. None of the patients had a history of overseas travel for a long period. All 5 isolates had a mutation conferring azithromycin resistance. The 3 patients who were followedup responded well to standard therapy with penicillin.
These data strongly suggest that T. pallidum subsp. endemicum is transmitted domestically in Japan by MSM. Our findings provide molecular epidemiologic evidence for a local spread of T. pallidum subsp. endemicum in eastern Asia and the Pacific region.
Clinical manifestations of venereal syphilis and bejel are similar, especially in the early stage for adults, which makes diagnosis difficult (7). Infectious diseases that have been historically not considered to be sexually transmitted infections (STIs), such as amebiasis, hepatitis A, and shigellosis, often show manifestations of STIs. Likewise, bejel might be changing from an endemic tropical disease to a global STI.
Treatment for venereal syphilis is also effective for bejel. For the 5 patients we report, laboratory test results showed a strong correspondence to the stage of bejel disease progression. Clinicians should be aware of the spread of nonvenereal treponematosis worldwide, especially in low-prevalence areas. Nucleic acid tests that can differentiate T. pallidum strains might be helpful (3,10). Molecular epidemiology might help determine which populations are affected and provide an effective means to prevent the further spread of treponematosis.
Dr. Kawahata is a principal research scientist at the Osaka Institute of Public Health, Osaka, Japan. His primary research interests are HIV infections, sexually transmitted infections, and syphilis.

Acknowledgment

This study was partially supported by grants-in-aid for research on HIV/AIDS from the Ministry of Health, Labour and Welfare of Japan (grants H26-AIDS-006 and H29-AIDS-007) to T.K. and a grant from the Daido Life Welfare Foundation for Regional Health and Welfare Research in 2017 to Y.K.

References

  1. Fenton  KABreban  RVardavas  ROkano  JTMartin  TAral  Set al. Infectious syphilis in high-income settings in the 21st century.Lancet Infect Dis2008;8:24453DOIExternal LinkPubMedExternal Link
  2. Mitjà  OŠmajs  DBassat  QAdvances in the diagnosis of endemic treponematoses: yaws, bejel, and pinta. PLoS Negl Trop Dis2013;7:e2283DOIExternal LinkPubMedExternal Link
  3. Mikalová  LStrouhal  MOppelt  JGrange  PAJanier  MBenhaddou  Net al. Human Treponema pallidum 11q/j isolate belongs to subsp. endemicum but contains two loci with a sequence in TP0548 and TP0488 similar to subsp. pertenue and subsp. pallidum, respectively. PLoS Negl Trop Dis2017;11:e0005434DOIExternal LinkPubMedExternal Link
  4. Lipozenčić  JMarinović  BGruber  FEndemic syphilis in Europe. Clin Dermatol2014;32:21926DOIExternal LinkPubMedExternal Link
  5. Giacani  LLukehart  SAThe endemic treponematoses. Clin Microbiol Rev2014;27:89115DOIExternal LinkPubMedExternal Link
  6. Fanella  SKadkhoda  KShuel  MTsang  RLocal transmission of imported endemic syphilis, Canada, 2011. Emerg Infect Dis2012;18:10024DOIExternal LinkPubMedExternal Link
  7. Noda  AAGrillová  LLienhard  RBlanco  ORodríguez  IŠmajs  DBejel in Cuba: molecular identification of Treponema pallidumsubsp. endemicum in patients diagnosed with venereal syphilis. Clin Microbiol Infect2018;24:1210.e15DOIExternal LinkPubMedExternal Link
  8. Takahashi  TArima  YYamagishi  TNishiki  SKanai  MIshikane  Met al. Rapid increase in reports of syphilis associated with men who have sex with women and women who have sex with men, Japan, 2012 to 2016. Sex Transm Dis2018;45:13943DOIExternal LinkPubMedExternal Link
  9. Kojima  YFurubayashi  KKawahata  TMori  HKomano  JCirculation of distinct Treponema pallidum strains in individuals with heterosexual orientation and men who have sex with men. J Clin Microbiol2019;57:e0114818.PubMedExternal Link
  10. Staudová  BStrouhal  MZobaníková  MCejková  DFulton  LLChen  Let al. Whole genome sequence of the Treponema pallidumsubsp. endemicum strain Bosnia A: the genome is related to yaws treponemes but contains few loci similar to syphilis treponemes.PLoS Negl Trop Dis2014;8:e3261DOIExternal LinkPubMedExternal Link
Figure
Cite This Article

DOI: 10.3201/eid2508.181690
Original Publication Date: 7/1/2019

No comments:

Post a Comment