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Int J STD AIDS OnlineFirst, published on September 15, 2014 as doi:10.1177/0956462414551236
Original research article
Epidemiology of sexually transmitted infections in rural Haitian men
International Journal of STD & AIDS 0(0) 1–6 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0956462414551236 std.sagepub.com
Robert F Downey1,2, Donna Hammar1,3, Kathleen A Jobe1,4, Terri A Schmidt1,5, Lori Van Slyke1,6, Yassi Yassemi1,7 and Dana Zive5
Summary The study attempts to determine the prevalence of organisms associated with urethritis in men in rural southwestern Haiti and to determine the association with demographic, clinical and laboratory variables. A standardised oral interview was conducted; genital examinations were done; urethral swabs were collected for nucleic acid amplification testing, and first void urine was obtained for urinalysis. The mean participant age was 54; 88.8% lived in a rural area. Swabs were positive for Trichomonas vaginalis in 13.7% (28/205), Mycoplasma genitalium in 6.3% (13/205), Chlamydia trachomatis in 4.4% (9/205) and Neisseria gonorrhoeae in 0% (0/205). Subjects who never reported using condoms were nearly 3.5 times more likely to have any positive swab result (OR: 3.46, 95% CI 1.31–9.14). Subjects who reported their partners had other sexual partners or were unsure were more than three times likely to have any positive swab result (OR: 3.44, 95% CI 1.33–8.92). Infections with Trichomonas vaginalis and Mycoplasma genitalium were the most common.
Keywords Haiti, urethritis, prevalence, screening, treatment, chlamydia, gonorrhoeae, Mycoplasma genitalium, trichomonas, urine, men, leukocyte esterase test Date received: 26 June 2014; accepted: 14 August 2014
Introduction Urethritis in men is an important international public health concern because untreated infections with Neisseria gonorrhoeae and Chlamydia trachomatis may progress to epididymitis, orchitis and infertility. These organisms can also be sexually transmitted to women causing vaginitis, pelvic inflammatory disease (PID), infertility and increased incidence of ectopic pregnancy. Additionally, the disruption of the urethral endothelium in urethritis may foster the spread of bloodborne pathogens such as HIV.1 Treatment of urethritis leads to decreases in HIV-1 expression in semen.2 Symptoms of urethritis include urethral discharge, dysuria, hematuria and penile itching. However, infections with Trichomonas vaginalis, Mycoplasma genitalium, C. trachomatis and N. gonorrhoeae can also be asymptomatic. M. genitalium is an emerging sexually transmitted pathogen that is a cause of urethritis in men and possible infertility.3 In women, it is implicated in cervicitis and PID.4 The Grand’Anse department is located in southwestern Haiti and has a population of approximately
433,000 people.5 The capital city of the Grand’Anse department is Je´re´mie with a county population of approximately 124,000 people.5 Residents in this region are largely subsistence farmers who have limited access to health care.
1
Seattle-King County Disaster Team, Seattle, WA, USA Laboratory Application Services, Sysmex America, Inc., San Diego, CA, USA 3 Providence Health and Services, North Coast Urgent Care Clinics, Seaside, OR, USA 4 Division of Emergency Medicine, University of Washington, Seattle, WA, USA 5 Department of Emergency Medicine, Oregon Health & Science University, Portland, OR, USA 6 Department of Social Work, MultiCare Health System, Tacoma, WA, USA 7 Summit Surgery Center, Flagstaff, AZ, USA 2
Corresponding author: Robert F Downey, Seattle-King County Disaster Team, PO Box 17306, Seattle, WA 98127 USA. Email: [email protected]
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The Seattle-King County Disaster Team has supported a rural primary care health clinic in the town of Leon in the mountains of the Grand’Anse department of Haiti since 1998. This clinic is associated with the local Catholic parish. Although the partnership exists with the Catholic parish, all residents of the area who come to the clinic are seen regardless of faith affiliation or belief system. Complaints of dysuria and urethral discharge are common complaints of men presenting at the clinic with approximately 10% of men complaining of these symptoms. While limited data exist regarding prevalence of sexually transmitted infections (STIs) in women in Haiti, including a recently submitted study on the prevalence of sexually transmitted organisms in women in the Grand’Anse, no data exist regarding prevalence in Haitian men.6–8 Our study of women in the Grand’Anse department showed a 17.7% prevalence of T. vaginalis infection.9 The purpose of this study was to determine the prevalence of T. vaginalis, M. genitalium, C. trachomatis and N. gonorrhoeae in men in the Grand’Anse department and to evaluate the association with symptoms of urethritis, demographic results and laboratory findings.
Methodology Subjects A convenience sample of subjects presenting to a men’s health clinic during the week of 21 October 2013 was used. All men presenting to the clinic were screened and not only those with signs or symptoms of urethritis. The clinic and study were promoted by local health committee members, health workers, and announcements at the local church and school. After an explanation of the study in Creole, verbal consent was obtained because most of the potential subjects are non-literate. The Oregon Health & Science University Institutional Review Board approved the study and the consent procedures. (OHSU IRB Approval Number 00009987) Symptomatic subjects were treated according to existing clinic protocols based on history, examination findings and urinalysis results obtained during the clinic visit.
Study design Subjects were interviewed in Creole, the primary language in rural Haiti, by either a clinical social worker (LVS) with a local Haitian interpreter or a nurse practitioner (DH) fluent in Creole using a standardised questionnaire to obtain demographic information and sexual history. Subjects were also asked about symptoms of urethritis such as burning on urination or urethral discharge as well as genital lesions or sores.
Subjects were classified as living in an urban or rural area. Urban was defined as residing within the cities of Je´re´mie or Port au Prince. Rural was defined as residing outside of the cities of Je´re´mie or Port au Prince.
Laboratory analysis Subjects were instructed to not urinate for 1 h prior to being seen for examination. Urethral swab samples were obtained for nucleic acid amplification testing (NAAT) for N. gonorrhoeae, C. trachomatis, M. genitalium and T. vaginalis. First void urine samples were provided after physical examination and collection of urethral swabs. Urinalysis was done at the clinic on freshly collected urine samples by a trained laboratory professional according to manufacturer’s instructions and clinic protocols. Urinalysis was done using Multistix 10SG Reagent Strips read with a Clinitek 50 Urine Chemistry Analyzer (Siemens Healthcare Diagnostics, Tarrytown, New York). Urethral swab samples were obtained and shipped to the United States for NAAT testing. Samples were stored according to collection kit instructions and shipped to the United States for testing at a later date. NAAT samples were packed and shipped according to International Air Transport Association regulations. NAAT testing for N. gonorrhoeae, C. trachomatis, M. genitalium and T. vaginalis was done with the Gen-Probe APTIMA assays (Hologic Gen-Probe, Inc., San Diego, California).
Data analysis Descriptive univariate statistics (Chi square) were used to characterise the primary sample. Associations between demographic data and clinical findings with any positive swab result were assessed using logistic regression with all variables of interest. Analyses were conducted using IBM SPSS Statistics v.21 (IBM Corp., Armonk, New York).
Results Samples were collected, and interviews conducted on 205 subjects with a mean age of 54.0 years (range 18–93 years). Most (88.8%) lived in rural areas of the Grand’Anse department (Table 1). (Refer to Table 2 for sexual history summary data.) Swabs were positive for at least one organism in 18.5% (38/205) of the subjects, and 2.9% (6/205) were positive for two or more organisms: 13.7% (28/205) were positive for T. vaginalis, 6.3% (13/205) for M. genitalium, 4.4%, (9/205) for C. trachomatis, and 0% (0/205) for N. gonorrhoeae. Figure 1 shows the distribution of positive results by age group.
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Urinalysis found 22.5% (46/204) of the samples had positive (trace or greater) urine leukocyte esterase (LE). (One subject was unable to provide a urine sample.) Using an LE positive cutoff of trace to identify men with any positive NAAT swab test result, the sensitivity was 32.6% (95% CI 19.1–48.5%), specificity 81.1% (95% CI 74.2–86.9%), positive predictive value 31.8% (95% CI 18.6–47.6%) and negative predictive value 81.7% (95% CI 74.7–87.4%). (Two subjects with positive nitrite results and other symptoms suggesting a urinary tract infection were excluded from this analysis.)
We developed a logistic regression model to identify factors associated with increased likelihood of any positive swab result. The model controlled for age (over or under 31 years), urban or rural residence, relationship status, number of recent sexual partners, symptoms of urethritis, urine LE results, condom use, partner’s monogamy status and report that current sexual partner is from Port au Prince. The results of the model identified two primary factors associated with positive swab test results: never using condoms (OR: 3.46, 95% CI 1.31– 9.14) and report that partner has or may have other partners (OR: 3.44, 95% CI 1.33–8.92) (Table 3).
Table 1. Demographic information (n ¼ 205).
Discussion
Characteristic
Number/per cent
Range
Mean age (years) Rural residence Own a mobile phone Median travel time to clinic (min) Walked to clinic Took motorcycle or other vehicle to clinic
54.0 88.8% 66.8% 30 86.8% 13.2%
18–93 n/a n/a 0–420a n/a n/a
a
Many men could not indicate how long it took them to get to the clinic or simply stated ‘a long time’.
Somewhat surprisingly, we found no cases of N. gonorrhoeae in our sample. We also found a very low prevalence of N. gonorrhoeae in our previous study of women in this region.9 N. gonorrhoeae is a common cause of urethritis in the United States and Europe. In a US study of 768 men, the prevalence of N. gonorrhoeae was 21.6% in symptomatic and 1.4% in asymptomatic men.10 In 2012, the overall incidence of gonorrhoeae cases among men reported to the United States Centers for Disease Control and Prevention was 105.8 per 100,000 men.11 Gonococcal urethritis may be more common in certain regions of the developing world. In
Table 2. Sexual history information. Characteristic
Number/per cent
Range
Mean age of onset of sexual activity (years) Mean number of sexual partners in the last three months Mean number of lifetime sexual partners Paid for or exchanged something for sex Reported condom use Never used Sometimes used Always used Sexual partner has other partners or partner’s monogamy status is unknown Subject or partner has lived or worked in Port au Prince Subject reported burning on urination Subject reported urethral discharge Subject reported sores on penis Subject reported ANY of above symptoms Gender of partners Female only Both female and male Male only Not reported
19.4 1.3 12.9 38%
6–45 0–20 1–200 n/a
60% 32.7% 7.3% 25.4%
n/a n/a n/a n/a
32.2% 39.5% 9.8% 4.9% 42.9%
n/a n/a n/a n/a n/a
92.2% 6.3% 0% 1.5%
n/a n/a n/a n/a
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Figure 1. Positive results by subject age.
Table 3. Demographic and risk factors and positive swab test results. Factor
Odds ratio
95% confidence interval
Subject reported never having used condomsa Sexual partner has other partners or partners monogamy status is unknowna Self-reported symptoms of STI Subject or partner has lived or worked in Port-au-Prince Age 2 sexual partners in the last three months Urban residence location Married or Plasaj
3.46 3.44
1.31–9.14 1.33–8.92
1.07 0.61 2.35 1.61 0.98 1.77 0.49
0.50–2.27 0.25–1.52 0.66–8.42 0.70–3.73 0.25–3.87 0.50–6.33 0.16–1.54
a
Significantly associated with any positive swab result.
a South African study, N. gonorrhoeae was detected in 62% of men with symptoms of urethritis.12 The low prevalence of N. gonorrhoeae in our sample may be related to the fact that subjects being tested were from a largely rural area and were an older group. C. trachomatis typically accounts for 30–50% of cases of non-gonococcal urethritis (NGU).13 Another US study of men with NGU reported the prevalence of C. trachomatis as 43%, M. genitalium 31% and T. vaginalis 13%.14 We found a C. trachomatis prevalence of 4.4%, again lower than reported US rates; however, we had both symptomatic and asymptomatic subjects included in the study group. The 6.3% prevalence of M. genitalium seen in this study is similar to prevalence rates seen elsewhere in the world.15 This organism is important because in addition to causing urethritis in men, it causes cervicitis
and PID in women.15–18 M. genitalium infection in women may also be a co-factor in acquisition of HIV infection.19 T. vaginalis is an important cause of NGU in Africa. In one study, it was the most common pathogen identified in urethral samples and found in 14% of symptomatic and 9% of asymptomatic men.20 We found a significant amount of T. vaginalis infection. The amount of trichomonas infection is not surprising considering the 17.7% prevalence of T. vaginalis we found in our previous study of women in this region. Until that study, local treatment protocols typically did not incorporate any treatment for trichomonas for men with urethritis. We considered LE as a surrogate marker because other studies have incorporated this simple test into STI screening algorithms for men.21 Although in
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univariate analysis it initially appeared that LE was associated with positive swab results, this did not hold true in the multivariate analysis where only use of condoms and if the subject’s partner has or may have other partners were associated with a positive swab result. This lends support to the value of education on condom use in decreasing transmission of these organisms. Current clinic treatment protocols are based on patient symptoms at presentation and World Health Organization syndromic treatment guidelines.22 The guidelines recommend treatment for N. gonorrhoeae and C. trachomatis in men with discharge and to consider treatment for T. vaginalis if symptoms persist or recur after treatment. Patients seen at the clinic often walk long distances to seek care and often cannot return for follow-up. The modifications to our clinic treatment protocols based on these data included adding 2 g of metronidazole as treatment for T. vaginalis in men as well as recommending 1 g of oral azithromycin for suspected C. trachomatis, rather than doxycycline. Azithromycin is at least 100-fold more active in vitro against M. genitalium than any of the fluoroquinolones or tetracyclines.23 In areas with a high prevalence of T. vaginalis, we feel consideration should be given to modifying syndromic treatment guidelines to include treatment for trichomoniasis along with N. gonorrhoeae and C. trachomatis on initial presentation for men with discharge or urethritis. Azithromycin is more expensive than doxycycline but is far more effective in the treatment of M. genitalium. Azithromycin is available locally and the treatment cost for 1 g of azithromycin ranges from 40 to 200 Haitian Gourdes (US $0.93–$4.65). In addition to providing coverage for both C. trachomatis and M. genitalium, this single dose of azithromycin has the advantage of use in directly observed therapy protocols for immediate on-site treatment. Metronidazole was also easily incorporated into our directly observed therapy regimen. Our experience at the Leon clinic suggests that patients often have difficulty completing treatment or returning for follow-up because of transportation or other difficulties. Patients sharing medicines with others or reselling them in the market is also common. When possible, we try to use protocols that allow for directly observed therapy at the provider station.
Limitations This study was limited by the logistical challenges of working in rural Haiti. Despite promotion of the clinic to younger men in the community, we did not have a large number of younger participants. Although the participants represented those patients normally seen
at the Leon clinic, inclusion of more participants from the urban center of Je´re´mie, as well as younger participants, may have added more value to this study. Testing participants for HIV, syphilis and viral hepatitis was not performed and may have added additional value to the study. STI prevalence in urban Haitian men is an important topic that would be valuable for additional study. In addition, although we had interpreters and one investigator who is fluent in Creole, there may have been cultural or language barriers in interpreting the questions. For example, one of the questions asked if the participant had ever paid for sex or exchanged something for sex. The interviewers found that many men had a difficult time understanding this question. The concept of paying for or exchanging something for sex typically elicited much discussion and commentary from the subjects during the interview.
Conclusion The study has produced accurate epidemiologic data regarding the causative agents of urethritis in southwestern Haiti. This information should help to guide clinical evaluation and treatment for clinicians working in this region. Acknowledgements The authors gratefully acknowledge the following individuals and organisations for their support of this study: the men in the Grand’Anse department who agreed to participate in the study; Hologic Gen-Probe, Inc. for providing molecular diagnostic testing supplies and services; Hardy Diagnostics for providing testing and sample collection supplies; Bette Gebrian, RN, Ph.D., MPH of the Haitian Health Foundation for manuscript review. The clinics in Leon would not be possible without our dedicated volunteers, the on-going financial and logistical support of the Seattle-King County Disaster Team or the financial support of St. Francis of Assisi Parish (Derwood, Maryland). The authors are grateful for their on-going support of the medical clinics.
Conflict of interest The authors declare no conflict of interest.
Funding SKCDT and St. Francis Parish did not provide any funding for this study. While they support the regular clinics (described previously in the acknowledgement section) they did not provide financial support for this special study. This study was separate from the regular clinics. The authors contributed for all costs associated with the study as stated. Any costs paid by SKCDT on behalf of the authors were reimbursed to SKCDT. Funding for transportation, medicine, interpreters, and clinic supplies was provided by the authors.
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References 1. Brill J. Diagnosis and treatment of urethritis in men. Am Fam Physician 2010; 81: 873–878. 2. Cohen M, Hoffman I, Royce R, et al. Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1. Lancet 1997; 349: 1868–1873. 3. McGowin C and Anderson-Smits C. Mycoplasma genitalium: an emerging cause of sexually transmitted disease in women. PLoS Pathog 2011; 7: e1001324. 4. Daley G, Russell D, Tabrizi S, et al. Mycoplasma genitalium: a review. Int J STD AIDS 2014; 25: 475–487. 5. Haiti Ministe`re de la Sante´ Publique et de la Population. 2010 estimate, De´partement Sanitaire de la Grand’Anse, Etat Des Lieux de la Situation du De´partement: Rapport Final. 2011. 6. Fitzgerald D, Behets F, Caliendo A, et al. Economic hardship and sexually transmitted diseases in Haiti’s rural Artibonite Valley. Am J Trop Med Hyg 2000; 62: 496–501. 7. Behets F, Desormeaux J, Joseph D, et al. Control of sexually transmitted diseases in Haiti: results and implications of a baseline study among pregnant women living in Cite´ Soleil shantytowns. J Infect Dis 1995; 172: 764–771. 8. Fawzi M, Lambert W, Singler J, et al. Identification of chlamydia and gonorrhoea among women in rural Haiti: maximising access to treatment in a resource poor setting. Sex Transm Infect 2006; 82: 175–181. 9. Jobe K, Downey R, Hammar D, et al. Epidemiology of sexually transmitted infections in rural Haiti: the Grand’Anse Women’s Health Study. Manuscript submitted for publication. 2013. 10. Taylor S, Liesenfeld O, Lillis R, et al. Evaluation of the Roche Cobas CT/NG test for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in male urine. Sex Transm Dis 2012; 39: 543–549. 11. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2012. Atlanta: U.S. Department of Health and Human Services, 2013. 12. Black V, Magooa P, Radebe F, et al. The detection of urethritis pathogens among patients with the male urethritis syndrome, genital ulcer syndrome and HIV voluntary counselling and testing clients: should South Africa’s
13.
14.
15. 16.
17.
18.
19.
20.
21.
22.
23.
syndromic management approach be revised? Sex Transm Infect 2008; 84: 254–258. Bradshaw C, Tabrizi S, Read T, et al. Etiologies of nongonococcal urethritis: bacteria, viruses, and the association with orogenital exposure. J Infect Dis 2006; 193: 336–345. Schwebke J, Rompalo A, Taylor S, et al. Re-evaluating the treatment of nongonococcal urethritis: emphasizing emerging pathogens–a randomized clinical trial. Clin Infect Dis 2011; 52: 163–170. Taylor-Robinson D. Mycoplasma genitalium–an up-date. Int J STD AIDS 2002; 13: 145–151. Hamasuna R. Mycoplasma genitalium in male urethritis: diagnosis and treatment in Japan. Int J Urol 2013; 20: 676–684. Mezzini T, Waddell R, Douglas R, et al. Mycoplasma genitalium: prevalence in men presenting with urethritis to a South Australian public sexual health clinic. Intern Med J 2013; 43: 494–500. Bjartling C, Osser S and Persson K. Mycoplasma genitalium in cervicitis and pelvic inflammatory disease among women at a gynecologic outpatient service. Am J Obstet Gynecol 2012; 206: 476–471. Vandepitte J, Weiss H, Bukenya J, et al. Association between Mycoplasma genitalium infection and HIV acquisition among female sex workers in Uganda: evidence from a nested case–control study. Sex Transm Infect. Epub ahead of print 31 March 2014. DOI: 10.1136/sextrans-2013-051467. Watson-Jones D, Mugeye K, Mayaud P, et al. High prevalence of trichomoniasis in rural men in Mwanza, Tanzania: results from a population based study. Sex Transm Infect 2000; 76: 355–362. Tyndall M, Nasio J, Maitha G, et al. Leukocyte esterase urine strips for the screening of men with urethritis–use in developing countries. Genitourin Med 1994; 70: 3–6. World Health Organization. Sexually transmitted and other reproductive tract infections A guide to essential practice [Internet]. 1st ed. Geneva: World Health Organization, Department of Reproductive Health and Research, http://whqlibdoc.who.int/publications/2005/ 9241592656.pdf (2005, accessed 22 June 2014). Taylor-Robinson D and Jensen J. Mycoplasma genitalium: from Chrysalis to multicolored butterfly. Clin Microbiol Rev 2011; 24: 498–514.
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Int J STD AIDS OnlineFirst, published on September 15, 2014 as doi:10.1177/0956462414551236
Original research article
Epidemiology of sexually transmitted infections in rural Haitian men
International Journal of STD & AIDS 0(0) 1–6 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0956462414551236 std.sagepub.com
Robert F Downey1,2, Donna Hammar1,3, Kathleen A Jobe1,4, Terri A Schmidt1,5, Lori Van Slyke1,6, Yassi Yassemi1,7 and Dana Zive5
Summary The study attempts to determine the prevalence of organisms associated with urethritis in men in rural southwestern Haiti and to determine the association with demographic, clinical and laboratory variables. A standardised oral interview was conducted; genital examinations were done; urethral swabs were collected for nucleic acid amplification testing, and first void urine was obtained for urinalysis. The mean participant age was 54; 88.8% lived in a rural area. Swabs were positive for Trichomonas vaginalis in 13.7% (28/205), Mycoplasma genitalium in 6.3% (13/205), Chlamydia trachomatis in 4.4% (9/205) and Neisseria gonorrhoeae in 0% (0/205). Subjects who never reported using condoms were nearly 3.5 times more likely to have any positive swab result (OR: 3.46, 95% CI 1.31–9.14). Subjects who reported their partners had other sexual partners or were unsure were more than three times likely to have any positive swab result (OR: 3.44, 95% CI 1.33–8.92). Infections with Trichomonas vaginalis and Mycoplasma genitalium were the most common.
Keywords Haiti, urethritis, prevalence, screening, treatment, chlamydia, gonorrhoeae, Mycoplasma genitalium, trichomonas, urine, men, leukocyte esterase test Date received: 26 June 2014; accepted: 14 August 2014
Introduction Urethritis in men is an important international public health concern because untreated infections with Neisseria gonorrhoeae and Chlamydia trachomatis may progress to epididymitis, orchitis and infertility. These organisms can also be sexually transmitted to women causing vaginitis, pelvic inflammatory disease (PID), infertility and increased incidence of ectopic pregnancy. Additionally, the disruption of the urethral endothelium in urethritis may foster the spread of bloodborne pathogens such as HIV.1 Treatment of urethritis leads to decreases in HIV-1 expression in semen.2 Symptoms of urethritis include urethral discharge, dysuria, hematuria and penile itching. However, infections with Trichomonas vaginalis, Mycoplasma genitalium, C. trachomatis and N. gonorrhoeae can also be asymptomatic. M. genitalium is an emerging sexually transmitted pathogen that is a cause of urethritis in men and possible infertility.3 In women, it is implicated in cervicitis and PID.4 The Grand’Anse department is located in southwestern Haiti and has a population of approximately
433,000 people.5 The capital city of the Grand’Anse department is Je´re´mie with a county population of approximately 124,000 people.5 Residents in this region are largely subsistence farmers who have limited access to health care.
1
Seattle-King County Disaster Team, Seattle, WA, USA Laboratory Application Services, Sysmex America, Inc., San Diego, CA, USA 3 Providence Health and Services, North Coast Urgent Care Clinics, Seaside, OR, USA 4 Division of Emergency Medicine, University of Washington, Seattle, WA, USA 5 Department of Emergency Medicine, Oregon Health & Science University, Portland, OR, USA 6 Department of Social Work, MultiCare Health System, Tacoma, WA, USA 7 Summit Surgery Center, Flagstaff, AZ, USA 2
Corresponding author: Robert F Downey, Seattle-King County Disaster Team, PO Box 17306, Seattle, WA 98127 USA. Email: [email protected]
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The Seattle-King County Disaster Team has supported a rural primary care health clinic in the town of Leon in the mountains of the Grand’Anse department of Haiti since 1998. This clinic is associated with the local Catholic parish. Although the partnership exists with the Catholic parish, all residents of the area who come to the clinic are seen regardless of faith affiliation or belief system. Complaints of dysuria and urethral discharge are common complaints of men presenting at the clinic with approximately 10% of men complaining of these symptoms. While limited data exist regarding prevalence of sexually transmitted infections (STIs) in women in Haiti, including a recently submitted study on the prevalence of sexually transmitted organisms in women in the Grand’Anse, no data exist regarding prevalence in Haitian men.6–8 Our study of women in the Grand’Anse department showed a 17.7% prevalence of T. vaginalis infection.9 The purpose of this study was to determine the prevalence of T. vaginalis, M. genitalium, C. trachomatis and N. gonorrhoeae in men in the Grand’Anse department and to evaluate the association with symptoms of urethritis, demographic results and laboratory findings.
Methodology Subjects A convenience sample of subjects presenting to a men’s health clinic during the week of 21 October 2013 was used. All men presenting to the clinic were screened and not only those with signs or symptoms of urethritis. The clinic and study were promoted by local health committee members, health workers, and announcements at the local church and school. After an explanation of the study in Creole, verbal consent was obtained because most of the potential subjects are non-literate. The Oregon Health & Science University Institutional Review Board approved the study and the consent procedures. (OHSU IRB Approval Number 00009987) Symptomatic subjects were treated according to existing clinic protocols based on history, examination findings and urinalysis results obtained during the clinic visit.
Study design Subjects were interviewed in Creole, the primary language in rural Haiti, by either a clinical social worker (LVS) with a local Haitian interpreter or a nurse practitioner (DH) fluent in Creole using a standardised questionnaire to obtain demographic information and sexual history. Subjects were also asked about symptoms of urethritis such as burning on urination or urethral discharge as well as genital lesions or sores.
Subjects were classified as living in an urban or rural area. Urban was defined as residing within the cities of Je´re´mie or Port au Prince. Rural was defined as residing outside of the cities of Je´re´mie or Port au Prince.
Laboratory analysis Subjects were instructed to not urinate for 1 h prior to being seen for examination. Urethral swab samples were obtained for nucleic acid amplification testing (NAAT) for N. gonorrhoeae, C. trachomatis, M. genitalium and T. vaginalis. First void urine samples were provided after physical examination and collection of urethral swabs. Urinalysis was done at the clinic on freshly collected urine samples by a trained laboratory professional according to manufacturer’s instructions and clinic protocols. Urinalysis was done using Multistix 10SG Reagent Strips read with a Clinitek 50 Urine Chemistry Analyzer (Siemens Healthcare Diagnostics, Tarrytown, New York). Urethral swab samples were obtained and shipped to the United States for NAAT testing. Samples were stored according to collection kit instructions and shipped to the United States for testing at a later date. NAAT samples were packed and shipped according to International Air Transport Association regulations. NAAT testing for N. gonorrhoeae, C. trachomatis, M. genitalium and T. vaginalis was done with the Gen-Probe APTIMA assays (Hologic Gen-Probe, Inc., San Diego, California).
Data analysis Descriptive univariate statistics (Chi square) were used to characterise the primary sample. Associations between demographic data and clinical findings with any positive swab result were assessed using logistic regression with all variables of interest. Analyses were conducted using IBM SPSS Statistics v.21 (IBM Corp., Armonk, New York).
Results Samples were collected, and interviews conducted on 205 subjects with a mean age of 54.0 years (range 18–93 years). Most (88.8%) lived in rural areas of the Grand’Anse department (Table 1). (Refer to Table 2 for sexual history summary data.) Swabs were positive for at least one organism in 18.5% (38/205) of the subjects, and 2.9% (6/205) were positive for two or more organisms: 13.7% (28/205) were positive for T. vaginalis, 6.3% (13/205) for M. genitalium, 4.4%, (9/205) for C. trachomatis, and 0% (0/205) for N. gonorrhoeae. Figure 1 shows the distribution of positive results by age group.
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Urinalysis found 22.5% (46/204) of the samples had positive (trace or greater) urine leukocyte esterase (LE). (One subject was unable to provide a urine sample.) Using an LE positive cutoff of trace to identify men with any positive NAAT swab test result, the sensitivity was 32.6% (95% CI 19.1–48.5%), specificity 81.1% (95% CI 74.2–86.9%), positive predictive value 31.8% (95% CI 18.6–47.6%) and negative predictive value 81.7% (95% CI 74.7–87.4%). (Two subjects with positive nitrite results and other symptoms suggesting a urinary tract infection were excluded from this analysis.)
We developed a logistic regression model to identify factors associated with increased likelihood of any positive swab result. The model controlled for age (over or under 31 years), urban or rural residence, relationship status, number of recent sexual partners, symptoms of urethritis, urine LE results, condom use, partner’s monogamy status and report that current sexual partner is from Port au Prince. The results of the model identified two primary factors associated with positive swab test results: never using condoms (OR: 3.46, 95% CI 1.31– 9.14) and report that partner has or may have other partners (OR: 3.44, 95% CI 1.33–8.92) (Table 3).
Table 1. Demographic information (n ¼ 205).
Discussion
Characteristic
Number/per cent
Range
Mean age (years) Rural residence Own a mobile phone Median travel time to clinic (min) Walked to clinic Took motorcycle or other vehicle to clinic
54.0 88.8% 66.8% 30 86.8% 13.2%
18–93 n/a n/a 0–420a n/a n/a
a
Many men could not indicate how long it took them to get to the clinic or simply stated ‘a long time’.
Somewhat surprisingly, we found no cases of N. gonorrhoeae in our sample. We also found a very low prevalence of N. gonorrhoeae in our previous study of women in this region.9 N. gonorrhoeae is a common cause of urethritis in the United States and Europe. In a US study of 768 men, the prevalence of N. gonorrhoeae was 21.6% in symptomatic and 1.4% in asymptomatic men.10 In 2012, the overall incidence of gonorrhoeae cases among men reported to the United States Centers for Disease Control and Prevention was 105.8 per 100,000 men.11 Gonococcal urethritis may be more common in certain regions of the developing world. In
Table 2. Sexual history information. Characteristic
Number/per cent
Range
Mean age of onset of sexual activity (years) Mean number of sexual partners in the last three months Mean number of lifetime sexual partners Paid for or exchanged something for sex Reported condom use Never used Sometimes used Always used Sexual partner has other partners or partner’s monogamy status is unknown Subject or partner has lived or worked in Port au Prince Subject reported burning on urination Subject reported urethral discharge Subject reported sores on penis Subject reported ANY of above symptoms Gender of partners Female only Both female and male Male only Not reported
19.4 1.3 12.9 38%
6–45 0–20 1–200 n/a
60% 32.7% 7.3% 25.4%
n/a n/a n/a n/a
32.2% 39.5% 9.8% 4.9% 42.9%
n/a n/a n/a n/a n/a
92.2% 6.3% 0% 1.5%
n/a n/a n/a n/a
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Figure 1. Positive results by subject age.
Table 3. Demographic and risk factors and positive swab test results. Factor
Odds ratio
95% confidence interval
Subject reported never having used condomsa Sexual partner has other partners or partners monogamy status is unknowna Self-reported symptoms of STI Subject or partner has lived or worked in Port-au-Prince Age 2 sexual partners in the last three months Urban residence location Married or Plasaj
3.46 3.44
1.31–9.14 1.33–8.92
1.07 0.61 2.35 1.61 0.98 1.77 0.49
0.50–2.27 0.25–1.52 0.66–8.42 0.70–3.73 0.25–3.87 0.50–6.33 0.16–1.54
a
Significantly associated with any positive swab result.
a South African study, N. gonorrhoeae was detected in 62% of men with symptoms of urethritis.12 The low prevalence of N. gonorrhoeae in our sample may be related to the fact that subjects being tested were from a largely rural area and were an older group. C. trachomatis typically accounts for 30–50% of cases of non-gonococcal urethritis (NGU).13 Another US study of men with NGU reported the prevalence of C. trachomatis as 43%, M. genitalium 31% and T. vaginalis 13%.14 We found a C. trachomatis prevalence of 4.4%, again lower than reported US rates; however, we had both symptomatic and asymptomatic subjects included in the study group. The 6.3% prevalence of M. genitalium seen in this study is similar to prevalence rates seen elsewhere in the world.15 This organism is important because in addition to causing urethritis in men, it causes cervicitis
and PID in women.15–18 M. genitalium infection in women may also be a co-factor in acquisition of HIV infection.19 T. vaginalis is an important cause of NGU in Africa. In one study, it was the most common pathogen identified in urethral samples and found in 14% of symptomatic and 9% of asymptomatic men.20 We found a significant amount of T. vaginalis infection. The amount of trichomonas infection is not surprising considering the 17.7% prevalence of T. vaginalis we found in our previous study of women in this region. Until that study, local treatment protocols typically did not incorporate any treatment for trichomonas for men with urethritis. We considered LE as a surrogate marker because other studies have incorporated this simple test into STI screening algorithms for men.21 Although in
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univariate analysis it initially appeared that LE was associated with positive swab results, this did not hold true in the multivariate analysis where only use of condoms and if the subject’s partner has or may have other partners were associated with a positive swab result. This lends support to the value of education on condom use in decreasing transmission of these organisms. Current clinic treatment protocols are based on patient symptoms at presentation and World Health Organization syndromic treatment guidelines.22 The guidelines recommend treatment for N. gonorrhoeae and C. trachomatis in men with discharge and to consider treatment for T. vaginalis if symptoms persist or recur after treatment. Patients seen at the clinic often walk long distances to seek care and often cannot return for follow-up. The modifications to our clinic treatment protocols based on these data included adding 2 g of metronidazole as treatment for T. vaginalis in men as well as recommending 1 g of oral azithromycin for suspected C. trachomatis, rather than doxycycline. Azithromycin is at least 100-fold more active in vitro against M. genitalium than any of the fluoroquinolones or tetracyclines.23 In areas with a high prevalence of T. vaginalis, we feel consideration should be given to modifying syndromic treatment guidelines to include treatment for trichomoniasis along with N. gonorrhoeae and C. trachomatis on initial presentation for men with discharge or urethritis. Azithromycin is more expensive than doxycycline but is far more effective in the treatment of M. genitalium. Azithromycin is available locally and the treatment cost for 1 g of azithromycin ranges from 40 to 200 Haitian Gourdes (US $0.93–$4.65). In addition to providing coverage for both C. trachomatis and M. genitalium, this single dose of azithromycin has the advantage of use in directly observed therapy protocols for immediate on-site treatment. Metronidazole was also easily incorporated into our directly observed therapy regimen. Our experience at the Leon clinic suggests that patients often have difficulty completing treatment or returning for follow-up because of transportation or other difficulties. Patients sharing medicines with others or reselling them in the market is also common. When possible, we try to use protocols that allow for directly observed therapy at the provider station.
Limitations This study was limited by the logistical challenges of working in rural Haiti. Despite promotion of the clinic to younger men in the community, we did not have a large number of younger participants. Although the participants represented those patients normally seen
at the Leon clinic, inclusion of more participants from the urban center of Je´re´mie, as well as younger participants, may have added more value to this study. Testing participants for HIV, syphilis and viral hepatitis was not performed and may have added additional value to the study. STI prevalence in urban Haitian men is an important topic that would be valuable for additional study. In addition, although we had interpreters and one investigator who is fluent in Creole, there may have been cultural or language barriers in interpreting the questions. For example, one of the questions asked if the participant had ever paid for sex or exchanged something for sex. The interviewers found that many men had a difficult time understanding this question. The concept of paying for or exchanging something for sex typically elicited much discussion and commentary from the subjects during the interview.
Conclusion The study has produced accurate epidemiologic data regarding the causative agents of urethritis in southwestern Haiti. This information should help to guide clinical evaluation and treatment for clinicians working in this region. Acknowledgements The authors gratefully acknowledge the following individuals and organisations for their support of this study: the men in the Grand’Anse department who agreed to participate in the study; Hologic Gen-Probe, Inc. for providing molecular diagnostic testing supplies and services; Hardy Diagnostics for providing testing and sample collection supplies; Bette Gebrian, RN, Ph.D., MPH of the Haitian Health Foundation for manuscript review. The clinics in Leon would not be possible without our dedicated volunteers, the on-going financial and logistical support of the Seattle-King County Disaster Team or the financial support of St. Francis of Assisi Parish (Derwood, Maryland). The authors are grateful for their on-going support of the medical clinics.
Conflict of interest The authors declare no conflict of interest.
Funding SKCDT and St. Francis Parish did not provide any funding for this study. While they support the regular clinics (described previously in the acknowledgement section) they did not provide financial support for this special study. This study was separate from the regular clinics. The authors contributed for all costs associated with the study as stated. Any costs paid by SKCDT on behalf of the authors were reimbursed to SKCDT. Funding for transportation, medicine, interpreters, and clinic supplies was provided by the authors.
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References 1. Brill J. Diagnosis and treatment of urethritis in men. Am Fam Physician 2010; 81: 873–878. 2. Cohen M, Hoffman I, Royce R, et al. Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1. Lancet 1997; 349: 1868–1873. 3. McGowin C and Anderson-Smits C. Mycoplasma genitalium: an emerging cause of sexually transmitted disease in women. PLoS Pathog 2011; 7: e1001324. 4. Daley G, Russell D, Tabrizi S, et al. Mycoplasma genitalium: a review. Int J STD AIDS 2014; 25: 475–487. 5. Haiti Ministe`re de la Sante´ Publique et de la Population. 2010 estimate, De´partement Sanitaire de la Grand’Anse, Etat Des Lieux de la Situation du De´partement: Rapport Final. 2011. 6. Fitzgerald D, Behets F, Caliendo A, et al. Economic hardship and sexually transmitted diseases in Haiti’s rural Artibonite Valley. Am J Trop Med Hyg 2000; 62: 496–501. 7. Behets F, Desormeaux J, Joseph D, et al. Control of sexually transmitted diseases in Haiti: results and implications of a baseline study among pregnant women living in Cite´ Soleil shantytowns. J Infect Dis 1995; 172: 764–771. 8. Fawzi M, Lambert W, Singler J, et al. Identification of chlamydia and gonorrhoea among women in rural Haiti: maximising access to treatment in a resource poor setting. Sex Transm Infect 2006; 82: 175–181. 9. Jobe K, Downey R, Hammar D, et al. Epidemiology of sexually transmitted infections in rural Haiti: the Grand’Anse Women’s Health Study. Manuscript submitted for publication. 2013. 10. Taylor S, Liesenfeld O, Lillis R, et al. Evaluation of the Roche Cobas CT/NG test for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in male urine. Sex Transm Dis 2012; 39: 543–549. 11. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2012. Atlanta: U.S. Department of Health and Human Services, 2013. 12. Black V, Magooa P, Radebe F, et al. The detection of urethritis pathogens among patients with the male urethritis syndrome, genital ulcer syndrome and HIV voluntary counselling and testing clients: should South Africa’s
13.
14.
15. 16.
17.
18.
19.
20.
21.
22.
23.
syndromic management approach be revised? Sex Transm Infect 2008; 84: 254–258. Bradshaw C, Tabrizi S, Read T, et al. Etiologies of nongonococcal urethritis: bacteria, viruses, and the association with orogenital exposure. J Infect Dis 2006; 193: 336–345. Schwebke J, Rompalo A, Taylor S, et al. Re-evaluating the treatment of nongonococcal urethritis: emphasizing emerging pathogens–a randomized clinical trial. Clin Infect Dis 2011; 52: 163–170. Taylor-Robinson D. Mycoplasma genitalium–an up-date. Int J STD AIDS 2002; 13: 145–151. Hamasuna R. Mycoplasma genitalium in male urethritis: diagnosis and treatment in Japan. Int J Urol 2013; 20: 676–684. Mezzini T, Waddell R, Douglas R, et al. Mycoplasma genitalium: prevalence in men presenting with urethritis to a South Australian public sexual health clinic. Intern Med J 2013; 43: 494–500. Bjartling C, Osser S and Persson K. Mycoplasma genitalium in cervicitis and pelvic inflammatory disease among women at a gynecologic outpatient service. Am J Obstet Gynecol 2012; 206: 476–471. Vandepitte J, Weiss H, Bukenya J, et al. Association between Mycoplasma genitalium infection and HIV acquisition among female sex workers in Uganda: evidence from a nested case–control study. Sex Transm Infect. Epub ahead of print 31 March 2014. DOI: 10.1136/sextrans-2013-051467. Watson-Jones D, Mugeye K, Mayaud P, et al. High prevalence of trichomoniasis in rural men in Mwanza, Tanzania: results from a population based study. Sex Transm Infect 2000; 76: 355–362. Tyndall M, Nasio J, Maitha G, et al. Leukocyte esterase urine strips for the screening of men with urethritis–use in developing countries. Genitourin Med 1994; 70: 3–6. World Health Organization. Sexually transmitted and other reproductive tract infections A guide to essential practice [Internet]. 1st ed. Geneva: World Health Organization, Department of Reproductive Health and Research, http://whqlibdoc.who.int/publications/2005/ 9241592656.pdf (2005, accessed 22 June 2014). Taylor-Robinson D and Jensen J. Mycoplasma genitalium: from Chrysalis to multicolored butterfly. Clin Microbiol Rev 2011; 24: 498–514.
Downloaded from std.sagepub.com at CORNELL UNIV on June 23, 2015
