Epidemiology of Haemophilus ducreyi infections.
Haemophilus ducreyi, a fastidious gram-negative bacterium, is the causative agent of chancroid, a genital ulcer disease (GUD). The organism is usually spread during sexual intercourse through microabrasions, and the disease usually manifests as multiple painful superficial ulcers associated with inguinal lymphadenitis (1). As a result of the painful nature of the lesions, patients usually seek immediate treatment, and asymptomatic carriage is therefore uncommon (2). In addition to causing GUD, H. ducreyi has been found in several recent studies to be a major cause of chronic skin ulceration in children from developing countries (3-5).
The global epidemiology of chancroid is poorly documented, and it is not included in World Health Organization estimates of the global incidence of curable sexually transmitted infections (STIs). There are some key challenges in interpreting data on the epidemiology of H. ducreyi as a causative agent of GUD. First, genital herpes cases are easily misdiagnosed as chancroid on clinical examination. Thus, reports based only on clinical diagnosis can be erroneous. Second, laboratory culture is technically difficult, and the highly sensitive and specific nucleic acid amplification tests, such as PCR, are rarely available outside national reference laboratories or specialized STI research settings, which makes it difficult to confirm clinical diagnoses.
Determination of the true global incidence of chancroid is made more difficult by widespread adoption of syndromic management for bacterial GUD (i.e., treatment with antimicrobial drugs effective against syphilis and chancroid) without microbiological confirmation in many countries. Therefore, countries often report only the total number of GUD cases. In addition, identification of GUD etiology is rarely conducted in resource-poor countries to validate syndromic management for which chancroid could also be common.
Earlier studies of tropical skin ulcers did not generally test for H. ducreyi, with the exception of a small number of case reports. There are major limitations in describing the prevalence of causative agents in tropical skin lesions that typically occur in children in rural areas where there is no access to laboratory facilities. Pathogens such as Fusobacterium fusiforme, Staphylococcus aureus, and Streptococcus pyogenes have been reported from Gram staining of exudative material collected from tropical ulcers (6). However, cultures or PCR testing for definitive identification of fastidious pathogens involved has not been traditionally conducted. The purpose of this study was to improve our understanding of the epidemiology of H. ducreyi infection through a systematic review of published data on the proportion of genital and skin ulcers caused by this bacterium.
Search Strategy and Selection Criteria
A systematic review was conducted to identify all relevant studies that examined the etiology of GUD and nongenital skin ulcers involving H. ducreyi. We searched the National Library of Medicine through PubMed for "H. ducreyi," "chancroid," "genital ulcer," OR "skin ulceration" AND "proportion" OR "prevalence." The search was limited to studies published during January 1, 1980-December 31, 2014. In addition, we searched references of identified articles and other databases for other articles, and we reviewed abstracts, titles, and selected studies potentially containing information on chancroid epidemiology. We contacted researchers who were working with H. ducreyi to identify unpublished literature for inclusion. No language restrictions were set for searches.
The decision tree for inclusion or exclusion of articles is shown in Figure 1. We included studies if the proportion of etiologic agents in genital ulcers and nongenital skin ulcers, including H. ducreyi, was confirmed by laboratory techniques. Clinical diagnosis of chancroid is often based on the appearance of the ulcer, which is characteristically painful, purulent, and deep with ragged, undermined edges (Figure 2). However, because the appearance of these ulcers is similar to ulcers caused by other bacteria, clinical diagnosis can be nonspecific or insensitive and often requires laboratory confirmation (1). In addition, microscopy identification of typical morphologic features and serologic detection lack sensitivity and specificity (7,8). Thus, we only considered the following diagnostic methods as providing acceptable evidence of H. ducreyi infection: 1) isolation and identification by culture; or 2) PCR/real-time PCR.
Data Extraction and Synthesis
For all qualifying studies, extracted data included study country, year of study, diagnostic test used for confirmation, total number of H. ducreyi--positive cases, and sample size. Descriptive analyses of extracted data were conducted, and the number of H. ducreyi---confirmed cases was divided by the total number of cases to calculate the proportion of cases caused by H. ducreyi. Studies qualifying for data extraction were grouped into 2 categories: studies conducted before 2000 and studies after 2000. This date separates studies before and after widespread implementation of syndromic management of GUD. Study sites were also plotted by geographic region. No quantitative metaanalysis was undertaken.
We identified 277 records in which we found 46 articles describing 49 studies on GUD that met our inclusion criteria (Tables 1, 2; online Technical Appendix, http://wwwnc.cdc.gov/EID/artide/21/1/15-0425-TechappLpdf). All identified studies were based on cohorts of patients attending STI clinics, including 3 studies that enrolled only commercial sex workers. The age group for all cases was adults >18 years of age, except for 3 studies in Zambia, South Africa, and China, which included patients >16 years of age, and 1 study in Madagascar, which included patients >14 years of age. A total of 9 published studies and 2 unpublished reports that described nongenital skin ulcers caused by H. ducreyi were also included in our systematic review.
Laboratory confirmation of chancroid by PCR or culture was reported in 33 (67%) and 16 (32%) of the 49 studies, respectively. Of 16 studies that used culture, 7 (43%) used Mueller-Hinton agar with a nutritional supplement (e.g., Iso-Vitalex; Becton Dickinson, Franklin Lakes, NJ, USA), 1% used hemoglobin, and 5 (31%) used chocolate agar-based media; the remaining studies used other culture media. Five (31%) of 16 studies incubated agar plates at low temperatures (33[degrees]C-35[degrees]C), and 2 (12%) incubated plates at 36[degrees]C. Remaining articles did not specify incubating temperature.
Different PCR primer targets were used to amplify DNA sequences, including the 16S rRNA gene, the groEL gene, and the hemolysin gene. In addition to herpes simplex virus (HSV) PCR, 23 studies used a multiplex PCR that could simultaneously detect the 3 major causes of GUD (H. ducreyi, Treponema pallidum, and HSV types 1 and 2) (9). Studies encompassed 33 countries: 17 in Africa, 4 in Southeast Asia, 3 in Europe, 2 in the Middle East, 3 in South America, and 2 in the Caribbean, 1 in the United States, and 1 in Australia.
Incidence of Chancroid
Of 49 studies on chancroid analyzed, 35 were published during 1980-1999 (Table 1) and 14 during 2000-2014 (Table 2). In general, data showed a clear decrease in the proportion of chancroid during 1980-2014 in all areas analyzed (Figure 3).
During 1980-1999, the proportion of genital ulcers caused by H. ducreyi in these studies ranged from 0.0% in Thailand and China to 68.9% in South Africa (Table 1). Eleven (31.4%) studies reported high proportions (>40%) of cases of infection with H. ducreyi. All of these studies were conducted in countries in Africa (Cote d'Ivoire, Gambia, Kenya, Lesotho, Senegal, South Africa, and Swaziland). Slightly lower proportions (20%-40% of cases) were observed in 15 (42%) studies: 10 in countries in Africa, 2 in the United States during localized outbreaks, 1 in Jamaica, 1 in the Dominican Republic, and 1 in India.
Only a few countries reported low proportions (<10%) of genital ulcers infected with H. ducreyi, including Singapore (8.3%), Peru (5%), Greece (4.6%), the Netherlands (0.9%), United States (3.1%), and Saudi Arabia (2.1%). The study in Saudi Arabia was conducted during 1995-1999; a total of 27,490 patients were examined for STIs. Chancroid was diagnosed by culture and was reported as the least common STI during this survey. The only studies that reported no cases of chancroid were conducted in Thailand in 1996 and China in 1999; both studies used multiplex PCR for detection of GUD cases.
During 2000-2014, the proportion of H. ducreyi infections was low (<10%) in all studies analyzed, except for 1 study in Malawi (15%) (Table 2). Studies in 5 countries (Kenya, Namibia, Zambia, Brazil, and Australia) did not report any cases of infection with H. ducreyi. Other studies reporting proportions of infections <10% were conducted in Botswana, Mozambique, South Africa, Uganda, Pakistan, and France. No reports were found for studies in North America, Southeast Asia, or the Caribbean.
Nongenital Skin Infections with H. ducreyi
During 1988-2010, several case reports described 4 children and 4 adults with nonsexually transmitted infections with H. ducreyi that manifested as lower leg lesions but no genital lesions. The reported case-patients were travelers who had been to Fiji (reference 55 in online Technical Appendix), Samoa (reference 56 in online Technical Appendix), Vanuatu (reference 57 in online Technical Appendix), or Papua New Guinea (reference 58 in online Technical Appendix) (Table 3). Outside the south Pacific region, a 5-year-old refugee from Sudan who had lower leg ulceration was also given a diagnosis of infection with H. ducreyi (reference 59 in online Technical Appendix).
A cohort study conducted in Papua New Guinea in 2014 showed evidence that H. ducreyi is a major cause of chronic skin ulceration; H. ducreyi DNA was identified by PCR in 60.0% of skin lesions in children (3). Similar studies in other areas reported laboratory-confirmed skin ulcers in children caused by H. ducreyi in Papua New Guinea (reference 60 in online Technical Appendix), Solomon Islands (4), Vanuatu (C.Y. Chen, pers. comm.), and Ghana (5) (Table 3).
Our review confirmed 2 major findings. First, reduction in the proportion of genital ulcers caused by H. ducreyi has been sustained for the past decade and a half. Second, there is increasing evidence that H. ducreyi is a common and newly recognized causative agent of chronic skin ulceration in children from developing countries.
In the 1990s, the global prevalence of chancroid was estimated to be 7 million (11). Chancroid was one of the most prevalent GUDs, particularly in resource-poor countries in Africa, Asia, Latin America, and the Caribbean (1; reference 45 in online Technical Appendix). Recommendations to introduce syndromic management for treatment of GUD caused by bacteria were published by the World Health Organization in 1991 and fully implemented by 2000 (reference 61 in online Technical Appendix). Since that time, global incidence of GUDs, particularly chancroid, has decreased substantially, and genital herpes viruses (HSV-1 and HSV-2) have become the predominant cause of GUD (reference 47 in online Technical Appendix). Currently in Europe and the United States, chancroid is restricted to rare sporadic cases. Transmission of H. ducreyi remains ongoing in only a few countries that have limited access to health services (2; reference 60 in online Technical Appendix).
Our data show marked decreases in the proportion of GUD caused by H. ducreyi in several countries. Spinola et al. reported similar conclusions obtained from 25 PCR-based studies (reference 62 in online Technical Appendix). For example, in Botswana (10), Kenya, (14), and South Africa (23), the proportion of GUD caused by H. ducreyi decreased from 25%-69% to negligible (0.0%-1.2%) levels (10; references 42, 46 in online Technical Appendix). Studies in Zambia (reference 50 in online Technical Appendix), Namibia (reference 45 in online Technical Appendix), Brazil (reference 51 in online Technical Appendix), and China (30) did not report any cases of chancroid during 2000-2009. A study in Thailand reported elimination of chancroid by introduction of a condom use program in the 1990s (reference 63 in online Technical Appendix). Similar decreases have been reported from Cambodia and Sri Lanka, with rapid elimination of chancroid and congenital syphilis in most settings (reference 63 in online Technical Appendix). However, these findings should be interpreted with caution because, given the short duration of infectivity, even a low prevalence of H. ducreyi in a population with GUD implies that a reservoir of infected persons with a high rate of sex partners is present.
Recent research has identified H. ducreyi as a previously unrecognized cause of nongenital skin ulcers in tropical areas. In 2013-2015, six studies in Papua New Guinea (3; reference 60 in online Technical Appendix), the Solomon Islands (4), Vanuatu (C.Y. Chen et al., pers. comm.), and Ghana (5; C.Y. Chen et al., pers. comm.) showed that a high proportion of laboratory-confirmed skin ulcers were caused by H. ducreyi. Nearly half of the 690 enrolled patients with ulcers in these 6 studies had H. ducreyi detectable by PCR, whereas other bacteria, such as T. pallidum subsp. pertenue, the causative agent of yaws, were detected in 25% of patients.
These cases of infection with H. ducreyi confirmed by molecular analysis suggest that clinicians should be more aware of this newly recognized bacterium in skin ulcers of persons in tropical areas. In the context of new efforts to eradicate yaws, mass treatment with azithromycin in Papua New Guinea reduced the absolute prevalence of ulcers not caused by yaws, which were mainly caused by H. ducreyi, from 2.7% to 0.6% (prevalence ratio 0.23, 95% CI 0.18-0.29) at 12 months after treatment (6). However, persistence of H. ducreyi at low levels after mass treatment in Papua New Guinea (3) and Ghana (5) suggest that 1 round of mass treatment might not be successful in eradicating H. ducreyi skin ulcers.
Our review has several limitations. First, the increase in HSV-related GUD as a result of immunosuppression by HIV infection would result in a decrease in the proportion of chancroid among all GUD case-patients. Second, the lack of sequential studies performed in similar clinical settings at multiple time points precludes an optimal interpretation of the apparent decrease. Third, results might be affected by poor-quality data from many developing countries and might be inflated by publication bias. Fourth, PCR is more sensitive than culture. Therefore, increasing diagnostic yield might have partially masked the scale of the decrease in H. ducreyi as a cause of GUD.
In summary, we observed a quantitative and sustained reduction in cases of chancroid as a result of antimicrobial drug syndromic management and major social changes. In addition, data from several research groups indicate that H. ducreyi can cause nongenital skin lesions in persons residing in different regions. Further studies of this newly described pathogen skin disease association are required, and appropriate policies are needed that include the routine practice of managing tropical skin ulcers.
M.M. is supported by a Wellcome Trust Clinical Research Fellowship (WT102807).
Ms. Gonzalez-Beiras is a predoctoral fellow at Instituto de Higiene e Medicina Tropical, Lisbon, Portugal. Her primary research interests are strategies for elimination of neglected tropical diseases.
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Release date: December 17, 2015; Expiration date: December 17, 2016 Learning Objectives
Upon completion of this activity, participants will be able to:
* Distinguish the clinical presentation of genital ulcer disease with Haemophilus ducreyi
* Assess the means used to diagnose H. ducreyi infection
* Identify global areas disproportionately affected by H. ducreyi-related genital ulcer disease
* Assess worldwide trends in the epidemiology of infection with H. ducreyi
Thomas J. Gryczan, MS, Technical Writer/Editor, Emerging Infectious Diseases. Disclosure: Thomas J. Gryczan, MS, has disclosed no relevant financial relationships.
Charles P. Vega, MD, Clinical Professor of Family Medicine, University of California, Irvine. Disclosure: Charles P. Vega, MD, has disclosed the following financial relationships: served as an advisor or consultant for Lundbeck, Inc.; McNeil Pharmaceuticals; Takeda Pharmaceuticals North America, Inc.
Disclosures: Camila Gonzalez-Beiras, BSc, MSC; Michael Marks, MBBS; Cheng-Yen Chen, PhD; Sally Roberts, MBChB, FRACP, FRCPA; and Oriol Mitja, MD, PhD, have disclosed no relevant financial relationships.
Camila Gonzalez-Beiras, Michael Marks, Cheng Y. Chen, Sally Roberts, Oriol Mitja
Author affiliations: Nova University of Lisbon, Lisbon, Portugal (C. Gonzalez-Beiras); Barcelona Institute for Global Health, Barcelona, Spain (C. Gonzalez-Beiras, O. Mitja); London School of Hygiene and Tropical Medicine, London, UK (M. Marks); Hospital for Tropical Diseases, London (M. Marks); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (C.Y. Chen); Auckland District Health Board, Auckland, New Zealand (S. Roberts); Lihir Medical Centre, Lihir Island, Papua New Guinea (O. Mitja)
1. You are seeing a 21-year-old woman who recently emigrated from rural South Africa. She complains of genital ulcers. You consider whether Haemophilus ducreyi may be responsible for her symptoms. Which of the following statements regarding genital ulcer disease and H. ducreyi is most accurate?
A. H. ducreyi is a gram-positive organism
B. H. ducreyi promotes painless genital ulcers
C. Many patients with genital ulcer disease stemming from H. ducreyi have inguinal lymphadenitis
D. Most carriers of H. ducreyi are asymptomatic and are unaware of their infection
2. You perform an evaluation for genital ulcer disease in this patient. Which of the following statements regarding the diagnosis of H. ducreyi infection in the current study is most accurate?
A. Most cases of H. ducreyi were confirmed by PCR
B. All culture studies used low temperatures to grow H. ducreyi
C. All PCR studies used the hemolysin gene as a target
D. Multiplex studies that can detect H. ducreyi, Treponema pallidum, and herpes viruses were not used
3. Which of the following continents featured nations with the highest proportions of cases of H. ducreyi from 1980-1999?
A. South America
B. Australia and the South Pacific
4. Which of the following statements regarding trends in the diagnosis of chancroid in the current study is most accurate?
A. No study found a proportion of H. ducreyi genital ulcers above 10%
B. No African country reported rates of H. ducreyi below 10% between 2000 and 2014
C. More recent studies found that H. ducreyi was an emerging cause of chronic skin ulceration
D. The proportion of H. ducreyi found in genital ulcer disease remained relatively stable between 1980 and 2014
(1.) Lewis DA. Chancroid: clinical manifestations, diagnosis, and management. Sex Transm Infect. 2003; 79:68-71. http://dx.doi.org/10.1136/sti.79.1.68
(2.) Schmid G, Steen R, N'Dowa F. Control of bacterial sexually transmitted diseases in the developing world is possible. Clin Infect Dis. 2005; 41:1313-5. http://dx.doi.org/10.1086/496987
(3.) Mitja O, Lukehart SH, Pokowas G, Moses P, Kapa A, Godornes C, et al. Haemophilus ducreyi as a cause of skin ulcers in children from a yaws-endemic area of Papua New Guinea: a prospective cohort study. Lancet Glob Health. 2014; 2:e235-41. http://dx.doi.org/10.1016/S2214-109X(14)70019-1
(4.) Marks M, Chi KH, Vahi V, Pillay A, Sokana O, Pavluck A, et al. Haemophilus ducreyi associated with skin ulcers among children, Solomon Islands. Emerg Infect Dis. 2014;20: 1705-7. http://dx.doi.org/10.3201/eid2010.140573
(5.) Ghinai R, El-Duah P, Chi KH, Pillay A, Solomon AW, Bailey RL, et al. A cross-sectional study of 'yaws' in districts of Ghana which have previously undertaken azithromycin mass drug administration for trachoma control. PLoS Negl Trop Dis. 2015;9:e0003496. http://dx.doi.org/10.1371/journal.pntd.0003496
(6.) Mitja O, Houinei W, Moses P, Kapa A, Paru R, Hays R, et al. Mass treatment with single-dose azithromycin for yaws. N Engl J Med. 2015; 372:703-10. http://dx.doi.org/10.1056/NEJMoa1408586
(7.) Marckmann P, H0jbjerg T, von Eyben FE, Christensen I. Imported pedal chancroid: case report. Genitourin Med. 1989; 65:126-7.
(8.) Ussher JE, Wilson E, Campanella S, Taylor SL, Roberts S. Haemophilus ducreyi causing chronic skin ulceration in children visiting Samoa. Clin Infect Dis. 2007; 44:e85-7. http://dx.doi.org/10.1086/515404
(9.) McBride WJ, Hannah R, Le Cornec G, Bletchly C. Cutaneous chancroid in a visitor from Vanuatu. Australas J Dermatol. 2008;49:98-9. http://dx.doi.org/10.1111/j.1440-0960.2008.00439.x
(10.) Peel TN, Bhatti D, De Boer J, Stratov I, Spelman D. Chronic cutaneous ulcers secondary to Haemophilus ducreyi infection. Med J Aust. 2010; 192:348-50.
(11.) Humphrey S, Romney M, Au S. Haemophilus ducreyi ulceration in a 5-year-old boy. Presented at: 65th Annual Conference of the American Academy of Dermatology; 2007 Feb 6-7; Washington, DC, USA.
(12.) Montgomery J. The aerobic bacteriology of infected skin lesions in children of the Eastern Highlands Province. P N G Med J. 1985; 28:93-103.
(13.) O'Farrell N, Hoosen AA, Coetzee KD, van den Ende J. Genital ulcer disease: accuracy of clinical diagnosis and strategies to improve control in Durban, South Africa. Genitourin Med. 1994; 70:7-11.
(14.) Chen CY, Mertz KJ, Spinola SM, Morse S. Comparison of enzyme immunoassays for antibodies to Haemophilus ducreyi in a community outbreak of chancroid in the United States. J Infect Dis. 1997; 175:1390-5. http://dx.doi.org/10.1086/516471
(15.) Beyrer C, Jitwatcharanan K, Natpratan C, Kaewvichit R, Nelson KE, Chen CY, et al. Molecular methods for the diagnosis of genital ulcer disease in a sexually transmitted disease clinic population in northern Thailand: predominance of herpes simplex virus infection. J Infect Dis. 1998; 178:243-6. http://dx.doi.org/10.1086/515603
(16.) Paz-Bailey G, Rahman M, Chen C, Ballard R, Moffat HJ, Keyton T, et al. Changes in the etiology of sexually transmitted diseases in Botswana between 1993 and 2002: implications for the clinical management of genital ulcer disease. Clin Infect Dis. 2005;41:1304-12. http://dx.doi.org/10.1086/496979
(17.) Steen R. Eradicating chancroid. Bull World Health Organ. 2001; 79:818-26.
(18.) Mabey DC, Wall R, Bello CS. Aetiology of genital ulceration in the Gambia. Genitourin Med. 1987; 63:312-5.
(19.) Hawkes S, Wes B, Wilson S, Whittle H, Mabey D. Asymptomatic carriage of Haemophilus ducreyi confirmed by the polymerase chain reaction. Genitourin Med. 1995; 71:224-7.
(20.) Nsanze H, Fats MV, D'Costa LJ, Tukei P, Curran J, Ronald A, et al. Genital ulcers in Kenya. Clinical and laboratory study. Br J Vener Dis. 1981; 57:378-81.
(21.) Kaul R, Kimani J, Nagelkerke, NJ, Plummer FA, Bwayo JJ, Brunham RC, et al. Risk factors for genital ulcerations in Kenyan sex workers. The role of human immunodeficiency virus type 1 infection. Sex Transm Dis. 1997; 24:387-92. http://dx.doi.org/10.1097/00007435-199708000-00001
(22.) Morse SA, David LT, Htun Y, Radebe F, Orle KA, Dangor Y, a et al. Comparison of clinical diagnosis and standard laboratory and molecular methods for the diagnosis of genital ulcer disease in Lesotho: association with human immunodeficiency virus infection. J Infect Dis. 1997; 75:583-9. http://dx.doi.org/10.1093/infdis/175.3.583
(23.) Harms G, Matull R, Randrianasolo D, Andriamiadana J, Rasamindrakotroka A, Kirsch T, et al. Pattern of sexually transmitted diseases in a Malagasy population. Sex Transm Dis. 1994; 21:31520. http://dx.doi.org/10.1097/00007435-199411000-00004
(24.) Behets FM, Andriamiadana J, Randrianasolo D, Randriamanga R, Rasamilalao D, Chen CY, et al. Chancroid, primary syphilis, genital herpes, and lymphogranuloma venereum in Antananarivo, Madagascar. J Infect Dis. 1999; 180:1382-5. http://dx.doi.org/10.1086/315005
(25.) Behets FM, Liomba G, Lule G, Dallabetta G, Hoffman IF, Hamilton HA, et al. Sexually transmitted diseases and human immunodeficiency virus control in Malawi: a field study of genital ulcer disease. J Infect Dis. 1995; 171:451-5. http://dx.doi.org/10.1093/infdis/171.2.451
(26.) Hoyo C, Hoffman I, Moser BK, Hobbs MM, Kazembe P, Krysiak RG, et al. Improving the accuracy of syndromic diagnosis of genital ulcer disease in Malawi. Sex Transm Dis. 2005; 32:2317. http://dx.doi.org/10.1097/01.olq.0000149669.98128.ce
(27.) Bogaerts J, Vuylsteke B, Martinez Tello W, Mukantabana V, Akingeneye J, Laga M, et al. Simple algorithms for the management of genital ulcers: evaluation in a primary health care centre in Kigali, Rwanda. Bull World Health Organ. 1995; 73:761-7.
(28.) Totten PA, Kuypers JM, Chen CY, Alfa MJ, Parsons LM, Dutro SM, et al. Etiology of genital ulcer disease in Dakar, Senegal, and comparison of PCR and serologic assays for detection of Haemophilus ducreyi. J Clin Microbiol. 2000; 38:268-73.
(29.) Crewe-Brown HH, Krige FK, Davel GH, Barron C, Jasen Van Vuuren JA, Shipham SO, et al. Genital ulceration in males at Ga-Rankuwa Hospital, Pretoria. S Afr Med J. 1982; 62:861-3.
(30.) Dangor Y, Fehler G, Exposto F, Koornhof H. Causes and treatment of sexually acquired genital ulceration in southern Africa. S Afr Med J. 1989; 76:339-41.
(31.) Chen CY, Ballard RC, Beck-Sague CM, Dangor Y, Radebe F, Schmid S, et al. Human immunodeficiency virus infection and genital ulcer disease in South Africa. Sex Transm Dis. 2000; 27:21-9. http://dx.doi.org/10.1097/00007435-200001000-00005
(32.) Lai W, Chen CY, Morse SA, Htun Y, Fehler HG, Liu H, et al. Increasing relative prevalence of HSV-2 infection among men with genital ulcers from a mining community in South Africa. Sex Transm Infect. 2003; 79:202-7. http://dx.doi.org/10.1136/sti.79.3.202
(33.) Meheus A, Van Dyck E, Ursi JP, Ballard RC, Piot P. Etiology of genital ulcerations in Swaziland. Sex Transm Dis. 1983; 10:33-5. http://dx.doi.org/10.1097/00007435-198301000-00007
(34.) Ahmed HJ, Mbwana J, Gunnarsson E, Ahlman K, Guerino C, Svensson LA, et al. Etiology of genital ulcer disease and association with human immunodeficiency virus infection in two Tanzanian cities. Sex Transm Dis. 2003; 30:114-19. http://dx.doi.org/10.1097/00007435-200302000-00004
(35.) Le Bacq F, Mason PR, Gwanzura L, Robertson VL, Latif AS. HIV and other sexually transmitted diseases at a rural hospital in Zimbabwe. Genitourin Med. 1993; 69:352-6.
(36.) Wang Q, Yang P, Zhong M, Wang G. Validation of diagnostic algorithms for syndromic management of sexually transmitted diseases. Chin Med J (Engl). 2003; 116:181-6.
(37.) Risbud A, Chan-Tack K. The etiology of genital ulcer disease by multiplex polymerase chain reaction and relationship to HIV infection among patients attending sexually transmitted disease clinics in Pune, India. Sex Transm Dis. 1999; 26:55-62. http://dx.doi.org/10.1097/00007435-199901000-00009
(38.) Rajan VS, Sng E, Lim A. The isolation of H. ducreyi in Singapore. Ann Acad Med Singapore. 1983; 12:57-60.
(39.) Dillon SM, Cummings M, Rajagopalan S, McCormack WC. Prospective analysis of genital ulcer disease in Brooklyn, New York. Clin Infect Dis. 1997; 24:945-50. http://dx.doi.org/10.1093/clinids/24.5.945
(40.) Mertz KJ, Weiss JB, Webb RM, Levine WC, Lewis JS, Orle KA, et al. An investigation of genital ulcers in Jackson, Mississippi, with use of a multiplex polymerase chain reaction assay: high prevalence of chancroid and human immunodeficiency virus infection. J Infect Dis. 1998; 178:1060-6. http://dx.doi.org/10.1086/515664
(41.) Mertz KJ, Trees D, Levine W. Etiology of genital ulcers and prevalence of human immunodeficiency virus coinfection in 10 US cities. J Infect Dis. 1998; 178:1795-8. http://dx.doi.org/10.1086/314502
(42.) Sanchez J, Volquez C, Totten PA, Campos PE, Ryan C, Catlin M, et al. The etiology and management of genital ulcers in the Dominican Republic and Peru. Sex Transm Dis. 2002; 29:559-67. http://dx.doi.org/10.1097/00007435-200210000-00001
(43.) Behets FM, Brathwaite R, Hylton-Kong T. Genital ulcers: etiology, clinical diagnosis, and associated human immunodeficiency virus infection in Kingston, Jamaica. Clin Infect Dis. 1999; 28:1086-90. http://dx.doi.org/10.1086/514751
(44.) Bauwens JE, Orlander E, Gomez H. Epidemic Lymphogranuloma venereum during epidemics of crack cocaine use and HIV infection in the Bahamas. Sex Transm Dis. 2002; 29:253-9. http://dx.doi.org/10.1097/00007435-200205000-00001
(45.) Madani TA. Sexually transmitted infections in Saudi Arabia. BMC Infect Dis. 2006; 6:3. http://dx.doi.org/10.1186/1471-2334-6-3
(46.) Kyriakis KP, Hadjivassiliou M, Paparizos VA, Flemetakis A, Stavrianeas N, Katsambas A. Incidence determinants of gonorrhea, chlamydial genital infection, syphilis and chancroid in attendees at a sexually transmitted disease clinic in Athens, Greece. Int J Dermatol. 2003;42:876-81. http://dx.doi.org/10.1046/j.1365-4362.2003.01737.x
Address for correspondence: Oriol Mitja, Department of Community Health, Lihir Medical Center Post Office Box 34, Lihir Island, New Ireland Province, Lihir 00, Papua New Guinea; email: firstname.lastname@example.org
Table 1. Characteristics of 35 studies of genital ulcers caused by Haemophilus ducreyi, 1980-1999 * Year of Area, reference ([dagger]) Country study Africa Paz-Bailey et al. (16) Botswana 1993 Steen (17) Cote d'Ivoire 1996 Mabey et al. (18) Gambia 1987 Hawkes et al. (19) Gambia 1995 Nsanze et al. (20) Kenya 1980 Kaul et al. (21) Kenya 1997 Morse et al. (22) Lesotho 1994 Harms et al. (23) Madagascar 1992 Behets et al. (24) Madagascar 1997 Behets et al. (25) Malawi 1995 Hoyo et al. (26) Malawi 1999 Bogaerts et al. (27) Rwanda 1992 Totten et al. (28) Senegal 1992 Crewe-Brown et al. (29) South Africa 1981 Dangor et al. (30) South Africa 1989 Chen et al. (31) South Africa 1994 Lai et al. (32) South Africa 1994 South Africa 1998 Meheus et al. (33) Swaziland 1979 Ahmed et al. (34) Tanzania 1999 Le Bacq et al. (35) Zimbabwe 1991 Asia Wang et al. (36) China 1999 Risbud et al. (37) India 1994 Rajan et al. (38) Singapore 1983 Beyrer et al. (15) Thailand 1996 North America Dillon et al. (39) United States 1990 Mertz et al. (40) United States 1995 Mertz et al. (41) United States 1996 South America Sanchez et al. (42) Peru 1995 Caribbean Sanchez et al. (42) Dominican 1996 Republic Behets et al. (43) Jamaica 1996 Bauwens et al. (44) Bahamas 1992 Middle East Madani et al. (45) Saudi Arabia 1999 Europe Kyriakis et al. (46) Greece 1996 Bruisten et al. (47) The Netherlands 1996 Diagnostic No. patients Area, reference ([dagger]) method with GUD Africa Paz-Bailey et al. (16) Culture 108 Steen (17) PCR NA Mabey et al. (18) Culture 104 Hawkes et al. (19) M-PCR 18 Nsanze et al. (20) Culture 97 Kaul et al. (21) Culture 189 Morse et al. (22) M-PCR 105 Harms et al. (23) Culture 12 Behets et al. (24) M-PCR 196 Behets et al. (25) M-PCR 778 Hoyo et al. (26) M-PCR 137 Bogaerts et al. (27) Culture 395 Totten et al. (28) PCR 39 Crewe-Brown et al. (29) Culture 100 Dangor et al. (30) Culture 240 Chen et al. (31) M-PCR 538 Lai et al. (32) M-PCR 160 M-PCR 94 Meheus et al. (33) Culture 155 Ahmed et al. (34) PCR 102 Le Bacq et al. (35) Culture 90 Asia Wang et al. (36) M-PCR 96 Risbud et al. (37) M-PCR 302 Rajan et al. (38) Culture 670 Beyrer et al. (15) M-PCR 38 North America Dillon et al. (39) Culture 82 Mertz et al. (40) M-PCR 143 Mertz et al. (41) M-PCR 516 South America Sanchez et al. (42) M-PCR 61 Caribbean Sanchez et al. (42) M-PCR 81 Behets et al. (43) M-PCR 304 Bauwens et al. (44) PCR 47 Middle East Madani et al. (45) Culture 3,679 Europe Kyriakis et al. (46) Culture 695 Bruisten et al. (47) M-PCR 368 No. cases H. ducreyi Area, reference ([dagger]) infection % (95% CI) Africa Paz-Bailey et al. (16) 27 25.0 (17.7-33.9) Steen (17) NA 47 Mabey et al. (18) 54 51.9 (42.4-61.2) Hawkes et al. (19) 8 44.4 (24.5-66.2) Nsanze et al. (20) 60 61.8 (51.9-70.9) Kaul et al. (21) 54 28.5 (22.6-35.3) Morse et al. (22) 55 53.3 (43.8-62.6) Harms et al. (23) 61 19.6 (11.6-31.3) Behets et al. (24) 64 32.6 (26.4-39.5) Behets et al. (25) 204 26.2 (23.2-29.4) Hoyo et al. (26) 41 29.0 (22.8-38.0) Bogaerts et al. (27) 115 29.1 (24.8-33.7) Totten et al. (28) 22 56.4 (40.9-70.7) Crewe-Brown et al. (29) 45 45 (35.5-54.7) Dangor et al. (30) 164 68.3 (62.2-73.8) Chen et al. (31) 171 31.7 (27.9-35.8) Lai et al. (32) 232 68.9 (62.7-74.5) 186 50.5 (43.4-57.6) Meheus et al. (33) 68 43.8 (36.3-51.7) Ahmed et al. (34) 12 11.7 (6.8-19.4) Le Bacq et al. (35) 22 24.4 (16.7-34.2) Asia Wang et al. (36) 0 0.0 (0.0-3.8) Risbud et al. (37) 84 27.8 (23.0-33.1) Rajan et al. (38) 56 83 (64-107) Beyrer et al. (15) 0 0.0 (0.0-9.1) North America Dillon et al. (39) 27 32.9 (23.7-43.6) Mertz et al. (40) 56 39.1 (231.5-47.3) Mertz et al. (41) 16 3.1 (1.9-4.9) South America Sanchez et al. (42) 3 4.9 (1.6-13.4) Caribbean Sanchez et al. (42) 21 25.9 (17.6-36.4) Behets et al. (43) 72 236 (19.2-28.7) Bauwens et al. (44) 7 148 (7.4-27.6) Middle East Madani et al. (45) 78 2.1 (1.7-2.5) Europe Kyriakis et al. (46) 32 4.6 (3.2-6.4) Bruisten et al. (47) 3 0.8 (0.2-2.3) * GUD, genital ulcer disease; NA, not available; M-PCR, multiplex PCR. ([dagger]) References 41-47 provided in the online Technical Appendix (http://wwwnc.cdc.gov/EID/article/22/1/15-0425-Techapp1.pdf). Table 2. Characteristics of 14 studies of genital ulcers caused by Haemophilus ducreyi, 2001-2014 * Area, reference Year of ([dagger]) Country study Africa Paz-Bailey et al. (16) Botswana 2002 Mehta et al. (48) Kenya 2007 Phiri et al. (49) Malawi 2006 Zimba et al. (50) Mozambique 2005 Tobias et al. (51) Namibia 2007 O'Farrell et al. (52) South Africa 2004 Lewis et al. (53) South Africa 2006 Nilsen et al. (54) Tanzania 2001 Suntoke et al. (55) Uganda 2006 Makasa et al. (56) Zambia 2010 South America Gomes Naveca et al. (57) Brazil 2009 Middle East Maan et al. (58) Pakistan 2009 Europe Hope-Rapp et al. (59) France 2005 Oceania Mackay et al. (60) Australia 2002 Area, reference Diagnostic No. patients ([dagger]) method with GUD Africa Paz-Bailey et al. (16) PCR 137 Mehta et al. (48) M-PCR 59 Phiri et al. (49) M-PCR 398 Zimba et al. (50) PCR 79 Tobias et al. (51) PCR 199 O'Farrell et al. (52) M-PCR 162 Lewis et al. (53) M-PCR 613 Nilsen et al. (54) PCR 232 Suntoke et al. (55) M-PCR 100 Makasa et al. (56) PCR 200 South America Gomes Naveca et al. (57) PCR 434 Middle East Maan et al. (58) Culture 521 Europe Hope-Rapp et al. (59) Culture 278 Oceania Mackay et al. (60) M-PCR 64 Area, reference No. cases H. ([dagger]) ducreyi infection % (95% CI) Africa Paz-Bailey et al. (16) 1 0.7 (0.1-4.0) Mehta et al. (48) 0 0.0 (0.0-6.1) Phiri et al. (49) 60 15.0 (11.8-18.9) Zimba et al. (50) 3 3.8 (1.3-10.9) Tobias et al. (51) 0 0.0 (0.0-1.8) O'Farrell et al. (52) 2 1.2 (0.3-4.6) Lewis et al. (53) 10 1.6 (0.9-2.9) Nilsen et al. (54) 12 5.1 (2.9-8.8) Suntoke et al. (55) 2 2.0 (0.5-7.0) Makasa et al. (56) 0 0 (0.0-1.8) South America Gomes Naveca et al. (57) 0 0 (0.0-0.8) Middle East Maan et al. (58) 20 3.8 (2.5-5.8) Europe Hope-Rapp et al. (59) 8 2.8 (1.4-5.5) Oceania Mackay et al. (60) 0 0.0 (0.0-5.6) * GUD, genital ulcer disease; M-PCR, multiplex PCR. ([dagger]) References 48-60 provided in the online Technical Appendix (http://wwwnc.cdc.gov/EID/article/22/1/15-0425-Techapp1.pdf). Table 3. Characteristics of 11 studies on skin ulcers caused by Haemophilus ducreyi, 1988-2014 * Year Reference Country of study Marckmann et al. (7) Fiji Islands 1988 Ussher et al. (8) Samoa 2005 McBride et al. (9) Vanuatu 2007 Peel et al. (10) Vanuatu and Papua 2010 New Guinea Humphrey et al. (11) Sudan 2007 Mitja et al. (3) Papua New Guinea 2013 Mitja et al. (6) Papua New Guinea 2014 Marks et al. (4) Solomon Islands 2013 Chen et al. ([dagger]) Vanuatu 2013 Chen et al. ([dagger]) Ghana 2013 Ghinai et al. (5) Ghana 2014 No. patients Diagnostic with skin Reference method ulcers Marckmann et al. (7) Culture 1 man Ussher et al. (8) PCR 3 girls <10 y of age McBride et al. (9) PCR 1 woman Peel et al. (10) PCR 2 men Humphrey et al. (11) PCR 1 boy Mitja et al. (3) PCR 90 Mitja et al. (6) PCR 114 Marks et al. (4) PCR 41 Chen et al. ([dagger]) PCR 176 Chen et al. ([dagger]) PCR 179 Ghinai et al. (5) PCR 90 No cases H. ducreyi Reference infection % (95% CI) Marckmann et al. (7) 1 NA Ussher et al. (8) 3 NA McBride et al. (9) 1 NA Peel et al. (10) 2 NA Humphrey et al. (11) 1 NA Mitja et al. (3) 54 60.0 (49.6-69.5) Mitja et al. (6) 60 60.1 (54.3-65.5) Marks et al. (4) 13 31.7 (19.5-46.9) Chen et al. ([dagger]) 68 38.6 (31.7-46.0) Chen et al. ([dagger]) 49 27.3 (21.3-34.3) Ghinai et al. (5) 8 8.8 (4.5-16.5) * NA, not applicable. ([dagger]) Pers. comm.
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|Author:||Gonzalez-Beiras, Camila; Marks, Michael; Chen, Cheng Y.; Roberts, Sally; Mitja, Oriol|
|Publication:||Emerging Infectious Diseases|
|Date:||Jan 1, 2016|
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