B
r ie f
R
epo r ts
MILITARY MEDICINE, 180,1:17,2015
G o n o rrh e a S u rv e illa n c e in G h an a, A frica Christopher Duplessis*; Naiki Puplam puf; Edward Nyarkof; John Carrollt; Helena D elaf; Akussah MensahJ; Akussah Am ponsahf, COL Jose Sanchez, MC USA (Ret.)§
ABSTRACT Objectives: We face the specter of global transmission of highly resistant Neisseria gonorrhoeae. The U.S. Department of Defense’s Armed Forces Health Surveillance Center has engaged many military and civilian partners (including Ghana) in a sexually transmitted infections (STI) program to address emerging needs in STI surveillance. We implemented gonorrhea surveillance in Ghana to fill the gap in knowledge regarding gonorrhea prevalence and antimicrobial resistance characterization in Ghana. Methods: Gonorrhea surveillance was conducted from June 2012 to March 2013 as one of the AFHSC surveillance network partners at two Ghana Armed Forces (GAF) military clinics. The population encompassed a convenience sampling of patients presenting with STI symp toms. Urine was taken for nucleic acid amplification testing (NAAT). A urethral or cervical/vaginal specimen was obtained for culture and antibiotic susceptibility testing. Results: 13/220 (6%) specimens tested were positive by culture (7 of which were confirmed); and 39/213 (18%) specimens tested were positive by NAAT. Positive results were biased toward men. Cultures were resistant to ciprofloxacin, penicillin and tetracycline and sensitive to cephalo sporins. Conclusion: This investigation provides data on gonorrhea prevalence and resistance profiles in Ghana hitherto poorly characterized. We note significant resistance to fluoroquinolones without the presence of resistance yet to the cephalosporins.
INTRODUCTION Emergence of multidrug resistant (MDR) Neisseria gonor rhoeae is a major global public health issue. The WHO estimates over 498 million new cases of sexually transmit ted infections (STI) annually in adults aged 15 to 49 years.1 STIs engender appreciable health care costs ranking among the top five indications for adults seeking medical treat ment in developing countries. Gonorrhea is one of the most
*Naval Medical Research Center, Biological Defense Research Direc torate, Silver Spring, MD 20904. tU.S. Naval Medical Research Unit No. 3, NAMRU-3, PSC 452 Box 5000, FPO AE 09835-9998, 3A Imtidad Ramses Street, Adjacent to Abbassia Fever Hospital Abbassia, Cairo, Egypt 11517. /Ghana Armed Forces, Ghana Africa General Headquarters Burma Camp-Accra. §Armed Forces Health Surveillance Center (AFHSC) and Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF), 11800 Tech Road, Suite 220, Silver Spring, MD 20904. Mention of any commercial product does not imply DoD endorsement or recommendation for or against the use of any such product. No infringement on the rights of the holders of the registered trademarks is intended The opinions stated are those of the authors and do not represent the official position of the U.S. Department of Defense, Ghana Ministries of Health, Agriculture, or Defense, or other contributing network partner organizations. doi: 10.7205/MILMED-D-13-00418
MILITARY MEDICINE, Vol. 180, January 2015
prevalent etiologies of STIs both in the United States and worldwide,23 an appreciable percentage of which is shouldered by developing countries. Well-described compli cations and morbidity include increasing HIV acquisition and transmission. N. gonorrhoeae has developed increasing resistance to antimicrobials, including the fluoroquinolones (FQ) and, more recently, cephalosporins necessitating increasing vigi lance to STI surveillance. N. gonorrhoeae is particularly adept at developing resistance to antibiotics via a host of mechanisms including mutations, and promiscuous genetic transfer; seamlessly developing resistance to each class of antimicrobial introduced.4 FQs emerged in the 1980s, recom mended as first-line treatment by the Center for Disease Control (CDC) in 1993.5 Alas, soon thereafter, resistant iso lates emerged via mutations in the gyrA and parC genes.5 Mirroring trends in global resistance transmission, FQ resis tance surfaced in the Far East and migrated westward.4 As of 2007, FQs were no longer recommended by the CDC, defer ring to the third-generation cephalosporin antibiotics (includ ing the orally administered cefixime and ceftriaxone).4,6 The inexorable resistance propensity of N. gonorrhoeae has engendered the emergence of strains resistant to cefixime and ceftriaxone. Treatment failures with cefixime have been
17
Gonorrhea Surveillance in Ghana, Africa verified in Japan, Norway, England, Austria, France, Canada, Vietnam, England, Wales, and Sweden.7-10 Cefixime resis tance of 3.5% was reported in isolates acquired in Norway in 2009n ; and 1% cefixime resistance in British Columbia in isolates acquired between 2007 and 2011.12 European gonorrhea surveillance (Euro-GASP) noted that 31% of iso lates in 2009/2010 exhibited decreased susceptibility to cefixime (MIC >0.125 mg/L).13 Decreased susceptibility or frank resistance to cefixime increased from less than 1% to 8% in Sweden from 2007 to 2011.14 Per the Gonococcal Isolate Surveillance Project (GISP), from 2000 to 2010 in the United States, the percentage of isolates with elevated MICs (>0.25 pg/mL for cefixime) increased from 0.2% to 1.4%. The increases were most pronounced in known highrisk groups including men having sex with men (MSM).5 Recently, ceftriaxone-resistant isolates have been identi fied in Japan (2009), France (2010), Vietnam,9 Norway11 (2009), and Spain (2011).15,16 Decreased susceptibility to ceftriaxone was reported in Sweden (2007-2011),14 China17 (2005-2008), and Australia (2010).18 The GISP network in the United States revealed an increase in elevated MICs to ceftriaxone from 0% to 0.4% from 2006 to 2011. Ceftriaxone treatment failures of pharyngeal gonorrhoea have been verified in Sweden (2010), and Slovenia (2011).14,1:1 Thus, there is concern over the potential widespread emergence of N. gonorrhoeae resistance to cephalosporins. Gonorrhea resistance may be predicted in Ghana given contemporary (1) indiscriminate antimicrobial use, (2) lack of antimicrobial stewardship, (3) suspect antimicrobial com pliance, (4) increase in cosmopolitan lifestyle and migration, and (5) lack of laboratory infrastructure. We implemented gonorrhea surveillance in Ghana as an integral component of the AFHSC-GEIS supported STI program to fill the gap in knowledge regarding gonorrhea prevalence and antimicrobial resistance characterization.
METHODS Participating facilities included three outpatient military clinics of the Ghana Armed Forces in the port city of Takoradi, and the 37 Military Hospital (Accra, Ghana). These military clinics serve the military, their dependents, and civil ian population in their catchment area (comprising about 80% of the census). Subjects were 12 years of age and older (those 0.001) and not significant for gender and Chlamydia NAAT (p 0.2). Age showed a trend toward significance by Fisher’s exact testing for gonorrhea NAAT (p = 0.086) and for Chlamydia NAAT (p = 0.663). The concordance rate (gonor rhea culture + accompanied by gonorrhea NAAT +) was 13/13 (100%); while the concordance rate (gonorrhea NAAT + accompanied by gonorrhea culture +) was 13/38 (34%). The seven confirmed specimens were all resistant to ciprofloxacin, penicillin, and tetracycline, and sensitive to ceftriaxone and cefixime. Six of seven specimens were sensi tive to spectinomycin.
DISCUSSION Treatment options are becoming limited given the increasing antibiotic resistance in the absence of novel antimicrobials in the pipeline. The emergence of MDR N. gonorrhoeae is ushering in an era of unbeatable gonorrhea. Therefore, sur veillance for gonorrhea and resistant gonococcal isolates coupled to an integrated public health response is required to (1) expedite identification and subsequent containment of resistant isolates mitigating transmission; (2) optimize individual-level treatment; (3) contribute to local, regional, TABLE I.
and national surveillance networks; (4) support epidemiologic investigations, (5) facilitate lab capacity in cultures and AST; and (6) identify risk factors for harboring gonorrhea and resis tant isolates that will assist policy makers in allocating limited resources for the adoption of prevention, health promotion, and educational campaigns targeting at-risk populations.20 This concerted surveillance strategy will extend the duration of efficacy of the few existing antimicrobial drug options in our armamentarium for treatment of gonorrhea.6 The preponderance of resistant gonococcal isolates has hitherto been identified through active surveillance networks thus substantiating the efficacy of maintaining global sur veillance. The mission of the Global Emerging Infections Surveillance and Response System Division at the U.S. Department of Defense's (DoD) Armed Forces Health Sur veillance Center (AFHSC-GEIS), is to develop, implement, support, and evaluate an integrated global emerging infec tious disease surveillance and response system that contrib ute to enhancement of U.S. Forces’ health, the collaborating host nations Public Health Systems, and the global public health community. The consortium’s objectives in establish ing global STI surveillance networks have been described elsewhere.21 There is a dearth of cross-sectional and longitudinal gon orrhea surveillance in West Africa (including Ghana). These countries are not engaged in surveillance activities due to limited resources in addition to potential impeding cultural issues (possible aversion to stigmatization and clinical inva siveness). Cross-sectional investigations have been conducted in Uganda, Benin, Malawi, Tanzania, Zimbabwe, Ethiopia, and Kenya focusing on gonorrhea incidence and acquisition of risk factors, but longitudinal studies are lacking as are data on resistance levels. Mirroring developed nations, the empha sis on STI syndromic management has stagnated the develop ment of clinical laboratory capacity to execute N. gonorrhoeae AST.’’ Implementing surveillance networks throughout Africa will contribute to the global surveillance networks serving as a beacon on potential resistant isolates migrating into and out of the continent.
Results of Gonorrhea and Chlamydia Culture and NAAT Testing Stratified by Age and Gender* Gender
Culture +
Gonorrhea NAAT +“
Chlam ydia NAAT +“
Age
M
F
M
F
M
F
M
F
Age 50 Totals
0 10 34 42 28 10 7 4 3 138
1 2 16 19 24 6 6 1 1 76
0
0 0
0
1
3
1 2 0
0 0 1
0
1
4 4 3 0 0 0 0 12
1
0 0 0 0 0 0 1
8 10
6 5
0
4 1 2
0 1
2 3
0
0 0 0 0
0
0 0 0 0
33
4
9
6
0 1
1 0
“M issing demographic data on two Gonorrhea NAAT and one Chlam ydia NAAT.
MILITARY MEDICINE, Vol. 180. January 2015
19
Gonorrhea Surveillance in Ghana, Africa
There is a dramatic variation in STI prevalence across surveyed African countries and targeted populations. Hetero geneous studies conducted in Africa among patients presenting with STI symptoms exhibited prevalence rates of gonorrhea of 0.4% (Congo),22 5.7% in Benin,23 8.4% in Tanzania, 17.1% in Malawi,24 2% in Tanzania,19 5.6% in Kenya (young HIV negative males),25 and 1.4% in Zambia26 (HIV positive women). Gonorrhea was identified in 11.6% (Chlamydia 5%) of surveyed clinical sex workers (CSW) in Rwanda—5% each in Benin and 1.6% (30%) in Tanzania—and 16% (3%) in general surveys of CSW in West Africa.27 We noted that within a convenience sampling of a populationbased survey of patients presenting with STI symptoms, 13/220 (6%) specimens tested were positive by local culture. We noted that 39/213 (18%) specimens tested were positive by NAAT. Our gonorrhea culture results are consistent with the prior investigations executed in Africa. The discrepancy in positivity solicited from culture and NAAT testing may be attributed to several factors: (1) superiority in NAAT testing over culture, (2) the ubiquitous access to over-the-counter antimicrobials, and (3) suboptimal culture conditions. Studies have demon strated superiority in molecular testing over culture-based diagnosis in gonorrhea.28 There is a ubiquitous lack of anti microbial stewardship in Ghana. An appreciable percentage of patients presenting to our participating clinics have taken anti biotics obtained from pharmacies, chemists, or family/friends (29%). The indiscriminate access to antimicrobials has been a consistent finding observed in other GEIS-funded surveillance efforts in this region including acute febrile illness and antimalarial resistance surveillance investigations. This practice undermines successful pathogen cultivation, undermining health objectives and complicating surveillance. Additionally, pelvic examinations with endocervical sampling should be emphasized as opposed to accepting high vaginal swabs. Finally, subjecting the swab itself to molecular testing may provide a higher yield than culture.28 There was a significant difference in the yield of positive cultures between enrolled men and women. The bias in positive cultures favoring males contradicts the bias to greater positivity identified in woman within the GISP sur veillance activities.29 The population-based data accumu lated within GISP activities may have integrated female health programs (biasing toward positive female isolates). Additionally, differential positivity may be attributed to the difficulty in specimen acquisition described above, and the dilution of STI presentations in females attributed to gonor rhea due to the wider differential in females. A large attrib utable fraction of syndromic STI symptoms in women stem from candidiasis, bacterial vaginosis, and Trichomonas vaginalis30 likely diluting the percentage of gonorrhea recovery. For example, specimens acquired from Kenyan women presenting with vaginal discharge yielded rates of candidiasis (50%), trichomoniasis (23%), bacterial vaginosis (9%), gonorrhea (7%), Chlamydia (9%), and syphilis (7%), respectively.31 Acknowledging this, empiric treatment algo
20
rithms have adopted integration of metronidazole coupled to dual gonorrhea and Chlamydia treatment. Ideally, future sur veillance will integrate more expansive testing for the afore mentioned pathogens into diagnostic algorithms to further optimize treatment (reducing indiscriminate and unnecessary antimicrobial prescriptions). Of note, military personnel composed 17% of the cohort and there was no significant difference in positive recovery rates in military vice non military patients. All confirmed isolates were MDR (resistant to ciprofloxa cin, tetracycline, and penicillin). Regrettably, 6/13 of the isolates originally suspected to be gonorrhea from the local labs could not be confirmed. Confirmatory testing failed because of inappropriate cold chain storage, contaminated samples stemming from suboptimal processing, and technical (staffing) issues. Nonetheless, the prevalence of ciprofloxacin resistance in all tested isolates is noteworthy and has already altered the empiric treatment paradigm in our participating clinics from dual therapy with ciprofloxacin and doxycycline to ceftriaxone and doxycycline. Our data were biased to subjects older than 18 years of age. Gonorrhea prevalence is historically highest in the youn ger cohorts and particularly between the ages of 15 and 24. There appears to be some reluctance from subjects
r ie f
R
epo r ts
MILITARY MEDICINE, 180,1:17,2015
G o n o rrh e a S u rv e illa n c e in G h an a, A frica Christopher Duplessis*; Naiki Puplam puf; Edward Nyarkof; John Carrollt; Helena D elaf; Akussah MensahJ; Akussah Am ponsahf, COL Jose Sanchez, MC USA (Ret.)§
ABSTRACT Objectives: We face the specter of global transmission of highly resistant Neisseria gonorrhoeae. The U.S. Department of Defense’s Armed Forces Health Surveillance Center has engaged many military and civilian partners (including Ghana) in a sexually transmitted infections (STI) program to address emerging needs in STI surveillance. We implemented gonorrhea surveillance in Ghana to fill the gap in knowledge regarding gonorrhea prevalence and antimicrobial resistance characterization in Ghana. Methods: Gonorrhea surveillance was conducted from June 2012 to March 2013 as one of the AFHSC surveillance network partners at two Ghana Armed Forces (GAF) military clinics. The population encompassed a convenience sampling of patients presenting with STI symp toms. Urine was taken for nucleic acid amplification testing (NAAT). A urethral or cervical/vaginal specimen was obtained for culture and antibiotic susceptibility testing. Results: 13/220 (6%) specimens tested were positive by culture (7 of which were confirmed); and 39/213 (18%) specimens tested were positive by NAAT. Positive results were biased toward men. Cultures were resistant to ciprofloxacin, penicillin and tetracycline and sensitive to cephalo sporins. Conclusion: This investigation provides data on gonorrhea prevalence and resistance profiles in Ghana hitherto poorly characterized. We note significant resistance to fluoroquinolones without the presence of resistance yet to the cephalosporins.
INTRODUCTION Emergence of multidrug resistant (MDR) Neisseria gonor rhoeae is a major global public health issue. The WHO estimates over 498 million new cases of sexually transmit ted infections (STI) annually in adults aged 15 to 49 years.1 STIs engender appreciable health care costs ranking among the top five indications for adults seeking medical treat ment in developing countries. Gonorrhea is one of the most
*Naval Medical Research Center, Biological Defense Research Direc torate, Silver Spring, MD 20904. tU.S. Naval Medical Research Unit No. 3, NAMRU-3, PSC 452 Box 5000, FPO AE 09835-9998, 3A Imtidad Ramses Street, Adjacent to Abbassia Fever Hospital Abbassia, Cairo, Egypt 11517. /Ghana Armed Forces, Ghana Africa General Headquarters Burma Camp-Accra. §Armed Forces Health Surveillance Center (AFHSC) and Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF), 11800 Tech Road, Suite 220, Silver Spring, MD 20904. Mention of any commercial product does not imply DoD endorsement or recommendation for or against the use of any such product. No infringement on the rights of the holders of the registered trademarks is intended The opinions stated are those of the authors and do not represent the official position of the U.S. Department of Defense, Ghana Ministries of Health, Agriculture, or Defense, or other contributing network partner organizations. doi: 10.7205/MILMED-D-13-00418
MILITARY MEDICINE, Vol. 180, January 2015
prevalent etiologies of STIs both in the United States and worldwide,23 an appreciable percentage of which is shouldered by developing countries. Well-described compli cations and morbidity include increasing HIV acquisition and transmission. N. gonorrhoeae has developed increasing resistance to antimicrobials, including the fluoroquinolones (FQ) and, more recently, cephalosporins necessitating increasing vigi lance to STI surveillance. N. gonorrhoeae is particularly adept at developing resistance to antibiotics via a host of mechanisms including mutations, and promiscuous genetic transfer; seamlessly developing resistance to each class of antimicrobial introduced.4 FQs emerged in the 1980s, recom mended as first-line treatment by the Center for Disease Control (CDC) in 1993.5 Alas, soon thereafter, resistant iso lates emerged via mutations in the gyrA and parC genes.5 Mirroring trends in global resistance transmission, FQ resis tance surfaced in the Far East and migrated westward.4 As of 2007, FQs were no longer recommended by the CDC, defer ring to the third-generation cephalosporin antibiotics (includ ing the orally administered cefixime and ceftriaxone).4,6 The inexorable resistance propensity of N. gonorrhoeae has engendered the emergence of strains resistant to cefixime and ceftriaxone. Treatment failures with cefixime have been
17
Gonorrhea Surveillance in Ghana, Africa verified in Japan, Norway, England, Austria, France, Canada, Vietnam, England, Wales, and Sweden.7-10 Cefixime resis tance of 3.5% was reported in isolates acquired in Norway in 2009n ; and 1% cefixime resistance in British Columbia in isolates acquired between 2007 and 2011.12 European gonorrhea surveillance (Euro-GASP) noted that 31% of iso lates in 2009/2010 exhibited decreased susceptibility to cefixime (MIC >0.125 mg/L).13 Decreased susceptibility or frank resistance to cefixime increased from less than 1% to 8% in Sweden from 2007 to 2011.14 Per the Gonococcal Isolate Surveillance Project (GISP), from 2000 to 2010 in the United States, the percentage of isolates with elevated MICs (>0.25 pg/mL for cefixime) increased from 0.2% to 1.4%. The increases were most pronounced in known highrisk groups including men having sex with men (MSM).5 Recently, ceftriaxone-resistant isolates have been identi fied in Japan (2009), France (2010), Vietnam,9 Norway11 (2009), and Spain (2011).15,16 Decreased susceptibility to ceftriaxone was reported in Sweden (2007-2011),14 China17 (2005-2008), and Australia (2010).18 The GISP network in the United States revealed an increase in elevated MICs to ceftriaxone from 0% to 0.4% from 2006 to 2011. Ceftriaxone treatment failures of pharyngeal gonorrhoea have been verified in Sweden (2010), and Slovenia (2011).14,1:1 Thus, there is concern over the potential widespread emergence of N. gonorrhoeae resistance to cephalosporins. Gonorrhea resistance may be predicted in Ghana given contemporary (1) indiscriminate antimicrobial use, (2) lack of antimicrobial stewardship, (3) suspect antimicrobial com pliance, (4) increase in cosmopolitan lifestyle and migration, and (5) lack of laboratory infrastructure. We implemented gonorrhea surveillance in Ghana as an integral component of the AFHSC-GEIS supported STI program to fill the gap in knowledge regarding gonorrhea prevalence and antimicrobial resistance characterization.
METHODS Participating facilities included three outpatient military clinics of the Ghana Armed Forces in the port city of Takoradi, and the 37 Military Hospital (Accra, Ghana). These military clinics serve the military, their dependents, and civil ian population in their catchment area (comprising about 80% of the census). Subjects were 12 years of age and older (those 0.001) and not significant for gender and Chlamydia NAAT (p 0.2). Age showed a trend toward significance by Fisher’s exact testing for gonorrhea NAAT (p = 0.086) and for Chlamydia NAAT (p = 0.663). The concordance rate (gonor rhea culture + accompanied by gonorrhea NAAT +) was 13/13 (100%); while the concordance rate (gonorrhea NAAT + accompanied by gonorrhea culture +) was 13/38 (34%). The seven confirmed specimens were all resistant to ciprofloxacin, penicillin, and tetracycline, and sensitive to ceftriaxone and cefixime. Six of seven specimens were sensi tive to spectinomycin.
DISCUSSION Treatment options are becoming limited given the increasing antibiotic resistance in the absence of novel antimicrobials in the pipeline. The emergence of MDR N. gonorrhoeae is ushering in an era of unbeatable gonorrhea. Therefore, sur veillance for gonorrhea and resistant gonococcal isolates coupled to an integrated public health response is required to (1) expedite identification and subsequent containment of resistant isolates mitigating transmission; (2) optimize individual-level treatment; (3) contribute to local, regional, TABLE I.
and national surveillance networks; (4) support epidemiologic investigations, (5) facilitate lab capacity in cultures and AST; and (6) identify risk factors for harboring gonorrhea and resis tant isolates that will assist policy makers in allocating limited resources for the adoption of prevention, health promotion, and educational campaigns targeting at-risk populations.20 This concerted surveillance strategy will extend the duration of efficacy of the few existing antimicrobial drug options in our armamentarium for treatment of gonorrhea.6 The preponderance of resistant gonococcal isolates has hitherto been identified through active surveillance networks thus substantiating the efficacy of maintaining global sur veillance. The mission of the Global Emerging Infections Surveillance and Response System Division at the U.S. Department of Defense's (DoD) Armed Forces Health Sur veillance Center (AFHSC-GEIS), is to develop, implement, support, and evaluate an integrated global emerging infec tious disease surveillance and response system that contrib ute to enhancement of U.S. Forces’ health, the collaborating host nations Public Health Systems, and the global public health community. The consortium’s objectives in establish ing global STI surveillance networks have been described elsewhere.21 There is a dearth of cross-sectional and longitudinal gon orrhea surveillance in West Africa (including Ghana). These countries are not engaged in surveillance activities due to limited resources in addition to potential impeding cultural issues (possible aversion to stigmatization and clinical inva siveness). Cross-sectional investigations have been conducted in Uganda, Benin, Malawi, Tanzania, Zimbabwe, Ethiopia, and Kenya focusing on gonorrhea incidence and acquisition of risk factors, but longitudinal studies are lacking as are data on resistance levels. Mirroring developed nations, the empha sis on STI syndromic management has stagnated the develop ment of clinical laboratory capacity to execute N. gonorrhoeae AST.’’ Implementing surveillance networks throughout Africa will contribute to the global surveillance networks serving as a beacon on potential resistant isolates migrating into and out of the continent.
Results of Gonorrhea and Chlamydia Culture and NAAT Testing Stratified by Age and Gender* Gender
Culture +
Gonorrhea NAAT +“
Chlam ydia NAAT +“
Age
M
F
M
F
M
F
M
F
Age 50 Totals
0 10 34 42 28 10 7 4 3 138
1 2 16 19 24 6 6 1 1 76
0
0 0
0
1
3
1 2 0
0 0 1
0
1
4 4 3 0 0 0 0 12
1
0 0 0 0 0 0 1
8 10
6 5
0
4 1 2
0 1
2 3
0
0 0 0 0
0
0 0 0 0
33
4
9
6
0 1
1 0
“M issing demographic data on two Gonorrhea NAAT and one Chlam ydia NAAT.
MILITARY MEDICINE, Vol. 180. January 2015
19
Gonorrhea Surveillance in Ghana, Africa
There is a dramatic variation in STI prevalence across surveyed African countries and targeted populations. Hetero geneous studies conducted in Africa among patients presenting with STI symptoms exhibited prevalence rates of gonorrhea of 0.4% (Congo),22 5.7% in Benin,23 8.4% in Tanzania, 17.1% in Malawi,24 2% in Tanzania,19 5.6% in Kenya (young HIV negative males),25 and 1.4% in Zambia26 (HIV positive women). Gonorrhea was identified in 11.6% (Chlamydia 5%) of surveyed clinical sex workers (CSW) in Rwanda—5% each in Benin and 1.6% (30%) in Tanzania—and 16% (3%) in general surveys of CSW in West Africa.27 We noted that within a convenience sampling of a populationbased survey of patients presenting with STI symptoms, 13/220 (6%) specimens tested were positive by local culture. We noted that 39/213 (18%) specimens tested were positive by NAAT. Our gonorrhea culture results are consistent with the prior investigations executed in Africa. The discrepancy in positivity solicited from culture and NAAT testing may be attributed to several factors: (1) superiority in NAAT testing over culture, (2) the ubiquitous access to over-the-counter antimicrobials, and (3) suboptimal culture conditions. Studies have demon strated superiority in molecular testing over culture-based diagnosis in gonorrhea.28 There is a ubiquitous lack of anti microbial stewardship in Ghana. An appreciable percentage of patients presenting to our participating clinics have taken anti biotics obtained from pharmacies, chemists, or family/friends (29%). The indiscriminate access to antimicrobials has been a consistent finding observed in other GEIS-funded surveillance efforts in this region including acute febrile illness and antimalarial resistance surveillance investigations. This practice undermines successful pathogen cultivation, undermining health objectives and complicating surveillance. Additionally, pelvic examinations with endocervical sampling should be emphasized as opposed to accepting high vaginal swabs. Finally, subjecting the swab itself to molecular testing may provide a higher yield than culture.28 There was a significant difference in the yield of positive cultures between enrolled men and women. The bias in positive cultures favoring males contradicts the bias to greater positivity identified in woman within the GISP sur veillance activities.29 The population-based data accumu lated within GISP activities may have integrated female health programs (biasing toward positive female isolates). Additionally, differential positivity may be attributed to the difficulty in specimen acquisition described above, and the dilution of STI presentations in females attributed to gonor rhea due to the wider differential in females. A large attrib utable fraction of syndromic STI symptoms in women stem from candidiasis, bacterial vaginosis, and Trichomonas vaginalis30 likely diluting the percentage of gonorrhea recovery. For example, specimens acquired from Kenyan women presenting with vaginal discharge yielded rates of candidiasis (50%), trichomoniasis (23%), bacterial vaginosis (9%), gonorrhea (7%), Chlamydia (9%), and syphilis (7%), respectively.31 Acknowledging this, empiric treatment algo
20
rithms have adopted integration of metronidazole coupled to dual gonorrhea and Chlamydia treatment. Ideally, future sur veillance will integrate more expansive testing for the afore mentioned pathogens into diagnostic algorithms to further optimize treatment (reducing indiscriminate and unnecessary antimicrobial prescriptions). Of note, military personnel composed 17% of the cohort and there was no significant difference in positive recovery rates in military vice non military patients. All confirmed isolates were MDR (resistant to ciprofloxa cin, tetracycline, and penicillin). Regrettably, 6/13 of the isolates originally suspected to be gonorrhea from the local labs could not be confirmed. Confirmatory testing failed because of inappropriate cold chain storage, contaminated samples stemming from suboptimal processing, and technical (staffing) issues. Nonetheless, the prevalence of ciprofloxacin resistance in all tested isolates is noteworthy and has already altered the empiric treatment paradigm in our participating clinics from dual therapy with ciprofloxacin and doxycycline to ceftriaxone and doxycycline. Our data were biased to subjects older than 18 years of age. Gonorrhea prevalence is historically highest in the youn ger cohorts and particularly between the ages of 15 and 24. There appears to be some reluctance from subjects
