Sharaf Ali Shah ( BIRDGE Consultants Foundation, Karachi, Pakistan. )
Ghazala Usman ( BIRDGE Consultants Foundation, Karachi, Pakistan. )
Asifa Ghazi ( BIRDGE Consultants Foundation, Karachi, Pakistan. )
Sibylle Kristensen ( Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA. )
Nalini Sathiakumar ( Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA. )
Mohammad Ashraf Memon ( Sindh AIDS Control Program, Karachi, Pakistan. )
Rubina John ( Civil Hospital Karachi, Pakistan. )
Sten Havlor Vermund ( Institute for Global Health and Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. )
Objectives: To assess the prevalence and associated risk factors of syphilis among antenatal clinic attendees by a multi-center cross-sectional study in Karachi, Pakistan.
Methods: We administered a structured questionnaire and obtained a blood sample for syphilis serology (rapid plasma reagin test with Treponema pallidum hemagglutination assay confirmation) from all women giving informed consent over six weeks in 2007. Prevalence was calculated at 95% confidence intervals. Multivariate analysis was adapted to assess risk factors.
Results: There were seven (0.9%) confirmed cases of syphilis (95%CI: 0.4, 1.8) in a sample size of 800 women recruited from three urban sites (~1% refusal rate). Women who lived in an area where male drug use is prevalent had 1.5% higher prevalence rates than women from the other two sites 0.5%.
Conclusions: We documented higher-than-expected syphilis seroprevalence rates in a low risk population of antenatal clinic attendees in Pakistan. Bridge populations for syphilis may include drug users, who are usually married, and Hijras or their clients. In accordance with our results, the national policy for syphilis control in Pakistan should be modified to include universal syphilis screening in antenatal clinics with subsequent partner notification.
Keywords: Syphilis, Prevalence, Pregnancy, Antenatal care, Policy, Pakistan (JPMA 61:993; 2011).
As in most resource-limited countries, widespread screening is not conducted in Pakistan for many important infectious and metabolic diseases during pregnancy and in newborns, including syphilis, HIV, gonorrhea, chlamydia, and inborn errors of metabolism.1 In addition, Pakistan has one of the highest fertility rates of any country in the world, estimated by UNICEF to be 3.6 per women.2 Syphilis in pregnant women is associated with low birth weight, prematurity, and intrauterine death.3 The World Health Organization (WHO) estimated that 1 million pregnancies are affected by syphilis worldwide in 2004.4 Nearly half (n=460 000) will result in abortion or perinatal death, 270 000 will be born with low birth weight and/or prematurity, and 270 000 will be born with congenital syphilis.4 Because of the serious complications of syphilis in pregnancy, WHO has recommended universal antenatal screening; WHO further recommended screening for syphilis at the first antenatal visit, as early as possible in pregnancy, repeating in the third trimester if resources permit, to detect infection acquired during pregnancy.5,6 The effectiveness of such antenatal syphilis screening and its treatment for the prevention of adverse pregnancy outcomes has been well documented.7 However among Pakistani opinion leaders or most government officials, moat sexually transmitted infections (STIs), including syphilis, are not considered to be problems of public health significance. There is social stigma associated with STIS, along with a paucity of published data, and a generalized lack of STIs awareness among the lay public and medical practitioners alike. Many believe that STIs cannot be very important in a sexually conservative Muslim nation.
This study was therefore conducted to assess the prevalence and associated risk factors of syphilis among antenatal clinic (ANC) attendees in Karachi, Pakistan.
Study design and study site: This was a cross-sectional prevalence study of women attending ANC in Karachi, the principal port, the largest city and the economic hub of Pakistan (2007 estimate population >12 million). To improve the generalizability of our findings, we included three antenatal clinics of Karachi: (1) the Civil Hospital, (2) the Kharadar General Hospital Karachi, and (3) the Ibrahim Hyderi Hospital. The Civil Hospital is a tertiary care teaching hospital affiliated with Dow University of Health Sciences and located in the center of Karachi. It provides health care services not only to the people of Karachi, but also to a large number of patients from the interior of Sindh and other provinces. All three hospitals mostly provide services to patients from poor and/or middle socio-economic class. The Ibrahim Hyderi Hospital is located near the harbour and mainly serves the fishermen community. The majority of inhabitants are poor and drug use is common, the drug users are all men and most are married.
Recruitment: A trained research officer conducted a daily session with all the pregnant women in the ANC who were 18 to 45 years old and willing to participate. After signing an informed consent form, the women were enrolled for the questionnaire and syphilis test.
Sample Size Calculation: The sample size was calculated using an online, open source statistical calculator for public health\\\'. With 95% confidence level, and expected frequency of the outcome of 2%, and 1% of bond on the error, we required at least 753 study participants for the assessment of the outcome. The sample size was inflated by 5% for refusals and drop outs. Therefore we required at least 791 participants for the study purpose.
The sample size was equally divided into three different sites including urban and peri-urban and public and private health facilities. We used convenient sampling technique (first 270 women who walked in clinics were approached for enrollment in the study). Our response rate was overs 95.
The study protocol and questionnaire were approved by all relevant Pakistani and United States Ethical Review Boards.
Data Collection: Data were collected through a face-to-face interviewer-administered structured questionnaire. The study questionnaire was originally developed in English, and was then translated into Urdu. Reverse translation of the questionnaire ensured the correctness and compatibility of the first translation. The questionnaire included information about socio-demographic characteristics and sexual behaviors of study subjects and their husbands. Obstetrical histories of study subjects were obtained, including history of spontaneous or therapeutic abortions, stillbirths and low birth weight babies. Prior to data collection, the questionnaire was pre-tested among five women and appropriate changes were made according to the feedback received. Data collectors were trained in research techniques, the purpose of the study, and ethical considerations. As blood is routinely drawn during the antenatal checkup for haemoglobin, a free syphilis test was offered to all participants. Five mL of blood were drawn by a trained phlebotomist and transferred to a designated laboratory.
Laboratory analysis: Blood samples were tested by rapid plasma reagin (RPR) card test (Randox kit). All reactive samples were tested for titration on dilution method. All were considered positive with titre more than 1:64. RPR-reactive specimens were confirmed with a Treponema pallidum haemagglutination assay (TPHA) test (Randox kit). Specimen positive on both RPR and TPHA were considered as syphilis seroreactive (syphilis positive). All syphilis positive study participants were provided counseling and free treatment with injectable benzathine penicillin 2.4 million units intramuscularly once every week for three consecutive weeks as per Sindh AIDS & SITs Provincial guidelines.
Data management and analysis: All questionnaires were checked for completeness and double data entry was performed by trained data entry operators in Statistical Package for Social Sciences (SPSS) version 13.0™ (SPSS, Inc., College Station, TX, USA). Before final analysis, data were validated and cleaned for possible data entry errors. The prevalence of syphilis infection was computed with 95% confidence intervals (95% CI) for the entire group and for risk-defined subgroups. Syphilis prevalence was compared between the high-risk and the low-risk women using a prevalence odds ratio (POR) with 95% CI. When PORs could not be computed because of zero cells, a Chi-square test or a Fisher\\\'s exact test was used to assess the extent to which differences might be due to chance alone. Exact logistic regression procedures were used to adjust for multiple risk factors. A potential risk factor was included in the multivariable model if there was moderate association in either direction (positive or inverse) between the risk factor and the prevalence of syphilis (that is, POR > 2 or < 0.5). Data analysis was conducted using the SAS version 9.1™ (SAS, Inc., Cary, NC, USA).
Among 800 pregnant women, the prevalence of TPHA-confirmed syphilis was found in seven women (0.9%; 95%CI: 0.4, 1.8). The prevalence of syphilis among women attending Ibrahim Hyderi was 1.5% higher than among women from the other two sites. Women married to men with a lower educational background had a higher syphilis prevalence (p =0.04). Women >25 years of age, of Sindhi ethnicity, of a lower educational background, married to self-employed men, employed as housewives, and with an income <5,000 rupees/month had higher syphilis prevalence rates, but these differences may have been due to chance (Table-1). Multiparous women, women with more than one child still alive, women with a history of stillbirth, abortion or low birth weight, women married for >5 years, women with genitourinary symptoms, and women who never used contraceptives had a higher syphilis prevalence rate, but again these differences might have been due to chance (Table-1).
None of the seven infected women were aware of any symptoms in their husbands or partners. Women\\\'s extramarital relations and drug use predicted significantly higher syphilis prevalence, while a husband\\\'s extramarital relations and drug use predicted higher syphilis prevalence but differences may have been due to chance (Table-2).
Of the seven infected women, four were from the Ibrahim Hyderi Hospital (4/264, 1.5%) and three were from either the Civil Hospital, or the Kharadar General Hospital (3/536, 0.5%).
Multivariate analysis: Ten risk factors were included in multivariable analysis based on the strength of association criteria cited in methods above: maternal age, husband\\\'s occupation, income, gravidity, number of live children, previous history of low birth weight infant, years of marriage, extramarital relations, husband\\\'s extramarital relations, and husband\\\'s habitual drug use. None of these associations were statistically significant with our comparisons of seven infected and 793 uninfected women.
The 0.9% seroprevalence rate for syphilis among ANC attendees in three major hospitals of Karachi, Pakistan was relatively high when compared to rates in Europe and North America. While it is true that several studies have found few or no cases of syphilis among the general population,8,9 women in Pakistan who have sex with high-risk men such as drug users or sex partner of hijras can be at considerable risk. Baqi et al reported a 37% prevalence of syphilis among Hijras (male transvestites and/or transgenders) in Karachi.10 A 2004 survey of high-risk subgroups in Lahore and Karachi by the National AIDS Control Program reported a syphilis prevalence of 60% among Hijras and 36% among other male sex workers (MSW).11 Altaf et al reported a13.1% prevalence among registered male injection drug users (IDUs) at a needle exchange and harm reduction programme in Karachi.12 Thus, Hijras, their male sexual clients, and male IDUs are likely STI bridge populations to women; Hijras practice sex work with married men also. Outreach workers estimates that 25-30% clients of hijras are married men (Personal Communication Wajid Ali & Reema-outreach workers for transgenders HIV Prevention Project-Karachi). While IDUs are likely to be married unless they are very young. All these factors make Pakistani married women vulnerable who are mostly unable to negotiate safe sex with their husbands due to socio cultural constraints.
There is no data available at this moment regarding prevalence of syphilis of other STIs and HIV/AIDS among clients of hijras and other sex workers in Pakistan. Compared to other commercial sex workers it is relatively easier to buy sex from hijras because they are easily accessible, cheaper and culturally tolerable in the society. Therefore hijra sex workers has much higher number of clientele. Given the survey data among Hijras, MSW, and IDUs, the potential for increasing syphilis rates in Pakistani women is therefore substantial with the current syphilis situation reminiscent of the HIV epidemic where the problem is worst in one specific subgroup (IDUs), but has the potential to jump to others very quickly.
In addition it should be noted that in neighboring India, the prevalence of syphilis ranges between 2.0-4.8 % among women of reproductive age.13-16 In Bangladesh a largely Muslim nation that shares many customs with Pakistan, a cross sectional clinic based study conducted in two urban primary health care level clinics among 1103 women found 1.5% prevalence of syphilis.17 Another study conducted in Dhaka Bangladesh among 284 pregnant women found an estimated prevalence of 3%.18 A preponderance of our syphilis cases were among the attendees of the Ibrahim Hyderi Hospital; unlike the catchment area serving the other two sites (the Civil Hospital and the Kharadar General Hospital), Ibrahim Hyderi Hospital serves a peri-urban settlement around the fish harbour of Karachi. Persons working in the fishing industry include men on fishing boats and trawlers that remain at-sea for weeks or even months. Many Pakistani fishermen in the process of actual or perceived fishing around national boundaries, may be imprisoned in neighboring countries for a time, thus increasing their chances for potential sexual contact with high-risk infected partners.
The strengths of our study include a sample size of 800 women and the use of three diverse sites representing all of the major ethnic and socio-economic levels, as well as both urban and peri-urban areas. The Ibrahim Hyderi Hospital population is the poorest, has a high illiteracy rate, especially among wives of fisherman. Drug use, including IDU, is more common in this district. In contrast, the Civil Hospital and the Kharadar General Hospital are located in the center of Karachi, and serve a lower and middle class population. The Civil Hospital is the teaching hospital of Dow University of Health Sciences and gets patients from throughout Karachi and from elsewhere in Sindh or Balochistan Provinces. Kharadar General Hospital is a charitable institution established by the business community (Memon Community) and is situated in the old town, catering mainly to the needs of the Memon ethnic population and other communities in the area. The limitations included the absence of data from rural areas and an insufficient sample size to determine risk factors given the 0.9% syphilis prevalence rate. There are few (statistically non-significant) correlations that could have become significant if we had a larger sample size such as the correlation between the woman\\\'s lack of work, woman\\\'s or the husband\\\'s low educational status and low household income.
Gestational syphilis is of particular concern in under-equipped health systems and wherever access to health care is a major limiting factor for programme effectiveness. Adverse pregnancy outcomes include direct placental, foetal, or neonatal infection, or preterm birth associated with some long term neurological damage. Infant mortality rates in Pakistan were estimated at 66.95/1000 live births in 2008.19 Congenital syphilis poses a significant challenge especially because infants may be stillborn, asymptomatic at birth but nonetheless infected, or present with a highly variable clinical picture, thereby precluding easy clinical diagnosis. The high risk of congenital syphilis in untreated or inadequately treated mothers (14%) is one reason why 40% of these pregnancies end in fetal loss or perinatal death.20 All these adverse outcomes continue to make syphilis a global problem of major medical and public health consequences.21,23 Moreover, syphilis predisposes to HIV infection and can, in turn, increase the transmissibility of HIV.24,25
A seroprevalence of nearly 1% among low-risk Pakistani women suggests the need to recommend that universal syphilis screening in pregnancy be instituted in Pakistan with subsequent partner notification, to reduce the prevalence of a potentially dangerous disease, reduce gestational and congenital syphilis, and reduce the potential risk of HIV transmission.
This work was funded, in part, by the AIDS International Research and Training Programme of the Fogarty International Center, National Institutes of Health (grant # D43TWO1035).
1.Khan EA. Antenatal screening for infectious diseases: an effective preventive opportunity. Infect Dis J 2006; 15: 71-7.
2.UNICEF PAKISTAN: Statistics. (Online) (Cited 2008 July). Available from URL: www.unicef.org/infobycountry/pakistan_pakistan_statistics.html.
3.Chakraborty R, Luck S. Syphilis is on the increase: the implications for child health. Arch Dis Child 2008; 93: 105-9.
4.Walker DG, Walker GJ. Prevention of congenital syphilis--time for action. Bull World Health Organ 2004; 82: 401
5.World Health Organization: Detecting Sexually Transmitted Infections: Reproductive Tract Infections. (Online) (Cited 2008 May). Available from URL: http://www.who.int/reproductive-health/publications/rtis_gep/ syphilis.htm.
6.World Health Organization: Sexually Transmitted Infections: Reproductive Tract Infection assessment in pregnancy, childbirth and the postpartum period. (Online) (Cited 2008 May). Available from URL:http://www.who.int/reproductive-health/publications/rtis_gep/pregnancy.htm.
7.Watson-Jones D, Gumodoka B, Weiss H, Changalucha J, Todd J, Mugeye K, et al. Syphilis in pregnancy in Tanzania II. The effectiveness of antenatal syphilis screening and single-dose benzathine penicillin treatment for the prevention of adverse pregnancy outcomes. J Infect Dis 2002; 186: 948-57.
8.Sami S, Baloch SN. Vaginitis and sexually transmitted infections in a hospital based study. J Pak Med Assoc 2005; 55: 242-4.
9.Sultan F, Mehmood T, Mahmood MT. Infectious pathogens in volunteer and replacement blood donors in Pakistan: a ten-year experience. Int J Infect Dis 2007; 11: 407-12.
10.Baqi S, Shah SA, Baig MA, Mujeeb SA, Memon A. Seroprevalence of HIV, HBV and Syphilis and associated risk behaviours in male transvestites (Hijras) in Karachi, Pakistan. Int J STD AIDS 1990; 10: 300-4.
11.National study of reproductive tract and sexually transmitted infections. Survey of high risk groups in Lahore and Karachi, 2005. National AIDS control program. Ministry of Health Government of Pakistan (Unpublished).
12.Altaf A, Shah SA, Zaidi NA, Memon A, Nadeem-ur-Rehman, Wray N. High risk behaviors of injection drug users registered with harm reduction programme in Karachi, Pakistan. Harm Reduct J 2007; 4: 7.
13.Panda S, Kumar MS, Saravanamurthy PS, Mahalingam P, Vijaylakshmi A, Balakrishnan P, et al. Sexually transmitted infections and sexual practices in injection drug users and their regular sex partners in Chennai, India. Sex Transm Dis 2007; 34: 250-3.
14.Carey MP, Ravi V, Chandra PS, Desai A, Neal DJ. Prevalence of HIV, Hepatitis B, syphilis, and chlamydia among adults seeking treatment for a mental disorder in southern India. AIDS Behav 2007; 11: 289-97.
15.Bhalla P, Chawla R, Garg S, Singh MM, Raina U, Bhalla R, et al. Prevalence of bacterial vaginosis among women in Delhi, India. Indian J Med Res 2007; 125: 167-72.
16.Chawla R, Bhalla P, Garg S, Meghachandra SM, Bhalla K, Sodhani P, et al. Community based study on sero-prevalence of syphilis in New Delhi (India). J Commun Dis 2004; 36: 205-11.
17.ICDDR, B. Screening for Syphilis in Routine Antenatal Care. Health Sci Bull 2003; 1: 5-8.
18.Bogaerts J, Ahmed J, Akhter N, Begum N, Rahman M, Nahar S, et al. Sexually transmitted infections among married women in Dhaka, Bangladesh: unexpected high prevalence of herpes simplex type 2 infection. Sex Transm Inf 2001; 77: 114-9.
19.CIA. World Fact Book: Pakistan. (Online) (Cited 2008 July). Available from URL: https://www.cia.gov/library/publications/the-world-factbook/geos/ pk.html.
20.CDC. Congenital syphilis -- New York City, 1986-1988. MMWR Morb Mortal Wkly Rep 1989; 38: 825-9.
21.Sanchez PJ, Wendel GD. Syphilis in Pregnancy. Clin Perinatol 1997; 24: 71-90.
22.Goldenberg RL, Culhane JF, Johnson DC. Maternal infection and adverse fetal and neonatal outcomes. Clin Perinatol 2005; 32: 523-59.
23.Sangtawesin V, Lertsutthiwong W, Kanjanapattanakul W, Khorana M, Horpaopan S. Outcome of maternal syphilis at Rajavithi Hospital on offsprings. J Med Assoc Thai 2005; 88: 1519-25.
24.Onorato IM, Klaskala W, Morgan WM, Withum D. Prevalence, incidence, and risks for HIV-1 infection in female sex workers in Miami, Florida. J Acquir Immune Def Syndr Hum Retrovirol 1995; 9: 395-400.
25.Laga M, Alary M, Nzila N, Manoka AT, Tuliza M, Behets F, et al. Condom promotion, sexually transmitted diseases treatment, and declining incidence of HIV-1 infection in female Zairian sex workers, Lancet 1994; 344: 246-8.