The prevalence of syphilis in HIV-seropositive patients: a retrospective study at the regional hospital in Agadir, Morocco

The prevalence of syphilis in HIV-seropositive patients: a retrospective study at the regional hospital in Agadir, Morocco

Mohamed Bourouache^1,&, Rachida Mimouni¹, Mohamed Nejmeddine², Smail Chadli³, Fatima Benlmeliani⁴, Jamila Sardi⁴, Mourad Malmoussi⁵, Zineb Ouagari⁵, Maryam El Basbassi⁴, Mohamed Aghrouch⁴

 

¹Department of Biology, Faculty of Sciences, Ibn Zohr University, Agadir, Morocco, ²Infectious Diseases Group, Laboratory of Cell Biology and Molecular Genetics, Faculty of Sciences, Ibn Zohr University, Agadir, Morocco, ³Higher Institute for Nursing Professions and Health Techniques, Agadir, Morocco, ⁴Laboratory of Bio-Medical Analysis, Hassan II Regional Hospital, Agadir, Morocco, ⁵Department of Infectious Diseases, Hassan II Regional Hospital, Agadir, Morocco

 

 

^&Corresponding author
Mohamed Bourouache, Department of Biology, Faculty of Sciences, Ibn Zohr University, Agadir, Morocco

 

 

 

 

Syphilis is a sexually transmitted infection (STI), associated with the bacterium Treponema pallidum [1]. The vast majority of infections are sexually transmitted [2]. However, the infection might also be transmitted from an infected woman to her newborn child [3]. During pregnancy, the syphilis can lead to spontaneous abortion, congenital deformities, or severe neonatal disease [4-6]. This infection, which can cause long-term complications if not treated appropriately [7, 8], continues to be a major health concern in Morocco [9, 10]. The syphilis is a progressive disease, which could be classified according to the degree of severity; from primary stage, to the tertiary that leads to a disease of the central nervous system, called neurosyphilis [11]. Different signs and symptoms are associated with each stage [12]. The overall incidence of syphilis in the world have increased in recent years [13-15], partially due to its association with HIV infection [16]; Especially, in high-risk groups, including drug users (IDUs), female sex workers (FSWs) and men who have sex with men (MSM) [17-19]. The HIV is still a common causes of morbidity and mortality around the world, particularly in the developing countries [20, 21]. Interestingly, syphilis itself facilitates HIV infection in several ways and vice versa [22]. In 2009, an analysis of the medical records shows that 24.6% of all HIV cases registered in the country were from the region of Souss-Massa, in the south-west of Morocco [10]. Previous reports that evaluated the association between HIV and syphilis in Morocco focused mostly on some high risk groups; in particular, female sex workers and men who have sex with men [9, 23]. This led to an overestimation of the prevalence of syphilis in the general population of Souss-Massa. The aim of this study is to establish a more accurate assessment of the prevalence of syphilis in patients tested positive for HIV.

 

 

Collecting data: the department of infectious disease of the regional hospital in Agadir covers all HIV patients from the whole region of Souss-Massa, Morocco. The medical records of HIV-infected patients, tested between 2011 and 2016, were examined for the presence of syphilis and neurosyphilis cases.

 

Screening for HIV: screening for HIV infection was performed according to the Moroccan Health Ministry recommendations (Figure 1). The diagnostic of HIV infection included a rapid test (Alere Determine^®HIV-1/2, Alere Inc, Japan) white visual read; qualitative immunoassay for the detection of antibodies to HIV-1 and HIV-2; or the ELISA test (Murex^®HIV Ag/Ab Combination, Dia-Sorin S.p.A, Saluggia, Italy). In addition, a confirmation test was performed using a Western blot test (MP Diagnostics (MPD) HIV BLOT 2.2, Japan). The interpretations of the tests were performed in accordance with the recommendations of the World Health Organization (WHO), based on the detection of two ENV bands, with or without GAG or POL bands.

 

Serological tests for the detection syphilis: the serological diagnosis of syphilis was based on a series of two types of serological tests. The first test was a non-treponemal antigen test (VDRL), used for the screening for syphilis in serum or cerebral spinal fluid. The Venereal Disease Research Laboratory test (VDRL; carbon antigen plasmatec laboratory products Ltd, Bridport, UK) allowed the detection of antibodies directed against non-treponemic antigens, called cardiolipins. The second test was a treponemal antigen test TPHA (treponema pallidum hemagglutination assay; immutrep^® TPHA, Omega Diagnostics, UK). This test was based on an indirect hemagglutination assay for the detection and titration of antibodies against the causative agent of syphilis, treponema pallidum. The samples that were positive in both tests were then identified as seropositive for syphilis.

 

Statistical analysis: statistical analysis of data was performed using the R software, version 3.16. The results were summarized using descriptive statistics. The Welch two sample t-test was used to evaluate the differences between gender (male and female) for both HIV and syphilis prevalence. The Pearson´s correlation coefficient was used to assess the correlation between HIV and syphilis. The patients details obtained during the study were kept confidential.

 

Ethical considerations: as data were collected in patient's register, no informed consent was necessary. Patients informations obtained during the study were kept confidential. The study was approved by the Department of Infectious Disease of the Regional Hospital in Agadir.

 

 

A total of 2808 HIV seropositive patients were included in the present study. The calculated sex ratio was 0.97, for a gender distribution of 1381 males (49.18%) and 1427 females (50.82%). The average annual incidence of HIV infection between 2011 and 2016 was estimated to be about 468 ± 94.41 cases per year. The highest number of new cases was recorded in 2014, with 623 (22.19%) cases. By contrast, the lowest number of new cases was recorded in 2012 with 346 (12.32%) cases (Table 1). We did not detect a statistically significant difference between the male and female seropositive patients (p = 0.788). Among the 2808 HIV seropositive patients, 481 were tested positive for syphilis and 3 cases were diagnosed with neurosyphilis. Syphilis was therefore prevalent in 16.42% in this population, slightly more in males (17.63%) than in females (15.28%). However, this difference was not statistically significant (p = 0,492). The three cases of neurosyphilis detected were all males, placing the prevalence of neurosyphilis in the HIV seropositive patients around 0.11% (Table 2). Statistical analysis of the data showed a significant positive correlation between HIV and syphilis (r = 0.828; p = 0.042).

 

 

Souss Massa (SM) is home to 2,677 million inhabitants (according to the latest general population and housing census in 2014), many of whom live in Agadir the region's capital and largest city. The Infectiology Department of the Agadir Regional Hospital provides reception, medical care and drug distribution to almost all HIV and STIs patients in the region [24]. Like everywhere else in the world, in particular in Africa, the sexually transmitted infections (STIs) in Morocco constitute a public health burden. Around 400,000 new cases are registered through public health clinics every year, but the true burden is believed to be higher, as cases that are not symptomatic and not treated, or which are managed by private health providers or self-treated, are not reported [19]. We report on the seroprevalence of HIV, syphilis and neurosyphilis among the population in the region of Souss-Massa, than compared the results with previous data in the region of Souss-Massa as well as with recently reported data in other regions of Morocco. According to the Health Ministry Department, the region of Souss-Massa is the most affected regions by HIV/AIDS in Morocco. In 2009, this region recorded the highest prevalence of HIV/AIDS in the country (0.9%) [10]. Since then, few studies have been carried out in the area [9, 17, 21, 23-28]; most of them were especially focused on groups that carried a high-risk (female sex workers, men who have sex with men, drug users) [9, 17, 23]. These groups are the core drivers of the HIV epidemic in Morocco and elsewhere in the world, with heterosexual sex-worker networks being the largest of the three kinds of high-risk groups, followed by MSM, and then IDUs [10]. These studies might have overestimated the influence and the prevalence of HIV and STIs in the general population. The purpose of this study was to examine more accurately the prevalence of syphilis and neurosyphilis in HIV seropositive-patients of SM region for the last six years. New HIV infections were about 468 ± 94.4 cases per year. This incidence was higher than those previously reported in 2012 [17]. The highest number of new HIV cases was recorded in 2014 (Table 1). This might be due to the higher number of screening campaigns that took place in the country in recent years. Also, the higher awareness about the disease within the population probably resulted in the decline of stigma towards HIV carriers and some high-risk groups such as MSM and FSWS. In accordance with recent reports [17, 20, 25], the statistical analysis did not show a significant difference in prevalence between male and female populations (p = 0.224). This is contrast to previous studies in Morocco, as well as in most Arab countries, that often showed a gender dominance [10, 17, 21, 25].

 

We noted a stable incidence of new syphilis cases, despite the peak incidence in 2014. The prevalence of syphilis between 2011 and 2016 was estimated at 17.13% and did not appear to be affected by the genders (Table 3). This result is comparable to that found by Johnson et al 2013 [9]. By contrast, Bennani et al. 2017, reported a decline in the incidence and prevalence of active syphilis between 1995-2016 in Morocco [19]. In developing countries, prisons played an important role in HIV and STIs epidemics [29-31]. Prisoners represented a special high-risk group, due to high rates of injected drug users, unprotected sex and the use of non-sterile equipment for tattooing or for shaving [19, 32, 33]. Heijnen et al 2016, estimated 496,000 prisoners in MENA, with drug-related offences being a major cause for incarceration [33]. In Morocco, the prevalence of HIV among prisoners is between 0.4% to 0.8%, with higher prevalence in the regions of Souss-Massa-Draa and Marrakech Tensift Al Haouz [32]. But not enough data is available about prisoners in the Souss-Massa region [10, 32], which makes it difficult to assess the contribution of this group in HIV and STIs transmission. The rate of co-infection (Syphilis and HIV) is increasing in North Africa [34-36]; especially, in the group of MSM [37]. A recent report showed that co-infection with HIV and syphilis was estimated to 31.6% in Agadir and 56.4% in Marrakesh [9]. It is well known that the syphilis chancre creates an integument discontinuity, which facilitates the penetration of HIV into the organism [38]. The presence of the virus in the syphilitic ulcers was previously reported [39]. The immunodeficiency state induced by HIV infection [40] can also influence the clinical features and treatment outcome of the syphilis [41]. This was confirmed by the high positive correlation between HIV and syphilis in the MS population (r = 0.828 ; p = 0.042). All neurosyphilis cases (3 cases) were found in males during the year of 2015. The prevalence of neurosyphilis was estimated at 0.11%. This result was in agreement with those reported in 2016 by Fekih et al. [42]. The male correlation was probably due to the high frequency of chronic meningo encephalitis observed in men, which was 4-7 times more common in males than in females [43]. The men who have sex with men (MSM) showed the most exposure to syphilis [2, 14, 44]. Almost 90% of the Moroccan population that engages in intermediate-to-high-risk life style were males [10]. Indeed, 71% of all HIV infections among women are due to an infected spouse [26]. There was no significant difference between male and female groups, for HIV and syphilis prevalence (Table 3). This is probably due to the low rate of MSM in Agadir compared to Marrakech, and to the increased awareness of the general population about sexually transmitted infections (STI) and AIDS.

 

 

Both HIV and syphilis infections reached alarming rates in the region of Souss-Massa in the south-west of Morocco. Despite the peak recorded in 2014, the prevalence of HIV appears to be stable. However, the prevalence of syphilis among HIV patients remained high, and following the same trend as HIV. In order to prevent or to anticipate any further change in the current situation, In order to prevent or to anticipate any further change in the current situation, it is important to keep a permanent scrutiny of the prevalence and incidence in the region of Souss-Massa. This will be essential to provide a better care and to put in place adapted strategies of prevention in Morocco, especially among the most vulnerable in the general population.

 

 

The authors declare no competing interests.

 

 

Mohamed Aghrouch and Mohamed Nejmeddine conceived of the study and participated in its design and coordination. Mourad Malmoussi, Zineb Ouagar and Maryam El Basbassi were involved in the data collection. Fatima Benlmeliani, Jamila Sardi contributed in interpretation of data. Mohamed Bourouache drafted the manuscript. Rachida Mimouni, Smail Chadli reviewed and finalized the version to be published. All authors read and approved the final manuscript.

 

 

We are grateful to all who participated in this research.

 

 

Table 1: seroprevalence of HIV infection in Souss-Massa between 2011 and 2016

Table 2: seroprevalence of syphilis in the HIV seropositive patients between 2011 and 2016

Table 3: summary of the Welch two sample t-test

Figure 1: recommended laboratory HIV testing algorithm for serum or plasma specimens

 

 

1. Carbone Peter N, Capra Gregory G, Nelson Brenda L. Oral secondary syphilis. Head Neck Pathol Springer. 2016;10(2):206-208. PubMed | Google Scholar


2. Stoltey Juliet, Cohen Stephanie. Syphilis transmission: a review of the current evidence. Sex Health CSIRO. 2015;12(2):103-109. PubMed | Google Scholar


3. Lago Eleonor. Current perspectives on prevention of mother-to-child transmission of syphilis. Cureus Cureus Inc. 2016 Mar 9;8(3):e525. PubMed | Google Scholar


4. Rac Martha WF, Revell Paula A, Eppes Catherine S. Syphilis during pregnancy: a preventable threat to maternal-fetal health. Am J Obstet Gynecol Elsevier. 2017;216(4):352-363. PubMed | Google Scholar


5. Singh Rita, McCloskey Jenny C. Syphilis in pregnancy. Venereology. 2016;14(3):121-131.


6. Bonawitz Rachael E, Duncan Julie, Hammond Emily, Hamomba Leoda, Nambule Jane, Sambambi Kennedy et al. Assessment of the impact of rapid syphilis tests on syphilis screening and treatment of pregnant women in Zambia. Int J Gynecol Obstet Wiley Online Library. 2015 Jun;130 Suppl 1:S58-62. PubMed | Google Scholar


7. Braccio Serena, Sharland Mike, Ladhani Shamez N. Prevention and treatment of mother-to-child transmission of syphilis. Curr Opin Infect Dis LWW. 2016;29(3):268-274. PubMed | Google Scholar


8. Edwards Erin, Barger Mary, Tilghman Winston. Improving Syphilis Follow-up Rates: A Quality Improvement Project. 2017. Google Scholar


9. Johnston Lisa, Alami Kamal, El Rhilani M Houssine, Karkouri Mehdi, Mellouk Othoman et al. HIV, syphilis and sexual risk behaviours among men who have sex with men in Agadir and Marrakesh, Morocco. Sex Transm Infect BMJ Publishing Group Ltd. 2013;89(Suppl 3):iii45-iii48. PubMed | Google Scholar


10. Mumtaz Ghina, Hilmi Nahla, Zidouh Ahmed, El Rhilani Houssine, Alami Kamal, Bennani Aziza. HIV modes of transmission analysis in Morocco. Rabat Kingdom Morocco Minist Heal Natl STI/AIDS Program Jt United Nations Program HIV/AIDS, Weill Cornell Med Coll. 2010.


11. Stamm Lola V. Syphilis: antibiotic treatment and resistance. Epidemiol Infect Cambridge University Press. 2015;143(8):1567-1574. Google Scholar


12. French Patrick, Gomberg Mikhail, Janier Michel, Schmidt Bruno, van Voorst Vader P, Young H. IUSTI: 2008 European guidelines on the management of syphilis. Int J STD AIDS SAGE Publications Sage UK: London, England. 2009;20(5):300-309. PubMed | Google Scholar


13. Kim Yun Hee, Song Ji Ho, Kim Chan Jong, Yang Eun Mi. Congenital Syphilis Presenting with Only Nephrotic Syndrome: Reemergence of a Forgotten Disease. J Korean Med Sci. 2017;32(8):1374-1376. PubMed | Google Scholar


14. Mattei Peter L, Beachkofsky Thomas M, Gilson Robert T, Wisco Oliver J. Syphilis: a reemerging infection. Am Fam Physician. 2012;86(5):433-440. PubMed | Google Scholar


15. Furtado João M, Arantes Tiago E, Nascimento Heloisa, Vasconcelos-Santos Daniel V, Nogueira Natalia, de Pinho Queiroz Rafael et al. Clinical manifestations and ophthalmic outcomes of ocular syphilis at a time of re-emergence of the systemic infection. Sci Rep Nature Publishing Group. 2018 Aug 13;8(1):12071. PubMed | Google Scholar


16. Bhai Salman, Lyons Jennifer L. Neurosyphilis update: atypical is the new typical. Curr Infect Dis Rep Springer. 2015 May;17(5):481. PubMed | Google Scholar


17. Johnston Lisa, Oumzil Hicham, El Rhilani Houssine, Latifi Amina, Bennani Aziza, Alami Kamal. Sex Differences in HIV prevalence, behavioral risks and prevention needs among anglophone and francophone sub-Saharan African migrants living in Rabat, Morocco. AIDS Behav Springer. 2016;20(4):746-753. PubMed | Google Scholar


18. Maleke Kabelo, Makhakhe Nosipho, Peters Remco PH, Jobson Geoffrey, De Swardt Glenn, Daniels Joseph et al. HIV risk and prevention among men who have sex with men in rural South Africa. African J AIDS Res Taylor & Francis. 2017;16(1):31-38. PubMed | Google Scholar


19. Bennani Aziza, El-Kettani Amina, Hançali Amina, El-Rhilani Houssine, Alami Kamal, Youbi Mohamed et al. The prevalence and incidence of active syphilis in women in Morocco, 1995-2016: Model-based estimation and implications for STI surveillance. PLoS One. 2017 Aug 24;12(8):e0181498. PubMed | Google Scholar


20. Noska Amanda J, Belperio Pamela S, Loomis Timothy P, O'Toole Thomas P, Backus Lisa I. Prevalence of Human Immunodeficiency Virus, Hepatitis C Virus, and Hepatitis B Virus Among Homeless and Nonhomeless United States Veterans. Clin Infect Dis Oxford University Press US. 2017 Jul 15;65(2):252-258. PubMed | Google Scholar


21. Traoré Youssouf, Bensghir Rajaa, Lahsen Ahd Oulad, Lamdini Hassam, El Filali Kamal Marhoum. Exposition sexuelle potentielle au VIH: expérience du service des maladies infectieuses de Casablanca et revue de la littérature. Presse Med Masson. 2014;43(2):215-218.


22. Karp Galia, Schlaeffer Francisc, Jotkowitz Alan, Riesenberg Klaris. Syphilis and HIV co-infection. Eur J Intern Med. 2009 Jan;20(1):9-13. PubMed | Google Scholar


23. Johnston Lisa, Bennani A, Latifi A, Oumzil H, Omari BE, Rhoufrani FE et al. Using Respondent-Driven Sampling to Estimate HIV and Syphilis Prevalence Among Female Sex Workers in Agadir, Fes, Rabat and Tangier, Morocco. Sex Transm Infect. 2013;89(Suppl 1):A180-A180. Google Scholar


24. Eloudyi Houda, Lemrabet Sanae, Aghrouch Mohamed, Kharbouch Samira, Oumzil Hicham. Decentralising hiv viral load testing to a regional laboratory in agadir, southern morocco. Sex Transm Infect BMJ Publishing Group Ltd. 2015;91:P17.27. Google Scholar


25. Kouyoumjian SP, Mumtaz GR, Hilmi N, Zidouh A, El Rhilani H, Alami K et al. The epidemiology of HIV infection in Morocco: systematic review and data synthesis. Int J STD AIDS SAGE Publications Sage UK: London, England. 2013;24(7):507-516. PubMed | Google Scholar


26. Mumtaz Ghina R, Kouyoumjian Silva P, Hilmi Nahla, Zidouh Ahmed, El Rhilani Houssine, Alami Kamal et al. The distribution of new HIV infections by mode of exposure in Morocco. Sex Transm Infect BMJ Publishing Group Ltd. 2013;89(Suppl 3):iii49-iii56. PubMed | Google Scholar


27. Eloudyi Houda, Lemrabet Sana, Malmoussi Mourad, Ouagari Zineb, Elharti Elmir, Akrim Mohammed et al. Assessment of hiv-1 primary drug resistance mutations in antiretroviral therapy-naive cases in morocco. Sex Transm Infect BMJ Publishing Group Ltd. 2015;91:P17.28. Google Scholar


28. Chadli Smail, Aghrouch Mohamed, Taqarort Naima, Malmoussi Mourad, Ouagari Zineb, Moustaoui Fatima et al. Neuromeningeal cryptococcosis in patients infected with HIV at Agadir regional hospital,(Souss-Massa, Morocco). J Mycol Med. 2018;28(1):161-166. PubMed | Google Scholar


29. Zamani Saman, Kihara Masahiro, Gouya Mohammad M, Vazirian Mohsen, Nassirimanesh Bijan, Ono-Kihara Masako et al. High prevalence of HIV infection associated with incarceration among community-based injecting drug users in Tehran, Iran. JAIDS J Acquir Immune Defic Syndr LWW. 2006;42(3):342-346. PubMed | Google Scholar


30. Jürgens Ralf, Ball Andrew, Verster Annette. Interventions to reduce HIV transmission related to injecting drug use in prison. Lancet Infect Dis Elsevier. 2009;9(1):57-66. PubMed | Google Scholar


31. Amin-Esmaeili Masoumeh, Rahimi-Movaghar Afarin, Haghdoost Ali-akbar, Mohraz Minoo. Evidence of HIV epidemics among non-injecting drug users in Iran: a systematic review. Addiction Wiley Online Library. 2012;107(11):1929-1938. PubMed | Google Scholar


32. Ministère de la Santé, Royaume du Maroc. Mise en oeuvre de la declaration politique sur le VIH/SIDA, Rapport National. Rabat: Ministère de la Santé, Royaume du Maroc. 2015.


33. Heijnen Marieke, Mumtaz Ghina R, Abu-Raddad Laith J. Status of HIV and hepatitis C virus infections among prisoners in the Middle East and North Africa: review and synthesis. J Int AIDS Soc The International AIDS Society. 2016 May 27;19(1):2087. PubMed | Google Scholar


34. Aidaoui M, Bouzbid S, Laouar M. Seroprevalence of HIV infection in pregnant women in the Annaba region (Algeria). Rev Epidemiol Sante Publique. 2008;56(4):261-266. PubMed | Google Scholar


35. Znazen Abir, Frikha-Gargouri Olfa, Berrajah Lamia, Bellalouna Sihem, Hakim Hela, Gueddana Nabiha, Hammami Adnene. Sexually transmitted infections among female sex workers in Tunisia: high prevalence of Chlamydia trachomatis. Sex Transm Infect The Medical Society for the Study of Venereal Disease. 2010;86(7):500-505. PubMed | Google Scholar


36. Mirzoyan Lusine, Berendes Sima, Jeffery Caroline, Thomson Joanna, Othman Hussain Ben, Danon Leon et al. New evidence on the HIV epidemic in Libya: why countries must implement prevention programs among people who inject drugs. JAIDS J Acquir Immune Defic Syndr LWW. 2013;62(5):577-583. PubMed | Google Scholar


37. Mumtaz Ghina R, Riedner Gabriele, Abu-Raddad Laith J. The emerging face of the HIV epidemic in the Middle East and North Africa. Curr Opin HIV AIDS Wolters Kluwer Health. 2014;9(2):183. PubMed | Google Scholar


38. Lynn WA, Lightman S. Syphilis and HIV: a dangerous combination. Lancet Infect Dis. 2004 Jul;4(7):456-66. PubMed | Google Scholar


39. Gevorgyan Ofelya, Owen Benjamin D, Balavenkataraman Arvind, Weinstein Mitchell R. A nodular-ulcerative form of secondary syphilis in AIDS. Baylor Univ Med Cent Proc Taylor & Francis. 2017 Jan;30(1):80-82. PubMed | Google Scholar


40. Wang Yi-Jen, Chi Chih-Yu, Chou Chia-Huei, Ho Cheng-Mao, Lin Po-Chang, Liao Chia-Hung, Ho Mao-Wang, Wang Jen-Hsian. Syphilis and neurosyphilis in human immunodeficiency virus-infected patients: a retrospective study at a teaching hospital in Taiwan. J Microbiol Immunol Infect Elsevier. 2012;45(5):337-342. PubMed | Google Scholar


41. Fonteneau Laure, Da Silva Nathalie Jourdan, Fabre Laetitia, Ashton Philip, Torpdahl Mia, Müller Luise et al. Multinational outbreak of travel-related Salmonella Chester infections in Europe, summers 2014 and 2015. Eurosurveillance [Internet] European Centre for Disease Prevention and Control. 2017;22(7):30463. PubMed | Google Scholar


42. Fekih Y, Kort Y, Abdelhedi H, Khammassi N, Cherif O. Neurosyphilis à propos de 4 cas. La Rev Médecine Interne Elsevier. 2016;37(Suppl 2):A217-A218.


43. Simon Roger P. Neurosyphilis. Arch Neurol American Medical Association. 1985;42(6):606-613. PubMed | Google Scholar


44. Pokharel RP. History of syphilis. J Nepal Med Assoc. 2010 Oct-Dec;50(180):338. PubMed | Google Scholar