My Boyfriend Seroconverted to Herpes but I Was Negative
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Prevalence of Herpes Simplex Virus 2 (HSV-two) infection and associated run a risk factors in a cohort of HIV negative women in Durban, South Africa
BMC Enquiry Notes book 9, Article number:510 (2016) Cite this article
Abstract
Background
Canker Simplex Virus ii (HSV-2) is i of the well-nigh common sexually transmitted infections (STIs) worldwide and is a risk factor for the acquisition and transmission of other STIs, including HIV. We determined the prevalence and predictors of HSV-2 infection among women screened for a HIV prevention trial in Durban, South Africa. Univariate and multivariate logistic and Cox regression models were used to determine the correlates and predictors of HSV-2 infection at enrolment and seroconversion during the study respectively.
Results
Prevalence of HSV-two at screening was 65% and crude incidence was 22.3 per 100 person-years (PY) (95% CI xx.4–24.three). The HIV seroconversion was significantly higher among those testing positive for HSV-ii at baseline compared to women who were negative [8.7 per 100 person years (PY) versus 5.ii per 100 PY; (p < 0.001)]. In univariate analysis, age was determined to be the most significant predictor for HSV-ii diagnosis, while co-infection with syphilis was also a significant predictor, while historic period and co-infection with syphilis remained the two most significant predictors of having HSV-2 in multivariate assay at baseline. Consistent with these results, along with HIV seroconversion, age was likewise identified as a significant predictor for incidence of HSV-two.
Conclusion
Given the unacceptably loftier prevalence and incidence rates of HSV-two infection reported here, HSV-2 and general STI didactics needs to be reinforced in these communities, with a focus on safety instruction for prevention. HSV-2 has emerged as the most prevalent STI which is most often asymptomatic and unrecognized, and which increases women'due south run a risk of acquiring other STIs, including HIV.
Background
Herpes Simplex Virus ii (HSV-ii) is a chronic, sexually transmitted infection (STI) which is infectious during both its symptomatic and asymptomatic periods [one]. This asymptomatic nature of HSV-2 infection assists in the spread of the infection in the general population [2]. It has been estimated that around 500 million people are currently infected with HSV-2 worldwide and that approximately 20 million new cases occur each year. In European countries, the prevalence of HSV-two fluctuates significantly between countries, varying from approximately v% for England and Spain, approximately twenty–thirty% for countries such every bit Germany and Sweden up to xl% for Turkey [3]. Considerably higher rates of HSV-2 take been observed in sub-Saharan Africa (SSA), with age‐adjusted prevalence in adults ranging from 10 to 50% in men and 30 to 80% in women [4]. Cross exclusive studies in SSA take shown a prevalence of 5–53% in 13–24 year old men and women, respectively [five]. In Uganda, men aged 15–19 years sometime had ten% prevalence while 20–24 year old men had a 27% prevalence. Ugandan women, showed a 35% prevalence amid 15–19 twelvemonth olds versus a 74% prevalence in women aged 20–24 years old [5]. In Due south Africa, studies have shown a 31% prevalence of HSV-2 in women aged 15–26 [vi], while an 84% prevalence was shown among female commercial sex workers in the province of KwaZulu-Natal (KZN) [vii]. The Methods for Improving Reproductive Health in Africa (MIRA) diaphragm written report showed a 73% HSV-2 prevalence in Durban, with 41% of these women co-infected with Human Immunodeficiency Virus (HIV) [8].
Ii decades of observational and biological enquiry supports the theory that HSV-2 increases the risk of HIV-1 acquisition up to four fold [1, 2, 4, 9–eleven] and increases the risk of HIV-1 transmission and infectiousness [4, 9, 12]. A meta-analysis demonstrated that HSV-ii seropositivity was associated with a HIV conquering gamble ratio of 2.7 in men and iii.1 in women. HSV-ii infection has likewise been associated with increased incidence of other STIs, such as Neisseria gonorrhoeae (NG), Treponema pallidum (TP) and Trichomonas vaginalis (Tv) [11]. This would emphasize the need to test HSV-2 control strategies as a means to reduce the transmission non but of HIV, but also of other STIs [11].
In the KZN province, HIV prevalence among sexually active women attending three clinics was estimated to be xl% [13]. There are many reasons equally to why the epidemic is spreading uncontrollably in this region; socio-economical conditions and specific population dynamics (such as patterns of sexual networking, levels of condom use and STI infections), are known to be important determinants in the spread of HIV infection [14]. Poor socioeconomic conditions often result in women engaging in commercial sexual activity activity. Poverty is also known to result in male person migrant labour, resulting in men being away from their master sexual partners for extended periods of time. This oftentimes leads to men having multiple sexual partners [fourteen, 15]. In KZN, a high rate of multiple, concurrent and age-discrepant sexual relationships also contribute to the spread of HIV in the region. In this largely patriarchal society, gender inequality and the inability of women to negotiate condom use further contribute to these factors [14, 15]. Given the relationship betwixt HSV-ii and HIV infection, it is important to define the factors that put HIV uninfected women at take a chance of HSV-2 infection in regions of loftier HIV endemicity.
The electric current study estimates the prevalence and risk factors associated with HSV-ii infection amid women who tested HIV-1 negative in a accomplice from an HIV prevention trial. We as well estimated the incidence of HIV-1 and HSV-two infection among these women during study follow-upwards. These data provide an opportunity to proceeds further insight into the HSV-ii epidemic in the KZN region and to inform the design of time to come HIV/STI prevention strategies.
Methods
The Microbicide Development Programme (MDP) 301 study (2005–2009), was a multicenter, international, double-blind, randomized, placebo-controlled trial assessing the condom and efficacy of 0.5 and ii% PRO 2000/5 gels for the prevention of vaginally acquired HIV infection [16, 17]. Women from six enquiry centers (xiii sites) in Africa were enrolled. However, since KwaZulu-Natal is considered the epicenter of the HIV epidemic, only women enrolled at the three Durban sites of the Medical Inquiry Council (MRC) of South Africa enquiry center were considered in this analysis. The protocol was canonical by the Biomedical Research Ethics Committee based at the University of KwaZulu-Natal, the Medicines Control Council in South Africa and the U.s. Nutrient and Drug Administration. The eligibility criteria included: willingness and ability to give informed consent; HIV-seronegative status at screening; age 18 years or older; not-pregnant and non planning to become pregnant for the duration of the trial; willing to have regular speculum examinations and urinary pregnancy tests; willing to be tested for HIV infection; willingness to use study gel as advised; likely to be sexually active; and willingness to receive counseling virtually condoms. Women were excluded if they had any severe clinical, laboratory or gynecological abnormalities; had sex activity >14 times per week, and/or were unlikely to comply with the protocol. Women were followed up every 4 weeks for a total of 52 weeks. Women were provided with HIV testing and counseling, risk reduction education and diagnosis and treatment of STIs. Participants diagnosed with curable STIs were invited to bring their male partners to the study site for handling or were provided with referral cards to access STI treatment at local clinics. Women received unrestricted supplies of condoms at all study visits and were counseled to use condoms during all sex acts. The chief efficacy endpoint of the MDP301 trial was HIV-ane infection, using a novel HIV confirmatory testing algorithm [18]. Briefly, the algorithm included parallel HIV-1 rapid tests at the clinics, with positive or discordant tests subsequently enrolment prompting Enzyme Immunoassay testing at local laboratories and confirmation at a fundamental laboratory in South Africa. The central laboratory analysed samples from the report visit at which the showtime positive rapid test effect was obtained, in add-on to previous study visits at which samples were obtained. At enrolment and at predefined study visits, boosted procedures were carried out according to the written report schedule. These included a clinical evaluation with genital examination, and the collection of additional specimens for the confirmation of the diagnosis of HIV (Enrolment, week 12, week 24, week 40 and week 52), HSV-2 (Enrolment, calendar week 40 and week 52), syphilis (Enrolment, calendar week 24 and week 52), and other infections [Northward. gonorrhoeae (NG), C. trachomatis (CT), Trichomonas vaginalis (TV), bacterial vaginosis and candida] at the Enrolment and calendar week 24 visits. HSV-2 was assessed using the HerpeSelect 2 IgG ELISA (FOCUS Diagnostics, California, USA); Focus index values of ≥three.5 were considered HSV-ii seropositive [sensitivity of 92% (95% confidence interval (CI) 82–98) and specificity of 91% (95% CI 79–98)] [19]. Chlamydial and gonococcal infections were assessed using amplicor swabs collected during the genital examination by using nucleic acid amplification assays (COBAS Amplicor, Roche Molecular Diagnostics, Pleasanton, CA, USA). Baseline and confirmatory syphilis testing was conducted on sera using the rapid plasma reagin (RPR) (BD Macrovue) and Treponema palladium haemagglutination (TPHA) (Fujibrio) methods respectively. Testing for Television was conducted using sterile swabs with the In-Pouch-TV exam kit [16].
The primary outcome measure out of this assay was HSV-2 seropositivity at baseline and the risk factors associated with HSV-2 seropositivity. In addition, nosotros assessed the risk factors associated with HSV-ii incidence during study follow-upwards. The post-obit variables were considered: age (in quartiles), education level (secondary school completed vs not completed), number of sex acts in last week (less than 3 vs more than three), number of lifetime sexual partners (1 partner vs 2 or more partners), employment (yep/no), organized religion (Christian vs other), age at first sexual practice act (15 and younger vs 16 and over), contraception use [none (reference), hormonal contraception, condoms, other (tubal ligation, rhythm method)] and being infected with another STI (CT, NG, TV or syphilis). Univariate and multivariate logistic regression models were used to identify the correlates of HSV-2 infection at screening. The multivariate model was synthetic using a forward stepwise method. We used data driven cut betoken methods, such as quartiles, to categorize the continuous age variable. Regarding the number of sex acts per week, the data driven method was used in such a style that each level had enough observations; therefore they will not exist over- or nether-representative of the respective groups. Key tendency measures, such equally the median, and dispersion measures [interquartile ranges (IQRs)] were as follows: the median for overall age was 27 (IQR 22–37), with the median for HSV-ii negative women being 23 (IQR twenty–29) and the median for HSV-ii positive women being 31 (IQR 23-39) (p value for rank test is <0.001); the median for number of sex activity acts per week was three for the study population overall (IQR ii–4), with a median of 3 (IQR 2–4) for both the HSV-2 positive and negative populations (p value for rank test was 0.511). Independent predictors of HSV-two infection were assessed using Cox proportional chance regression model. A univariate logistic regression was conducted outset; risk factors with a p value of <0.10 were considered as candidates for the multivariate model. We used a forward stepwise technique to build the final model. All the factors with a p value of <0.05 were retained in the final multivariate model. Variables were considered statistically meaning if p < 0.05. HIV incidence was defined as the time from enrolment to seroconversion and/or censoring at the finish of report follow-up on the basis of a discrete fourth dimension scale adamant by a woman's report visits at 12, 24, xl and 52 weeks. The time of seroconversion was defined as the time of the initial positive HIV test issue. If one or more than visit between the last negative HIV tests and the get-go positive tests were missed, the time of seroconversion was presumed to be the visit comprising the midpoint betwixt these two time points. Similarly, the time to an HSV-two positive issue subsequently enrolment (tested for at weeks 40 and 52) or censoring was used to calculate the HSV-2 incidence charge per unit during written report follow-upwardly. All analyses were conducted using STATA 12.0 (College Station, Texas, USA).
Results
A total of 2236 HIV-negative women were screened and enrolled into the MDP 301 trial at clinical research sites in Durban, South Africa. The HSV-two prevalence at baseline in this cohort of women was 65%. The HIV incidence among HSV-2 negative women was 5.2 per 100 person years (PY), compared to viii.7 per 100 PY for women that were HSV-2 positive at baseline (p < 0.001, log rank test). The HSV-2 incidence during report follow-up was 22.3 per 100 PY (95% CI 20.4–24.3).
Table 1 presents the take a chance factors for existence diagnosed with HSV-2 at baseline. In the univariate analysis, the chance of HSV-2 infection increased with age [23–27 years old odds ratios (OR) i.76, 95% confidence intervals (CI) ane.39–2.two; age 28–37 years onetime OR 3.forty, 95% CI 2.67–4.33; age >38 years old OR 6.72, 95% CI 5.06–8.92, respectively]. Withal, engaging in their first sexual activity act at an age younger than xv years old did not significantly increment a woman's risk of being HSV-2 positive (OR ane.33, 95% CI 0.88–2.02), but having two or more than lifetime sexual activity partners did significantly increase take chances of existence HSV-2 positive (OR 1.27, 95% CI one.06–1.55). In addition to age, being unemployed (OR i.85, 95% CI ane.43–2.4) or having less than high school education (OR 1.78, 95% CI ane.47–2.14) increased the odds of a woman being HSV-two positive at baseline. The type of contraception used by women as well had an impact on HSV-2 positivity; women using "tubal ligation, rhythm, intrauterine devices or traditional" forms of contraception were more than at risk of being HSV-2 positive (OR 1.745, 95% CI 1.09–2.8) than women using no contraception, whereas women using hormonal contraception or condoms were less at risk of being HSV-two positive (OR 0.vi, 95% CI 0.44–0.89; OR 0.515, 95% CI 0.36–0.74, respectively) than women using no contraception. When considering STIs, infection with CT did not increase the odds of beingness HSV-2 positive, while being infected with GC, Tv set and/or Syphilis did (OR 1.89, 95% CI 1.07–3.31, OR 1.51, 95% CI one.09–ii.09 and OR four.62, 95% CI i.97–10.81 respectively); although all STIs significantly increased the risk of being HSV-two positive at screening in the multivariate analysis. These adventure factors remained in the multivariate analysis, except for religion, number of sex acts per week and hormonal contraception (as these were not constitute to be significant in the univariate analysis).
Table 2 presents the predictors of HSV-2 incidence during study follow-up. Beingness over 38 years old was a significant predictor for HSV-2 incidence [risk ratio (HR) 1.57 (95% CI ane.23–ii.00)], which was sustained in the multivariate analysis [HR ane.71 (95% CI 1.34–ii.xix)]. Christianity was too a predictor of HSV-2 incidence in the study [Hour 1.21 (95% CI 1.01–1.44)], although this was non sustained in the multivariate analysis. HIV seroconversion during study follow-up was a significant predictor for HSV-ii seroconversion in the univariate [HR 1.71 (95% CI 1.thirty–ii.24)] and in the multivariate assay [HR 1.84 (95% CI one.40–two.42)]. Contrary to this, a woman who had an STI at baseline or during the study was non at greater gamble of HSV-2 seroconversion. Similar to our HSV-2 prevalence data, women who used "other" methods of contraception were more than at take chances of becoming HSV-two positive during the written report. Some other interesting observation was that pregnancy incidence increased a woman's hazard of HSV-ii infection, both in univariate [Hr 1.25 (95% CI 0.93–1.67) (p < 0.133)] and multivariate analysis [HR one.37 (95% CI 1.08–i.83) (p < 0.038)], although this was simply statistically pregnant in the multivariate analysis.
Discussion
Although the HSV-2 prevalence in this study is loftier, it is similar to previous studies from developing countries [four, v] and other Due south African studies [6, 7, 20, 21]. This study was conducted at iii urban clinical enquiry sites in Durban. Interestingly, the MIRA study, which was conducted by the MRC at ane rural and one semi-rural clinical inquiry site in the Durban surface area two years prior to the MDP 301 trial, showed a HSV-two prevalence of 73% (median historic period was 26; IQR 22–34) [viii]. This higher prevalence in rural/semi-rural areas of Durban could exist explained by several factors. Since women would have less access to jobs in a rural expanse, they may engage in more transactional sex; rural areas accept poorer access to healthcare, including STI treatment and costless condoms; and women in rural areas may accept had less opportunity for educational activity than those women from urban areas, which may increase their risk of acquiring HSV-two. The HSV-2 incidence during study follow-upwards is staggering and is much higher than previously seen in other S African studies. The HSV-2 incidence seen in our study compares to HSV-two studies in Kenya and Republic of uganda among female sexual activity workers [22]. However, another cohort of Kenyan women, who considered themselves to exist at high risk of HIV infection simply were not sexual practice workers, had a like incidence of 22.1 per 100 person-years [23], while a study at an STI clinic in Alabama showed women had a HSV-2 incidence of 20.5 per 100 woman-years [24]. Women participating in these HIV prevention trials usually consider themselves at high take chances of HIV infection, which could explain this high incidence of HSV-2 due to risky sexual behavior. The HIV incidence seen in this cohort of women was comparable to the HIV incidence amid HSV-2 positive women in the MIRA trial [twenty].
Previous analyses of HSV-2 risk factors have shown that women whose sexual debut was at an historic period younger than 16 were at higher gamble of being HSV-2 positive, however this was non significant in our cohort [viii, 25]. Similar to other studies, our results showed that women who had not attended high school were at greater risk of having acquired HSV-two [26] and this is possibly due to high school attendance influencing the structure of sexual networks [27]. Unemployment also put a woman at take a chance of beingness HSV-2 positive, most likely due to unemployed women existence dependent on their partner for income, which may result in them beingness unable to negotiate condom sex with partners. Additionally, unemployment tin bulldoze women to engage in transactional sexual activity. Consistent with other studies, the risk of being HSV-ii positive increased with historic period [25, 28]. This is nearly likely due to an increased number of sexual partners and increased years of sexual practice with age (both gamble factors of HSV-2 infection [25, 26, 28]). Women presenting for this clinical trial in Durban, who were infected with an STI were significantly more than likely to be co-infected with HSV-2 than women in the trial that did not have an STI, although syphilis showed the greatest risk of HSV-2 co-infection. Nosotros did notation some instances of co-infections with STIs. Thirty three women were co-infected with Tv set and CT, while 31 women were found to be co-infected with NG and CT (data not shown). The relationships between HSV-2 and other STIs were expected, since it is widely known that at that place is increased incidence of STIs with HSV-2 infection, specifically NG, Television, and T. pallidum infections [xi, 25, 28]. Withal, the aforementioned was not observed when considering HSV-2 incidence during study follow-up. This is not surprising, as women would have been treated for their STIs as soon equally they were diagnosed, according to the study protocol requirements, which could explain why having an STI is a run a risk factor prior to written report enrolment, but not during the study. The increased take chances of HSV-2 infection we experienced in pregnant women is not surprising, since both are every bit a result of participating in unprotected sex.
Another written report looking at HSV-two in an HIV prevention trial in rural/semi-rural Durban sites found that women older than 25, having less than high school education, being unmarried or cohabiting, beingness a Christian, young age of sexual debut, more than four lifetime partners, giving nascency to more than than i child and co-infection with NG put women at an increased take chances of being HSV-two positive [8]. Together with this report, our analysis provides united states of america with a detailed ready of take chances factors suited to this region that has high HSV-two and HIV infection.
The use of hormonal contraceptives has recently come under the spotlight for possibly increasing the risk of HIV-i acquisition. Nonetheless, our results showed that a woman on hormonal contraception was less likely to be HSV-2 infected at baseline in addition to existence at less risk of HSV-2 infection during study follow-up. The link betwixt hormonal contraception and HIV infection is a highly debated one, with the majority of experts agreeing that hormonal contraception does not increase risk of HIV infection, while the use specifically of depot medroxyprogesterone acetate may pose a take a chance of infection [29, 30]. In fact, some studies have shown a decreased risk of HIV infection with progesterone only pills and combined oral contraception [adjusted gamble ratio (60 minutesa) = 0.86, 95% confidence interval (CI) 0.32, 1.78] [31]. Of notation with our data is that hormonal contraception includes injectable contraception and oral contraceptives, which accept not shown an increased risk in HIV acquisition. One written report evaluating the effect of hormonal contraception on take a chance of HSV-two infection showed that injectable contraception did not increase this run a risk [32]. Further studies demand to be conducted to confirm these findings.
HSV-ii has emerged as the almost prevalent STI, and since information technology is most often asymptomatic, unrecognized and, most importantly, incurable, it puts individuals at increased risk of acquiring other STIs in addition to HIV. Given the high prevalence and incidence of HSV-ii infection reported here, screening for symptomatic HSV-2 among high take a chance populations should be incorporated into HIV and STI screening and handling packages. Women as well need to be encouraged to seek treatment for STIs, including symptomatic HSV-2. Young women demand to be educated nigh the risk of HSV-ii infection, its bear upon on HIV and STI conquering, and how to foreclose HIV and STI acquisition. Despite condoms being an constructive method of HIV prevention, they have only been shown to reduce the manual of HSV-two by 30% [33]. Agreement the prevalence and risk factors for common causes of ulcerative genital disease in the general population would inform current STI syndromic management and HIV testing strategies in high HIV prevalence regions. Lastly, it is vital that prevention approaches integrate the management of both bacterial and viral STIs for young women in these high prevalence regions.
Several limitations need to be considered when interpreting our results: this data was taken from the responses of women participating in a large, randomized, controlled, HIV prevention trial, and therefore may have limited representativeness. Women participating in these trials often participate because they perceive themselves to exist at high chance of HIV infection and therefore may not represent the general population. The trial protocol also limits the sex and historic period of participants. In add-on to this, we have not considered the furnishings of unmeasured characteristics, such as cultural differences (east.k. polygamy), poverty, commercial sex and multiple or concurrent sex partners in our findings. Equally this analysis was limited to data that was collected as part of an HIV prevention trial, the independent variables included are express. No socioeconomic or behavioral data was collected from the male partners of these women. Due to the fact that nosotros could non determine the characteristics of women who did non present for enrollment into this clinical trial, we must be cautious when extrapolating these results to the population as a whole. Nevertheless, these results provide valuable information nearly HIV negative women presenting to participate in a HIV prevention trial. These results could too bespeak that in that location is a much higher prevalence of HSV-2 in the HIV-1 positive population in KZN.
Abbreviations
- CI:
-
conviction interval
- CT:
-
C. trachomatis
- HIV:
-
man immunodeficiency virus
- HR:
-
run a risk ratio
- HSV-2:
-
Herpes Simplex Virus 2
- IQR:
-
interquartile ranges
- KZN:
-
KwaZulu-Natal
- MDP:
-
Microbicide Development Programme
- MIRA:
-
Methods for Improving Reproductive Wellness in Africa
- MRC:
-
Medical Research Council
- NG:
-
N. gonorrhoeae
- OR:
-
odds ratio
- PY:
-
person years
- SSA:
-
sub-Saharan Africa
- STI:
-
sexually transmitted infection
- TPHA:
-
Treponema palladium haemagglutination
- TV:
-
Trichomonas vaginalis
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Authors' contributions
GR, BD and HW developed the concept. GR was the Clinical trials unit PI for the study. HW completed the statistical analysis. BD performed the data interpretations and wrote the manuscript with input from HW and GR. All authors read and approved the final manuscript.
Acknowledgements
Nosotros would like to thank all the women who participated in MDP 301 trial, besides as the staff of the Due south African Medical Enquiry Quango clinical trial sites in Durban, S Africa. Thank you lot to Dr. Nathlee Abbai for proof reading this manuscript.
Competing interests
The authors declare that they accept no competing interests.
Availability of information and materials
Data from this analysis will not be shared. This is due to the data being role of a large clinical trial. Therefore only the study sponsors may make this information available.
Ethics approval and consent to participate
The protocol was approved by the Biomedical Research Ethics Commission based at the University of KwaZulu-Natal, the Medicines Control Council in S Africa and the US Food and Drug Administration.
Funding
Nosotros gratefully acknowledge the funding of the MDP301 trial past the UK Department for International Development and the Medical Enquiry Council (Grant Number G0100137). The Microbicides Development Programme (MDP) is a partnership of African, UK and Spanish bookish/regime institutions and commercial organisations. MDP was funded past the British Regime Department for International Development (DIFD) and the Uk Medical Research Council.
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Open Access This article is distributed nether the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(southward) and the source, provide a link to the Creative Commons license, and indicate if changes were fabricated. The Creative Eatables Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made bachelor in this commodity, unless otherwise stated.
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Daniels, B., Wand, H., Ramjee, G. et al. Prevalence of Herpes Simplex Virus two (HSV-two) infection and associated gamble factors in a cohort of HIV negative women in Durban, Southward Africa. BMC Res Notes 9, 510 (2016). https://doi.org/10.1186/s13104-016-2319-5
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DOI : https://doi.org/10.1186/s13104-016-2319-5
Keywords
- HSV-2
- Women
- Risk factors
- Due south Africa
Source: https://bmcresnotes.biomedcentral.com/articles/10.1186/s13104-016-2319-5
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