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. Author manuscript; available in PMC: 2021 Sep 1.
Published in final edited form as: Int J Infect Dis. 2020 Jun 17;98:130–137. doi: 10.1016/j.ijid.2020.06.046

Population Prevalence of sexually transmitted infections in a high HIV burden district in KwaZulu-Natal, South Africa: Implications for HIV epidemic control

Ayesha BM Kharsany a,b, Lyle R McKinnon a,c, Lara Lewis a, Cherie Cawood d, David Khanyile d, Domiciled Venessa Maseko e, Tawni C Goodman a,f, Sean Beckett g, Kaymarlin Govender g, Gavin George g, Kassahun Abere Ayalew h, Carlos Toledo h
PMCID: PMC7484252  NIHMSID: NIHMS1619750  PMID: 32562845

Abstract

Background:

Sexually transmitted infections (STIs) and Human immunodeficiency virus (HIV) share a complex bidirectional relationship, however, population prevalence and the association between the presence of STIs and HIV in a high HIV burden district in KwaZulu-Natal, South Africa is not known.

Methods:

A total of 9812 participants aged 15–49 years were enrolled in a cross-sectional population-based household survey. Participants completed a structured questionnaire and provided first-pass urine (males) or self-collected vulvo-vaginal swabs (females) for the detection of STIs.

Results:

Prevalence of herpes simplex virus type-2 (HSV-2) was 57.8%, syphilis was 1.6%, Neisseria gonorrhoeae was 2.8%, Chlamydia trachomatis was 7.1%, Trichomonas vaginalis was 9.0%, Mycoplasma genitalium was 5.5% and HIV was 36.3%. HIV positive status was associated with an increased probability of having M. genitalium (aPR=1.49, 95% CI 1.02–2.19) among males and syphilis (aPR=2.54, 95% CI 1.32–4.86), N. gonorrhoeae (aPR=2.39, 95% CI 1.62–3.52), T. vaginalis (aPR=1.70, 95% CI 1.43–2.01) and M. genitalium (aPR=1.60, 95% CI 1.15–2.22) among females. HIV viral load ≥400 copies per mL was associated with an increased probability of N. gonorrhoeae (aPR=1.91, 95% CI 1.36–2.70), C. trachomatis (aPR=1.52, 95% CI 1.12–2.05) and M. genitalium (aPR=1.83, 95% CI 1.27–2.63).

Conclusions:

The high prevalence of STIs and the association between STIs and HIV, and HIV viral load underscores the public health implications of sustained transmission risk of STIs and HIV. These findings highlight the urgent need for expanding STI surveillance and implementing interventions to monitor and reduce the STI burden.

Keywords: household survey, population prevalence, sexually transmitted infections, HIV, HIV viral load, KwaZulu-Natal, South Africa

Introduction

Sexually transmitted infections such as herpes simplex virus type 2 (HSV-2), syphilis, Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis and Mycoplasma genitalium are of major public health concern and are key epidemiological markers of unprotected sex (World Health Organization. 2016). Whilst STIs affect individuals of all ages, adolescents and young people are disproportionately affected (Dehne and Riedner 2005), STIs contribute adversely to sexual, reproductive and maternal-child health; lead to pelvic inflammatory disease, genital malignancies and infertility (World Health Organization. 2016) and increase the risk of HIV acquisition and transmission (Wasserheit 1992, Rottingen et al. 2001, Freeman et al. 2006, Looker et al. 2017, Unemo et al. 2017, Cohen et al. 2019).

South Africa monitors the HIV epidemic through nationally representative population-based household surveys (Human Sciences Research Council. 2018). With a national HIV prevalence of 20.6% for among 15–49-year-old, the epidemic in the region is characterized as generalized and hyperendemic. At the provincial level, HIV prevalence in KwaZulu-Natal was the highest at 27.0% while prevalence in the Western Cape was 12.6%. However, there are no similar surveys to monitor the STI burden and surveillance for STIs is limited to the use of convenience or clinic based sampling, limiting generalizability to groups of interest (Johnson et al. 2005, Kularatne et al. 2017, Francis et al. 2018). Notwithstanding such limitations, the studies have provided useful point estimates in select sub-populations and highlight the need for population-representative surveys to determine the burden and patterns of STIs and to reliably monitor and assess the effectiveness of STI prevention programs.

With the onset of the HIV epidemic interest in STIs has grown substantially as both share a complex, synergistic bidirectional relationship (Wasserheit 1992, Barnabas et al. 2011, Looker et al. 2017). Evidence suggests that for HIV positive individuals, persistent high risk behaviours increase susceptibility to STIs (Erbelding et al. 2003, Chen et al. 2007, Lurie et al. 2014, Khaw et al. 2018). and advancing HIV infection may increase the frequency of STI treatment failures (Wolday et al. 2004, Unemo et al. 2017, Khaw et al. 2018). Conversely, asymptomatic or symptomatic STIs strongly predict susceptibility to HIV, enhance HIV shedding at genital mucosal sites and increase infectiousness from HIV positive individuals (Mwatelah et al. 2019). Potential biologic mechanisms that facilitate and activate HIV replication include alterations in the genital tract microbiome, localized inflammation, recruitment of CD4+ T-cells, monocytes, Langerhans’ cells, and increased levels of interleukin-10 (Abdool Karim et al. 2019, Cohen et al. 2019, Mwatelah et al. 2019). Whilst these findings provide strong biological plausibility for STI control as an effective HIV prevention strategy, clinical trial evidence has produced conflicting results (Grosskurth et al. 1995, Wawer et al. 1999, Kamali et al. 2003, Hayes et al. 2010, Torrone et al. 2018). The differences in trial design, robustness of the interventions, population characteristics, stage of the HIV epidemic at the time of the study and baseline prevalence of STIs may have contributed to these mixed results Stillwaggon and Sawers 2015), but nonetheless, treatment of STIs remains a public health priority (Hayes et al. 2010, Cohen 2012, Stillwaggon and Sawers 2015).

These findings suggest that monitoring, early diagnosis and treatment of STIs may reduce STI related HIV acquisition and transmission and achieve the goal of HIV epidemic control in the region (Joint United Nations Programme on HIV/AIDS (UNAIDS). 2017, Galvani et al. 2018).

The objectives of this study were to measure the population prevalence of STIs and to assess the association between STIs and HIV, CD4 cell counts and HIV viral load in a high HIV burden setting.

Methods

Study population, design, and procedures

The HIV incidence Provincial Surveillance System (HIPSS) was designed to measure HIV prevalence and incidence in association with the scale-up of HIV prevention and treatment efforts in a “real-world non-trial” setting in rural Vulindlela and peri-urban Greater Edendale area in the uMgungundlovu district of KwaZulu-Natal, South Africa. The study area has a population of approximately 360 000, is predominantly Zulu speaking, and is characterized by high levels of unemployment, poverty, teenage pregnancy and high rates of HIV. Primary health-care clinics and community-based organizations provide health care and psychosocial support. The cross-sectional survey was undertaken between June 2014 and June 2015. Households were randomly selected using a multistage random sampling method to select the enumeration areas and households. One individual per household, within the age range of 15–49 years, was randomly selected from a list of eligible household members. Overall, from a total of 15,100 households, 11,289 consented for household participation and from these households a total of 9812 (86.9% response rate) individuals were enrolled. All enrolled participants provided written informed consent and/or parental consent/child assent for those participants below the age of 18 years for study participation. All participants completed interviewer administered questionnaires, had peripheral blood samples collected and first pass urine (males) and self-collected vulvo-vaginal swab (females) samples. Details of the study sampling and survey procedures have been described elsewhere (Kharsany et al. 2018).

Questionnaire measures

Structured questionnaires were administered to obtain sociodemographic and behavioural data, HIV testing history, use of antiretroviral therapy (ART), symptoms of genital ulceration and /or genital discharge, alcohol and substance use [includes use of cannabis, barbiturates, benzodiazepines, cocaine, methaqualone, opioids, whoonga (locally mixed street drugs), or tik (crystal methamphetamine)] and medical male circumcision status.

Laboratory measures

Peripheral blood samples were tested for HIV, HSV-2, and syphilis antibodies. HIV status was determined using the 4th generation HIV enzyme Biomerieux Vironostika Uniform II Antigen / Antibody Microelisa system (BioMérieux, Marcy I’Etoile, France). HIV positive samples were confirmed with the HIV 1/2 Combi Roche Elecsys (Germany) (Roche Diagnostics, Penzberg, Germany) and tested for CD4 cell counts using Becton Dickinson (BD) FACS Calibur flow cytometry (BD Biosciences, San Jose, CA, USA) and HIV viral load using the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 v2.0 assay (CAP/CTM HIV-1 V2.0, Roche Diagnostics, Penzberg, Germany).

HSV-2 serostatus was determined by the detection of human IgG class antibodies using the HerpeSelect® HSV-2 enzyme-linked immunosorbent assay (Focus Diagnostics, Cypress, CA, USA) test. Syphilis serostatus was determined by a non-treponemal rapid plasma reagin (RPR) assay (Immutrep® RPR, Omega Diagnostics Ltd., Alva, UK) and a quantitative titer of 1:8 or higher was considered as positive for active syphilis.

First pass urine (males) and self-collected vulvo-vaginal swab samples (females) were tested for N. gonorrhoeae, C. trachomatis, T. vaginalis and M. genitalium using a multiplex real-time polymerase chain reaction (PCR) assay on the RotorGene 3000/6000/ Q real-time platforms (QIAGEN, Hilden Germany) (Mhlongo et al. 2010). Primers and probes targeted the N. gonorrhoeae cytosine-specific DNA methyltransferase gene, the cryptic plasmid of C. trachomatis, the T. vaginalis repeated DNA fragment and the M. genitalium pdhD gene (encoding for dihydrolipoamide dehydrogenase). Strains of N. gonorrhoeae (ATCC 700825), C. trachomatis (ATCC VR-885), T. vaginalis (ATCC 30001), and M. genitalium (ATCC 33530) were used as positive controls. Females 15–35 years were tested for a current pregnancy using beta human chorionic gonadotropin (BHCG) quantitative blood assay (Siemens Centaur XP, USA).

Ethical approvals

The protocol, informed consent and data collection forms were reviewed and approved by the Biomedical Research Ethics Committee of the University of KwaZulu-Natal, (Reference number BF269/13), the KwaZulu-Natal Provincial Department of Health (HRKM 08/14) and the Centers for Disease Control and Prevention (CDC), United States of America. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines.(von Elm et al. 2007) (Supplementary Table 1)

Statistical Analysis

Questionnaire data and laboratory test results were linked for analysis. Statistics were weighted using survey weights to account for the sample design and non-response (Kharsany et al. 2018). As STIs were detected in some individuals who reported never having had sex, all individuals were included in the analyses unless otherwise stated. Demographic, behavioural and clinical characteristics were summarised with frequencies and proportions for categorical variables and with medians and interquartile ranges (IQR) for continuous variables. The prevalence of each STI and 95% confidence interval (CI) were calculated overall, by sex, 5-year age group, HIV, and pregnancy status (for women aged 15–35 years).

The association between pregnancy status and STI presence was tested using logistic regression adjusting for 5-year age groups. The association between the presence of STIs and HIV status was measured using log binomial regression for each of the curable STIs (syphilis, N. gonorrhoeae, C. trachomatis, T. vaginalis and M. genitalium). Crude and adjusted prevalence ratios (aPR) were estimated for each sex group. APRs controlled for factors previously identified as being associated with HIV prevalence that could possibly act as confounders to measuring the relationship between presence of curable STIs and HIV status (Kharsany et al. 2018). The factors included 5-year age group, education level (completed high-school or not), relationship status (married or living together as husband and wife, versus not), the number of lifetime sexual partners (none, one, 2–5, 6 or more, or refused to report) and male medical circumcision status (yes or no). For the sample of HIV positive individuals the association between CD4 cell count <350 versus ≥ 350 cells per μL) and between HIV viral load <400 (suppressed) and ≥400 (unsuppressed) copies per ml and the presence of a curable STI was measured using log binomial regression adjusting for sex and age group. HSV-2 was not included in the models as presence of antibodies do not provide an indication of recent sexual risk behaviours.

All analyses, except for log binomial regression, were performed using SAS survey procedures (SAS Institute, Cary, North Carolina, version 9.4). Log binomial regression was performed in STATA 13 (StataCorp. 2013. Stata Statistical Software: Release 13. College Station, TX: StataCorp LP).

Results

Participant characteristics

A total of 9812 participants were enrolled and assessed for the prevalence of STIs (Table 1). Females accounted for 63.9% with a median age of 27 years [Interquartile range (IQR) 21–36], whilst 36.1% were males with a median age of 26 years (IQR 20–35). About 43.5% of males and 46.7% of females had completed high school education, 63.6% of males and 63.9% of females reported a household income of <ZAR2500 and more than 80% of participants reported their relationship status as not married or living with partner as husband and wife. Of those reporting ever having had sex, 68.6% of males and 74.1% of females were currently in a sexual relationship. The median number of lifetime sex partners for males was 3 (IQR 1–6) and for females was 2 (IQR 1–3). Overall, 40.6% of males and 9.1% of females reported any lifetime alcohol use, 19.3% of males and 1.5% of females reported any lifetime substance use. Prevalence of HIV was 28.0% in males and 44.1% in females. Among HIV positive individuals 41% of males and 23.1% of females had CD4 cell counts of <350 cells per μL, whilst 36.7% of males and 45.6% of females self-reported to be ART and 41.9% of males and 54.8% of females had HIV viral load of <400 copies per mL.

Table 1:

Characteristics of enrolled participants

Participants characteristics Overall
(n=9812)		 Males
(n=3547)		 Females
(n=6265)
Socio demographic
 Age [median (IQR)] 27 (20–36) 26 (20–35) 27 (21–36)
 Completed high school education (n, %) 4561 45.1 1613 43.5 2948 46.7
 Household income of ≤ZAR 2500a (n, %) 6353 63.8 2253 63.6 4100 63.9
 Relationship status: not married or living with partner as husband and wife (n, %) 8714 88.8 3306 92.1 5408 85.8
Behavioral
 Ever had sex (n, %) 8302 83.3 2855 80.8 5447 85.6
 Currently in a sexual relationship (n, %) 7195 71.4 2459 68.6 4736 74.1
 Concurrently in 2 or more heterosexual relationships
 in the last 12 months (n, %)		 269 4.2 206 7.5 63 1.1
 Engaged in any transactional sex with last three sexual partners (n, %) 1383 11.6 458 10.6 925 12.4
 Total sex partners in the last 12 months [median (IQR)]a 1 (0–1) 1 (0–1) 1 (0–1)
 Total lifetime sex partners [median (IQR)]a 2 (1–4) 3 (1–6) 2 (1–3)
 Ever tested for HIV (n, %) 7265 75.5 2326 68.8 4939 81.9
 Knows HIV status of all sex partners from the last 12 monthsb (n, %) 1821 25.6 521 21.0 1300 29.8
 Any lifetime alcohol use (n, %) 2075 24.3 1432 40.6 643 9.1
 Any lifetime substance usec (n, %) 830 10.1 697 19.3 133 1.5
 Male condom used always during sex in the last 12 monthsb (n, %) 1587 24.5 593 26.5 994 22.7
Biological
 Any genital symptoms (n, %) 394 3.0 80 1.9 314 4.1
 Medically circumciseda (n, %) 1102 31.9 1102 31.9 NA
 Ever pregnanta (n, %) 4391 70.7 NA 4391 70.7
 Currently pregnantd (n, %) 305 6.8 NA 305 6.8
 HIV positive (n, %) 3969 36.3 1014 28.0 2955 44.1
  CD4 cell count <350 cells per μL e, f 1135 29.8 439 41.0 696 23.1
  On ART f, g 1592 42.3 341 36.7 1251 45.6
  HIV viral suppression <400 copies per mLh 1975 50.0 401 41.9 1574 54.8
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ZAR = South African Rand;

a =

Missing observations were excluded from percentage or median (IQR) calculations.

b=

percentage for those that reported having sex in last 12 months;

c =

includes any of cannabis, barbiturates, benzodiazepines, cocaine, methaqualone, opioids, whoonga, tik;

d =

only women aged 15–35 years received pregnancy tests;

e =

Five men and twenty– seven women were missing CD4 cell count data;

f =

as a percentage of all HIV positives;

g =

self–report;

h =

Four men and nine women were missing viral load data

%=

population–weighted percentage calculation

Prevalence of STIs

The prevalence of laboratory diagnosed STIs overall, by sex and age is shown in table 2. Among males compared to females respectively, prevalence of HSV-2 was 46.1% (95% CI 43.4–48.7) versus (vs) 68.8% (95% CI 66.9–70.7), syphilis was 1.5% (95% CI 1.0– 2.01) vs 1.7% (95% CI 1.3– 2.1), N. gonorrhoeae was 1.8% (95% CI 1.0–2.5) vs 3.7% (95% CI 3.1–4.3), C. trachomatis was 5.1% (95% CI 4.2–6.0) vs 9.0% (95% CI 8.1–9.9), T. vaginalis was 3.9% (95% CI 3.1–4.6) vs 13.8% (95% CI 12.3–15.2) and M. genitalium was 5.7% (95% CI 4.8–6.7) vs 5.2% (95% CI 4.5–6.0). Prevalence of curable STIs was higher in the younger age groups, whilst prevalence of HSV-2 was high across all age groups and peaked at 92.5% among females in the 45–49 year age group and 84.2% among males in the 40–44 year age group. Mean prevalence of STIs was higher among pregnant compared to non-pregnant females, though these differences were not significant (Supplementary Table 2).

Table 2.

Prevalence of sexually transmitted infections by sex and age among enrolled participants

Age group Overall Males Females
n/N % 95% CI n/N % 95% CI n/N % 95% CI
Herpes simplex virus type 2 antibodies
 15–19 320/1609 16.5 14.2–18.9 55/657 8.4 6.0– 10.9 265/952 24.7 21.0–28.4
 20–24 935/2074 40.5 37.3–43.6 189/812 21.8 17.7– 26.0 746/1262 59.0 55.3–62.8
 25–29 1146/1682 63.7 60.1–67.4 306/596 51.5 45.4– 57.5 840/1086 75.3 70.8–79.8
 30–34 1029/1293 76.2 72.8–79.6 316/460 66.0 60.8– 71.2 713/833 85.8 82.6– 88.9
 35–39 962/1163 80.1 76.3–83.8 297/403 73.1 67.1– 79.1 665/760 86.5 83.0– 89.9
 40–44 865/979 87.7 84.5–91.0 261/319 84.2 79.1– 89.3 604/660 90.7 87.1– 94.3
 45–49 872/986 86.5 83.2–89.8 220/286 77.7 71.2– 84.2 652/700 92.5 90.1– 95.0
 Overall 6129/9786 57.8 56.1–59.6 1644/3533 46.1 43.4– 48.7 4485/6253 68.8 66.9– 70.7
Syphilis antibodiesa
 15–19 17/1613 0.9 0.4 – 1.5 5/658 0.5 0.5– 1.1 12/955 1.3 0.3– 2.3
 20–24 57/2080 2.3 1.5 – 3.1 17/814 1.9 0.7– 3.2 40/1266 2.6 1.7– 3.6
 25–29 33/1688 1.5 0.8 – 2.2 9/602 0.9 0.1– 1.7 24/1086 2.1 0.9– 3.3
 30–34 24/1294 1.7 0.7 – 2.8 8/461 1.9 0– 3.9 16/833 1.5 0.5– 2.5
 35–39 17/1165 2.0 0.7 – 3.2 9/405 3.1 0.7– 5.5 8/760 1.0 0.1– 1.8
 40–44 19/980 1.8 0.9 – 2.7 8/320 2.0 0.5– 3.4 11/660 1.7 0.4– 3.0
 45–49 7/988 0.5 0 – 1.0 1/287 0.5 0– 1.5 6/701 0.5 0.1– 1.0
 Total 174/9808 1.6 1.2 – 2.0 57/3547 1.5 1.0– 2.0 117/6261 1.7 1.3– 2.1
Neisseria gonorrhoeae
 15–19 54/1611 2.6 1.7–3.4 11/656 1.0 0.3– 1.6 43/955 4.2 2.7– 5.7
 20–24 98/2074 4.7 3.5–6.0 21/811 2.9 1.4– 4.5 77/1263 6.5 4.9– 8.2
 25–29 59/1683 3.6 2.3–4.8 20/600 2.8 1.1– 4.4 39/1083 4.4 2.4– 6.3
 30–34 37/1288 2.9 1.6–4.2 11/458 2.5 0.4– 4.7 26/830 3.2 1.6– 4.8
 35–39 21/1162 1.0 0.4–1.6 3/403 0.5 0.0– 1.1 18/759 1.5 0.7– 2.3
 40–44 15/974 1.5 0.5–2.5 3/315 0.7 0.0– 1.5 12/659 2.2 0.6– 3.8
 45–49 11/986 0.6 0.2–1.1 0/286 – – 11/700 1.1 0.3– 1.8
 Total 295/9778 2.8 2.3–3.3 69/3529 1.8 1.0– 2.5 226/6249 3.7 3.1– 4.3
Chlamydia trachomatis
 15–19 171/1611 9.2 7.6–10.9 31/656 4.4 2.5– 6.2 140/955 14.1 11.6– 16.7
 20–24 257/2074 12.1 10.3–13.9 67/811 8.6 6.2– 11.0 190/1263 15.6 13.1– 18.2
 25–29 163/1683 8.6 6.9–10.4 52/600 7.5 5.1– 10.0 111/1083 9.7 7.3– 12.2
 30–34 74/1288 5.4 3.6–7.1 23/458 5.5 2.5– 8.5 51/830 5.2 3.5– 6.9
 35–39 45/1162 3.0 1.8–4.2 10/403 1.3 0.4– 2.2 35/759 4.5 2.5– 6.6
 40–44 22/974 1.9 1.0–2.9 4/315 1.1 0.0– 2.3 18/659 2.6 1.1– 4.1
 45–49 11/986 0.7 0.2–1.3 1/286 0.4 0.0– 1.3 10/700 1.0 0.2– 1.7
 Total 743/9778 7.1 6.5–7.7 188/3529 5.1 4.2 –6.0 555/6249 9.0 8.1 – 9.9
Trichomonas vaginalis
 15–19 113/1611 6.0 4.6–7.3 6/656 0.6 0.0– 1.1 107/955 11.4 9.0– 13.8
 20–24 210/2074 7.3 6.0–8.7 14/811 1.8 0.7– 3.0 196/1263 12.8 10.3– 15.2
 25–29 204/1682 8.3 6.5–10.1 24/599 3.2 1.5– 5.0 180/1083 13.2 10.5– 15.8
 30–34 129/1288 7.7 5.9–9.6 17/458 4.3 1.7– 6.9 112/830 11.0 8.2– 13.8
 35–39 174/1162 12.1 9.2–15.1 29/403 6.6 3.3– 9.9 145/759 17.3 13.4– 21.1
 40–44 161/974 13.6 10.7–16.6 46/315 11.2 7.4– 15.1 115/659 15.6 11.7– 19.5
 45–49 166/986 14.2 11.3–17.1 19/286 6.5 2.9– 10.1 147/700 19.5 15.4– 23.5
 Total 1157/9777 9.0 8.1–9.9 155/3528 3.9 3.1– 4.6 1002/6249 13.8 12.3 – 15.2
Mycoplasma genitalium
 15–19 69/1611 3.6 2.5–4.7 17/656 1.9 0.8– 3.0 52/955 5.3 3.4– 7.2
 20–24 138/2074 5.8 4.4–7.1 29/811 3.2 1.8– 4.5 109/1263 8.4 6.2– 10.5
 25–29 130/1683 8.1 6.4–9.7 52/600 9.2 6.3– 12.1 78/1083 7.0 5.0– 8.9
 30–34 80/1288 6.9 4.8–8.9 47/458 10.4 6.9– 13.8 33/830 3.6 2.0– 5.1
 35–39 65/1162 6.4 4.5–8.4 33/403 8.2 4.9– 11.4 32/759 4.8 2.6– 7.0
 40–44 37/974 3.3 2.0–4.5 19/315 4.4 1.9– 6.9 18/659 2.3 1.1– 3.5
 45–49 13/986 1.7 0.5–2.9 7/286 2.6 0.0– 5.3 6/700 1.1 0.1– 2.1
 Total 532/9778 5.5 4.8–6.1 204/3529 5.7 4.8– 6.7 328/6249 5.2 4.5– 6.0
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a=

Rapid plasma reagin (RPR) assay with a quantitative titer of 1:8 or higher was considered as positive for active syphilis.

Association between prevalent STIs and HIV, CD4 cell count and HIV viral load

Tables 3 shows the prevalence of STIs among HIV positive participants. Prevalence of HSV-2 was higher among HIV positive compared to HIV negative males (86.3%, 95% CI 83.2–89.5 vs 30.3%, 95% CI 27.9–32.8) and similarly higher among HIV positive compared to negative females (93.3%, 95% CI 92–94.5 vs 49.4%, 95% CI 47.0–51.9). Tables 4 and 5 show the association of STIs among HIV positive participants by CD4 cell counts and HIV viral load. Among males after adjusting for age, relationship status, education, number of lifetime sexual partners and medical male circumcision, being HIV positive was associated with an increased probability of having M. genitalium (aPR=1.49, 95% CI 1.02–2.19). Similarly among females after adjusting for age, relationship status, education, number of lifetime sexual partners, being HIV positive was associated with an increased probability of having syphilis (aPR=2.54, 95% CI 1.32–4.86), N. gonorrhoeae (aPR=2.39, 95% CI 1.62–3.52), T. vaginalis (aPR=1.70, 95% CI 1.43–2.01).

Table 3.

Prevalence of sexually transmitted infections by sex. age and HIV status

Age Group Males Females
HIV negative HIV Positive P value HIV Negative HIV Positive P value
% (95% CI) % (95% CI) % (95% CI) % (95% CI)
Herpes simplex virus type 2 antibodies
 15–19 7.6 5.1–10.1 24.1 7.2–41 0.0051 20.4 16.8–24.0 58.2 46.2–70.2 <0.0001
 20–24 17.3 13.5–21.0 62.3 48.9–75.7 <0.0001 45.2 40.4–50.0 87.8 83.5–92.1 <0.0001
 25–29 38.2 31.9–44.5 86.6 79.9–93.4 <0.0001 57.4 50.5–64.3 93.3 90.7–96.0 <0.0001
 30–34 50.5 42.3–58.8 85.7 78.8–92.6 <0.0001 63.0 55.6–70.5 97.4 95.9–98.9 <0.0001
 35–39 51.4 41.5–61.3 93.5 88.4–98.6 <0.0001 67.8 59.2–76.4 95.9 93.3–98.6 <0.0001
 40–44 70.2 60.0–80.3 93.7 89.4–98.1 <0.0001 78.9 71.0–86.9 98.4 96.5–100 <0.0001
 45–49 64.9 55.3–74.6 99.2 98.1–100 <0.0001 88.4 84.4–92.3 98.3 96.8–99.8 <0.0001
Total 30.3 27.9–32.8 86.3 83.2–89.5 <0.0001 49.4 47.0–51.9 93.3 92.0–94.5 <0.0001
Syphilis antibodiesa
 15–19 0.8 0.1–1.4 1.6 0–4.7 0.5012 0.7 0.2–1.1 8.4 1–15.9 <0.0001
 20–24 2.3 0.3–4.2 8.0 1.8–14.2 0.019 3.5 1.7–5.2 8.5 5.5–11.4 0.0013
 25–29 1.8 0–3.9 4.4 0–9.0 0.2415 2.1 0.3–3.9 5.1 2.4–7.8 0.0753
 30–34 2.9 0–6.3 2.3 0.2–4.5 0.7531 1.4 0–2.8 3.5 1.4–5.5 0.0938
 35–39 4.4 0–8.9 3.3 0.5–6.1 0.6684 1.5 0–3.1 1.7 0.5–3.0 0.8095
 40–44 2.1 0–4.3 3.6 0.5–6.7 0.4451 2.6 0–5.7 3.8 1.8–5.8 0.5756
 45–49 2.8 0.6–4.9 2.3 0–5.5 0.8142 3.3 1.1–5.5 0.6 0–1.4 0.0132
Total 2.1 1.2–2.9 3.5 2.2–4.9 0.0659 2.1 1.4–2.7 4.2 3.3–5.1 <0.0001
Neisseria gonorrhoeae
 15–19 0.8 0.2–1.5 3.5 0–8.3 0.0578 3.1 1.6–4.6 12.7 5.3–20.1 0.0002
 20–24 2.6 1–4.3 5.4 0–11.0 0.2451 4.0 2.2–5.8 11.9 7.9–15.8 0.0001
 25–29 1.7 0.2–3.1 5.7 0.7–10.8 0.0468 3.5 0.8–6.2 5.2 2.6–7.8 0.3831
 30–34 3.4 0–7.0 1.4 0.1–2.8 0.2143 0.5 0–1.0 4.6 2.2–6.9 <0.0001
 35–39 0.4 0–1.0 0.5 0–1.6 0.808 0.6 0–1.4 1.9 0.8–3.0 0.0821
 40–44 1.3 0–3.3 0.2 0–0.6 0.0965 1.6 0–4.4 2.6 0.5–4.6 0.6249
 45–49 - - - - 0.6 0–1.3 1.6 0.2–3.1 0.1638
Total 1.7 0.9–2.5 2.0 0.9–3.1 0.5706 2.6 2.0–3.3 5.1 4.1–6.1 <0.0001
Chlamydia trachomatis
 15–19 4.6 2.6–6.5 - - 14 11.2–16.8 15.3 6.7–23.9 0.7724
 20–24 8.7 6.2–11.2 7.9 0–16.6 0.8772 16.5 13.1–19.9 13.9 9.7–18.0 0.3631
 25–29 6.4 3.9–8.9 10.6 4.4–16.7 0.1561 7.7 4.8–10.6 11.8 8.1–15.5 0.0715
 30–34 8.3 3.2–13.4 1.8 0.4–3.3 0.0006 3.5 1.1–5.9 6.1 3.9–8.4 0.1527
 35–39 1.9 0.4–3.5 0.8 0–1.7 0.2101 2.6 1.1–4.2 5.5 2.6–8.4 0.0393
 40–44 - - 1.9 0–3.8 - 2.3 0.1–4.4 2.8 0.7–5.0 0.7281
 45–49 - - 1.2 0–3.5 - 0.7 0–1.5 1.3 0–2.7 0.4375
Total 5.7 4.5–6.8 3.5 2.0–5.0 0.048 9.8 8.6–11.1 7.9 6.5–9.2 0.0371
Trichomonas vaginalis
 15–19 0.5 0–1.1 1.6 0–4.7 0.289 10.9 8.3–13.5 15.1 7.7–22.4 0.2662
 20–24 1.7 0.4–2.9 3.5 0–7.4 0.2603 10.0 7.3–12.7 18.5 14.3–22.7 0.0001
 25–29 1.4 0.4–2.4 8.2 2.4–13.9 0.0001 7.1 4.6–9.5 19.3 14.8–23.8 <0.0001
 30–34 4.2 0.4–7.9 4.5 0.7–8.2 0.9078 6.5 3.3–9.7 13.3 9.7–16.9 0.0051
 35–39 5.0 1.8–8.2 8.1 2.2–14.0 0.3344 11.0 6.2–15.7 20.5 15.3–25.7 0.0107
 40–44 10.2 5–15.3 12.0 6.2–17.7 0.6566 11.1 5.7–16.6 18.6 13.6–23.5 0.0467
 45–49 6.7 1.4–12 6.1 2–10.2 0.8596 17.6 12.1–23.1 22.0 16.4–27.7 0.2632
Total 2.6 1.8–3.3 7.3 5.1–9.4 <0.0001 10.3 8.9–11.8 18.1 16.0–20.2 <0.0001
Mycoplasma genitalium
 15–19 1.7 0.6–2.7 6.6 0–14.7 0.0375 4.8 2.8–6.8 9.5 3.6–15.4 0.0747
 20–24 2.7 1.4–4 7.3 1.4–13.3 0.0353 6.6 4.3–9 12.0 8.2–15.9 0.0069
 25–29 9.1 5.5–12.6 9.7 5–14.4 0.8208 5.3 2.8–7.8 8.7 5.4–11.9 0.1083
 30–34 7.2 3–11.4 14.5 8.4–20.6 0.0544 3.1 0.6–5.6 3.8 1.8–5.9 0.6673
 35–39 5.8 1.8–9.9 10.4 4.9–15.9 0.2126 1.7 0–3.6 6.4 3.3–9.5 0.0172
 40–44 3.3 0–7.2 5.2 2.5–7.9 0.4453 1.4 0–3.2 2.8 1.2–4.5 0.3104
 45–49 2.6 0–6.6 2.8 0.2–5.3 0.9365 0.9 0–2.4 1.3 0–2.7 0.7629
Total 4.4 3.3–5.5 9.2 7.2–11.2 <0.0001 4.4 3.3–5.4 6.4 5.2–7.5 0.0086
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a=

qualitative detection of antibodies suggestive of a past or current infection

Table 4.

Adjusted prevalence ratios for the association of curable sexually transmitted infections and HIV positive status

Males Females
STI Prevalence STI Prevalence
HIV positive HIV negative HIV positive HIV negative
% (95% CI) % (95% CI) PR aPR* (% CI) % (95% CI) % (95% CI) PR aPR** (% CI)
Syphilis 2.1 (1.1–3.1) 1.3 (0.7–1.9) 1.62 1.15 (0.46–2.86) 2.5 (1.8–3.2) 1.0 (0.7–1.4) 2.50 2.54 (1.32–4.86)
N. gonorrhoeae 2.0 (0.9–3.1) 1.7 (0.9–2.5) 1.18 1.73 (0.67–4.5) 5.1 (4.1–6.1) 2.6 (2.0–3.3) 1.96 2.39 (1.62–3.52)
C. trachomatis 3.5 (2.0–5.0) 5.7 (4.5–6.8) 0.61 0.96 (0.57–1.63) 7.9 (6.5–9.2) 9.8 (8.6–11.1) 0.81 1.01 (0.82–1.25)
T. vaginalis 7.3 (5.1–9.4) 2.6 (1.8–3.3) 2.81 1.50 (0.93–2.41) 18.1 (16.0–20.2) 10.3 (8.9–11.8) 1.76 1.70 (1.43–2.01)
M. genitalium 9.2 (7.2–11.2) 4.4 (3.3–5.5) 2.09 1.49 (1.02–2.19) 10.3 (8.9–11.8) 4.4 (3.3–5.4) 2.34 1.60 (1.15–2.22)
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PR=prevalence ratio; aPR=Adjusted prevalence ratio; 95% CI= 95% confidence interval

*

adjusted for age, relationship status, education, number of lifetime sexual partners and medical male circumcision status

**

adjusted for age, relationship status, education and number of lifetime sexual partners.

Table 5.

Adjusted prevalence ratios for the association of curable sexually transmitted infections among HIV positive participants stratified by CD4 cell counts and HIV viral load

STI Prevalence STI Prevalence
CD4 cell count <350 per μL CD4 cell count ≥350 per μL HIV viral load ≥ 400 copies per mL HIV viral load <400 copies per mL
% (95% CI) % (95% CI) PR aPR* (% CI) % (95% CI) % (95% CI) PR aPR* (% CI)
Syphilis 2.6 (1.5–3.7) 2.2 (1.6–2.9) 1.16 1.26 (0.82–1.94) 3.2 (2.1–4.2) 1.5 (0.9–2.2) 2.06 1.71 (0.97–3.02)
N. gonorrhoeae 4.6 (2.8–6.4) 3.7 (2.9–4.5) 1.26 1.59 (1.00–2.52) 5.5 (4.3–6.7) 2.3 (1.5–3.1) 2.39 1.91 (1.36–2.70)
C. trachomatis 4.3 (2.7–5.9) 7.1 (5.9–8.3) 0.61 0.72 (0.47–1.11) 8.0 (6.6–9.5) 4.5 (3.2–5.7) 1.80 1.52 (1.12–2.05)
T. vaginalis 13.6 (11–16.2) 14.3 (12.5–16.1) 0.95 1.11 (0.92–1.35) 13.2 (11–15.3) 15.0 (12.9–17.1) 0.88 1.01 (0.83–1.21)
M. genitalium 11.7 (9.4–14.1) 5.6 (4.5–6.7) 2.10 2.01 (1.52–2.66) 10.1 (8.3–11.9) 4.7 (3.4–6) 2.16 1.82 (1.27–2.63)
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PR=prevalence ratio; aPR=Adjusted prevalence ratio; 95% CI= 95% confidence interval

*

adjusted for sex and age

Adjusting for sex and age, among HIV positive individuals having a CD4 cell counts of <350 cells per μL was associated with an increased probability of having N. gonorrhoeae (aPR=1.59, 95% CI 1.00–2.52) and M. genitalium (aPR=2.01, 95% CI 1.52–2.52); whilst having an HIV viral load ≥400 copies per mL was associated with an increased probability of having N. gonorrhoeae (aPR=1.91, 95% CI 1.36–2.70), C. trachomatis (aPR= 1.52, 95% CI 1.12–2.05) and M. genitalium (aPR=1.83, 95% CI 1.27–2.63).

Discussion

This population-based survey undertaken in rural and peri-urban KwaZulu-Natal, the province with the highest HIV prevalence in South Africa (Human Sciences Research Council. 2018) showed that over half of the participants in the study area had HSV-2 infection and just under one-quarter had at least one curable STI [syphilis (1.6%), N. gonorrhoeae (2.8%), C. trachomatis (7.1%), T. vaginalis (9.0%), and / or M. genitalium (5.5%)]. Similar to the low levels of reporting of genital symptoms among 15-to 24 year old’s in rural KwaZulu-Natal (Francis et al. 2018), only 3% of our participants reported having any genital symptoms, suggesting that majority of participants with STIs were either asymptomatic or that individuals were unable to recognize signs and symptoms of STIs precluding them from seeking care and treatment. In addition to contributing to adverse health outcomes, STIs interact with the immune system in genital mucosa sites facilitating HIV acquisition and transmission (Wasserheit 1992, Mayer and Venkatesh 2011, Abdool Karim et al. 2019, Mwatelah et al. 2019). Estimates of curable STIs were higher in the younger age groups, particularly in younger females, which is the same group among whom a peak in HIV incidence occurs (Kharsany et al. 2019), thus the importance of enhanced STI surveillance (Taylor and Wi 2019) and investment in targeted STI control programs for younger populations (Francis et al. 2018, Kharsany et al. 2019).

Globally and in the sub-Saharan African region, HSV-2 is the leading cause of genital ulceration and there is substantial overlap between the HSV-2 and HIV syndemics (Freeman et al. 2006). Prevalent HSV-2 leads to subclinical HSV-2 viral shedding (Wald et al. 2002) which may be exacerbated by incident HIV infections whilst incident HSV-2 infections has been associated with an elevated risk of HIV acquisition (Reynolds et al. 2003, Brown et al. 2007). The high prevalence of HSV-2 infection reflects either markers of risky sexual behaviours with HSV-2 and HIV acquired simultaneously (Corey 2007) or the biological basis of the plausibility of the increased shedding of HIV during acute, early or subclinical reactivation of HSV-2 infection thus enhancing transmission of both infections (Celum et al. 2005, Cohen et al. 2019). In this study by age 24 years, 60% of females were already HSV-2-positive, which underscores the rapid speed at which HSV-2 transmission is occurring and its potential for escalating HIV risk (Looker et al. 2017). The high HSV-2 prevalence may also help to explain the magnitude of the HIV epidemic in the region (Freeman et al. 2006, Kharsany et al. 2019).

The prevalence of T. vaginalis was higher among females and more importantly among males and females in the older age groups, suggesting that biological factors contribute to prevalence in older individuals (Lazenby et al. 2020) and that individuals’ perceptions and behaviours on sexual and reproductive health may result in sub-optimal health seeking behaviours (Rietmeijer 2019). Furthermore, as T. vaginalis is strongly associated with HIV acquisition and transmission (Kissinger and Adamski 2013), the high prevalence contributes to the spread of both infections. Similarly, the high prevalence of N. gonorrhoeae and C. trachomatis also suggests that many of these STIs remain untreated and could increase ascending genital tract infections (World Health Organization. 2016). M. genitalium has emerged as an important sexually transmitted pathogen with evidence of a temporal association between M. genitalium infection and HIV acquisition (Vandepitte et al. 2014). The prevalence of active syphilis at the population-level was 3.0% in females which is higher than the 2.3% among pregnant women in KwaZulu-Natal (South African National Department of Health. 2017). Despite the successful implementation of public health programs for the management of syphilis among pregnant women during prenatal care; programmatic interventions should be aimed at the population-level to diagnose, treat and to prevent long-term negative sequelae of untreated syphilis and of potential congenital syphilis.

The findings on the association of HIV positive status and curable STIs has important implications for the region. Recent studies have delineated the role and biologic mechanisms of STIs with disturbances in the vaginal microbiome, inducing mucosal inflammation, yielding unique cytokine profiles that evoke an influx of HIV receptor cells in genital mucosal epithelium (Abdool Karim et al. 2019, Mwatelah et al. 2019). The regression analyses revealed that HIV positive status increased the prevalence of curable STIs, though risk behaviours of more than 80% of sexually active participants reported not being married or living with partner as husband and wife, low levels of condom use, concurrent heterosexual partnerships, high number of lifetime sex partners and high levels of alcohol and substance use at a population-level could worsen and contribute to sustaining both STI and HIV epidemics in region. Even though our analysis adjusted for sexual risk behaviors, these behaviours might have been underestimated as survey procedures may not have adequately assessed the characteristics of the individual’s sexual networks or that participants may underreport on sexual risk-taking behaviours.

Among HIV positive individuals the association of CD4 cell counts of <350 cells per mL with N. gonorrhoeae and M. genitalium suggests that even with advancing HIV disease, susceptibility to STIs remains elevated. HIV-positive individuals tend to increase condom use at ART initiation (Risher et al. 2016), so it was not surprising that in this study HIV-positive individuals who were virally suppressed had a lower prevalence of curable STIs, suggestive of practicing safer sex behaviours.

In the absence of ART, STIs augment HIV viral shedding (Johnson and Lewis 2008). A meta-analysis of 39 studies showed that STIs that elicit a leukocyte response in the genital tract was associated with almost a three-fold increase in HIV viral shedding promoting potential sexual transmission of HIV (Johnson and Lewis 2008). However, HIV positive individuals using ART correctly and consistently benefit by achieving HIV viral suppression to prevent onward transmission (Abdool Karim 2019). However, whilst ART itself has no impact on STIs (Champredon et al. 2015), and as STIs remain untreated, HIV viral shedding persists in genital secretions including semen (Cohen et al. 2019) though shedding may be transient or intermittent (Chun et al. 2013). Our findings on the association of HIV viral load ≥ 400 copies per mL and STIs, highlights the sustained potential elevated risk of onward HIV transmission. It is critical that combination HIV prevention programs include the early diagnosis and treatment of STIs to reduce HIV viral shedding towards the goal of achieving HIV epidemic control (Joint United Nations Programme on HIV/AIDS (UNAIDS). 2017, Galvani et al. 2018).

Strengths and limitations of this study

The strength of this study was the use of biological measurements of STIs on self-collected genital samples rather than relying on signs and symptoms of STIs. Despite the robust sampling strategy, given the cross-sectional design of the study, temporality of any associations cannot be inferred, and generalizability of our findings are limited to the study area or to similar high HIV burden settings. As the sociodemographic, behavioural and clinical data were self-report, these could potentially be prone to social desirability bias. The data on sexual partnerships were reported over the previous 12 months or further and may be subject to recall bias. Even though participants were guided on the self-collection method of obtaining genital samples, some samples may have been of inadequate quality resulting in an underestimation of the prevalence of STIs.

Conclusions

The high prevalence of STIs and the association with HIV and HIV viral load ≥400 copies per mL underscores the public health implications of sustained onward transmission risk of STIs and HIV. STIs remain a threat towards realizing the goal of achieving HIV epidemic control in this high HIV burden region.

Supplementary Material

Supplementary

Supplementary Table 1: STROBE Statement—Checklist of items included in reporting of cross-sectional study, Population Prevalence of sexually transmitted infections in a high HIV burden district in KwaZulu-Natal, South Africa: Implications for HIV epidemic control

Supplementary Table 2: Prevalence of sexually transmitted infections by current pregnancy statusa among participants, 15–35 years

Highlights.

  • The high prevalence of STIs provides compelling evidence for enhanced surveillance for STI control

  • Prevalence of curable STIs was higher in the younger age groups among whom a peak in HIV incidence occurs

  • The association between STIs and HIV, HIV viral load ≥400 copies per mL contributes to sustaining the STI and HIV epidemics.

  • STIs threaten the goal of achieving HIV epidemic control in this high HIV burden region

Acknowledgements

Our sincere thanks to all household members and individual study participants. We acknowledge the ongoing support of the District Manager of the uMgungundlovu Health District, members of the Provincial Department of Health, uMgungundlovu district municipality, Provincial Health Research and Knowledge Management, traditional leadership, and community members for their support throughout the study. A special thank you to the study staff for the field work, laboratory staff and to the Primary Health Care clinic staff in the district.

Funding

This work was supported by the President’s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC), grant number U2GGH000372-02W1. ABMK is supported by the joint South Africa-US Program for Collaborative Biomedical Research from the National Institutes of Health, grant number R01HD083343.

Role of Funding source

The funders of the survey contributed to the survey design and study monitoring and did not interact with human subjects or have access to identifiable data or specimens for research purposes. ABMK and LL had full access to all the data. ABMK, CC and DK had final responsibility for the decision to submit for publication.

Footnotes

Data sharing statement

Data are available upon reasonable request. Kindly contact Professor Ayesha BM Kharsany at Ayesha.kharsany@caprisa.org

Competing interest

All authors declare that they have no competing interests.

Publisher's Disclaimer: Disclaimer

Publisher's Disclaimer: The contents of this publication are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or other funding agencies.

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Supplementary Materials

Supplementary

Supplementary Table 1: STROBE Statement—Checklist of items included in reporting of cross-sectional study, Population Prevalence of sexually transmitted infections in a high HIV burden district in KwaZulu-Natal, South Africa: Implications for HIV epidemic control

Supplementary Table 2: Prevalence of sexually transmitted infections by current pregnancy statusa among participants, 15–35 years

NIHMS1619750-supplement-Supplementary.docx (47.7KB, docx)

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