Trends in Sexually Transmitted Infections

Abstract

Sexually transmitted infections have increased dramatically in the past 10 years. Rates are higher in Missouri than nationally, and higher in the large urban areas, in young adults, racial minority groups, among men having sex with men, and are associated with injection drug and methamphetamine use. Clinicians need to perform an appropriate sexual history and follow guidelines for screening and treatment. There is increasing concern for resistance among gonococcal isolates which limits future treatment options.

Introduction

After previous declines in morbidity, sexually transmitted infections (STIs) have been increasing in the United States.¹ STIs have long been associated with stigma and social inequality. The Institute of Medicine report in 1997 noted that despite the tremendous health and economic burden of STIs, the scope and impact of the STI epidemic are underappreciated and the STI epidemic is largely hidden from public discourse.² More than twenty years later, the burden of STIs is increasing.

Disease Burden

Gonorrhea cases in the United States reached a historic low of 98 cases per 100,000 population in 2009 but has increased 82.6% to 179 in 2018, a rate not seen since 1992 (Table 1).¹ The rate in Missouri and its two largest metropolitan areas are higher than the national average. Nationally, the rate is 46% higher among males than females, and highest among those aged 20–24. There is a marked disparity among racial/Hispanic ethnicity groups. Provisional data from 2019 show a further increase in cases in 2019 in Missouri.³

Table 1.

Rates of reported cases of gonorrhea (GC), chlamydia (CT) and syphilis per 100,000 population.¹

	GC	CT	Syphilis
			All stages	Primary and Secondary	Early non-primary and secondary	Congenital*
National US Rate 2018	177	540	35.3	10.8	11.8	33.1
National US Rate 2009	98	405	14.6	4.6	4.3	10.4
Missouri 2018 Rate	247	568	31.3	13.2	8.9	22.8
Kansas City Metro 2018 Rate	266	604	37.3	16.7	11.6
St. Louis Metro 2018 Rate	259	613	31.2	12.3	8.3
National rate by Sex 2018
Male	211	381		18.7
Female	144	693		3.0
National rate by Age 2018
15–19	432	2110		4.3
20–24	713	2899		10.0
National Rate by Race/Hispanic Ethnicity 2018
Blacks	549	1192		28.1		86.6
Whites	71	212		6.0		13.5
Hispanics	116	393		13.0		44.7

^*Congenital syphilis rates are per 100,000 live births.

Chlamydia is three-fold more common than gonorrhea.¹ Cases in the United States have increased by 33.3% since 2009. Similar to gonorrhea, the rates in Missouri and its two largest metropolitan areas are higher than the national average. In contrast to gonorrhea, the rate in females is higher than in males. The ages most affected are among 15–24 year olds, and there remains a marked disparity among racial/Hispanic ethnicity groups. Provisional data from 2019 in Missouri show a similar number of cases as in 2018.³

Syphilis rates (all stages) have increased 315% in 2018 since reaching a low in 2000.¹ Congenital syphilis increased 394% since 2012, representing 1306 cases in the United States. Syphilis is approximately six-fold more common in men than in women. The most common age group is 25–29 in men, and 20–24 in women. Similar to gonorrhea and chlamydia, there is a marked disparity among racial/Hispanic ethnicity groups.

High-Risk Populations

Men who have sex with men (MSM) account for 64.3% of national reported primary and secondary syphilis cases, and account for 66.6% of the cases among men.¹ 35% of the MSM cases were in those who also reported to be HIV positive. The rate of primary and secondary syphilis infection per 100,000 MSM in Missouri is 462.

Nationally, data for chlamydial and gonorrheal disease are not reported according to sexual partners. In a study at the Kansas City Health Department Sexual Health Clinic, we observed gonococcal infections approximately twice as commonly among MSM than among men having sex with women (MSW).⁴ As has been reported widely, more than 80% of the gonococcal disease burden among MSM would be missed if testing at pharyngeal and rectal sites were not performed. Similarly for chlamydia, rectal chlamydia is more than twice as common as urogenital chlamydia among MSM engaging in anal receptive sex, and more than 90% would be missed if not tested at the extragenital site. Almost all of those tested at extragenital sites were asymptomatic.

Although most primary and secondary syphilis is observed in MSM, rates of infection between 2014 and 2018 are increasing at a faster rate in MSW (99%) and in women (156%) than in MSM (48%).¹ This increasing rate of infection in MSW and women is associated with a marked increase in infections associated with injection drug use, methamphetamine use, heroin use and in sex with a person who injects drugs. This has been particularly observed among MSW and women living in Western and Midwestern states. As an example, in 2014 only 2.4% of MSW and 3.4% of women with primary and secondary syphilis in the Midwest reported methamphetamine use in the prior 12 months, compared to 14.8% of MSW and 22.4% of women in 2018. During this time, there was a decline in the primary and secondary syphilis cases among MSM that were associated with methamphetamine use from 8.3% in 2014 to 6.3% in 2018. In Kansas City, 47% of primary and secondary syphilis cases reported substance use of any kind during sex in 2019 compared to 31% in 2018 (data provided by Lesha Dennis, KC Health Department)

The higher rates of STIs in MSM may be exacerbated by the uptake in the use of preexposure prophylaxis (PrEP) among MSM. In an Australian study, 48% of those entering a PrEP trial developed an STI in a mean follow-up of 1.1 years.⁵ Among those with preenrollment data, the number of STIs increased by 12% after being initiated on PrEP and after adjusting for testing frequency. Risk factors for STIs included younger age, greater partner number and group sex.

Clinical Care

Clinicians should obtain a sexual history in a nonjudgmental approach avoiding terms that make assumptions regarding behavior or orientation. Questions that should be asked when evaluating a patient for the risk of STIs are found in table 2.

Table 2.

Questions for assessment of risk for STIs. (modified from Savoy, et al.⁶)

Are you currently sexually active? Have you been? what is your gender? How do you identify? How do your partners identify? Do they identify as male, female or another? what are the genders of your partners? How many partners have you had in the last month? In the last six months? Your lifetime? Do you participate in vaginal sex? Oral sex? Anal sex? Have you been tested for STIs and HIV? Have you ever had any STIs? Have your sex partners? Do you or your sexual partners use intravenous drugs and/or methamphetamines? How do you protect yourself from STIs and HIV?

Screening

The United States Preventive Services Task Force recommends screening for HIV for all people age 15 to 65, and to also include those younger and older who are at increased risk.⁷ Repeat screening is recommended for person who are increased risk, including sexually active MSM, a person with a sex partner with HIV, injection drug users, sex partners of injection drug users, exchanging sex for drugs or money, having another STI or a sex partner with a STI, or having a new sex partner whose HIV status is unknown. Key to obtaining appropriate screening is obtaining a thorough history for risks of STIs.

All sexually active females <25 years old should be screened for chlamydia and gonorrhea annually, and screened for syphilis if there are risk factors, including new or multiple sex partners, recent STI diagnosis, HIV disease, exchanging sex for money or drugs, or intravenous drug use or methamphetamine use.^7,8 Women ≥ 25 should be screened for chlamydia, gonorrhea and syphilis if there are similar risk factors, including a STI in the previous 24 months.

Pregnant women should be screened for chlamydia and gonorrhea in the first trimester if <25 or if there is an increased risk. ^7,8 All women should be screened for HIV, HBV and syphilis in the first trimester. Repeat screening should be done in the third trimester if there is an increased risk. Pregnant women with HIV should also be screened for trichomonas in the first trimester.

MSW without HIV should be screened for gonorrhea, chlamydia and syphilis if they had a previous STI in the last two years, on the basis of exposure to a known infection, or in targeted settings, such as adolescent and STI clinics and correctional facilities. ^7,8

MSM should be screened for genital chlamydia and gonorrhea, rectal chlamydia, rectal gonorrhea and pharyngeal gonorrhea if exposed, and syphilis annually. ^7,8 More frequent screening (every three months) should be done for those with multiple or anonymous sexual partners, and those who engage or whose sexual partners engage in injection drug or methamphetamine use.

Newer Aspects of Treatment and Prevention

Current guidelines for the treatment of cervical, urethral, rectal and pharyngeal gonorrhea in the United States is the combination of ceftriaxone 250 mg intramuscularly in addition to 1g of oral azithromycin.⁹ Although the combination was initially advocated for the high rate of coinfection with chlamydia, which has been reported as high as 46% in older national surveys,¹⁰ is also advocated even in those not co-infected with chlamydia because of concerns of rising minimum inhibitory concentrations (MIC) and the hope that the combination would lessen the chance of further development of resistance of gonococci to ceftriaxone. Ceftriaxone remains the best treatment option for all forms of gonococcal infections but there is a trend in the US and word-wide noting higher MICs associated with mosaic penA alleles that can lead to treatment failure.^11,12 Drug resistant gonococci has been listed by the CDC as one of the five urgent antibiotic threats in the US. ¹³ There is also a recent trend for higher MICs for azithromycin and frank azithromycin resistance, and it has not been clear that the combination of the two agents is beneficial in the absence of concomitant chlamydia infection. Guidelines in the UK and Japan utilize higher doses of ceftriaxone to reflect the concern for rising MICs, and it is anticipated that US guidelines may also evolve.

Pharyngeal gonorrhea infections are usually asymptomatic but are of concern because they may act as a reservoir promoting sustained infection, be less susceptible to treatment, and contribute to the evolution of antimicrobial resistance. In our study at the Kansas City Sexual Health Clinic, pharyngeal gonorrhea was found in 8.5% of MSM, but also in 3.8% of women and 3.1% of MSW.⁴ Extragenital infection in the absence of genitourinary infection is particularly common in MSM, but also was noted in about a third of MSW and women and would be missed in absence of extragenital screening. Current US guidelines recommend that providers should ask their patients with urogenital or rectal gonorrhea about oral sexual exposure and that any person with pharyngeal gonorrhea who is treated with a regimen other than the combination of ceftriaxone plus azithromycin should return 14 days after treatment for a test-of cure.⁹

Mycoplasma genitalium is likely the second most common cause of nongonococcal urethritis in males and has been associated with cervicitis and pelvic inflammatory disease in women. Macrolide resistance rates vary from 50 to 88% and when utilized, a five-day treatment is more effective than a single dose.¹⁴ Moxifloxacin is also recommended for suspected or confirmed Mycoplasma genitalium, but resistance to quinolones is also increasing. The organism is on the CDC’s Watch List for antimicrobial resistance threats for 2019.¹³ In 2019, the first Food and Drug Administration approved assay became available on the market. Concerns for single dose azithromycin in the treatment of nongonococcal urethritis, along with evidence of greater efficacy of doxycycline given for seven days over single-dose azithromycin for rectal chlamydia have called into question the routine use of single-dose azithromycin in the management of nongonococcal urethritis.

A French study among MSM using tenofovir disoproxil and emtricitabine for preexposure prophylaxis for HIV randomized participants to taking doxycycline 200 mg within 24h after sex or no prophylaxis.¹⁵ 42% of those in the control group developed a STI over a nine-month period. Those receiving doxycycline had a 70% lower rates of both chlamydia and syphilis, but no decrease in rate of gonorrhea. Most of the infections were asymptomatic.

Conclusions

Sexually transmitted infections are increasing in the United States. Although chlamydia is more common, of concern is marked increase in cases of gonorrhea and syphilis, including cases of congenital syphilis. Clinicians need to be thorough in obtaining an appropriate sexual history and basing screening decisions accordingly. Antimicrobial resistance, particularly for Neisseria gonorrhea and Mycoplasma genitalium, is increasing, with concerns that available therapies will lose efficacy.