Lorraine L. Janeczko, MPH

 has shown that correlations between HIV infection, older age, lower CD4 counts, and the prevalence of ocular syphilis may suggest that development of the disease may be affected by immune status.

, Matilde Ruiz-Cruz, MD, MSc, a researcher at the Center for Research in Infectious Diseases at the National Institute of Respiratory Diseases (INER) in Mexico City, Mexico, characterized the immunologic profile in the aqueous (AqH) humor of HIV-infected patients who have cytomegalovirus retinitis (CMVr) or ocular syphilis, and they examined whether AqH and plasma represent independent cytokine compartments.

"Our results support previous findings indicating elevated levels of AqH IP-10 and MCP-1 in individuals with CMVr, and we corroborated the notion of elevated concentrations of MCP-1 and IL-8 previously reported in AqH of individuals with uveitis, as well as the intraocular production of IL-8 by the ciliary processes," the authors wrote.

Dr. Ruiz-Cruz and her colleagues measured concentrations of 27 cytokines in the AqH and plasma of 23 patients with CMVr and of 16 patients with ocular syphilis. The researchers enrolled the participants over a two-year period, and they measured and compared the cytokine profiles of patients in both groups.

The authors took plasma and AqH samples from participants before treating them for their ocular infection (OI). The medical workup for HIV-infected patients included CD4 T-cell counts and HIV RNA load determinations. To detect ocular involvement in HIV infection, the authors examined all patients with a slit-lamp biomicroscope and an indirect ophthalmoscope.

They diagnosed ocular infections on clinical exam. White retinal lesions, vasculitis, intraretinal hemorrhages, and retinal edema without vitritis indicated CMVr. Uveitis, retinitis, vitritis, choroiditis, papillitis, and panuveitis, with positive serum Venereal Disease Research Laboratory (VDRL) and fluorescent treponemal antibody absorption (

After the researchers obtained plasma and AqH samples, they treated the patients who had CMVr with oral valganciclovir and those who had ocular syphilis with intravenous penicillin.

They took 20 mL of peripheral ethylenediaminetetraacetic acid (

) anticoagulated blood from HIV-infected patients. The plasma was centrifuged and separated, and it was stored at —80ºC for testing. Aqueous humor samples (100–150μL) were collected by anterior chamber puncture with a 30-gauge needle using topical anesthesia and were also stored at –80ºC.

As reported online January 12, 2017 in the journal, 

, patients with CMVr had higher plasma cytokine levels than those with ocular syphilis. Those with CMVr had higher plasma concentrations of interleukin (IL)-7, IL-8, IL-10, interferon (IFN)-γ, IFN-α2, G-CSF, IP-10 and IL-1α; they also had greater AqH concentrations of IL-1α, IP-10 and GM-CSF than participants with ocular syphilis. In both infections, AqH and plasma levels correlated only for IP-10.

"To our knowledge, this is the first study comparing the immunologic profile in AqH and plasma of HIV-infected individuals with CMVr versus those with ocular syphilis," the authors wrote.

"Individuals with CMVr have a more advanced HIV infection than individuals with ocular syphilis, and plasma cytokine concentrations seem to be determined mostly by the stage of HIV disease and in a lesser extent by the type of ocular infection," they added.

Because the immunologic profiles in aqueous humor and plasma are independent, the authors noted, aqueous humor cytokine concentrations cannot be inferred from plasma cytokine concentrations in these patients.

Identifying the cytokines involved in the pathogenesis of ocular infections in HIV-infected patients may lead to the development of drugs targeting these cytokines, especially in cases of inflammation that persists after active ocular infections have been successfully treated, they added.

Lorraine L. Janeczko, MPH, is a medical science writer who creates news, continuing medical education and feature content in a wide range of specialties for clinicians, researchers and other readers. She has completed a Master of Public Health degree through the Department of Epidemiology of the Johns Hopkins Bloomberg School of Public Health and a Dana Postdoctoral Fellowship in Preventive Public Health Ophthalmology from the Wilmer Eye Institute, the Johns Hopkins University School of Medicine and the Bloomberg School. 

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Researchers have found that individuals with cytomegalovirus retinitis have a more advanced HIV infection than individuals with ocular syphilis.

Ocular Syphilis and Cytomegalovirus Retinitis Have Different Immunologic Profiles

The number of patients with ocular syphilis (OS) is increasing, and OS may be more common in syphilis patients who have concurrent HIV than in those who don't, recent research from North Carolina suggests.

"Reports of primary, secondary, and early latent syphilis have increased in North Carolina in recent years. Between 2014 and 2015, early syphilis increased from 1137 cases to almost 1900 cases, representing a 64% increase in reported cases... We found ocular syphilis in all stages of syphilis," lead author Anna Barry Cope, PhD, MPH, said in her late-breaker presentation September 22, 2016 at the Centers for Disease Control and Prevention (CDC) 2016 STD Prevention Conference in Atlanta, Georgia.

"Nearly half of all syphilis cases in North Carolina are co-infected with HIV. They were infected with HIV either prior to their syphilis diagnosis or within 30 days after," added Dr. Cope, an epidemiologist at CDC in Atlanta.

"Clinicians need to look for ocular syphilis in their at-risk patients. Patients need to know whether they have ocular syphilis, and that if they have it, they need to get treated quickly to prevent complications, including possible blindness," Thomas Peterman, MD, MSc, chief of the Field Epidemiology Unit for the Epidemiology and Surveillance Branch of the Division of STD Prevention at CDC in Atlanta, who moderated the late-breaker session, told 

Dr. Cope and her colleagues compared OS prevalence by HIV status and timing of HIV diagnosis among all syphilis patients in North Carolina. They reviewed all syphilis cases reported in the North Carolina Electronic Disease Surveillance System (NC EDSS) in 2014 and 2015.

The researchers identified potential ocular syphilis cases in NC EDSS and matched ocular and non-ocular syphilis cases with the Enhanced HIV/AIDS Reporting System (eHARS) to obtain HIV diagnosis date.

They grouped all syphilis cases with HIV co-infection into previously diagnosed (HIV diagnosed more than 30 days before syphilis diagnosis) and concurrently diagnosed (HIV diagnosed within 30 days before or after syphilis diagnosis) cases. Cases with HIV diagnosed more than 30 days after syphilis diagnosis were considered HIV-uninfected. Prevalence ratios were used to match OS prevalence with HIV status.

Of 4232 confirmed syphilis cases, 63 (1.5%) had ocular syphilis; of these 63 cases, 35 (56%) were co-infected with HIV; and of the 35, the diagnosis was concurrent in 11 cases (31%).

Of the 4169 confirmed syphilis cases without OS, 1659 (40%) were co-infected with HIV; of the 1,659, the diagnosis was concurrent in 253 (15%).

 The prevalence of ocular syphilis was almost twice as high among HIV-positive patients as among those who were HIV negative or HIV unknown (prevalence ratio 1.9; 95% confidence interval, 1.1 to 3.1).

Of the 1694 HIV-infected syphilis cases, 264 were diagnosed with HIV at the same time as their syphilis diagnosis, and 4.2% of the 264 cases were classified as ocular syphilis cases (prevalence ratio 2.5; 1.2 to 5.0).

Among syphilis patients with a previous HIV infection, those with OS were older than those without OS (median age 42 years vs 33 years; 

=.008), and they had a lower CD4 cell count (median 384 cells vs 521 cells/mL; 

=.03). The viral load was roughly equal between OS and non-OS patients (median 40 copies vs 20 copies/ml, 

Syphilis patients concurrently diagnosed with HIV who had OS were also older than those without OS (median age 48 years versus 27 years; 

=.0004) and had a lower CD4 cell count (260 cells vs 382 cells/mL; 

=.04). Patients with OS had a higher viral load (median 65,780 copies versus 44,024 copies/ml, 

 to US clinicians urging them to be aware of ocular syphilis, screen for visual complaints in patients at risk for syphilis, and test all patients with syphilis for HIV if their status is unknown or has been negative.

"The associations we found between older age, lower CD4 counts, and the prevalence of ocular syphilis suggests that OS development may be affected by immune status," Dr. Cope said in an interview.

"All syphilis patients, especially those with ocular syphilis, should be screened for HIV," she noted.

Drs. Cope and Peterman called for further related research.

DISCLOSURES: The authors of both studies and Dr. Peterman did not report any conflicts of interest with the studies.

2016 CDC STD Prevention Conference p 78 (

https://www.cdc.gov/stdconference/2016/STD_Conference_2016_Program_Book.pdf

) Late-Breaker abstract 3F1 Ocular Syphilis and HIV Coinfection: An Opportunity to Identify Previously Undetected HIV (

https://cdc.confex.com/cdc/std2016/webprogram/Paper38074.html

Cytokine Profiles in Aqueous Humor and Plasma of HIV-infected Individuals with Ocular Syphilis or Cytomegalovirus Retinitis. 

http://www.tandfonline.com/doi/pdf/10.1080/09273948.2016.1268170?needAccess=true

Researchers have found that cases of ocular syphilis have been increasing in North Carolina and that the prevalence of ocular syphilis was almost twice as high among HIV-positive patients as among those who were HIV negative or HIV unknown.

Ocular Syphilis May Suggest HIV Co-Infection

Women who report having rectal intercourse should have rectal screening for chlamydia and gonorrhea, but often those tests are overlooked, according to study results presented at the Centers for Disease Control and Prevention (CDC) 2016 STD Prevention Conference in Atlanta, Georgia.

In their study, the researchers found that giving only a urogenital test to patients who had rectal-only chlamydia and/or gonorrhea infections led to 54 (30%) of the rectal infections being missed.

"While anal sex is commonly associated with MSM (men who have sex with men), in a recent round of the National Survey of Family Growth, heterosexual anal sex was reported in nearly 36% of women age 15 to 44 years over their lifetime, suggesting this type of sexual practice is not entirely uncommon," lead author Eloisa Llata, MD, said in her presentation.

"Using a large multisite dataset of routinely collected sexually transmitted disease (STD) clinic visits, we demonstrated a substantial rectal chlamydia and gonorrhea infection burden in the women reporting anal intercourse," said Dr. Llata, a medical epidemiologist in the Division of Sexually Transmitted Disease (STD) Prevention at the CDC in Atlanta.

Dr. Llata and her colleagues reviewed the electronic medical records of female patients attending any of 24 STD clinics in 5 US cities that participated in the STD Surveillance Network (SSuN) of STDs in 2015. The authors analyzed data from women reporting having rectal intercourse in the 3 months before their visit. The women ranged in age from 12 through 68 years and slightly more than two-thirds were 25 and above; almost half the women were African-American; 14 (0.6%) had documented HIV infection, and 172 (8%) reported having both male and female sex partners. Women reported anal intercourse in 2,307 visits (5.1%), made by 2,156 unique women, of 45,503 visits.

Rectal chlamydia and gonorrhea swabs were collected in 1822 (79%) of the 2307 visits where women reported anal intercourse. All screening was performed by nucleic acid amplification test (NAAT). A total of 135 (7.4%) tests were positive for rectal chlamydia only; 42 (2.3%) tests were positive for gonorrhea only; and 15 (0.8%) were infected with both, bringing the total to 192 patients who tested positive for rectal chlamydia or gonorrhea. The number of rectal infections detected overall increased by about 30%, from 128 to 192. Rectal infections (10.5%) were almost as common as urogenital infections (13.0%).

"Currently, chlamydia and gonorrhea screening is recommended for all sexually active women up to age 24 and for older women at increased risk for infection," Dr. Llata told 

"In MSM who report receptive anal intercourse, routine anorectal screening is recommended. But, guidelines for women mainly involve genitourinary screening. We have no guidelines for rectal chlamydia and gonorrhea screening in women, even in women who report anal intercourse," she added.

Ina Park, MD, who moderated the session, but was not involved in the study, said in an interview, "This is an important study. Chlamydia and gonorrhea are very common and the organisms can migrate from the rectum to the vagina."

"Most infections in women don't have symptoms so they may not be treated on time or treated at all, possibly leading to pelvic inflammatory disease, chronic pelvic pain, or pregnancy complications," added Dr. Park, chief of the Office of Medical and Scientific Affairs of the California Department of Public Health Sexually Transmitted Disease Control Branch in Richmond, California.

Drs. Llata and Park recommended further studies to explore the clinical and public health impacts of detecting and treating these infections.

DISCLOSURES: The authors of all three studies and Dr. Park did not report any conflicts of interest with the study.

Abstract 4A2 The Bottom Line: Possible Missed Infections Among Women Reporting Rectal Intercourse in STD Clinics, Sexually Transmitted Diseases Surveillance Network — United States, 2015: (

https://cdc.confex.com/cdc/std2016/webprogram/Paper37519.html

Centers for Disease Control and Prevention researchers find that in women who have rectal intercourse, rectal sexually transmitted infections chlamydia and gonorrhea can be almost as common as urogenital infections.

Women Who Report Rectal Intercourse Should Receive Rectal Screening for Chlamydia and Gonorrhea

Recent research has found that a significant proportion of adolescents who presented to the emergency department (ED) of a large urban hospital were overtreated (OT) and an even higher proportion were undertreated (UT) for 

Adolescents and young adults screened for sexually transmitted infections [STIs] have a high prevalence of GC/CT. A significant proportion of these patients end up over-treated and an even higher proportion are under-treated. … Adolescent females who are more likely to suffer from the sequelae of GC/CT are more likely to be under-treated," the authors, led by Mutimbwa Anaene, MD, MPH, a pediatrician in the Department of Pediatrics at the University of Illinois at Chicago, wrote in their 

, published in the December 2016 issue of the 

International Journal of Infectious Diseases

Because STI prevalence among patients in this ED is high, adolescents and young adults are screened for these infections regardless of the reason for their visit, although they can opt out of testing if they choose to.

The researchers investigated the prevalence of GC/CT, the rates of OT and UT, and factors associated with OT and UT for female and male adolescent and young adult patients.

They conducted a retrospective chart review of patients ages 13 through 24 treated at the Pediatric Emergency Department who were screened for GC/CT from July 2014 through June 2015.

Overall, 797 adolescents and young adults were screened for GC/CT and 171 of these patients (21.6%) tested positive for an STI (either GC, CT, or both): 152 patients (19.1%) were positive for CT, 44 patients (5.5%) were positive for GC, and 25 patients (3.1%) were co-infected with GC/CT. A total of 136 patients were overtreated for their infection and 74 of the patients who were positive for an STI were undertreated.

Female patients with OT were more likely to be between 18 and 19 years of age (risk ratio [RR] 2.13, 95% confidence interval (CI) 1.18 to 3.84), to present with STI exposure (RR 97.83, 95% CI 12.50 to 763.4), to have a history of STIs (RR 3.78, 95% CI 2.07 to 6.88), and to present with genito-urinary (GU) symptoms (RR 2.34, 95% CI 1.36 to 4.02).

Male patients with OT were more likely to present with STI exposure (RR 31.76, 95% CI 7.35 to 137.22) and to have GU symptoms (RR 8.07, 95% CI 3.26 to 19.95).

A patient was more likely to be UT if female (RR 3.28, 95% CI 1.34 to 8.05) and was less likely to be UT if presenting with STI exposure (RR 0.03, 95% CI 0.003 to 0.21), having a prior history of STIs (RR 0.13, 95% CI 0.05 to 0.33), and having GU symptoms (RR 0.26, 95% CI 0.12 to 0.57).

The authors call for more research into improving communication with patients to improve follow-up. They also recommend enrolling adolescents and young adults in health insurance plans so they can receive appropriate medical care. Recent research has shown that 

 can go a long way in helping to appropriately diagnose GC/CT infections in the ED by providing timely detection of infectious organisms and allowing for targeted antibiotic therapy.

Lorraine L. Janeczko, MPH, is a medical science writer who creates news, continuing medical education and feature content in a wide range of specialties for clinicians, researchers and other readers. She has completed a Master of Public Health degree through the Department of Epidemiology of the Johns Hopkins Bloomberg School of Public Health and a Dana Postdoctoral Fellowship in Preventive Public Health Ophthalmology from the Wilmer Eye Institute, the Johns Hopkins University School of Medicine and the Bloomberg School.

Recent research has revealed that some adolescents may be overtreated or undertreated for the sexually transmitted infections (STIs) chlamydia and gonorrhea when presenting to the emergency department (ED).

Some Adolescents May be Inappropriately Treated for STIs in the ED

Researchers are working to improve the testing and treatment of patients for chlamydia and gonorrhea, and the results of recent studies highlight some areas of progress.

The introduction of rapid diagnostic testing (RDT) can help Emergency Department (ED) providers notify their patients of an infection more quickly and help to treat them appropriately, while avoiding unnecessary antimicrobial use and costs, a new 

] in the ED significantly improved initial treatment appropriateness by sparing unnecessary antimicrobial use, decreased time to patient notification, and resulted in cost savings," the authors, led by Kaitlyn R. Rivard, PharmD, of the Department of Pharmaceutical Services of Mercy Health Saint Mary's in Grand Rapids, Michigan, wrote in the February 2017 issue of 

Diagnostic Microbiology & Infectious Disease

Dr. Rivard and her colleagues assessed the impact of RDT for NG/CT in an urban ED. They used electronic medical records to retrospectively identify all patients 15 years of age and above who were tested for NG/CT during the study period and collected data about the patients and their testing and treatment details.  

Overall, 200 consecutive patients in the "RDT" group were tested for NG/CT by RDT in December 2014 and January 2015. These patients were then compared with 200 consecutive patients in the "traditional" historical control group who had been tested between December 2013 and January 2014 using traditional nucleic acid amplification tests (NAAT).

The patients in the RDT group had significantly more appropriate treatment, 72.5% vs 60% (

= .008) and significantly faster test time to results notification (median 17.4 versus 51.5 hours, 

Patients who received their test results before they were discharged also received more appropriate treatment (odds ratio 22.65 [95% confidence interval, 2.86 to 179.68]), and thus RDT could save approximately $37,000 annually. These results support the use of NG/CT RDT to expand antimicrobial stewardship efforts within the ED.

For the RDT group, testing was performed on male and female urine and endocervical and vaginal swabs. For the traditional group, NAAT testing was performed on male urine or urethral samples and female endocervical samples.

 The median time to test results dropped significantly in the RDT group compared with the traditional group: (2.4vs 31.7 hours, 

<0.001), as did time to patient notification of positive results (17.4 vs 53.7 hours, 

The mean time to appropriate treatment for test-positive patients in the traditional group was 23.0 hours. The mean time to appropriate treatment in the RDT group was 4.9 hours.

Testing via RDT saved $4,891 ($24.46 per patient) over NAAT testing over the course of the study ($343,566 vs $348,457).

Nonculture methods, including NAAT, are widely available for the detection of genital NG/CT and are the preferred diagnostic tests recommended by the Centers for Disease Control and Prevention (CDC). With traditional NAAT, many health care facilities have a turnaround time between 1 and 4 days for results of NG/CT.

However, this prolonged time to results impacts time to patient and partner notification as well as treatment for test-positive patients who do not receive empiric therapy. Meanwhile, excessive empiric antimicrobial use in test-negative patients may contribute to increasing rates of antimicrobial resistance.

Antimicrobial stewardship programs have been developed within hospitals to promote optimal prescribing of antimicrobial agents in an effort to increase efficacy, improve patient safety, and reduce antimicrobial resistance.

The development of RDTs can help to achieve these goals by providing timely detection of infectious organisms and allowing for targeted antibiotic therapy. The Infectious Diseases Society of America and Society for Healthcare Epidemiology of America advocate for the use of RDT to improve detection capabilities and to guide appropriate treatment as part of an antimicrobial stewardship program.

Researchers find that rapid diagnostic testing may be the key to improving testing and treatment for chlamydia and gonorrhea.

Researchers are Improving Chlamydia and Gonorrhea Testing and Treatment

The Centers for Disease Control and Prevention (CDC)'s updated guidelines for treating survivors of sexual assault include recommendations for treating them appropriately and minimizing further trauma. Women who have been forced to have sex are at greater risk for sexually transmitted diseases (STDs) than other women, but they are also less likely to be treated for their illness, according to study results presented at the 2016 CDC STD Prevention Conference in Atlanta.

"Overall, 19.5% of the women experienced forced sex in their life, which is consistent with what we saw in the literature, that about 1 in every 5 women experienced forced sex," Dr. Oscar Beltran, a research fellow in the Division of Sexually Transmitted Disease Prevention at CDC, said in his session at the conference.

"Sexual violence against women is a great issue right now in the United States. We need to better understand the links between the experiences, diagnoses, and treatment of sexual violence so clinicians evaluating the sexual history of their patients can identify the women at higher risk and give them timely referrals to interventions and programs that can assist them," he told 

Survivors of sexual assault should be examined by an experienced clinician who chooses to obtain genital or other specimens for STD diagnosis based on the individual survivor. Care systems for survivors should deliver continuity of care, including timely test results, support, and monitoring of any adverse reactions to treatment.

Dr. Beltran, a research fellow, and his co-authors Drs. Kate Brookmeyer and Neetu Abad, behavioral scientists in the Division of Sexually Transmitted Diseases in Atlanta, investigated how STD treatment pathways may be altered for women who have been coerced into sex.

They collected 2011 through 2013 data from the National Survey of Family Growth (NSFG) nationwide representative household survey of individuals aged 15 through 44 years, and they performed logistic regressions controlling for age, race/ethnicity, poverty level and education.

Overall, 25% of the 4962 women identified were 18 through 24 years of age; 38% were 25 through 34, and 37% were 35 through 44. A total of 20% of the women were Hispanic; 14% were non-Hispanic Black, 59% were non-Hispanic White, and 7% identified as other. A total of 11% of the women had not completed high school studies, 27% had graduated from high school or had completed their General Educational Development (GED) requirements, and 62% had education beyond high school.

For women 18 years of age and above who were sexually active, the researchers examined the links between forced vaginal intercourse perpetrated by anyone and the following conditions: risky sex (no condom use during most recent sex or 2 or more male partners in 12 months, no condom use at last sex, paid sex), risky partners (partner who is a man who has sex with men (MSM), an injection-drug user, or is HIV positive), and substance abuse (4 or more drinks within two hours within the last 30 days, use of cocaine, crack cocaine, crystal meth, or injection drugs within the last 12 months).

The researchers assessed the link between forced vaginal intercourse and lifetime diagnosis of herpes, syphilis, or genital warts; 12-month diagnosis of chlamydia or gonorrhea; and 12-month STD treatment.

 After adjusting for demographics, women who were coerced into having sex were more likely to report risky sex (adjusted odds ratio (AOR) 1.56, 95% confidence interval (CI), 1.08 to 2.24), risky partners (AOR 1.90, 95% CI, 1.11 to 3.23), and substance abuse (AOR 1.80, 95% CI, 1.28 to 2.53).

Women who were forced to have sex were more likely to have had STD testing in the past 12 months (AOR 1.67 95% CI, 1.34 to 2.09).

Women forced to have sex were also more likely to ever be diagnosed with herpes (AOR 1.94, 95% CI, 1.13 to 3.32) and genital warts (AOR 2.55, 95% CI, 1.90 to 3.41) but were no more likely to be diagnosed with chlamydia, syphilis, or gonorrhea than women who were never coerced.

Women who were forced to have sex and were diagnosed with an STD were less likely to receive STD treatment compared with women who did not experience forced sex (AOR 1.44, 95% CI, 0.95 to 2.18).

The researchers noted that limitations to the study included its cross-sectional design that was based on a self-reported survey, the short time period involved, and the low number of syphilis and gonorrhea cases, which might have affected the results. The authors would like to conduct further related longitudinal studies.

"This study highlights the fact that sexual violence and STDs are major concerns in this country. We need to eliminate the barriers that women in danger have to seeking the care they need to protect themselves and maintain their health," Dr. Cheryl Kovar, assistant professor and director of the Nursing Leadership Concentration at East Carolina University College of Nursing in Greenville, North Carolina, said in an interview.

The CDC updated sexual assault, abuse, and STD guidelines are at 

https://www.cdc.gov/std/tg2015/sexual-assault.htm#riskHIV

DISCLOSURES: The authors and Dr. Kovar did not report any conflicts of interest with the study.

2016 CDC STD Prevention Conference p 95 (

Abstract 6C2: Understanding How Sexual Coercion Affects STD Treatment Pathways: Findings from the National Survey of Family Growth (2011-2013) 

https://cdc.confex.com/cdc/std2016/webprogram/Paper37531.html

Research has found that women who were forced to have sex and were diagnosed with an sexually transmitted disease (STD) were less likely to receive treatment compared with women who did not experience forced sex.

Lorraine L. Janeczko, MPH

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