After 3 decades, STD epidemic reaches ‘decisive moment’

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To mark our 30th anniversary, Infectious Disease News will be examining some of the infectious diseases that have defined and changed the field over the past 3 decades.

In 1987, almost 977,000 cases of chlamydia, gonorrhea and syphilis were reported nationwide in the United States. The next year, that number surpassed 1 million, where it would remain for the next several years.

Proximate to this burden was the recognition that physicians needed better training in diagnosing and treating STDs, according to Anne Rompalo, MD, professor of medicine at the Johns Hopkins University School of Medicine. Additionally, experts grew aware of the importance of surveillance.

Jonathan H. Mermin
Elizabeth Torrone

“Over the last 30 years, I think we’ve made progress in understanding the epidemiology and diagnosis of the diseases and we’ve tried to do better with the treatment, but people are sexually active and the diseases aren’t going away,” Rompalo said in an interview. “If anything, they’re increasing, so we have a lot of challenges.”

Indeed, the CDC announced last year that a record number of STDs were reported in the U.S. in 2015 — a troubling development that federal health officials said was partly a result of budget cuts in state and local health departments. But improved diagnostics have also undoubtedly played a role in the increase.

“When you look for things, you’ll find them,” Rompalo said.

Each year, physicians are testing a new cohort of sexually active patients, and those who have just become sexually active are at the highest risk for infection, Rompalo said. In fact, according to prevalence estimates reported by the CDC, young people aged 15 to 24 years acquire half of all new STDs and are at a higher risk for infection than older patients for a combination of behavioral, biological and cultural reasons.

The CDC offers STD prevention training activities geared toward helping practitioners better diagnose, treat and prevent STDs and HIV, and Rompalo explained that one of the biggest goals is helping clinicians feel more comfortable opening a dialogue about reproductive health with their patients.

“Are we getting better at that? God, I hope so,” she said. “I think the younger generation is more comfortable in discussing sexual preference, sexual identity, and they may be more open to discussing sexual health.”

This article focuses on the three nationally reportable bacterial STDs tracked by the CDC: chlamydia, gonorrhea and syphilis. A future article marking the publication’s 30th anniversary will address HPV, the most common sexually transmitted infection in the country.

“All STDs are treatable and most are curable — that’s the good news,” Elizabeth Torrone, MSPH, PhD, epidemiologist in the CDC’s Division of STD Prevention, said in an interview. “We have really tried to bring STDs into the conversation, meaning we want people to feel comfortable talking about STDs both to their partners and providers. I hope over the past couple of decades some of those efforts have been successful in the sense that when people think about STDs, they think of them as something that they need to be concerned about, but also something that they can do something about.”

A record number of cases

If left untreated, STDs can cause severe health problems. For example, untreated chlamydia or gonorrhea can lead to infertility problems, and untreated syphilitic infections can cause blindness.

In 2015, 1,996,576 cases of chlamydia, gonorrhea and syphilis were reported to the CDC. The burden was particularly high in young people, with patients aged between 15 and 24 years accounting for nearly two-thirds of the more than 1.5 million cases of chlamydia and half of the nearly 400,000 cases of gonorrhea. It also was high in men who have sex with men (MSM), who accounted for the majority of new gonorrhea and primary and secondary syphilis cases. Moreover, the rate of syphilis diagnosis among women rose more than 27% since 2014, with a 6% increase in congenital syphilis, according to the CDC.

Jonathan H. Mermin, MD, MPH, director of the CDC center overseeing STD prevention, called it “a decisive moment for the nation.”

“STD rates are rising, and many of the country’s systems for preventing STDs have eroded. We must mobilize, rebuild and expand services — or the human and economic burden will continue to grow,” he said.

All three reportable STDs are curable with antibiotics — particularly chlamydia and syphilis — and widespread access to screening and treatment can limit their spread, but budget cuts in over half of state and local STD programs have resulted in more than 20 health departments closing, according to the CDC, limiting patients’ access to screening and treatment.

“Many of our partners locally have faced cuts to their STD clinics,” Torrone said. “When people may not have places to go, that means they’re infectious for a longer period, increasing the chance that they can spread their infection to their partners.”

Advances in testing

The primary tools for preventing STDs are screening and appropriate treatment. Rompalo said diagnostics — as least for chlamydia and gonorrhea — are “light years” better than they were 30 years ago. A dependence on cultures has given way to very sensitive nucleic acid amplification tests (NAATs), which make it easier to collect specimens for testing. Patients can even do it themselves.

“That is both exciting and helps us understand the epidemiology of the disease better and perhaps — hopefully — prevent it,” Rompalo said. “But syphilis is still an enigma, meaning that the diagnosis often depends on the clinical presentation, and even though we’ve mapped the whole genome of Treponema pallidum, the causative agent of syphilis, we still don’t have excellent diagnostic tests either from lesions or blood or even from cerebrospinal fluid. We need [to devote] a lot of attention to those issues.”

According to Torrone, understanding trends in STDs is complicated because the diseases are complex and their prevalence is affected by several underlying factors. Budget cuts to STD programs are concerning, but some of the increase in infections over the past 30 years can be explained by increased testing — infections that would otherwise have gone unnoticed are being diagnosed and treated.

For example, reported cases of chlamydia have skyrocketed in the past 30 years from 7,594 in 1984 — when the CDC first began tracking the disease nationally — to more than 1.5 million in 2015. Clinicians have gotten better at diagnosing chlamydia as the method for detection has evolved, Rompalo explained.

“The diagnosis became easier, and consequently we started to pick it up and report it more frequently,” she said. “If you go back to 1976, there were no chlamydia data because nobody was reporting it. It was discovered in the early 1900s, but it wasn’t aggressively looked for.”

Torrone said the increased number of diagnosed and reported STDs is partly a good thing because it means that asymptomatic infections that could be transmitted to others are being caught.

“We are looking for more infections and finding more infections, but that also means we’re treating more infections and potentially preventing spread of disease,” she said.

Drug-resistant gonorrhea

Unlike chlamydia and syphilis, which are still reliably treated with antibiotics, gonorrhea has developed extensive resistance to many of the drugs that have been developed to treat it.

“Gonorrhea is a particularly smart bug, and it has been successfully developing resistance over time, so it is becoming more difficult to treat,” Torrone said. “Luckily, we have systems in place to monitor susceptibility patterns to gonorrhea so we know what antimicrobials are still treating it and we’re able to make national recommendations based on those data, but we are running out of treatment options.”

In fact, there is just one remaining recommended treatment for gonorrhea — a dual therapy of ceftriaxone and azithromycin that is recommended by both WHO and the CDC. According to a recent study in PLoS Medicine, 66% of the countries reporting data between 2009 and 2014 reported seeing gonococcal isolates with decreased susceptibility or resistance to extended-spectrum cephalosporins, the only remaining effective drugs against gonorrhea in most countries.

The antibiotic pipeline for gonorrhea treatment currently includes just three candidate drugs. Among them, solithromycin (Cempra) is currently in a phase 3 trial, whereas phase 2 trials have finished on zoliflodacin (Entasis) and gepotidacin (GlaxoSmithKline). The Global Antibiotic Research and Development Partnership, a project established last year by WHO, has said it will partner with Entasis to accelerate development of zoliflodacin, which has shown activity against resistant strains of gonorrhea.

“Thirty years ago, I wouldn’t have been surprised if you told me resistance was increasing, but it was an exciting time because there were a lot of drugs coming through the pipeline for a lot of bacteria. But I would never have thought it was going to be totally resistant,” Rompalo said.

Unlike certain viral STDs like HPV, there are no vaccines for the three nationally reportable bacterial STDs. However, researchers in New Zealand reported recently in The Lancet that they found the first evidence of a vaccine being protective against gonorrhea. The vaccine, MeNZB, was developed to combat an epidemic of meningitis B in New Zealand last decade. However, according to the results of a retrospective study, it also offered protection against gonorrhea, with a vaccine effectiveness of 31% against the infection — an unforeseen benefit the researchers said was of greater importance in view of the increase in antibiotic resistant gonorrhea.

“Nobody wants to have gonorrhea that can’t be treated,” Rompalo said. “So far we’ve been able to get around it.”

Torrone said the problem of antibiotic-resistant gonorrhea can be addressed in ways beyond new drug development. For instance, providers can make sure they are following the current treatment recommendation — 250 mg of intramuscular ceftriaxone and 1 g of oral azithromycin.

“Make sure patients go back to see their providers in their symptoms don’t resolve,” she said.

Threat of syphilis

Despite worldwide alarm over drug-resistant gonorrhea, among the three nationally reportable bacterial STDs, syphilis may be the most problematic, according to Rompalo.

“We’re concerned about increasing syphilis rates — among MSM, surely, but it’s also increasing in women, and if it increases in women, you’re going to see congenital syphilis,” Rompalo said.

According to data presented at last year’s CDC Epidemic Intelligence Service conference, reports of syphilis among pregnant women increased 25% from 2012 to 2014 and accompanied rises in rates of congenital syphilis and syphilitic stillbirths. CDC statistics for 2015 showed increased reports of cases of syphilis in all its stages and in congenital syphilis infections.

“We have a good screening test, we have excellent therapy and Treponema pallidum has not become resistant to penicillin,” Rompalo said. “We shouldn’t have to deal with congenital syphilis in this day and age.”

Nonreportable and emerging diseases

The CDC does not track the incidence of genital herpes, a chronic and lifelong viral infection that affects tens of millions of people in the U.S. However, like its surveillance of HPV, the agency uses other strategies to monitor the burden of the disease, primarily with the National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of results from interviews and examinations of patients, according to Torrone.

“We use those estimates here at CDC to help monitor burden of disease for those nonreportable diseases,” she said.

Much less is known about other STDs, including emerging infections like Mycoplasma genitalium, which was identified more than 30 years ago, but whose pathogenic role remains poorly defined. Rompalo said the infection seems to be associated with urethritis, cervicitis and pelvic inflammatory disease.

“We just don’t know enough about it,” Rompalo said. “We’re probably at the same stage we were with chlamydia in the 1970s. Is it an STD? What’s it causing? The problem is that it’s developing resistance quickly.” – by Gerard Gallagher

Disclosures: Mermin, Rompalo and Torrone report no relevant financial disclosures.

To mark our 30th anniversary, Infectious Disease News will be examining some of the infectious diseases that have defined and changed the field over the past 3 decades.

In 1987, almost 977,000 cases of chlamydia, gonorrhea and syphilis were reported nationwide in the United States. The next year, that number surpassed 1 million, where it would remain for the next several years.

Proximate to this burden was the recognition that physicians needed better training in diagnosing and treating STDs, according to Anne Rompalo, MD, professor of medicine at the Johns Hopkins University School of Medicine. Additionally, experts grew aware of the importance of surveillance.

Jonathan H. Mermin
Elizabeth Torrone

“Over the last 30 years, I think we’ve made progress in understanding the epidemiology and diagnosis of the diseases and we’ve tried to do better with the treatment, but people are sexually active and the diseases aren’t going away,” Rompalo said in an interview. “If anything, they’re increasing, so we have a lot of challenges.”

Indeed, the CDC announced last year that a record number of STDs were reported in the U.S. in 2015 — a troubling development that federal health officials said was partly a result of budget cuts in state and local health departments. But improved diagnostics have also undoubtedly played a role in the increase.

“When you look for things, you’ll find them,” Rompalo said.

Each year, physicians are testing a new cohort of sexually active patients, and those who have just become sexually active are at the highest risk for infection, Rompalo said. In fact, according to prevalence estimates reported by the CDC, young people aged 15 to 24 years acquire half of all new STDs and are at a higher risk for infection than older patients for a combination of behavioral, biological and cultural reasons.

The CDC offers STD prevention training activities geared toward helping practitioners better diagnose, treat and prevent STDs and HIV, and Rompalo explained that one of the biggest goals is helping clinicians feel more comfortable opening a dialogue about reproductive health with their patients.

“Are we getting better at that? God, I hope so,” she said. “I think the younger generation is more comfortable in discussing sexual preference, sexual identity, and they may be more open to discussing sexual health.”

This article focuses on the three nationally reportable bacterial STDs tracked by the CDC: chlamydia, gonorrhea and syphilis. A future article marking the publication’s 30th anniversary will address HPV, the most common sexually transmitted infection in the country.

“All STDs are treatable and most are curable — that’s the good news,” Elizabeth Torrone, MSPH, PhD, epidemiologist in the CDC’s Division of STD Prevention, said in an interview. “We have really tried to bring STDs into the conversation, meaning we want people to feel comfortable talking about STDs both to their partners and providers. I hope over the past couple of decades some of those efforts have been successful in the sense that when people think about STDs, they think of them as something that they need to be concerned about, but also something that they can do something about.”

A record number of cases

If left untreated, STDs can cause severe health problems. For example, untreated chlamydia or gonorrhea can lead to infertility problems, and untreated syphilitic infections can cause blindness.

In 2015, 1,996,576 cases of chlamydia, gonorrhea and syphilis were reported to the CDC. The burden was particularly high in young people, with patients aged between 15 and 24 years accounting for nearly two-thirds of the more than 1.5 million cases of chlamydia and half of the nearly 400,000 cases of gonorrhea. It also was high in men who have sex with men (MSM), who accounted for the majority of new gonorrhea and primary and secondary syphilis cases. Moreover, the rate of syphilis diagnosis among women rose more than 27% since 2014, with a 6% increase in congenital syphilis, according to the CDC.

Jonathan H. Mermin, MD, MPH, director of the CDC center overseeing STD prevention, called it “a decisive moment for the nation.”

“STD rates are rising, and many of the country’s systems for preventing STDs have eroded. We must mobilize, rebuild and expand services — or the human and economic burden will continue to grow,” he said.

All three reportable STDs are curable with antibiotics — particularly chlamydia and syphilis — and widespread access to screening and treatment can limit their spread, but budget cuts in over half of state and local STD programs have resulted in more than 20 health departments closing, according to the CDC, limiting patients’ access to screening and treatment.

PAGE BREAK

“Many of our partners locally have faced cuts to their STD clinics,” Torrone said. “When people may not have places to go, that means they’re infectious for a longer period, increasing the chance that they can spread their infection to their partners.”

Advances in testing

The primary tools for preventing STDs are screening and appropriate treatment. Rompalo said diagnostics — as least for chlamydia and gonorrhea — are “light years” better than they were 30 years ago. A dependence on cultures has given way to very sensitive nucleic acid amplification tests (NAATs), which make it easier to collect specimens for testing. Patients can even do it themselves.

“That is both exciting and helps us understand the epidemiology of the disease better and perhaps — hopefully — prevent it,” Rompalo said. “But syphilis is still an enigma, meaning that the diagnosis often depends on the clinical presentation, and even though we’ve mapped the whole genome of Treponema pallidum, the causative agent of syphilis, we still don’t have excellent diagnostic tests either from lesions or blood or even from cerebrospinal fluid. We need [to devote] a lot of attention to those issues.”

According to Torrone, understanding trends in STDs is complicated because the diseases are complex and their prevalence is affected by several underlying factors. Budget cuts to STD programs are concerning, but some of the increase in infections over the past 30 years can be explained by increased testing — infections that would otherwise have gone unnoticed are being diagnosed and treated.

For example, reported cases of chlamydia have skyrocketed in the past 30 years from 7,594 in 1984 — when the CDC first began tracking the disease nationally — to more than 1.5 million in 2015. Clinicians have gotten better at diagnosing chlamydia as the method for detection has evolved, Rompalo explained.

“The diagnosis became easier, and consequently we started to pick it up and report it more frequently,” she said. “If you go back to 1976, there were no chlamydia data because nobody was reporting it. It was discovered in the early 1900s, but it wasn’t aggressively looked for.”

Torrone said the increased number of diagnosed and reported STDs is partly a good thing because it means that asymptomatic infections that could be transmitted to others are being caught.

“We are looking for more infections and finding more infections, but that also means we’re treating more infections and potentially preventing spread of disease,” she said.

Drug-resistant gonorrhea

Unlike chlamydia and syphilis, which are still reliably treated with antibiotics, gonorrhea has developed extensive resistance to many of the drugs that have been developed to treat it.

“Gonorrhea is a particularly smart bug, and it has been successfully developing resistance over time, so it is becoming more difficult to treat,” Torrone said. “Luckily, we have systems in place to monitor susceptibility patterns to gonorrhea so we know what antimicrobials are still treating it and we’re able to make national recommendations based on those data, but we are running out of treatment options.”

In fact, there is just one remaining recommended treatment for gonorrhea — a dual therapy of ceftriaxone and azithromycin that is recommended by both WHO and the CDC. According to a recent study in PLoS Medicine, 66% of the countries reporting data between 2009 and 2014 reported seeing gonococcal isolates with decreased susceptibility or resistance to extended-spectrum cephalosporins, the only remaining effective drugs against gonorrhea in most countries.

The antibiotic pipeline for gonorrhea treatment currently includes just three candidate drugs. Among them, solithromycin (Cempra) is currently in a phase 3 trial, whereas phase 2 trials have finished on zoliflodacin (Entasis) and gepotidacin (GlaxoSmithKline). The Global Antibiotic Research and Development Partnership, a project established last year by WHO, has said it will partner with Entasis to accelerate development of zoliflodacin, which has shown activity against resistant strains of gonorrhea.

“Thirty years ago, I wouldn’t have been surprised if you told me resistance was increasing, but it was an exciting time because there were a lot of drugs coming through the pipeline for a lot of bacteria. But I would never have thought it was going to be totally resistant,” Rompalo said.

Unlike certain viral STDs like HPV, there are no vaccines for the three nationally reportable bacterial STDs. However, researchers in New Zealand reported recently in The Lancet that they found the first evidence of a vaccine being protective against gonorrhea. The vaccine, MeNZB, was developed to combat an epidemic of meningitis B in New Zealand last decade. However, according to the results of a retrospective study, it also offered protection against gonorrhea, with a vaccine effectiveness of 31% against the infection — an unforeseen benefit the researchers said was of greater importance in view of the increase in antibiotic resistant gonorrhea.

PAGE BREAK

“Nobody wants to have gonorrhea that can’t be treated,” Rompalo said. “So far we’ve been able to get around it.”

Torrone said the problem of antibiotic-resistant gonorrhea can be addressed in ways beyond new drug development. For instance, providers can make sure they are following the current treatment recommendation — 250 mg of intramuscular ceftriaxone and 1 g of oral azithromycin.

“Make sure patients go back to see their providers in their symptoms don’t resolve,” she said.

Threat of syphilis

Despite worldwide alarm over drug-resistant gonorrhea, among the three nationally reportable bacterial STDs, syphilis may be the most problematic, according to Rompalo.

“We’re concerned about increasing syphilis rates — among MSM, surely, but it’s also increasing in women, and if it increases in women, you’re going to see congenital syphilis,” Rompalo said.

According to data presented at last year’s CDC Epidemic Intelligence Service conference, reports of syphilis among pregnant women increased 25% from 2012 to 2014 and accompanied rises in rates of congenital syphilis and syphilitic stillbirths. CDC statistics for 2015 showed increased reports of cases of syphilis in all its stages and in congenital syphilis infections.

“We have a good screening test, we have excellent therapy and Treponema pallidum has not become resistant to penicillin,” Rompalo said. “We shouldn’t have to deal with congenital syphilis in this day and age.”

Nonreportable and emerging diseases

The CDC does not track the incidence of genital herpes, a chronic and lifelong viral infection that affects tens of millions of people in the U.S. However, like its surveillance of HPV, the agency uses other strategies to monitor the burden of the disease, primarily with the National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of results from interviews and examinations of patients, according to Torrone.

“We use those estimates here at CDC to help monitor burden of disease for those nonreportable diseases,” she said.

Much less is known about other STDs, including emerging infections like Mycoplasma genitalium, which was identified more than 30 years ago, but whose pathogenic role remains poorly defined. Rompalo said the infection seems to be associated with urethritis, cervicitis and pelvic inflammatory disease.

“We just don’t know enough about it,” Rompalo said. “We’re probably at the same stage we were with chlamydia in the 1970s. Is it an STD? What’s it causing? The problem is that it’s developing resistance quickly.” – by Gerard Gallagher

Disclosures: Mermin, Rompalo and Torrone report no relevant financial disclosures.