Closing window of opportunity to save the medicines that save us from sexually transmitted infections

Shobha Shukla *

Antimicrobials have been widely used to fight diseases, including sexually transmitted infections (STIs), for nearly 80 years. Penicillin, the world's first antibiotic, was used for the first time to treat and cure syphilis in 1943. However, bacteria that cause STIs have fought back so that many of the antibiotics once used to treat them no longer work, even as STIs continue to cause high rates of infections worldwide.

In 2016, the World Health Organization (WHO) estimated the annual global burden of curable STIs to be 376 million new infections mainly of gonorrhoea, chlamydia, syphilis and trichomoniasis - over 1 million cases everyday. However, the emergence of antimicrobial-resistant strains of bacteria (that cause STIs) is making STIs difficult to treat and may even render the disease incurable as these antimicrobial-resistant strains become dominant.

Heading the list of bacterial STIs that have stopped responding to many drugs used earlier to treat them is gonorrhoea. The WHO estimates that 82.4 million people were newly infected with gonorrhoea in 2020. As per a study the gonorrhoea causing bacteria Neisseria gonorrhoea has already become resistant to penicillin, tetracycline, and fluoroquinolones. And now there is a rising global emergence of azithromycin/ ceftriaxone resistant Neisseria gonorrhoeae that threatens the current WHO recommended azithromycin/ceftriaxone dual therapy to treat gonorrhoea, which is being used in many countries.

Dr Rossaphorn Kittiyaowamarn, Chief of Bangrak STIs Center, Department of Disease Control, Ministry of Public Health, Thailand, told CNS that the first case of antibiotic non-susceptible Neisseria gonorrhoea (which is the most common bacterial sexually transmitted infections in Thailand, affecting both men and women) was reported in Thailand in 2017 and the number of cases is rising. Therefore, it is necessary to expand antimicrobial-resistant gonorrhoea surveillance and strengthen gonorrhoea laboratory tests to guide proper antibiotics use for reducing the risk of antimicrobial resistance in the coming future.

Professor Tadashi Kimura, Chairperson of Executive Board of Japan Society of Obstetrics and Gynaecology and Professor of Gynaecology and Obstetrics, Osaka University School of Medicine, also raised similar concerns. He said that while MRSA (Methicillin-Resistant Staphylococcus Aureus - MRSA) is the most prevalent antimicrobial-resistant bacterial strain in Japan, Ceftriaxone-resistant gonorrhoea cases are there and one has to be very careful and prevent this drug resistant strain from spreading. Another problem he was concerned about is that STIs are often treated in 'underground' clinics in Japan (for a variety of reasons), which do not have the wherewithal to do drug susceptibility tests and so cannot detect antimicrobial resistance, thus, not helping in checking the spread of antimicrobial resistance.

Due to limited access and affordability of STI laboratory diagnosis at the primary level of care where the majority of STI cases seek care, syndromic case management remains the cornerstone of STI control in many developing countries. Dr Ishwar Gilada, President of AIDS Society of India, and Governing Council member of International AIDS Society voiced his concern about this in lead up to the International Conference on Family Planning 2022 (ICFP 2022).

Dr Gilada said that in the case of STIs, other than HIV infection, patients are often treated empirically based upon their clinical presentation, without obtaining a microbiologic diagnosis.

"This syndromic management of STIs is a culprit resulting in developing antimicrobial resistance. Earlier molecular tests (such as, Cartridge-based nucleic acid amplification test or CBNAAT or polymerase chain reaction (PCR) tests) were not available and at times it was cheaper to treat than diagnose STIs. But now we are in 2022, and science is much more advanced."

Etiological diagnosis of STIs using laboratory tests to identify the causative agent is important. Syndromic diagnosis may miss individuals with asymptomatic STIs and thus help in spreading antimicrobial resistance, he said.

Regarding treatment of HIV, he said that some doctors have been treating HIV patients with the same old drugs to which their patients have stopped responding. "One example of human made antimicrobial resistance is the use of single dose nevirapine in the past for prevention of mother to child transmission of HIV. Its use as a single drug has caused a great harm by creating antimicrobial resistance to that class of antiviral drug."

According to Dr Gilada it is important to do a drug sensitivity test (DST) before starting a patient on antiretroviral therapy. But in many developing countries, including India, "we are using a deductive logic" and not doing a DST before putting the person on an antiretroviral regimen that is best suited for him/ her/ them. He also calls for a careful use of new antiretroviral medicines, like Dolutegravir, which has been used as a preferred combination antiretroviral medicine since 2018 by most countries. Apart from being highly effective and well tolerated, it has a high genetic barrier to developing resistance. But cases of resistance to this new antiviral have already surfaced. One has to use antimicrobials (including the new ones) very judiciously so that they do not lose their effectiveness.

"we should train medical caregivers properly both by way of formal training and by way of up-to-date knowledge" so that they can make a proper diagnosis and ensure rational use of existing drugs. If that is not done, we are going to face a problem of both primary as well as secondary resistance to antimicrobial drugs, Dr Gilada cautions.

Chlamydia and syphilis are other STIs to watch out. Macrolide resistance in syphilis is now present in many geographic regions. Although significant antibiotic resistance has not emerged in Chlamydia species pathogenic to humans, these organisms can express significant resistant phenotypes. So clinicians have to remain vigilant for the emergence of resistant strains in the future.

Thomas Joseph, Head, Antimicrobial Stewardship and Awareness Unit, at WHO, rightly points out "if antibiotics and other antimicrobials lose their effectiveness, we lose the ability not only to treat infections, but also to manage these other health conditions. A person with a drug-resistant infection is more likely to be sick and absent from work and family commitments, for longer, and require more expensive medicines and medical care. This has major implications on health-care costs and productivity, both for patients and their caregivers, as well as more broadly on the health system and national economy."

Antimicrobial resistance is already among the top threats looming over global health security today. Will we be able to protect the medicines that protect us? Let us hope the answer in the womb of time is affirmative. But as of now, a lot depends on actions we all take unitedly across sectors and geographies, to stem the tide of antimicrobial resistance.