Sexually transmitted infections (STIs) are caused by bacteria, viruses, or parasites. STIs have a devastating impact on adults and infants and annually affect millions of people in the United States. Certain STIs can increase a person’s risk of developing cancer and increase the likelihood of acquiring or transmitting HIV. In addition, STIs can cause long-term health complications, especially in the reproductive and central nervous systems. In rare cases, they can lead to serious illness or death. 

NIAID supports research across the spectrum from basic to clinical science to develop effective diagnostic, preventive and therapeutic approaches to STIs in alignment with the National STI Strategic Plan. In recognition of National STI Awareness Week, NIAID shares a snapshot of new projects and recent scientific advances in STI research. 

Improving treatment for syphilis and trichomoniasis

New reports of syphilis and congenital syphilis are increasing at an alarming rate in the United States. Syphilis is caused by the bacterium Treponema pallidum. Benzathine penicillin G (BPG) is one of only a few antibiotics known to effectively treat syphilis. There is currently a shortage of BPG, and some people are allergic to penicillin antibiotics. In February 2024, NIAID convened a workshop with a wide range of experts on alternative therapies to BPG for the treatment of adult syphilis, neurosyphilis, and syphilis in pregnant persons and infants. The workshop addressed preclinical evaluation of candidate drugs, the potential need for studies on how candidate drugs are processed in the body during pregnancy, and how to approach clinical trials of treatment for congenital syphilis. This work is part of NIAID’s comprehensive portfolio of syphilis diagnosis, prevention, and treatment research. 

Trichomoniasis is the most common parasitic STI, caused by Trichomonas vaginalis. Trichomoniasis can increase the risk of getting or spreading other STIs, including HIV. The parasite can also cause inflammation of the cervix and the urethra. T. vaginalis is treated with an antibiotic drug class called nitroimidazoles. The currently recommended nitroimidazole, called metronidazole, cures 84-98% of T. vaginalis cases but does have high rates of breakthrough infection. A new project led by Tulane University will examine a single dose of secnidazole, a medicine in the same drug class, as a more effective and cost-effective treatment option for women and men. 

Developing a vaccine for herpes simplex virus 2

Herpes simplex virus 2 (HSV-2) is a common subtype of herpes simplex virus that is transmitted through sexual contact. The Centers for Disease Control and Prevention estimates that 18.6 million people aged 15 years and older United States live with HSV-2. In severe cases, HSV-2 may lead to life-threatening or long-term complications. There is no licensed preventive HSV-2 vaccine, and there is no cure. A new project led by the University of Pennsylvania seeks to define correlates of protection for HSV-2, meaning they intend to identify immune processes involved in preventing HSV-2 disease. They will do this by analyzing laboratory samples from animal studies of a promising preventive vaccine candidate that they developed with prior funding. That vaccine candidate is also now in an industry-sponsored early-stage clinical trial. The same project will expand on the HSV-2 targets in the preventive vaccine to develop a therapeutic vaccine concept to reduce recurrent outbreaks. This research responds to the scientific priorities in the NIH Strategic Plan for Herpes Simplex Virus Research.

Increasing fundamental knowledge of bacterial vaginosis 

Bacterial vaginosis (BV) results from an imbalance in the vaginal microbiome. BV can be caused by sexual activity, douches and menstrual products. BV can increase women’s biological susceptibility to HIV and other STIs and can cause premature birth or low birthweight if untreated in pregnant people. In a recent publication, NIAID-supported researchers, led by researchers at the University of Washington and University of California San Diego, shared findings on how damage to the vaginal skin barrier occurs during bacterial vaginosis. Those skin barrier cells, called epithelial cells, are covered in carbohydrate molecules called glycans. The research team found that people with BV had damaged glycans on their vaginal epithelial cells. They suggested that future work should examine the relationship between treatment and restoration of normal glycans. If an association is detected, it could help healthcare providers monitor for successful treatment outcomes to reduce the likelihood that BV will return after a course of treatment. The findings were published in Science Translational Medicine. 

These activities are among the research investments in NIAID’s STI portfolio. For more information on STIs, please visit:

• NIAID Diseases & Conditions: Sexually Transmitted Infections
• U.S. Department of Health and Human Services STI National Strategic Plan

Following a peak in the summer of 2022, new infections in the mpox clade IIb outbreak have decreased, due in part to the rapid availability and uptake of vaccines and other preventive measures. However, mpox remains a health threat, and no treatment has been proven safe and effective for people experiencing mpox disease.

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, launched the STOMP trial to determine whether the antiviral drug tecovirimat can safely and effectively treat mpox. Tecovirimat, also known as TPOXX, was initially developed and approved by the Food and Drug Administration to treat smallpox—a species of virus closely related to mpox—but the drug’s safety and efficacy as an mpox treatment has not been established. The STOMP trial is a phase 3 study that aims to enroll about 500 people—a process that may require considerable time while mpox burden is low in study countries. NIAID continues to prioritize this study even while case counts are low.

VIDEO: Cyrus Javan of NIAID’s Division of AIDS explains the importance of the STOMP trial (audio description version here):

The STOMP trial was designed to be as inclusive as possible to ensure study results provide information on how tecovirimat works in the diverse populations affected by mpox. The trial is enrolling adults and children of all races and sexes, people with HIV, and pregnant and lactating people across 60 sites in the United States and Mexico, with an option for remote enrollment from other U.S. locations. More sites are expected to open in East Asia and South America.

The mpox virus has been endemic—occurring regularly—in west, central and east Africa since the first case of human mpox disease was identified in 1970. Mpox can cause flu-like symptoms and painful blisters or sores on the skin. People who acquire mpox tend to clear the infection on their own, but the virus can cause serious disease in children, pregnant people, and other people with compromised immune systems, including individuals with advanced HIV disease. Rare but serious complications of mpox include dehydration, bacterial infections, pneumonia, brain inflammation, sepsis, eye infections and death.

Completing the STOMP trial is essential, not only to evaluate a therapeutic option for the current mpox outbreak, but also to guide preparation for future outbreaks and provide evidence that could inform medical practice in historically endemic countries. The STOMP trial is sponsored by NIAID and led by the NIAID-funded Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG).

Beyond STOMP, NIAID is co-sponsoring the PALM007 trial of tecovirimat as treatment for clade I mpox in the Democratic Republic of the Congo (DRC) with the DRC’s National Institute of Biomedical Research. PALM007 is actively enrolling. In addition, NIAID is sponsoring an immunogenicity study of the JYNNEOS preventive vaccine, which has completed enrollment and is expected to report initial results in 2024. More information about these studies, including enrollment in STOMP and PALM007, is available here:

STOMP tecovirimat treatment study 
PALM007 tecovirimat treatment study
JYNNEOS vaccine study

Mpox has been present in west, central and east Africa for decades, with the first human case identified in 1970. In May 2022, a global mpox outbreak caused by a specific strain of the virus (referred to as “clade IIb”) was the first epidemiologic evidence of community mpox transmission outside of the historically affected African regions. More than 80,000 cases and 140 mpox-related deaths have been reported across 111 countries since the outbreak began, including more than 30,000 cases and 42 deaths in the United States. The origin of mpox remains unknown, but it belongs to a family of viruses called orthopox viruses. Variola virus (the cause of smallpox) is also an orthopox virus, but mpox disease is not as deadly as smallpox.

Since the start of the global outbreak, researchers, epidemiologists and healthcare providers have been monitoring transmission patterns and conducting research to better understand the natural history, clinical features and disease progression of mpox. These efforts are essential for informing the response to the current global outbreak, preventing future outbreaks and reducing the burden of mpox in countries where it has been a longstanding health threat.

A majority of cases in the global clade IIb outbreak have been reported in gay and bisexual men and other men who have sex with men, and an estimated 40% of reported U.S. mpox cases have been in people living with HIV. Individuals with advanced HIV disease are vulnerable to severe mpox infection, and most reported mpox deaths have been in immunocompromised individuals. 

While much has been learned about mpox in the past year, limited data are available on the immune response to mpox infection in people living with HIV, and even less information is available on women living with HIV who acquire mpox. Scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), recently described the clinical and immunological features of a woman living with HIV who acquired mpox while participating in a long-term NIAID study at the NIH Clinical Center. They reported these findings in the Journal of Infectious Diseases.

In the reported case, the study participant presented with lesions consistent with mpox in August 2022 and laboratory results confirmed mpox infection. Her HIV viral load was suppressed on antiretroviral therapy, and she experienced a mild mpox case with lesions on her face, wrist and forearm. She did not receive any mpox treatment due to her mild case. Despite these minor symptoms, laboratory results showed the study participant experienced dramatic changes in several types of immune cells suggesting her body mounted a robust immune response to mpox infection: data showed increased levels of B cells (associated with antibody production) and changes in some types of T cells (which trigger other immune functions and destroy viruses). Of interest, laboratory findings showed no significant change in the size of the participant’s HIV reservoirs, which suggests mpox infection did not have any effect on the clinical HIV status of this participant.

The study authors indicate more research is needed to understand the impact of mpox in people living with HIV and suggest this study may offer insights to guide future, larger studies.

NIAID is sponsoring several studies on mpox vaccination and treatment. More information about active studies, including contact details for enrollment, is available here:

JYNNEOS vaccine study
STOMP tecovirimat treatment study 
PALM tecovirimat treatment study

Reference: MA Rai et al. Impact of Monkeypox Virus Infection on Immune Parameters in a Woman With Human Immunodeficiency Virus Receiving Clinically Effective Antiretroviral Therapy. Journal of Infectious Diseases DOI: 10.1093/infdis/jiad096 (2023).