Shigellosis in men who have sex with men: an overlooked opportunity to counsel with pre-exposure prophylaxis for HIV

Introduction

With over 500,000 cases reported annually, shigellosis is one of the most common causes of bacterial dysentery in the United States. ¹ Contracted via the faecal-oral route, shigellosis has emerged as a sexually transmitted infection (STI) among men who have sex with men (MSM), with multiple notable local, regional, and national outbreaks.^2–11

Clinical case

A man in his late 40s presented to the Emergency Room with one week of nausea, vomiting, diarrhoea, and weight loss of twenty pounds. His past medical history was notable for remote history of syphilis, and social history was remarkable for several unprotected male sexual partners. On exam, he was non-toxic, without fevers or signs of haemodynamic instability. His laboratory results showed a normal leukocyte count, normal liver tests, and normal comprehensive metabolic panel. He was admitted to the hospital and received intravenous (IV) fluids. He was screened for STIs (chlamydia, gonorrhoea, HIV, syphilis, hepatitis A virus and hepatitis B virus) as well as Clostridium difficile, norovirus, and Escherichia coli O157:H7. All of these tests were negative. He improved and was discharged. After discharge he continued to improve for a few days, but then the diarrhoea and cramping abdominal pain returned. His stool cultures from the original admission grew Shigella flexneri 2a (resistant to ampicillin and trimethoprim-sulfamethoxazole, sensitive to ciprofloxacin). He was re-admitted and received IV ciprofloxacin due to significant nausea and vomiting. His GI symptoms slowly improved and he was discharged approximately three days later on two weeks of oral ciprofloxacin. During his hospitalization, the idea of pre-exposure prophylaxis (PrEP) for HIV was introduced. He reported that several of his previous partners had HIV and expressed interest in learning more about PrEP.

Discussion

Shigellosis has re-emerged as a non-traditional STI with increasing incidence in MSM. In the 1970s and 1980s, Shigella flexneri was seen with increasing incidence among men aged 20 to 49, postulating that shigellosis may also be transmitted sexually. ¹² Since then, outbreaks of Shigella flexneri and Shigella sonnei among MSM have been reported in Chicago, ⁴ Minneapolis, ⁴ San Francisco, ⁵ Québec, ⁶ London,^7,13 Berlin, ⁸ Australia, ⁹ and Tokyo. ¹⁰ This shift in epidemiology has been linked to sexual encounters involving direct and indirect oral-anal contact without appropriate prophylaxis barriers. ¹⁴ Epidemiological studies with bacterial genome sequencing have found that clusters of shigellosis in MSM are frequently resistant to first-line antibiotics including ampicillin, azithromycin, and trimethoprim/sulfamethoxazole.^{4,6,13,15–17}

There are several areas along the cascade of care for MSM with shigellosis where providers can intervene with education about harm reduction techniques. ¹⁸ Although the specific sexual risk factors are not entirely clear, a recent study reports that the majority of HIV-positive MSM with shigellosis sought partners for condomless anal sex. ¹⁹ Providers should be encouraged to have open and non-judgmental conversations with their patients about the varying levels of risk for STIs based on sexual activity. Condom use should be strongly encouraged for prevention of all STIs; however, in cases of shigellosis, the removal of the condom following sex also presents a point of possible infection as an inoculum of as few as 10 organisms can cause shigellosis. ²⁰ Individuals with shigellosis are infectious during the period of diarrhoea and should be counseled to avoid sex and oral-anal contact during this time. Counseling should also include mention that MSM living with HIV are at increased risk for Shigella infection, and that resolution of diarrhoea does not necessarily mean cessation of infectivity.^14,21,22

There have been no studies tracking HIV incidence following Shigella infection; however, there are several studies showing links between diagnosis with other STIs, especially syphilis, and subsequent HIV infection. ²³ A recent analysis from New York City found that MSM diagnosed with syphilis had a 3.6% annual incidence of HIV diagnosis, and the authors concluded that populations with STIs represent the top priority for PrEP initiation. ²³ Although less common than syphilis, diagnosis with shigellosis similarly presents a prime opportunity to begin a discussion about taking PrEP to prevent HIV. Guidelines available on-line from the Centers for Disease Control and Prevention (CDC) (http://www.cdc.gov/hiv/pdf/prepprovidersupplement2014.pdf) help to guide providers through this process. In order to determine eligibility, all patients should have a negative HIV antibody and if there is concern for the patient being in the ‘window’ period, a negative HIV viral load may also be useful to exclude acute HIV. Screening for hepatitis A, B, and C viruses are recommended and creatinine clearance should be >60 mL per minute (Cockcroft-Gault formula). The main medication used for PrEP, 300 mg tenofovir-200 mg emtricitabine (co-formulated as one pill, Truvada [Gilead Sciences]), has proven efficacious and well tolerated in preventing incident HIV infection among MSM.^24,25 Discussions about taking PrEP should include conversations about adherence, potential side-effects, and the necessary post-initiation testing including regular HIV testing every three months. Some providers may find it useful to use statistics from previous studies, which have showed that PrEP provides protection against HIV. These studies have shown a relative risk reduction of upwards of 90% in people who were taking PrEP as prescribed.^25,26 It is important to discuss with patients that PrEP will decrease, but not eliminate, the risk for HIV. As such, condom use should still be strongly encouraged.

We acknowledge that in Massachusetts, unlike several other states in the United States and other developed countries including England, we have insurance and regulatory infrastructure in place that allows for easier access of prescription PrEP to individuals at risk for HIV. We hope that the growing breadth of research supporting the efficacy of PrEP will convince national and international regulatory bodies to expedite increased access to this important medication.

Case follow-up

Two weeks following discharge the patient had an outpatient follow-up appointment and reported that his abdominal pain had improved. After counseling and discussing the benefits and risks of PrEP initiation, he expressed interest to try the medication. Upon future follow-up appointments, no side effects were reported.