Demographic, Behavioural, and Biological Factors Seen in Men Who Have Sex with Men with Salmonella spp.: A Systematic Review

Abstract

Background: The sexual transmissibility of enteric pathogens, including Salmonella spp., has been described in men who have sex with men (MSM). However, the factors seen in MSM with Salmonella spp. are poorly understood. Method: We aimed to systematically review the literature to explore any factors seen in MSM with Salmonella spp. (MSM). We searched six databases—Medline, PubMed, CINAHL, Embase, Emcare, and Global Health—in April 2024 for manuscripts which contained primary peer-reviewed data in English and the measurement of any risk factors observed in MSM with Salmonella spp. This review was registered on PROSPERO (CRD42023472864). Results: Eleven manuscripts were included in the final review and highlighted demographic (living with HIV), behavioural (oral–anal sex, receptive and penetrative anal sex, hand licking to stimulate their partner, group sex, non-condom use), and biological (co-infection with CMV, Mycobacterium avium complex, Strongyloides stercoralis, Blastocystis hominis, Klebsiella spp. Herpes simplex virus, Cytomegalovirus, Cryptosporidium, Histoplasmosis, Shigella spp.; previous infection with Treponema pallidum, Neisseria gonorhoeae, Chlamydia trachomatis and hepatitis B; and antimicrobial treatment failure) factors seen in MSM with Salmonella spp. Conclusion: Despite a limited number of manuscripts and individuals, this review highlighted some potential demographic, behavioural, and biological factors implicated in the transmission of Salmonella spp. in MSM. These data will provide insights for future guidelines, public health control strategies, and research.

1. Introduction

Salmonella spp. are Gram-negative, rod-shaped bacteria; they are highly diverse zoonotic bacteria which occur in the intestinal tracts of animals, including birds and reptiles, and there are more than 2600 serovars described [1]. There are two broad species of Salmonella: Salmonella enterica and Salmonella bongori [2]. S. bongori are generally restricted to cold-blooded animals and can rarely affect humans. S. Enterica can be divided into typhoidal salmonella (e.g. Salmonella typhi, Salmonella paratyphi) and non-typhoidal salmonella (e.g. Salmonella typhimurium) which are exclusively human pathogens and can cause severe invasive disease; thus, we will refer to these human salmonella pathogens as Salmonella spp. [2]. According to the global burden of disease study of 2017, human Salmonella affected 14.3 million people and caused 135,000 deaths annually [3]. In contrast, there are thousands of non-typhoidal salmonella subtypes affecting human and non-human hosts; these generally cause diarrhoeal illness [2]. Salmonella can persist in the natural environment, including fresh and salty water, soil, dust, and on or inside plant material [4]. Transmission of Salmonella spp. is generally due to poor sanitation regulations and limited access to clean, drinkable water [1]. In high-income settings, transmission is increasingly being driven by the commercial production of meat, eggs, and processed food, including chocolate, jalapeno peppers, and peanuts [5]. In humans, Salmonella spp. infection ranges from asymptomatic disease to severe invasive systemic disease, particularly in the extremes of age and in immunosuppressed hosts. Symptomatic salmonellosis can present with abdominal pain, diarrhoea, fever, and rash [1]. The antimicrobial resistance to first- and second-line antimicrobial regimens for Salmonella spp. is a global public health threat and includes the transmission of multi-drug and extensively drug-resistant isolates in the UK [6].

The sexual transmissibility of enteric pathogens has been described in sexual networks of men who have sex with men (MSM) since the late 1960s [7]. These include bacterial infections (Shigella spp. Campylobacter spp., diarrhoeagenic E. coli, and Salmonella spp.), hepatitis A, and parasites (Giardia duodenalis, Entamoeba histolytica, and Cryptosporidium) [8]. Sexual behaviour in MSM, particularly oro-anal sex, can risk faecal contamination and subsequent transmission of faeco-oral pathogens [9]. Selma Dritz described an outbreak of Salmonella spp. causing typhoid fever in men who have sex with men in the San Francisco area in 1977, before the discovery of HIV [10]. There have been sporadic and persistent outbreaks of other enteric bacteria in MSM, including extensively drug-resistant Shigella spp. in high-income settings [11]. Unlike Shigella spp., little is known about the transmission of Salmonella spp. in MSM [9]. Understanding the factors associated with Salmonella spp. in MSM may provide important insights for the design of future targeted interventions for Salmonella control, clinical guidelines, and research. This systematic review aimed to explore the published literature for the factors seen in MSM with Salmonella spp.

2. Materials and Methods

We followed PRISMA guidelines to perform a systematic review of the published literature in April 2024 [12]. We searched 6 bibliographical databases (PubMed, MEDLINE, EMBASE, CINAHL, EMCARE, and Global Health). We used the following search terms ((“Salmonella” OR “typhoid fever”) AND (“MSM” OR “Men who have sex with men” OR “gay” OR “homosexual” OR “bisexual”)). We only included manuscripts containing primary data exploring factors seen in MSM with Salmonella spp., written in English. For manuscripts that contained mixed populations (MSM and other non-MSM groups), or mixed pathogens, we only extracted and analysed the MSM data. There was no restriction on the year the studies were completed. Grey literature, non-peer-reviewed manuscripts, and conference abstracts were excluded.

Study Selection and Data Synthesis

We used a sequential step process to select the manuscripts in this review. In the initial step, the primary researcher (VS) reviewed the citations and abstracts and removed any duplicates. The primary author and a second researcher (NW) independently reviewed full-text manuscripts for eligibility. Any discrepancy was discussed with the research team to make a final decision. The quality and the bias risk were assessed independently by VS and NW using the Joanna Briggs Institute critical appraisal tools, and each manuscript was rated as having either a low, medium, or high risk of bias [13]. Any discrepancy was discussed with the research team to make a final decision. The final manuscript reference lists were hand-searched for any manuscripts which were not included in the initial search for eligibility review. We synthesised the narrative data into a table (

Table 1. Factors associated with Salmonella spp. in men who have sex with men.

Manuscript	Characteristics of Manuscript	Study Design	Factors Associated with Salmonella spp.
Dritz et al., 1977 [7]	Department of public health, San Francisco, California; n = 4 (2 symptomatic, 2 asymptomatic)	Case series	Antimicrobial treatment failure (Ampicillin)
Bottone EJ et al., 1984 [14]	Infectious diseases department, Mount Sinai hospital, New York, USA. Case series of 4 including n = 2 MSM with Salmonella spp.	Case series	Living with HIV, CMV, Mycobacterium avium complex (MAC)
Whimbey E et al., 1986 [15]	Infectious diseases department at Memorial Sloan Kettering cancer center, New York, USA. Thirty-three MSM living with HIV with positive blood cultures, n = 7 cases of Salmonella spp.	Cross-sectional	Living with HIV, antimicrobial treatment failure
Jarrett et al., 1986 [16]	Gastroenterology department in a London (UK) hospital, cases n = 1	Case report	Living with HIV, attending sex-on-premises venues (Turkish bath) Previous hepatitis B, Treponema pallidum, and Neisseria gonorrhoeae
Smith PD et al., 1988 [17]	Thirty-two MSM living with HIV recruited into an observational trial (National institute of health, Bethesda, USA), including n = 5 with Salmonella spp.	Cross-sectional	Living with HIV, antimicrobial treatment failure
Antony et al., 1988 [18]	One hundred people living with HIV (thirty-five MSM) attending Montefiore medical centre/North Central Bronx hospital, New York, USA. n= 4 MSM diagnosed with Salmonella spp.	Cross-sectional	Living with HIV, co-infection: Strongyloides stercoralis, Blastocystis hominis, Klebsiella spp. Herpes simplex virus, Cytomegalovirus, Mycobacterium avium complex
Crowley S et al., 1992 [19]	Sexually transmitted infection/HIV clinic, London, UK. n = 1, Salmonella typhimurium	Case report	Living with HIV, co-infection with histoplasmosis
Nelson et al., 1992 [20]	Two HIV departments in London hospitals (UK). n = 42 Salmonella spp.	Cross-sectional	Living with HIV, co-infection with CMV, Cryptosporidium, Shigella spp., antimicrobial treatment failure
Reller et al., 2003 [21]	Hospital emergency department, Ohio, USA. n = 7 (6 symptomatic, 1 asymptomatic)	Case series	Living with HIV, engaging in oral–anal, oral–genital, and receptive anal sex, licked hand to stimulate partner
Williamson DA. et al., 2019 [22]	Five hundred and nineteen asymptomatic MSM attending a Melbourne sexual health clinic, Australia. Fifty-seven (11%) tested positive for enteric pathogen and n= 2/519 Salmonella spp.	Cross-sectional	(Having any enteric pathogen.) Insertive oral–anal sex (past month), group sex (past 12 months)
Miller et al., 2024 [23]	Laboratory database, Seattle, USA, of 361 MSM with diarrhoea, 224 (62%) tested positive for an enteric pathogen, n= 2/361 MSM Salmonella spp.	Cross-sectional	(Having any enteric pathogen.) Oral sex anal sex, >1 sexual partner, non-condom use, previous T. pallidum, N. gonorrhoeae, C. trachomatis

). The review was registered on PROSPERO (CRD42023472864).

3. Results

The flowchart in Figure 1 demonstrates the screening process for the final manuscripts included in this review. Our initial search found 291 citations and 128 duplicates that were removed. There were 163 abstracts screened, of which 126 were excluded. Thirty-nine full-text manuscripts were reviewed by the two researchers, and thirty-two were excluded. Eight additional manuscripts were found from handsearching, and four of these were eligible for inclusion. Eleven manuscripts published between 1977 and 2024 were included in the final review [7,14,15,16,17,18,19,20,21,22,23]. The manuscripts consisted of two case reports, three cases series, and six cross-sectional studies from the USA (n = 7), the UK (n = 3), and Australia (n = 1), with a total of 77 MSM with Salmonella spp. Risk of bias was assessed as medium in six manuscripts and high in four manuscripts (Appendix A).

• Demographic factors

We found that living with HIV was a factor observed in MSM with Salmonella spp. in MSM [14,15,16,17,18,19,20,21] (

Table 2. Risk factors seen in MSM with Salmonella spp.

Demographic	Living with HIV
Behavioural	Sex-on-premises venues (bath houses) Oral–anal sex Anal sex Hand licking Group sex Non-condom use
Biological	Co-infection with Mycobacterium avium complex, Strongyloides stercoralis, Blastocystis hominis, Klebsiella spp. Herpes simplex virus, Cytomegalovirus, Cryptosporidium, Histoplasmosis, Shigella spp. Previous Treponema pallidum, Neisseria gonorrhoeae, Chlamydia trachomatis, and hepatitis B. Antimicrobial treatment failure

).

• Behavioural factors

Oral–anal sex, receptive and penetrative anal sex, hand licking to stimulate their partner, group sex, and non-condom use was seen in MSM with Salmonella spp. [21,22,23]. Attending sex-on-premises venues (Turkish baths) was seen in MSM with Salmonella spp. [16].

• Biological factors

Co-infection with Mycobacterium avium complex, Strongyloides stercoralis, Blastocystis hominis, Klebsiella spp. Herpes simplex virus, Cytomegalovirus, Cryptosporidium, Histoplasmosis, and Shigella spp. was seen in MSM with Salmonella spp. [14,18,19,20]. Previous infection with Treponema pallidum, Neisseria gonorrhoeae, Chlamydia trachomatis, and hepatitis B was seen in MSM with Salmonella spp. [16,23]. Antimicrobial treatment failure was observed in MSM with Salmonella spp. [7,15,17,20].

4. Discussion

This review highlighted an association between MSM living with HIV and being diagnosed with gastrointestinal Salmonella spp. In the pre-antiretroviral era of HIV, it was not uncommon to see MSM living with HIV affected by enteric infections, most commonly Shigella spp., Entamoeba histolytica, and Campylobacter spp. [8,19]. It is unclear whether the risk of Salmonella spp. in MSM living with HIV is biological, as there is little evidence to support this [16,18,20,21]. Furthermore, the mode of transmission of Salmonella spp. in individuals living with HIV is not always clear. Some MSM living with HIV or advanced HIV, who lack access to antiretrovirals or experience poor adherence to antiretroviral treatment, also experience other poor determinants of health that may impact their access to interventions for STI prevention and increased rates of STIs and Salmonella spp. transmission [16,18,20,24]. In the era of HIV pre-exposure prophylaxis, it is likely that the discrete sexual networks of MSM living with HIV and HIV-negative MSM will merge, and the effect of living with HIV be less important in the transmission of enteric pathogens [25].

This review has highlighted some specific sexual behaviours associated with Salmonella spp. in MSM [16,21,22,23]. These sexual behaviours, which increase the risk of faecal contamination during sexual activity, are associated with the transmission of other enteric infections in MSM, including Shigella spp. [9]. An interesting association was hand licking after sexually stimulating a partner, highlighting how hygiene practices, particularly after faecal contamination during sex, may impact the transmission of Salmonella spp. and other sexually transmissible enteric infections [21]. An Australian study showed that poor hygiene practice in a sex-on-premises venue in Sydney was associated with the transmission of Shigella spp. in MSM [26]. Our review describes a case of an individual living with advanced HIV who acquired Salmonella spp. following a sexual encounter in a bathhouse [16].

This review has highlighted co-infection with other pathogens, including STIs and enteric pathogens, observed in MSM with Salmonella spp. (Mycobacterium avium complex, Strongyloides stercoralis, Blastocystis hominis, Klebsiella spp. Herpes simplex virus, Cytomegalovirus, Cryptosporidium, Histoplasmosis, Shigella spp. Treponema pallidum, Neisseria gonorrhoeae, Chlamydia trachomatis, and hepatitis B).

The incidence of STIs, including antimicrobial-resistant enteric infections, has increased over the past 3 decades [11,27,28,29]. Antimicrobial-resistant Salmonella spp. leads to limited treatment options for individuals affected and the further transmission of resistant organisms [30]. Some individuals with antimicrobial-resistant Salmonella spp. may end up becoming asymptomatic carriers, therefore risking transmission of resistant Salmonella spp. to other MSM in their sexual networks [30]. This is well described in other studies of Shigella spp. in MSM in the UK and Australia, where circulating strains have become extensively antimicrobial-resistant [11,31]. This review has shown some antimicrobial treatment failure, suggesting that some Salmonella spp. isolates in MSM have antimicrobial drug resistance [7,17,20]. There have also been reports of multi-drug antimicrobial-resistant strains of Salmonella spp. identified in Pakistan [32].

Sexual behaviours, such as attending sex-on-premises venues (such as bath houses), having multiple sexual partners, and condomless sex, also have a part to play in the transmission of antimicrobial-resistant strains of enteric pathogens [9,26]. Climate change, environmental changes, the increasing use of antimicrobials, and access to antimicrobials are likely to result in the transmission of antimicrobial-resistant STIs and sexually transmissible enteric pathogens, including Salmonella spp. [33,34]. Enteric pathogens remain neglected diseases and globally affect disadvantaged people living in poverty with poor access to sanitation and healthcare [35].

The demographic, behavioural, and biological factors seen in MSM with Salmonella spp. in this review are broadly similar to what has been observed in MSM with other enteric bacteria (Shigella spp. Camplylobacter spp.) and parasites (Entamoeba histolytica, Giardia duodenalis), suggesting a similar profile of MSM or similar sexual networks [9,25,35,36]. Understanding these factors can contribute to effective surveillance and design, the development and delivery of infection control measures, and other interventions.

This review suggests that there is the potential for limited sexual transmission of Salmonella spp. in sexual networks of MSM and attempts to raise awareness of the importance of testing for Salmonella in sporadic cases or outbreaks of diarrhoeal illness in networks of MSM. Lack of appropriate testing, including antimicrobial sensitivity testing, could lead to significant uncontrolled outbreaks and morbidity. It is curious that some bacterial pathogens appear to be readily transmitted amongst sexual networks of MSM, such as Shigella spp.; however, others are rarely reported (such as Salmonella spp.), which may be a result of the inoculum dose required for transmission [30,37,38,39].

There are several limitations to this review, including significant publication bias. All of the MSM included in this review were from high-income settings. There is a lack of data on sexually transmissible enteric infections in MSM from the global south and low-/middle-income settings. It is challenging to delineate the mode of transmission of enteric pathogens where surveillance mechanisms are unable to distinguish between food-/waterborne infections and possible sexual transmissibility. There is significant reporting bias, as the data collected from the manuscripts were from MSM who presented to healthcare with symptoms, provided faecal and blood samples, and disclosed sexual behaviour. MSM with mild symptoms of Salmonella spp. may not have presented to health settings or provided a specimen of stool for analysis and therefore would not have been included in this review, and some MSM may not have participated in studies due to fear of stigma. The studies in this review did not report on the method used to detect and diagnose Salmonella spp.; we can assume that most of the older studies used traditional culture, which is limited by sensitivity. Stigma could also have affected data collected on sexual orientation and the types of sexual activities individuals engaged in. There was a broad heterogeneity of studies, including quality, sample size, and data collection in the manuscripts included (including case reports and case series, which are low in the hierarchy of evidence), making the interpretation of the findings in this review challenging. Some of the data included were for all enteric pathogens as it was not possible to extract Salmonella spp.-specific data, making the overall interpretation challenging.

5. Conclusions

Salmonella spp. and other enteric pathogens continue to be neglected diseases with a high risk of antimicrobial resistance, and they affect some of the most vulnerable people globally [1,35]. This review provides some evidence to suggest that Salmonella spp. can be sexually transmissible, albeit in small outbreaks. The magnitude of this relationship is inconclusive. Our understanding of the dynamics of the sexual transmission of Salmonella spp. remains unclear as there are some large datasets exploring the prevalence of enteric pathogens in MSM where no Salmonella spp. has been found [24,35,40]. Understanding the intersectionality of demographic, behavioural, and antimicrobial factors contributing to the transmission of Salmonella spp. and other sexually transmissible enteric pathogens in MSM can underpin the design and delivery of future public health control measures, including increasing awareness and the opportunities for research.