Background Evidence suggests that sexual transmission between men has replaced foreign travel as the predominant mode of Shigella transmission in England. However, sexuality and HIV status are not routinely recorded for laboratory-reported Shigella, and the role of HIV in the Shigella epidemic is not well understood.
Methods The Modular Open Laboratory Information System containing all Shigella cases reported to Public Health England (PHE) and the PHE HIV and AIDS Reporting System holding all adults living with diagnosed HIV in England were matched using a combination of Soundex code, date of birth and gender.
Results From 2004 to 2015, 88 664 patients were living with HIV, and 10 269 Shigella cases were reported in England; 9% (873/10 269) of Shigella cases were diagnosed with HIV, of which 93% (815/873) were in men. Shigella cases without reported travel history were more likely to be living with HIV than those who had travelled (14% (751/5427) vs 3% (134/4854); p<0.01). From 2004 to 2015, the incidence of Shigella in men with HIV rose from 47/100 000 to 226/100 000 (p<0.01) peaking in 2014 at 265/100 000, but remained low in women throughout the study period (0–24/100 000). Among Shigella cases without travel and with HIV, 91% (657/720) were men who have sex with men (MSM). HIV preceded Shigella diagnosis in 86% (610/720), and 65% (237/362) had an undetectable viral load (<50 copies/mL).
Discussion We observed a sustained increase in the national rate of shigellosis in MSM with HIV, who may experience more serious clinical disease. Sexual history, HIV status and STI risk might require sensitive investigation in men presenting with gastroenteritis.
- SEXUAL HEALTH
- EPIDEMIOLOGY (CLINICAL)
- GAY MEN
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The sexual transmission of Shigella was first described in a population with diagnosed HIV in the USA in the 1970s.1 Since that time, international case reports and epidemiological studies have provided further evidence of sexually transmitted Shigella, in particular for Shigella flexneri 3a, S. flexneri 2a and S. sonnei, and this has been predominantly reported among men who have sex with men (MSM).2–5 Sexual behaviour is therefore now considered an important risk factor for Shigella 6 and, in some instances, this is also linked to travel. For example, an outbreak of Shigella among MSM in London in 2006 coincided with a similar outbreak in Berlin, and the epidemiology suggested that both travel and sexual behaviour linked these outbreaks.7
In England, Shigella epidemiology has changed substantially over the past decade. Whereas travel-associated cases previously predominated, by 2015, more than half of cases were not travel associated. There has been a large increase in the number of cases reported in men over these years and this is thought due to sexual transmission of Shigella between men.7 ,8 Outbreak investigations and case reports have indicated that many of these men might be HIV positive.8–11
There are around 35 000 MSM living with diagnosed HIV in England. New HIV diagnoses among MSM have risen steadily over the past decade, with 3320 diagnosed in 2015.12 However, sexual identity and HIV status are not routinely recorded for laboratory-reported Shigella cases, and the extent to which patients with HIV are affected by Shigella is not well understood at a population level.
This study investigated the overlap between Shigella and HIV epidemics in England, by linking two public health surveillance data sets (the Modular Open Laboratory Information System (MOLIS) and the HIV and AIDS Reporting System (HARS)). Our aim was to understand the number of individuals diagnosed with both infections and explore their characteristics and the timing of their infections to inform public health interventions and clinical management.
Shigella reporting in England
The reporting of Shigella cases in England has been described elsewhere and is summarised below.7 Faecal specimens from cases with symptoms of gastrointestinal infection are submitted to local hospital, private and regional laboratories for culture of potential agents, including Shigella species.8 Local hospital laboratories are recommended to submit presumptive strains of S. flexneri and other Shigella species to the Public Health England (PHE) national reference laboratory in London, the Gastrointestinal Bacteria Reference Unit (GBRU), for confirmation and typing, using standard biochemistry and serological tests.8 All results reported by laboratories at PHE are recorded in MOLIS, with regular updates and duplicate records removed. This study included Shigella cases reported in England from 2004 to 2015.
HIV and AIDS reporting in England
The HARS was developed by PHE in conjunction with Department of Health and the National Reference Group for HIV, replacing the previously used Survey of Prevalent HIV Infections Diagnosed (SOPHID) surveillance system in 2014 and incorporating the HIV & AIDS New Diagnoses and Deaths (HANDD) surveillance system.13 HARS collects comprehensive information covering demographics, service provider, clinic attendance, testing history and diagnosis, treatment, clinical information and death. Information has been used to understand HIV transmission, plan services, monitor the quality of care received by patients and their clinical outcomes.13 This study included adults (aged >15 years) living with diagnosed HIV in England between 2004 and 2015.
Data set matching
A patient-level matching protocol was designed and applied to anonymously match records of individuals diagnosed with Shigella between 2004 and 2015 with records of individuals appearing in the HARS data set between 2004 and 2015 using a combination of Soundex code, date of birth and gender. Cases missing any of these variables were excluded from the study. Soundex is a coding system for names based on phonetic spelling that generates an anonymous identifier.14 The code consists of the first letter of the surname and three digits that represent the first three phonetic sounds in the name.
We estimated the proportion of patients diagnosed with Shigella in England between 2004 and 2015 who were known to be diagnosed with HIV and stratified the analysis by reported travel association, age, gender and Shigella strain/serotype. The χ2 test was used to compare differences between men and women in the proportion with diagnosed HIV.
The national cohort of people attending for HIV care was used as the denominator to estimate annual rates of shigellosis among HIV-diagnosed persons, and the clinical characteristics and timing of diagnoses were described.
The 2015 mid-year population data for England calculated by year of age by the Office of National Statistics were used to estimate age-adjusted incidence rates and age-adjusted incidence rate ratios for men and women.
All analyses were undertaken using STATA statistical software V.13.1.
From 2004 to 2015, there were 88 664 adults (aged >15 years) living with diagnosed HIV in England. From 2004 to 2015, 16 244 Shigella cases were reported in England, of which 10 269 had adequate completion of identifying variables to permit data set matching. The 5975 cases not included in the analysis were similar in their gender profile (54% (3220/5975) were men), but were more likely to have a travel history associated with their Shigella diagnosis (70% (1813/5975)).
Overall, 8% (873/10 269) of Shigella cases were identified as living with HIV, of whom 93% (715/873) were men, and 15% (815/5533) of male Shigella cases were living with HIV (table 1). Shigella cases without known travel history were more likely than those who had travelled to be diagnosed with HIV (14% (751/5527) vs 3% (134/4854); p<0.01).
We focused on non-travel-associated Shigella cases and found that among Shigella cases not associated with travel in men, the proportion living with diagnosed HIV varied by Shigella species and phage type, from 16% (242/1488) for S. sonnei to 31% (190/616) for S. flexneri 3a. Overall, among non-travel-associated cases of Shigella in men, the proportion with diagnosed HIV was 21% (720/3481), while in women, this proportion was low (2% (31/1946); p<0.01).
Most Shigella cases in individuals living with diagnosed HIV were reported to be MSM in the HARS data set (91% (657/720)). The Shigella diagnosis was found to precede HIV diagnosis in 14% (100/720), and 65% (237/362) had an undetectable viral load (where available within 3 months of shigellosis).
We observed year-on-year increases in Shigella incidence in men living with diagnosed HIV, with the rate rising nearly sevenfold from 47 per 100 000 HIV-diagnosed population in 2004 to 226 per 100 000 in 2015 (p<0.01) peaking in 2014 at 265/100 000 (table 2), and a similar but more pronounced trend among MSM with HIV. Shigella incidence in HIV-positive women remained low throughout the study period and was 6.8/100 000 in 2005 and 19.5/100 000 in 2015. Overall, age-adjusted incidence rates in individuals diagnosed with HIV were estimated to be 4.9 (95% CI 4.5 to 5.2) per 100 000 in men and 0.3 (95% CI 0.3 to 0.4) per 100 000 in women throughout the study period, with an age-adjusted incidence rate ratio between men and women of 14.4 (11.1 to 19.3).
This study provides a unique insight at a national level into the overlap between Shigella and HIV epidemics. Over one-fifth of men diagnosed with Shigella without reported travel were living with diagnosed HIV, and most were MSM. We observed a sharp year-on-year increase in Shigella incidence in men and MSM living with HIV. Around 14% of co-diagnosed men were diagnosed with HIV after Shigella, a finding that supports the 2008 UK national guidelines for HIV testing which cite Shigella diagnosis as an indicator for HIV testing.15
Until now, the role of sexual transmission between men in the Shigella epidemic has been largely inferred from gender ratio studies, case series and small epidemiological studies.8 ,9 ,11 ,16 Our study adds to this evidence base and suggests that the national increase in Shigella incidence in England might be due, at least in part, to Shigella infections in MSM with HIV. The observed increase in Shigella incidence in men living with diagnosed HIV is consistent with previously noted increases in high-risk sexual behaviours leading to faecal–oral transmission among networks of HIV-positive MSM.17 During the period under observation, there were simultaneous large increases in diagnoses of gonorrhoea, lymphogranuloma venereum and other STIs within the MSM population, particularly those living with diagnosed HIV.18 Similarities in the characteristics of men affected may indicate sexual networking among HIV-diagnosed MSM engaging in HIV seroadaptive behaviours, possibly facilitated by geospatial apps.8 Three social phenomema, highlighted in the literature, might be important in driving Shigella transmission and deserve further research. These are: (1) sex parties and the use of chemsex, which might influence decision making about risky sexual behaviour,19 ,20 ,21 (2) the use of social media apps to meet previously unknown partners, which might facilitate serosorting practices9 and (3) acceptability of sexual practices leading to faecal–oral contact.7 ,9
There are also plausible biological explanations for the overlap between Shigella and HIV epidemics, including increased shedding of Shigella species, a prolonged infectious period and increased susceptibility to Shigella in people living with HIV.16 While our data suggest that most MSM with HIV and Shigella were not clinically immunosuppressed, HIV might still affect immunological responses to Shigella, increasing the severity of clinical disease and duration of infectiousness.22
We observed a small number of Shigella diagnoses in women living with diagnosed HIV. However, the extent to which heterosexual sex, including heterosexual sex between MSM and women, has a role in Shigella transmission remains an area for further research.
The key strength of this study is the linking of two national data sets to estimate the proportion of individuals diagnosed with Shigella and living with HIV, allowing year-on-year comparisons to be made. However, patients with mild gastrointestinal symptoms might not seek attention from health services, leading to incomplete Shigella case ascertainment and underestimation of Shigella incidence. There might also be bias introduced by under-reporting of same sex behaviour in HIV databases, such that Shigella incidence in MSM may be underestimated. The matching protocol used key variables to enable individual-level matching, which might generate false-positive and false-negative matches, and our study might underestimate the true number of Shigella diagnoses in people living with HIV due to cases excluded from the study with incomplete identifying variables, and because an estimated 17% of people living with HIV are unaware of their infection.23 We also recognise that neither the health consequences of Shigella infection nor the antimicrobial susceptibility of Shigella isolates is reported here, which might assist in understanding the impact on health services and the implications for people living with HIV. Nevertheless, overall, our study is likely to have underestimated rather than overestimated the extent to which HIV and Shigella epidemics have overlapped.
This study has important and immediate clinical and public health implications, highlighting the need for clinicians to consider and test for enteric pathogens such as Shigella in men presenting with gastrointestinal symptoms, who might not disclose male partners, and for increased awareness about Shigella among MSM, particularly those living with HIV infection. Sexual history, HIV status and STI risk might require sensitive investigation in men presenting with gastrointestinal symptoms and/or Shigella.
We used national surveillance data sets for HIV and Shigella to investigate the role of HIV in the recent Shigella epidemic in England.
Shigella cases without reported travel history were most likely to be living with HIV (14%).
Among cases of Shigella without travel history and diagnosed with HIV, 91% were reported to be men who have sex with men.
In most cases, HIV preceded the Shigella diagnosis and for most patients with HIV, the most recent viral load was undetectable.
These data emphasise the importance of sensitively asking about sexual history, HIV status and STIs in men presenting with gastrointestinal symptoms and/or Shigella.
Handling editor Jackie A Cassell
Contributors KM, VD, ZY, GH and NF conceived this article. KM wrote the first draft with further contributions from MH, VD, GH, IS, CJ, PK and NF. KM did the literature review. MH, TC, PK and ZY managed data and undertook data cleaning and linkage. KM undertook the statistical analysis with support from MH, GR, MC, TC, PK and NF. All authors interpreted data, reviewed successive drafts and approved the final version of the article.
Funding Undertaken as part of PHE-funded public health surveillance.
Competing interests None declared.
Ethics approval No individual patient consent was required or sought as PHE has authority to handle patient for public health monitoring and infection control under section 251 of the UK National Health Service Act of 2006 (previously section 60 of the Health and Social Care Act of 2001).
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The study used national surveillance data sets held by PHE.