Whole-genome sequencing of Shigella for surveillance purposes shows (inter)national relatedness and multidrug resistance in isolates from men who have sex with men.

In the Netherlands, more than half of domestic shigellosis cases are among men who have sex with men (MSM), particularly in the Amsterdam region. However, there is limited insight into which Shigella strains circulate in the Netherlands. Our objective was to assess the added value of whole-genome sequencing (WGS)-based surveillance for Shigella. To this end, we determined the relatedness among Shigella spp. isolates from patients in the Amsterdam region, as well as in an international context, including antimicrobial resistance markers, using WGS. The following criteria were used: it should provide insight into (1) clustering of shigellosis cases and the affected population, (2) the extent of admixture of MSM-associated isolates with those from the broader population and (3) the presence of antimicrobial resistance. It should then lead to more opportunities for targeted control measures. For this study, Shigella isolates from three laboratories in the Amsterdam region obtained between February 2019 and October 2021 were subjected to Illumina WGS at the National Institute for Public Health and the Environment (RIVM). Raw data were quality-checked and assembled, the Shigella serotype was determined with ShigaTyper, and antimicrobial resistance markers were detected using ResFinder and PointFinder. For Shigella sonnei, subclades were determined using Mykrobe. Relatedness of isolates, including 21 international reference genomes, was assessed with core genome multilocus sequence typing. In total, 109 isolates were included, of which 27 were from females (25 %) and 66 were from males (61 %), with which the majority (n=48, 73 %) being from MSM. No information on sex was available for the remaining 16 cases. The WGS data for all isolates, comprising 55 S. sonnei, 52 Shigella flexneri, 1 Shigella boydii and 1 Shigella dysenteriae, met the quality criteria. In total, 14 clusters containing 51 isolates (49 %) were identified, with a median cluster size of 2.5 cases (range: 2-15). Nine out of 14 clusters were MSM-associated, and 8 clusters (57 %) were travel-related. Six of the MSM clusters were related to international reference genomes. The prevalence of antimicrobial resistance markers was higher among isolates from MSM than non-MSM patients, particularly for ciprofloxacin (89 vs 33 %) and azithromycin (58 vs 17 %). In conclusion, about half of Shigella spp. patients were part of a cluster, of which a substantial part were related to international reference genomes, particularly among MSM, and a high prevalence of antimicrobial resistance markers was found. These findings indicate widespread international circulation of Shigella spp., particularly among MSM, with multidrug resistance that hampers treatment of patients. Moreover, the results of this study led to the implementation of a national WGS-based laboratory surveillance programme for Shigella spp. that started in April 2022.

Correction to: Perceived barriers and enablers for preventing the spread of carbapenemase-producing gram-negative bacteria during patient transfers: a mixed methods study among healthcare providers.

After publication of the original article [1], we have noticed that the word 'Carbapenem-producing' should be replaced with 'Carbapenemase-producing'.

Perceived barriers and enablers for preventing the spread of carbapenem producing gram-negative bacteria during patient transfers: a mixed methods study among healthcare providers.

BACKGROUND: Antimicrobial resistance (AMR) increasingly threatens public health. Carbapenem-producing gram-negative bacteria (CPB) pose the biggest threat. The risk for CPB spread is heightened during the transfer of a CPB-positive patient between different healthcare institutions or healthcare providers. We aimed to gain insight into the frequency of CPB-positive patients in the Dutch provinces of Noord-Holland (NH) and Flevoland (FL). Secondly, we aimed to obtain a deeper understanding of the communication between healthcare providers during transfers of CPB-positive patients and explore possible communication-related risk situations for CPB spread. METHODS: This mixed-methods study consisted of a quantitative and qualitative section. For the quantitative section, 14 laboratories that provide diagnostics in NH and FL voluntarily reported carbapenem-producing Enterobacteriaceae (CPE) positive patients between February 2018 and February 2019. Additionally, two laboratories reported carbapenem-resistant Acinetobacter spp. (CRA) and carbapenem-resistant Pseudomonas aeruginosa (CRP) positive patients. For the qualitative section, healthcare providers of reported patients were interviewed about information exchange during patient transfers, precautionary measures and knowledge and beliefs concerning CPB. RESULTS: In total, 50 CPE-positive, 10 CRA-positive and 4 CRP-positive patients were reported during the inclusion period. Eighteen index-specific and 2 general interviews were conducted with 20 different care providers of 9 patients. The interviews revealed that, in most cases, information concerning the patient was transferred timely, but often a standardized method for sharing the information within and between institutions was lacking. Factors that enhanced care providers' motivation to adhere to precautionary measures were taking responsibility for the health of other patients, (pregnant) colleagues and for ones own health. Factors that reduced motivation were not acknowledging the relevance of the precautionary measures, a perceived negative impact of the measures on patients' recovery, differences in precautionary measures between healthcare settings and incomprehension for changes in precautionary measures. CONCLUSIONS: CPB-positivity occurred more frequently than expected in the Dutch provinces of NH and FL. Standardizing the transference of information concerning CPB-positive patients, implementing transmural agreements, training personnel on CPB knowledge and procedures, launching a national website on CPB and assigning one or several designated employees for CPB within healthcare institutions could improve communication between healthcare providers and thereby decrease the risk of CPB transmission.

Hepatitis A outbreak among men who have sex with men (MSM) predominantly linked with the EuroPride, the Netherlands, July 2016 to February 2017.

Between July 2016 and February 2017, 48 male cases of hepatitis A were notified in the Netherlands. Of these, 17 identified as men who have sex with men (MSM). Ten of the 13 cases for whom sequencing information was available, were infected with a strain linked with the EuroPride that took place in Amsterdam in 2016. This strain is identical to a strain that has been causing a large outbreak among MSM in Taiwan.

Evaluation of hepatitis A vaccine in post-exposure prophylaxis, The Netherlands, 2004-2012.

BACKGROUND: The secondary attack rate of hepatitis A virus (HAV) among contacts of cases is up to 50%. Historically, contacts were offered immunoglobulin (IG, a human derived blood product) as post-exposure prophylaxis (PEP). Amid safety concerns about IG, HAV vaccine is increasingly recommended instead. Public health authorities' recommendations differ, particularly for healthy contacts ≥40 years old, where vaccine efficacy data is limited. We evaluated routine use of HAV vaccine as an alternative to immunoglobulin in PEP, in those considered at low risk of severe infection in the Netherlands. METHODS: Household contacts of acute HAV cases notified in Amsterdam (2004-2012) were invited ≤14 days post-exposure, for baseline anti-HAV testing and PEP according to national guidelines: immunoglobulin if at risk of severe infection, or hepatitis A vaccine if healthy and at low risk (aged <30, or, 30-50 years and vaccinated <8 days post-exposure). Incidence of laboratory confirmed secondary infection in susceptible contacts was assessed 4-8 weeks post-exposure. In a vaccinated subgroup, relative risk (RR) of secondary infection with estimated using Poisson regression. RESULTS: Of 547 contacts identified, 191 were susceptible to HAV. Per-protocol, 167 (87%) were vaccinated (mean:6.7 days post-exposure, standard deviation(sd)=3.3) and 24 (13%) were given immunoglobulin (mean: 9.7 days post-exposure, sd=2.8). At follow-up testing, 8/112 (7%) had a laboratory confirmed infection of whom 7 were symptomatic. All secondary infections occurred in vaccinated contacts, and half were >40 years of age. In healthy contacts vaccinated per-protocol ≤8 days post-exposure, RR(ref. ≤15 years) of secondary infection in those >40 years was 12.0 (95%CI:1.3-106.7). CONCLUSIONS: Timely administration of HAV vaccine in PEP was feasible and the secondary attack rate was low in those <40 years. Internationally, upper age-limits for post-exposure vaccination vary. Pending larger studies, immunoglobulin should be considered PEP of choice in people >40 years of age and those vulnerable to severe disease.

Risk factors for secondary transmission of Shigella infection within households: implications for current prevention policy.

BACKGROUND: Internationally, guidelines to prevent secondary transmission of Shigella infection vary widely. Cases, their contacts with diarrhoea, and those in certain occupational groups are frequently excluded from work, school, or daycare. In the Netherlands, all contacts attending pre-school (age 0-3) and junior classes in primary school (age 4-5), irrespective of symptoms, are also excluded pending microbiological clearance. We identified risk factors for secondary Shigella infection (SSI) within households and evaluated infection control policy in this regard. METHODS: This retrospective cohort study of households where a laboratory confirmed Shigella case was reported in Amsterdam (2002-2009) included all households at high risk for SSI (i.e. any household member under 16 years). Cases were classified as primary, co-primary or SSIs. Using univariable and multivariable binomial regression with clustered robust standard errors to account for household clustering, we examined case and contact factors (Shigella serotype, ethnicity, age, sex, household size, symptoms) associated with SSI in contacts within households. RESULTS: SSI occurred in 25/ 337 contacts (7.4%): 20% were asymptomatic, 68% were female, and median age was 14 years (IQR: 4-38). In a multivariable model adjusted for case and household factors, only diarrhoea in contacts was associated with SSI (IRR 8.0, 95% CI:2.7-23.8). In a second model, factors predictive of SSI in contacts were the age of case (0-3 years (IRRcase≥6 years:2.5, 95% CI:1.1-5.5) and 4-5 years (IRRcase≥6 years:2.2, 95% CI:1.1-4.3)) and household size (>6 persons (IRR2-4 persons 3.4, 95% CI:1.2-9.5)). CONCLUSIONS: To identify symptomatic and asymptomatic SSI, faecal screening should be targeted at all household contacts of preschool cases (0-3 years) and cases attending junior class in primary school (4-5 years) and any household contact with diarrhoea. If screening was limited to these groups, only one asymptomatic adult carrier would have been missed, and potential exclusion of 70 asymptomatic contacts <6 years old from school or daycare, who were contacts of cases of all ages, could have been avoided.

Increased seroprevalence of IgG-class antibodies against cytomegalovirus, parvovirus B19, and varicella-zoster virus in women working in child day care.

BACKGROUND: Primary maternal infection with cytomegalovirus (CMV), parvovirus B19 (B19V), and varicella-zoster virus (VZV) may result in adverse pregnancy outcomes like congenital infection or foetal loss. Women working in child day care have an increased exposure to CMV, B19V, and VZV. By comparing the seroprevalence of IgG-class antibodies against CMV, VZV and B19V in female day care workers (DCW) with the seroprevalence in women not working in day care this study aimed to assess the association between occupation and infection. METHODS: A cross-sectional design was used. Out of a random sample of 266 day care centres, demographic data, data on work history, and blood samples were collected from 285 women from 38 centres. In addition, blood samples and basic demographics from women who participated in a cross-sectional survey of the Amsterdam population (2004) were used. All blood samples were tested for IgG-class antibodies against CMV, B19V, and VZV. RESULTS: Twenty-seven percent of the DCW were still susceptible to B19V or CMV. Working in day care was independently associated with B19V infection in all DCW (prevalence ratio [PR] 1.2; 95 % CI 1.1-1.3), and with CMV infection in DCW of European origin only (PR 1.7; 95 % CI 1.3-2.3). Almost all women born outside Europe tested seropositive for CMV (96 %). All DCW tested seropositive for VZV, compared to only 94 % of the women not working in day care. CONCLUSION: This study confirms the clear association between employment in child day care centres and infection with CMV and B19V. Intervention policies, like screening of new employees and awareness campaigns emphasizing hygienic measures among DCW, should be implemented urgently to improve the maternal health of these women and the health of their offspring.

Trends in hepatitis A, B, and shigellosis compared with gonorrhea and syphilis in men who have sex with men in Amsterdam, 1992-2006.

BACKGROUND: Since the mid-1990s, sexually transmitted infections (STIs) among men who have sex with men (MSM) have increased and appear to be related to more risky sexual behavior. We compare trends in hepatitis A, acute hepatitis B, and shigellosis with the trends of gonorrhea and infectious syphilis in Amsterdam MSM more than a period of 15 years. METHODS: We used data of all reported hepatitis A, acute hepatitis B, and shigellosis, and from all patients newly diagnosed with gonorrhea and infectious syphilis who visited the Public Health Service STI outpatient department in Amsterdam between January 1, 1992 and December 31, 2006. RESULTS: Hepatitis A incidence remained unchanged in MSM (mean 0.97 per 1000 MSM, range 0.04-2.27), who had 21% of all 1697 infections. Hepatitis B likewise remained unchanged in MSM (mean 0.47 per 1000 MSM, range 0.19-0.77), who had 41% of all 448 infections. Most shigellosis is travel-related (657/974), and 16% of the infections occurred in MSM. Its incidence dropped in general, but not in MSM. Both gonorrhea and infectious syphilis in MSM show a steep increase, mainly after 1998. DISCUSSION: Hepatitis A, B, and shigellosis do not follow the rising trends of conventional STI in MSM, which are believed to result from increased risky sexual behavior. This disparity in trends implies differences in transmission dynamics. Recent molecular epidemiologic studies suggest that clustered transmission in social MSM networks plays a major role.

Impact of a targeted hepatitis B vaccination program in Amsterdam, The Netherlands.

To evaluate hepatitis B virus (HBV) risk group vaccination in Amsterdam, which started in 1998, we examined 342 reported acute HBV-cases and sequenced 85 DNA isolates. The reported number of cases declined from 214 in 1992-1997 to 128 in 1998-2003, due to a decline in injecting drug users (IDU) and their heterosexual partners. Phylogenetic analyses showed that after 1998, the IDU cluster nearly disappeared, probably due to a decline in injecting. Acute HBV remained stable among men having sex with men; given their increased sexual risk behavior, vaccination has probably prevented an increase in their acute infections. Currently, 48-72% of the people who should be included in the program are still susceptible to HBV.

Occupational exposure to bloodborne viruses in the Amsterdam police force, 2000-2003.

OBJECTIVES: To assess and evaluate the rate and outcome of occupational exposure to hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) in the Amsterdam police force. METHODS: Retrospectively, all accidents with risk for viral transmission reported to the Municipal Health Service between January 1, 2000 and December 31, 2003 were described and analyzed in 2004. RESULTS: Over a 4-year period, 112 exposures with a viral transmission risk were reported (the estimated exposure rate was 68/10,000/year). Of these exposures, 89 (79%) sources were tested, finding 4% HBV-positive, 4% HIV-positive, and 18% HCV-positive. Immunoglobulin for HBV infection was given 44 times; HIV post-exposure prophylaxis was prescribed 16 times and 13 of 16 discontinued the course within a few days because the transmission source tested HIV-negative. No seroconversions were seen in persons exposed. CONCLUSIONS: The rate of exposure is low. The majority of the sources could be traced and tested. However, a comprehensive and effective protocol is essential in minimizing the risk of occupational HBV, HCV, and HIV infection in police officers, even if HBV vaccination is provided.

Hepatitis A virus immunity and seroconversion among contacts of acute hepatitis A patients in Amsterdam, 1996-2000: an evaluation of current prevention policy.

OBJECTIVES: We evaluated the hepatitis A virus (HAV) control policy (hygienic precautions and passive immunization with immune globulin) for "household contacts" (defined as all people who lived in the same house and who shared the same toilet with the patient, people who took care of an HAV-infected child, and sexual partners of the patient) of acute hepatitis A patients between 1996 and 2000. METHODS: We examined the characteristics and the serological outcomes of household contacts. All susceptible contacts were invited for retesting 6 weeks after they received immune globulin. RESULTS: Of 1242 contacts of 569 HAV patients, more than 50% (n = 672) were found to be HAV immune. Among the remaining contacts, 161 (28.2%) had a concurrent infection, and 86 of these individuals were symptomatic. The remaining 409 susceptible contacts received immune globulin, with 186 (45%) returning for retesting 6 weeks later (64 [34%] were infected, but only 12 had symptoms). CONCLUSIONS: Immune globulin does not protect all household contacts from HAV infection; however, it attenuates symptoms and effectively reduces further HAV transmission.