Epidemiology and antimicrobial resistance profile of Neisseria gonorrhoeae in Catalonia, Spain, 2016-2019.

Antimicrobial resistance data for Neisseria gonorrhoeae is globally sparse and resistant strains are emerging in Catalonia. We aim to describe epidemiological and antimicrobial resistance in all patients infected with N. gonorrhoeae during the period from 2016 to 2019, using available antimicrobial susceptibility data. We retrospectively analysed confirmed N. gonorrhoeae cases notified to Catalonia's microbiological reporting system. Antibiotic susceptibility testing (azithromycin, cefixime, ceftriaxone, ciprofloxacin, penicillin, spectinomycin, and tetracycline) was assessed using clinical breakpoints published by the European Committee on Antimicrobial Susceptibility Testing. Incidence rates were calculated and proportions were compared using the χ2 test or Fisher's exact test, and analysed using the Statistical Package for Social Sciences (SPSS 18.0). A total of 14,251 confirmed cases of N. gonorrhoeae were notified. Incidence increased from 30.7 cases/100,000 person-years (p < 0.001) in 2016 to 64.7 in 2019. Culture was available in 6,292 isolates (44.2%), of which 5,377 (85.5%) were resistant to at least one of the antibiotics tested. Azithromycin resistance rose from 6.1% in 2016 to 16% in 2019 (p < 0.001). Only 1.0% (45 cases) were resistant to ceftriaxone. Multidrug-resistant N. gonorrhoeae increased from 0.25% in 2016 to 0.42% in 2019 (p = 0.521). One case presented extensively drug-resistant N. gonorrhoeae. In Catalonia, 10% of the N. gonorrhoeae isolates were resistant to azithromycin in the 2016-2019 period. According to World Health Organization guidelines, resistance above 5% indicates an alert to review treatment guidelines. Antimicrobial susceptibility testing in clinical practice followed by surveillance and interventions are essential to monitor trends and prevent the spread of antimicrobial resistance.

Indirect effects of paediatric conjugate vaccines on invasive pneumococcal disease in older adults.

OBJECTIVES: The aim of this study was to assess the indirect effect of paediatric 13-valent pneumococcal conjugate vaccine (PCV13) vaccination on people ≥65 years of age with invasive pneumococcal disease (IPD) in Catalonia and to determine factors predictive of mortality. METHODS: During 2014-2016, 1285 IPD cases were reported to the Public Health Agency of Catalonia. The indirect effect of paediatric PCV13 vaccination was calculated by comparing the incidence rate (IR) in 2016 (PCV13 year) with that in 2009 (pre-PCV13). Predictors of mortality were determined using multivariate logistic regression. RESULTS: Comparing 2016 and 2009, IPD decreased by 19% (IR 40.1 and 32.5 per 100 000 person-years, respectively). PCV13 serotypes decreased by 57% (IR 23.7 and 10.1), while non-PCV13 serotypes increased by 36% (IR 16.4 and 22.4). During 2014-2016, the mortality rate was 17.5%, and mortality was associated with age ≥85 years (adjusted odds ratio (aOR) 2.91, 95% confidence interval (CI) 1.89, 4.48), meningitis (aOR 2.29, 95% CI 1.25, 4.19), non-focal bacteraemia (aOR 3.73, 95% CI 2.00, 6.94), and ≥1 high-risk condition (aOR 1.89, 95% CI 1.08, 3.32). PPV23non13 serotypes were associated with lower mortality than PCV13 serotypes (aOR 0.54, 95% CI 0.34, 0.86). CONCLUSIONS: The incidence of IPD in people ≥65 years of age decreased after the introduction of paediatric PCV13, and this was due to a reduction in PCV13 serotypes, although an increase in non-PCV13 serotypes was observed. Mortality was associated with age, meningitis, non-focal bacteraemia, ≥1 high-risk condition, and PCV13 serotypes.

The changing epidemiology of invasive pneumococcal disease after PCV13 vaccination in a country with intermediate vaccination coverage.

BACKGROUND: We studied the impact of 13-valent pneumococcal conjugate vaccine (PCV13) on the incidence of invasive pneumococcal disease (IPD) and serotype distribution in a region with intermediate levels of vaccination (around 64% in children aged <2 years). METHODS: Surveillance data on IPD cases reported by microbiologists participating in the Microbiological Reporting System of Catalonia during 2006-2014 were analysed. We compared estimated incidence rate (IR) ratios for serotypes included in PCV7, PCV10non7, PCV13non10 and non-PCV13 between the PCV7 (2006-2009) and PCV13 periods (2010-2014). IR were corrected for missing serotypes according to year and age groups: <2 years, 2-4 years, 5-64 years and ≥65 years. RESULTS: A total of 9338 IPD cases were reported. Overall IPD incidence declined by 26.2% (from 16.4 to 12.1) in the PCV13 period. The largest decrease was observed in children aged 2-4 years (44.5%, from 37.4 to 20.8). Pneumonia fell in all age groups with the largest reduction in children aged 2-4 years (49.3%) and <2 years (42%). PCV13 serotypes decreased significantly in all age groups, from 52% (31.6 to 15.1) in children aged 2-4 years to 35% (22.8 to 14.8) in adults aged ≥65 years. Non-PCV13 serotypes rose by 13% (14.8 to 16.8) in people aged ≥65 years. CONCLUSIONS: In a region with intermediate vaccination coverage, the introduction of PCV13 has reduced the overall incidence of IPD, mainly due to the decrease in PCV13 serotypes in all age groups, suggesting herd immunity. Non-PCV13 serotypes have increased in adults aged ≥65 years, suggesting serotype replacement. Higher PCV13 vaccination coverage in children will further reduce IPD incidence in all age groups.

Invasive pneumococcal disease rates linked to meteorological factors and respiratory virus circulation (Catalonia, 2006-2012).

BACKGROUND: To study the impact of meteorological data and respiratory viral infections on invasive pneumococcal disease (IPD) rates. METHODS: We analysed all notifications of IPD and respiratory viral infections to the Microbiological Reporting System of Catalonia (2006-2012). Correlations between rates of IPD and viral infections (influenza virus, respiratory syncytial virus [RSV] and adenovirus), and meteorological variables (temperature, humidity, hours of sunshine, wind speed and number of days with rainfall) were assessed using Spearman's correlation coefficient and negative binomial regression models. RESULTS: We found significant correlations between monthly rates of IPD and monthly rates of all respiratory viruses and meteorological factors. However, after multiple regression analysis, associations remained between IPD rates and influenza rates and reductions in temperature in the total population, and between IPD rates and adenovirus rates in children aged <5 years. When models were repeated for the total population using data from the preceding month, IPD rates increased when RSV was circulating and when the temperature was lower. In children aged <5 years, RSV circulation was associated with increased IPD rates. CONCLUSIONS: IPD rates were linked to increased activity of some respiratory viruses and reductions in temperature. Preventive measures, including influenza vaccination, may help reduce IPD.

Epidemiology of Acute Gastroenteritis Outbreaks Caused by Human Calicivirus (Norovirus and Sapovirus) in Catalonia: A Two Year Prospective Study, 2010-2011.

BACKGROUND: The epidemiology of cases of acute gastroenteritis (AGE) of viral etiology is a relevant public health issue. Due to underreporting, the study of outbreaks is an accepted approach to investigate their epidemiology. The objective of this study was to investigate the epidemiological characteristics of AGE outbreaks due to norovirus (NoV) and sapovirus (SV) in Catalonia. MATERIAL AND METHODS: Prospective study of AGE outbreaks of possible viral etiology notified during two years in Catalonia. NoV and SV were detected by real time reverse transcription polymerase (RT-PCR). RESULTS: A total of 101 outbreaks were registered affecting a total of 2756 persons and 12 hospitalizations (hospitalization rate: 0.8x1,000,000 persons-year); 49.5% of outbreaks were foodborne, 45.5% person to person and 5% waterborne. The distribution of outbreaks according to the setting showed a predominance of catering services (39.6%), nursing homes and long term care facilities (26.8%) and schools (11.9%). The median number of cases per outbreak was 17 (range 2-191). The total Incidence rate (IR) was 18.3 per 100,000 persons-years (95%CI: 17.6-19.0). The highest IR was in persons aged ≥65 years (43.6x100,000 (95% CI: 41.0-46.2)) (p<0.001). A total of 1065 samples were analyzed with a positivity rate of 60.8%. 98% of positive samples were NoV (GII 56.3%; GI 4.2%; GII+GI 4.2%; non- typable 33.0%). SV was identified in two person-to-person transmission outbreaks in children. CONCLUSIONS: These results confirm the relevance of viral AGE outbreaks, both foodborne and person-to-person, especially in institutionalized persons. SV should be taken into account when investigating viral AGE outbreaks.

Economic costs of outbreaks of acute viral gastroenteritis due to norovirus in Catalonia (Spain), 2010-2011.

BACKGROUND: To determine the direct and indirect costs of outbreaks of acute viral gastroenteritis (AVG) due to norovirus in closed institutions (hospitals, social health centers or nursing homes) and the community in Catalonia in 2010-11. METHODS: Information on outbreaks were gathered from the reports made by epidemiological surveillance units. Direct costs (medical visits, hospital stays, drug treatment, sample processing, transport, diagnostic tests, monitoring and control of the outbreaks investigated) and indirect costs (lost productivity due to work absenteeism, caregivers time and working hours lost due to medical visits) were calculated. RESULTS: Twenty-seven outbreaks affecting 816 people in closed institutions and 74 outbreaks affecting 1,940 people in the community were detected. The direct and indirect costs of outbreaks were € 131,997.36 (€ 4,888.79 per outbreak) in closed institutions and € 260,557.16 (€ 3,521.04 per outbreak) in community outbreaks. The cost per case was € 161.76 in outbreaks in closed institutions and € 134.31 in community outbreaks. The main costs were surveillance unit monitoring (€ 116,652.93), laboratory diagnoses (€ 119,950.95), transport of samples (€ 69,970.90), medical visits (€ 25,250.50) and hospitalization (€ 13,400.00). CONCLUSIONS: The cost of outbreaks of acute viral gastroenteritis due to norovirus obtained in this study was influenced by the number of people affected and the severity of the outbreak, which determined hospitalizations and work absenteeism. Urgent reporting of outbreaks would allow the implementation of control measures that could reduce the numbers affected and the duration of the illness and thus the costs derived from them.

Changes in the epidemiology of hepatitis A outbreaks 13 years after the introduction of a mass vaccination program.

A hepatitis A+B vaccine vaccination program of 12-year-olds was introduced in Catalonia in 1998. The aim of this study was to investigate the evolution of hepatitis A outbreaks in Catalonia and estimate the preventable fraction of cases associated with outbreaks as a measure of the impact of the vaccination program. Hepatitis A outbreaks reported to the Health Department between 1991 and 2012 were analyzed. The incidence rates of outbreaks, outbreak-associated cases and hospitalizations were calculated. The preventable fraction (PF) and 95% confidence intervals (CI) were estimated for the whole study period (pre-vaccination and post-vaccination) and the post-vaccination period.   One-hundred-eight (108) outbreaks (rate of 2.21 per 10(6) persons-year) were reported in the pre-vaccination period and 258 outbreaks (rate of 2.82 per 10(6) persons-year) in the post-vaccination period. The rate of cases associated with outbreaks was 1.52 per 10(5) persons-year in the pre-vaccination period and 1.28 per 10(5) persons-year in the post-vaccination period. Hospitalization rates were 0.08 and 0.75 per 10(6) persons-year, respectively. The number of person-to-person outbreaks whose index case was a school contact decreased in the post-vaccination period (aOR 2.72; 95%CI 1.35-5.48), but outbreaks whose index case was a man who has sex with men (MSM) or an immigrant increased. The PF of all outbreak-associated cases was 6.46% (95%CI 3.11-9.82) and the highest PF was in the 15-24 years age group (42.53%; 95%CI 29.30-55.75). In the 0-4 years age group, the PF was 18.35% (95%CI 9.59-27.11), suggesting a protective herd effect in unvaccinated subjects. Vaccination of immigrants traveling to endemic countries and MSM should be reinforced.

Characteristics of pertussis outbreaks in Catalonia, Spain, 1997 to 2010.

In Catalonia, pertussis outbreaks must be reported to the Department of Health. This study analyzed pertussis outbreaks between 1997 and 2010 in general and according to the characteristics of the index cases. The outbreak rate, hospitalization rate and incidence of associated cases and their 95%CI were calculated. Index cases were classified in two groups according to age (<15 years and ≥15 years) and the vaccine type received: whole cell vaccine (DTwP) or acellular vaccine (DTaP). During the study period, 230 outbreaks were reported. The outbreak rate was 2.43 × 10(-6) persons-year, and outbreaks ranged from 2 to 32 cases, with a median duration of 18 days. There were 771 associated cases, with an incidence rate of 0.8 × 10(-5) persons-year.   After classifying outbreaks according to the age of the index case, 126 outbreaks (1.3 × 10(-6) persons-year) had an index case aged <15 y and 87 (0.87 × 10(-6) person-year) had an index case aged ≥15 y (RR = 1.44, 95%CI 1.10-1.90; P = 0.007). Between 2003 and 2010, after the introduction of the acellular vaccine, the index case was vaccinated with DTwP vaccine in 25 outbreaks (0.43 × 10(-6) persons-year) and with DTaP vaccine in 32 outbreaks (0.55 × 10(-6) person-year) (RR = 0.78, 95%CI 0.46-1.31; P = 0.35). Of cases, 37.2% were correctly vaccinated, suggesting waning immunity of pertussis vaccine protection and endogenous circulation of pertussis. A greater number of outbreaks had an index case aged <15 y. No changes in the disease incidence, associated cases and hospitalization rate were observed after the introduction of DTaP.

Seroprevalence study of B. pertussis infection in health care workers in Catalonia, Spain.

Pertussis is a re-emerging infection in countries with high infant immunization coverage. Healthcare workers (HCW) are exposed and can transmit the infection to especially-vulnerable patients. Therefore, pertussis vaccination of HCW is recommended. Between June 2008 and December 2010, 460 HCW from hospital and primary healthcare centers were recruited to determine susceptibility to pertussis. IgG antibodies against pertussis (anti-pertussis ab) were measured, using a routine technique that detects antibodies against pertussis including pertussis toxin (PT) and filamentous hemagglutinin (FHA). Positive results were confirmed with a more-specific technique that only assesses anti-PT IgG antibodies. The median age was 42 years (range, 21-65), 77.3% were female. 172 were nurses, 133 physicians, 60 other clinical workers and 95 non-clinical workers. None had received pertussis vaccination since childhood. The overall prevalence of anti-pertussis antibodies was 51.7%, (95% CI 47.1-56.4). Anti-PT antibodies were determined in the 220 HCW with positive anti-pertussis antibodies: 4 (1.8%) were negative and 33 (15%) had a high titer (≥ 45 IU/mL). No significant differences between the prevalence of anti-pertussis antibodies or anti-TP antibodies were found according to age, type of occupation or type of center. Our study confirms the need for vaccination of HCW because at least half are susceptible to pertussis. High anti-PT titers found in 15% of seropositive HCW showed that they had had recent contact with B. pertussis.

Are healthcare workers immune to rubella?

Healthcare workers (HCW) have high exposure to infectious diseases, some of which, such as rubella, are vaccine-preventable. The aim of this study was to determine the immunity of HCW against rubella. We performed a seroprevalence study using a self-administered survey and obtained blood samples to determine rubella Immunoglobulin G (IgG) antibody levels in HCW during preventive examinations by five Primary Care Basic Prevention Units and six tertiary hospitals in Catalonia. Informed consent was obtained. IgG was determined using an antibody capture microparticle direct chemiluminometric technique. The odss ratio (OR) and 95% confidence intervals (CI) were calculated. Logistic regression was made to calculate adjusted OR. Of 642 HCW who participated (29.9% physician, 38.8% nurses, 13.3% other health workers and 18% non-health workers), 46.6% were primary care workers and 53.4% hospital workers. Of total, 97.2% had rubella antibodies. HCW aged 30-44 years had a higher prevalence of antibodies (98.4%) compared with HCW aged<30 years (adjusted OR 3.92; 95% CI 1.04-14.85). The prevalence was higher in nurses than in other HCW (adjusted OR: 5.57, 95% CI 1.21-25.59). Antibody prevalence did not differ between females and males (97.4% vs. 97.1%, P 0.89), type of center (97.7% vs. 96.8%, P 0.51) or according to history of vaccination (97.3% vs. 96.8%, P 0.82). Seroprevalence of rubella antibodies is high in HCW, but workers aged<30 years have a higher susceptibility (5.5%). Vaccination should be reinforced in HCW in this age group, due to the risk of nosocomial transmission and congenital rubella.

Prevalence of measles antibodies among health care workers in Catalonia (Spain) in the elimination era.

BACKGROUND: Interruption of measles transmission was achieved in Catalonia (Spain) in 2000. Six years later, a measles outbreak occurred between August 2006 and June 2007 with 381 cases, 11 of whom were health care workers (HCW).The objective was to estimate susceptibility to measles in HCW and related demographic and occupational characteristics. METHODS: A measles seroprevalence study was carried out in 639 HCW from six public tertiary hospitals and five primary healthcare areas. Antibodies were tested using the Vircell Measles ELISA IgG Kit. Data were analyzed according to age, sex, type of HCW, type of centre and vaccination history.The odds ratios (OR) and their 95% CI were calculated to determine the variables associated with antibody prevalence. OR were adjusted using logistic regression.Positive predictive values (PPV) and the 95% confidence intervals (CI) of having two documented doses of a measles containing vaccine (MCV) for the presence of measles antibodies and of reporting a history of measles infection were calculated. RESULTS: The prevalence of measles antibodies in HCW was 98% (95% CI 96.6-98.9), and was lower in HCW born in 1981 or later, after the introduction of systematic paediatric vaccination (94.4%; 95% CI 86.4-98.5) and higher in HCW born between 1965 and 1980 (99.0%; 95% CI 97.0-99.8). Significant differences were found for HCW born in 1965-1980 with respect to those born in 1981 and after (adjusted OR of 5.67; 95% CI: 1.24-25.91).A total of 187 HCW reported being vaccinated: the proportion of vaccinated HCW decreased with age. Of HCW who reported being vaccinated, vaccination was confirmed by the vaccination card in 49%. Vaccination with 2 doses was documented in only 50 HCW, of whom 48 had measles antibodies. 311 HCW reported a history of measles.The PPV of having received two documented doses of MCV was 96% (95% CI 86.3-99.5) and the PPV of reporting a history of measles was 98.7% (95% CI 96.7-99.6). CONCLUSIONS: Screening to detect HCW who lack presumptive evidence of immunity and vaccination with two doses of vaccine should be reinforced, especially in young workers, to minimize the risk of contracting measles and infecting the susceptible patients they care for.

Epidemiology of vaccine-preventable invasive diseases in Catalonia in the era of conjugate vaccines.

We investigated the incidence and distribution of cases of invasive pneumococcal disease (IPD), invasive meningococcal disease (IMD) and invasive Hemophilus influenzae disease (IHiD) notified by hospital laboratories to the Microbiological Reporting System of Catalonia between 2005 and 2009. Incidence rates were compared using the rate ratio (RR) and 95% CI were calculated. A value of p < 0.05 was considered statistically significant. Of the 6,661 cases, 6,012 were IPD, 436 IMD and 213 IHiD. The global annual incidence per 10 ( 5) inhabitants was 16.62 (95% CI 16.20-17.04) for IPD, 1.21 (95% CI 1.09-1.32) for IMD and 0.59 (95% CI 0.51-0.67) for IHiD. IPD increased in 2009 compared with 2005 (RR:1.55, 95%CI: 1.43-1.70) and IMD and IHiD remained stable. Pneumonia was the most-frequent clinical manifestation of IPD (75.6%) and IHiD (44.1%) and meningoencephalitis with or without sepsis for IMD (70.6%). The male:female ratio was 1.37 for IPD, 1.0 for IMD and 1.15 for IHiD. The age groups with the highest incidence were the ≤ 2 y and 2-4 y groups for IPD (66.40 and 50.66/100,000 persons-year) and IMD (14.88 and 7.26/100,000 persons-year) and the ≤ 2 y and ≥ 65 y groups for IHiD (1.88 and 1.89/100,000 persons-year). The most-frequent serotypes were serotype 1 (19.0%) in IPD and untypeable serotypes (60.8%) in IHiD. Serogroup B (78.3%) was the most frequent in IMD. S. pneumoniae is the most-frequent agent causing invasive disease in Catalonia. The main clinical manifestations were pneumonia in IPD and IHiD and meningitis in IMD. The main causative agent of meningitis was N. meningitidis in people aged < 20 y and S. pneumoniae in people aged ≥ 20 y. Vaccination with conjugate vaccines may reduce the risk of infectious disease in our setting.

Serological survey of mumps immunity among health care workers in the Catalonia region of Spain.

Susceptible health care workers are at risk of acquiring and transmitting mumps to or from patients. A survey was carried out in 639 health care workers from tertiary public hospitals and primary care centers in the Catalonia region of Spain during 2009 to determine the prevalence of immunity to mumps among this group. The prevalence of immune health care workers was 87.5% (95% confidence interval, 84.7-89.9). Vaccination with 2 doses of vaccine should be reinforced in health care workers to minimize the risk of mumps transmission in health care settings.

Prevalence of susceptibility to tetanus and diphtheria in health care workers in Catalonia.

A seroprevalence study of tetanus and diphtheria was carried out in a sample of 537 health care workers in Catalonia. The prevalence of protective antibodies against tetanus was 93.9% (95% confidence interval: 91.5-95.7). The prevalence of protective antibodies against diphtheria was 46.4% (95% confidence interval: 42.1-50.7). Tetanus protection should be improved in health care workers born before 1975. The immune status against diphtheria was poor, with less than half of people born before 1975 correctly immunized.

Factors associated to duration of hepatitis a outbreaks: implications for control.

Even though hepatitis A mass vaccination effectiveness is high, outbreaks continue to occur. The aim of this study was to investigate the association between duration and characteristics of hepatitis A outbreaks. Hepatitis A (HA) outbreaks reported between 1991 and 2007 were studied. An outbreak was defined as ≥2 epidemiologically-linked cases with ≥1 case laboratory-confirmed by detection of HA immunoglobulin M (IgM) antibodies. Relationships between explanatory variables and outbreak duration were assessed by logistic regression. During the study period, 268 outbreaks (rate 2.45 per million persons-year) and 1396 cases (rate 1.28 per 10(5) persons-year) were reported. Factors associated with shorter duration were time to intervention (OR = 0.96; 95% CI: 0.94-0.98) and school setting (OR = 0.39; 95% CI: 0.16-0.92). In person-to-person transmission outbreaks only time to intervention was associated with shorter outbreak duration (OR = 0.96; 95% CI: 0.95-0.98). The only variables associated with shorter outbreak duration were early administration of IG or vaccine and a school setting. Timely reporting HA outbreaks was associated with outbreak duration. Making confirmed HA infections statutory reportable for clinical laboratories could diminish outbreak duration.

Hepatitis A outbreaks in the vaccination era in Catalonia, Spain.

Hepatitis A outbreaks have a major impact on public health services and involve case investigation and intervention measures to susceptible contacts. At the end of 1998 a universal vaccination program with a combined hepatitis A+B vaccine was started in Catalonia (Spain) in 12-years-old preadolescents. The objective of this study was to compare the characteristics of hepatitis A outbreaks in the periods before and after the introduction of the preadolescent vaccination program and to estimate the preventable fraction of cases associated to outbreaks. The incidence rates of outbreaks, cases and hospitalization associated with each outbreak were calculated. Two periods were considered: before (1991-1998) and after (2000-2007) the introduction of mass vaccination. The preventable fraction and 95% confidence intervals (CI) of cases associated with outbreaks was calculated. The rate of associated cases with outbreaks was higher in the period before the vaccination program than in the post vaccination period (1.53 per 100,000 person-year vs 1.12 ; p< 0.001), but the rate of hospitalization was greater in the period after the introduction of vaccination program than in the period previous to vaccination (0.70 per million persons-year vs 0.08; p< 0.001). The preventable fraction of cases associated to outbreaks was 19.6%(95%CI 6.7-32.5) in the 0-4 years group and 16.7% (95% CI 6.0-27.5) in the 5-14 years group, but the highest figure (38.6%; 95%CI 21.3-55.9) was observed in the 15-24 years age group. The estimated proportion of cases associated with outbreaks that would theoretically have been prevented with the vaccination program suggests that substantial benefits have been obtained in Catalonia in people aged less than 25 years.