Impact of COVID-19 Pandemic in Antibiotic Consumption in Navarre (Spain): An Interrupted Time Series Analysis.

On 11 March 2020, the World Health Organization declared coronavirus disease 19 (COVID-19) a global pandemic. This exceptional situation changed the world not only in terms of mortality and morbidity, but also in terms of epidemiology and health system resources consumption. The objective of this work was to analyze the consumption of antibiotics during the period around the pandemic in our region. A drug utilization study was performed comparing the antibiotic consumption in the community during the years 2018, 2019, 2020, and 2021. Quarterly antibiotic use (defined daily doses (DDD) per 1000 inhabitants per day (DID)) and number of patients treated were the outcomes. Interrupted time series regression analysis was performed to estimate the statistical significance of the change in level of consumption before and after the COVID-19 pandemic. The drop of global antibiotic consumption was statistically significant, both in number of patients and in DID when analyzing pre-pandemic period versus pandemic period. The use of strategic antibiotics for respiratory infections such as amoxicillin, amoxicillin-clavulanic acid, and levofloxacin also decreased significantly. Seasonal pattern of use of antibiotics disappeared due to the global measures imposed over the world to work against COVID-19.

Pneumococcal Vaccination and Pneumonia Associated With Pleural Effusion in a Pediatric Population.

OBJECTIVE: The aim was to assess the effect of the nonsystematic pneumococcal conjugate vaccine (PCV) on incidence of pneumonia associated with parapneumonic pleural effusion (PPE) in vaccinated and unvaccinated children. METHODS: Cases were patients <15 years of age who had been diagnosed with pneumonia associated with PPE in a tertiary hospital in Navarra (Spain) between 1995 and 2014. The population <15 years of age and covered by the public health service was used as reference. The vaccination status of the cases and population was obtained from computerized medical records. Logistic regression analyses included vaccination status, age group and time periods: prevaccine (1995-2001) and vaccination with PCV7 (2002-2010) and PCV13 (2011-2014). RESULTS: A total of 321 cases of PPE were included. The risk of PPE increased between the prevaccine and PCV7 period (adjusted odds ratio [OR], 3.34; 95% confidence interval [CI]: 2.37-4.71), while vaccination with PCV7 was found to be an independent risk factor (OR, 1.44; 95% CI: 1.09-1.89) in the same analysis. In the PCV13 period, the risk of PPE returned to the prevaccination incidence level among children vaccinated with PCV13 (OR, 1.07; 95% CI: 0.56-2.04), while unvaccinated children (OR, 1.69; 95% CI: 0.96-2.98) and overall those vaccinated with PCV7 (OR, 3.64; 95% CI: 2.15-6.17) maintained an increased risk of PPE. CONCLUSION: The nonsystematic introduction of PCV7 was followed by an increased incidence of PPE. The subsequent introduction of PCV13 was associated with a return to the incidence level in the prevaccine period, mainly in children vaccinated with PCV13.

Direct, indirect and total effects of 13-valent pneumococcal conjugate vaccination on invasive pneumococcal disease in children in Navarra, Spain, 2001 to 2014: cohort and case-control study.

We estimated the direct, indirect and total effects of the 13-valent pneumococcal conjugate vaccine (PCV13) on invasive pneumococcal disease (IPD) in children. A population-based cohort study followed children aged between 2.5 and 59 months between 2001 and 2014 in Navarra, Spain. IPD incidence was compared by PCV status and period. All cases diagnosed from July 2010 to December 2014 and eight matched controls per case were analysed to estimate the adjusted direct effect of PCV13. A total of 120,980 children were followed and 206 IPD cases were detected. Compared with unvaccinated children in the baseline period (2001-2004), overall IPD incidence in 2011-2014 (76% average PCV coverage) declined equally in vaccinated (total effect: 76%; hazard ratio (HR): 0.24; 95% confidence interval (CI): 0.14-0.40) and unvaccinated children (indirect effect: 78%; HR: 0.22; 95% CI: 0.09-0.55). IPD incidence from non-PCV13 serotypes increased among vaccinated children (HR: 2.84; 95% CI: 1.02-7.88). The direct effect of one or more doses of PCV13 against vaccine serotypes was 95% (odds ratio: 0.05; 95% CI: 0.01-0.55). PCV13 was highly effective in preventing vaccine-serotype IPD. The results suggest substantial and similar population-level vaccine benefits in vaccinated and unvaccinated children through strong total and indirect effects.

Reduced incidence of invasive pneumococcal disease after introduction of the 13-valent conjugate vaccine in Navarre, Spain, 2001-2013.

Pneumococcal conjugate vaccines (PCVs) were licensed for use in children and became available for private purchase in Spain in 2001 (PCV7), 2009 (PCV10) and 2010 (PCV13). This study evaluates changes in the incidence of invasive pneumococcal disease (IPD) and the pattern of serotypes isolated in Navarre, Spain, between the period of use of PCV7 (2004-2009) and that of PCV13 (2010-2013). The percentage of children <2 years who received at least one dose of PCV in these periods ranged from 25 to 61% and 61 to 78%, respectively. Between the periods 2004-2009 and 2010-2013 IPD incidence declined by 37%, from 14.9 to 9.4 cases/100,000 inhabitants (p<0.001). In children <5 years it fell by 69% (p<0.001), in persons aged 5-64 years, by 34% (p<0.001), and in those ≥ 65, by 23% (p=0.024). The incidence of cases due to PCV13 serotypes declined by 81% (p<0.001) in children <5 years and by 52% (p<0.001) in the whole population. No significant changes were seen in the distribution of clinical presentations or in disease severity. The incidence of IPD has declined and the pattern of serotypes causing IPD has changed notably in children and moderately in adults following the replacement of PCV7 by PCV13.

Effectiveness of rotavirus vaccines in preventing cases and hospitalizations due to rotavirus gastroenteritis in Navarre, Spain.

Two rotavirus vaccines have been available since 2006. This study evaluates the effectiveness of these vaccines using a test-negative case-control design in Navarre, Spain. We included children 3-59 months of age who sought medical care for gastroenteritis and for whom stool samples were taken between January 2008 and June 2011. About 9% had received the pentavalent vaccine (RotaTeq) and another 8% received the monovalent vaccine (Rotarix). Cases were the 756 children with confirmed rotavirus and controls were the 6036 children who tested negative for rotavirus. Thirty-five percent of cases and 9% of controls had required hospitalization (p<0.0001). The adjusted effectiveness of complete vaccination was 78% (95% CI: 68-85%) in preventing rotavirus gastroenteritis and 83% (95% CI: 65-93%) in preventing hospitalization for rotavirus gastroenteritis. No differences between the two vaccines were detected (p=0.4523). Both vaccines were highly effective in preventing cases and hospital admissions in children due to rotavirus gastroenteritis.

[Imported histoplasmosis in Navarra: presentation of four cases]. / Descripción de cuatro casos de histoplasmosis importada en Navarra.

OBJECTIVE: Histoplasmosis is a fungal infection caused by the dimorphic fungi Histoplasma capsulatum. Its incidence in Spain has increased in recent years, mainly due to the increased presence of immigrants from Latin America and increased travel to the continent for tourism and cooperation. Our aim was to review the clinical characteristics of cases of histoplasmosis diagnosed in our hospital during the last six years. CASE REPORTS: We diagnosed 4 cases from 4 patients from South America, 3 of whom were HIV positive and 1 diagnosed with dermatomyositis was treated with immunosuppressive drugs. The laboratory diagnosis was carried out by histological and microbiological study, by culture and specific PCR directly on the sample. DISCUSSION: As it is an imported infection there needs to be a high level of suspicion and a detailed history taken to get a diagnosis. This infection requires a differential diagnosis between febrile syndrome in immunosuppressed patients, both HIV positive and immunosuppressive therapy, which originate from endemic areas, or who have a history of staying in them.

[Loa Loa and Mansonella perstans coinfection in a patient from Guinea]. / Coinfección por dos filarias (Loa loa y Mansonella perstans) en una paciente proveniente de Guinea.

We present a case of mixed infection by two filariae (Loa loa and Mansonella perstans). It seems that the infection was suspected due to a pronounced eosinophilia in a routine analysis. Sheathed and unsheathed microfilariae were observed in the spread of peripheral blood, which enabled a diagnosis to be established of mixed infection by filariae. The definitive diagnosis of the species was carried out at the National Centre of Microbiolgy of Majadahonda. A treatment was initiated with dietilcarbamazina and mebendazole which resulted in the patient's being cured and in the elimination of the microfilariae in the patient's blood. Filariasis is still endemic in many countries. Due to the increase of travellers to such zones and the migratory movements from such areas it is not unusual for us to come across such a diagnosis. The implantation of massive treatments against filariae in endemic zones by the World Health Organisation is reducing their transmission and is managing to eliminate the disease in some areas.

[Genotyping of Chlamydia trachomatis in an area of northern Spain]. / Genotipado de Chlamydia trachomatis en un área del norte de España.

INTRODUCTION: Circulating Chlamydia trachomatis genotypes that cause infection in our geographic area were studied with the aim of detecting possible epidemiological peculiarities. METHODS: A total of 177 strains obtained between 2006 and 2008 were genotyped using a PCR with primers targeting the ompA gene, and later sequenced. RESULTS: The most frequent genotypes were: E (45.3%), D (15.3%), G (10.2%) and F (9.6%). Other genotypes found were: B, H, I, J, K and LGV II. CONCLUSION: The molecular assay used had a high yield (89%).

[Invasive pneumococcal disease in children younger than 5 years in Navarra, Spain (2000-2005). Impact of the conjugate vaccine]. / Enfermedad neumocócica invasiva en la población menor de 5 años de edad de Navarra (2000-2005): impacto de la vacuna conjugada.

BACKGROUND AND OBJECTIVE: The 7-valent pneumococcal conjugate vaccine (PCV7) has been commercialized in Spain since June 2001. We aim to evaluate the impact of this vaccine in the incidence of invasive pneumococcal disease (IPD) in Navarre. POPULATION AND METHOD: The laboratories of microbiology of Navarre declare all the isolations of Streptococcus pneumoniae in samples of normally sterile corporal fluids. We analyzed the incidence of IPD in children younger than 5 years between weeks 41 of 2000 and 40 of 2005. RESULTS: The doses of PCV7 sold up to 2005 would provide a cover of 27% in children younger than 5 years, having assumed 4 dose schedules. In the 5 seasons, 103 cases of IPD were diagnosed. From the 2 first seasons (2000-2002) to the last one (2004-2005) a reduction of 69% in the incidence rate of IPD caused by vaccine serotypes was observed (from 33 to 10 cases by 100,000 children under 5 years; p = 0.003). Between those same periods the incidence of IPD caused by non-vaccine serotypes increased a 36% (from 42 to 57 by 100,000; p = 0.405). The global incidence of IPD diminished a 12% (from 77 to 67 by 100,000; p = 0.689). The percentage of cases that had received PCV7 increased until 45% in season 2004-2005 (p < 0.001). The meningitis and bacteraemic pneumonias supposed 42% of the IPD, without significant changes during the period (p = 0.442). CONCLUSIONS: Since the PCV7 was marketed the pattern of serotypes has changed, but the expected reduction in the total IPD incidence has not been achieved.

Effectiveness of the 7-valent pneumococcal conjugate vaccine: a population-based case-control study.

BACKGROUND: The 7-valent pneumococcal conjugate vaccine (PCV7) has shown high efficacy in preventing invasive pneumococcal disease (IPD) caused by vaccine serotypes. We aimed to assess the overall effectiveness of PCV7 against IPD in Navarra, Spain. METHODS: All children aged <5 years who were diagnosed with IPD during the period 2001-2005 (n=85) and 5 control subjects per case patient (n=425), individually matched by birth date and birth hospital, were analyzed. Vaccination records were obtained from the regional immunization registry. Conditional logistic regression was used to estimate odds ratios. RESULTS: Eighteen case patients (21%) and 114 control subjects (27%) had received >or=1 dose of PCV7. PCV7 serotypes were responsible for 34 (51%) of the cases in unvaccinated children. The overall effectiveness for case prevention was 31% (odds ratio, 0.69; 95% confidence interval, 0.37-1.27). In a separate analysis, vaccination with PCV7 was 88% effective in preventing IPD due to vaccine serotypes (odds ratio, 0.12; 95% confidence interval, 0.02-0.91) and was associated with a higher risk of IPD due to nonvaccine serogroups (odds ratio, 6.16; 95% confidence interval, 1.63-23.3). CONCLUSIONS: These data reveal a higher risk of IPD caused by non-PCV7 serogroups among vaccinated children. Consequently, the overall effectiveness of PCV7 for IPD prevention may be greatly reduced.

The aetiology of paediatric inflammatory vulvovaginitis.

UNLABELLED: Vulvovaginitis is the most common gynaecological problem in prepubertal girls and clear-cut data on the microbial aetiology of moderate to severe infections are lacking. Many microorganisms have been reported in several studies, but frequently the paediatrician does not know the pathogenic significance of an isolate reported in vaginal specimens of girls with vulvovaginitis. A multicentre study was performed, selecting 74 girls aged 2 to 12 years old with a clinical picture of vulvovaginitis and inflammatory cells on Gram stain. All the specimens were cultured following standard microbiological techniques and the paediatricians completed a questionnaire to highlight risk factors after interviewing the parents or tutors. The data were compared with those obtained in a control group of 11 girls without vulvovaginitis attending a clinic. Streptococcus pyogenesand Haemophilus spp.were isolated in 47 and 12 cases, respectively. Upper respiratory infection in the previous month ( P<0.001) and vulvovaginitis in the previous year ( P<0.05) were identified as significant risk factors. Foreign bodies, sexual abuse, poor hygiene and bad socioeconomic situation were not identified as risk factors for the infection. CONCLUSION: Paediatric inflammatory vulvovaginitis is mainly caused by pathogens of the upper respiratory tract and the most common risk factor for this infection is to have suffered an upper respiratory tract infection in the previous month.

[Primary trimethylaminuria or fish odor syndrome. A novel mutation in the first documented case in Spain]. / Trimetilaminuria o síndrome del olor a pescado. Nueva mutación génica y primer caso documentado en España.

BACKGROUND AND OBJECTIVE: Trimethylaminuria or fish odor syndrome is a metabolic disorder characterized by a failure in the oxidation route from trimethylamine (TMA) to trimethylamineN-oxide (TMA-O). Primary trimethylaminuria is an inherited autosomic recessive disease due to mutations in the human FMO3 gene. High levels of free TMA in urine and other body fluids confer an unpleasant body odor resembling that of fish. Here we report a case of primary trimethylaminuria in a 4-year-old girl. PATIENT AND METHOD: A 4-year-old girl who presented with a strong corporal scent resembling that of fish from the age of 9 months agreeing with the introduction of fish in the diet. The patient did not have other relevant personal history and had a correct psychomotor and growing development. Liver function, urea and creatinine levels were normal. The biochemical diagnosis was done by spectrometry, measuring the amount of TMA and TMA-O prior to and after fish intake. RESULTS: Genetic analysis evinced that the patient was homozygous for a novel mutation in exon 3, R51G (c. 151A > G). Both parents were heterozygous. CONCLUSIONS: R51G (c. 151 A > G) mutation had not been found in other patients with trimethylaminuria.

[Non-typhoid salmonellosis in in a basic health area of Navarra, Spain]. / Salmonelosis no tifoidea en un Area de Salud de Navarra, España.

BACKGROUND: Salmonella gastro-enteritis is a Zoonoses transmitted by the ingestion of food products and water or fomites contaminated by the faeces of infected people or animals. At present, constitutes a world-wide pandemic. The aim of the present study has been to in progress examine cases of non-typhoidal salmonellosis in the Health Area I of Navarra (376,079 inhabitants). METHODS: 39,697 outpatient specimens submitted for culture during 1993-2000 were analysed retrospectively. Standard procedures to isolate enteropathogens were employed. The Salmonella strains were serotyped. Data was collected on age, sex, specimen date and result of culture and antimicrobial susceptibility testing for all isolates. RESULTS: 2,924 salmonellae were isolated (7.4%) with the most frequent serotype being Salmonella Enteritidis (62%). The highest isolation rate was associated with children, particularly infants (1,117.3 per 100,000 inhabitants). Salmonella Typhimurium was typically more resistant than Salmonella Enteritidis, although resistance rates in both have increased in recent time. CONCLUSIONS: In spite of the socio-economic improvements, the incidence of gastro-enteritis associated with Salmonella spp. has continued to increase in recent years, mainly affecting infants, and constitutes an important public health problem.