Epidemiological and molecular characterization of Streptococcus pneumoniae carriage strains in pre-school children in Arkhangelsk, northern European Russia, prior to the introduction of conjugate pneumococcal vaccines.

BACKGROUND: The 13-valent Pneumococcal Conjugate Vaccine (PCV-13) was introduced in the National Immunization Programme (NIP) schedule in Russia in March 2014. Previously, the 7-valent Pneumococcal Conjugate Vaccine (PCV-7) was marketed in Russia in 2009 but has never been offered for mass vaccination. A carriage study was performed among children in Arkhangelsk in 2006. The objective was to determine the prevalence of carriage, serotype distribution, antimicrobial susceptibility and the molecular structure of Streptococcus pneumoniae strains before marketing and introduction of PCV-13. METHODS: A cross-sectional study was conducted on a cluster-randomized sample of children and a self-administrated questionnaire for parents/guardians.  Nasopharyngeal samples were collected from 438 children younger than 7 years attending nurseries and kindergartens in the Arkhangelsk region, Russia. Detailed demographic data, as well as information about the child's health, traveling, exposure to antimicrobials within the last 3 months and anthropometric measurements were collected for all study subjects. Variables extracted from the questionnaire were analysed using statistic regression models to estimate the risk of carriage. All pneumococcal  isolates were examined with susceptibility testing, serotyping and multilocus sequence typing. RESULTS: The overall prevalence of asymptomatic carriage was high and peaking at 36 months with a rate of 57%. PCV-13 covered 67.3% of the detected strains. High rates of non-susceptibility to penicillin, macrolides and multidrug resistance were associated with specific vaccine serotypes, pandemic clones, and local sequence types. Nine percent of isolates represented three globally disseminated disease-associated pandemic clones; penicillin- and macrolide-resistant clones NorwayNT-42 and Poland6B-20, as well as penicillin- and macrolide-susceptible clone Netherlands3-31. A high level of antimicrobial consumption was noted by the study. According to the parent's reports, 89.5% of the children used at least one antimicrobial regime since birth. None of the hypothesised predictors of S. pneumoniae carriage were statistically significant in univariable and multivariable logistic models. CONCLUSIONS: The study identified a high coverage of the PCV-13-vaccine, but serotype replacement and expansion of globally disseminated disease-associated clones with non-vaccine serotypes may be expected. Further surveillance of antimicrobial resistance and serotype distribution is therefore required.

Characteristics and practices of National Immunisation Technical Advisory Groups in Europe and potential for collaboration, April 2014.

In many countries, national vaccination recommendations are developed by independent expert committees, so-called national immunisation technical advisory groups (NITAG). Since the evaluation of vaccines is complex and resource-demanding, collaboration between NITAGs that evaluate the same vaccines could be beneficial. We conducted a cross-sectional survey among 30 European countries in February 2014, to explore basic characteristics and current practices of European NITAGs and identify potential modes and barriers for collaboration. Of 28 responding countries, 26 reported to have a NITAG or an equivalent expert group. Of these, 20 apply a systematic approach in the vaccine decision-making process, e.g. by considering criteria such as country-specific disease epidemiology, vaccine efficacy/effectiveness/safety, health economics, programme implementation/logistics or country-specific values/preferences. However, applied frameworks and extent of evidence review differ widely. The use of systematic reviews is required for 15 of 26 NITAGs, while results from transmission modelling and health economic evaluations are routinely considered by 18 and 20 of 26 NITAGs, respectively. Twenty-five countries saw potential for NITAG-collaboration, but most often named structural concerns, e.g. different NITAG structures or countries' healthcare systems. Our survey gathered information that can serve as an inventory on European NITAGs, allowing further exploration of options and structures for NITAG collaboration.

Seasonal influenza immunisation in Europe. Overview of recommendations and vaccination coverage for three seasons: pre-pandemic (2008/09), pandemic (2009/10) and post-pandemic (2010/11).

Since 2008, annual surveys of influenza vaccination policies, practices and coverage have been undertaken in 29 European Union (EU)/ European Economic Area (EEA) countries. After 2009, this monitored the impact of European Council recommendation to increase vaccination coverage to 75% among risk groups. This paper summarises the results of three seasonal influenza seasons: 2008/09, 2009/10 and 2010/11. In 2008/09, 27/29 countries completed the survey; in 2009/10 and 2010/11, 28/29 completed it. All or almost all countries recommended vaccination of older people (defined as those aged ≥50, ≥55, ≥59, ≥60 or ≥65 years), and people aged ≥6 months with clinical risk and healthcare workers. A total of 23 countries provided vaccination coverage data for older people, but only 7 and 10 had data for the clinical risk groups and healthcare workers, respectively. The number of countries recommending vaccination for some or all pregnant women increased from 10 in 2008/09 to 22 in 2010/11. Only three countries could report coverage among pregnant women. Seasonal influenza vaccination coverage during and after the pandemic season in older people and clinical groups remained unchanged in countries with higher coverage. However, small decreases were seen in most countries during this period. The results of the surveys indicate that most EU/EEA countries recommend influenza vaccination for the main target groups; however, only a few countries have achieved the target of 75% coverage among risk groups. Coverage among healthcare workers remained low.

Epidemiology and clinical features of human infection with Coxiella burnetii in Denmark during 2006-07.

Query (Q) fever was virtually unknown in Denmark in 2005, when, after the introduction of new sensitive diagnostic methods for Coxiella burnetii, an increasing number of positive cattle created concern among people with frequent exposure. This led to a dramatic rise in examinations for Q fever among humans in the following 2 years. The aim of our study was to assess indication for testing and symptoms in individuals with serological signs of infection with C. burnetii. We performed a case-review study of seropositives among all humans tested for Q fever in 2006-07 in Denmark. Seropositive cases were categorized with acute infection: 4-fold increase in immunoglobulin G (IgG) phase II or concomitant IgM phase II ≥ 1 : 256 and IgG phase II ≥ 1 : 1024; and previous infection: IgG phase II ≥ 1 : 1024. A borderline result was defined as: IgG phase II = 1 : 512. Physicians completed a questionnaire retrospectively. Of the 1613 people tested, 177 (11%) were seropositive [37 (2%) acute infection, 140 (9%) previous infection], 180 had a borderline result. Among 127 seropositives responders, 31% were tested due to symptoms compatible with Q fever after a possible exposure to C. burnetii, 64% were asymptomatic and were tested following relevant exposure only; 64% were males, 43% farmers, 39% veterinarians, 84% had been exposed to cattle. The most frequently reported symptoms were asthenia (25%), myalgia (21%), fever (17%) and headache (13%). About two-thirds of seropositives reported asymptomatic infections, and were tested for Q fever because of concern for occupational exposure to cattle. One-third of the seropositives reported symptoms consistent with Q fever, the majority being mild. Our study provided important evidence that increased requests for Q fever testing in 2006-07 arose from heightened public awareness of the disease, and not from an outbreak of clinical disease. Nonetheless, Q fever should be considered endemic in Denmark.

National surveillance of pandemic influenza A(H1N1) infection-related admissions to intensive care units during the 2009-10 winter peak in Denmark: two complementary approaches.

Surveillance of 2009 pandemic influenza A(H1N1) in Denmark was enhanced during the 2009­10 winter season with a system monitoring the burden of the pandemic on intensive care units (ICUs), in order to inform policymakers and detect shortages in ICUs in a timely manner. Between week 46 of 2009 and week 11 of 2010, all 36 relevant Danish ICUs reported in two ways: aggregate data were reported online and case-based data on paper. Cases to be reported were defined as patients admitted to an ICU with laboratory-confirmed 2009 pandemic influenza A(H1N1) infection or clinically suspected illness after close contact with a laboratory-confirmed case. Aggregate numbers of cases were reported weekly: during weeks 48-51 (the peak), reporting was daily. The case-based reports contained demographic and clinical information. The aggregate surveillance registered 93 new cases, the case-based surveillance 61, of whom 53 were laboratory confirmed. The proportion of beds used for influenza patients did not exceed 4.5% of the national capacity. Hospitals with cases used a median of 11% of bed capacity (range: 3­40%). Of the patients for whom information was available, 15 of 48 patients developed renal insufficiency, 19 of 50 developed septic shock and 17 of 53 died. The number of patients with pandemic influenza could be managed within the national bed capacity, although the impact on some ICUs was substantial. The combination of both reporting methods (collecting aggregate and case-based data) proved to be useful for monitoring the burden of the pandemic on ICUs.

Characterization of incompletely typed rotavirus strains from Guinea-Bissau: identification of G8 and G9 types and a high frequency of mixed infections.

Among 167 rotavirus specimens collected from young children in a suburban area of Bissau, Guinea-Bissau, from 1996 to 1998, most identifiable strains belonged to the uncommon P[6], G2 type and approximately 50% remained incompletely typed. In the present study, 76 such strains were further characterized. Due to interprimer interaction during the standard multiplex PCR approach, modifications of this procedure were implemented. The modified analyses revealed a high frequency of G2, G8, and G9 genotypes, often combined with P[4] and/or P[6]. The Guinean G8 and G9 strains were 97 and 98%, respectively, identical to other African G8 and G9 strains. Multiple G and/or P types were identified at a high frequency (59%), including two previously undescribed mixed infections, P[4]P[6], G2G8 and P[4]P[6], G2G9. These mixed infections most likely represent naturally occurring reassortance of rotavirus strains. Detection of such strains among the previously incompletely typed strains indicates a potential underestimation of mixed infections, if only a standard multiplex PCR procedure is followed. Furthermore cross-priming of the G3 primer with the G8 primer binding site and silent mutations at the P[4] and P[6] primer binding sites were detected. These findings highlight the need for regular evaluation of the multiplex primer PCR method and typing primers. The high frequency of uncommon as well as reassortant rotavirus strains in countries where rotavirus is an important cause of child mortality underscores the need for extensive strain surveillance as a basis to develop appropriate rotavirus vaccine candidates.

Seven years' experience with Cryptosporidium parvum in Guinea-Bissau, West Africa.

In community-based studies conducted from 1991 to 1997 in Guinea-Bissau, West Africa, stool specimens from children aged less than 5 years with diarrhoea were routinely examined for enteric parasites. Cryptosporidium parvum, found in 7.7% of 4,922 samples, was the second most common parasite, exceeded only by Giardia lamblia which was found in 14.8% of the samples. The highest prevalence of cryptosporidium was found in children aged 6-11 months, whereas the prevalence of other enteric parasites increased with age. Cryptosporidiosis showed a marked seasonal variation, with peak prevalences found consistently at the beginning of or just before the rainy seasons, May through July. By contrast, no seasonality was found for the enteric parasites Giardia lamblia or Entamoeba histolytica. We conclude that Cryptosporidium parvum is an important pathogen in children with diarrhoea.

Community-based controlled trial of dietary management of children with persistent diarrhea: sustained beneficial effect on ponderal and linear growth.

BACKGROUND: Uncontrolled hospital-based studies in developing countries have reported promising results of dietary rehabilitation of children with persistent diarrhea. OBJECTIVE: The objective was to determine the immediate and long-term effects of a dietary supplement and micronutrients given to children with persistent diarrhea during the episode and for 1 wk during convalescence. DESIGN: The study was open, controlled, and community-based and was conducted in a periurban area in Guinea-BISSAU: Children <3 y of age with persistent diarrhea were identified during weekly household visits. The children randomly assigned to the treatment and control groups were examined by a physician and all medical conditions were treated. The children in the treatment group were offered home-based dietary treatment consisting of locally available foods and micronutrient supplements. RESULTS: There were 141 episodes of persistent diarrhea during the study: 70 in the treatment group (in 58 children) and 71 in the control group (in 62 children). During the intervention period (median: 17 d), weight gain in the treatment group exceeded that of the control group by 61.5 g/wk (95% CI: 49.2, 73.8), whereas there was no significant difference in linear growth on the basis of knee-heel length. At a median follow-up period of 6.6 mo after the intervention was stopped, weight gain in the treatment group exceeded that of the control group by 12.5 g/wk (95% CI: 7.7, 17.3); knee-heel length was 7.5 mm/y (4.8, 10.2) greater and total length was 0.65 cm/y (0.11, 1.19) greater in the treatment group. CONCLUSION: Therapeutic feeding and micronutrient supplementation had an immediate and sustained beneficial effect on growth in children with persistent diarrhea.

Genotype profiles of rotavirus strains from children in a suburban community in Guinea-Bissau, Western Africa.

The P (VP4) and G (VP7) genotypes of 167 group A rotavirus strains obtained during the period 1996 to 1998 from 149 children living in a suburban community in Guinea-Bissau, western Africa, were determined by the reverse transcription-PCR technique. A total of nine combinations including five different P types and five different G types were identified. The globally common genotype pairs P[8], G1; P[4], G2; P[8], G3 and P[8], G4 were underrepresented in this study area. We found a substantial year-to-year variation in the occurrence of the genotype combinations. In 1996 and 1997, P[6], G2 was the most frequent, whereas P[8], G1 was more common in 1998. The unusual type P[9], G3 and a few mixed infections were detected. Sixteen percent of the rotavirus-positive samples were nontypeable.

Community-based randomized controlled trial of reduced osmolarity oral rehydration solution in acute childhood diarrhea.

OBJECTIVE: The standard oral rehydration solution (ORS) recommended by WHO and UNICEF does not reduce the volume or frequency of stools or the length of the episode. Hospital-based studies from developing and developed countries and intestinal perfusion studies suggest a beneficial effect on water and sodium absorption with reduced osmolarity ORS as compared with standard ORS. We conducted a community-based study comparing the efficacy of reduced osmolarity ORS (224 mmol/l) with standard ORS (311 mmol/l) in acute childhood diarrhea in a West African community. METHODS: Infants and toddlers age 0 to 30 months having 738 episodes of diarrhea identified by weekly household visits were randomly assigned to treatment with either standard ORS (n = 376) or reduced osmolarity ORS (n = 362). The children were followed by daily home visits to assess ORS intake and clinical characteristics. Duration of diarrhea was compared by proportional hazards regression analysis, the hazard ratio being interpreted as the relative recovery rate between the children receiving the two types of ORS. Because earlier reports have suggested that weaning status might be an important modifier for the performance of reduced osmolarity ORS, the effect was assessed overall and as an interaction between type of ORS and weaning status and age. Maternal satisfaction was assessed in a paired analysis among mothers whose children participated at least twice in the study. RESULTS: In the overall analysis reduced osmolarity ORS was as efficacious as standard ORS as assessed by duration of diarrheal episode and total number of stool evacuations on Days 1 and 2. Non-breast-fed toddlers (i.e. children ages 12 to 30 months) treated with reduced osmolarity ORS had significantly shorter diarrheal episodes [1.14 days vs. 1.78 days with standard ORS; hazard ratio, 1.50; 95% confidence interval (CI), 1.07 to 2.09] and lower total number of stool evacuations on Days 1 and 2 (3.9 stool evacuations vs. 5.0 stool evacuations with standard ORS; ratio of geometric means, 0.77; 95% CI 0.60 to 1.01). No significant difference was found for breast-fed toddlers or for infants. There was no statistically significant difference in the ORS intake between the two treatment groups. The odds ratio for the mother preferring reduced osmolarity ORS to standard ORS was 1.92 (95% CI 0.97 to 3.85). CONCLUSIONS: Reduced osmolarity ORS was as efficacious as standard ORS. Non-breast-fed children treated with reduced osmolarity ORS had significantly shorter diarrheal episodes and a tendency toward lower stool frequency. These findings may be of importance, especially in developing countries where early weaning is common.