Pre-epidemic Period Research Articles

CURRENT CONCEPTIONS CONCERNING THE OBJECTIVE LAWS OF A CHOLERA EPIDEMIC PROCESS: ECOLOGICAL AND MOLECULAR BIOLOGICAL ASPECTS

Modern conceptions about the objective laws of cholera epidemic process are reviewed taking into account the peculiarities of molecular biological properties and adaptable potential of the causative agent in the endemic, epidemic and cholera safe areas. It is shown that aquatic ecosystems at the endemic territories play the significant role both in the phase of the agent reservation (when it can pass to persistent forms or remain in viable but not culturable condition) and during the pre-epidemic period. During this period the molecular genetically heterogeneity of Vibrio cholerae population in the environments gives occasion to the subsequent selection of a pandemic clone in a susceptible host. This pandemic line is low enough in water ecosystem that is proved by the data of molecular typing of clinical and aquatic V. cholerae isolates. The phase of epidemic distribution of the given type can be realized most effectively at occurring of a “fast” way of the agent dissemination from person to person at preservation of the pathogen high infectivity. The leading role in the development of epidemiological complications in the epidemic and cholera free areas belongs to importation of high infective V. cholerae clone generated in endemic foci with its subsequent accumulation in environment objects under favorable climatic, hydrological and ecological conditions. Thus, intensity of epidemic process is defined by the action both natural climatic and social factors that are limiting in the safe areas but can promote scale epidemiological complications and also the infection persistence in the epidemic regions.

Large-scale analysis of B-cell epitopes of envelope: Implications for Zika vaccine and immunotherapeutic development

Background: Cases of the re-emergence of Zika virus in 2015 were associated with severe neurologic complications, including Gillien-Barre syndrome in adults and congenital Zika syndrome in newborns. The major structural determinant of immunity to the Zika virus is the E protein. Although B-cell epitopes of Zika E protein were recently identified, data regarding epitope variations among Zika strains in pre-epidemic and epidemic periods are lacking. Methods: Here, we conducted systematic bioinformatics analyses of Zika strains isolated between 1968 and 2017. Multiple sequence alignment of E protein as well as B-cell epitopes annotations were performed. In addition, homology-based approach was utilized to construct three-dimensional structures of monomeric E glycoproteins to annotate epitope variations. Lastly, of N-glycosylation patterns and prediction of protein stability upon mutations were also investigated. Results: Our analyses indicates that epitopes recognized by human mAbs ZIKV-117, ZIKV-15, and ZIKV-119 were highly conserved, suggesting as attractive targets for the development of vaccines and immunotherapeutics directed against diverse Zika strains. In addition, the epitope recognized by ZIKV-E-2A10G6 mAb derived from immunized mice was highly conserved across Zika strains. Conclusions: Our data provide new insights regarding antigenic similarities between Zika strains circulating worldwide. These data are essential for understanding the impact of evolution on antigenic cross-reactivity between Zika lineages and strains. Further in-vitro analyses are needed to determine how mutations could impact the development of vaccines that can effectively neutralize Zika viruses.

Evaluating neighborhood structures for modeling intercity diffusion of large-scale dengue epidemics

BackgroundDengue fever is a vector-borne infectious disease that is transmitted by contact between vector mosquitoes and susceptible hosts. The literature has addressed the issue on quantifying the effect of individual mobility on dengue transmission. However, there are methodological concerns in the spatial regression model configuration for examining the effect of intercity-scale human mobility on dengue diffusion. The purposes of the study are to investigate the influence of neighborhood structures on intercity epidemic progression from pre-epidemic to epidemic periods and to compare definitions of different neighborhood structures for interpreting the spread of dengue epidemics.MethodsWe proposed a framework for assessing the effect of model configurations on dengue incidence in 2014 and 2015, which were the most severe outbreaks in 70 years in Taiwan. Compared with the conventional model configuration in spatial regression analysis, our proposed model used a radiation model, which reflects population flow between townships, as a spatial weight to capture the structure of human mobility.ResultsThe results of our model demonstrate better model fitting performance, indicating that the structure of human mobility has better explanatory power in dengue diffusion than the geometric structure of administration boundaries and geographic distance between centroids of cities. We also identified spatial–temporal hierarchy of dengue diffusion: dengue incidence would be influenced by its immediate neighboring townships during pre-epidemic and epidemic periods, and also with more distant neighbors (based on mobility) in pre-epidemic periods.ConclusionsOur findings suggest that the structure of population mobility could more reasonably capture urban-to-urban interactions, which implies that the hub cities could be a “bridge” for large-scale transmission and make townships that immediately connect to hub cities more vulnerable to dengue epidemics.

ОЦЕНКА НАПРЯЖЕННОСТИ КОЛЛЕКТИВНОГО ИММУНИТЕТА ЖИТЕЛЕЙ Г. ЕКАТЕРИНБУРГА И СВЕРДЛОВСКОЙ ОБЛАСТИ К ВИРУСУ ГРИППА В ЭПИДЕМИЧЕСКИЕ ПЕРИОДЫ 2015-17 Г.Г

Thе aim of this research was acomparative assessment of the herd immunity to epidemic and seasonal influenza virus strains in the epidemic periods of 2015-2016 and 2016-2017 in compliance with the results of a sampling research of the donated blood sera in Yekaterinburg and Sverdlovsk Oblast, the Russian Federation. Hemagglutination inhibition assay test was used to assess 817 samples for antibodies to A/ California/07/09(HlNlpdm09), A/HongKong/4801/14(H3N2) and В/Phuket/3073/13 influenza viruses. Index >1:40was considered a positive antibody titre. In the pre-epidemic period of 2015, the proportion of serapositive to A/California/07/09(HlNlpdm09) virus was 36.4%. In the pre-epidemic period of 2017, this proportion for A/Hong Kong/4801/14(H3N2) virus was 38,0%, in 2017 this proportion for A/California/07/09(HlNlpdm09) virus was 58,7%. The epidemic increases in the incidence caused by the corresponding current influenza virus serotypes in these years imply that prior to every epidemic season the herd immunity of the population was insufficient for the prevention of epidemics.

Zika Virus Epidemic in the Dominican Republic, 2016

BackgroundThe first cases of Zika (ZIKV) in the Americas were reported in Easter Island, Chile in 2014. The epidemic spread to Brazil and Central America in 2015. We describe the extent and distribution of the countrywide ZIKV epidemic in the Dominican Republic.MethodsThe DR Ministry of Health (MoH) instituted active surveillance, monitoring and mandatory reporting of suspected cases of ZIKV in 2015 through the National System of Epidemiologic Surveillance (SINAVE). In the pre-epidemic period, the MoH conducted active search and blood testing of suspected cases in communities rumored to have cases of the disease. During the epidemic, the MoH conducted weekly monitoring of all cases of febrile exanthems, flaccid paralysis and meningitis, and also conducted rapid surveys in highly populated areas to identify local outbreaks. Data from SINAVE was exported and analyzed using SAS.ResultsA total of 5226 cases ZIKV were reported to the MoH from January 2016 to December 2016 (figure). Cases were 74% female, of whom 1275 (33%) were pregnant. Most of the cases (51%) were diagnosed in the age group of 20 to 39, and did not differ by gender. The majority (58%) of cases were reported from a metropolitan area. Almost all cases (82%) were treated in the outpatient setting, while 17% were hospitalized. Only 3 patients died and 95% had an uncomplicated course. There were 285 cases of Guillain BarrŽ Syndrome (GBS; Figure), with the epidemic curve showing a peak 2–4 weeks following the peak of the epidemic. Compared with patients with suspected ZIKV (n = 1054), those with GBS were more likely to be male (47% vs. 19%, P < 0.001), aged ≥40 years (53% vs. 19%, P < 0.001),, more likely to have complications (18% vs. 6%, P < 0.001) and comorbidity (2% vs. 0.2%, P = 0.04) Seventeen (6%) of confirmed GBS cases resulted in death.FigureCases of Zika and GBS, Dominican Republic, 2016ConclusionThe DR reported one of the largest ZIKV outbreaks in the Americas. The epidemic started early in 2016 and had all but subsided by May 2017. Although most cases had an uncomplicated course, incidence of GBS was high.Disclosures All authors: No reported disclosures.

Global reaction to the recent outbreaks of Zika virus: Insights from a Big Data analysis.

ObjectiveThe recent spreading of Zika virus represents an emerging global health threat. As such, it is attracting public interest worldwide, generating a great amount of related Internet searches and social media interactions. The aim of this research was to understand Zika-related digital behavior throughout the epidemic spreading and to assess its consistence with real-world epidemiological data, using a behavioral informatics and analytics approach.MethodsIn this study, the global web-interest and reaction to the recently occurred outbreaks of the Zika Virus were analyzed in terms of tweets and Google Trends (GT), Google News, YouTube, and Wikipedia search queries. These data streams were mined from 1st January 2004 to 31st October 2016, with a focus on the period November 2015—October 2016. This analysis was complemented with the use of epidemiological data. Spearman’s correlation was performed to correlate all Zika-related data. Moreover, a multivariate regression was performed using Zika-related search queries as a dependent variable, and epidemiological data, number of inhabitants in 2015 and Human Development Index as predictor variables.ResultsOverall 3,864,395 tweets, 284,903 accesses to Wikipedia pages dedicated to the Zika virus were analyzed during the study period. All web-data sources showed that the main spike of researches and interactions occurred in February 2016 with a second peak in August 2016. All novel data streams-related activities increased markedly during the epidemic period with respect to pre-epidemic period when no web activity was detected. Correlations between data from all these web platforms resulted very high and statistically significant. The countries in which web searches were particularly concentrated are mainly from Central and South Americas. The majority of queries concerned the symptoms of the Zika virus, its vector of transmission, and its possible effect to babies, including microcephaly. No statistically significant correlation was found between novel data streams and global real-world epidemiological data. At country level, a correlation between the digital interest towards the Zika virus and Zika incidence rate or microcephaly cases has been detected.ConclusionsAn increasing public interest and reaction to the current Zika virus outbreak was documented by all web-data sources and a similar pattern of web reactions has been detected. The public opinion seems to be particularly worried by the alert of teratogenicity of the Zika virus. Stakeholders and health authorities could usefully exploited these internet tools for collecting the concerns of public opinion and reply to them, disseminating key information.

Зміна протеїназно-інгібіторної системи організму здорових білих мишей під дією поляризованого, некогерентного, поліхроматичного світла

Introduction. Along with specific flu prevention, using vaccines other ways do not lose relevance to prevent influenza and SARS, which are non-specific and folk medicines, especially their use in pre-epidemic period. But unspecific methods are related to immune stimulation and focused on antiviral effect. These include stimulants interferon, gamma globulin, Arbidol, Laferon and polarized, polychromatic, incoherent (Payler) light.The aim of the study – to learn enzyme-inhibitory system in a healthy body of white mice and its amendments arising under Payler light.Research Methods. Trypsyn-like proteinase activity was determined by the method of K. I. Veremeienko modified by S. V. Vovchuk. Protein was determined by the method of O. Lowry. Definition proteinase trypsyn-like inhibitor was performed by A. P. Levytskyi.Results and Discussion. As the results of studies in lungs of mice healthy active proteinase inhibitor trypsyn-like lung was 1.16 mg/ml, and serum – 168.7 mg/ml. Proteinases activity in the lungs of mice was 66.4 mg of arginine in 0.1 ml/1 hr; in serum of healthy mice – 51.5 micrograms in 0.1 ml/1 hr. The protein content in the lungs of mice at 6.28 mg/ml in serum of mice – 13.77 mg/ml. In mice that received 11 sessions of exposure Payler-light inhibitory activity in lungs was not determined and in blood serum was recorded at 80.12 mg/ml, under Payler light inhibitory activity decreased by 50 % in serum and completely disappeared in the lungs of experimental animals. Proteinases activity increased to 86.0 mc arg/0.1ml/1 hr. in serum of mice it was 26.7 mg arg/0.1ml/1 hr. The content of total protein in serum blood and lungs of mice was significantly reduced.Conclusions. Under the influence of light-Payler proteinases we observed an increase in activity in the lungs of mice, and protein in the serum. Activity reducing of inhibitor on 50 % was noted in the serum of mice. At the same time, in lungs of animals we observed its complete disappearance.

Effect of Ebola virus disease on maternal and child health services in Guinea: a retrospective observational cohort study.

SummaryBackgroundThe 2014 west African epidemic of Ebola virus disease posed a major threat to the health systems of the countries affected. We sought to quantify the consequences of Ebola virus disease on maternal and child health services in the highly-affected Forest region of Guinea.MethodsWe did a retrospective, observational cohort study of women and children attending public health facilities for antenatal care, institutional delivery, and immunisation services in six of seven health districts in the Forest region (Beyla, Guéckédou, Kissidougou, Lola, Macenta, and N’Zérékoré). We examined monthly service use data for eight maternal and child health services indicators: antenatal care (≥1 antenatal care visit and ≥3 antenatal care visits), institutional delivery, and receipt of five infant vaccines: polio, pentavalent (diphtheria, tetanus, pertussis, hepatitis B virus, and Haemophilus influenzae type b), yellow fever, measles, and tuberculosis. We used interrupted time series models to estimate trends in each indicator across three time periods: pre-Ebola virus disease epidemic (January, 2013, to February, 2014), during-epidemic (March, 2014, to February, 2015) and post-epidemic (March, 2015, to Feb, 2016). We used segmented ordinary least-squares (OLS) regression using Newey-West standard errors to accommodate for serial autocorrelation, and adjusted for any potential effect of birth seasonality on our outcomes.FindingsIn the months before the Ebola virus disease outbreak, all three maternal indicators showed a significantly positive change in trend, ranging from a monthly average increase of 61 (95% CI 38–84) institutional deliveries to 119 (95% CI 79–158) women achieving at least three antenatal care visits. These increasing trends were reversed during the epidemic: fewer institutional deliveries occurred (–240, 95% CI −293 to −187), and fewer women achieved at least one antenatal care visit (–418, 95% CI −535 to −300) or at least three antenatal care visits (–363, 95% CI −485 to −242) per month (p<0·0001 for all). Compared with the negative trend during the outbreak, the change in trend during the post-outbreak period showed that 173 more women per month (95% CI 51–294; p=0·0074) had at least one antenatal care visit, 257 more (95% CI 117–398; p=0·0010) had at least three antenatal care visits and 149 more (95% CI 91–206; p<0·0001) had institutional deliveries. However, although the numbers for these indicators increased in the post-epidemic period, the trends for all stagnated. Similarly, the increasing trend in child vaccination completion during the pre-epidemic period was followed by significant immediate and trend reductions across most vaccine types. Before the outbreak, the number of children younger than 12 months who had completed each vaccination ranged from 5752 (95% CI 2821–8682) for tuberculosis to 8043 (95% CI 7621–8464) for yellow fever. Immediately after the outbreak, significant reductions occurred in the level of all vaccinations except for yellow fever for which the reduction was marginal. The greatest reductions were noted for polio and tuberculosis at −3594 (95% CI −4811 to −2377; p<0·0001) and −3048 (95% CI −5879 to −216; p=0·0362) fewer vaccines administered, respectively. Compared with pre-Ebola virus disease outbreak trends, significant decreases occurred for all vaccines except polio, with the trend of monthly decreases in the number of children vaccinated ranging from −419 (95% CI −683 to −155; p=0·0034) fewer for BCG to −313 (95% CI–446 to −179; p<0·0001) fewer for pentavalent during the outbreak. In the post-Ebola virus disease outbreak period, vaccination coverage for polio, measles, and yellow fever continued to decrease, whereas the trend in coverage for tuberculosis and pentavalent did not significantly differ from zero.InterpretationMost maternal and child health indicators significantly declined during the Ebola virus disease outbreak in 2014. Despite a reduction in this negative trend in the post-outbreak period, the use of essential maternal and child health services have not recovered to their pre-outbreak levels, nor are they all on a course that suggests that they will recover without targeted interventions.

Dynamic Modelling of Dengue Epidemics in Function of Available Enthalpy and Rainfall

In this work, we present results of an investigation of environmental precursors of infectious epidemic of dengue fever in the Metropolitan Area of Rio de Janeiro, RJ, Brazil, obtained by a numerical model with representation of infection and reinfection of the population. The period considered extend between 2000 and 2011, in which it was possible to pair meteorological data and the reporting of dengue patients worsening. These data should also be considered in the numerical model, by assimilation, to obtain simulations of Dengue epidemics. The model contains compartments for the human population, for the vector Aedes aegypti and four virus serotypes. The results provide consistent evidence that worsening infection and disease outbreaks are due to the occurrence of environmental precursors, as the dynamics of the accumulation of water in the breeding and energy availability in the form of metabolic activation enthalpy during pre-epidemic periods.

Метод профилактики острых респираторных инфекций у детей с врожденными пороками сердца

Цель: изучить эффективность и безопасность рекомбинантного липосомального интерферона альфа-2β в профилактике острых респираторных инфекций (ОРИ) у детей с врожденными пороками сердца. Материалы и методы. В предэпидемический период ОРИ 31 ребенку 3–12 лет с врожденными пороками сердца (основная группа) проводили оценку эффективности профилактической программы рекомбинантным липосомальным интерфероном альфа-2β: 250 000 ЕД 1 раз в сутки 2 раза в неделю в течение 1 месяца (методика I). В связи с недостаточной эффективностью в дальнейшем продолжили профилактику по методике II: 250 000 ЕД 2 раза в сутки в течение 3 дней, затем по 250 000 ЕД 1 раз в сутки 2 раза в неделю в течение 1 месяца. Клинико-лабораторное обследование (в том числе оценку уровня лизоцима, лактоферрина и секреторного иммуноглобулина А) проводили до начала профилактического воздействия, на 30, 120, 180-й день. Оценивали удовлетворенность результатами профилактики, побочные явления. Контрольную группу составили 20 здоровых сверстников. Результаты. Исходно у детей с врожденными пороками сердца выявлено снижение в ротоглоточном секрете уровня лизоцима, лактоферрина и секреторного иммуноглобулина А. После профилактической программы по методике I констатировано уменьшение частоты и продолжительности ОРИ и осложнений. Профилактическая программа по методике II продемонстрировала большую эффективность по названным выше показателям. Все дети хорошо переносили профилактическое лечение, побочных эффектов не было. Выводы. Выявлено снижение показателей местного иммунитета у детей с врожденными пороками сердца, что повышает риск заболеваемости ОРИ. Высокая эффективность и безопасность рекомбинантного липосомального интерферона альфа-2β являются основанием для его использования у детей с целью профилактики ОРИ.

The spatio-temporal characteristics of potential dengue risk assessed by Aedes aegypti and Aedes albopictus in high-epidemic areas

Aedes aegypti (AE) and Aedes albopictus (AA) are the two major dengue vectors in the world. To control dengue, monitoring vectors is essential. The abundance and distribution of mosquitoes are usually considered as a proxy for dengue outbreaks. Most of the researches catch the abundance and distribution of vectors by using traps, but this kind of information only can reflect partial relationship between the mosquitoes and dengue since human factors were not taken into account. To have a better proxy for dengue risk, this research evaluated the spatiotemporal distribution of dengue vectors by a human population-stratified ovitrap survey. We demonstrated the potential intensity of dengue transmission spatio-temporally in the high epidemic areas. We analyzed the temporal patterns of vector abundances, compared the levels of vector aggregation indoors with outdoors, and assess the vector concentration tendency around residential centers and administration edges form June 2010 to June 2011. We found significantly more AA outdoors than indoors, and no matter outdoor or indoor settings were, the abundances of AA were descending from the pre-epidemic period to post-epidemic period. AE also had the descending pattern, but there were no significant differences detected between outdoor and indoor settings. AA hotspots appeared almost the same locations from the pre-epidemic period to post-epidemic period, but no obvious repetitive AE hotspots were shown. We also found that AA tended to aggregate around the residential centers while AE likely clustered around the district boundaries. Our study concluded these spatio-temporal characteristics of AE and AA addressed from a population adjusted ovitrap method implied the risks of dengue in different times and locations. To more efficiently control dengue, except for routine unspecific control interventions, the authorities should realize different environmental management strategies were needed for AE and AA.

Population and Genetic Study of Vibrio cholerae from the Amazon Environment Confirms that the WASA-1 Prophage Is the Main Marker of the Epidemic Strain that Circulated in the Region

Vibrio cholerae is a natural inhabitant of many aquatic environments in the world. Biotypes harboring similar virulence-related gene clusters are the causative agents of epidemic cholera, but the majority of strains are harmless to humans. Since 1971, environmental surveillance for potentially pathogenic V. cholerae has resulted in the isolation of many strains from the Brazilian Amazon aquatic ecosystem. Most of these strains are from the non-O1/non-O139 serogroups (NAGs), but toxigenic O1 strains were isolated during the Latin America cholera epidemic in the region (1991-1996). A collection of environmental V. cholerae strains from the Brazilian Amazon belonging to pre-epidemic (1977-1990), epidemic (1991-1996), and post-epidemic (1996-2007) periods in the region, was analyzed. The presence of genes related to virulence within the species and the genetic relationship among the strains were studied. These variables and the information available concerning the strains were used to build a Bayesian multivariate dependency model to distinguish the importance of each variable in determining the others. Some genes related to the epidemic strains were found in environmental NAGs during and after the epidemic. Significant diversity among the virulence-related gene content was observed among O1 strains isolated from the environment during the epidemic period, but not from clinical isolates, which were analyzed as controls. Despite this diversity, these strains exhibited similar PFGE profiles. PFGE profiles were significant while separating potentially epidemic clones from indigenous strains. No significant correlation with isolation source, place or period was observed. The presence of the WASA-1 prophage significantly correlated with serogroups, PFGE profiles, and the presence of virulence-related genes. This study provides a broad characterization of the environmental V. cholerae population from the Amazon, and also highlights the importance of identifying precisely defined genetic markers such as the WASA-1 prophage for the surveillance of cholera.

Laboratory-confirmed invasive meningococcal disease: effect of the Hajj vaccination policy, Saudi Arabia, 1995 to 2011

Saudi Arabia (SA) experienced two large invasive meningococcal disease (IMD) outbreaks during the 2000 and 2001 Hajj pilgrimages. In 2002, polysaccharide quadrivalent ACWY vaccines became mandatory for Mecca and Medina pilgrims/residents older than two years. This study aimed to analyse IMD surveillance data among citizens, residents and pilgrims in SA from 1995 to 2011, focusing on changes before and after the new vaccination policy. For all laboratory-confirmed IMD cases in the national surveillance database from 1995 to 2011, serogroup and age were retrieved. The cases' seasonal distribution as well as the case fatality ratios (CFR) were obtained. For Saudi citizens/residents and Hajj pilgrims, annual rates were calculated using mid-year population estimates. The Student's t-test was used to compare means between the pre-epidemic (1995-1999) and post-epidemic (2002-2011) periods, excluding outbreak years. From 1995 to 2011, laboratories notified 1,103 cases. Between the pre- and post-epidemic periods, mean annual IMD rates decreased from 0.20 (standard deviation (SD): 0.1) to 0.06 cases/100,000 (SD: 0.06; p=0.02), mean numbers of Hajj-related cases from 13 (SD: 9.3) to 2 cases/year (SD: 2.3; p=0.02) and the mean age from 31 (SD: 1.3) to 18 years (SD: 1.4; p<0.01). The CFR in Saudi citizens (10.4) was lower than among foreign pilgrims (28.9) and decreased from 19.3% (SD: 1.8) in the pre-epidemic to 11.4% (SD: 7.0; p=0.04) in the post-epidemic phase. The decrease of annual IMD rates, CFR and Hajj-related cases between the pre- and post- vaccine era suggests a possible positive effect of the mandatory ACWY vaccination for pilgrims/residents in Mecca and Medina. Regular surveillance with an annual data analysis is necessary to monitor trends and circulating serotypes and to implement appropriate public health measures to avoid new IMD epidemics during upcoming Hajj seasons.

High Burden of Non-Influenza Viruses in Influenza-Like Illness in the Early Weeks of H1N1v Epidemic in France

BackgroundInfluenza-like illness (ILI) may be caused by a variety of pathogens. Clinical observations are of little help to recognise myxovirus infection and implement appropriate prevention measures. The limited use of molecular tools underestimates the role of other common pathogens.ObjectivesDuring the early weeks of the 2009–2010 flu pandemic, a clinical and virological survey was conducted in adult and paediatric patients with ILI referred to two French University hospitals in Paris and Tours. Aims were to investigate the different pathogens involved in ILI and describe the associated symptoms.MethodsH1N1v pandemic influenza diagnosis was performed with real time RT-PCR assay. Other viral aetiologies were investigated by the molecular multiplex assay RespiFinder19®. Clinical data were collected prospectively by physicians using a standard questionnaire.ResultsFrom week 35 to 44, endonasal swabs were collected in 413 patients. Overall, 68 samples (16.5%) were positive for H1N1v. In 13 of them, other respiratory pathogens were also detected. Among H1N1v negative samples, 213 (61.9%) were positive for various respiratory agents, 190 in single infections and 23 in mixed infections. The most prevalent viruses in H1N1v negative single infections were rhinovirus (62.6%), followed by parainfluenza viruses (24.2%) and adenovirus (5.3%). 70.6% of H1N1v cases were identified in patients under 40 years and none after 65 years. There was no difference between clinical symptoms observed in patients infected with H1N1v or with other pathogens.ConclusionOur results highlight the high frequency of non-influenza viruses involved in ILI during the pre-epidemic period of a flu alert and the lack of specific clinical signs associated with influenza infections. Rapid diagnostic screening of a large panel of respiratory pathogens may be critical to define and survey the epidemic situation and to provide critical information for patient management.

Factors associated with infection by 2009 pandemic H1N1 influenza virus during different phases of the epidemic

The focus of this study was to ascertain the factors associated with 2009 pandemic influenza H1N1 (pH1N1) infection during different phases of the epidemic. In central Taiwan, 306 persons from households with schoolchildren were followed sequentially and serum samples were taken at three sampling time-points starting in the fall of 2008, shortly after influenza vaccination. Participants who seroconverted between two consecutive blood samplings were considered as having serological evidence of infection. A generalized estimation equation (GEE) with a logistic link to account for household correlations was applied to identify factors associated with pH1N1 infections during the pre-epidemic (April-June) and epidemic (September-October) periods. The results showed that receiving an inactivated seasonal influenza vaccine (ISIV) and having a hemagglutination inhibition assay (HI) titer of 40 or higher resulted in a significantly lower likelihood of pH1N1 infection during the pre-epidemic period only, for both children and adults (adjusted odds ratio (OR) 0.3, 95% confidence interval (CI) 0.12-0.9). Having a previous infection by pH1N1 with a baseline titer of 20 or higher resulted in a significantly lower likelihood of infection by pH1N1 during the epidemic period (adjusted OR 0.06, 95% CI 0.02-0.16). Our results provide the first serological evidence to suggest a protection effect from receiving an ISIV against pH1N1 infection only when the HI titer reaches 40 or higher during the pre-epidemic period. This study gives an important insight into the control and intervention measures required for preventing infections during future influenza epidemics.

Importation and spread of pandemic influenza virus a(H1N1) in Autonomous Province of vojvodina in preepidemic period

Influenza is the most frequently reported communicable disease, having epidemic and pandemic potential. The first influenza pandemic in this century started in Mexico and spread quickly throughout the world. This paper analyses importation of pandemic influenza cases and local transmission among population in the Autonomous Province of Vojvodina. According to the WHO guidelines and national recommendations, the influenza surveillance activities were conducted in Vojvodina in order to detect, isolate and treat affected international travelers and their close contacts. Patients whose pandemic influenza infection was laboratory confirmed were classified as confirmed cases, while those with symptoms who were epidemiologically linked with confirmed cases were classified as probable cases. During the period from the 24th of June to 17th of August 2009, 123 pandemic influenza cases were recorded in Vojvodina. Infection was imported through international travelers and our citizens coming from countries affected by influenza outbreaks. Majority of cases had mild clinical picture. Most frequently reported symptoms were high fever (above 38 degrees C) (85.6%), and cough (61.6%). Difficulty in breathing was recorded in 20 (16.0%) cases, while pneumonia developed in 4 (3.2%) cases but none of the cases required mechanical ventilation. The imported cases of pandemic influenza in the pre-epidemic period led to limited local transmission in general population and caused a small outbreak among visitors of International music festival called EXIT.

Brief communication: Rethinking the impact of the 1918 influenza pandemic on sex differentials in mortality

This study will assess the general impact of the 1918 influenza on overall mortality and its impact on mortality attributable to pulmonary tuberculosis in a small-scale population. Using life table and decomposition methodologies, changes in mortality in Gibraltar used a scheme that identified a pre-epidemic period (1904-1917), the epidemic year (1918), and the post-epidemic period (1919-1927). Overall health in both sexes fell significantly in 1918 with a drop in life expectancy at birth, however, health quickly rebounded in the post-epidemic period. In the case of women, there was a significant increase in life expectancy at birth after the epidemic. The impact of influenza on the magnitude of sex differentials in the life expectancy at birth fell during epidemic year but returned to a level comparable to that of the pre-epidemic period. With respect to respiratory tuberculosis deaths, the immediate impact of influenza was restricted to only a significant increase in the rate among women (aged 15-54). In the post-epidemic period, tuberculosis mortality rates returned to the pre-epidemic state in both sexes. The findings from Gibraltar stand in contrast opposition to results reported for experience in the United States during the 1918 flu.

Clostridium difficile Infections in a Canadian Tertiary Care Hospital before and during a Regional Epidemic Associated with the BI/NAP1/027 Strain

Since 2002, an epidemic of Clostridium difficile infections has occurred in southern Quebec, Canada. At Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada, the incidence of C. difficile infections increased from 11/1,000 admissions (1999 to 2002) to 27/1,000 admissions (2003 to 2005). We compared the exposures and outcomes for patients infected with strains with different ribopatterns isolated before (n = 55) and during (n = 175) the epidemic, as well as the in vitro activities of antibiotics against those isolates. During the preepidemic period, 46 isolates (84%) were of ribotype 001, 1 was of ribotype 027, and 8 were of other ribopattern types. During the epidemic period, ribotype 027 strains accounted for 140 (80%) isolates; 26 (15%) were of ribotype 001, and 7 were of other ribopattern types. Ribotype 027 strains were highly resistant to fluoroquinolones (FQs) but were susceptible to clindamycin. A pattern of prior specific antibiotic exposure that selected for antibiotic-resistant ribotype C. difficile infections was observed for FQs (ribotype 027) and clindamycin (ribotype 001). The rate of mortality was higher among older patients, those with a high Charlson comorbidity index, and those with longer previous hospitalizations. By multivariate analysis, patients infected with ribotype 027 were twice as likely to die within 30 days of diagnosis than patients infected with other ribotypes (adjusted odds ratio, 2.06; 95% confidence interval, 1.00 to 4.22). The observations from this study support the notion that continued selective antibiotic pressure resulted in the superimposition of the hypertoxigenic ribotype 027 clone on top of the prior dominant ribotype 001 clone in a setting of preexisting high endemicity, thus leading to the high rates of morbidity and mortality seen in the Quebec outbreak. Stringent antibiotic stewardship measures, combined with aggressive infection control, are required to curtail the epidemic of C. difficile infections.

Antibiotic use and other risk factors at hospital level for outbreaks with Clostridium difficile PCR ribotype 027

The first Dutch outbreak due to Clostridium difficile ribotype 027 was observed in mid-2005; by the end of that year, eight hospitals were affected. To study the relationship between hospital-wide antibiotic use and the incidence of 027-linked C. difficile-associated disease (CDAD) three study groups were made: group A, all eight hospitals with an 027-associated epidemic; group B, five of a total of six hospitals with occasional 027 cases, without an increase in CDAD; and group C, ten randomly selected hospitals with no reported 027 epidemics or isolated 027 cases. Quarterly data on CDAD incidences, hygiene measures and the use of fluoroquinolones, second- and third-generation cephalosporins, extended-spectrum penicillins, penicillins with beta-lactamase inhibitors, carbapenems, lincomycins and macrolides were collected for 2004 and 2005, and divided into pre-epidemic and epidemic periods. Using a multilevel Poisson regression analysis, CDAD incidence was linked to antibiotic use in the previous quarter and to certain hygiene measures. In the pre-epidemic period, the total use of the studied antibiotics was comparable between affected and unaffected hospitals. Higher use of second-generation cephalosporins, macrolides and all of the studied antibiotics were independently associated with a small increase in CDAD incidence [relative risk (95% confidence interval): 1.14 per increase of 100 defined daily doses per 10,000 bed days (1.06-1.23), 1.10 (1.01-1.19) and 1.02 (1.01-1.03), respectively]. However the effect was too small to predict which hospitals might be more prone to 027-associated outbreaks.

Outcomes of Clostridium difficile-Associated Disease Treated With Metronidazole or Vancomycin Before and After the Emergence of NAP1/027

To reassess the comparative efficacy of vancomycin versus metronidazole in the treatment of Clostridium difficile-associated disease (CDAD) after the emergence in 2003 of the hypervirulent NAP1/027 strain. A retrospective cohort study was conducted in a tertiary-care Canadian hospital among 1,616 patients treated initially with metronidazole (N=1,360), vancomycin (N=219), or both (N=37), between 1991 and 2006, and followed for 60 days after diagnosis. Primary outcome was severe/complicated CDAD (SC-CDAD) defined as any of: (a) death within 30 days, (b) septic shock, (c) megacolon, (d) perforation, or (e) emergency colectomy. Adjusted odds ratios (AOR) and their 95% confidence intervals (CI) were calculated, stratifying into pre-epidemic (1991-2002) and epidemic (2003-2006) periods. Secondary outcome was recurrence within 60 days. Risk factors for SC-CDAD were the same in both periods: age>or=65 yr, male sex, immunosuppression, hospital acquisition, tube feeding, short duration of diarrhea, fever, elevated leukocytosis, or creatinine. Adjusting for confounders and using metronidazole therapy as baseline, vancomycin therapy was associated with a lower probability of developing SC-CDAD in 1991-2002 (AOR 0.21, 95% CI 0.05-0.99, P=0.048) but not during 2003-2006 (AOR 0.90, 95% CI 0.53-1.55, P=0.71). For both metronidazole and vancomycin, risk of recurrence increased in 2003-2004 but decreased in 2005-2006. Loss of superiority of vancomycin over metronidazole coincided with the emergence of NAP1/027. Toxin hyperproduction by NAP1/027 might be such that the disease follows its natural course. Novel therapeutic approaches are needed. The higher risk of recurrence in 2003-2004 probably reflected reinfections rather than relapses.