The Belgian data (2003–2010) for the European Antimicrobial Resistance Surveillance Network (EARS-Net) showed a significant decreasing trend in the proportion of penicillin non-susceptible Streptococcus pneumoniae (9·4% to <1%) from blood and CSF isolates. We found that 75% of this decrease was explained by a change in Clinical and Laboratory Standards Institute (CLSI) breakpoints as the trend disappeared if only the new breakpoints were applied. Applying only European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints also resulted in a relatively stable proportion of penicillin non-susceptibility (average 5%), but this proportion was 7–13 times higher than with the new CLSI breakpoints. When the new CLSI breakpoints alone are used, fewer than 1% of bacteraemia isolates were penicillin non-susceptible during the entire period, but the proportion of non-susceptible meningitis isolates rose from 6·3% in 2003 to 15·9% between 2003 and 2010. Changing breakpoints should lead to retrospective analysis of historical data to minimize wrongly interpreting resistance trends.
Antibiotic resistance; clinical microbiology; Streptococcus pneumoniae (pneumococcus); surveillance system
Dengue is the most frequent arboviral disease and is expanding geographically. Dengue is also increasingly being reported in travellers, in particular in travellers to Thailand. However, data to quantify the risk of travellers acquiring dengue when travelling to Thailand are lacking. Using mathematical modelling, we set out to estimate the risk of non-immune persons acquiring dengue when travelling to Thailand. The model is deterministic with stochastic parameters and assumes a Poisson distribution for the mosquitoes' biting rate and a Gamma distribution for the probability of acquiring dengue from an infected mosquito. From the force of infection we calculated the risk of dengue acquisition for travellers to Thailand arriving in a typical year (averaged over a 17-year period) in the high season of transmission. A traveller arriving in the high season of transmission and remaining for 7 days has a risk of acquiring dengue of 0·2% (95% CI 0·16–0·23), whereas the risk for travel of 15 and 30 days' duration is 0·46% (95% CI 0·41–0·50) and 0·81% (95% CI 0·76–0·87), respectively. Our data highlight that the risk of non-immune travellers acquiring dengue in Thailand is substantial. The incidence of 0·81% after a 1-month stay is similar to that reported in prospective seroconversion studies in Israeli travellers to Thailand, highlighting that our models are consistent with actual data. Risk estimates based on mathematical modelling offer more detailed information depending on various travel scenarios, and will help the travel medicine provider give better evidence-based advice for travellers to dengue-endemic countries.
Dengue; mathematical modelling; risk estimates; Thailand; travellers
Case-ascertained household transmission studies, in which households including an ‘index case’ are recruited and followed up, are invaluable to understanding the epidemiology of influenza. We used a simulation approach parameterized with data from household transmission studies to evaluate alternative study designs. We compared studies that relied on self-reported illness among household contacts versus studies that used home visits to collect swab specimens for virologic confirmation of secondary infections, allowing for the trade-off between sample size versus intensity of follow-up given a fixed budget. For studies estimating the secondary attack proportion, 2–3 follow-up visits with specimens collected from all members regardless of illness were optimal. However, for studies comparing secondary attack proportions between two or more groups, such as controlled intervention studies, designs with reactive home visits following illness reports in contacts were most powerful, while a design with one home visit optimally timed also performed well.
The Poisson model can be applied to the count of events occurring within a specific time period. The main feature of the Poisson model is the assumption that the mean and variance of the count data are equal. However, this equal mean-variance relationship rarely occurs in observational data. In most cases, the observed variance is larger than the assumed variance, which is called overdispersion. Further, when the observed data involve excessive zero counts, the problem of overdispersion results in underestimating the variance of the estimated parameter, and thus produces a misleading conclusion. We illustrated the use of four models for overdispersed count data that may be attributed to excessive zeros. These are Poisson, negative binomial, zero-inflated Poisson and zero-inflated negative binomial models. The example data in this article deal with the number of incidents involving human papillomavirus infection. The four models resulted in differing statistical inferences. The Poisson model, which is widely used in epidemiology research, underestimated the standard errors and overstated the significance of some covariates.
Excessive zero-count data; HPV infection; incidence rate; overdispersion; zero-inflated model
We sought to explain seasonality and other aspects of Campylobacter jejuni epidemiology by integrating population genetic and epidemiological analysis in a large three-year longitudinal, two centre, population based study. Epidemiological information was collected for 1,505 isolates, which were multilocus sequence typed. Analyses compared pathogen population structure between areas, over time, and between clinical presentations. Pooled analysis was performed with published international datasets. Subtype association with virulence was not observed. UK sites had nearly identical C. jejuni populations. A clade formed by ST-45 and ST-283 clonal complexes showed a summer peak. This clade was common in a Finnish dataset but not in New Zealand and Australian collections, countries with less marked seasonality. The UK, New Zealand and Australian collections were otherwise similar. These findings map to known in-vitro differences of this clade. This identifies a target for studies to elucidate the drivers of the summer peak in human C. jejuni infection.
We examined the spatiotemporal distribution of laboratory-confirmed multidrug-resistant tuberculosis (MDR TB) cases and that of other TB cases in Lima, Peru with the aim of identifying mechanisms responsible for the rise of MDR TB in an urban setting. All incident cases of TB in two districts of Lima, Peru during 2005–2007 were included. The spatiotemporal distributions of MDR cases and other TB cases were compared with Ripley's K statistic. Of 11 711 notified cases, 1187 received drug susceptibility testing and 376 were found to be MDR. Spatial aggregation of patients with confirmed MDR disease appeared similar to that of other patients in 2005 and 2006; however, in 2007, cases with confirmed MDR disease were found to be more tightly grouped. Subgroup analysis suggests the appearance of resistance may be driven by increased transmission. Interventions should aim to reduce the infectious duration for those with drug-resistant disease and improve infection control.
Geographic information systems; multidrug-resistant tuberculosis (MDR TB); Peru; tuberculosis; spatial analysis
Referral bias can influence the results of studies performed at tertiary-care centers. In this study, we evaluated demographic and microbiologic factors that influenced referral of patients with gram-negative bloodstream infection (BSI). We identified 2919 and 846 unique patients with gram-negative BSI in a referral cohort of patients treated at Mayo Clinic Hospitals and a population-based cohort of Olmsted County, Minnesota, residents between 1/1/1998 and 12/31/2007, respectively. Multivariable logistic regression analysis was used to determine factors associated with referral. Elderly patients aged ≥ 80 years with gram-negative BSI were less likely to be referred than younger patients (odds ratio [OR]=0.43, 95% confidence intervals [CI]: 0.30-0.62) as were females (OR=0.63, 95% CI: 0.53-0.74). After adjusting for age and gender, bloodstream isolates of Escherichia coli (OR=0.50, 95% CI: 0.43-0.58) and Proteus mirabilis (OR=0.49, 95% CI: 0.30-0.82) were underrepresented in the referral cohort; and Pseudomonas aeruginosa (OR=2.26, 95% CI: 1.70-3.06), Enterobacter cloacae (OR=2.31, 95% CI: 1.53-3.66), Serratia marcescens (OR=2.34, 95% CI: 1.33-4.52) and Stenotrophomonas maltophilia (OR=17.94, 95% CI: 3.98-314.43) were overrepresented in the referral cohort. We demonstrated that demographic and microbiologic characteristics of patients with gram-negative BSI had an influence on referral patterns. These factors should be considered when interpreting results of investigations performed at tertiary-care centers.
gram-negative; bacteremia; epidemiology; selection bias; population-based; Rochester Epidemiology Project
This study aimed to describe the transmission dynamics, the serological and virus excretion patterns of Nipah virus (NiV) in Pteropus vampyrus bats. Bats in captivity were sampled every 7–21 days over a 1-year period. The data revealed five NiV serological patterns categorized as high and low positives, waning, decreasing and increasing, and negative in these individuals. The findings strongly suggest that NiV circulates in wild bat populations and that antibody could be maintained for long periods. The study also found that pup and juvenile bats from seropositive dams tested seropositive, indicating that maternal antibodies against NiV are transmitted passively, and in this study population may last up to 14 months. NiV was isolated from the urine of one bat, and within a few weeks, two other seronegative bats seroconverted. Based on the temporal cluster of seroconversion, we strongly believe that the NiV isolated was recrudesced and then transmitted horizontally between bats during the study period.
Antibody pattern; horizontal transmission; isolation; Malaysia; Nipah virus; Pteropus bats; recrudesced
Population-based studies of gram-negative bloodstream infection (BSI) in children are lacking. Therefore, we performed this population-based investigation in Olmsted County, Minnesota, to determine the incidence rate, site of acquisition, and outcome of gram-negative BSI in children under 18 years old. We used Kaplan-Meier method and Cox proportional hazard regression for mortality analysis. We identified 56 unique children with gram-negative BSI during the past decade. The gender-adjusted incidence rate of gram-negative BSI per 100,000 person-years was 129.7 (95% confidence interval [CI]: 77.8-181.6]) in infants, with a sharp decline to 14.6 (95% CI: 6.0-23.2) and 7.6 (95% CI: 4.3-10.9) in children 1-4 and 5-18 years old, respectively. The urinary tract was the most common identified source of infection (34%) and Escherichia coli was the most common pathogen isolated (38%). Over two-thirds (68%) of children had underlying medical conditions that predisposed to gram-negative BSI. The overall 28-day and 1-year all-cause mortality rates were 11% (95% CI: 3-18%) and 18% (95% CI: 8-28%), respectively. Younger age and number of underlying medical conditions were associated with 28-day and 1-year mortality, respectively. Nosocomial or healthcare-associated acquisition was associated with both 28-day and 1-year mortality.
bacteremia; gram-negative; paediatric; incidence; mortality
We identified eight consecutive patients who presented with a skin or soft tissue infection due to MRSA. Of seven household members of these cases, three were found to be colonized with MRSA. The mean duration of MRSA colonization among index cases was 33 days (range 14-104), while mean duration of colonization among household cases was 54 days (range 12-95). There was a borderline significant association between having a concurrent colonized household member and a longer duration of colonization (mean 44 days vs. 26 days, p=0.08).
MRSA; Colonization; Household
To characterize the association between county-level risk factors and the incidence of mumps in the 2006 Iowa outbreak, we used generalized linear mixed models with the number of mumps cases per county as the dependent variable. To assess the impact of spring-break travel, we tested for differences in the proportions of mumps cases in three different age groups. In the final multivariable model, the proportion of Iowa’s college students per county was positively associated (P<0.0001) with mumps cases, but the number of colleges was negatively associated with cases (P=0.0002). Thus, if the college students in a county were spread among more campuses, this was associated with fewer mumps cases. Finally, we found the proportion of mumps cases in both older and younger persons increased after 1 April (P=0.0029), suggesting that spring-break college travel was associated with the spread of mumps to other age groups.
College students; spatial; travel; mumps; outbreaks
Due to its extensive polymorphism, a partial sequence of the Cryptosporidium surface glycoprotein gene gp60 has been frequently used as a genetic marker. I explored the global diversity of this protein, and compared its sequence diversity in Cryptosporidium parvum and Cryptosporidium hominis. In marked contrast to the geographical partition of C. parvum and C. hominis multi-locus genotypes, gp60 allelic groups showed no evidence of segregating in space, or of differing with respect to geographical diversity. Globally, genetic diversity of C. hominis gp60 exceeded that of C. parvum. Within C. parvum, gp60 alleles originating from human isolates were more diverse than those infecting ruminants. Phylogenetic analysis grouped gp60 sequences into a small number of relatively homogenous allelic groups, with only a small number of alleles having evolved independently. With the notable exception of a group of alleles restricted to humans, C. parvum alleles are found in ruminants and humans.
Cryptosporidiosis; Cryptosporidium parvum; Cryptosporidium hominis; gp60; gp40/15
Recent studies have provided evidence that endemic pathogens may affect dynamics in animals. However, such studies have not typically considered that infected individuals might have a preceding underlying poor condition. We examined whether individuals in poor condition are more likely to become infected by an endemic pathogen, using as a system the dynamics of cowpox virus in field voles. With data from monthly sampled vole populations, a nested case-control study evaluated whether susceptible individuals with poorer condition had higher probabilities of contracting cowpox. The influence of condition was found to be considerable, especially for males. At times when a susceptible male with good body condition had a relatively low probability of becoming infected, a susceptible male with poor body condition was twice as likely to contract cowpox; if this male was also anaemic, the chances were almost quadrupled. We discuss the care needed when interpreting the findings of wildlife disease studies.
Cowpox; disease ecology; Microtus; population dynamics; wildlife disease
Historical studies of influenza pandemics can provide insight into transmission and mortality patterns, and may aid in planning for a future pandemic. Here, we analyse historical vital statistics and quantify the age-specific mortality patterns associated with the 1918–1920 influenza pandemic in Japan, USA, and UK. All three countries showed highly elevated mortality risk in young adults relative to surrounding non-pandemic years. By contrast, the risk of death was low in the very young and very old. In Japan, the overall mortality impact was not limited to winter 1918–1919, and continued during winter 1919–1920. Mortality impact varied as much as threefold across the 47 Japanese prefectures, and differences in baseline mortality, population demographics, and density explained a small fraction of these variations. Our study highlights important geographical variations in timing and mortality impact of historical pandemics, in particular between the Eastern and Western hemispheres. In a future pandemic, vaccination in one region could save lives even months after the emergence of a pandemic virus in another region.
Age patterns; excess mortality; geography; influenza; pandemic
We surveyed antimicrobial susceptibility in faecal Escherichia coli in primary schoolchildren in rural Tamil Nadu, India. Resistance profiles of E. coli samples from local water sources were also obtained. We investigated sociodemographic characteristics as risk factors for resistance and local paediatric prescription patterns. In 119 stool samples, carriage of resistance to ≥1 antibiotic was 63% and multiple drug resistance was 32%. Resistance outcomes were associated with school of attendance, having a sibling attend the same school, younger age, and less crowded households. Eight of nine water samples were resistant to ≥1 antibiotic. Recent history of medication use was not associated with resistance carriage. Resistance patterns may have been influenced by local paediatric prescription patterns and veterinary antibiotic use. Frequent, low-cost surveillance of commensal resistance can guide development of locally appropriate treatment guidelines. School-based hygiene programmes should be considered as means of limiting the spread of antibiotic resistance.
Antibiotic resistance; children; E. coli; epidemiology; India
Demographic and clinical risk factors are important in guiding vaccination policy for pneumococcal pneumonia. We present data on these variables from a population-based surveillance network covering adult bacteremic pneumococcal pneumonia (BPP) in the Delaware Valley region from 2002−2004. Surveillance data were used with U.S. Census data and a community health survey to calculate stratified incidence rates. Missing data were handled using multiple imputation. Overall adult rates of adult BPP were 10.6 cases per 100,000 person-years. Elevated rates were seen in the elderly (> 65 years), Native-Americans, African-Americans, the less-educated (< high school education), the poor, smokers, and individuals with histories of asthma, cancer, or diabetes. Multivariable modeling suggested that income was more robustly associated with risk than African-American race. Of methodological interest, this association was not apparent if census blockgroup median income was used as a proxy for self-reported income. Further research on socioeconomic risk factors for BPP is needed.
We evaluated the effectiveness of a measles vaccine campaign in rural Kenya,
based on oral-fluid surveys and mixture-modelling analysis. Specimens were
collected from 886 children aged 9 months to 14 years pre-campaign and from a
comparison sample of 598 children aged 6 months post-campaign. Quantitative
measles-specific antibody data were obtained by commercial kit. The estimated
proportions of measles-specific antibody negative in children aged
0–4, 5–9 and 10–14 years were 51%, 42% and 27%,
respectively, pre- campaign and 18%, 14% and 6%, respectively, post-campaign. We
estimate a reduction in the proportion susceptible of 65–78%, with
~85% of the population recorded to have received vaccine. The proportion of
‘weak’ positive individuals rose from 35% pre-campaign to
54% post-campaign. Our results confirm the effectiveness of the campaign in
reducing susceptibility to measles and demonstrate the potential of oral-fluid
studies to monitor the impact of measles vaccination campaigns.
Campaign vaccination; measles antibodies; mixture modelling; oral fluid; Kenya
The measurement and analysis of common recurrent conditions such as diarrhoea,
respiratory infections or fever pose methodological challenges with regard to
case definition, disease surveillance and statistical analysis. In this paper we
describe a flexible and robust model that can generate simulated longitudinal
datasets for a range of recurrent infections, reflecting the stochastic
processes that underpin the data collected in the field. It can be used to
evaluate and compare alternative disease definitions, surveillance strategies
and statistical methods under ‘controlled conditions’.
Parameters in the model include: characterizing the distributions of the
individual disease incidence and the duration of disease episodes; allowing the
average disease duration to depend on an individual's number of episodes
(simulating a correlation between incidence and duration); making the individual
risk of disease depend on the occurrence of previous episodes (simulating
autocorrelation of successive episodes); finally, incorporating seasonal
variation of disease.
Diarrhoea; mathematical model; respiratory infection; statistical methods; surveillance
One of the central tenets of modern infectious disease epidemiology is that an
understanding of heterogeneities, both in host demography and transmission, allows control
to be efficiently optimized. Due to the strong interactions present, households are one of
the most important heterogeneities to consider, both in terms of predicting epidemic
severity and as a target for intervention. We consider these effects in the context of
pandemic influenza in Great Britain, and find that there is significant local (ward-level)
variation in the basic reproductive ratio, with some regions predicted to suffer 50%
faster growth rate of infection than the mean. Childhood vaccination was shown to be
highly effective at controlling an epidemic, generally outperforming random vaccination
and substantially reducing the variation between regions; only nine out of over 10 000
wards did not obey this rule and these can be identified as demographically atypical
regions. Since these benefits of childhood vaccination are a product of correlations
between household size and number of dependent children in the household, our results are
qualitatively robust for a variety of disease scenarios.
Household; influenza; modelling; transmission
We evaluated the effectiveness of a measles vaccine campaign in rural Kenya, based on oral-fluid surveys and mixture-modelling analysis. Specimens were collected from 886 children aged 9 months to 14 years pre-campaign and from a comparison sample of 598 children aged 6 months post-campaign. Quantitative measles-specific antibody data were obtained by commercial kit. The estimated proportions of measles-specific antibody negative in children aged 0-4, 5-9 and 10-14 years were 51%, 42% and 27%, respectively, pre- campaign and 18%, 14% and 6%, respectively, post-campaign. We estimate a reduction in the proportion susceptible of 65-78%, with ~85% of the population recorded to have received vaccine. The proportion of ‘weak’ positive individuals rose from 35% pre-campaign to 54% post-campaign. Our results confirm the effectiveness of the campaign in reducing susceptibility to measles and demonstrate the potential of oral-fluid studies to monitor the impact of measles vaccination campaigns.
Campaign vaccination; measles antibodies; mixture modelling; oral fluid; Kenya
Recurrent epidemics of influenza are observed seasonally around the world with considerable health and economic consequences. A key quantity for the control of infectious diseases is the reproduction number, which measures the transmissibility of a pathogen and determines the magnitude of public health interventions necessary to control epidemics. Here we applied a simple epidemic model to weekly indicators of influenza mortality to estimate the reproduction numbers of seasonal influenza epidemics spanning three decades in the United States, France, and Australia. We found similar distributions of reproduction number estimates in the three countries, with mean value 1.3 and important year-to-year variability (range 0.9–2.1). Estimates derived from two different mortality indicators (pneumonia and influenza excess deaths and influenza-specific deaths) were in close agreement for the United States (correlation = 0.61, P < 0.001) and France (correlation = 0.79, P < 0.001), but not Australia. Interestingly, high prevalence of A/H3N2 influenza viruses was associated with high transmission seasons (P = 0.006), while B viruses were more prevalent in low transmission seasons (P = 0.004). The current vaccination strategy targeted at people at highest risk of severe disease outcome is suboptimal because current vaccines are poorly immunogenic in these population groups. Our results suggest that interrupting transmission of seasonal influenza would require a relatively high vaccination coverage (> 60 %) in healthy individuals who respond well to vaccine, in addition to periodic re-vaccination due to evolving viral antigens and waning population immunity.
Helicobacter pylori prevalence is elevated in German submarine crews and in United States Navy (USN) surface fleet personnel, but H. pylori prevalence in USN submariners was unknown. The goal of the study was to determine the prevalence of H. pylori in the crews of USN nuclear submarines compared to other military personnel and to the general US population. The presence of H. pylori IgG antibodies was determined in serum samples using a commercial ELISA. Only 47 out of 451 submariners (9·4%) were H. pylori positive, which is similar to that of the US general population with a similar level of education. In contrast, H. pylori prevalence is significantly higher in US Army recruits (26%), USN surface fleet personnel (25%), and German diesel submariners (38%). These data demonstrate that submarine service (and by inference activity requiring isolation and close contact, per se) is not a risk factor for H. pylori infection.
Asymptomatic enteric infections are important where sequelae or protection from subsequent illness is an outcome measure. The use of reverse transcription–polymerase chain reaction (RT–PCR) to identify asymptomatic enteric infections in a birth cohort followed for rotaviral infections in a south Indian urban slum is reported. Of 1191 non-diarrhoeal samples from 371 children collected in May–June 2003, 22 (1·9%) were positive by ELISA. A total of 147 (40·6%) of 362 samples tested by VP6 RT–PCR were positive. In those samples that could be typed, a high diversity of G types including G1, G2, G4, G8, G9 and G10, and a high proportion (34·4%) of mixed infections were detected. Noroviruses were identified in 6/28 (21·4%) samples tested. The identification of infections undetectable by conventional techniques indicates the importance of the use of sensitive diagnostic techniques in research studies. Asymptomatically infected children may also act as a source of infection for other susceptible hosts.
The spatial epidemiology of intestinal nematodes in Uganda was investigated using generalized additive models and geostatistical methods. The prevalence of Ascaris lumbricoides and Trichuris trichiura was unevenly distributed in the country with prevalence greatest in southwest Uganda whereas hookworm was more homogeneously distributed. A. lumbricoides and T. Trichiura prevalence were non-linearly related to satellite sensor-based estimates of land surface temperature; hookworm was non-linearly associated with rainfall. Semivariogram analysis indicated that T. trichiura prevalence exhibited no spatial structure and that A. lumbricoides exhibited some spatial dependency at small spatial distances, once large-scale, mainly environmental, trends had been removed. In contrast, there was much more spatial structure in hookworm prevalence although the underlying factors are at present unclear. The implications of the results are discussed in relation to parasite spatial epidemiology and the prediction of infection distributions.
intestinal nematodes; Ascaris lumbricoides; Trichuris trichiura; hookworm; geographical distribution; spatial analysis; Uganda
A total of 279 Vibrio anguillarum strains were serotyped and examined for plasmid content. Plasmids were subjected to digestion with restriction enzymes. Most strains belonged to serogroup O1 (39%) and O2 (16%). In total 164 strains (53%) carried plasmids. Of the O1 and O2 isolates, 92% and 30%, respectively, carried one or more plasmids. Restriction fragment length polymorphism (RFLP) analysis of plasmid DNA indicated that plasmids belonged to several groups. Each group seemed to be restricted to a single O-serovar. The largest group was the pJM1-like plasmids among most serovar O1 strains. Most of these plasmids were about 67 kb like the pJM1 plasmid, but various derivatives ranged from 26-77 kb. RFLP studies of the 67 kb plasmids revealed 17 different restriction patterns. Some patterns were dominant among European strains whereas others were dominant among North American strains. The results confirmed the applicability of O-serotyping together with plasmid profile and restriction analysis of plasmids for typing of V. anguillarum. They also indicated that plasmids among strains which belonged to the traditional fish pathogenic serogroups, O1 and O2, showed more homology than did strains from most other serogroups, that were usually non-pathogenic, environmental bacteria.