A Bayesian MCMC approach to study transmission of influenza: application to household longitudinal data

We propose a transmission model to estimate the main characteristics of influenza transmission in households. The model details the risks of infection in the household and in the community at the individual scale. Heterogeneity among subjects is investigated considering both individual susceptibility and infectiousness. The model was applied to a data set consisting of the follow-up of influenza symptoms in 334 households during 15 days after an index case visited a general practitioner with virologically confirmed influenza.Estimating the parameters of the transmission model was challenging because a large part of the infectious process was not observed: only the dates when new cases were detected were observed. For each case, the data were augmented with the unobserved dates of the start and the end of the infectious period. The transmission model was included in a 3-levels hierarchical structure: (i) the observation level ensured that the augmented data were consistent with the observed data, (ii) the transmission level described the underlying epidemic process, (iii) the prior level specified the distribution of the parameters. From a Bayesian perspective, the joint posterior distribution of model parameters and augmented data was explored by Markov chain Monte Carlo (MCMC) sampling.The mean duration of influenza infectious period was estimated at 3.8 days (95 per cent credible interval, 95 per cent CI [3.1,4.6]) with a standard deviation of 2.0 days (95 per cent CI [1.1,2.8]). The instantaneous risk of influenza transmission between an infective and a susceptible within a household was found to decrease with the size of the household, and established at 0.32 person day(-1) (95 per cent CI [0.26,0.39]); the instantaneous risk of infection from the community was 0.0056 day(-1) (95 per cent CI [0.0029,0.0087]). Focusing on the differences in transmission between children (less than 15 years old) and adults, we estimated that the former were more likely to transmit than adults (posterior probability larger than 99 per cent), but that the mean duration of the infectious period was similar in children (3.6 days, 95 per cent CI [2.3,5.2]) and adults (3.9 days, 95 per cent CI [3.2,4.9]). The posterior probability that children had a larger community risk was 76 per cent and the posterior probability that they were more susceptible than adults was 79 per cent.     

A longitudinal study of natural infection of piglets with Streptococcus suis types 1 and 2

Streptococcus suis types 1 and 2 were detected in nasal swabs taken from five litters of piglets sampled twice weekly from birth. The two types had been detected in all pigs by the time they were 38 and 25 days old respectively with mean ages of first detectable infection being 13.5 and 8.5 days. The prevalence of infection was not affected by housing conditions or the population density of pigs. Piglets originating from a sow with vaginal swabs positive for S. suis type 2 were infected earlier than piglets from non-vaginal carriers. It is concluded that infection of piglets with S. suis type 2 may occur during the birth process.     

Use of stochastic epidemic modeling to quantify transmission rates of colonization with methicillin-resistant Staphylococcus aureus in an intensive care unit.

OBJECTIVE: To consider statistical methods for estimating transmission rates for colonization of patients with methicillin-resistant Staphylococcus aureus (MRSA) in an intensive care unit (ICU) from three different sources: background contamination, non-isolated patients, and isolated patients. METHODS: We developed statistical methods that allowed for the analysis of interval-censored, routine surveillance data and extended the general epidemic model for the flow of patients through the ICU. RESULTS: Within this ICU, the rate of transmission to susceptible patients from a background source of MRSA (0.0092 case per day; 95% confidence interval [CI95], 0.0062-0.0126) is approximately double the rate of transmission from a non-isolated patient (0.0052 case per day; CI95, 0.0013-0.0096) and six times the rate of transmission from an isolated patient (0.0015 case per day; CI95, 0.0001-0.0043). We used the methodology to investigate whether transmission rates vary with workload. CONCLUSION: Our methodology has general application to infection by and transmission of pathogens in a hospital setting and is appropriate for quantifying the effect of infection control interventions.     

Experimental colonization of pigs with methicillin-resistant Staphylococcus aureus (MRSA): insights into the colonization and transmission of livestock-associated MRSA

Two models were used for colonizing pigs under experimental conditions. In the first model, six 5-week old piglets were challenged by nasal and gastrointestinal inoculation with a mixture of four strains representing the most prevalent methicillin-resistant Staphylococcus aureus (MRSA) sequence types (ST398, ST9) and spa types (t08, t011, t034, t899) associated with pig farming. In the second model, the vagina of a pregnant sow was inoculated with the same MRSA mixture shortly before farrowing. While MRSA carriage was unstable following nasal-gastrointestinal inoculation of piglets, vaginal inoculation of the sow resulted in persistent carriage of t011-ST398 and t899-ST9 in all newborn piglets. The results from the two models provide evidence that livestock-associated MRSA can efficiently spread by vertical perinatal transmission and that direct colonization of weaned piglets is hampered by unknown host, bacterial or environmental factors. The vaginal inoculation model described in this study represents a useful tool for studying MRSA-host interactions in pigs having the same genetic background.     

Methicillin-resistant Staphylococcus aureus infection and colonization among hospitalized prisoners.

We assessed methicillin-resistant Staphylococcus aureus (MRSA) infection and colonization in hospitalized prisoners. Of 434 admission surveillance cultures, 58 (13%) were positive for MRSA. The sensitivity of admission surveillance cultures of samples from the anterior nares was 72% and increased to 84% when the calculation included cultures of wound samples. Hospitalized prisoners are at high risk for MRSA infection and colonization, and surveillance should include cultures of nares and wound samples.     

Nosocomial transmission of methicillin-resistant Staphylococcus aureus: a blinded study to establish baseline acquisition rates.

OBJECTIVE: To define the extent of nosocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA) in patients admitted to a tertiary-care hospital. DESIGN: A blinded, prospective surveillance culture study of patients admitted to the hospital to determine the transmission (acquisition) rate of MRSA. Risk factors associated with the likelihood of MRSA colonization on admission were investigated. SETTING: Tertiary-care military medical facility. PARTICIPANTS: All patients admitted to the medicine, surgery, and pediatric wards, and to the medical, surgical, and pediatric intensive care units were eligible for inclusion. RESULTS: Five hundred thirty-five admission and 374 discharge samples were collected during the study period. One hundred forty-one patients were colonized with methicillin-susceptible S. aureus (MSSA) and 20 patients (3.7%) were colonized with MRSA on admission. Of the 354 susceptible patients, 6 acquired MRSA during the study for a transmission rate of 1.7%. Patients colonized with MRSA on admission were more likely to be older than non-colonized or MSSA-colonized patients, to have received antibiotics within the past year, to have been hospitalized within the prior 3 years, or to have a known history of MRSA. Patients acquiring MRSA had an average hospital stay of 17.7 days compared with 5.3 days for those who did not acquire MRSA. Pulsed-field gel electrophoresis of the 6 MRSA isolates from patients who acquired MRSA revealed 4 distinct band patterns. CONCLUSIONS: Most patients colonized with MRSA were identified on admission samples. Surveillance cultures of patients admitted may help to prevent MRSA transmission and infection.     

Treatment of infection and colonization caused by methicillin-resistant Staphylococcus aureus.

The mechanism of methicillin resistance confers resistance to all available beta-lactam antibiotics; consequently, beta-lactam antibiotics have no role in therapy of methicillin-resistant Staphylococcus aureus (MRSA) infections. Vancomycin remains the drug of choice. Teicoplanin and daptomycin are two investigational antibiotics related to vancomycin in structure and in spectrum of activity. In clinical trials employing relatively low doses, neither was as effective as vancomycin. Trials at higher doses are on-going. Quinolones, ciprofloxacin in particular, have been used successfully to treat infections caused by MRSA; however, the usefulness of quinolones may be limited by the tendency of resistance to emerge during therapy. Quinolones probably should be used only in combination with another active agent, such as rifampin, when treating serious infections caused by MRSA. Other agents may be active in vitro against MRSA, but clinical data showing their effectiveness are lacking. Rifampin combination regimens appear most effectively to eradicate colonization with MRSA.     

Estimation of methicillin-resistant Staphylococcus aureus transmission by considering colonization pressure at the time of hospital admission

Our objective was to evaluate the accuracy of a methicillin-resistant Staphylococcus aureus (MRSA) rate using the imported MRSA reservoir identified at the time of hospital admission. Two indicators were used: the number of imported MRSA patient-days/total number of patient-days [representing colonization pressure (CP) at the time of admission] and the incidence of hospital-acquired MRSA isolated from clinical samples expressed as density/100 patient-days for carriers identified at the time of admission [representing the incidence taking CP into account (ICP)]. The variations of these indicators were analysed and compared with two more common indicators: percentage of MRSA acquired in our hospital and the incidence of hospital-acquired MRSA isolated from clinical samples expressed as density/1000 patient-days within three four-month periods during 2002. Common indicators varied similarly, with marked decline during the third period; first-period CP was twice that of other periods (P<10(-6)) and the highest (>two-fold) ICP was seen in the summer (second) period (P<0.001) when the personnel/patient ratio was the lowest. Thus, comparison of different indicators within four-month periods underlines important differences between common and novel indicators. Despite several limitations, ICP should be helpful in the interpretation of MRSA surveillance data, particularly for estimating the extent of MRSA transmission.     

Methicillin-resistant Staphylococcus aureus colonization in nursing home residents: a prevalence study in Northamptonshire.

A prevalence study of methicillin-resistant Staphylococcus aureus (MRSA) colonization was carried out in 17 nursing homes in Northamptonshire over a 20-month period. Thirteen of 275 residents swabbed (4.7%) were found to be colonized and six of the 17 homes (35%) had colonized residents. Only two homes had more than one colonized resident. Individual risk factors for colonization were gender (male) and the presence of skin ulcers and sores. There were no significant risk factors identified for homes. Spread may have occurred in the two homes which had more than one colonized resident. Both these homes had the epidemic strain EMRSA-15 whereas three of the four homes with a single colonized resident had EMRSA-16. It is suggested that homes with residents colonized with EMRSA-16 may be able to prevent spread by adherence to good infection control procedures but that this may not be adequate to prevent spread of EMRSA-15.     

Personality scores and smoking behaviour. A longitudinal study.

The personality scores at 16 years of age of 2753 people, all members of the National Survey of Health and Development, were related, in a follow-up study, to cigarette smoking behaviour in their young adult years. Survey members who recorded high neuroticism scores were found to be more likely to smoke than those with low scores and, among the smokers, deep inhalers formed the most neurotic group. Extraverts were more likely to smoke than introverts, the mean extraversion score being greatest for the male smokers with a high daily consumption of cigarettes. The personality scores were found to have some power in predicting changes in smoking behaviour. Neurotics and extraverts who had not started to smoke by the time of completing the personality inventory at 16 were more likely than the stable and introverted to take up the habit subsequently. Among survey members who were regular smokers at the time of completing the personality inventory the proportion giving up smoking by the time they reached the age of 25 years was related to consumption level recorded at 20 years and the personality scores recorded at 16, stable extraverts among the men being most likely to stop smoking.     

Staphylococcus aureus colonization of the newborn in a Darlington hospital.

Evidence from research studies suggests a relationship between neonatal infection with Staphylococcus aureus and the level of umbilical colonization. During a 3-month prospective study (September-December 1990) the incidence and levels of S. aureus colonization were determined for all 370 live births in the Darlington Unit by taking swabs at 48 h and 8/9 days from the base of the umbilical cord. Infants were situated in one of four locations (The Special Care Unit, one of two wards or home) and the location at the time of swabbing was recorded. The overall percentages colonized at 48 h and 8/9 d were 68% and 65% respectively. Forty-eight hours after delivery, 49% showed a high level of S. aureus colonization. Although the percentage of infants colonized with S. aureus was almost identical at each sampling, only 62% were culture-positive on both occasions. Between 48 h and 8/9 days, 12% (44) of infants developed S. aureus infections of whom 35 showed heavy growth. Statistical analysis showed a significant relationship between levels of colonization at the two sampling times but no relationship between location and levels of colonization over the time period.     

A longitudinal study of adolescent transition from virgin to nonvirgin status.

PURPOSE: To identify demographic and psychosocial predictors for early sexual initiation (ESI) among middle school midwestern suburban and rural youth. METHODS: A total of 884 middle school students completed a pretest and a 1-year follow-up questionnaire. At Time 1, 52 students reported already having initiated sexual behavior; the remaining 832 students were included in our analyses. The sample was 58.5% female and 92.8% white, with a mean age of 12.84 years. At Time 2, 105 students (12.6%) had changed their coital status from virgin to nonvirgin. A stepwise logistic regression was conducted to explore the relationship between the demographic and psychosocial variables measured at Time 1 (including grade, academic performance, mother's education, family structure, religiosity, self-esteem [school, home, and peer], perceived sexual norms, abstinence self-efficacy, peer pressure, etc.) and reported sexual behavior at Time 2. The analyses were conducted separately by gender. RESULTS: For both genders, academic achievement was positively related and peer self-esteem was negatively related to ESI. In addition, self-efficacy and frequency of prayer were negatively related to ESI for boys, and peer pressure, age, and traditional family structure were negatively related to ESI for girls. CONCLUSIONS: Risk and protective factors for ESI should be examined separately by gender. Use of a facet-specific measure of self-esteem revealed very different relationships among the peer, home, and school aspects of self-esteem and transition to nonvirgin status; therefore, researchers are encouraged to use area-specific rather than global measures of self-esteem.     

A longitudinal study of military performance subsequent to civilian drug use.

This study evaluates the military performance of soldiers who were identified by the Army's urine screening program as having used drugs at the time they reported for active duty. The study used prospectively defined cohorts of large size (over 1,600 urinalysis positive and over 2,400 urinalysis negative entering males) and used longitudinal outcome measures drawn from existing medical and personnel files. The major findings are that the urinalysis positive individuals were significantly more likely not to complete their tour of duty, were more likely to be hospitalized, and had more bed-days per hospitalization than their urinalysis negative fellow soldiers. In terms of cohorts entering the Army, however, minimal improvement in outcome was found by considering an entirely drug-free cohort (obtained by omitting the urinalysis positive individuals) compared to a random cohort which contained positives at the then current prevalence of 2 per cent.     

The development of polypharmacy. A longitudinal study

BACKGROUND: To date, only a few studies have been carried out on the development and progress of polypharmacy in relation to morbidity in general practices in The Netherlands. OBJECTIVE: The aim of this study was to investigate the relationship between an increase in long-term drug use and the incidence and severity of some chronic diseases, particularly in the elderly. METHODS: Data on medication and morbidity of 1544 elderly people were collected for the period 1994-1997 from three family practices in the medication and morbidity Registration Network of Groningen (RNG) in the northern part of The Netherlands. Polypharmacy is defined as the long-term simultaneous use of two or more drugs; long-term is defined as >240 days in a year. We looked for differences in incidences of some chronic diseases in those subgroups of the elderly in whom multiple long-term drug use respectively increased, stayed constant or did not exist. Polypharmacy at the end of the period was predicted using regression analysis. RESULTS: Polypharmacy occurred in 42% of the elderly at the end of 1997, with major polypharmacy (>5 drugs) in only 4%. The average number of drugs used long-term increased from 1.3 to 1.8 in 4 years. Predictors for the increase of polypharmacy were the number of drugs at the start, age, diabetes, coronary ischaemic diseases and use of medication without a clear indication (P < 0.005). The average number of diseases also increased, especially in the elderly who showed the greatest increase in long-term drug use; however, there was no significant difference from the groups with a slow or no increase in drug use. DISCUSSION: Polypharmacy showed a slow increase over 4 years: almost 20% of the elderly developed polypharmacy, i.e. going from no drugs or one drug to two or more drugs. Polypharmacy develops mainly in elderly patients who already use several drugs, who are known to suffer from cardiovascular diseases, diabetes or stomach symptoms, those who often take drugs (especially sedatives/hypnotics) without clear indication and those who develop hypertension or atrial fibrillation over time.     

Neighborhood design and walking. A quasi-experimental longitudinal study

BACKGROUND: Few studies have employed longitudinal data to examine associations between the physical environment and walking. METHODS: Using cross-sectional (n=70) and longitudinal (n=32) data (collected 2003-2006), associations of neighborhood design and demographics with walking were examined. Participants were low-income, primarily African-American women in the southeastern U.S. Through a natural experiment, some women relocated to neo-traditional communities (experimental group) and others moved to conventional suburban neighborhoods (control group). RESULTS: Post-move cross-sectional comparisons indicated that women in neo-traditional neighborhoods did not, on average, walk more than women in suburban neighborhoods. Race and household size were significant predictors of physical activity. Additionally, using longitudinal data, this study controlled for the effects of pre-move walking and demographics. Analyses examined the effects of environmental factors (e.g., density, land-use mix, street-network patterns) on post-move walking. Women who moved to places with fewer culs-de-sac, on average, walked more. Unexpectedly, increases in land-use mix were associated with less walking. CONCLUSIONS: Results suggest that neo-traditional neighborhood features alone (e.g., sidewalks, front porches, small set-back distances) may not be enough to affect walking; however, changes in street patterns may play a role.     

Staphylococcus aureus colonization and the risk of infection in critically ill patients.

OBJECTIVE: To evaluate the relationship between Staphylococcus aureus nasal and tracheal colonization and infection in medical intensive care unit (MICU) patients. The primary outcome was the incidence of S. aureus infection in colonized versus non-colonized patients. DESIGN: Prospective, observational cohort study. Patients admitted to the MICU during the study period were screened for S. aureus nasal and tracheal colonization by culture and a PCR assay twice weekly. Demographic, clinical, and microbiologic data were collected in the MICU and for 30 days after discharge. PFGE and antibiotic susceptibility testing were performed on all S. aureus nasal, tracheal, and clinical isolates. RESULTS: Twenty-three percent of patients (47 of 208) were nasally colonized with S. aureus. Twenty-four percent of these patients developed S. aureus infections versus 2% of non-colonized patients (P < .01). Nine of 11 patients with both nasal colonization and infection were infected by their colonizing strain. Two of 47 nasally colonized patients developed an infection with a different strain of S. aureus. Fifty-three percent of intubated patients with nasal colonization (10 of 19) had tracheal colonization with S. aureus as opposed to 4.9% of intubated, non-colonized patients (3 of 61) (P < .01). Parenteral antibiotics were ineffective at clearing nasal colonization. PCR detected S. aureus colonization (nasal and tracheal) within 6.5 hours with a sensitivity of 83% and a specificity of 99%. CONCLUSIONS: The incidence of S. aureus infection was significantly elevated in nasally colonized MICU patients. Techniques to rapidly detect colonization in this population may make targeted topical prevention strategies feasible.     

Evolution of Staphylococcus aureus during human colonization and infection

The diversification of bacterial pathogens during infection is central to their capacity to adapt to different anatomical niches, evade the host immune system, and overcome therapeutic challenges. For example, antimicrobial treatment may fail due to the development of resistance during infection, which is often accompanied by transition to a less virulent state during chronic, persistent infection. In this review, the adaptation of the major human pathogen Staphylococcus aureus to its host environment during infection will be discussed, particularly in the context of new sequencing technologies which have opened a gateway towards understanding of the molecular processes underlying those adaptations. We now have the capacity to address previously intractable questions regarding bacterial diversification during infection which will ultimately lead to enhanced understanding of pathogenesis and the nature of epidemics, and will inform the design of effective therapeutic measures.     

A longitudinal analysis of methicillin-resistant Staphylococcus aureus in a Hong Kong teaching hospital.

OBJECTIVES: To review the incidence and trends of MRSA during a 12-year (1989-2000) period at a university teaching hospital and the relationship between strain distribution by antibiogram and molecular typing. DESIGN: Retrospective review of laboratory-based surveillance records on MRSA isolation and characterization of strains by antimicrobial susceptibility and PFGE. A patient episode was counted at the time when MRSA was first isolated. SETTING: A 1,350-bed university teaching hospital in Hong Kong. PATIENTS: Those with clinical isolates of MRSA. RESULTS: During 1989 to 2000, the hospital recorded 1,203,175 deaths and discharges (D&D) and encountered 5,707 patient episodes of new MRSA isolation. The overall incidence of patient episodes of MRSA was 0.47/100 D&D. In 1989, the incidence was 0.81/100 D&D and fell to a low of 0.33/100 D&D in 1995, but then rose to 0.50/100 D&D in 2000. Antibiogram and DNA typing identified 5 major types. PFGE type A constituted 68% (211/312) of isolates and was present throughout the 12-year period. PFGE type B constituted 13% (40/312) of isolates and was only present from 1995 to 2000. These isolates form a distinct clone and had unique antibiotic resistance profiles. CONCLUSIONS: The study showed the establishment of a dominant MRSA clone (PFGE type A group) in the intensive care, medical, and surgical units and the appearance of a new MRSA strain in 1995 (PFGE type B), which partly explained the rise in incidence of MRSA cases and a disproportionate rise in MRSA bacteremia from 1995 to 2000.     

The utility of polysporin ointment in the eradication of methicillin-resistant Staphylococcus aureus colonization: a pilot study.

We evaluated the efficacy of an ointment containing bacitracin, polymyxin B, and gramicidin for the eradication of colonization by methicillin-resistant Staphylococcus aureus in 11 medical patients, 10 (91%) of whom had previously failed a 1-week course of topical mupirocin. Mupirocin resistance was documented in 5 (45%) of 11 patients. Successful decolonization was achieved in 9 (82%) of 11 patients (based on 2 months of follow-up).