Stuart Paynter

Delay in the diagnosis of pulmonary tuberculosis, London, 1998-2000: analysis of surveillance data

Noted cases of tuberculosis each year have doubled in London since 1987. In 2000, 12.9 cases per 100 000 population in England and Wales were recorded compared with 40.3 cases in London.1 A delay in the diagnosis of tuberculosis increases the risk of poor clinical outcome—including death and transmission of tuberculosis. 2 3 Understanding which factors influence this delay is crucial for controlling tuberculosis. Only one small study has previously investigated delays in the diagnosis of pulmonary tuberculosis in the United Kingdom.4 Using surveillance data from London, we estimated the delays in diagnosis of tuberculosis and investigated the factors independently associated with delays. We analysed surveillance data collected by doctors (1999-2000) and an anonymised national survey (1998) for cases of tuberculosis in London from 1998 to 2000. We calculated the delay in …

Biodiversity and leptospirosis risk: a case of pathogen regulation?

Well balanced ecosystems have an essential role in disease regulation, and consequently their correct functioning is increasingly recognised as imperative for maintaining human health. Disruptions to ecosystems have been found to increase the risk of several diseases, including Hantavirus, Lyme disease, Ross River virus, malaria and Ciguatera fish poisoning. Leptospirosis is a globally important emerging zoonosis, caused by spirochaete bacteria, borne by many mammalian hosts, and also transmitted environmentally. We propose that leptospirosis incidence in humans is also linked to ecosystem disruption, and that reduced biodiversity (the diversity of species within an ecological community) may be associated with increased leptospirosis incidence. To investigate this hypothesis, the relationship between biodiversity levels of island nations and their annual leptospirosis incidence rates (adjusted for GDP per capita) was examined by linear correlation and regression. Supportive, statistically significant negative associations were obtained between leptospirosis incidence and (a) total number of species (r2=0.69, p<0.001) and (b) number of mammal species (r2=0.80, p<0.001) in univariate analysis. In multivariable analysis only the number of mammal species remained significantly associated (r2=0.81, p=0.007). An association between biodiversity and reduced leptospirosis risk, if supported by further research, would emphasise the importance of managing the emergence of leptospirosis (and other infectious diseases) at a broader, ecosystem level.

Outbreak of E. coli O157 infection in the south west of the UK: risks from streams crossing seaside beaches

In August 2004 seven cases of Escherichia coli O157 infection were identified in children on holiday in Cornwall, southwest England, all of whom had stayed at different sites in the area. Isolates from all seven cases were confirmed as E. coli serogroup O157 phage type 21/28. We carried out a case-control study among holidaymakers who visited the beach. A standardised questionnaire was administered by telephone to parents. They were asked where on the beach the children had played, whether they had had contact with the stream that flowed across the beach, and about their use of food outlets and sources of food eaten. Cases were more likely to have played in the stream than controls (OR [1.72- undefined]). The time spent in the stream by cases was twice spent there by controls. Cases and controls were equally exposed to other suspected risk factors. PFGE profiles for all the cases were indistinguishable. Increased numbers of coliforms were found in the stream prior to the outbreak. Cattle were found grazing upstream. We suggest that the vehicle of infection for an outbreak of acute gastrointestinal illness caused by E. coli O157 was a contaminated freshwater stream flowing across a seaside beach. The onset dates were consistent with a point source. Heavy rainfall in the days preceding the outbreak might have lead to faeces from the cattle potentially contaminated by E. coli O157 contaminating the stream, thereby leading to the outbreak. Control measures included fencing off the part of the stream in which children played, and putting up warning signs around the beach.

Humidity and respiratory virus transmission in tropical and temperate settings

Influenza and respiratory syncytial virus (RSV) are similarly structured viruses with similar environmental survival, but different routes of transmission. While RSV is transmitted predominantly by direct and indirect contact, influenza is also transmitted by aerosol. The cold, dry conditions of temperate winters appear to encourage the transmission of both viruses, by increasing influenza virus survival in aerosols, and increasing influenza and RSV survival on surfaces. In contrast, the hot, wet conditions of tropical rainy seasons appear to discourage aerosol transmission of influenza, by reducing the amount of influenza virus that is aerosolized, and probably also by reducing influenza survival in aerosol. The wet conditions of tropical rainy seasons may, however, encourage contact transmission of both viruses, by increasing the amount of virus that is deposited on surfaces, and by increasing virus survival in droplets on surfaces. This evidence suggests that the increased incidence of influenza and RSV in tropical rainy seasons may be due to increased contact transmission. This hypothesis is consistent with the observation that tropical rainy seasons appear to encourage the transmission of RSV more than influenza. More research is required to examine the environmental survival of respiratory viruses in the high humidity and temperature of the tropics.

Comparable outcomes for β-lactam/β-lactamase inhibitor combinations and carbapenems in definitive treatment of bloodstream infections caused by cefotaxime-resistant Escherichia coli or Klebsiella pneumoniae

BackgroundExtended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae are often susceptible in vitro to β-lactam/β-lactamase inhibitor (BLBLI) combination antibiotics, but their use has been limited by concerns of clinical inefficacy. We aimed to compare outcomes between patients treated with BLBLIs and carbapenems for bloodstream infection (BSI) caused by cefotaxime non-susceptible (likely ESBL- or AmpC β-lactamase-producing) Escherichia coli and Klebsiella pneumoniae.MethodsAll adult patients with a BSI caused by cefotaxime non-susceptible E. coli or K. pneumoniae were included from May 2012-May 2013. We compared outcomes between patients who had definitive monotherapy with a carbapenem to those who had definitive monotherapy with a BLBLI.ResultsThere were 92 BSIs that fulfilled the microbiological inclusion criteria. 79 (85.9%) were caused by E. coli and 13 (14.1%) by K. pneumoniae. Four out of 23 (17.4%) patients treated with carbapenem monotherapy and 2 out of 24 (8.3%) patients treated with BLBLI monotherapy died (adjusted HR for survival 0.91, 95% CI 0.13 to 6.28; p = 0.92). The time to resolution of systemic inflammatory response syndrome (SIRS) criteria did not vary between the treatment groups (adjusted HR 0.91, 95% CI 0.32 to 2.59; p = 0.97). The length of hospital admission post-positive blood culture was slightly longer in patients treated with BLBLIs (median duration 15 vs. 11 days), although this was not significant (adjusted HR 0.62; 95% CI 0.27 to 1.42; p = 0.26). There were no significant differences in subsequent isolation of carbapenem resistant organisms (4.3% vs. 4.2%, p = 1.0), C. difficile infection (13.0% vs. 8.3%, p = 0.67) or relapsed BSI (0% vs. 2%, p = 0.23).ConclusionsBLBLIs appear to have a similar efficacy to carbapenems in the treatment of cefotaxime-resistant E. coli and K. pneumoniae bloodstream infections. Directed therapy with a BLBLI, when susceptibility is proven, may represent an appropriate carbapenem-sparing option.

Using mathematical transmission modelling to investigate drivers of respiratory syncytial virus seasonality in children in the Philippines.

We used a mathematical transmission model to estimate when ecological drivers of respiratory syncytial virus (RSV) transmissibility would need to act in order to produce the observed seasonality of RSV in the Philippines. We estimated that a seasonal peak in transmissibility would need to occur approximately 51 days prior to the observed peak in RSV cases (range 49 to 67 days). We then compared this estimated seasonal pattern of transmissibility to the seasonal patterns of possible ecological drivers of transmissibility: rainfall, humidity and temperature patterns, nutritional status, and school holidays. The timing of the seasonal patterns of nutritional status and rainfall were both consistent with the estimated seasonal pattern of transmissibility and these are both plausible drivers of the seasonality of RSV in this setting.

Seasonal immune modulation in humans: Observed patterns and potential environmental drivers

INTRODUCTION Cyclical fluctuations in host immunity have been proposed as a driver of respiratory infection seasonality, however few studies have attempted to directly assess whether or not seasonal immune modulation occurs in humans. MATERIALS AND METHODS We reviewed studies assessing immune status at different times of the year, restricting our review to studies assessing any of the following three biomarkers: antibody responses following vaccination, delayed-type hypersensitivity responses following skin testing, and clinical responses following experimental infection. RESULTS After systematic review and critical appraisal of the literature, six separate studies were available for final discussion. These results indicate that human immunity does vary by season. In the tropical setting of West Africa, both cell mediated and humoral immune responses appear to be reduced in children during the rainy season. In the tropical setting of Bangladesh, cell mediated immune responses also appear to be reduced in children during the rainy season. In the temperate setting of Russia, resistance to influenza infection appears to be reduced in young adults during winter. CONCLUSIONS Seasonal variation in immunity appears to occur in humans, and it is plausible that this variation may contribute to the seasonality of respiratory infections. Further research to assess the extent of seasonal immune modulation is required. We outline a number of recommendations to minimise bias in future studies.

Sunshine, rainfall, humidity and child pneumonia in the tropics: time-series analyses.

Few studies have formally examined the relationship between meteorological factors and the incidence of child pneumonia in the tropics, despite the fact that most child pneumonia deaths occur there. We examined the association between four meteorological exposures (rainy days, sunshine, relative humidity, temperature) and the incidence of clinical pneumonia in young children in the Philippines using three time-series methods: correlation of seasonal patterns, distributed lag regression, and case-crossover. Lack of sunshine was most strongly associated with pneumonia in both lagged regression [overall relative risk over the following 60 days for a 1-h increase in sunshine per day was 0·67 (95% confidence interval (CI) 0·51-0·87)] and case-crossover analysis [odds ratio for a 1-h increase in mean daily sunshine 8-14 days earlier was 0·95 (95% CI 0·91-1·00)]. This association is well known in temperate settings but has not been noted previously in the tropics. Further research to assess causality is needed.

Malnutrition: a risk factor for severe respiratory syncytial virus infection and hospitalization

Background: Longitudinal information examining the effect of poor infant growth on respiratory syncytial virus (RSV) severity is limited. Children hospitalized with RSV lower respiratory infection represent those at the severe end of the disease spectrum. Methods: We followed up a cohort of 12,191 infants enrolled in a previous pneumococcal vaccine trial in Bohol, Philippines. Exposure measures were weight for age z-score at the first vaccination visit (median age 1.8 months) as well as the growth (the difference in weight for age z-score) between the first and third vaccination visits. The outcome was hospitalization with RSV lower respiratory infection. Results: Children with a weight for age z-score ⩽ −2 at their first vaccination visit had the highest rate of hospitalization with RSV lower respiratory infection, but this association was only evident in children whose mothers had >10 years of education (hazard ratio: 3.38; 95% confidence interval: 1.63–6.98). Children who had lower than median growth between their first and third vaccinations had a higher rate of RSV-associated hospitalization than those with growth above the median (hazard ratio: 1.34; 95% confidence interval: 1.02–1.76). Conclusions: Poor infant growth increases the risk for severe RSV infection leading to hospitalization.

Factors Influencing Acquisition of Burkholderia cepacia Complex Organisms in Patients with Cystic Fibrosis

ABSTRACT Burkholderia cepacia complex organisms are important transmissible pathogens found in cystic fibrosis (CF) patients. In recent years, the rates of cross-infection of epidemic strains have declined due to effective infection control efforts. However, cases of sporadic B. cepacia complex infection continue to occur in some centers. The acquisition pathways and clinical outcomes of sporadic B. cepacia complex infection are unclear. We sought to determine the patient clinical characteristics, outcomes, incidence, and genotypic relatedness for all cases of B. cepacia complex infection at two CF centers. We also sought to study the external conditions that influence the acquisition of infection. From 2001 to 2011, 67 individual organisms were cultured from the respiratory samples of 64 patients. Sixty-five percent of the patients were adults, in whom chronic infections were more common (68%) (P = 0.006). The incidence of B. cepacia complex infection increased by a mean of 12% (95% confidence interval [CI], 3 to 23%) per year. The rates of transplantation and death were similar in the incident cases who developed chronic infection compared to those in patients with chronic Pseudomonas aeruginosa infection. Multilocus sequence typing revealed 50 individual strains from 65 isolates. Overall, 85% of the patients were infected with unique strains, suggesting sporadic acquisition of infection. The yearly incidence of nonepidemic B. cepacia complex infection was positively correlated with the amount of rainfall in the two sites examined: subtropical Brisbane (r = 0.65, P = 0.031) and tropical Townsville (r = 0.82, P = 0.002). This study demonstrates that despite strict cohort segregation, new cases of unrelated B. cepacia complex infection continue to occur. These data also support an environmental origin of infection and suggest that climate conditions may be associated with the acquisition of B. cepacia complex infections.