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Triple therapy is commonly used for the treatment of Helicobacter pylori infection. We determined risk factors associated with its failure in compliant patients focusing on H. pylori density, virulence marker and 23S ribosomal RNA (rRNA) point mutations associated with clarithromycin resistance. H. pylori infection was diagnosed by 14C urea breath test (14C UBT) and rapid urease test or histology. Triple therapy with esomeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d. and clarithromycin 500 mg b.i.d. was prescribed for 10 days. 14C UBT was repeated 4 weeks after treatment. In total, 111 patients [69 (62%) males] with a mean age of 46±16 years were enrolled. The mean age of treatment failure was 39±14 years compared to 48±16 years with eradication (P=0·002). Treatment failure was associated with younger mean age, point mutations in the 23S rRNA gene of H. pylori and vacA s1a and m1 when associated with cagA negativity.
Faecal specimens of diarrhoea cases (n=2495, collected between November 2007 and October 2009) from Infectious Diseases and Beliaghata General (ID&BG) Hospital, Kolkata, India, were screened by RT–PCR using specific primers targeting region C of the capsid gene of noroviruses (NoVs) to determine the seasonal distribution and clinical characteristics of NoVs associated with diarrhoea. NoV infection was detected in 78 cases, mostly in children aged <2 years. In 22/78 positive cases, the virus was detected as the sole agent; others were as mixed infections with other enteric pathogens. Sequencing of NVGII strains showed clustering with GII.4 NoVs followed by GII.13 and GII.6 NoVs. Clinical characteristics of the diarrhoeic children and adults in Kolkata indicated that NoV infections were detected throughout the year and were associated with a mild degree of dehydration.
Despite the increasing burden of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, the risk factors are not well understood. We conducted a hypothesis-generating study using three parallel case-control studies to identify risk factors for CA-MRSA and community-associated methicillin-susceptible S. aureus (CA-MSSA) infections. In the multivariate model, antimicrobial use in the 1–6 months prior to culture was associated with CA-MRSA infection compared to CA-MSSA [adjusted odds ratio (aOR) 1·7, P=0·07] cases. Antimicrobial use 1–6 months prior to culture (aOR 1·8, P=0·04), history of boils (aOR 1·6, P=0·03), and having a household member who was a smoker (aOR 1·3, P=0·05) were associated with CA-MRSA compared to uninfected community controls. The finding of an increased risk of CA-MRSA infection associated with prior antimicrobial use highlights the importance of careful antimicrobial stewardship.
Information about the changing epidemiology of drug-resistant tuberculosis (TB) in hospitals in China over the past decade remains largely unknown. This study examined the susceptibility patterns and trends of drug-resistant TB cases in the 309 Hospital in Beijing, China. Mycobacterium tuberculosis isolates were retrospectively identified, drug susceptibility test (DST) results and clinical data were analysed for the period 1997–2009. Of the 5523 culture-positive TB patients, 47·1% had resistance to any anti-TB drug, 14·8% had mono-resistant TB, 19·8% had poly-resistant TB, 19·4% had multidrug-resistant TB (MDR-TB), and 1·3% had extensively drug-resistant TB (XDR-TB). Drug-resistant TB was significantly associated with age group, residential situation, and TB treatment history (P<0·001). During 1997–2000, the percentage of TB patients with any resistance, mono-resistant TB, poly-resistant TB, MDR-TB and XDR-TB all increased significantly (P<0·001). During 2000–2003, the increasing trends of MDR-TB and XDR-TB cases were reversed. During 2004–2009, the percentage of TB patients with any resistance, mono-resistant TB, poly-resistant TB, MDR-TB and XDR-TB all declined significantly (P<0·001), but the prevalence of MDR-TB and poly-resistant TB cases remained high. Our study provides evidence demonstrating that intensive TB control measures have helped reverse the increasing trends of drug-resistant TB in China, but continuous surveillance of drug-resistant TB and better case management are still needed to further reduce the remaining high prevalence of drug-resistant TB.
In 2008, a cow with marked gross lesions suspicious for bovine tuberculosis (bTB) was identified by meat inspection at home slaughtering in north-western Germany. Epidemiological investigations led to the identification of another 11 affected farms with a total of 135 animals which reacted positive to the skin test. Eight affected farms had been in trade contact with the putative index farm. While the source for the initial introduction remained unknown, it was shown that all isolates tested shared the same molecular characteristics suggesting a common source of infection. The findings demonstrate that bTB can easily be transmitted via animal trade and may remain undetected for years in herds in the absence of tuberculin testing. Hence, we believe that bTB surveillance should not rely only on meat inspection, but on a combination of both meat inspection and intradermal tuberculin testing.
Targets for maximum acceptable levels of Salmonella in pigs and pork are to be decided. A stochastic simulation model accounting for herd and abattoir information was used to evaluate food safety and economic consequences of different surveillance and control strategies, based among others on Danish surveillance data. An epidemiological module simulated the Salmonella carcass prevalence for different scenarios. Cost-effectiveness analysis was used to compare the costs of the different scenarios with their expected effectiveness. Herd interventions were not found sufficient to attain Salmonella carcass prevalence <1%. The cost-effectiveness of abattoir interventions changed with abattoir size. The most cost-effective strategy included the use of steam vacuum and steam ultrasound. Given uncertainty of the effect of steam vacuum and steam ultrasound, model results should be updated as more information becomes available. This framework contributes to informed decision-making for a more cost-effective surveillance and control of Salmonella in pigs and pork.
We retrospectively studied patients diagnosed with P. aeruginosa bloodstream infections (BSIs) in two Italian university hospitals. Risk factors for the isolation of multidrug-resistant (MDR) or non-MDR P. aeruginosa in blood cultures were identified by a case-case-control study, and a cohort study evaluated the clinical outcomes of such infections. We identified 106 patients with P. aeruginosa BSI over the 2-year study period; 40 cases with MDR P. aeruginosa and 66 cases with non-MDR P. aeruginosa were compared to 212 controls. Independent risk factors for the isolation of MDR P. aeruginosa were: presence of central venous catheter (CVC), previous antibiotic therapy, and corticosteroid therapy. Independent risk factors for non-MDR P. aeruginosa were: previous BSI, neutrophil count <500/mm3, urinary catheterization, and presence of CVC. The 21-day mortality rate of all patients was 33·9%. The variables independently associated with 21-day mortality were presentation with septic shock, infection due to MDR P. aeruginosa, and inadequate initial antimicrobial therapy.
Following an outbreak of vanA-positive Enterococcus faecium in 2005 in Kyoto prefecture, regional surveillance of vancomycin-resistant enterococci (VRE) was initiated. This revealed vanA- or vanB-positive Enterococcus gallinarum in multiple facilities. Eighty-eight vanA-positive E. gallinarum faecal carriers from 12 facilities and ten vanB-positive E. gallinarum faecal carriers from eight facilities were found. Pulsed-field gel electrophoresis profiles of the first isolate from each facility showed that 11 of the 12 vanA isolates and three of the eight vanB-positive E. gallinarum isolates belonged to a single clone. This study confirms the clonal spread of vanA- or vanB-positive E. gallinarum in a region and underlines the importance of surveillance of VRE for the presence of vancomycin resistance determinants.
In 2005, over 600 clinically diagnosed typhoid fever cases occurred in South Africa, where an outbreak had been previously described in 1993. Case-control and molecular investigations, including Salmonella enterica serovar Typhi (S. Typhi) isolates from that area from 1993, 2005 and later, were undertaken. Controls were significantly older than cases (P=0·003), possibly due to immunity from previous infection, and a significantly larger proportion had attended a gathering (P=0·035). Exposure to commercial food outlets and person-to-person transmission was not significant. Pulsed-field gel electrophoresis and multi-locus tandem repeat analysis revealed common clusters of S. Typhi strains identified in 1993 and 2005 as well as in 2007 and 2009. This outbreak probably occurred in a non-immune population due to faecally contaminated water. S. Typhi strains appeared to be related to strains from 1993; failure to address unsafe water may lead to further outbreaks in the area if the current population immunity wanes or is lost.
The role of domestic dogs in the long-distance spread of bluetongue virus (BTV) remains unproven. It is currently known that dogs are capable of being infected with BTV, can mount an antibody response to the virus and in some cases die showing severe clinical signs of disease. Infection of dogs is currently thought to be by oral ingestion of infected meat or meat products rather than through vector feeding. In this study we show that a high percentage of domestic dogs in Morocco (21%) were seropositive for BTV and, as these dogs were fed tinned commercial food only, and had no access to other meat products, the most likely source of infection was through Culicoides midges. This finding increases the chances of dogs being infected with BTV during an outbreak but their role in the onward transmission of BTV remains unproven.
A survey of 788 pigs from 120 farms was conducted to determine the within-farm prevalence of pathogenic Yersinia enterocolitica and a questionnaire of management conditions was mailed to the farms afterwards. A univariate statistical analysis with carriage and shedding as outcomes was conducted with random-effects logistic regression with farm as a clustering factor. Variables with a P value <0·15 were included into the respective multivariate random-effects logistic regression model. The use of municipal water was discovered to be a protective factor against carriage and faecal shedding of the pathogen. Organic production and buying feed from a certain feed manufacturer were also protective against total carriage. Tonsillar carriage, a different feed manufacturer, fasting pigs before transport to the slaughterhouse, higher-level farm health classification, and snout contacts between pigs were risk factors for faecal shedding. We concluded that differences in management can explain different prevalences of Y. enterocolitica between farms.
Measles vaccine efficacy is higher at 12 months than 9 months because of maternal immunity, but delaying vaccination exposes the children most vulnerable to measles mortality to infection. We explored how this trade-off changes as a function of regionally varying epidemiological drivers, e.g. demography, transmission seasonality, and vaccination coverage. High birth rates and low coverage both favour early vaccination, and initiating vaccination at 9–11 months, then switching to 12–14 months can reduce case numbers. Overall however, increasing the age-window of vaccination decreases case numbers relative to vaccinating within a narrow age-window (e.g. 9–11 months). The width of the age-window that minimizes mortality varies as a function of birth rate, vaccination coverage and patterns of access to care. Our results suggest that locally age-targeted strategies, at both national and sub-national scales, tuned to local variation in birth rate, seasonality, and access to care may substantially decrease case numbers and fatalities for routine vaccination.
Acute diarrhoea remains a major public health challenge in developing countries. We examined the role of a probiotic in the prevention of acute diarrhoea to discover if there was an effect directed towards a specific aetiology. A double-blind, randomized, controlled field trial involving 3758 children aged 1–5 years was conducted in an urban slum community in Kolkata, India. Participants were given either a probiotic drink containing Lactobacillus casei strain Shirota or a nutrient drink daily for 12 weeks. They were followed up for another 12 weeks. The primary outcome of this study was the occurrence of first episodes of diarrhoea. We assessed this during 12 weeks of intake of study agent and also for 12 weeks of follow-up. There were 608 subjects with diarrhoea in the probiotic group and 674 subjects in the nutrient group during the study period of 24 weeks. The level of protective efficacy for the probiotic was 14% (95% confidence interval 4–23, P<0·01 in adjusted model). The reduced occurrence of acute diarrhoea in the probiotic group compared to nutrient group was not associated with any specific aetiology. No adverse event was observed in children of either probiotic or nutrient groups. The study suggests that daily intake of a probiotic drink can play a role in prevention of acute diarrhoea in young children in a community setting of a developing country.
The study's objectives were to determine herd- and animal-level prevalence and herd-level risk factors for Salmonella in dairy-bred veal calves at slaughter in Denmark. In total, 1296 faecal samples were collected at five cattle abattoirs in Denmark during 2007–2008. The animals came from 71 randomly selected specialized veal-calf producers that delivered more than 100 animals to slaughter per year. Salmonella Dublin bacteria were isolated from 19 samples from 12 herds and Salmonella Typhimurium was isolated from one sample. The apparent prevalence of herds delivering Salmonella-shedding animals to slaughter was 18% (95% CI 9–27). The overall estimated true prevalence of shedding calves at slaughter was 1·3%. Veal-calf herds that purchased animals from herds not classified as low risk in the Danish Salmonella surveillance programme had significantly (P=0·03) higher risk of delivering Salmonella-shedding calves to slaughter. The results emphasize the importance of efforts in the dairy industry to ensure food safety for consumers.
The occurrence of a gastrointestinal illness among a class of 96 undergraduate veterinary students in New Zealand prompted laboratory and questionnaire-based investigations. Cryptosporidium parvum was the only enteropathogen identified in 4/7 faecal specimens analysed. The C. parvum isolates carried a rare IIa GP60 allele, indicating a point-source outbreak. The infection source could not be microbiologically traced, but the investigation suggested contact with calves during a practical class as the most likely exposure. A total of 25/80 respondents to a questionnaire were defined as cases using a clinical case definition (31% attack rate). The inferred median incubation period was 5 days (range 0–11 days), and the median illness duration was 5–6 days (range 2–23 days), corroborating previous observations in experimental cryptosporidiosis. Disease was self-limiting, characterized by abdominal discomfort, diarrhoea, and in some cases, vomiting. Originating from a rural area and having had previously handled ruminants were associated with a significant risk reduction in males. All the three students who reported chronic use of steroid inhalers for treatment of asthma were cases. This case highlighted, once again, the potential hazard for explosive outbreaks of cryptosporidiosis.
This study characterized the current epidemiology of vibrio infections in Florida and examined cases reported from 1998 to 2007. Logistic regression was used to determine risk of death. There were 834 vibrio infections in 825 individuals (average annual incidence rate 4·8/1 000 000). Common Vibrio species reported were Vibrio vulnificus (33%), V. parahaemolyticus (29%), and V. alginolyticus (16%). Most exposures were attributed to wounds (42%), and the most common clinical syndromes were wound infections (45%) and gastroenteritis (42%). Almost half of individuals reported an underlying health condition. Risk of death was associated with any underlying condition and increased with the number of conditions (P<0·0001). In Florida, incidence of vibriosis associated with raw oyster consumption has decreased while incidence associated with wound infections has increased. Most prevention efforts to date have focused on oyster consumption. New educational messages focusing on the risk of vibriosis from wound infections should target high-risk populations.
Listeriosis is a foodborne disease associated with significant mortality. This study attempts to identify risk factors for sporadic listeriosis in Australia. Information on underlying illnesses was obtained from cases' treating doctors and other risk factors were elicited from the patient or a surrogate. We attempted to recruit two controls per case matched on age and primary underlying immune condition. Between November 2001 and December 2004 we recruited 136 cases and 97 controls. Of perinatal cases, living in a household where a language other than English was spoken was the main risk factor associated with listeriosis (OR 11·3, 95% CI 1·5–undefined). Of non-perinatal cases we identified the following risk factors for listeriosis: prior hospitalization (OR 4·3, 95% CI 1·0–18·3), use of gastric acid inhibitors (OR 9·4, 95% CI 2·4–37·4), and consumption of camembert (OR 4·7, 95% CI 1·1–20·6). Forty percent of cases with prior hospitalization were exposed to high-risk foods during hospitalization.
Noroviruses are an important aetiological agent of acute gastroenteritis. They are responsible for large outbreaks of disease in the community, hospitals and long-term-care facilities. The clinical manifestations of norovirus outbreaks in psychiatric units are rarely described. The disease burden and impact highlight the importance of timely notification and investigation of these outbreaks. We analysed the characteristics of four norovirus outbreaks which occurred during a 3-year period in an in-patient psychiatric care unit. A total of 184 patients were affected which included 172 hospitalized patients, seven healthcare workers (HCWs) and five psychiatric nursing-home residents. The mean incidence rate of norovirus gastroenteritis (NVG) in hospitalized patients during these outbreaks was 12·7%. These outbreaks were characterized by higher incidence in middle-aged male patients, predominant sickness of diarrhoea, short duration of illness, peaks in late winter and early spring, and higher susceptibility in acute psychiatric patients. HCWs had longer duration of illness than psychiatric patients. More than 10% of affected patients experienced ⩾2 infections. Infection control measures were instituted and a comprehensive, responsive standard operating procedure for NVG and outbreak management was developed. After implementation of these measures, no further outbreaks of NVG occurred during the study period.
Referral bias can influence the results of studies performed at tertiary-care centres. In this study, we evaluated demographic and microbiological 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 January 1998 and 31 December 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 microbiological 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 centres.
Understanding local perceptions of disease causation could help public health officials improve strategies to prevent bloody diarrhoea. A cross-sectional survey was conducted in Dhaka, Bangladesh to elicit community beliefs about the causes of and prevention strategies for bloody diarrhoea. Between March and June 2003, we interviewed 541 randomly selected respondents. Overall, 507 (93%) respondents perceived that a vaccine could prevent bloody diarrhoea. If a vaccine provided lifetime protection, 445 (83%) respondents stated that they would opt to get the vaccine and would pay a median of $0·05 (range U.S.$0·01–0·15) for it, equivalent to <1% of their median weekly income. There was almost universal perception that an effective vaccine to prevent bloody diarrhoea was highly beneficial and acceptable. While respondents valued a vaccine for prevention of bloody diarrhoea, they were only willing to pay minimally for it. Therefore, achieving a high rate of Shigella vaccine coverage may require subsidy of vaccine purchase.