Epidemiology & Infection - Latest issue

Leprosy is a granulomatous disease, infectious and transmissible, which affects the skin and peripheral nerves, having Mycobacterium leprae as causative agent. The manifestation of this disease causes cutaneous lesions, peripheral neuropathies and, in more extreme cases, may generate deformities and disabilities in affected individuals. Patents were identified using the descriptor ‘leprosy’ and code A61K of the international patent classification, which indicates only products that meet human needs. The analysis was made using the WIPO, ESPACENET and USPTO databases, until the month of September 2016. Through this review, we found a variety of in vitro, pre-clinical and clinical studies relating to the treatment of leprosy with different types of compounds and forms of administration. New treatment proposals should include pain reduction capabilities, prevention or limitation of the appearance of cutaneous lesions, as well as prevention of the progression of the disease to more severe stages that may lead to loss of function or potentiate the individual's immune response to the M. leprae bacillus in order to prevent bacterial spread. We concluded that any patents developed with natural products were not found in the treatment of leprosy. All the deposited products were synthetic origin, mostly tested in humans and of varied forms of administration.

Leprosy still represents a serious health problem in a number of countries, including Brazil. Although leprosy has been associated with poverty for a long time, it is still difficult to accurately define this relationship. Here, we evaluated in an endemic municipality the progress from 1995 to 2015 of epidemiological indicators to establish if there were any strong associations between social indicators and the occurrence of leprosy. An ecological study was conducted using the SINAN database (Brazilian leprosy-national notifiable diseases information system) in combination with georeferencing of leprosy cases. The georeferencing used the ArcGis programme and occurrence of cases was evaluated in relation to the Health Vulnerability Index (HVI), an indicator that categorises socio-economic and sanitation factors. The data identified a marked decrease in the overall prevalence of leprosy, a reduction in the new case-detection rate and a reduction in the number of cases with grade 2 disabilities (albeit with transient peaks in 2007 and 2015). Logistic regression analysis showed association of detection rates with elevated HVI. Thus, while the epidemiological indicators point to the elimination of leprosy, there is evidence of hidden cases and an association between higher rates of leprosy detection and greater social vulnerability remain.

We evaluated and compared the completeness, timeliness, simplicity, usefulness and flexibility between the former National Tuberculosis (TB) Surveillance System (NTBSS) and the newer Computerised Infectious Disease Reporting System (CIDR). Completeness was assessed by examining the field completion of key variables and median time from diagnosis to notification was calculated to evaluate timeliness. Differences between the two systems on completeness and timeliness were statistically assessed using χ2 and Wilcoxon rank-sum test, respectively. An online questionnaire on simplicity, flexibility and usefulness was sent to key stakeholders. Time and diagnosis-related variables were more complete in NTBSS, while variables on drug susceptibility, HIV and laboratory tests were more complete in CIDR (P < 0.05). The median time notification interval increased significantly in CIDR (P < 0.05). Stakeholders thought that CIDR is simpler (37.5%), more useful (41.7%) and more flexible (29.2%) than NTBSS. This study demonstrated that CIDR did not improve data completeness and decreased timeliness of notification. Simplicity, usefulness and flexibility were improved but qualitative methods should be applied to further explore these results.

The goal of this study was to analyse the spatial pattern of tuberculosis (TB) mortality using different approaches, namely: mortality rates (MR), spatial relative risks (RR) and Bayesian rates (Global and Local) and their association with human development index (HDI), Global and its three dimensions: education, longevity and income. An ecological study was developed in Curitiba, Brazil based on data from Mortality Information System (2008–2014). Spatial scan statistics were used to compute RR and identify high-risk clusters. Bivariate Local Indicator of Spatial Associations was used to assess associations. MR ranged between 0 and 25.24/100.000 with a mean (standard deviation) of 1.07 (2.66). Corresponding values for spatial RR were 0–27.46, 1.2 (2.99) and for Bayesian rates (Global and Local) were 0.49–1.66, 0.90 (0.19) and 0–6.59, 0.98 (0.80). High-risk clusters were identified for all variables, except for HDI-income and Global Bayesian rate. Significant negative spatial relations were found between MR and income; between RR and HDI global, longevity and income; and Bayesian rates with all variables. Some areas presented different patterns: low social development/low risk and high risk/high development. These results demonstrate that social development variables should be considered, in mortality due TB.

The objective was to evaluate the distribution of coagulase-negative staphylococci (CNS) involved in periprosthetic-joint infections (PJIs) and to describe their susceptibility profile to antibiotics. We conducted a multicentre retrospective study in France, including 215 CNS PJIs between 2011 and 2015. CNS PJIs involved knees in 54% of the cases, hips in 39%, other sites in 7%. The distribution of the 215 strains was: Staphylococcus epidermidis 129 (60%), Staphylococcus capitis 24 (11%), Staphylococcus lugdunensis 21 (10%), Staphylococcus warneri 8 (4%), Staphylococcus hominis 7 (3%), Staphylococcus haemolyticus 7 (3%). More than half of the strains (52.1%) were resistant to methicillin, 40.9% to ofloxacin, 20% to rifampicin. The species most resistant to antibiotics were S. hominis, S. haemolyticus, S. epidermidis, with 69.7% of the strains resistant to methicillin and 30% simultaneously resistant to clindamycin, cotrimoxazole, ofloxacin and rifampicin. No strain was resistant to linezolid or daptomycin. In this study on CNS involved in PJIs, resistance to methicillin is greater than 50%. S. epidermidis is the most frequent and resistant species to antibiotics. Emerging species such S. lugdunensis, S. capitis and Staphylococcus caprae exhibit profiles more sensitive to antibiotics. The antibiotics most often active in vitro are linezolid and daptomycin.

The study objective was to determine the prevalence of Staphylococcus aureus colonisation in the nares and oropharynx of healthy persons and identify any risk factors associated with such S. aureus colonisation. In total 263 participants (177 adults and 86 minors) comprising 95 families were enrolled in a year-long prospective cohort study from one urban and one rural county in eastern Iowa, USA, through local newspaper advertisements and email lists and through the Keokuk Rural Health Study. Potential risk factors including demographic factors, medical history, farming and healthcare exposure were assessed. Among the participants, 25.4% of adults and 36.1% minors carried S. aureus in their nares and 37.9% of adults carried it in their oropharynx. The overall prevalence was 44.1% among adults and 36.1% for minors. Having at least one positive environmental site for S. aureus in the family home was associated with colonisation (prevalence ratio: 1.34, 95% CI: 1.07–1.66). The sensitivity of the oropharyngeal cultures was greater than that of the nares cultures (86.1% compared with 58.2%, respectively). In conclusion, the nares and oropharynx are both important colonisation sites for healthy community members and the presence of S. aureus in the home environment is associated with an increased probability of colonisation.

Current knowledge of methicillin-resistant Staphylococcus aureus (MRSA) colonisation in relation to epidemiological characteristics is incomplete. We conducted a cross-sectional study at an acute-care tertiary infectious diseases hospital of MRSA isolates identified through routine surveillance from January 2009 to December 2011. We randomly selected 205 MRSA isolates (119 inpatients) from 798 isolates (427 inpatients) for molecular profiling using multilocus sequence typing. Multilevel multinomial logistic regression was used to estimate odds ratio (OR) assessing the predilection of MRSA strains for anatomic sites, and associations of strains with human immunodeficiency virus (HIV) infection. The most frequent sequence types (STs) were 239, 22 and 45. The proportion of ST22 increased over the sampling period, replacing ST239 as the dominant lineage. However, ST239 remained the most prevalent among HIV-seropositive individuals who were six times more likely to be colonised with this strain than non-HIV patients (adjusted OR (aOR) 6.44, 95% confidence interval (CI) 1.94–21.36). ST45 was >24 times more likely to be associated with perianal colonisation than in the nares, axillae and groin sites (aOR 24.20, 95% CI 1.45–403.26). This study underlines the clonal replacement of MRSA in Singapore as previously reported but revealed, in addition, key strain differences between HIV-infected and non-infected individuals hospitalised in the same environment.

Pneumococcal serotype replacement is an important issue after the introduction of pneumococcal conjugate vaccine (PCV) in children. After the introduction of 13-valent PCV, the incidence of invasive pneumococcal diseases (IPD) caused by Streptococcus pneumoniae serotype 12F (Sp12F) have increased in some countries; however, an outbreak of Sp12F has not reported in the post-13-valent PCV era. We experienced a local outbreak of Sp12F during March through May 2016 in Tsuruoka city, Japan after the introduction of 13-valent PCV in 2013. The IPD patients were two children and seven adults, three of whom died with a rapid disease progress. Although the clear transmission route was not determined, eight of the nine patients (89%) had close contact with children, which suggests that transmitted colonisation of Sp12F among children and adults might be the source of transmission. Continuous monitoring of IPDs, along with the determination of pneumococcal serotypes, is warranted in the post–13-valent PCV era. New IPD control strategies may be needed if this fatal outbreak continues to occur.

The 13-valent pneumococcal conjugate vaccine (PCV) has been part of routine immunisation in a 2 + 1 schedule (two primary infant doses and one booster during the second year of life) in the UK since 2010. Recently, the UK's Joint Committee on Vaccination and Immunisation recommended changing to a 1 + 1 schedule while conceding that this will increase disease burden; however, uncertainty remains on how much pneumococcal burden – including invasive pneumococcal disease (IPD) and non-invasive disease – will increase. We built a dynamic transmission model to investigate this question. The model predicted that a 1 + 1 schedule would incur 8777–27 807 additional cases of disease and 241–743 more deaths over 5 years. Serotype 19A caused 55–71% of incremental IPD cases. Scenario analyses showed that booster dose adherence, effectiveness against carriage and waning in a 1 + 1 schedule had the most influence on resurgence of disease. Based on the model assumptions, switching to a 1 + 1 schedule will substantially increase disease burden. The results likely are conservative since they are based on relatively low vaccine-type pneumococcal transmission, a paradigm that has been called into question by data demonstrating an increase of IPD due to several vaccine serotypes during the last surveillance year available.

Serosurveys have established data about the distribution of immunoglobulin G (IgG)-antibodies to pertussis toxin (PT) in various populations. We tried to detect whether small serosurveys in blood donors could serve as a simple and inexpensive means to collect information about the circulation of Bordetella pertussis. We screened every donation in 307 adult blood donors aged 19–69 years for IgG-anti-PT by standardised enzyme-linked immunosorbent assays (ELISA), and the donors were followed between 2014 and 2016 for a total of 426 person-years. When we used a vertical survey with cut-offs of 100, 62.5 and 40 IU/ml, respectively, as an indicator for recent contacts with B. pertussis, nine (2.9%), 22 (7.2%) and 54 (17.6%) of donors had IgG-anti-PT titres above the respective levels. During the horizontal observation period of 426 person years, six significant increases and two conversions were found, which lead to an estimate of 1878 contacts/100.000 person-years (1.9% per year). Median and mean IgG-anti-PT concentrations remained relatively stable from year to year during the observation period. Our findings show that small serosurveys of blood donors offer a simple and cheap method for the surveillance of B. pertussis.

Otitis externa is the inflammation of the external auditory canal. The disease is common and shows a seasonal variation with a greater incidence in warmer months. Pseudomonas aeruginosa is a common pathogen in otitis externa and in this retrospective study, we show a corresponding seasonal variation in the proportional incidence of P. aeruginosa isolates from otitis externa in South East England. In total 7770 patients were diagnosed with otitis externa over a period of 9 years from January 2008 to December 2016. P. aeruginosa was isolated from 2802 patients (proportional incidence of 36%). Incidence was higher in the months of August, September and October and in patients between 5 and 15 years of age. We postulate a combination of increased contact with water during warm weather in the holiday season and increased rainfall in the preceding season as a putative mechanism for the seasonal trends.

Capsular type K54 of Klebsiella pneumoniae is associated with hypervirulence and we sought to discover the basis for this among isolates submitted to the UK reference laboratory between 2012 and 2017. Isolates were typed by variable number tandem repeat analysis, and capsular type and virulence elements sought by PCR. The most prevalent type found (15/31 isolates) corresponded to clonal group (CG) 29 and included five representatives carrying rmpA, rmpA2 (regulators of mucoid phenotype), iutA and iroD (from the aerobactin and salmochelin siderophore clusters) associated with virulence plasmids. These included isolate KpvK54, recovered from pus. The remaining isolates did not carry a virulence plasmid. We also noted 11 further related isolates, including NCTC 9159, not of capsular type K54, but nevertheless sometimes associated with sepsis and abscesses. Whole-genome sequencing showed that KpvK54 carried a large virulence plasmid and an ICEKp3-like structure carrying the yersiniabactin cluster, absent in NCTC 9159. Comparative chromosomal analysis with an additional four genomes showed that KpvK54 shared further genes with K1-ST23 hypervirulent isolates, and with LS358, a K54-ST29 isolate from liver abscess puncture fluid. While CG29 isolates displayed varying degrees of virulence, some, especially those with the virulence plasmid (all K54), were clearly associated with hypervirulence.

According to the Centers for Disease Control and Prevention (CDC), from 2000 to 2014, reported cases of legionellosis per 100 000 population increased by 300% in the USA, although reports on disease seasonality are inconsistent. Using two national databases, we assessed seasonal patterns of legionellosis in the USA. We created a monthly time series from 1993 to 2015 of reported cases of legionellosis from the CDC, and from 1997 to 2006 of medical claims of legionellosis-related hospitalisation in older adults from the Centers for Medicaid and Medicare Services (CMS). We split the study time interval into two segments (before and after 2003), and applied a Poisson harmonic regression model to each dataset and each segment. The time series of monthly counts exhibited a significant shift of seasonal peaks from mid-September (9.676 ± 0.164 months) before 2003 to mid-August (8.452 ± 0.042 months) after 2003, along with an alarming increase in the amplitude of seasonal peaks in both CDC and CMS data. The lowest monthly reported cases of legionellosis in 2015 (281) exceed the maximum value reported before 2003 (206). We also observed a discrepancy between CDC and CMS data, suggesting that not all cases of legionellosis diagnosed by hospital-based laboratories were reported to the CDC. Improved reporting of legionellosis is required to better inform the public and organise disease prevention.

Gastric cancer is the third leading cause of cancer death worldwide. Gastric cancer screening using upper gastrointestinal series, endoscopy and serological testing has been performed in population-based (employee-based and community-based) and opportunistic cancer screening in Japan. There were 45 531 gastric cancer deaths in 2016, with the low screening and detection rates. Helicobacter pylori (H. pylori) screening followed by eradication treatment is recommended in high-risk population settings to reduce gastric cancer incidence. The aim of this study was to evaluate the cost-effectiveness of H. pylori screening followed by eradication treatment for a high-risk population in the occupational health setting. Decision trees and Markov models were developed for two strategies; H. pylori antibody test (HPA) screening and no screening. Targeted populations were hypothetical cohorts of employees aged 20, 30, 40, 50 and 60 years using a company health payer perspective on a lifetime horizon. Per-person costs and effectiveness (quality-adjusted life-years) were calculated and compared. HPA screening yielded greater benefits at the lower cost than no screening. One-way and probabilistic sensitivity analyses using Monte-Carlo simulation showed strong robustness of the results. H. pylori screening followed by eradication treatment is recommended to prevent gastric cancer for employees in Japan, on the basis of cost-effectiveness.

Surgical site infection (SSI) following cardiovascular surgery has been well documented, possibly owing to its highly invasive nature, but SSI following surgery on the thoracic aorta has not. This study aimed to describe the epidemiology and assess risk factors associated with the latter in Japan using a national database for SSI. Data on surgery on thoracic aorta performed between 2012 and 2014 were extracted from the Japan Nosocomial Infections Surveillance (JANIS) database. Risk factors were assessed initially by univariate analysis, and then entered into a logistic regression model for final evaluation. The cumulative incidence of SSI was 4.1% (146/3538) and staphylococci were the most frequent pathogens isolated. Factors such as the duration of operation, emergency surgery and male gender were significantly associated with SSI. These findings differ from previous studies on open heart and coronary artery bypass surgery, in which the American Society of Anesthesiologists (ASA) score was significantly associated with SSI, but gender was not. This study suggests that risk stratification in the JANIS system might be improved by incorporating additionally identified factors for risk adjustment, when comparing the incidence of SSI between hospitals.

Mixing matrices quantify how people with similar or different characteristics make contact with each other, creating potential for disease transmission. Little empirical data on mixing patterns among persons who inject drugs (PWID) are available to inform models of blood-borne disease such as HIV and hepatitis C virus. Egocentric drug network data provided by PWID in Baltimore, Maryland between 2005 and 2007 were used to characterise drug equipment-sharing patterns according to age, race and gender. Black PWID and PWID who were single (i.e. no stable sexual partner) self-reported larger equipment-sharing networks than their white and non-single counterparts. We also found evidence of assortative mixing according to age, gender and race, though to a slightly lesser degree in the case of gender. Highly assortative mixing according to race and gender highlights the existence of demographically isolated clusters, for whom generalised treatment interventions may have limited benefits unless targeted directly. These findings provide novel insights into mixing patterns of PWID for which little empirical data are available. The age-specific assortativity we observed is also significant in light of its role as a key driver of transmission for other pathogens such as influenza and tuberculosis.

The adenovirus vaccine and benzathine penicillin G (BPG) have been used by the US military to prevent acute respiratory diseases (ARD) in trainees, though these interventions have had documented manufacturing problems. We fit Poisson regression and random forest models (RF) to 26 years of weekly ARD incidence data to explore the impact of the adenovirus vaccine and BPG prophylaxis on respiratory disease burden. Adenovirus vaccine availability was among the most important predictors of ARD in the RF, while BPG was the ninth most important. BPG was a significant protective factor against ARD (incidence rate ratio (IRR) = 0.68; 95% confidence interval (CI) 0.67–0.70), but less so than either the old or new adenovirus vaccine (IRR = 0.39, 95% CI 0.38–0.39 and IRR = 0.11, 95% CI 0.11–0.11), respectively. These results suggest that BPG is moderately predictive of, and significantly protective against ARD, though to a lesser extent than either the old or new adenovirus vaccine.

We investigated risk factors for severe acute lower respiratory infections (ALRI) among hospitalised children <2 years, with a focus on the interactions between virus and age. Statistical interactions between age and respiratory syncytial virus (RSV), influenza, adenovirus (ADV) and rhinovirus on the risk of ALRI outcomes were investigated. Of 1780 hospitalisations, 228 (12.8%) were admitted to the intensive care unit (ICU). The median (range) length of stay (LOS) in hospital was 3 (1–27) days. An increase of 1 month of age was associated with a decreased risk of ICU admission (rate ratio (RR) 0.94; 95% confidence intervals (CI) 0.91–0.98) and with a decrease in LOS (RR 0.96; 95% CI 0.95–0.97). Associations between RSV, influenza, ADV positivity and ICU admission and LOS were significantly modified by age. Children <5 months old were at the highest risk from RSV-associated severe outcomes, while children >8 months were at greater risk from influenza-associated ICU admissions and long hospital stay. Children with ADV had increased LOS across all ages. In the first 2 years of life, the effects of different viruses on ALRI severity varies with age. Our findings help to identify specific ages that would most benefit from virus-specific interventions such as vaccines and antivirals.

Early, conforming antibiotic treatment in elderly patients hospitalised for community-acquired pneumonia (CAP) is a key factor in the prognosis and mortality. The objective was to examine whether empirical antibiotic treatment was conforming according to the Spanish Society of Pulmonology and Thoracic Surgery guidelines in these patients. Multicentre study in patients aged ⩾65 years hospitalised due to CAP in the 2013–14 and 2014–15 influenza seasons. We collected socio-demographic information, comorbidities, influenza/pneumococcal vaccination history and antibiotics administered using a questionnaire and medical records. Bivariate analyses and multilevel logistic regression were made. In total, 1857 hospitalised patients were included, 82 of whom required intensive care unit (ICU) admission. Treatment was conforming in 51.4% (95% confidence interval (CI) 49.1–53.8%) of patients without ICU admission and was associated with absence of renal failure without haemodialysis (odds ratio (OR) 1.49, 95% CI 1.15–1.95) and no cognitive dysfunction (OR 1.71, 95% CI 1.25–2.35), when the effect of the autonomous community was controlled for. In patients with ICU admission, treatment was conforming in 45.1% (95% CI 34.1–56.1%) of patients and was associated with the hospital visits in the last year (<3 vs. ⩾3, OR 2.70, 95% CI 1.03–7.12) and there was some evidence that this was associated with season. Although the reference guidelines are national, wide variability between autonomous communities was found. In patients hospitalised due to CAP, health services should guarantee the administration of antibiotics in a consensual manner that is conforming according to clinical practice guidelines.