A systematic literature review was performed on full economic evaluations of infectious disease interventions using disability-adjusted life years (DALY) as outcome measure. The search was limited to the period between 1994 and September 2011 and conducted in Medline, SciSearch and EMBASE databases. We included 154 studies, mostly targeting HIV/AIDS and malaria with most conducted for African countries (40%) and <10% in high-income countries. Third-payer perspective was applied in 29% of the studies, 25% used the societal perspective and 12% used both. Only 16% of the studies took indirect effects (i.e. herd immunity) of interventions into account. Intervention, direct healthcare and indirect non-healthcare costs were taken into account in respectively 100%, 81% and 36% of the studies. The majority of the studies followed the Global Burden of Disease method for DALY estimations, but most studies deviated from WHO cost-effectiveness guidelines. Better adherence to freely accessible guidelines will improve generalizability between full economic evaluations.

In this paper we propose a debate on the role of mathematical models in evaluating control strategies for vector-borne infections. Mathematical models must have their complexity adjusted to their goals, and we have basically two classes of models. At one extreme we have models that are intended to check if our intuition about why a certain phenomenon occurs is correct. At the other extreme, we have models whose goals are to predict future outcomes. These models are necessarily very complex. There are models in between these classes. Here we examine two models, one of each class and study the possible pitfalls that may be incurred. We begin by showing how to simplify the description of a complicated model for a vector-borne infection. Next, we examine one example found in a recent paper that illustrates the dangers of basing control strategies on models without considering their limitations. The model in this paper is of the second class. Following this, we review an interesting paper (a model of the first class) that contains some biological assumptions that are inappropriate for dengue but may apply to other vector-borne infections. In conclusion, we list some misgivings about modelling presented in this paper for debate.

There were multiple waves of influenza-like illness in 1918, the last of which resulted in a highly lethal pandemic killing 50 million people. It is difficult to study the initial waves of influenza-like illness in early 1918 because few deaths resulted and few morbidity records exist. Using extant military mortality records, we constructed mortality maps based on location of burial in France and Belgium in the British Army, and on home town in Vermont and New York in the USA Army. Differences between early and more lethal later waves in late 1918 were consistent with historical descriptions in France. The maps of Vermont and New York support the hypothesis that previous exposure may have conferred a degree of protection against subsequent infections; soldiers from rural areas, which were likely to have experienced less mixing than soldiers from urban areas, were at higher risk of mortality. Differences between combat and disease mortality in 1918 were consistent with limited influenza virus circulation during the early 1918 wave. We suggest that it is likely that more than one influenza virus was circulating in 1918, which might help explain the higher mortality rates in those unlikely to have been infected in early 1918.

The first human infection with avian influenza A(H7N9) virus was reported in Shanghai, China in March 2013. An additional 32 cases of human H7N9 infection were identified in the following months from March to April 2013 in Shanghai. Here we conducted a case-control study of the patients with H7N9 infection (n = 25) using controls matched by age, sex, and residence to determine risk factors for H7N9 infection. Our findings suggest that chronic disease and frequency of visiting a live poultry market (>10 times, or 1–9 times during the 2 weeks before illness onset) were likely to be significantly associated with H7N9 infection, with the odds ratios being 4·07 [95% confidence interval (CI) 1·32–12·56], 10·61 (95% CI 1·85–60·74), and 3·76 (95% CI 1·31–10·79), respectively. Effective strategies for live poultry market control should be reinforced and ongoing education of the public is warranted to promote behavioural changes that can help to eliminate direct or indirect contact with influenza A(H7N9) virus.

No published studies have discussed details of the prognosis and survival of patients with severe avian influenza A(H7N9) infection. In this study we analysed 128 laboratory-confirmed cases of severe H7N9 infection in Zhejiang province, the most affected region during the H7N9 epidemic in mainland China. We found that an increase in patient age by 5 years was associated with a 1·41 [95% confidence interval (CI) 1·19–1·67] times odds ratio for fatality. In addition, the time interval between the first clinical visit after symptom onset and hospital admission was inversely associated with survival time since admission. Of the 47 patients who died of the disease, when the time interval between the first clinical visit and hospital admission increased by 1 day, the duration of survival was 0·78 times (95% CI 0·62–0·98) as long. Our results suggest that patients with severe influenza H7N9 infection at older ages were at a higher risk of fatality, and that a delay in hospital admission was associated with more rapid death. More studies are required to corroborate our major findings.

We compared the epidemiological and clinical features of avian influenza A(H7N9) virus infections in the population in Zhejiang province, China, between March and April 2013 (first wave) and October 2013 and February 2014 (second wave). No statistical difference was found for age, sex, occupation, presence of underlying conditions, exposure history, white blood cell count, lymphocyte percentage and illness timeline and duration (all P > 0·05). The virus spread to 30 new counties compared to the first wave. The case-fatality rate was 22% in the first wave and 42% in the second (P = 0·023). Of those infected, 66% in the first wave and 62% in the second wave had underlying conditions. The proportion of those exposed to live poultry markets were 80% and 66%, respectively. We recommend permanent closure of live poultry markets and reformation of poultry supply and sales.

The purpose of this paper was to determine how contact behaviour change influences the indoor transmission of influenza A(H1N1)pdm09 among school children. We incorporated transmission rate matrices constructed from questionnaire responses into an epidemiological model to simulate contact behaviour change during an influenza epidemic. We constructed a dose–response model describing the relationships between contact rate, viral load, and respiratory symptom scores using published experimental human infection data for A(H1N1)pdm09. Findings showed that that mean numbers of contacts were 5·66 ± 6·23 and 1·96 ± 2·76 d−1 in the 13–19 and 40–59 years age groups, respectively. We found that the basic reproduction number (R0) was <1 during weekends in pandemic periods, implying that school closures or class suspensions are probably an effective social distancing policy to control pandemic influenza transmission. We conclude that human contact behaviour change is a potentially influential factor on influenza infection rates. For substantiation of this effect, we recommend a future study with more comprehensive control measures.

Significant gaps in immunity to polio, measles, and rubella may exist in adults in Cambodia and threaten vaccine-preventable disease (VPD) elimination and control goals, despite high childhood vaccination coverage. We conducted a nationwide serological survey during November–December 2012 of 2154 women aged 15–39 years to assess immunity to polio, measles, and rubella and to estimate congenital rubella syndrome (CRS) incidence. Measles and rubella antibodies were detected by IgG ELISA and polio antibodies by microneutralization testing. Age-structured catalytic models were fitted to rubella serological data to predict CRS cases. Overall, 29·8% of women lacked immunity to at least one poliovirus (PV); seroprevalence to PV1, PV2 and PV3 was 85·9%, 93·4% and 83·3%, respectively. Rubella and measles antibody seroprevalence was 73·3% and 95·9%, respectively. In the 15–19 years age group, 48·2% [95% confidence interval (CI) 42·4–54·1] were susceptible to either PV1 or PV3, and 40·3% (95% CI 33·0–47·5) to rubella virus. Based on rubella antibody seroprevalence, we estimate that >600 infants are born with CRS in Cambodia annually. Significant numbers of Cambodian women are still susceptible to polio and rubella, especially those aged 15–19 years, emphasizing the need to include adults in VPD surveillance and a potential role for vaccination strategies targeted at adults.

To investigate whether single nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs) 3 and 9 affect the susceptibility of hepatitis B virus (HBV) intrauterine transmission, we genotyped 399 neonates for TLR3 (c.1377C/T) [rs3775290] and TLR9 (G2848A) [rs352140] using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). A femoral venous blood sample was obtained from these subjects. Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were measured using chemiluminescence immunoassay kits and hepatitis B virus DNA (HBV DNA) levels were determined by fluorescence quantitative PCR assay. Our results showed that when adjusting for maternal HBeAg, maternal HBV DNA and mode of delivery, allele ‘T’ for SNP c.1377C/T was significantly associated with HBV intrauterine transmission susceptibility [adjusted OR (aOR) 0·55, 95% confidence interval (CI) 0·34–0·91, P = 0·020] and the TT genotype decreased the risk of HBV intrauterine transmission (aOR 0·28, 95% CI 0·09–0·91, P = 0·033). Allele ‘A’ for SNP G2848A was significantly associated with HBV intrauterine transmission susceptibility (aOR 0·62, 95% CI 0·39–1·00, P = 0·048) and the GA genotype protected neonates from HBV intrauterine transmission (aOR 0·45, 95% CI 0·22–0·93, P = 0·031). The TLR3 (c.1377C/T) and TLR9 (G2848A) polymorphisms may be relevant for HBV intrauterine transmission susceptibility, although the reduction in risk to HBV intrauterine transmission is modest and the biological mechanism of the observed association merits further investigation.

Human rhinoviruses (HRVs) are widespread respiratory pathogens and a major cause of acute respiratory tract infections. The aim of this study was to investigate the molecular epidemiology of rhinovirus infections in children in Cyprus over three consecutive winter seasons. From a total of 116 rhinovirus-positive samples, 68 were sequenced in the 5’-UTR and VP4/VP2 regions. Thirty-six (52·9%) samples were identified as HRV-A and 27 (39·7%) as HRV-C, with only five (7·4%) samples belonging to the HRV-B species. Of these, a total of 46 different genotypes were identified. In the VP2/VP4 phylogenetic tree all strains clustered in three different well-defined clades, whereas the 5’-UTR tree exhibited clades with a mixed clustering of HRV-A and HRV-C strains reflecting the evolutionary history of recombination between HRV-A and HRV-C that has been observed previously. In summary, a high intra- and inter-season diversity of HRV types was observed. Despite its geographical isolation the frequency of HRV species in Cyprus is comparable to that reported in other regions of the world supporting the concept of an unrestricted global circulation. This study assesses, for the first time, the epidemiology of rhinovirus infections in Cypriot children and will be helpful to clinicians and researchers interested in the treatment and control of viral respiratory tract infections.

Mycoplasma pneumoniae outbreaks cause increased use of macrolides and tetracyclines. We aimed to investigate whether drug use data, in addition to laboratory data, could improve understanding of the spread of M. pneumoniae epidemics. Number of users of Mycoplasma antibiotics (erythromycin, doxycycline, clarithromycin) per week and county of residence in an indicator age group (6–12 years) was retrieved from the Norwegian prescription database for the epidemic season 2011–2012 and compared to non-epidemic seasons. In 2011, increased use of Mycoplasma antibiotics was first observed in September on the west coast of Norway. The Norwegian laboratory-based surveillance system showed the first increase in positive tests in August 2011 and an epidemic was announced on 25 October 2011. At that time the use of Mycoplasma antibiotics had already exceeded three times the use in non-epidemic periods. Data for three counties from the regional microbiological laboratories showed that the increase in number of positive samples coincided in time with the increase in prescription data. Laboratory data cannot accurately determine the extent of an epidemic, and drug use data cannot identify the cause. Establishing a systematic interaction between the two monitoring systems will enhance surveillance and probably contribute to improved infection control and prudent antibiotic prescribing.

We describe the seasonal variation of acute toxoplasmosis in the United States. Acute toxoplasmic lymphadenopathy (ATL) can be a surrogate of acute toxoplasmosis in patients in whom the date of onset of lymphadenopathy matches the window of acute infection predicted by serological tests performed at a reference laboratory. We used the electronic database of the Palo Alto Medical Foundation Toxoplasma Serology Laboratory (PAMF-TSL) (1997–2011) to identify cases of ATL. We tested the uniformity of distribution of ATL cases per month, across the 12 calendar months, using circular statistics uniformity tests. We identified 112 consecutive cases of ATL. The distribution of cases was not uniform across the 12 calendar months. We observed the highest peak of cases in December and a second highest peak in September. Similar months were identified in patients with acute toxoplasmosis in rural areas in France. The results were similar when we performed weighted analyses, weighting for the total number of Toxoplasma gondii IgG tests performed per month in the PAMF-TSL laboratory. This is the largest study to date of the seasonal variation of ATL in the United States. Physicians should advise high-risk individuals to avoid risk factors associated with T. gondii infections especially around those months.

This study estimated the seroprevalence and risk factors for acquiring Toxoplasma gondii infection by undergraduate female university students in Jordan. A cross-sectional study from September 2013 to July 2014 analysed 202 blood samples for IgG and IgM antibodies by enzyme-linked immunosorbent assay and a semi-constructed questionnaire was completed by participants to gather information about Toxoplasma infection risk factors. T. gondii IgG antibodies were detected in 66·5% of the females. Only one sample was positive for both IgG and IgM. Using χ2 test, six factors showed significant association with T. gondii infection (P ⩽ 0·01). The multivariate logistic regression model showed that female students living in houses, wet areas, with income >US$750/month and using spring (untreated) water were 47·42, 10·20, 5·00, 3·25 more times at risk to be seropositive for T. gondii, respectively, compared to female students living in apartments, dry areas, with income ≤US$750/month and using treated water, respectively. This study concluded that T. gondii infection in female university students in Jordan is high and most women become infected before marriage; however, congenital toxoplasmosis is still likely to occur in Jordan. Thus, dissemination of protective measures and knowledge by healthcare professionals is essential especially for pregnant women.

About 20–90% of the world's population has had contact with Toxoplasma gondii parasites. The aim of this study was to determine the seroprevalence and risk factors associated with T. gondii infection in the Central Region, Ghana. A community-based cross-sectional study was conducted in three selected communities. Serum samples were tested for the presence of anti-T. gondii IgG and IgM antibodies by ELISA. A serological criterion for seropositivity was a positive test result for any of the two anti-Toxoplasma IgG or IgM antibodies or a combination of both. In all, 390 participants of mean age 47·0 years consisting of 118 (30·3%) males and 272 (69·7%) females were tested. The overall seroprevalence of T. gondii was 85% (333/390) where fishermen, farmers and fishmongers, respectively, had the highest seropositivity. IgG and IgM antibodies were detected in 329 (84%) and 25 (6%), respectively, while both IgG and IgM antibodies were detected in 21 (5%) of the participants. Respectively, 1% (4/390) and 79% (308/390) of participants tested positive for IgM-only and IgG-only antibodies. There was a significant relationship between Toxoplasma seropositivity and contact with soil, presence of a cat in the surrounding area, age, sources of drinking water, level of formal education, and socioeconomic status. The results suggest that the seashore may serve as a good ground for sporulation and survival of Toxoplasma oocysts.

Toxoplasma gondii is a zoonotic protozoan parasite, infecting a wide range of warm-blooded animals. The Swedish wild boar population is expanding and increased hunting provides its meat to a growing group of consumers. We performed a spatio-temporal investigation of T. gondii seroprevalence in Swedish wild boars. An ELISA was set up and evaluated against a commercial direct agglutination test, using Bayesian latent class analysis. The ELISA sensitivity and specificity were estimated to 79% and 85%, respectively. Of 1327 serum samples, 50% were positive. Thirty-four per cent of young wild boars and 55% of adults were positive (P < 0·001). The total seroprevalence ranged from 72% in 2005 to 38% in 2011 (P < 0·001), suggesting a declining trend. The highest seroprevalence, 65%, was recorded in South Sweden. In other regions it varied from 29% in Stockholm to 46% in East Middle Sweden.

This paper explores the utility of cluster- and case-based surveillance established in government hospitals in Bangladesh to detect Nipah virus, a stage III zoonotic pathogen. Physicians listed meningo-encephalitis cases in the 10 surveillance hospitals and identified a cluster when ⩾2 cases who lived within 30 min walking distance of one another developed symptoms within 3 weeks of each other. Physicians collected blood samples from the clustered cases. As part of case-based surveillance, blood was collected from all listed meningo-encephalitis cases in three hospitals during the Nipah season (January–March). An investigation team visited clustered cases’ communities to collect epidemiological information and blood from the living cases. We tested serum using Nipah-specific IgM ELISA. Up to September 2011, in 5887 listed cases, we identified 62 clusters comprising 176 encephalitis cases. We collected blood from 127 of these cases. In 10 clusters, we identified a total of 62 Nipah cases: 18 laboratory-confirmed and 34 probable. We identified person-to-person transmission of Nipah virus in four clusters. From case-based surveillance, we identified 23 (4%) Nipah cases. Faced with thousands of encephalitis cases, integrated cluster surveillance allows targeted deployment of investigative resources to detect outbreaks by stage III zoonotic pathogens in resource-limited settings.

This study describes the first large-scale serosurvey on West Nile virus (WNV) conducted in the equine population in Pakistan. Sera were collected from 449 equids from two provinces of Pakistan during 2012–2013. Equine serum samples were screened using a commercial ELISA kit detecting antibodies against WNV and related flaviviruses. ELISA-positive samples were further investigated using virus-specific microneutralization tests (MNTs) to identify infections with Japanese encephalitis virus (JEV), WNV and tick-borne encephalitis virus (TBEV). Anti-WNV antibodies were detected in 292 samples by ELISA (seroprevalence 65·0%) and WNV infections were confirmed in 249 animals by MNT. However, there was no animal found infected by JEV or TBEV. The detection of WNV-seropositive equines in Pakistan strongly suggests a widespread circulation of WNV in Pakistan.

Expansion of sandflies and increasing pet travel have raised concerns about canine leishmaniasis (CanL) spread to new areas of Europe. This study aimed to estimate the probability of CanL introduction and persistence following movements of infected dogs. Stochastic modelling was used to estimate the probabilities of (1) CanL infection during travels or imports of infected dogs (Pinf and PinfCA, respectively), (2) CanL persistence in a dog network with sandflies after introduction of an infected dog (Pper), and (3) persistence in a CanL-free region (Pper region) for N dogs moving between endemic and free regions. Different mitigation measures (MMs) were assessed. Pinf [7·8%, 95% predictive interval (PI) 2·6–16·4] and Pper (72·0%, 95% PI 67·8–76·0) were reduced by use of repellent, vaccine, prophylactic medication, and insecticide, in decreasing order of effectiveness. Testing and exclusion of positive dogs was most effective in reducing Pper region for a small N. The spread of CanL to CanL-free areas with sandflies is thus likely, but can be reduced by MMs.

Active symptom surveillance was applied to three selected communities ( 160 147 persons) in Tianjin from 2010 to 2012. We examined 1089 individuals showing pertussis-like symptoms, of which 1022 nasopharyngeal specimens were tested for pertussis by polymerase chain reaction and 802 sera for anti-pertussis toxin antibodies. Of the total cases tested, 113 were confirmed, and their demographic, clinical, and vaccination-related data were collected. The annual incidence was 23·52 cases/100 000 persons among communities, which was 16·22 times that obtained via hospital reports for the same period (P < 0·001). The actual incidence in the 15–69 years age group was most significantly underestimated by hospitals, given that it was 43·08 times that of the reported hospital rate. Among the cases aged <15 years, 84·5% were individuals who had been fully vaccinated. The misdiagnosis rate was as high as 94·69%, and only 5·31% of the confirmed pertussis cases were properly diagnosed as pertussis at their first medical visit. Pertussis incidence in China has been severely underestimated and this was in part due to a high misdiagnosis rate. Adolescents and adults have become new high-risk populations. Future work should focus on reinforcing immunization programmes, especially among adolescents and adults.

In August 2012, an explosive outbreak of severe lower respiratory tract infection (LRTI) due to Streptococcus pneumoniae serotype-8 occurred in a highly vaccinated elderly institutionalized population in England. Fifteen of 23 residents developed LRTI over 4 days (attack rate 65%); 11 had confirmed S. pneumoniae serotype-8 disease, and two died. Following amoxicillin chemoprophylaxis and pneumococcal polysaccharide vaccine (PPV) re-vaccination no further cases occurred in the following 2 months. No association was found between being an outbreak-associated case and age (P = 0·36), underlying comorbidities [relative risk (RR) 0·84 95% confidence interval (CI) 0·34–2·09], or prior receipt of PPV (RR 1·4, 95% CI 0·60–3·33). However, the median number of years since PPV was significantly higher for cases (n = 15, 10·2 years, range 7·3–17·9 years) than non-cases (n = 8, 7·2 years, range 6·8–12·8 years) (P = 0·045), provided evidence of waning immunity. Alternative vaccination strategies should be considered to prevent future S. pneumoniae outbreaks in institutionalized elderly populations.