Hepatitis delta virus (HDV) is a defective RNA virus that depends on the presence of hepatitis B virus (HBV) for the creation of new virions and propagation of the infection to hepatocytes. Chronic infection with HDV is usually associated with a worsening of HBV infection, leading more frequently to cirrhosis, increased risk of liver decompensation and hepatocellular carcinoma (HCC) occurrence. In spite of a progressive declining prevalence of both acute and chronic HDV infection observed over several years, mainly due to increased global health policies and mass vaccination against HBV, several European countries have more recently observed stable HDV prevalence mainly due to migrants from non-European countries. Persistent HDV replication has been widely demonstrated as associated with cirrhosis development and, as a consequence, development of liver decompensation and occurrence of HCC. Several treatment options have been attempted with poor results in terms of HDV eradication and improvement of long-term prognosis. A global effort is deemed urgent to enhance the models already existing as well as to learn more about HDV infection and correlated tumourigenesis mechanisms.

Hepatitis E virus (HEV) is a well-known cause of acute hepatitis. Immunocompromised subjects, including liver transplant recipients, are considered to be at risk for HEV infection, which occasionally follows a chronic course. The diagnosis of HEV infection in these patients must be based on HEV RNA testing, as serology has variable performance. The aim of this study was to assess the prevalence of HEV infection in liver transplant recipients in Greece by means of HEV RNA testing. Liver transplant recipients followed in the sole transplant centre in Greece were prospectively included. HEV RNA was detected by real-time RT-PCR. Positive samples were further analysed using a nested reverse transcription RT-PCR kit, which amplifies a 137-nucleotide sequence within the ORF2/ORF3 overlapping region to detect the HEV genotype and perform phylogenetic analysis. The mean age of the included patients (n = 76) was 54 years. The most common indication for liver transplantation was viral hepatitis (57%). The majority of the patients (75%) received a calcineurin inhibitor as part of their immunosuppressive regimen and had normal liver enzymes. HEV RNA was found positive in only 1/76 (1.3%) patient. Phylogenetic analysis showed that the sequence clustered into the HEV genotype 3 clade. This patient experienced an acute hepatitis flare, which nonetheless did not become chronic. The prevalence of HEV infection in liver transplant recipients in Greece is similar (1.3%) to that reported previously in other countries. Transplant physicians should be aware of this condition and its associated consequences.

Vaccinating monkeys against yellow fever (YF) has been a common practice in the beginning of the 17D vaccine development. Although it may seem strange at first sight, vaccinating monkeys as a public health strategy is, we think, feasible and theoretically could eliminate the infection among non-human primates, interrupting the virus circulation (or significantly reducing it) and therefore reducing the risk of spilling over to the human population. We propose a series of studies that could demonstrate (or not) the efficacy and feasibility of vaccinating non-human primates YF reservoirs living in green areas of urban centres to cut off or curb the virus circulation that recurrently spill over to the human population. Therefore, vaccinating monkeys in relatively small green areas of the urban centres is perhaps the ultimate solution for the Brazilian recurrent YF epizootics.

Zika virus infection in humans has been linked to severe neurological sequels and foetal malformations. The rapidly evolving epidemics and serious complications made the frequent updates of Zika virus mandatory. Web search query has emerged as a low-cost real-time surveillance system to anticipate infectious diseases’ outbreaks. Hence, we developed a prediction model that could predict Zika-confirmed cases based on Zika search volume in Google Trends. We extracted weekly confirmed Zika cases of two epidemic countries, Brazil and Colombia. We got the weekly Zika search volume in the two countries from Google Trends. We used standard time-series regression (TSR) to predict the weekly confirmed Zika cases based on the Zika search volume (Zika query). The basis TSR model – using 1-week lag of Zika query and using 1-week lag of Zika cases as a control for autocorrelation – was the best for predicting Zika cases in Brazil and Colombia because it balanced the performance of the model and the advance time in the prediction. Our results showed that we could use Google search queries to predict Zika cases 1 week earlier before the outbreak. These findings are important to help healthcare authorities evaluate the outbreak and take necessary precautions.

In 2016, imported Zika virus (ZIKV) infections and the presence of a potentially competent mosquito vector (Aedes albopictus) implied that ZIKV transmission in New York City (NYC) was possible. The NYC Department of Health and Mental Hygiene developed contingency plans for a urosurvey to rule out ongoing local transmission as quickly as possible if a locally acquired case of confirmed ZIKV infection was suspected. We identified tools to (1) rapidly estimate the population living in any given 150-m radius (i.e. within the typical flight distance of an Aedes mosquito) and (2) calculate the sample size needed to test and rule out the further local transmission. As we expected near-zero ZIKV prevalence, methods relying on the normal approximation to the binomial distribution were inappropriate. Instead, we assumed a hypergeometric distribution, 10 missed cases at maximum, a urine assay sensitivity of 92.6% and 100% specificity. Three suspected example risk areas were evaluated with estimated population sizes of 479–4,453, corresponding to a minimum of 133–1244 urine samples. This planning exercise improved our capacity for ruling out local transmission of an emerging infection in a dense, urban environment where all residents in a suspected risk area cannot be feasibly sampled.

Dengue virus type 3 genotype III (DENV-3/III) is widely distributed in most dengue-endemic regions. It emerged in Malaysia in 2008 and autochthonously spread in the midst of endemic DENV-3/I circulation. The spread, however, was limited and the virus did not cause any major outbreak. Spatiotemporal distribution study of DENV-3 over the period between 2005 and 2011 revealed that dengue cases involving DENV-3/III occurred mostly in areas without pre-existing circulating DENV-3. Neutralisation assays performed using sera of patients with the respective infection showed that the DENV-3/III viruses can be effectively neutralised by sera of patients with DENV-3 infection (50% foci reduction neutralisation titres (FRNT50) > 1300). Sera of patients with DENV-1 infection (FRNT50 ⩾ 190), but not sera of patients with DENV-2 infection (FRNT50 ⩽ 50), were also able to neutralise the virus. These findings highlight the possibility that the pre-existing homotypic DENV-3 and the cross-reacting heterotypic DENV-1 antibody responses could play a role in mitigating a major outbreak involving DENV-3/III in the Klang Valley, Malaysia.

Co-circulation of Chikungunya and Dengue viral infections (CHIKV and DENV) have been reported mainly due to transmission by common Aedes vector. The purpose of the study was to identify and characterise the circulating strains of CHIKV and DENV in DENV endemic region of New Delhi during 2016. CHIKV and DENV were identified in the blood samples (n = 130) collected from suspected patients by RT-PCR. CHIKV was identified in 26 of 65 samples (40%). Similarly, DENV was detected in 48 of 120 samples (40%). Co-infection with both the viruses was identified in five (9%) of the samples. Interestingly, concurrent infection with DENV, CHIKV and Plasmodium vivax was detected in two samples. CHIKV strains (n = 11) belonged to the ECSA genotype whereas DENV-3 sequences (n = eight) clustered in Genotype III by phylogenetic analysis. Selection pressure of E1 protein of CHIKV and CprM protein of DENV-3 revealed purifying selection with four and two positive sites, respectively. Four amino acids of the CHIKV were positively selected and had high entropy suggesting probable variations. Co-circulation of both viruses in DENV endemic regions warrants effective monitoring of these emerging pathogens via comprehensive surveillance for implementation of effective control measures.

Human movement contributes to the probability that pathogens will be introduced to new geographic locations. Here we investigate the impact of human movement on the spatial spread of Chikungunya virus (CHIKV) in Southern Thailand during a recent re-emergence. We hypothesised that human movement, population density, the presence of habitat conducive to vectors, rainfall and temperature affect the transmission of CHIKV and the spatiotemporal pattern of cases seen during the emergence. We fit metapopulation transmission models to CHIKV incidence data. The dates at which incidence in each of 151 districts in Southern Thailand exceeded specified thresholds were the target of model fits. We confronted multiple alternative models to determine which factors were most influential in the spatial spread. We considered multiple measures of spatial distance between districts and adjacency networks and also looked for evidence of long-distance translocation (LDT) events. The best fit model included driving-distance between districts, human movement, rubber plantation area and three LDT events. This work has important implications for predicting the spatial spread and targeting resources for control in future CHIKV emergences. Our modelling framework could also be adapted to other disease systems where population mobility may drive the spatial advance of outbreaks.

Tick-borne encephalitis (TBE) is an emerging vector-borne disease in Europe. The aim of the study was to evaluate sequelae and to analyse the potential risk factors predisposing to sequelae development. We performed a retrospective analysis of medical records of 1072 patients who received a 1-month follow-up appointment after hospital discharge. Medical data, such as patients’ age, gender, place of living, subjective complaints, neurological and psychiatric sequelae were evaluated twice: at the moment of discharge and at follow-up visits 1 month after discharge. We observed that sequelae may affect 20.6% of TBE patients. Subjective sequelae were more frequent than subjective complaints during the hospitalisation (P < 0.001), while objective neurological symptoms during the hospitalisation were more pronounced than neurological sequelae (P < 0.001). Patients with meningoencephalomyelitis were predisposed to neurological complications, while subjective symptoms were more common in meningoencephalitis. Independent risk factors for sequelae development were: age and cerebrospinal fluid (CSF) protein concentration. The risk of late neurological complications persisting was increased in patients with higher CSF protein concentration. Based on the results of our study we concluded that, there is a need for a better vaccination program, which would prevent the development of sequelae.

Haemorrhagic fever with renal syndrome (HFRS) is transmitted to humans mainly by rodents and this transmission could be easily influenced by meteorological factors. Given the long-term changes in climate associated with global climate change, it is important to better identify the effects of meteorological factors of HFRS in epidemic areas. Shandong province is one of the most seriously suffered provinces of HFRS in China. Daily HFRS data and meteorological data from 2007 to 2012 in Shandong province were applied. Quasi-Poisson regression with the distributed lag non-linear model was used to estimate the influences of mean temperature and Diurnal temperature range (DTR) on HFRS by sex, adjusting for the effects of relative humidity, precipitation, day-of-the-week, long-term trends and seasonality. A total of 6707 HFRS cases were reported in our study. The two peaks of HFRS were from March to June and from October to December, particularly, the latter peak in 2012. The estimated effects of mean temperature and DTR on HFRS were non-linear. The immediate and strong effect of low temperature and high DTR on HFRS was found. The lowest temperature −8.86°C at lag 0 days indicated the largest related relative risk (RRs) with the reference (14.85 °C), respectively, 1.46 (95% CI 1.11–1.90) for total cases, 1.33 (95% CI 1.00–1.78) for the males and 1.76 (95% CI 1.12–2.79) for the females. Highest DTR was associated with a higher risk on HFRS, the largest RRs (95% CI) were obtained when DTR = 15.97 °C with a reference at 8.62 °C, with 1.26 (0.96–1.64) for total cases and 1.52 (0.97–2.38) for the female at lag 0 days, 1.22 (1.05–1.41) for the male at lag 5 days. Non-linear lag effects of mean temperature and DTR on HFRS were identified and there were slight differences for different sexes.

Hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses is a serious public health problem in China, accounting for 90% of HFRS cases reported globally. In this study, we applied geographical information system (GIS), spatial autocorrelation analyses and a seasonal autoregressive-integrated moving average (SARIMA) model to describe and predict HFRS epidemic with the objective of monitoring and forecasting HFRS in mainland China. Chinese HFRS data from 2004 to 2016 were obtained from National Infectious Diseases Reporting System (NIDRS) database and Chinese Centre for Disease Control and Prevention (CDC). GIS maps were produced to detect the spatial distribution of HFRS cases. The Moran's I was adopted in spatial global autocorrelation analysis to identify the integral spatiotemporal pattern of HFRS outbreaks, while the local Moran's Ii was performed to identify ‘hotspot’ regions of HFRS at province level. A fittest SARIMA model was developed to forecast HFRS incidence in the year 2016, which was selected by Akaike information criterion and Ljung–Box test. During 2004–2015, a total of 165 710 HFRS cases were reported with the average annual incidence at province level ranged from 0 to 13.05 per 100 000 persons. Global Moran's I analysis showed that the HFRS outbreaks presented spatially clustered distribution, with the degree of cluster gradually decreasing from 2004 to 2009, then turned out to be randomly distributed and reached lowest point in 2012. Local Moran's Ii identified that four provinces in northeast China contributed to a ‘high–high’ cluster as a traditional epidemic centre, and Shaanxi became another HFRS ‘hotspot’ region since 2011. The monthly incidence of HFRS decreased sharply from 2004 to 2009 in mainland China, then increased markedly from 2010 to 2012, and decreased again since 2013, with obvious seasonal fluctuations. The SARIMA ((0,1,3) × (1,0,1)12) model was the most fittest forecasting model for the dataset of HFRS in mainland China. The spatiotemporal distribution of HFRS in mainland China varied in recent years; together with the SARIMA forecasting model, this study provided several potential decision supportive tools for the control and risk-management plan of HFRS in China.

In this study, we describe a contained measles outbreak in a London prison, the second such outbreak in a custodial setting. Once vaccination commenced, just under a third of eligible prisoners were immunised due to a low uptake of the vaccine. We conducted a root-cause analysis in order to identify factors which may have prevented or altered the course of the outbreak. Our analysis revealed that many of the factors identified are those that cannot be easily changed. It is unlikely that mass vaccination at the time, even in the absence of some of the more easily rectifiable issues, could have fully avoided further cases in the event of a mass outbreak. Both measles outbreaks in a custodial setting started with a member of staff and immunisation status of the staff were largely unknown. We argue that mass vaccination following an outbreak in a prison is unlikely to fully prevent a mass outbreak, and that implementing opt-out testing, empirical vaccination and insisting on full immunisation of staff are most likely to both prevent and contain outbreaks in the future.

We report an ongoing measles outbreak in Greece. The first cases were notified through the mandatory notification system on May 2017 in Northern Greece and concerned a cluster of three imported cases in unvaccinated Roma siblings. So far, 3150 cases have been reported in all 13 Regions. Initially, the outbreak mainly affected Greek Roma but as it progressed it spread to non-minority Greek nationals. The outbreak reached its ultimate peak on week 10/2018 but from week 15/2018 has been gradually declining. Most cases (60.6%) were Roma (especially children <10 year-old) followed by non-minority Greek nationals (29.3%; mostly young adults). The majority (80.4%) were unvaccinated. Interestingly, 129 (4.1%) cases were healthcare workers (HCWs). Genotype B3 was identified by molecular methods in all 87 cases tested. Overall, 61.3% of the cases were hospitalised. Complications were reported in 17.1% of the cases among which four deaths. The outbreak occurred after 3 years without local endemic measles transmission. Extensive vaccination implemented as the major public health measure managed to prevent the emergence of a large number of cases in refugee/migrant hosting sites. Mitigation efforts currently focus on raising awareness among HCWs and closing the immunisation gap in populations with suboptimal vaccination coverage.

Measles is a target for elimination in all six WHO regions by 2020, and over the last decade, there has been considerable progress towards this goal. Surveillance is recognised as a cornerstone of elimination programmes, allowing early identification of outbreaks, thus enabling control and preventing re-emergence. Fever–rash surveillance is increasingly available across WHO regions, and this symptom-based reporting is broadly used for measles surveillance. However, as measles control increases, symptom-based cases are increasingly likely to reflect infection with other diseases with similar symptoms such as rubella, which affects the same populations, and can have a similar seasonality. The WHO recommends that cases from suspected measles outbreaks be laboratory-confirmed, to identify ‘true’ cases, corresponding to measles IgM titres exceeding a threshold indicative of infection. Although serological testing for IgM has been integrated into the fever–rash surveillance systems in many countries, the logistics of sending in every suspected case are often beyond the health system's capacity. We show how age data from serologically confirmed cases can be leveraged to infer the status of non-tested samples, thus strengthening the information we can extract from symptom-based surveillance. Applying an age-specific confirmation model to data from three countries with divergent epidemiology across Africa, we identify the proportion of cases that need to be serologically tested to achieve target levels of accuracy in estimated infected numbers and discuss how this varies depending on the epidemiological context. Our analysis provides an approach to refining estimates of incidence leveraging all available data, which has the potential to improve allocation of resources, and thus contribute to rapid and efficient control of outbreaks.

We aimed to verify the effectiveness of real-time reverse transcription (rRT) polymerase chain reaction (PCR) for detecting cases of modified measles (M-Me) and for predicting super-spreader candidates through the experience of a measles outbreak dominated by M-Me in Yamagata, Japan, during March–April 2017. We applied rRT-PCR to specimens from 35 cases of M-Me, nine cases of typical measles (T-Me) and nine cases of prodromal stage of T-Me (P-Me). From rRT-PCR among the M-Me cases, peripheral blood mononuclear cells (PBMC) showed the highest positive rate (80.0%), followed by throat swab (48.6%), urine (33.3%) and serum (3.1%). The negative result of PBMC in M-Me cases was recovered by the result of a throat swab. In specimens of PBMC, throat swab and urine, M-Me group showed the significantly higher cycle of threshold (i.e., lower viral load) in the rRT-PCR than T-Me and P-Me groups, respectively. Furthermore, three super-spreaders in T-Me or P-Me showed an extremely low cycle of threshold in their throat swab specimens. rRT-PCR using PBMC and throat swab might be helpful for clinical management and measles control by certain detection of M-Me cases and by predicting super-spreading events resulting from measles cases with the high viral load.

Persistent infection with one or more highly oncogenic human papillomaviruses (HPVs) or high-risk-HPV (HR-HPV) is necessary but not a sufficient aetiological agent for the development of cervical neoplasia. A number of viral, host, environmental and behavioural factors are suggested to be associated with the progression of cervical disorder. This study aimed to evaluate the impact of environmental and behavioural cofactors on the development of cervical disorders in HR-HPV-infected women in Serbia. A total of 541 women have been tested by PCR for the presence of HPV on the cervix. HPV genotypes were determined by direct DNA sequencing. Women identified as HR-HPV-positive were further classified into four subgroups according to their cytological status. All relevant information about demographical and behavioural factors was obtained by interviewer-based questionnaire. A number of analytical and descriptive statistical methods were used for processing the data. The cofactors found to be of significance for the progression of cervical disease were older age, body mass index >25, lower educational level, long-term smoking, previous genital infections and cervical interventions. On the other hand, condom use was found to have a protective role. Information about these cofactors might be very important for the development of more efficient cancer prevention programmes and promotion of anti-HPV vaccination.

Human papillomavirus (HPV) is a DNA virus linked to mucosal and cutaneous carcinogenesis. More than 200 different HPV types exist. We carried out a transversal study to investigate the prevalence of HPV types in two regions of Mexico. A total of 724 genital and non-genital samples from women (F) and men (M) were studied; 241 (33%) from North-Eastern (NE) and 483 (66%) from South-Central (SC) Mexico. The overall prevalence was 87%. In genital lesions from females, the NE group showed a prevalence of HPV types 16 (37%), 6 (13%), 59 (6%), 11, 18 and 66 (5.4% each); and the SC group showed types 6 (17%), 16 (15%), 11 (14.5%), 18 (12%) and 53 (6%). In the genital lesions from males, NE group showed types 16 (38%), 6 (21%), 11 (13%) and 59 plus 31 (7.5%) and the SC group showed types 6 (25%), 11 (22%), 18 (17%) and 16 (11.5%). When the two regions were compared, a higher prevalence of low-risk HPV 6 and 11 was found in the SC region and of high-risk HPV 59, 31 and 66 (the latter can also be present in benign lesions) in the NE region. Our findings complement efforts to understand HPV demographics as a prerequisite to guide and assess the impact of preventive interventions.

Knowledge about the infection transmission routes is significant for developing effective intervention strategies. We searched the PubMed databases and identified 10 studies with 14 possible inflight influenza A(H1N1)pdm09 outbreaks. Considering the different mechanisms of the large-droplet and airborne routes, a meta-analysis of the outbreak data was carried out to study the difference in attack rates for passengers within and beyond two rows of the index case(s). We also explored the relationship between the attack rates and the flight duration and/or total infectivity of the index case(s). The risk ratios for passengers seated within and beyond the two rows of the index cases were 1.7 (95% confidence interval (CI) 0.98–2.84) for syndromic secondary cases and 4.3 (95% CI 1.25–14.54) for laboratory-confirmed secondary cases. Furthermore, with an increase of the product of the flight duration and the total infectivity of the index cases, the overall attack rate increased linearly. The study indicates that influenza A(H1N1)pdm09 may mainly be transmitted via the airborne route during air travel. A standardised approach for the reporting of such inflight outbreak investigations would help to provide more convincing evidence for such inflight transmission events.

Guillain Barré syndrome (GBS), which is triggered by autoantibodies produced in response to antigenic stimuli such as certain infections and vaccinations, is the most common cause of acute flaccid paralysis worldwide. Campylobacter, the most common bacterial enteric infection in the USA, is reported to be the most commonly diagnosed antecedent of GBS, yet little information is available about the risk of post-Campylobacter GBS. Data collected through active, population-based surveillance in the Emerging Infections Program during the 2009–2010 novel Influenza A (H1N1) vaccination campaign allowed us to compare confirmed and probable GBS cases to non-cases to determine whether antecedent Campylobacter infection (or a diarrhoeal illness consistent with campylobacteriosis) was more common among cases and to assess the risk of GBS following Campylobacter infection. We estimate that 8–12% of GBS cases in the USA are attributable to Campylobacter infection (or a diarrhoeal illness consistent with campylobacteriosis), with 434–650 cases of post-diarrhoeal GBS annually and about 49 cases of GBS per 100 000 Campylobacter infections. These results provide updated estimates for post-Campylobacter GBS incidence in the USA and highlight an important benefit of effective measures to prevent Campylobacter infections.