Objective To estimate the time-dependent measles effective reproduction number (Rt) as an indicator of the impact of three outbreak response vaccination (ORV) campaigns on measles transmission during a nationwide outbreak in Guinea. Methods Rt represents the average number of secondary cases generated by a single primary case in a partially immune population during a given time period. Measles Rt was estimated using daily incidence data for 3,952 outbreak-associated measles cases in Guinea in 2017 for the time periods prior to, between, and following each of three ORV campaigns using a simple and extensible mathematical model. Results Rt was estimated to be above the threshold value of 1 during the initial growth period of the outbreak until the first ORV campaign began on March 13 (Rt =1.60, 95% CI: 1.55–1.67). It subsequently dropped below 1 and remained < 1 through the end of the year (range: 0.71–0.91), although low levels of transmission persisted. Conclusions Reduction in Rt coincided with implementation of the ORV campaigns, indicating success of the campaigns at maintaining measles transmission intensity below epidemic growth levels. However, persistent measles transmission remains an issue in Guinea due to insufficient levels of herd immunity. Estimation of Rt should be further leveraged to help decision makers and field staff understand outbreak progress and the timing and type of vaccination efforts needed to halt transmission.

Objective: To map genomic diversity of Measles virus (MeV) isolates collected during 2009-2017 from ten states of India. Methods: Genome sequencing of Indian isolates and comparative genomics with global MeV using phylogeny, population stratification and selection pressure approaches were performed. Results: The first report of complete genome sequences of forty-three Indian MeV isolates belonging to genotypes D4 (eight) and D8 (thirty-five). Three Indian isolates mapped to named strains D4-Enfield, D8-Villupuram and D8-Victoria. Indian D4 isolates deviate from standard genome length due to indels in M-F intergenic region. Estimated nucleotide substitution rates of Indian MeV derived using genome and individual genes are lower than that of global isolates. Phylogeny revealed genotype-based temporal clustering, suggesting existence of two lineages of D4 and three lineages of D8 in India. Absence of spatial clustering suggests role of cross-border travel in MeV transmission. Conclusions: Evolutionary analyses suggest the need for surveillance of MeV in India, particularly in view of diversified trajectories of D4 and D8 isolates. This study contributes to global measles epidemiology and indicates no major impact on antigenicity in Indian isolates, thereby substantiating the use of current vaccines to meet measles elimination target of 2023 set by World Health Organization for South-East Asia Region.

Background : Mycobacterium chimaera, one of the Mycobacterium avium complex (MAC) members, was recently identified using modern gene sequencing analysis. Unlike M. avium and M. intracellulare, little is known about the clinical features, antimicrobial susceptibilities, and treatment outcomes of M. chimaera lung disease. Methods : This study was conducted in a medical center from December 2012 to July 2015. Patients who fulfilled the 2007 ATS/IDSA diagnostic criteria for nontuberculous mycobacterial lung disease were enrolled. M. chimaera isolates were identified based on the findings of sequencing of rpoB gene, the internal transcribed spacer (ITS) region of the 16S–23S rRNA gene, and the heat-shock protein 65 gene (hsp65). Minimum inhibitory concentrations (MICs) of 13 antimicrobial agents were determined. Results : During the study period, 247 patients with MAC lung disease were identified, and 11.3% (28/247) of the patients had lung disease caused by M. chimaera. Among these patients, 17 (60.7%) were female, and their median age was 72.5 (40–100) years. All M. chimaera isolates were susceptible to clarithromycin and rifabutin. All the isolates were resistant to moxifloxacin and only 10 (35.7%) and 2 (7.1%) were susceptible to amikacin and linezolid, respectively. Of the nine patients who received macrolide-based regimens, more achieved radiographic resolution than those treated with non-macrolide-based regimens (66.7% vs 15.8%, P=0.013), and they tended to have better survival (P=0.10). Conclusions : A substantial portion (11.3%) of MAC lung disease cases were caused by M. chimaera, and treatment with macrolide-based regimens resulted in better clinical outcomes for patients with M. chimaera lung disease.

Objectives The long-term dynamics of antibody responses in patients with influenza A(H7N9) virus infection are not well understood. Methods We conducted a longitudinal serological follow-up study in patients who were hospitalized with A(H7N9) virus infection, during 2013-2018. A(H7N9) virus-specific antibody responses were assessed by hemagglutination inhibition (HAI) and neutralization (NT) assays. A random intercept model was used to fit a curve to HAI antibody responses over time. HAI antibody responses were compared by clinical severity. Results Of 67 patients with A(H7N9) virus infection, HAI antibody titers reached 40 on average 11 days after illness onset and peaked at a titer of 290 after three months, and average titers of ≥80 and ≥40 were present until 11 months and 22 months respectively. HAI antibody responses were significantly higher in patients who experienced severe disease, including respiratory failure and acute respiratory distress syndrome, compared with patients who experienced less severe illness. Conclusions Patients with A(H7N9) virus infection who survived severe disease mounted higher antibody responses that persisted for longer periods compared with those that experienced moderate disease. Studies of convalescent plasma treatment for A(H7N9) patients should consider collection of donor plasma from survivors of severe disease between 1-11 months after illness onset.

For the monitoring of wild boar interactions with conspecific carcasses, seven wild boar carcasses were placed in different sites in the Czech Republic during winter season. Data were collected by camera traps. In total, 732 visits were recorded of wild boars at the carcass sites. Direct contact with the carcass was detected in 81% of the records. Cannibalism was observed in 9.8% of all recorded visits. The first direct contact was observed on average 30 days after the carcass had been placed in its respective site. Cannibalism was observed on average after 70 days. The effect of sex‐age class on direct contact was not proven in our study. The presented findings show that cannibalism in wild boar can play a substantial role in the ASF epidemic. These results highlighted the importance of the removal of infected carcasses from the habitat, which is crucial for African swine fever eradication.

In recent years, reports indicated that PCV3 may be involved in porcine dermatitis and nephropathy syndrome (PDNS)‐like disease similar to that linked to PCV2. A total of 2,125 porcine samples from 910 cases were collected during 2016–2018 and tested for presence of PCV3 and PCV2 by real‐time PCR assays. Results showed high prevalence of PCV3 and PCV2: 28.4% samples from 41.2% cases were PCV3 positive and 16.4% samples from 16.7% cases were PCV2 positive. The overall coinfection rate was 5.4% and 8.4% at the sample and case level, respectively. Temporal analysis indicated that PCV3 positive case rate increased from 31.6% in 2016, 40.9% in 2017, to 55.6% in 2018. Although its prevalence was lower, PCV2‐positive case rate in 2018 (28.8%) doubled that in 2017 (14.4%). The coinfection case rate also increased from 3.4% in 2016, 8.0% in 2017 to 16.1% in 2018. The high positive rate of PCV3 (56.9%) and PCV2 (33.8%) in oral fluids, PCV3 in foetuses (57.1%) and PCV2 in tonsils (54.8%) implied viral transmission route and tissue tropism. In phylogenetic analysis, two small PCV3 clusters (1 and 2) were separated but others were clustered with low bootstrapping values indicating overall low genetic diversity. Genotypes, PCV2a‐h, were confirmed by analysing 2,944 strains, with a new genotype proposed as PCV2i. In this study, 61 PCV3 unique whole genomes were sequenced; 12 belonged to a separate cluster that were characterized by five consistent amino acid changes in the capsid protein (24V, 27K, 56D, 98R and 168K) and may be associated with potential differences in immunogenicity. Among the 43 unique PCV2 whole genomes sequenced, 31 belonged to PCV2d, 7 to PCV2a and 5 to PCV2b. Thus, our study demonstrates that PCV2d is the predominant genotype and PCV3 is widely circulating in the Midwest of the USA.

Dengue is a mosquito-borne viral disease caused by one of four serotypes (DENV1-4). Infection provides long-term homologous immunity against reinfection with the same serotype. Plaque reduction neutralization test (PRNT) is the gold standard to assess serotype-specific antibody levels. We analysed serotype-specific antibody levels obtained by PRNT in two serological surveys conducted in Singapore in 2009 and 2013 using cluster analysis, a machine learning technique that was used to identify the most common histories of DENV exposure. We explored the use of five distinct clustering methods (i.e. agglomerative hierarchical, divisive hierarchical, K-means, K-medoids and model-based clustering) with varying number (from 4 to 10) of clusters for each method. Weighted rank aggregation, an evaluating technique for a set of internal validity metrics, was adopted to determine the optimal algorithm, comprising the optimal clustering method and the optimal number of clusters. The K-means algorithm with six clusters was selected as the algorithm with the highest weighted rank aggregation. The six clusters were characterised by (i) dominant DENV2 PRNT titres; (ii) co-dominant DENV1 and DENV2 titres with average DENV2 titre > average DENV1 titre; (iii) co-dominant DENV1 and DENV2 titres with average DENV1 titre > average DENV2 titre; (iv) low PRNT titres against DENV1-4; (v) intermediate PRNT titres against DENV1-4; and (vi) dominant DENV1-3 titres. Analyses of the relative size and age-stratification of the clusters by year of sample collection and the application of cluster analysis to the 2009 and 2013 datasets considered separately revealed the epidemic circulation of DENV2 and DENV3 between 2009 and 2013. Cluster analysis is an unsupervised machine learning technique that can be applied to analyse PRNT antibody titres (without pre-established cut-off thresholds to indicate protection) to explore common patterns of DENV infection and infer the likely history of dengue exposure in a population.

The sensitivity of rapid diagnostic tests (RDTs) for malaria is inadequate for detecting low-density, often asymptomatic infections, such as those that can occur when screening pregnant women for malaria. The performance of the Alere™ Ultra-sensitive Malaria Ag Plasmodium falciparum RDT (uRDT) was assessed retrospectively in pregnant women in Indonesia. The diagnostic performance of the uRDT and the CareStart™ Malaria HRP2/pLDH VOM (Plasmodium vivax, Plasmodium ovale and Plasmodium malariae) Combo RDT (csRDT) were assessed using 270 stored red blood cell pellets and plasma samples from asymptomatic pregnant women. These included 112 P. falciparum negative and 158 P. falciparum positive samples detected by a composite test (qPCR, LAMP, nPCR) as reference standard. Diagnostic indicators: sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), diagnostic odds ratio (DOR) and the level of agreement (kappa) were calculated for comparison. Compared with the reference test, the uRDT had a sensitivity of 19.6% (95% CI 13.9–26.8) and specificity of 98.2% (93.1–99.7%). The csRDT was 22.8% (16.7–30.3) sensitive and 95.5% (89.4–98.3) specific for P. falciparum infections. Performance of the uRDT was non-significantly different to the csRDT (p = 0.169). RDT outcome was stratified by qPCR cycling threshold (Ct), and performance of the RDTs was found to be comparable across parasite loads. The uRDT performed similarly to the currently used csRDTs in detecting P. falciparum infections in asymptomatic pregnant women. In these settings, molecular diagnostics are currently the most sensitive for malaria.

Anopheles maculipennis complex, the historic vector of malaria, causes serious medical problems worldwide and exhibits different behaviours. Studying the odorant-binding proteins (OBPs), which influence the chemosensory system and behavioural responses, is essential to understanding the population structure and developing effective control measures against this vector. The present study was designed to identify and analyse the obp1 gene in An. maculipennis. Adults of An. maculipennis sensu stricto were collected in Zanjan Province, northwest of Iran, and gDNAs of female mosquitoes were extracted. Fragments of An. maculipennis obp1 (Amacobp1) gene were amplified using degenerate and specific primers, and some of amplicons were selected for sequencing. Analysis of amplified products identified that the sequence of Amacobp1 gene was 1341 bp long. This gene contains three exons (5′, internal, and 3′of 160, 256, and 18 bp, respectively) and encodes 144 amino acids. The sizes of introns I and II in deduced gene are 268 and 358 nucleotides, respectively. The amino acid sequence in the C-terminal of AmacOBP1 is similar to that of major malaria vector Anopheles species. However, its N-terminal has a specific signal peptide with 19 amino acids. This peptide is conserved in different studied populations, and its sequence of amino acids shows the most variation among anopheline species. Degenerate primers in this study are suggested for studying obp1 gene in Anopheles species. Amacobp1 gene is proposed as a molecular marker for the detection of intraspecific ecotypes and diagnosis of different species within Maculipennis Group. Moreover, the N-terminal of AmacOBP1 peptide is recommended as a molecular marker to identify the Amacobp1 expression patterns in different chemosensory organs for assessing the molecular mechanisms and developing novel behavioural disturbance agents to control An. maculipennis.

Malaria prevalence has significantly reduced since 2000, largely due to the scale-up of vector control interventions, mainly indoor residual spraying (IRS) and long-lasting insecticide-treated nets (LLINs). Given their success, these tools remain the frontline interventions in the fight against malaria. Their effectiveness relies on three key ingredients: the intervention, the mosquito vector and the end-user. Regarding the intervention, factors such as the insecticide active ingredient(s) used and the durability and/or bio-efficacy of the tool over time are critical. For the vectors, these factors include biting and resting behaviours and the susceptibility to insecticides. Finally, the end-users need to accept and properly use the intervention. Whilst human attitude and behaviour towards LLINs are well-documented both during and after distribution, only initial coverage is monitored for IRS and in a few geographic settings the residual efficacy of the used product. Here, the historical evidence on end-users modifying their wall surfaces post-spraying is presented, a behaviour that has the potential to reduce actual IRS coverage, effectiveness and impact, as fewer people are truly protected. Therefore, clear guidelines on how to monitor IRS acceptability and/or coverage, both before, during and after spraying, are urgently needed as part of the Monitoring and Evaluation of malaria programmes.

Malaria remains a global health problem and accurate surveillance of Plasmodium parasites that are responsible for this disease is required to guide the most effective distribution of control measures. Serological surveillance will be particularly important in areas of low or periodic transmission because patient antibody responses can provide a measure of historical exposure. While methods for detecting host antibody responses to Plasmodium falciparum and Plasmodium vivax are well established, development of serological assays for Plasmodium knowlesi, Plasmodium ovale and Plasmodium malariae have been inhibited by a lack of immunodiagnostic candidates due to the limited availability of genomic information. Using the recently completed genome sequences from P. malariae, P. ovale and P. knowlesi, a set of 33 candidate cell surface and secreted blood-stage antigens was selected and expressed in a recombinant form using a mammalian expression system. These proteins were added to an existing panel of antigens from P. falciparum and P. vivax and the immunoreactivity of IgG, IgM and IgA immunoglobulins from individuals diagnosed with infections to each of the five different Plasmodium species was evaluated by ELISA. Logistic regression modelling was used to quantify the ability of the responses to determine prior exposure to the different Plasmodium species. Using sera from European travellers with diagnosed Plasmodium infections, antigens showing species-specific immunoreactivity were identified to select a panel of 22 proteins from five Plasmodium species for serological profiling. The immunoreactivity to the antigens in the panel of sera taken from travellers and individuals living in malaria-endemic regions with diagnosed infections showed moderate power to predict infections by each species, including P. ovale, P. malariae and P. knowlesi. Using a larger set of patient samples and logistic regression modelling it was shown that exposure to P. knowlesi could be accurately detected (AUC = 91%) using an antigen panel consisting of the P. knowlesi orthologues of MSP10, P12 and P38. Using the recent availability of genome sequences to all human-infective Plasmodium spp. parasites and a method of expressing Plasmodium proteins in a secreted functional form, an antigen panel has been compiled that will be useful to determine exposure to these parasites.

Human brucellosis is a neglected public health issue in China and reports of HIV-infected individuals complicated with brucellosis are rare. This report describes the case of an HIV-infected patient complicated with brucellosis. We want to raise awareness of clinical diagnosis of brucellosis among clinicians. Furthermore, we should be more concerned about cases with pyrexia of unknown origin, especially in non-epidemic areas of brucellosis in China. We encountered the case of a 31-year-old HIV-infected male with a CD4+ T lymphocyte count of approximately 300. On May 1, 2019, the patient had onset of non-specific caustic irregular fever with body temperature reaching 41.0 °C. He was admitted to two medical institutions in Yunnan with pyrexia of unknown origin. Finally, on day 7 of hospitalization in the Public Health Clinical Medical Center in Chengdu City, he was diagnosed as having brucellosis infection based on blood culture results. This is the first reported case of brucellosis concomitant with HIV infection in China. Laboratories in infectious disease hospitals and category A level III hospitals in the southern provinces of China should be equipped with reagents for clinical diagnosis of brucellosis and to strengthen the awareness of brucellosis diagnosis in China. Secondly, in provinces with a high incidence of AIDS and brucellosis such as Xinjiang and Henan, it is recommended to implement a joint examination strategy to ensure the early detection, diagnosis, and treatment of this infection.

Opportunistic infections (OIs) are the leading cause of morbidity and mortality among children living with human immunodeficiency virus (HIV). For better treatments and interventions, current and up-to-date information concerning occurrence of opportunistic infections in HIV-infected children is crucial. However, studies regarding the incidence of common opportunistic infections in HIV-infected children in Ethiopia are very limited. Hence, this study aimed to determine the incidence of opportunistic infections among HIV-infected children on antiretroviral therapy (ART) at Debre Markos Referral Hospital. A facility-based retrospective cohort study was undertaken at Debre Markos Referral Hospital for the period of January 1, 2005 to March 31, 2019. A total of 408 HIV-infected children receiving ART were included. Data from HIV-infected children charts were extracted using a data extraction form adapted from ART entry and follow-up forms. Data were entered using Epi-data™ Version 3.1 and analyzed using Stata™ Version 14. The Kaplan Meier survival curve was used to estimate the opportunistic infections free survival time. Both bi-variable and multivariable Cox proportional hazard models were fitted to identify the predictors of opportunistic infections. This study included the records of 408 HIV-infected children-initiated ART between the periods of January 1, 2005 to March 31, 2019. The overall incidence rate of opportunistic infections during the follow-up time was 9.7 (95% CI: 8.13, 11.48) per 100 child-years of observation. Tuberculosis at 29.8% was the most commonly encountered OI at follow-up. Children presenting with advanced disease stage (III and IV) (AHR: 1.8, 95% CI: 1.2, 2.7), having “fair” or “poor” ART adherence (AHR: 2.6, 95% CI: 1.8, 3.8), not taking OI prophylaxis (AHR:1.6, 95% CI: 1.1, 2.4), and CD4 count or % below the threshold (AHR:1.7, 95% CI: 1.1, 2.6) were at a higher risk of developing opportunistic infections. In this study, the incidence rate of opportunistic infections among HIV-infected children remained high. Concerning predictors, such as advanced disease stage (III and IV), CD4 count or % below the threshold, “fair” or “poor” ART adherence, and not taking past OI prophylaxis were found to be significantly associated with OIs.

With the increase of awareness of mycoplasma pneumoniae pneumonia (MPP), we found thrombosis in severe MPP (SMPP) was not rare. The aim of the study was to investigate the clinical characteristics, treatment, and long-term prognosis of MPP-associated thrombosis. We retrospectively reviewed the medical records of 43 children with MPP-associated thrombosis between January 2013 and June 2019 at Beijing Children’s Hospital. The results of blood coagulation studies, autoimmune antibody, thrombophilia screening, contrast-enhanced lung computed tomography, echocardiography, and blood vessel ultrasonography were analyzed, as were treatment outcomes. Forty-two patients were diagnosed with SMPP. D-dimer was higher than 5.0 mg/L in 58.1% (25/43) of patients. The mean D-dimer level was 11.1 ± 12.4 mg/L. Anticardiolipin-IgM was positive in 60.0% of patients, β2-glycoprotein-IgM in 64.0%, and lupus anticoagulant in 42.1%. Chest imaging revealed pulmonary consolidation with lobe distribution in all patients (2/3–1 lobe in 10 patients, > 1 lobe in 29 patients). In our experience, thrombosis can occur in a vessel of any part of the body, and it can be initially detected as late as 31 days after disease onset. Thrombosis in the brain and abdomen can occur early, at 5 days after disease onset. Pulmonary vessels were the most commonly involved sites in the current study, and accordingly chest pain was the most common symptom (32.6%), followed by neurological symptoms (14.0%) and abdominal pain (9.3%). Thirty-five percent of patients were asymptomatic with regard to thrombosis. All patients underwent anticoagulant therapy, and thrombus absorption took > 3 months in most patients. All patients were followed until October 2019, at which time 41 were asymptomatic and 2 had mild recurrent cough. SMPP with pulmonary consolidation (> 2/3 lobe) was the most strongly associated risk factor for thrombosis. Thrombosis-associated symptoms may be subtle, even absent. Elevated D-dimer, specifically > 11.1 mg/L (even > 5.0 mg/L), would assist in the early diagnosis of thrombosis. The long-term prognosis of thrombosis was good after timely administration of anticoagulant therapy.

Faecal microbial transplantation (FMT) is currently the most effective treatment of recurrent Clostridioides difficile infection (CDI). However, up to 20% of patients experience further recurrences after single FMT. The mechanisms that lead to FMT failure and its risk factors are poorly understood. Comorbidity is one of the risk factors of the failure of standard antibiotic therapy of recurrent CDI. It is not known if comorbidity is also associated with the risk of FMT failure. We conducted a prospective observational cohort study in order to elucidate if comorbid status is associated with FMT failure. Patients with microbiologically proven recurrent CDI were recruited and underwent FMT via retention enema. Patients were followed up for 12 weeks after FMT for signs and symptoms of CDI recurrence. Single FMT failure was defined as recurrence of diarrhoea and a positive stool test for the presence of C. difficile antigen or toxin at any time point during the 12 weeks of follow-up. We assessed the association of single FMT failure with possible manageable and unmanageable risk factors. As a surrogate of comorbid status, we used Charlson Comorbidity Index (CCI) ≥ 7. A total of 60 patients that underwent single FMT (34 women, 26 men) were included in the study. Overall, 15 patients (25%) experienced single FMT failure. 24 patients (40%) had CCI ≥ 7, and 45.0% patients with CCI ≥ 7 experienced failure of single FMT. Patients who experienced single FMT failure had a significantly higher CCI and significantly lower albumin concentration as compared to patients who experienced single FMT success. There was no difference in age, C-reactive protein concentration, leukocyte count and time from FMT to first defecation. In multivariate analysis, CCI ≥ 7 was positively associated with the failure of single FMT. Analysis was controlled for sex, age, time from FMT to first defecation, concomitant PPI therapy, severe CDI, hospital-acquired infection and albumin concentration. Comorbid status surrogated by CCI is positively associated with the failure of single FMT in the treatment of recurrent CDI.

This study was conducted to understand the molecular epidemiology of circulating Chlamydia trachomatis (Ct) strains in Sapporo, Japan. A total of 713 endocervical samples collected from April 2016 to March 2019 were screened for Ct. The obtained Ct positive samples were analyzed by ompA genotyping and multilocus sequence analysis (MLSA). Eighty-three (11.6%) samples were positive for Ct plasmid DNA. Sequence analysis of the ompA gene from the 61 positive cases revealed eight genotypes: F (40.9%), E (19.6%), D (14.7%), G (9.8%), H (6.5%), I (3.2%), K (3.2%), and J (1.6%). The globally dominant genotype E and F strains were highly conserved with 13 ompA genetic variants being detected, whereas genotype D strains were the most diverse. Genetic characterization of D strains revealed that D1 genetic variants may be potentially specific to Sapporo. MLSA revealed 13 unique sequence types (STs) including four novel STs from 53 positive samples, with the globally dominant STs 39 and 19 being predominant. STs 39, 34, and 21 were exclusively associated with genotypes E and F indicating their global dominance. Novel ST70 and ST30 were specifically associated with genotype D. Our study has revealed the circulation of genetically diverse Ct strains in the women population of Sapporo, Japan. We suggest identifying a transmission network of those successful strains and implementing public health prevention strategies to control the spread of Ct in Sapporo.

Varicella is normally a self-limited childhood disease caused by varicella-zoster virus infection. However, it sometimes causes severe diseases, especially in immunocompromised individuals. We report a case of severe varicella in a young woman. A 19-year-old woman presented to the emergency department with abdominal pain and a rash after taking methylprednisolone for 2 weeks for systemic lupus erythematosis. The laboratory data showed leukocytosis, thrombocytopenia, an elevated level of the liver transaminases and disseminated intravascular coagulation. Computed tomography of the abdomen revealed multiple air-fluid levels in the intestines. Hemorrhagic varicella was considered and antiviral therapy as well as immunoglobin were applied. Her condition deteriorated and she eventually died due to multi-organ failure and refractory shock. Next-generation sequencing performed on fluid from an unroofed vesicle confirmed the diagnosis of varicella. In its severe form, VZV infection can be fatal, especially in immunocompromised patients. Hemorrhagic varicella can be misdiagnosed by clinicians because of unfamiliar with the disease, although it is associated with a high mortality rate. In patients with suspected hemorrhagic varicella infection, antiviral therapies along with supportive treatment need to be initiated as soon as possible in order to minimize the case fatality rate.

Candidaemia is the most common form of invasive candidiasis. Resistant Candida blood stream infection (BSI) is rising, with limitations on the development of broader-spectrum antifungal agents worldwide. Our study aimed to identify the occurrence of antifungal-resistant candidaemia and the distribution of these species, determine the risk factors associated with antifungal resistance and evaluate the association of antifungal-resistant candidaemia with the length of intensive care unit (ICU) and hospital stay and with 30-day mortality. A retrospective cohort study was conducted at King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia. Adult patients diagnosed with candidaemia from January 2006 to December 2017 were included. A total of 196 BSIs were identified in 94 males (49.74%) and 95 females (50.26%). C. glabrata was the most commonly isolated Candida species, with 59 (30%), followed by C. albicans with 46 (23%). Susceptibility data were available for 122/189 patients, of whom 26/122 (21%) were resistant to one or more antifungals. C. parapsilosis with available sensitivity data were found in 30/122 isolates, of which 10/30 (33%) were resistant to fluconazole. Risk factors significantly associated with antifungal-resistant candidaemia included previous echinocandin exposure (odds ratio (OR) =1.38; 95% confidence interval (CI) (1.02–1.85); P = 0.006) and invasive ventilation (OR = 1.3; 95% CI (1.08–1.57); P = 0.005). The median length of ICU stay was 29 days [range 12–49 days] in the antifungal-resistant group and 18 days [range 6.7–37.5 days] in the antifungal-sensitive group (P = 0.28). The median length of hospital stay was 51 days [range 21–138 days] in the antifungal-resistant group and 35 days [range 17–77 days] in the antifungal-sensitive group (P = 0.09). Thirty-day mortality was 15 (57.7%) and 54 (56.25%) among the antifungal-resistant and antifungal-sensitive groups, respectively (OR = 1.01; 95% CI (0.84–1.21); P = 0.89). Our results indicate a high frequancy of non- C. albicans candidaemia. The rise in C. parapsilosis resistance to fluconazole is alarming. Further studies are required to confirm this finding.

Nocardiosis is an uncommon disease caused by aerobic gram-positive bacteria Nocardia spp. Although it is usually an opportunistic infection affecting immunocompromised patients, even one third of cases occur in immunocompetent persons. The aim of the study was to describe the course of chronic meningitis due to Nocardia infection. A 52-year-old patient, chalk miner, suffered from a chronic meningitis caused by an extremely rare pathogen. The patient’s history was complicated and diagnostic process covered multiple examinations and consultations. Initially Kocuria rosea was cultured, yet after molecular examination the result was verified to Nocardia farcinica. Targeted antibiotic treatment was implemented, which resulted in gradual improvement of patients condition. A full recovery was achieved after one year antibiotic therapy.

Critically ill patients undergo extensive physiological alterations that will have impact on antibiotic pharmacokinetics. Up to 60% of intensive care unit (ICU) patients meet the pharmacodynamic targets of beta-lactam antibiotics, with only 30% in fluoroquinolones. Not reaching these targets might increase the chance of therapeutic failure, resulting in increased mortality and morbidity, and antibiotic resistance. The DOLPHIN trial was designed to demonstrate the added value of therapeutic drug monitoring (TDM) of beta-lactam and fluoroquinolones in critically ill patients in the ICU. A multi-centre, randomised controlled trial (RCT) was designed to assess the efficacy and cost-effectiveness of model-based TDM of beta-lactam and fluoroquinolones. Four hundred fifty patients will be included within 24 months after start of inclusion. Eligible patients will be randomly allocated to either study group: the intervention group (active TDM) or the control group (non-TDM). In the intervention group dose adjustment of the study antibiotics (cefotaxime, ceftazidime, ceftriaxone, cefuroxime, amoxicillin, amoxicillin with clavulanic acid, flucloxacillin, piperacillin with tazobactam, meropenem, and ciprofloxacin) on day 1, 3, and 5 is performed based upon TDM with a Bayesian model. The primary outcome will be ICU length of stay. Other outcomes amongst all survival, disease severity, safety, quality of life after ICU discharge, and cost effectiveness will be included. No trial has investigated the effect of early TDM of beta-lactam and fluoroquinolones on clinical outcome in critically ill patients. The findings from the DOLPHIN trial will possibly lead to new insights in clinical management of critically ill patients receiving antibiotics. In short, to TDM or not to TDM? EudraCT number: 2017–004677-14. Sponsor protocol name: DOLPHIN. Registered 6 March 2018 . Protocol Version 6, Protocol date: 27 November 2019.

Cytomegalovirus (CMV) infection is one of the most common opportunistic infections following organ transplantation, despite administration of CMV prophylaxis. CMV-specific T-cell immunity (TCI) has been associated with reduced rates of CMV infection. We describe for the first time clinical experience using the CMV T-Cell Immunity Panel (CMV-TCIP), a commercially available assay which measures CMV-specific CD4+ and CD8+ T-cell responses, to predict clinically significant CMV events. Adult (> 18-year-old) patients with CMV-TCIP results and ≥ 1 subsequent assessment for CMV DNAemia were included at Brown University and the University of Maryland Medical Center-affiliated hospitals between 4/2017 and 5/2019. A clinically significant CMV event was defined as CMV DNAemia prompting initiation of treatment. We excluded indeterminate results, mostly due to background positivity, allogeneic hematopoetic cell transplant (HCT) recipients, or patients who were continued on antiviral therapy against CMV irrespective of the CMV-TCIP result, because ongoing antiviral therapy could prevent a CMV event. We analyzed 44 samples from 37 patients: 31 were solid organ transplant recipients, 4 had hematologic malignancies, 2 had autoimmune disorders. The CMV-protection receiver operating characteristic (ROC) area under the curve (AUC) was significant for %CMV-specific CD4+ (AUC: 0.78, P < 0.001) and borderline for CD8+ (AUC: 0.66, P = 0.064) T-cells. At a cut-off value of 0.22% CMV-specific CD4+ T-cells, positive predictive value (PPV) for protection against CMV was 85% (95%CI 65–96%), and negative predictive value (NPV) was 67% (95%CI 41–87%). The CMV-TCIP, in particular %CMV-specific CD4+ T-cells, showed good diagnostic performance to predict CMV events. The CMV-TCIP may be a useful test in clinical practice, and merits further validation in larger prospective studies.

We queried hospital patients about international travel in the previous 30 days to assess potential importation of emerging infections. We used 12 months of deidentified data to analyze patient demographics, travel destinations, and diagnoses for exposure to Zika virus. Our approach could be used to analyze potential infectious disease exposures.

Yaws, a neglected tropical disease caused by the bacterium Treponema pallidum subspecies pertenue, manifests as ulcerative skin lesions. Nucleic acid amplification tests, like loop-mediated isothermal amplification (LAMP), are versatile tools to distinguish yaws from infections that cause similar skin lesions, primarily Haemophilus ducreyi. We developed a novel molecular test to simultaneously detect T. pallidum and H. ducreyi based on mediator displacement LAMP. We validated the T. pallidum and H. ducreyi LAMP (TPHD-LAMP) by testing 293 clinical samples from patients with yaws-like lesions. Compared with quantitative PCR, the TPHD-LAMP demonstrated high sensitivity and specificity for T. pallidum (84.7% sensitivity, 95.7% specificity) and H. ducreyi (91.6% sensitivity, 84.8% specificity). This novel assay provided rapid molecular confirmation of T. pallidum and H. ducreyi DNA and might be suitable for use at the point of care. TPHD-LAMP could support yaws eradication by improving access to molecular diagnostic tests at the district hospital level.

Observed peaks of acute flaccid myelitis (AFM) cases have occurred biennially since 2014 in the United States. We aimed to determine if AFM etiology differed between peak and nonpeak years, considering that clinical features of AFM differ by virus etiology. We compared clinical and laboratory characteristics of AFM cases that occurred during peak (2016 and 2018, n = 366) and nonpeak (2015 and 2017, n = 50) years. AFM patients in peak years were younger (5.2 years) than those in nonpeak years (8.3 years). A higher percentage of patients in peak years than nonpeak years had pleocytosis (86% vs. 60%), upper extremity involvement (33% vs. 16%), and an illness preceding limb weakness (90% vs. 62%) and were positive for enterovirus or rhinovirus RNA (38% vs. 16%). Enterovirus D68 infection was associated with AFM only in peak years. Our findings suggest AFM etiology differs between peak and nonpeak years.

We determined prevalence of Rickettsia spp. in 172 ticks of the Amblyomma maculatum group collected from 16 urban sites in Oklahoma City, Oklahoma, USA, during 2017 and 2018. Most ticks (59.3%) were collected from 1 site; 4 (2.3%) were infected with Rickettsia parkeri and 118 (68.6%) with Candidatus Rickettsia andeanae.

In July 2018, recombinant norovirus GII.Pe-GII.4 Sydney was detected in dogs who had diarrhea in a kennel and in children living on the same premises in Thailand. Whole-genome sequencing and phylogenetic analysis of 4 noroviruses from Thailand showed that the canine norovirus was closely related to human norovirus GII.Pe-GII.4 Sydney, suggesting human-to-canine transmission.

We describe Yersina pestis minimum infection prevalence in fleas collected from Tamias spp. chipmunks in the Sierra Nevadas (California, USA) during 2013–2015. Y. pestis–positive fleas were detected only in 2015 (year of plague epizootic), mostly in T. speciosus chipmunks at high-elevation sites. Plague surveillance should include testing vectors for Y. pestis.

An estimated one quarter of persons worldwide are infected with Mycobacterium tuberculosis. In 2018, the World Health Organization issued revised guidance on BCG vaccine for high-risk groups. The World Health Organization should consider guiding countries on a case-by-case basis in developing appropriate BCG policies to deliver equitable healthcare and protect public health.

International policy for treatment of multidrug- and rifampin-resistant tuberculosis (MDR/RR TB) relies largely on individual patient data (IPD) from observational studies of patients treated under routine conditions. We prepared guidance on which data to collect and what measures could improve consistency and utility for future evidence-based recommendations. We highlight critical stages in data collection at which improvements to uniformity, accuracy, and completeness could add value to IPD quality. Through a repetitive development process, we suggest essential patient- and treatment-related characteristics that should be collected by prospective contributors of observational IPD in MDR/RR TB.

We report the use of environmental samples to assess avian influenza virus activity in chickens at live poultry markets in China. Results of environmental and chicken samples correlate moderately well. However, collection of multiple environmental samples from holding, processing, and selling areas is recommended to detect viruses expected to have low prevalence.

We report isolation of a New Delhi metallo-β-lactamase-5–producing carbapenem-resistant Escherichia coli sequence type 167 from companion animals in the United States. Reports of carbapenem-resistant Enterobacteriaceae in companion animals are rare. We describe a unique cluster of blaNDM-5–producing E. coli in a veterinary hospital.

Human anthrax cases necessitate rapid response. We completed Bacillus anthracis nanopore whole-genome sequencing in our high-containment laboratory from a human anthrax isolate hours after receipt. The de novo assembled genome showed no evidence of known antimicrobial resistance genes or introduced plasmid(s). Same-day genomic characterization enhances public health emergency response.

The full geographic range of coccidioidomycosis is unknown, although it is most likely expanding with environmental change. We report an apparently autochthonous coccidioidomycosis patient from Spokane, Washington, USA, a location to which Coccidioides spp. are not known to be endemic.

Hepatitis E virus (HEV) RNA was detected in 6.3% and HEV IgG in 40% of 5,033 serum samples from market-weight pigs at 25 slaughterhouses in 10 US states. The prevalent HEV genotype was zoonotic genotype 3, group 2. Blood of HEV-viremic pigs from slaughterhouses may contaminate pork supply chains.

At the end of the 2013–2016 Ebola virus disease outbreak in Guinea, we implemented an alert system for early detection of Ebola resurgence among survivors. Survivors were asked to report health alerts in their household and provide body fluid specimens for laboratory testing. During April–September 2016, a total of 1,075 (88%) of 1,215 survivors participated in the system; follow up occurred at a median of 16 months after discharge (interquartile range 14–18 months). Of these, 784 acted as focal points and reported 1,136 alerts (including 4 deaths among survivors). A total of 372 (91%) of 408 eligible survivors had >1 semen specimen tested; of 817 semen specimens, 5 samples from 4 survivors were positive up to 512 days after discharge. No lochia (0/7) or breast milk (0/69) specimens tested positive. Our findings underscore the importance of long-term monitoring of survivors’ semen samples in an Ebola-affected country.

In North America, hantaviruses commonly cause hantavirus pulmonary syndrome (HPS). Clinical descriptions of hantavirus-associated renal disease in the Americas are scarce. Herein, we discuss the case of a 61-year-old man whose predominant manifestations were acute kidney injury and proteinuria. Clinical recognition of renal signs in hantavirus infections can reduce risk for death.

Crimean-Congo hemorrhagic fever virus (CCHFV) causes severe disease with fatalities. Awareness of potential sources of infection is important to reduce risk to healthcare workers and contacts. We detected CCHFV RNA in formalin-fixed, paraffin-embedded tissues from a spontaneous abortion that were submitted for histology 9 weeks after a suspected CCHFV infection in the mother.

We describe 6 clinical isolates of Elizabethkingia anophelis from a pediatric referral hospital in Cambodia, along with 1 isolate reported from Thailand. Improving diagnostic microbiological methods in resource-limited settings will increase the frequency of reporting for this pathogen. Consensus on therapeutic options is needed, especially for resource-limited settings.

We describe 2 human cases of infection with a new Neisseria species (putatively N. brasiliensis), 1 of which involved bacteremia. Genomic analyses found that both isolates were distinct strains of the same species, were closely related to N. iguanae, and contained a capsule synthesis operon similar to N. meningitidis.

Incidence of human granulocytic anaplasmosis is rising in Maine, USA. This increase may be explained in part by adoption of tick panels as a frequent diagnostic test in persons with febrile illness and in part by range expansion of Ixodes scapularis ticks and zoonotic amplification of Anaplasma phagocytophilum.

Pegivirus

Mycetoma is a chronic infection that is slow to develop and heal. It can be caused by fungi (eumycetoma) or bacteria (actinomycetoma). We describe a case of actinomycetoma caused by Actinomadura mexicana in the Caribbean region.

In November 2017, the mobile digital Surveillance Outbreak Response Management and Analysis System was deployed in 30 districts in Nigeria in response to an outbreak of monkeypox. Adaptation and activation of the system took 14 days, and its use improved timeliness, completeness, and overall capacity of the response.

We report the identification of astrovirus WI65268 in a white-tailed deer with respiratory disease in the United States in 2018. This virus is a recombinant of Kagoshima1-7 and Kagoshima2-3-2 (both bovine astroviruses from Japan) and was characterized as a potential new genotype. Further surveillance of deer might help identify related isolates.

Our retrospective study compared genotypic antimicrobial resistance in Mycoplasma genitalium–positive specimens collected from 48 community and 33 sexual health clinic (SHC) patients. Macrolide resistance was similar in community (75%) and SHC (76%) patients. We observed no significant difference in fluoroquinolone resistance between community (19%) and SHC (27%) patients (p = 0.66).

The incidence of hospitalized leptospirosis patients was positively associated with increased precipitation in Salvador, Brazil. However, Leptospira infection risk among a cohort of city residents was inversely associated with rainfall. These findings indicate that, although heavy rainfall may increase severe illness, Leptospira exposures can occur year-round.

Coronaviruses cause respiratory and gastrointestinal diseases in diverse host species. Deltacoronaviruses (DCoVs) have been identified in various songbird species and in leopard cats in China. In 2009, porcine deltacoronavirus (PDCoV) was detected in fecal samples from pigs in Asia, but its etiologic role was not identified until 2014, when it caused major diarrhea outbreaks in swine in the United States. Studies have shown that PDCoV uses a conserved region of the aminopeptidase N protein to infect cell lines derived from multiple species, including humans, pigs, and chickens. Because PDCoV is a potential zoonotic pathogen, investigations of its prevalence in humans and its contribution to human disease continue. We report experimental PDCoV infection and subsequent transmission among poultry. In PDCoV-inoculated chicks and turkey poults, we observed diarrhea, persistent viral RNA titers from cloacal and tracheal samples, PDCoV-specific serum IgY antibody responses, and antigen-positive cells from intestines.

We aimed to clarify the epidemiologic and clinical importance of evolutionary events that occurred in carbapenem-resistant Klebsiella pneumoniae (CRKP). We collected 203 CRKP causing bloodstream infections in a tertiary hospital in China during 2013–2017. We detected a subclonal shift in the dominant clone sequence type (ST) 11 CRKP in which the previously prevalent capsular loci (KL) 47 had been replaced by KL64 since 2016. Patients infected with ST11-KL64 CRKP had a significantly higher 30-day mortality rate than other CRKP-infected patients. Enhanced virulence was further evidenced by phenotypic tests. Phylogenetic reconstruction demonstrated that ST11-KL64 is derived from an ST11-KL47–like ancestor through recombination. We identified a pLVPK-like virulence plasmid carrying rmpA and peg-344 in ST11-KL64 exclusively from 2016 onward. The pLVPK-like–positive ST11-KL64 isolates exhibited enhanced environmental survival. Retrospective screening of a national collection identified ST11-KL64 in multiple regions. Targeted surveillance of this high-risk CRKP clone is urgently needed.

Most human pegivirus 2 (HPgV-2) infections are associated with past or current hepatitis C virus (HCV) infection. HPgV-2 is thought to be a bloodborne virus: higher prevalence of active infection has been found in populations with a history of parenteral exposure to viruses. We evaluated longitudinally collected blood samples obtained from injection drug users (IDUs) for active and resolved HPgV-2 infections using a combination of HPgV-2 specific molecular and serologic tests. We found evidence of HPgV-2 infection in 11.2% (22/197) of past or current HCV-infected IDUs, compared with 1.9% (4/205) of an HCV-negative IDU population. Testing of available longitudinal blood samples from HPgV-2 positive participants identified 5 with chronic infection (>6 months viremia in >3 timepoints); 2 were identified among the HCV-positive IDUs and 3 among the HCV-negative IDUs. Our findings indicate that HPgV-2 can establish chronic infection and replicate in the absence of HCV.

Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes a spectrum of respiratory illness, from asymptomatic to mild to fatal. MERS-CoV is transmitted sporadically from dromedary camels to humans and occasionally through human-to-human contact. Current epidemiologic evidence supports a major role in transmission for direct contact with live camels or humans with symptomatic MERS, but only limited evidence supports the possibility of transmission from camel products or asymptomatic MERS cases. Because a proportion of case-patients do not report direct contact with camels or with persons who have symptomatic MERS, further research is needed to conclusively determine additional mechanisms of transmission, to inform public health practice, and to refine current precautionary recommendations.

We conducted a retrospective analysis of all reports in ProMED-mail that were initially classified as undiagnosed diseases during 2007–2018. We identified 371 cases reported in ProMED-mail; 34% were later diagnosed. ProMED-mail could be used to supplement other undiagnosed disease surveillance systems worldwide.

Influenza A(H1N1)pdm09 (pH1N1) virus has become established in swine in the United Kingdom and currently co-circulates with previously enzootic swine influenza A virus (IAV) strains, including avian-like H1N1 and human-like H1N2 viruses. During 2010, a swine influenza A reassortant virus, H1N2r, which caused mild clinical disease in pigs in the United Kingdom, was isolated. This reassortant virus has a novel gene constellation, incorporating the internal gene cassette of pH1N1-origin viruses and hemagglutinin and neuraminidase genes of swine IAV H1N2 origin. We investigated the pathogenesis and infection dynamics of the H1N2r isolate in pigs (the natural host) and in ferrets, which represent a human model of infection. Clinical and virologic parameters were mild in both species and both intraspecies and interspecies transmission was observed when initiated from either infected pigs or infected ferrets. This novel reassortant virus has zoonotic and reverse zoonotic potential, but no apparent increased virulence or transmissibility, in comparison to pH1N1.

We report transcontinental expansion of Vibrio parahaemolyticus sequence type 36 into Lima, Peru. From national collections, we identified 7 isolates from 2 different Pacific Northwest complex lineages that surfaced during 2011–2016. Sequence type 36 is likely established in environmental reservoirs. Systematic surveillance enabled detection of these epidemic isolates.

Hand, foot and mouth disease (HFMD) is an emerging infection with pandemic potential. Knowledge of neutralizing antibody responses among its pathogens is essential to inform vaccine development and epidemiologic research. We used 120 paired-plasma samples collected at enrollment and >7 days after the onset of illness from HFMD patients infected with enterovirus A71 (EV-A71), coxsackievirus A (CVA) 6, CVA10, and CVA16 to study cross neutralization. For homotypic viruses, seropositivity increased from <60% at enrollment to 97%–100% at follow-up, corresponding to seroconversion rates of 57%–93%. Seroconversion for heterotypic viruses was recorded in only 3%–23% of patients. All plasma samples from patients infected with EV-A71 subgenogroup B5 could neutralize the emerging EV-A71 subgenogroup C4. Collectively, our results support previous reports about the potential benefit of EV-A71 vaccine but highlight the necessity of multivalent vaccines to control HFMD.

We report a case of Rickettsia sibirica mongolitimonae infection, an emerging tickborne rickettsiosis, with associated encephalitis in a 66-year-old man. Diagnosis was rapidly confirmed by quantitative PCR obtained from an eschar swab sample. The patient was successfully treated with oral doxycycline.

In the aftermath of a large Q fever (QF) epidemic in the Netherlands during 2007–2010, new chronic QF (CQF) patients continue to be detected. We developed a health-economic decision model to evaluate the cost-effectiveness of a 1-time screening program for CQF 7 years after the epidemic. The model was parametrized with spatial data on QF notifications for the Netherlands, prevalence data from targeted screening studies, and clinical data from the national chronic QF database. The cost-effectiveness of screening varied substantially among subpopulations and geographic areas. Screening that focused on cardiovascular risk patients in areas with high QF incidence during the epidemic ranged from cost-saving to €31,373 per quality-adjusted life year gained, depending on the method to estimate the prevalence of CQF. The cost per quality-adjusted life year of mass screening of all older adults was €70,000 in the most optimistic scenario.

Films illustrate 2 ways that epidemics can affect societies: fear leading to a breakdown in sociability and fear stimulating preservation of tightly held social norms. The first response is often informed by concern over perceived moral failings within society, the second response by the application of arbitrary or excessive controls from outside the community.

During a surveillance study of patients in a long-term care facility and the affiliated acute care hospital in the United States, we identified a Clostridioides difficile strain related to the epidemic PCR ribotype (RT) 027 strain associated with hospital outbreaks of severe disease. Fifteen patients were infected with this strain, characterized as restriction endonuclease analysis group DQ and RT591. Like RT027, DQ/RT591 contained genes for toxin B and binary toxin CDT and a tcdC gene of identical sequence. Whole-genome sequencing and multilocus sequence typing showed that DQ/RT591 is a member of the same multilocus sequence typing clade 2 as RT027 but in a separate cluster. DQ/RT591 produced a similar cytopathic effect as RT027 but showed delayed toxin production in vitro. DQ/RT591 was susceptible to moxifloxacin but highly resistant to clindamycin. Continued surveillance is warranted for this clindamycin-resistant strain that is related to the fluoroquinolone-resistant epidemic RT027 strain.

During December 2016–May 2017, an outbreak of chikungunya virus infection occurred across Pakistan. The East/Central/South African genotype was predominant. This study provides baseline data on the virus strain and emphasizes the need for active surveillance and implementation of preventive interventions to contain future outbreaks.

Alveolar echinococcosis is a parasitic disease caused by the tapeworm larval stage of Echinococcus multilocularis. This zoonotic disease has not been known to occur in Croatia. We report a confirmed case of human alveolar echinococcosis in a patient in Croatia who had never visited a known E. multilocularis–endemic area.