Endemic Infection Research Articles

Reducing Multidrug-Resistant (MDR) Klebsiella pneumoniae via the Efficient Use of Bacteriophages ZI3 and HI3

Klebsiella pneumoniae is a common cause of multidrug-resistant (MDR) pneumonia, bacteremia, urinary tract infections (UTIs), and other systemic infections. K. pneumoniae is the third most common pathogen in blood cultures from sepsis patients. It can cause severe epidemic and endemic nosocomial infections. Antibiotic treatment of K. pneumoniae infections is getting increasingly challenging due to the development of antimicrobial resistance among pathogens. Hence, a new alternative strategy is required to treat such infections. Bacteriophages are the most prevalent biological entity on the planet with an estimated 1031 particles. As obligatory intracellular parasites, they infect bacterial cells. They have a high host specificity and can replicate and lyse bacterial cells. In this research, two novel indigenous bacteriophages against K. pneumoniae strain kp8890 were isolated, characterized, and labeled as ZI3 and HI3. Both these phages were found to have a specific host range for K. pneumoniae. HI3 was able to lyse 7 out of 10 different K. pneumoniae clinical isolates, while ZI3 was able to lyse 5 out of 10 isolates, although it could not infect bacteria from other species. The isolated phages showed viability up to 50°C and pH ranging from 3 to 9. HI3 inhibited bacterial growth for 18 hours. Whereas, ZI3 showed an excellent bacterial reduction ability by inhibiting and decreasing the number of initial bacterial inoculum for 24 hours of observation. Keeping in view the excellent bacterial growth reduction, phage titer, pH and thermal stability, and host range, it is suggested that both bacteriophages, that is, ZI3 and HI3 can be potential phage therapy candidates after necessary animal modeling and clinical trials in the future.

Predicting the impact of COVID-19 non-pharmaceutical intervention on short- and medium-term dynamics of enterovirus D68 in the US

Recent outbreaks of enterovirus D68 (EV-D68) infections, and their causal linkage with acute flaccid myelitis (AFM), continue to pose a serious public health concern. During 2020 and 2021, the dynamics of EV-D68 and other pathogens have been significantly perturbed by non-pharmaceutical interventions against COVID-19; this perturbation presents a powerful natural experiment for exploring the dynamics of these endemic infections. In this study, we analyzed publicly available data on EV-D68 infections, originally collected through the New Vaccine Surveillance Network, to predict their short- and long-term dynamics following the COVID-19 interventions. Although long-term predictions are sensitive to our assumptions about underlying dynamics and changes in contact rates during the NPI periods, the likelihood of a large outbreak in 2023 appears to be low. Comprehensive surveillance data are needed to accurately characterize future dynamics of EV-D68. The limited incidence of AFM cases in 2022, despite large EV-D68 outbreaks, poses further questions for the timing of the next AFM outbreaks.

Ocular Manifestations of Flavivirus Infections.

Flaviviruses are a group of positive-sense, single-stranded RNA viruses predominantly transmitted by arthropods (mainly mosquitoes) that cause severe endemic infections and epidemics on a global scale. They represent a major cause of systemic morbidity and death and are expanding worldwide. Among this group, dengue fever, the West Nile virus, yellow fever, Japanese Encephalitis, and, recently, the Zika virus have been linked to a spectrum of ocular manifestations. These manifestations encompass subconjunctival hemorrhages and conjunctivitis, anterior and posterior uveitis (inclusive of vitritis, chorioretinitis, and retinal vasculitis), maculopathy, retinal hemorrhages, and optic neuritis. Clinical diagnosis of these infectious diseases is primarily based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular involvement. Diagnosis confirmation relies on laboratory testing, including RT-PCR and serological testing. Ocular involvement typically follows a self-limited course but can result in irreversible visual impairment. Effective treatments of flavivirus infections are currently unavailable. Prevention remains the mainstay for arthropod vector and zoonotic disease control. Effective vaccines are available only for the yellow fever virus, dengue virus, and Japanese Encephalitis virus. This review comprehensively summarizes the current knowledge regarding the ophthalmic manifestations of the foremost flavivirus-associated human diseases.

Estimation of Norovirus infections in Japan: An application of wastewater-based epidemiology for enteric disease assessment

Noroviruses of genogroup I (NoV GI) and NoV GII are the primary causes of acute gastroenteritis (AGE) in developed countries. However, asymptomatic and untested NoV infections lead to an underestimation of AGE cases, and the lack of mandatory viral identification in clinical cases hinders precise estimation of NoV infections. Back estimation of NoV infections in the community using a wastewater-based epidemiology (WBE) approach can provide valuable insights into the disease's extent, progression, and epidemiology, aiding in developing effective control strategies. This study employed a one-step reverse transcription-quantitative PCR to quantify NoVs GI and GII in wastewater samples (n = 83) collected twice a week from June 2022 to March 2023 in Japan. All samples from the Winter-Spring (n = 27) tested positive for NoV GI and GII RNA, while 73 % and 88 % of samples from the Summer-Autumn (n = 56) were positive for NoV GI and NoV GII RNA, respectively. Significantly higher concentrations of NoV GI/GII RNA were found in the Winter-Spring season compared to the Summer-Autumn season. NoV RNA was consistently detected in wastewater throughout the year, demonstrating the persistence of AGE cases in the catchment, suggesting an endemic NoV infection. Estimates of NoV infection incorporated viral RNA concentrations, wastewater parameters, and signal persistence in a mass balance equation using Monte Carlo Simulation. The median estimated NoV GI infections per 100,000 population for Summer-Autumn was 133 and for the Winter-Spring season, it was 881. Estimated NoV GII infections were 1357 for Summer-Autumn and 11,997 for the Winter-Spring season per 100,000 population. The estimated NoV infections exceeded by 3.2 and 23.9 folds than the reported AGE cases in Summer-Autumn and Winter-Spring seasons, respectively. The seasonal trend of estimated NoV infections closely matched that of AGE cases, highlighting the utility of WBE in understanding the epidemiology of enteric infections.

Evaluation of the Antiviral Activity of Tabamide A and Its Structural Derivatives against Influenza Virus.

Influenza viruses cause severe endemic respiratory infections in both humans and animals worldwide. The emergence of drug-resistant viral strains requires the development of new influenza therapeutics. Tabamide A (TA0), a phenolic compound isolated from tobacco leaves, is known to have antiviral activity. We investigated whether synthetic TA0 and its derivatives exhibit anti-influenza virus activity. Analysis of structure-activity relationship revealed that two hydroxyl groups and a double bond between C7 and C8 in TA0 are crucial for maintaining its antiviral action. Among its derivatives, TA25 showed seven-fold higher activity than TA0. Administration of TA0 or TA25 effectively increased survival rate and reduced weight loss of virus-infected mice. TA25 appears to act early in the viral infection cycle by inhibiting viral mRNA synthesis on the template-negative strand. Thus, the anti-influenza virus activity of TA0 can be expanded by application of its synthetic derivatives, which may aid in the development of novel antiviral therapeutics.

Unmet needs in the management of psoriasis in Latin America: a systematic review

BackgroundPsoriasis is a chronic, systemic inflammatory disease with a worldwide prevalence of approximately 2%. Currently, despite the difficulties faced every day by patients and physicians in low-resource countries, literature describing the exact needs of psoriasis treatment in Latin America remains scarce. ObjectiveTo investigate the unmet needs in psoriasis treatment in Latin America. MethodsThe authors conducted a systematic review following PRISMA statements in PubMed, Embase, and LILACS of studies published from January 2011 to March 2021 addressing challenges in psoriasis treatment in Latin America. ResultsThe search strategy identified 3,837 articles, of which 19 were included in the final analysis. Most were from Brazil (58%; n=11), all were observational, and most were cross-sectional (84%; n=16). Difficulties faced by psoriasis patients in Latin America included the high prevalence of opportunistic and endemic infections (42% of the studies addressed this matter; n=8), delay in diagnosis (5%; n=1), work productivity impairment (16%; n=3), limited access to medication/medical care (37%; n=7), poor adherence to treatment (5%; n=1) and poor adherence to guidelines (11%; n=2). Study limitationsNumber and quality of studies currently available on this subject. ConclusionsCurrent psoriasis guidelines do not always account for epidemiological, financial, and cultural characteristics. Most studies available are from Brazil, which might not accurately represent Latin America as a whole. In a region where neglected diseases and scarce resources remain a reality, it is imperative that dermatological training be offered to primary care providers, allowing for standardized conduct and earlier diagnosis.

Predictors of Acute Kidney Injury in Hospitalized Dengue Patients: A Cross-sectional Study

Background: Dengue is an endemic RNA viral infection in Bangladesh. It can affect different organ systems, acute kidney injury (AKI) is one of them. The study aimed to detect the prevalence and predictors of dengue-associated acute kidney injury (DAKI) and in-hospital outcome. Methods: This cross-sectional study was carried out from July to September 2023 at the peak of dengue outbreak in the Department of Medicine in Shaheed Monsur Ali Medical College Hospital, Dhaka, Bangladesh. A total of 203 confirmed cases of dengue aged > 12 years were finally included in the study. Results: The prevalence of DAKI was 7.9%. The mean age of DAKI cases was higher than the non-AKI cases (p-value 0.008). AKI was significantly associated with DHF (43.8% vs 17.6%), higher HCT, higher neutrophil count and lower lymphocytes. In multivariate analyses age more than 60 years, dengue haemorrhagic fever (DHF) and multiple organ dysfunction (MODS) were the independent predictors of DAKI. AKI itself was the independent predictor of hospital stay for more than three days (OR 4.67; 95% CI 1.29-16.92). There was no mortality in the study participants. All were discharged home with resolved AKI. Conclusion: Age more than 60 years, DHF and MODS are the independent risk factors of DAKI. Future studies are required to find out the risk factors for early diagnosis and prompt management. J Bangladesh Coll Phys Surg 2023; 41: 29-33

1103. Endemic Coronavirus Infections in a US Cohort of Children from Birth to 4 Years

Abstract Background Endemic coronaviruses (“CoVs”) OC43, HKU1, NL63 and 229E are “common cold viruses” related to SARS-CoV-2, but their natural histories are poorly understood. We documented endemic CoV infections in a prospective cohort of US infants and children to determine the extent to which natural infection protects against subsequent homotypic and heterotypic endemic CoV infections and SARS-CoV-2 infections. Methods Cincinnati mother-child pairs were enrolled in the third trimester of pregnancy in 2017-18 and children were followed from birth to 4 years with weekly collection of mid-turbinate nasal swabs. Blood was collected at 6 weeks; 6, 12, 18, 24 months; and annually thereafter. Mothers reported on socio demographics, risk factors, and the child’s weekly symptoms. Medical visits were documented from pediatric care providers. CoV infections were followed for the first 4 years of life (focusing on the most compliant subset of 116 children having >70% weekly sample collection). Infections were identified through nasal swabs tested using a RT-PCR multiplex pathogen panel, and by serum IgG responses using a validated kit at CDC and interpreted using classification and regression tree (CART) analysis. Results We detected 398 endemic CoV infections over 317.5 child-years of follow-up (1.1 infections/child-year). Endemic beta-coronaviruses, OC43 and HKU1, were associated with statistically significant homotypic protection (77% and 84%, respectively) after a single infection. Similarly protective homotypic associations (73%) were elicited by NL63, the dominant alpha-coronavirus, after two infections. 229E infections were uncommon. No heterotypic protective association was found for any of the endemic CoVs or for SARS-CoV-2 infections from June 2020 to Nov 2021. The majority of endemic CoVs and SARS-CoV-2 infections were asymptomatic, but this proportion varied by CoV strain. Symptomatic infections were mild for all CoV strains with no hospitalizations. Conclusion Natural infection resulted in homotypic immunity but not heterotypic immunity against other CoVs to the 4th birthday. Children were not protected against SARS-CoV-2 by prior endemic CoV infections. CoV infections in these young children were largely asymptomatic or mild. Disclosures Elizabeth P. Schlaudecker, MD, MPH, Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Mary A. Staat, MD, MPH, CDC: Grant/Research Support|Cepheid: Grant/Research Support|Merck: Grant/Research Support|NIH: Grant/Research Support|Pfizer: Grant/Research Support|Up-To-Date: Honoraria

2486. Winners and Losers: MDROs In The Time of COVID-19

Abstract Background NUH is a 1200 bed academic medical center in Singapore, with endemic multi-drug resistant infections (MDROs) including carbapenemase-producing Enterobacterales (CPE), vancomycin-resistant Enterococci (VRE), Clostridioides difficile infection (CDI), and multi-drug resistant(MDR) Acinetobacter spp. (AB), and MDR Pseudomonas aeruginosa (PA). We studied the impact of COVID-19 (C19) restrictions on the prevalence of hospital acquired (HA) MDROs. Methods A HA infection is defined as a positive clinical culture after hospital day 3. The rates of key MDROs were reviewed from 2018 to the start of the zero C19 policy in Feb 2020 through the lifting of zero COVID in Aug 2021 (Delta Surge) with services still diverted until Jan 2022, when the hospital policy shifted to Endemic C19 (all clinical services resumed). Incidence rates (IR) are expressed per 10,000 patient days, and incidence rate ratios (IRR) estimated for each time period, with p< 0.05 considered statistically significant. We compared DDD per 100 patient days of carbapenem usage for each time period.Table 1:Incidence rates of HO CPE, VRE, CDI, and MDR AS, KP, PA, comparing pre-pandemic 2018-2019, pandemic 2020-2021, and post-pandemic 2022-March 2023Table 2:Incidence rate ratios of HO CPE, VRE, CDI, and MDR AS, KP, PA, comparing pre-pandemic 2018-2019, Zero-COVID 2020 July 2021, Delta surge Aug- Dec 2021-and Endemic COVID Jan 2022- 2023 Results While HA-MDRAB rates declined during the zero C19 period, VRE and CDI rates were stable. CPE rates decreased during the pandemic but have almost doubled post-pandemic from 0.37 in the pandemic to 0.69 post-pandemic (p< 0.05). The mean DDD per 100 patient days for carbapenem usage pre-pandemic was 5.24 and fell to 4.64 (p< 0.05) in 2020-2021.Figure 3:Incidence rates of MDROs that significantly trended downwards during the zero COVID and the Delta surge periods.Figure 4:Incidence rates of VRE and CDI appeared stable, while CPE increased post-pandemic 2022-March 2023Figure 5:Procurement of alcohol-based hand rub pre-pandemic, during pandemic, and post-pandemic Conclusion Studies globally report increased MDROs during the pandemic, purportedly due to reuse of PPE and other reasons. We experienced either a significant decrease or no change in many MDRO clinical infections, followed by a rebound since Jan 2022, when all hospital services resumed (Endemic C19). Our decrease in MDROs may be due to our zero C19 policy, increased hand hygiene, enhanced PPE adherence and cleaning regimens, a decrease in our carbapenem usage (p< 0.05 Table 6), and reduced elective surgeries and admissions, including overseas patients . After endemicity, we had a rebound in CPE infections, and other MDROs possibly triggered by HH and PPE fatigue (Fig. 5), the return of medical tourists and elective surgeries. Further prospective studies are needed to better understand the epidemiology of the various MDROs and the impact of draconian measures such as the Asian Zero C19 approach.Table 6:Defined daily dose of antibiotics per 100 patient days (by quarter) Disclosures All Authors: No reported disclosures

Epidemiology of endemic human coronavirus infection during the COVID-19 pandemic

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the coronavirus family that also includes endemic human coronaviruses (HCoVs) types OC43, HKU1, 229E, and NL63. HCoVs share extensive sequence homology with SARS-CoV-2. It has been assumed that HCoV infection occur primarily in winter and spring in Japan before the coronavirus disease 2019 (COVID-19) pandemic and that its frequency is the same for all age groups. MethodsNasopharyngeal swab samples were collected for HCoVs and SARS-CoV-2. All medical data were retrospectively analyzed. Our primary objective was to describe the epidemiology of HCoV in the Furano, Japan during the COVID-19 pandemic. Our secondary objective was to compare the prevalence of HCoV with that of SARS-CoV-2. ResultsFrom September 2020 to August 2022, 113 (6.2 %) of 1823 cases were positive for any HCoV. The HCoV-NL63 activity peaked in January–March 2021. The HCoV-OC43 activity peaked in June–August 2021. HCoVs were mostly detected at age ≤11 years and most frequently at age ≤2 years. HCoVs showed high detection in 2021, while SARS-CoV-2 showed moderate detection in 2020–2021, but significantly increased in 2022. ConclusionsDuring the COVID-19 pandemic, HCoV-OC43 activity peaked in the summer. The frequency of HCoV infection varied widely by age group and was higher among those aged ≤11 years. These were different from those reported before the COVID-19 pandemic. These findings suggest that the disease dynamics of HCoVs remain unclear and that continued surveillance is essential in the post-COVID-19 pandemic.

Dynamics in a behavioral-epidemiological model for individual adherence to a nonpharmaceutical intervention.

The SARS-CoV-2 pandemic has highlighted the importance of behavioral drivers in epidemic dynamics. With the relaxation of mandated nonpharmaceutical interventions (NPIs) formerly in place to decrease transmission, such as mask-wearing or social distancing, adherence to an NPI is now the result of individual decision-making. To study these coupled dynamics, we embed a game-theoretic model for individual NPI adherence within an epidemiological model. When the disease is endemic, we find that our model has multiple (but none concurrently stable) equilibria: one each with zero, complete, or partial NPI adherence. Surprisingly, for the equilibrium with partial NPI adherence, the number of infections is independent of the transmission rate. Therefore, in that regime, a change in the rate of pathogen transmission, e.g., due to another (mandated) NPI or a new variant, has no effect on endemic infection levels. On the other hand, we show that vaccination successfully decreases endemic infection levels, and, unexpectedly, also reduces the number of susceptibles at equilibrium when there is partial adherence. From a game-theoretic perspective, we find that highly effective NPIs lead at most to partial adherence. As this effectiveness decreases, partially effective NPIs initially lead to increases in population-level adherence, especially if the risk is high enough. However, a completely ineffective NPI results in no adherence. Furthermore, we identify parameter regions where the individual incentives may not align with those of society as a whole. Overall, our findings illustrate complexities that can arise due to behavioral-epidemiological feedback and suggest appropriate measures to avoid more pessimistic population-level outcomes.

Cost of illness due to pertussis in adults ≥50 years of age in the United Kingdom

BackgroundPertussis is an endemic respiratory tract infection caused by Bordetella pertussis that may affect all individuals from infants to older adults. Pertussis incidence in adults is often underreported and in various countries, including the United Kingdom (UK), there are evidence gaps on pertussis-associated economic burden in the older adult population. We aimed to quantify the economic burden of pertussis in adults aged ≥50 years in the UK. MethodsA cost-of-illness study was conducted to estimate the cost of pertussis from a societal perspective. We utilized a sum diagnosis cost approach in which costs related to infection with pertussis were included. Medical, patient, and indirect costs were calculated individually and combined to calculate total costs. A framework was developed to assess costs for consecutive age groups from 50–54 years of age to ≥85 years of age. Sensitivity and scenario analyses were used to assess analysis uncertainty. ResultsThe base-case analysis estimated the total annual economic burden of pertussis to be approximately £238 million (M). This comprised approximately £159 M in indirect costs, £66 M in medical costs, and £13 M in patient costs. Costs for the age group 55–59 years had the highest impact on the economic burden, with approximately £79 M in total annual costs. Visits to general practitioners and nurses were the largest contributors to medical costs (∼£37 M) followed by inpatient visits (∼£21 M). Transportation costs (∼£10 M) were the major patient costs. Productivity loss (∼£71 M) and leisure time loss (∼£72 M) had comparable contributions to annual indirect costs. Sensitivity and scenario analyses suggested that incidence rates, indirect costs, and underreporting estimates had the highest impact on outcomes. ConclusionTotal cost of pertussis in the UK among adults ≥50 years of age is substantial and highest for adults 55–59 years of age. Indirect costs were the main contributors to the economic burden.

Feline Morbillivirus: Clinical Relevance of a Widespread Endemic Viral Infection of Cats.

Feline morbillivirus (FeMV) was first isolated in 2012 from stray cats in Hong Kong. It has been found in association with tubulointerstitial nephritis (TIN), the most common cause of feline chronic kidney disease (CKD). However, viral host spectrum and virus tropism go beyond the domestic cat and kidney tissues. The viral genetic diversity of FeMV is extensive, but it is not known if this is clinically relevant. Urine and kidney tissues have been widely tested in attempts to confirm associations between FeMV infection and renal disease, but samples from both healthy and sick cats can test positive and some cross-sectional studies have not found associations between FeMV infection and CKD. There is also evidence for acute kidney injury following infection with FeMV. The results of prevalence studies differ greatly depending on the population tested and methodologies used for detection, but worldwide distribution of FeMV has been shown. Experimental studies have confirmed previous field observations that higher viral loads are present in the urine compared to other tissues, and renal TIN lesions associated with FeMV antigen have been demonstrated, alongside virus lymphotropism and viraemia-associated lymphopenia. Longitudinal field studies have revealed persistent viral shedding in urine, although infection can be cleared spontaneously.

Shoulder Coccidioidomycosis Masquerading as Synovial Chondromatosis

Coccidioidomycosis is an endemic fungal infection in arid areas of Southwestern US and Northern Mexico. It is difficult to diagnose and treat, may take years to make the correct diagnosis, may leave sequelae and could even be fatal.

An agent-based multi-level model to study the spread of gonorrhea in different and interacting risk groups

IntroductionMathematical modeling has emerged as a crucial component in understanding the epidemiology of infectious diseases. In fact, contemporary surveillance efforts for epidemic or endemic infections heavily rely on mathematical and computational methods. This study presents a novel agent-based multi-level model that depicts the transmission dynamics of gonorrhea, a sexually transmitted infection (STI) caused by the bacterium Neisseria gonorrhoeae. This infection poses a significant public health challenge as it is endemic in numerous countries, and each year sees millions of new cases, including a concerning number of drug-resistant cases commonly referred to as gonorrhea superbugs or super gonorrhea. These drug-resistant strains exhibit a high level of resistance to recommended antibiotic treatments.MethodsThe proposed model incorporates a multi-layer network of agents' interaction representing the dynamics of sexual partnerships. It also encompasses a transmission model, which quantifies the probability of infection during sexual intercourse, and a within-host model, which captures the immune activation following gonorrhea infection in an individual. It is a combination of agent-based modeling, which effectively captures interactions among various risk groups, and probabilistic modeling, which enables a theoretical exploration of sexual network characteristics and contagion dynamics.ResultsNumerical simulations of the dynamics of gonorrhea infection using the complete agent-based model are carried out. In particular, some examples of possible epidemic evolution are presented together with an application to a real case study. The goal was to construct a virtual population that closely resembles the target population of interest.DiscussionThe uniqueness of this research lies in its objective to accurately depict the influence of distinct sexual risk groups and their interaction on the prevalence of gonorrhea. The proposed model, having interpretable and measurable parameters from epidemiological data, facilitates a more comprehensive understanding of the disease evolution.

Biology of Anemia: A Public Health Perspective

Our goal is to present recent progress in understanding the biological mechanisms underlying anemia from a public health perspective. We describe important advances in understanding common causes of anemia and their interactions, including iron deficiency (ID), lack of other micronutrients, infection, inflammation, and genetic conditions. ID develops if the iron circulating in the blood cannot provide the amounts required for red blood cell production and tissue needs. ID anemia develops as iron-limited red blood cell production fails to maintain the hemoglobin concentration above the threshold used to define anemia. Globally, absolute ID (absent or reduced body iron stores that do not meet the need for iron of an individual but may respond to iron supplementation) contributes to only a limited proportion of anemia. Functional ID (adequate or increased iron stores that cannot meet the need for iron because of the effects of infection or inflammation and does not respond to iron supplementation) is frequently responsible for anemia in low- and middle-income countries. Absolute and functional ID may coexist. We highlight continued improvement in understanding the roles of infections and inflammation in causing a large proportion of anemia. Deficiencies of nutrients other than iron are less common but important in some settings. The importance of genetic conditions as causes of anemia depends upon the specific inherited red blood cell abnormalities and their prevalence in the settings examined. From a public health perspective, each setting has a distinctive composition of components underlying the common causes of anemia. We emphasize the coincidence between regions with a high prevalence of anemia attributed to ID (both absolute and functional), those with endemic infections, and those with widespread genetic conditions affecting red blood cells, especially in sub-Saharan Africa and regions in Asia and Oceania.

Structure of glyceraldehyde-3-phosphate dehydrogenase from Paracoccidioides lutzii in complex with an aldonic sugar acid

The pathogen Paracoccidioides lutzii (Pb01) is found in South America countries Colombia, Ecuador, Venezuela and Brazil, especially in the central, west, and north regions of the latter. It belongs to the Ajellomycetaceae family, Onygenales order, and is typically thermodimorphic, presenting yeast cells when it grows in animal tissues, but mycelia when in the environment, where it produces the infectious propagule. This fungus is one of the etiologic agents of Paracoccidioidomycosis (PCM), the most important endemic fungal infection in Latin America. Investigations on its genome have contributed to a better understanding about its metabolism and revealed the complexity of several metabolic glycolytic pathways. Glyceraldehyde-3-Phosphate Dehydrogenase from Paracoccidioides lutzii (PlGAPDH) is considered a moonlighting protein and participates in several biological processes of this pathogen. The enzyme was expressed and purified, as seen in SDS-PAGE gel, crystallized and had its three dimensional structure (3D) determined in complex with NAD+, a sulphate ion and d-galactonic acid, therefore, a type of ‘GAA site’. It is the first GAPDH structure to show this chemical type in this site and how this protein can bind an acid derived from oxidation of a linear hexose.

Short-term temperature fluctuations increase disease in a Daphnia-parasite infectious disease system.

Climate change has profound effects on infectious disease dynamics, yet the impacts of increased short-term temperature fluctuations on disease spread remain poorly understood. We empirically tested the theoretical prediction that short-term thermal fluctuations suppress endemic infection prevalence at the pathogen's thermal optimum. This prediction follows from a mechanistic disease transmission model analyzed using stochastic simulations of the model parameterized with thermal performance curves (TPCs) from metabolic scaling theory and using nonlinear averaging, which predicts ecological outcomes consistent with Jensen's inequality (i.e., reduced performance around concave-down portions of a thermal response curve). Experimental observations of replicated epidemics of the microparasite Ordospora colligata in Daphnia magna populations indicate that temperature variability had the opposite effect of our theoretical predictions and instead increase endemic infection prevalence. This positive effect of temperature variability is qualitatively consistent with a published hypothesis that parasites may acclimate more rapidly to fluctuating temperatures than their hosts; however, incorporating hypothetical effects of delayed host acclimation into the mechanistic transmission model did not fully account for the observed pattern. The experimental data indicate that shifts in the distribution of infection burden underlie the positive effect of temperature fluctuations on endemic prevalence. The increase in disease risk associated with climate fluctuations may therefore result from disease processes interacting across scales, particularly within-host dynamics, that are not captured by combining standard transmission models with metabolic scaling theory.

Seroprevalence and incidence of hepatitisE virus infection in the general population of Iwate prefecture, Japan: A retrospective cohort study.

HepatitisE virus (HEV) causes subclinical or acute self-limiting hepatitis. We surveyed the current seroprevalence and incidence of HEV infection among the general population in Iwate Prefecture, Japan, where the endemic infection is presumed to be low. Between 2014 and 2016, we recruited individuals from Iwate Prefecture, Japan, who visited a general medical work-up program. Serum anti-HEV antibody and HEV RNA were measured twice, with an interval of 2years. Anti-HEV antibody was measured with enzyme-linked immunosorbent assay and HEV RNA with reverse transcription-polymerase chain reaction. Study participants comprised 1284 Japanese (650 men and 634 women) with age ranging 20-89years. A total of 90 participants were found to be positive for anti-HEV immunoglobulinG on the first visit, with a prevalence of 7.0% (95% confidence interval [CI] 5.6%-8.4%). Seroprevalence was higher in men than in women (10.1% vs. 3.7%, p<0.001), and in those aged in their 50s-80s than in those aged in their 20s-40s (p=0.006). Positive seroconversion indicating new HEV infection was found in seven of 1194 seronegative participants (0.59%; 95% CI 0.15%-1.0%), indicating the incidence of HEV infection to be 272 per 100000 person-years (95% CI 109-561). Our observations suggest that the incidence of HEV infection is high and that it is a leading cause of hepatitis virus infection in Iwate Prefecture, Japan.

Increased Fungal Infection Mortality Induced by Concurrent Viral Cellular Manipulations.

Certain respiratory fungal pathogen mono-infections can cause high mortality rates. Several viral pathogen mono-infections, including influenza viruses and coronaviruses including SARS-CoV-2, can also cause high mortality rates. Concurrent infections by fungal pathogens and highly manipulative viral pathogens can synergistically interact in the respiratory tract to substantially increase their mortality rates. There are at least five viral manipulations which can assist secondary fungal infections. These viral manipulations include the following: (1) inhibiting transcription factors and cytokine expressions, (2) impairing defensive protein expressions, (3) inhibiting defenses by manipulating cellular sensors and signaling pathways, (4) inhibiting defenses by secreting exosomes, and (5) stimulating glucocorticoid synthesis to suppress immune defenses by inhibiting cytokine, chemokine, and adhesion molecule production. The highest mortality respiratory viral pandemicsup to now have had substantially boosted mortalities by inducing secondary bacterial pneumonias. However, numerous animal species besides humans are also carriers of endemic infections by viral and multidrug-resistant fungal pathogens. The vast multi-species scope of endemic infection opportunities make it plausible that the pro-fungal manipulations of a respiratory virus can someday evolve to enable a very high mortality rate viral pandemic inducing multidrug-resistant secondary fungal pathogen infections. Since such pandemics can quickly spread world-wide and outrun existing treatments, it would be worthwhile to develop new antifungal treatments well before such a high mortality event occurs.