Asymptomatic Seroconversion Research Articles

Exposure to Dengue Virus During Pregnancy: Incidence and Impact on Maternal and Child Outcomes.

Dengue virus (DENV) is the most common arbovirus globally, with its incidence growing dramatically in recent decades. Although the effects of DENV infection during pregnancy are unclear, reported associations with adverse health outcomes include miscarriage, prematurity, and low birth weight. In this study, we used an IgG ELISA to identify mothers exposed to DENV during pregnancy by testing samples obtained from a previous study that followed a cohort of pregnant women in Kenya to investigate parasitic infections during pregnancy. We compared adverse pregnancy and infant health outcomes between seronegative mothers and those who seroconverted. Of the 289 participants tested for DENV exposure during pregnancy, we estimated that ∼12 women (4%) would have been exposed to DENV during their gestation period. However, we found that 34 mothers (11.8%) had been exposed to DENV during pregnancy. None of these mothers were hospitalized during pregnancy because of severe DENV infection, suggesting that many may have undergone asymptomatic seroconversion. The demographic risk factors of socioeconomic status, education level, bed net use, and maternal age were not associated with mild or asymptomatic DENV in pregnancy. Although mild or asymptomatic DENV during pregnancy was not associated with late prematurity, reduced postnatal childhood developmental measures, or adverse maternal pregnancy outcomes, we observed an increased risk of low birth weight. The larger-than-expected burden of DENV in pregnancy in this coastal Kenyan cohort and the observed potential risk of low birth weight provide evidence that a more comprehensive study is warranted to fully understand DENV infection during pregnancy.

A predictive analytics model using machine learning algorithms to estimate the risk of shock development among dengue patients

Dengue is a common viral disease in tropical and subtropical countries. The clinical manifestation of dengue has a wide spectrum, from asymptomatic seroconversion to severe dengue infection. Severe dengue is defined as dengue with the presence of specific symptoms, including severe plasma leakage leading to shock or the accumulation of fluids with respiratory distress, severe bleeding, and severe organ impairment. Examining the progression of shock with the integration of patients’ physiological information and biochemical parameters would help in understanding the progression of the disease and early detection of shock. In this study, physiological patient data diagnosed with dengue are collected from a University Malaya Medical Centre’s electronic record. A prediction model learned from the measurement of a patient’s physiological data is the basis for effective treatment and prevention of shock development in critically ill patients. Hence, this study presents the predictive performance of machine learning algorithms to estimate the risk of shock development among dengue patients. Logistic regression, decision trees, support vector machines and neural networks are evaluated. Lastly, ensemble learnings of bagging and boosting are also applied to the weak learner to optimize performance. The experimental results show that the bagging algorithm outperforms other competing methods with a 14.5% improvement from the individual decision tree. The full blood count (FBC) specifically haemoglobin (Hb) on day 2 is found to be a strong predictor for severe dengue occurrence.

Primary Herpetic Gingivostomatitis.

An 82-year-old female presented with painful oral lesions associated with fever and dysphagia since 3 days. Examination revealed multiple grouped tender white to yellow plaques and few discrete vesicles on an erythematous base over the tongue and palate [Figure 1] with tender cervical lymphadenopathy. Tzanck smear from the vesicles showed multinucleate epidermal giant cells [Figure 2]. A diagnosis of primary herpetic gingivostomatitis was made and the lesions resolved following treatment with oral valacyclovir 1 g twice daily for 7 days [Figure 3]. Herpetic gingivostomatitis is typically caused by Herpes simplex virus type-1 (HSV-1), but cases caused by HSV-2 have also been reported. HSV-1 spreads by direct contact, via droplets, or by sexual contact. Primary herpetic gingivostomatitis usually presents with yellow to white plaques and vesicles which rupture and coalesce to form ulcers over the buccal mucosa, tongue, palate, gingiva, and the lips. Severe cases can have associated fever, malaise, myalgia, and local lymphadenopathy. Following the primary episode, the virus being neurotropic may become latent in the peripheral nerves and ganglions, with subsequent reactivations causing recurrent infections in around one-thirds of patients. Recurrent herpes simplex infections can present as localized vesicles commonly on the vermillion border of the lips, perioral skin, or the hard palate.[1] The diagnosis of herpes gingivostomatitis is primarily clinical. The differential diagnoses include aphthous stomatitis, oral candidiasis, herpangina, Behcet disease, erythema multiforme, Steven–Johnson syndrome, hand, foot and mouth disease and immunobullous disorders.[2] Tzanck smear from vesicles demonstrating viral cytopathic changes can support the diagnosis; however, it cannot distinguish between HSV-1, HSV-2, or varicella zoster virus. Crusted or ulcerative lesions are diagnosed by more accurate tests like direct fluorescent antibody test, polymerase chain reaction, and viral cultures. Serological tests are useful but not generally indicated for acute infections; also many people exposed to HSV may demonstrate asymptomatic seroconversion.[12]Figure 1: Multiple grouped tender white to yellow plaques and discrete vesicles on an erythematous base over the tongue and palateFigure 2: Tzanck smear showing multinucleate epidermal giant cellFigure 3: Complete resolution post treatmentMost cases of herpes gingivostomatitis are self-resolving, requiring only supportive measures. Severe cases may require systemic antiviral therapy – oral Acyclovir 15 mg/kg five times a day; or valacyclovir, 1g twice daily; or famciclovir, 500 mg twice daily; for 5 to 7 days. In case of frequent recurrences, prophylactic suppressive acyclovir (400 mg twice daily), valacyclovir (500 mg orally once daily), or famciclovir (250 mg twice daily) may be considered.[23] Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Correlation of Clinico-Hematological Parameters in Adult Dengue with Survival and Death: Emphasis on Cause of Mortality

ABSTRACT Objective: Dengue is a systemic and dynamic disease ranging from asymptomatic seroconversion to severe dengue with hemorrhagic and organ impairment. Although many reports exist on clinical and hematological aspects, surprisingly there are no articles that take in to account these parameters in people who have survived and succumbed to the illness in a matched cohort study with healthy controls from an endemic region. The present study is carried out with this objective. Patients and Methods: This was a retrospective study conducted at Father Muller Medical College Hospital, a tertiary care hospital, at Mangalore, Karnataka from January 2017 to December 2019 to compare the clinico-hematological parameters in the adult patients diagnosed with dengue fever. The data collected were entered into Microsoft Excel, and statistical analysis was done by Student’s t-test. P < 0.05 was considered as statistically significant. Results: A total of 429 patients were included in the study, with 274 (63.87%) males and 237 (55.24%) patients belonging to the age group of 18–30 years. The most common symptoms were fever (100%), vomiting (96.04%), and headache (36.83%). The dengue patients had leukopenia, lymphocytosis, monocytosis, thrombocytopenia, raised erythrocyte sedimentation rate, and hematocrit. In addition to this, the deceased dengue patients (27) had deranged liver and renal parameters compared to alive. Conclusions: The results suggest that when a patient presents with fever, persistent vomiting, thrombocytopenia, and raised hematocrit, dengue fever should be the first differential diagnosis, especially in endemic area. Furthermore, the elderly and people with comorbidities are at high risk of death if medical care is delayed.

Crimean-Congo Hemorrhagic Fever Case Series: a Chronology of Biochemical and Hematological Parameters.

Introduction Crimean-Congo hemorrhagic fever (CCHF) is a widespread tick-borne zoonotic disease. Sporadic outbreaks of CCHF occur in endemic regions, including Pakistan. The clinical spectrum of the illness varies from asymptomatic seroconversion to severe disease which may end in death. The treatment is supportive, including blood and blood products. There is multi-organ involvement in CCHF including acute hepatitis, thrombocytopenia, coagulopathy, acute kidney injury (AKI), and encephalopathy. Hematological and biochemical parameters may identify patients at substantial risk of worse outcomes. Early detection of the disease and forecasting the clinical course may be helpful. This case series aims to evaluate the trends of hematological and biochemical parameters among the survivors and non-survivors of CCHF. Methods All consecutive patients aged 16 years and above admitted to the isolation unit of Hayatabad Medical Complex, Peshawar, Pakistan between 1st July and 30th July 2022 with the diagnosis of CCHF were included in this case series. The diagnosis of CCHF was made by detecting viral ribonucleic acid by a polymerase chain reaction. For all patients, age, gender, address, occupation, clinical presentation, history of contact with animals, and travel history were recorded.All the vitals were taken regularly. The hematological (complete blood count) and biochemical parameters (serum creatinine, alanine aminotransferase (ALT), and C-reactive protein (CRP)) were documented daily.The blood group was determined for all the cases. Results Out of 17 cases, the majority (16 cases, 94.1%) were male and butchers (eight cases, 47.1%) by profession. All cases had significant contact with animals. Four patients (23.5%) died.Three out of the four non-survivors (75%) had ALT < 5 times the upper limit of normal with a static pattern of liver enzymes without much decline in ALT till death. One non-survivor (25%) had marked elevation of ALT at presentation, which had a declining trend till death. Seven out of 13 survivors (53.8%) had moderate to marked elevation in the level of ALT at presentation. The ALT showed a downward trend during the course of illness in all these patients. The remaining survivors (six out of 13, 46.2%) had a mild elevation of ALT and 50% of them showed improvement in the ALT level during hospitalization. All patients had thrombocytopenia at presentation. None of the non-survivors showed a persistent increase in the platelet count, and three cases remained severely thrombocytopenic at the time of death. However, the trend in platelet count among all the survivors was increasing. The CRP level in the majority (three out of four cases, 75%) of the non-survivors remained elevated till death, while all survivors showed a progressive decline in CRP level. A majority (11 out of 17 cases) had blood group B. Half of the non-survivors (two out of four cases) and the majority of the survivors (nine out of 13 cases) had blood group B. AKI was found in all non-survivors, while all the survivors had normal renal function throughout the course. Conclusion A persistently raised ALT and CRP level, a persistently low or decreasing platelet count, and AKI were associated with mortality. Blood group B was the commonest blood group among patients of CCHF, which is not reflective of the blood group distribution of the general population from which this case series has been reported.

A Cross-sectional Study of Immune Seroconversion to SARS-CoV-2 in Frontline Maternity Health Professionals

(Anaesthesia. 2020;75:1614–1619) Seroconversion rates for COVID-19 provides data on the pervasiveness and spread of the infection. One challenge is the rate of asymptomatic seroconversion. This has implications for health care providers on the frontline of obstetric care, who may be at increased risk of COVID-19 transmission to and from patients and staff. To date, there are no studies that have provided a baseline rate of seroconversion in frontline, obstetric care providers. The aim of this study was to assess the prevalence of seroconversion in obstetric providers who were not previously diagnosed with SARS-CoV-2 and examine the associations among their characteristics, symptoms, and seroconversion.

Hijacking of the Host's Immune Surveillance Radars by Burkholderia pseudomallei.

Burkholderia pseudomallei (B. pseudomallei) causes melioidosis, a potentially fatal disease for which no licensed vaccine is available thus far. The host-pathogen interactions in B. pseudomallei infection largely remain the tip of the iceberg. The pathological manifestations are protean ranging from acute to chronic involving one or more visceral organs leading to septic shock, especially in individuals with underlying conditions similar to COVID-19. Pathogenesis is attributed to the intracellular ability of the bacterium to ‘step into’ the host cell’s cytoplasm from the endocytotic vacuole, where it appears to polymerize actin filaments to spread across cells in the closer vicinity. B. pseudomallei effectively evades the host’s surveillance armory to remain latent for prolonged duration also causing relapses despite antimicrobial therapy. Therefore, eradication of intracellular B. pseudomallei is highly dependent on robust cellular immune responses. However, it remains ambiguous why certain individuals in endemic areas experience asymptomatic seroconversion, whereas others succumb to sepsis-associated sequelae. Here, we propose key insights on how the host’s surveillance radars get commandeered by B. pseudomallei.

Occupational infection to Brucella abortus B19 vaccine despite antimicrobial prophylaxis

The authors report the case of a veterinarian who acquired brucellosis infection by accidental exposure to Brucella abortus vaccine (BRUCEL-VET B19) while performing animal vaccination. Antibiotic prophylaxis with doxycycline and rifampin for six weeks was indicated, but rifampin was discontinued after 10 days due to gastrointestinal intolerance. Despite prophylaxis, the patient seroconverted after 30 days, but was asymptomatic and did not require additional antibiotic therapy. Post-exposure prophylaxis of Brucella is not free from side effects and asymptomatic seroconversion can occur despite prophylaxis.

Antinociceptive and Discriminative Stimulus Effects of Six Novel Psychoactive Opioid Substances in Male Rats.

Compounds with novel or fentanyl-like structures continue to appear on the illicit drug market and have been responsible for fatalities, yet there are limited preclinical pharmacological data available to evaluate the risk of these compounds to public health. The purpose of the present study was to examine acetyl fentanyl, butyryl fentanyl, 3,4-dichloro-N-[[1-(dimethylamino)cyclohexyl]methyl]benzamide (AH-7921), 1-cyclohexyl-4-(1,2-diphenylethyl)piperazine (MT-45), 4-chloro-N-[1-(2-phenylethyl)-2-piperidinylidene]-benzenesulfonamide (W-15), and 4-chloro-N-[1-[2-(4-nitrophenyl)ethyl]-2-piperidinylidene]-benzenesulfonamide (W-18) for their relative potency to reference opioids and their susceptibility to naltrexone antagonism using the 55oC warm-water, tail-withdrawal assay of antinociception and a morphine drug discrimination assay in male, Sprague-Dawley rats. In the antinociception assay, groups of 8 rats per drug were placed into restraining tubes, their tails were immersed into 40o or 55oC water, and the latency for tail withdrawal was measured with a cutoff time of 15 seconds. In the drug discrimination assay, rats (n = 11) were trained to discriminate between 3.2 mg/kg morphine and saline, subcutaneously, in a two-choice, drug discrimination procedure under a fixed ratio-5 schedule of sucrose pellet delivery. Morphine, fentanyl, and four of the synthetic opioids dose dependently produced antinociception and fully substituted for morphine in the drug discrimination assay with the following rank order of potency: fentanyl > butyryl fentanyl > acetyl fentanyl > AH-7921 > MT45 > morphine. All drugs that produced antinociception or morphine-like discriminative stimulus effects were blocked by naltrexone. W-15 and W-18 did not show antinociceptive or morphine-like discriminative stimulus effects at the doses tested supporting a lack of opioid activity for these two compounds. These findings suggest that butyryl fentanyl, acetyl fentanyl, AH-7941, and MT-45 have abuse liability like other opioid agonists. SIGNIFICANCE STATEMENT: As novel psychoactive substances appear on the illicit drug market, preclinical pharmacological testing is required to assist law enforcement, medical professionals, and legal regulators with decisions about potential public health risks. In this study, four synthetic opioids, acetyl fentanyl, butyryl fentanyl, AH-7921, and MT-45 produced effects similar to fentanyl and morphine and were blocked by naltrexone. These data suggest the four synthetic opioids possess similar abuse liability risks as typical opioid agonists.

SARS-CoV-2 Testing of 11,884 Healthcare Workers at an Acute NHS Hospital Trust in England: A Retrospective Analysis.

Healthcare workers (HCWs) are known to be at increased risk of infection with SARS-CoV-2, although whether these risks are equal across all roles is uncertain. Here we report a retrospective analysis of a large real-world dataset obtained from 10 March to 6 July 2020 in an NHS Foundation Trust in England with 17,126 employees. 3,338 HCWs underwent symptomatic PCR testing (14.4% positive, 2.8% of all staff) and 11,103 HCWs underwent serological testing for SARS-CoV-2 IgG (8.4% positive, 5.5% of all staff). Seropositivity was lower than other hospital settings in England but higher than community estimates. Increased test positivity rates were observed in HCWs from BAME backgrounds and residents in areas of higher social deprivation. A multiple logistic regression model adjusting for ethnicity and social deprivation confirmed statistically significant increases in the odds of testing positive in certain occupational groups, most notably domestic services staff, nurses, and health-care assistants. PCR testing of symptomatic HCWs appeared to underestimate overall infection levels, probably due to asymptomatic seroconversion. Clinical outcomes were reassuring, with only a small minority of HCWs with COVID-19 requiring hospitalization (2.3%) or ICU management (0.7%) and with no deaths. Despite a relatively low level of HCW infection compared to other UK cohorts, there were nevertheless important differences in test positivity rates between occupational groups, robust to adjustment for demographic factors such as ethnic background and social deprivation. Quantitative and qualitative studies are needed to better understand the factors contributing to this risk. Robust informatics solutions for HCW exposure data are essential to inform occupational monitoring.

Melioidosis in Australia

Melioidosis is a potentially fatal bacterial infection caused by the Gram-negative bacillus, Burkholderia pseudomallei following contact with a contaminated environmental source, normally soil or water in tropical and subtropical locations. The disease spectrum varies from rapidly progressive bacteraemic infection with or without pneumonia, to focal lesions in deep soft tissues and internal organs to superficial soft tissue infection and asymptomatic seroconversion with possible long-term dormancy. Most infections occur with a background of chronic illness such as diabetes, chronic kidney disease and alcoholic liver disease. Improvements in diagnosis, targeted antimicrobial treatment and long term follow up have improved clinical outcomes. Environmental controls following rare point source case clusters and heightened awareness of melioidosis appear to have reduced the disease burden in some parts of northern Australia. However, the impact of climate change on dispersal of environmental B. pseudomallei, and changing land use in tropical Australia is expected to change the epidemiology of melioidosis in future.

SARS-CoV-2 seroprevalence and asymptomatic viral carriage in healthcare workers: a cross-sectional study

ObjectiveTo determine the rates of asymptomatic viral carriage and seroprevalence of SARS-CoV-2 antibodies in healthcare workers.DesignA cross-sectional study of asymptomatic healthcare workers undertaken on 24/25 April 2020.SettingUniversity Hospitals Birmingham NHS...

Management of Dengue in Children: An Update

Dengue viruses cause symptomatic infections or asymptomatic seroconversion. Symptomatic dengue infection is a systemic and dynamic disease. It has a wide clinical spectrum that includes both severe and non-severe clinical manifestations. Due to its dynamic nature, the severity of the disease will usually only be apparent around defervescence which often coincides with the onset of the critical phase. For a disease that is complex in its manifestations, management is relatively simple, inexpensive and very effective in saving lives, so long as correct and timely interventions are instituted. The main hemodynamic elements of dengue shock is hypovolemia with decreased vascular capacitance resulting from plasma leakage. Thus, the strategy of aggressive fluid resuscitation of septic shock is not applicable to severe dengue with plasma leakage. Volume replacement in children with dengue shock is a challenging management problem. Aggressive fluid resuscitation may indeed be harmful and should be limited to dengue shock with hypotension. There is a “narrow therapeutic index”; therefore, fluids have to be given timely, at the appropriate volume, rate, of the appropriate type (crystalloids, colloid and/or blood) and for the appropriate duration. Therein lies the challenge to physicians who are not familiar with the important practice of fluid titration through frequent and meticulous assessment. Progression of the disease through the critical phase should be tracked in hours of plasma leakage. Recognizing the cues to discontinue intravenous fluid therapy is just as important as knowing when to start it. Given time and hemodynamic stability, other issues such as thrombocytopenia, coagulopathy and raised liver enzymes will recover spontaneously or with supportive care.&#x0D; DS (Child) H J 2019; 35(2) : 162-178

Asymptomatic Seroconversion of Immunoglobulins to SARS-CoV-2 in a Pediatric Dialysis Unit

This case series describes subclinical development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in some patients and health care workers in a pediatric dialysis unit after contact with a seropositive patient.

Detection and Quantification of Antibody to SARS-CoV-2 Receptor Binding Domain Provides Enhanced Sensitivity, Specificity and Utility

Background: Accurate and sensitive detection of antibody to SARS-CoV-2 remains an essential component of the pandemic response. Measuring antibody that predicts neutralising activity and the vaccine response is an absolute requirement for laboratory-based confirmatory and reference activity.Methods: The viral receptor binding domain (RBD) constitutes the prime target antigen for neutralising antibody. A double antigen binding assay (DABA) provides the most sensitive format. It has been exploited in a novel hybrid manner employing an S1 solid-phase preferentially presenting RBD once solid-phase bound, coupled with a labelled RBD conjugate, used in a two-step sequential assay.Findings: This assay showed a specificity of 100% on 825 pre COVID-19 samples and a potential sensitivity of 99.6% on 276 recovery samples, predicting quantitatively the presence of neutralising antibody determined by pseudo-type neutralisation and by plaque reduction. Anti-RBD is also measurable in ferrets immunised with ChadOx1 nCoV-19 vaccine. The early response at presentation with illness, elevated responsiveness with disease severity, detection of asymptomatic seroconversion and persistence after the loss of antibody to the nucleoprotein (anti-NP) are all documented.Trial Registration: The ISARIC WHO CCP-UK study was registered at https://www.isrctn.com/ISRCTN66726260 and designated an Urgent Public Health Research Study by NIHR.Interpretation: The hybrid DABA displays the attributes necessary for an antibody test to be used in both clinical and reference serology. It allows the neutralising antibody response to be inferred early in infection and potentially in vaccine recipients. It is also of sufficient sensitivity to be used to provide serological confirmation of prior infection and provides a more secure measure for seroprevalence studies in the population generally than does anti-NP based on the Architect platform.Funding: This work is variously supported by grants from: the National Institute for Health Research (NIHR; award CO-CIN-01), the Medical Research Council (MRC; grant MC_PC_19059 and MC_PC_19078), MRC NIHR (grant CV220-111) and by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (award 200907), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200927), Wellcome Trust and Department for International Development (DID; 215091/Z/18/Z), the Bill and Melinda Gates Foundation (OPP1209135), Liverpool Experimental Cancer Medicine Centre (grant reference C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (IS-BRC-1215-20013), EU Platform for European Preparedness Against (Re-)emerging Epidemics (PREPARE; FP7 project 602525), and NIHR Clinical Research Network for providing infrastructure support for this research.Declaration of Interests: RST, MOM and PC report patent pending (Patent Application No. 2011047.4 for “SARS-CoV-2 antibody detection assay). All other authors declare no competing interests.Ethics Approval Statement: The use of tissues was approved by the CDRTB Steering Committee in accordance with the responsibility delegated by the National Research Ethics Service (South Central Ethics Committee – C, NRES reference 15/SC/0089).Written informed consent was obtained from all patients. Ethical approval was given by the South Central–Oxford C Research Ethics Committee in England (reference: 13/SC/0149), Scotland A Research Ethics Committee (reference: 20/SS/0028) and World Health Organization Ethics Review Committee (RPC571 and RPC572l; 25 April 2013)

Kinetics of serum antibodies in response to infection with Yersinia enterocolitica.

Information on the kinetics of the serum antibody response to infection with Yersinia enterocolitica is essential to allow the estimation and comparison of seroconversion rates in a diversity of pools of cross-sectional serum antibody measurements. Data from 94 patients with acute enteritis caused by Yersinia infection were used. The follow-up period for the longitudinal study was 36 months, addressed by questionnaire. An indirect enzyme-linked immunosorbent assay method was adapted to determine the concentration of antibodies against Y. enterocolitica in human sera. A mathematical within-host model was used to describe the interaction between pathogen and immune system and the waning of immunity after clearing of the pathogen. All observed antibodies (IgG, IgM, IgA) reached peak levels shortly after infection and then decayed slowly indicating that the median levels decreased only little during the observation period. Estimated maximum peak antibody levels were highest in IgG. Seroresponse curves of all antibodies showed large individual variation between patients. There was no apparent pattern of variation with age, nor any notable difference between genders. Estimated half-times were very long for all antibodies, and their posterior distributions were highly skewed. IgA appeared to have the most persistent antibody response, compared with IgG and IgM. Median peak levels of all three antibodies were similar. There was no significance found between peak antibody levels and severity of symptoms of gastrointestinal infection and severity of joint pain. Our findings allow the use of cross-sectional serum antibody measurements as biomarkers, to estimate seroconversion rates. Such seroincidence estimates include asymptomatic seroconversions, thereby avoiding under-reporting, and allows the comparison of infection pressures among countries, independent of their healthcare and surveillance systems.

Host genetic control of mosquito-borne Flavivirus infections.

Flaviviruses are arthropod-borne viruses, several of which represent emerging or re-emerging pathogens responsible for widespread infections with consequences ranging from asymptomatic seroconversion to severe clinical diseases and congenital developmental deficits. This variability is due to multiple factors including host genetic determinants, the role of which has been investigated in mouse models and human genetic studies. In this review, we provide an overview of the host genes and variants which modify susceptibility or resistance to major mosquito-borne flaviviruses infections in mice and humans.

Evidence of rickettsiae in Danish patients tested for Lyme neuroborreliosis: a retrospective study of archival samples

BackgroundWith a prevalence of 4.7–13% in Danish Ixodes ricinus ticks, Rickettsia helvetica is one of the most frequently detected tick-borne organisms in Denmark. Most reports of human exposure have described asymptomatic seroconversion or a mild, self-limiting flu-like illness but it has also been implicated as a cause of subacute lymphocytic meningitis. Because Borrelia burgdorferi sensu lato (Bbsl) and R. helvetica are both found in the same tick species, potential co-transmission is a possibility. We examined 1) the seroprevalence of anti-rickettsia antibodies in patients investigated for Lyme neuroborreliosis (LNB), and 2) the cerebrospinal fluid (CSF) and sera of same patients for the presence of Rickettsia DNA.MethodsNinety-nine sera and 87 CSF samples from patients with intrathecal synthesis of anti-Borrelia antibodies and 101 sera and 103 CSF samples from patients with no detectable intrathecal synthesis were retrospectively examined for this study. Sera were analyzed for antibodies against spotted fever group (SFG) rickettsiae and both the CSF and sera were tested for Rickettsia DNA using a genus-specific real-time PCR.ResultsOf the patients tested for LNB, 32% (64/200) had IgG antibodies against SFG rickettsiae. Among patients with confirmed intrathecal synthesis of Borrelia-specific antibodies, 38% (38/99) exhibited IgG antibodies. None of these values were statistically significant when compared with sera from healthy blood donors (p = 0.7 and 0.19). Rickettsia DNA was found in the CSF of 4% (8/190) of patients.ConclusionNo statistically significant difference was found in the seroprevalence of anti-rickettsia antibodies in patients tested for LNB and healthy blood donors, indicative of a low rate of exposure in this group of patients. Eight patients showed evidence of Rickettsia DNA in the CSF, five of whom had LNB. However, cycle threshold (Ct) values were high, indicating low concentrations of DNA, and no apparent alteration in the clinical manifestations of LNB were noted in the medical records of these patients.

Experimental Zika Virus Infection in the Pregnant Common Marmoset Induces Spontaneous Fetal Loss and Neurodevelopmental Abnormalities

During its most recent outbreak across the Americas, Zika virus (ZIKV) was surprisingly shown to cause fetal loss and congenital malformations in acutely and chronically infected pregnant women. However, understanding the underlying pathogenesis of ZIKV congenital disease has been hampered by a lack of relevant in vivo experimental models. Here we present a candidate New World monkey model of ZIKV infection in pregnant marmosets that faithfully recapitulates human disease. ZIKV inoculation at the human-equivalent of early gestation caused an asymptomatic seroconversion, induction of type I/II interferon-associated genes and proinflammatory cytokines, and persistent viremia and viruria. Spontaneous pregnancy loss was observed 16–18 days post-infection, with extensive active placental viral replication and fetal neurocellular disorganization similar to that seen in humans. These findings underscore the key role of the placenta as a conduit for fetal infection, and demonstrate the utility of marmosets as a highly relevant model for studying congenital ZIKV disease and pregnancy loss.

Immune Control of Burkholderia pseudomallei--Common, High-Frequency T-Cell Responses to a Broad Repertoire of Immunoprevalent Epitopes.

Burkholderia pseudomallei (Bp) is an environmental bacterial pathogen that causes potentially lethal sepsis in susceptible individuals and is considered a Category B, Tier-1 biothreat agent. As such, it is crucial to gain an improved understanding of protective immunity and potential vaccine candidates. The nature of immune correlates dictating why most exposed individuals in endemic regions undergo asymptomatic seroconversion while others succumb to life-threatening sepsis is largely uncharted. Bp seroreactive, immunogenic proteins have previously been identified by antigen microarray. We here set out to conduct an analysis of T-cell recognition of the Bp immunome using serodominant antigens represented in the original antigen microarray, examining immune correlates of disease in healthy seropositive individuals and those with acute disease or in convalescence. By screening a library of 739 overlapping peptides representing the sequences of 20 different Bp antigens, we aimed to define immune correlates of protection at the level of immunoprevalent T-cell epitopes. Responses to a large number of epitopes were common in healthy seropositive individuals: we found remarkably broad responsiveness to Bp epitopes, with 235 of 739 peptides recognized by ≥80% of all tested donors. The cumulative response to Bp epitopes in healthy, seropositive, donors from this endemic region were of the order of thousands of spot forming cells per million cells, making Bp recognition a significant component of the T-cell repertoire. Noteworthy among our findings, analysis revealed 10 highly immunoprevalent T-cell epitopes, able to induce Bp-specific IFNγ responses that were high in responding T-cell frequency within the repertoire, and also common across individuals with different human leukocyte antigen types. Acute melioidosis patients showed poor T-cell responses to the immunoprevalent epitopes, but acquired responsiveness following recovery from infection. Our findings suggest that a large repertoire of CD4 T cells, high in frequency and with broad coverage of antigens and epitopes, is important in controlling Bp infection. This offers an attractive potential strategy for subunit or epitope-based vaccines.