ResearchPad - viral-diseases https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Assessing entomological risk factors for arboviral disease transmission in the French Territory of the Wallis and Futuna Islands]]> https://www.researchpad.co/article/elastic_article_13872 The French overseas Territory of the Wallis and Futuna Islands, located in the South Pacific, has been affected by several dengue epidemics, but did not face Zika or chikungunya outbreaks, unlike other neighboring islands. The near-exclusive presence of the Aedes polynesiensis mosquito in the islands of Wallis and Futuna confirmed the role played by this mosquito as a vector of dengue fever. A local Ae. polynesiensis population was recently shown to be able to transmit the Zika virus under experimental conditions, but its susceptibility to the chikungunya virus was still unknown, and recent data on the presence of other potential arbovirus vectors were missing. Therefore, we investigated the entomological risk factors for the transmission of arboviral diseases in the Wallis and Futuna Islands. We reported the occurrence and distribution of different Aedes species, especially the abundant presence of Ae. polynesiensis across the territory and the spread of Ae. aegypti in the island of Wallis. Our results demonstrated the ability of local Ae. polynesiensis populations to transmit the chikungunya virus. These findings highlight the risk of arbovirus transmission in the Wallis and Futuna Islands and provide relevant data to guide prevention and vector control strategies in the territory.

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<![CDATA[Not sick enough to worry? "Influenza-like" symptoms and work-related behavior among healthcare workers and other professionals: Results of a global survey]]> https://www.researchpad.co/article/elastic_article_13852 Healthcare workers (HCWs) and non-HCWs may contribute to the transmission of influenza-like illness (ILI) to colleagues and susceptible patients by working while sick (presenteeism). The present study aimed to explore the views and behavior of HCWs and non-HCWs towards the phenomenon of working while experiencing ILI.MethodsThe study was a cross-sectional online survey conducted between October 2018 and January 2019 to explore sickness presenteeism and the behaviour of HCWs and non-HCWs when experiencing ILI. The survey questionnaire was distributed to the members and international networks of the International Society of Antimicrobial Chemotherapy (ISAC) Infection Prevention and Control (IPC) Working Group, as well as via social media platforms, including LinkedIn, Twitter and IPC Blog.ResultsIn total, 533 respondents from 49 countries participated (Europe 69.2%, Asia-Pacific 19.1%, the Americas 10.9%, and Africa 0.8%) representing 249 HCWs (46.7%) and 284 non-HCWs (53.2%). Overall, 312 (58.5%; 95% confidence interval [CI], 56.2–64.6) would continue to work when sick with ILI, with no variation between the two categories. Sixty-seven (26.9%) HCWs and forty-six (16.2%) non-HCWs would work with fever alone (p<0 .01) Most HCWs (89.2–99.2%) and non-HCWs (80%-96.5%) would work with “minor” ILI symptoms, such as sore throat, sinus cold, fatigue, sneezing, runny nose, mild cough and reduced appetite.ConclusionA future strategy to successfully prevent the transmission of ILI in healthcare settings should address sick-leave policy management, in addition to encouraging the uptake of influenza vaccine. ]]> <![CDATA[Virus detections among patients with severe acute respiratory illness, Northern Vietnam]]> https://www.researchpad.co/article/elastic_article_13805 Severe acute respiratory illness (SARI) is a major cause of death and morbidity in low- and middle-income countries, however, the etiologic agents are often undetermined due to the lack of molecular diagnostics in hospitals and clinics. To examine evidence for select viral infections among patients with SARI in northern Vietnam, we studied 348 nasopharyngeal samples from military and civilian patients admitted to 4 hospitals in the greater Hanoi area from 2017–2019. Initial screening for human respiratory viral pathogens was performed in Hanoi, Vietnam at the National Institute of Hygiene and Epidemiology (NIHE) or the Military Institute of Preventative Medicine (MIPM), and an aliquot was shipped to Duke-NUS Medical School in Singapore for validation. Patient demographics were recorded and used to epidemiologically describe the infections. Among military and civilian cases of SARI, 184 (52.9%) tested positive for one or more respiratory viruses. Influenza A virus was the most prevalent virus detected (64.7%), followed by influenza B virus (29.3%), enterovirus (3.8%), adenovirus (1.1%), and coronavirus (1.1%). Risk factor analyses demonstrated an increased risk of influenza A virus detection among military hospital patients (adjusted OR, 2.0; 95% CI, 1.2–3.2), and an increased risk of influenza B virus detection among patients enrolled in year 2017 (adjusted OR, 7.9; 95% CI, 2.7–22.9). As influenza A and B viruses were commonly associated with SARI and are treatable, SARI patients entering these hospitals would benefit if the hospitals were able to adapt onsite molecular diagnostics.

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<![CDATA[Placental transfer of Letermovir &amp; Maribavir in the <i>ex vivo</i> human cotyledon perfusion model. New perspectives for <i>in utero</i> treatment of congenital cytomegalovirus infection]]> https://www.researchpad.co/article/elastic_article_11236 Congenital cytomegalovirus infection can lead to severe sequelae. When fetal infection is confirmed, we hypothesize that fetal treatment could improve the outcome. Maternal oral administration of an effective drug crossing the placenta could allow fetal treatment. Letermovir (LMV) and Maribavir (MBV) are new CMV antivirals, and potential candidates for fetal treatment.MethodsThe objective was to investigate the placental transfer of LMV and MBV in the ex vivo method of the human perfused cotyledon. Term placentas were perfused, in an open-circuit model, with LMV or MBV at concentrations in the range of clinical peak plasma concentrations. Concentrations were measured using ultraperformance liquid chromatography coupled with tandem mass spectrometry. Mean fetal transfer rate (FTR) (fetal (FC) /maternal concentration), clearance index (CLI), accumulation index (AI) (retention of each drug in the cotyledon tissue) were measured. Mean FC were compared with half maximal effective concentrations of the drugs (EC50(LMV) and EC50(MBV)).ResultsFor LMV, the mean FC was (± standard deviation) 1.1 ± 0.2 mg/L, 1,000-fold above the EC50(LMV). Mean FTR, CLI and AI were 9 ± 1%, 35 ± 6% and 4 ± 2% respectively. For MBV, the mean FC was 1.4 ± 0.2 mg/L, 28-fold above the EC50(MBV). Mean FTR, CLI and AI were 10 ± 1%, 50 ± 7% and 2 ± 1% respectively.ConclusionsDrugs’ concentrations in the fetal side should be in the range for in utero treatment of fetuses infected with CMV as the mean FC was superior to the EC50 for both molecules. ]]> <![CDATA[Inferring the immune response from repertoire sequencing]]> https://www.researchpad.co/article/elastic_article_7765 High-throughput immune repertoire sequencing (RepSeq) experiments are becoming a common way to study the diversity, structure and composition of lymphocyte repertoires, promising to yield unique insight into individuals’ past infection history. However, the analysis of these sequences remains challenging, especially when comparing two different temporal or tissue samples. Here we develop a new theoretical approach and methodology to extract the characteristics of the lymphocyte repertoire response from different samples. The method is specifically tailored to RepSeq experiments and accounts for the multiple sources of noise present in these experiments. Its output provides expansion parameters, as well as a list of potentially responding clonotypes. We apply the method to describe the response to yellow fever vaccine obtained from samples taken at different time points. We also use our results to estimate the diversity and clone size statistics from data.

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<![CDATA[New estimates of the Zika virus epidemic attack rate in Northeastern Brazil from 2015 to 2016: A modelling analysis based on Guillain-Barré Syndrome (GBS) surveillance data]]> https://www.researchpad.co/article/elastic_article_7754 The mandatory reporting of the Zika virus (ZIKV) disease began region-wide in February 2016, and it is believed that ZIKV cases could have been highly under-reported before that. Given the Guillain-Barré syndrome (GBS) is relatively well reported, the GBS surveillance data has the potential to act as a reasonably reliable proxy for inferring the true ZIKV epidemics. We developed a mathematical model incorporating weather effects to study the ZIKV-GBS epidemics and estimated the key epidemiological parameters. It was found that the attack rate of ZIKV was likely to be lower than 33% over the two epidemic waves. The risk rate from symptomatic ZIKV case to develop GBS was estimated to be approximately 0.0061%. The analysis suggests that it would be difficult for another ZIKV outbreak to appear in Northeastern Brazil in the near future.

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<![CDATA[Prevalence, Severity and Mortality associated with COPD and Smoking in patients with COVID-19: A Rapid Systematic Review and Meta-Analysis]]> https://www.researchpad.co/article/elastic_article_7662 Coronavirus disease 2019 (COVID-19) is an evolving infectious disease that dramatically spread all over the world in the early part of 2020. No studies have yet summarized the potential severity and mortality risks caused by COVID-19 in patients with chronic obstructive pulmonary disease (COPD), and we update information in smokers.MethodsWe systematically searched electronic databases from inception to March 24, 2020. Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Study quality was assessed using a modified version of the Newcastle-Ottawa Scale. We synthesized a narrative from eligible studies and conducted a meta-analysis using a random-effects model to calculate pooled prevalence rates and 95% confidence intervals (95%CI).ResultsIn total, 123 abstracts were screened and 61 full-text manuscripts were reviewed. A total of 15 studies met the inclusion criteria, which included a total of 2473 confirmed COVID-19 patients. All studies were included in the meta-analysis. The crude case fatality rate of COVID-19 was 7.4%. The pooled prevalence rates of COPD patients and smokers in COVID-19 cases were 2% (95% CI, 1%–3%) and 9% (95% CI, 4%–14%) respectively. COPD patients were at a higher risk of more severe disease (risk of severity = 63%, (22/35) compared to patients without COPD 33.4% (409/1224) [calculated RR, 1.88 (95% CI, 1.4–2.4)]. This was associated with higher mortality (60%). Our results showed that 22% (31/139) of current smokers and 46% (13/28) of ex-smokers had severe complications. The calculated RR showed that current smokers were 1.45 times more likely [95% CI: 1.03–2.04] to have severe complications compared to former and never smokers. Current smokers also had a higher mortality rate of 38.5%.ConclusionAlthough COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD. Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate. Effective preventive measures are required to reduce COVID-19 risk in COPD patients and current smokers. ]]> <![CDATA[Adherence to antiretroviral therapy and associated factors among Human immunodeficiency virus positive patients accessing treatment at Nekemte referral hospital, west Ethiopia, 2019]]> https://www.researchpad.co/article/elastic_article_7637 Antiretroviral therapy has a remarkable clinical effect in reducing the progress of Acquired Immune Deficiency Syndrome. The clinical outcome of Anti-Retroviral therapy depends on strict adherence. Poor adherence reduces the effectiveness of antiretroviral therapy and increases viral replication. With changes in service delivery over time and differences in socio-demographic status from region to region, it is essential to measure adherence. Therefore, this study aimed to assess adherence to antiretroviral therapy and its associated factors among HIV/AIDS patients accessing treatment at Nekemte referral hospital, West Ethiopia.MethodsInstitutional based cross-sectional study was conducted on 311 HIV/AIDS patients from March 01 to March 30, 2019. The study participants were selected by a simple random sampling method and interviewed using structured questionnaires. Bivariable logistic regression was conducted to find an association between each independent variable and adherence to antiretroviral medication. Multivariable logistic regression was used to find the independent variables which best predict adherence. The statistical significance was measured using odds ratio at a 95% confidence interval with a p-value of less than 0.05.ResultsOut of a total of 311 patients sampled, 305 were participated in the study, making a response rate of 98.07%. From these 305 study participants,73.1% (95% CI = 68.2, 78.0) were adherent to their medication. Having knowledge about HIV and its treatment (AOR = 8.24, 95% CI: 3.10, 21.92), having strong family/social support (AOR = 6.21, 95% CI: 1.39, 27.62), absence of adverse drug reaction (AOR = 5.33, 95% CI: 1.95, 14.57), absence of comorbidity of other chronic diseases (AOR = 5.72, 95% CI: 1.91, 17.16) and disclosing HIV status to the family (AOR = 5.08, 95% CI: 2.09, 12.34) were significantly associated with an increased likelihood of adherence to antiretroviral medication.ConclusionThe level of adherence to antiretroviral therapy was found low compared to WHO recommendation. The clinician should emphasize reducing adverse drug reaction, detecting and treating co-morbidities early, improving knowledge through health education, and encouraging the patients to disclose their HIV status to their families. ]]> <![CDATA[A Novel HIV Vaccine Adjuvanted by IC31 Induces Robust and Persistent Humoral and Cellular Immunity]]> https://www.researchpad.co/article/5989dab9ab0ee8fa60badf30

The HIV vaccine strategy that, to date, generated immune protection consisted of a prime-boost regimen using a canarypox vector and an HIV envelope protein with alum, as shown in the RV144 trial. Since the efficacy was weak, and previous HIV vaccine trials designed to generate antibody responses failed, we hypothesized that generation of T cell responses would result in improved protection. Thus, we tested the immunogenicity of a similar envelope-based vaccine using a mouse model, with two modifications: a clade C CN54gp140 HIV envelope protein was adjuvanted by the TLR9 agonist IC31®, and the viral vector was the vaccinia strain NYVAC-CN54 expressing HIV envelope gp120. The use of IC31® facilitated immunoglobulin isotype switching, leading to the production of Env-specific IgG2a, as compared to protein with alum alone. Boosting with NYVAC-CN54 resulted in the generation of more robust Th1 T cell responses. Moreover, gp140 prime with IC31® and alum followed by NYVAC-CN54 boost resulted in the formation and persistence of central and effector memory populations in the spleen and an effector memory population in the gut. Our data suggest that this regimen is promising and could improve the protection rate by eliciting strong and long-lasting humoral and cellular immune responses.

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<![CDATA[Barriers to linking high-risk jail detainees to HIV pre-exposure prophylaxis]]> https://www.researchpad.co/article/N6cdd8894-eb56-44cf-b406-5a297c3ac14c

Individuals involved in the criminal justice (CJ) system continue to be at disproportionate risk for HIV infection, and often have a greater prevalence of substance use and sexual related risk behaviors relative to their non-CJ involved peers. Pre-exposure prophylaxis (PrEP), a once daily antiretroviral medicine, is an evidence-based approach for reducing the risk of contracting HIV but limited data exist regarding the use of PrEP among CJ populations, especially in the U.S. South. This study was conducted at the Pulaski County Regional Detention Facility (PCRDF) in Little Rock, Arkansas (AR), the largest county jail in the state. We explored knowledge about PrEP and HIV, perceptions about PrEP feasibility in both the jail and community settings and barriers to PrEP program implementation, through in-depth qualitative interviews with 21 jail detainees. We purposively sampled individuals based on specific self-reported risk behavior, including sexual risk (both heterosexual and same-sex) and drug related risk (e.g. IDU), among all eligible individuals. We identified five primary themes from the interviews: 1) accessing healthcare during community reentry was a low priority; 2) perception of risk and interaction with people with HIV was low; 3) there are many barriers to disclosing HIV risk behaviors in jail settings; 4) knowledge of PrEP is low but willingness to use is high; and 5) multiple barriers exist to PrEP uptake post-release. Our findings are contextually unique and therefore have important implications for future implementation of PrEP access either within jail settings or linkage to PrEP post release.

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<![CDATA[Baloxavir treatment of ferrets infected with influenza A(H1N1)pdm09 virus reduces onward transmission]]> https://www.researchpad.co/article/Nca8f7add-a1d9-4373-9c77-344aec55ea94

Influenza viruses cause seasonal outbreaks and pose a continuous pandemic threat. Although vaccines are available for influenza control, their efficacy varies each season and a vaccine for a novel pandemic virus manufactured using current technology will not be available fast enough to mitigate the effect of the first pandemic wave. Antivirals can be effective against many different influenza viruses but have not thus far been used extensively for outbreak control. Baloxavir, a recently licensed antiviral drug that targets the influenza virus endonuclease, has been shown to reduce virus shedding more effectively than oseltamivir, a widely used neuraminidase inhibitor drug. Thus it is possible that treatment with baloxavir might also interrupt onward virus transmission. To test this, we utilized the ferret model, which is the most commonly used animal model to study influenza virus transmission. We established a subcutaneous baloxavir administration method in ferrets which achieved similar pharmacokinetics to the approved human oral dose. Transmission studies were then conducted in two different locations with different experimental setups to compare the onward transmission of A(H1N1)pdm09 virus from infected ferrets treated with baloxavir, oseltamivir or placebo to naïve sentinel ferrets exposed either indirectly in adjacent cages or directly by co-housing. We found that baloxavir treatment reduced infectious viral shedding in the upper respiratory tract of ferrets compared to placebo, and reduced the frequency of transmission amongst sentinels in both experimental setups, even when treatment was delayed until 2 days post-infection. In contrast, oseltamivir treatment did not substantially affect viral shedding or transmission compared to placebo. We did not detect the emergence of baloxavir-resistant variants in treated animals or in untreated sentinels. Our results support the concept that antivirals which decrease viral shedding could also reduce influenza transmission in the community.

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<![CDATA[“It is always better for a man to know his HIV status” – A qualitative study exploring the context, barriers and facilitators of HIV testing among men in Nairobi, Kenya]]> https://www.researchpad.co/article/N633bb09e-858a-4016-b37a-13e5d588b21f

HIV testing services are an important component of HIV program and provide an entry point for clinical care for persons newly diagnosed with HIV. Although uptake of HIV testing has increased in Kenya, men are still less likely than women to get tested and access services. There is, however, limited understanding of the context, barriers and facilitators of HIV testing among men in the country. Data are from in-depth interviews with 30 men living with HIV and 8 HIV testing counsellors that were conducted to gain insights on motivations and drivers for HIV testing among men in the city of Nairobi. Men were identified retroactively by examining clinical CD4 registers on early and late diagnosis (e.g. CD4 of ≥500 cells/mm, early diagnosis and <500 cells/mm, late diagnosis). Analysis involved identifying broad themes and generating descriptive codes and categories. Timing for early testing is linked with strong social support systems and agency to test, while cost of testing, choice of facility to test and weak social support systems (especially poor inter-partner relations) resulted in late testing. Minimal discussions occurred prior to testing and whenever there was dialogue it happened with partners or other close relatives. Interrelated barriers at individual, health-care system, and interpersonal levels hindered access to testing services. Specifically, barriers to testing included perceived providers attitudes, facility location and set up, wait time/inconvenient clinic times, low perception of risk, limited HIV knowled ge, stigma, discrimination and fear of having a test. High risk perception, severe illness, awareness of partner’s status, confidentiality, quality of services and supplies, flexible/extended opening hours, and pre–and post–test counselling were facilitators. Experiences between early and late testers overlapped though there were minor differences. In order to achieve the desired impact nationally and to attain the 90-90-90 targets, multiple interventions addressing both barriers and facilitators to testing are needed to increase uptake of testing and to link the positive to care.

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<![CDATA[Detection of novel coronaviruses in bats in Myanmar]]> https://www.researchpad.co/article/N3669ab46-787e-4c30-a451-397d479219b9

The recent emergence of bat-borne zoonotic viruses warrants vigilant surveillance in their natural hosts. Of particular concern is the family of coronaviruses, which includes the causative agents of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and most recently, Coronavirus Disease 2019 (COVID-19), an epidemic of acute respiratory illness originating from Wuhan, China in December 2019. Viral detection, discovery, and surveillance activities were undertaken in Myanmar to identify viruses in animals at high risk contact interfaces with people. Free-ranging bats were captured, and rectal and oral swabs and guano samples collected for coronaviral screening using broadly reactive consensus conventional polymerase chain reaction. Sequences from positives were compared to known coronaviruses. Three novel alphacoronaviruses, three novel betacoronaviruses, and one known alphacoronavirus previously identified in other southeast Asian countries were detected for the first time in bats in Myanmar. Ongoing land use change remains a prominent driver of zoonotic disease emergence in Myanmar, bringing humans into ever closer contact with wildlife, and justifying continued surveillance and vigilance at broad scales.

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<![CDATA[Will COVID-19 become the next neglected tropical disease?]]> https://www.researchpad.co/article/N3ea3a36c-f707-4121-8cab-1c306bbb1993 ]]> <![CDATA[The inhibitor of apoptosis proteins antagonist Debio 1143 promotes the PD-1 blockade-mediated HIV load reduction in blood and tissues of humanized mice]]> https://www.researchpad.co/article/N65563527-6ce7-4ff1-862d-df2c817374ce

The immune checkpoint programmed cell death protein 1 (PD-1) plays a major role in T cell exhaustion in cancer and chronic HIV infection. The inhibitor of apoptosis protein antagonist Debio 1143 (D1143) enhances tumor cell death and synergizes with anti-PD-1 agents to promote tumor immunity and displayed HIV latency reversal activity in vitro. We asked in this study whether D1143 would stimulate the potency of an anti-human PD-1 monoclonal antibody (mAb) to reduce HIV loads in humanized mice. Anti-PD-1 mAb treatment decreased PD-1+ CD8+ cell population by 32.3% after interruption of four weeks treatment, and D1143 co-treatment further reduced it from 32.3 to 73%. Anti-PD-1 mAb administration reduced HIV load in blood by 94%, and addition of D1143 further enhanced this reduction from 94 to 97%. D1143 also more profoundly promoted with the anti-PD-1-mediated reduction of HIV loads in all tissues analyzed including spleen (71 to 96.4%), lymph nodes (64.3 to 80%), liver (64.2 to 94.4), lung (64.3 to 80.1%) and thymic organoid (78.2 to 98.2%), achieving a >5 log reduction of HIV loads in CD4+ cells isolated from tissues 2 weeks after drug treatment interruption. Ex vivo anti-CD3/CD28 stimulation increased the ability to activate exhausted CD8+ T cells in infected mice having received in vivo anti-PD-1 treatment by 7.9-fold (5 to 39.6%), and an additional increase by 1.7-fold upon D1143 co-treatment (39.6 to 67.3%). These findings demonstrate for the first time that an inhibitor of apoptosis protein antagonist enhances in a statistically manner the effects of an immune check point inhibitor on antiviral immunity and on HIV load reduction in tissues of humanized mice, suggesting that the combination of two distinct classes of immunomodulatory agents constitutes a promising anti-HIV immunotherapeutic approach.

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<![CDATA[Prediction model for dengue fever based on interactive effects between multiple meteorological factors in Guangdong, China (2008–2016)]]> https://www.researchpad.co/article/Nfe4e2064-ca0a-4d6d-a8b7-4f75eb296e9a

Introduction

In order to improve the prediction accuracy of dengue fever incidence, we constructed a prediction model with interactive effects between meteorological factors, based on weekly dengue fever cases in Guangdong, China from 2008 to 2016.

Methods

Dengue fever data were derived from statistical data from the China National Notifiable Infectious Disease Reporting Information System. Daily meteorological data were obtained from the China Integrated Meteorological Information Sharing System. The minimum temperature for transmission was identified using data fitting and the Ross-Macdonald model. Correlations and interactive effects were examined using Spearman’s rank correlation and multivariate analysis of variance. A probit regression model to describe the incidence of dengue fever from 2008 to 2016 and forecast the 2017 incidence was constructed, based on key meteorological factors, interactive effects, mosquito-vector factors, and other important factors.

Results

We found the minimum temperature suitable for dengue transmission was ≥18°C, and as 97.91% of cases occurred when the minimum temperature was above 18 °C, the data were used for model training and construction. Epidemics of dengue are related to mean temperature, maximum/minimum and mean atmospheric pressure, and mean relative humidity. Moreover, interactions occur between mean temperature, minimum atmospheric pressure, and mean relative humidity. Our weekly probit regression prediction model is 0.72. Prediction of dengue cases for the first 41 weeks of 2017 exhibited goodness of fit of 0.60.

Conclusion

Our model was accurate and timely, with consideration of interactive effects between meteorological factors.

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<![CDATA[Projections of Ebola outbreak size and duration with and without vaccine use in Équateur, Democratic Republic of Congo, as of May 27, 2018]]> https://www.researchpad.co/article/5c8accd5d5eed0c4849900f7

As of May 27, 2018, 6 suspected, 13 probable and 35 confirmed cases of Ebola virus disease (EVD) had been reported in Équateur Province, Democratic Republic of Congo. We used reported case counts and time series from prior outbreaks to estimate the total outbreak size and duration with and without vaccine use. We modeled Ebola virus transmission using a stochastic branching process model that included reproduction numbers from past Ebola outbreaks and a particle filtering method to generate a probabilistic projection of the outbreak size and duration conditioned on its reported trajectory to date; modeled using high (62%), low (44%), and zero (0%) estimates of vaccination coverage (after deployment). Additionally, we used the time series for 18 prior Ebola outbreaks from 1976 to 2016 to parameterize the Thiel-Sen regression model predicting the outbreak size from the number of observed cases from April 4 to May 27. We used these techniques on probable and confirmed case counts with and without inclusion of suspected cases. Probabilistic projections were scored against the actual outbreak size of 54 EVD cases, using a log-likelihood score. With the stochastic model, using high, low, and zero estimates of vaccination coverage, the median outbreak sizes for probable and confirmed cases were 82 cases (95% prediction interval [PI]: 55, 156), 104 cases (95% PI: 58, 271), and 213 cases (95% PI: 64, 1450), respectively. With the Thiel-Sen regression model, the median outbreak size was estimated to be 65.0 probable and confirmed cases (95% PI: 48.8, 119.7). Among our three mathematical models, the stochastic model with suspected cases and high vaccine coverage predicted total outbreak sizes closest to the true outcome. Relatively simple mathematical models updated in real time may inform outbreak response teams with projections of total outbreak size and duration.

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<![CDATA[Comparative performance of four rapid Ebola antigen-detection lateral flow immunoassays during the 2014-2016 Ebola epidemic in West Africa]]> https://www.researchpad.co/article/5c8acc8bd5eed0c48498f9b7

Background

Without an effective vaccine, as was the case early in the 2014–2016 Ebola Outbreak in West Africa, disease control depends entirely on interrupting transmission through early disease detection and prompt patient isolation. Lateral Flow Immunoassays (LFI) are a potential supplement to centralized reference laboratory testing for the early diagnosis of Ebola Virus Disease (EVD).

The goal of this study was to assess the performance of commercially available simple and rapid antigen detection LFIs, submitted for review to the WHO via the Emergency Use Assessment and Listing procedure. The study was performed in an Ebola Treatment Centre laboratory involved in EVD testing in Sierra Leone.

In light of the current Ebola outbreak in May 2018 in the Democratic Republic of Congo, which highlights the lack of clarity in the global health community about appropriate Ebola diagnostics, our findings are increasingly critical.

Methods

A cross-sectional study was conducted to assess comparative performance of four LFIs for detecting EVD. LFIs were assessed against the same 328 plasma samples and 100 whole EDTA blood samples, using the altona RealStar Filovirus Screen real-time RT-PCR as the bench mark assay. The performance of the Public Health England (PHE) in-house Zaire ebolavirus-specific real time RT-PCR Trombley assay was concurrently assessed. Statistical analysis using generalized estimating equations was conducted to compare LFI performance.

Findings

Sensitivity and specificity varied between the LFIs, with specificity found to be significantly higher for whole EDTA blood samples compared to plasma samples in at least 2 LFIs (P≤0.003). Using the altona RT-PCR assay as the bench mark, sensitivities on plasma samples ranged from 79.53% (101/127, 95% CI: 71.46–86.17%) for the DEDIATEST EBOLA (SD Biosensor) to 98.43% (125/127, 95% CI: 94.43–99.81%) for the One step Ebola test (Intec). Specificities ranged from 80.20% (158/197, 95% CI: 74.07–88.60%) for plasma samples using the ReEBOV Antigen test Kit (Corgenix) to 100.00% (98/98, 95% CI: 96.31–100.00%) for whole blood samples using the DEDIATEST EBOLA (SD Biosensor) and SD Ebola Zaire Ag (SD Biosensor). Results also showed the Trombley RT-PCR assay had a lower limit of detection than the altona assay, with some LFIs having higher sensitivity than the altona assay when the Trombley assay was the bench mark.

Interpretation

All of the tested EVD LFIs may be considered suitable for use in an outbreak situation (i.e. rule out testing in communities), although they had variable performance characteristics, with none possessing both high sensitivity and specificity. The non-commercial Trombley Zaire ebolavirus RT-PCR assay warrants further investigation, as it appeared more sensitive than the current gold standard, the altona Filovirus Screen RT-PCR assay.

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<![CDATA[Seasonal characteristics of influenza vary regionally across US]]> https://www.researchpad.co/article/5c897716d5eed0c4847d2428

Given substantial regional differences in absolute humidity across the US and our understanding of the relationship between absolute humidity and influenza, we may expect important differences in regional seasonal influenza activity. Here, we assessed cross-seasonal influenza activity by comparing counts of positive influenza A and B rapid test results during the influenza season versus summer baseline periods for the 2016/2017 and 2017/2018 influenza years. Our analysis indicates significant regional patterns in cross-seasonal influenza activity, with relatively fewer influenza cases during the influenza season compared to summertime baseline periods in humid areas of the US, particularly in Florida and Hawaii. The cross-seasonal ratios vary from year-to-year and influenza type, but the geographic patterning of the ratios is relatively consistent. Mixed-effects regression models indicated absolute humidity during the influenza season was the strongest predictor of cross-seasonal influenza activity, suggesting a relationship between absolute humidity and cross-seasonal influenza activity. There was also evidence that absolute humidity during the summer plays a role, as well. This analysis suggests that spatial variation in seasonal absolute humidity levels may generate important regional differences in seasonal influenza activity and dynamics in the US.

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<![CDATA[Epidemiological and clinical characteristics of Dengue virus outbreaks in two regions of China, 2014 – 2015]]> https://www.researchpad.co/article/5c8823dcd5eed0c4846391a6

Dengue virus (DENV), a single-stranded RNA virus and Flaviviridae family member, is transmitted by Aedes aegypti and Aedes albopictus mosquitoes. DENV causes dengue fever, which may progress to severe dengue. Hospital-based surveillance was performed in two Chinese regions, Guangzhou and Xishuangbanna, during the dengue epidemics in 2014 and 2015, respectively. Acute-phase serum was obtained from 133 patients with suspected dengue infections during the peak season for dengue cases. Viremia levels, virus sero-positivity, serotype distribution, infection type, clinical manifestations and virus phylogenetics were investigated. Of the 112 DENV-confirmed cases, 92(82.14%) were IgM antibody-positive for DENV, and 69(51.88%) were positive for DENV RNA. From these cases, 47(41.96%) were classified as primary infections, 39(34.82%) as secondary infections and 26 (23.21%) as undetermined infections. The viremia levels were negatively correlated with IgM presence, but had no relationship with the infection type. DENV-1 genotype V dominated in Guangzhou, whereas the DENV-2 Cosmopolitan genotype dominated in Xishuangbanna, where fewer DENV-1 genotype I cases occurred. DENV-2 is associated with severe dengue illness with more serious clinical issues. The strains isolated during 2014–2015 are closely related to the isolates obtained from other Chinese regions and to those isolated recently in Southeast Asian countries. Our results indicate that DENV is no longer an imported virus and is now endemic in China. An extensive seroepidemiological study of DENV and the implementation of vector control measures against it are now warranted in China.

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