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Background: Understanding the level of exposure to Lassa virus (LASV) in at-risk communities allows for the administration of effective preventive interventions to mitigate epidemics of Lassa fever. We assessed the seroprevalence of LASV antibodies in rural and semiurban communities of two cosmopolitan cities in Nigeria with poorly understood Lassa epidemiology., Methods: A cross-sectional study was conducted in ten communities located in the Abuja Municipal Area Council (AMAC), Abuja, and Ikorodu Local Government Area (LGA), Lagos, from February 2nd to July 5th, 2022. Serum samples collected from participants were analyzed for IgG and IgM antibodies using a ReLASV ® Pan-Lassa NP IgG/IgM enzyme-linked immunosorbent assay (ELISA) kit. A questionnaire administered to participants collected self-reported sociodemographic and LASV exposure information. Seroprevalence of LASV IgG/IgM was estimated overall, and by study site. Univariate and multivariate log-binomial models estimated unadjusted and adjusted prevalence ratios (aPRs) and 95% confidence intervals (CI) for site-specific risk factors for LASV seropositivity. Grouped Least Absolute Shrinkage and Selection Operator (LASSO) was used for variable selection for multivariate analysis., Results: A total of 628 participants with serum samples were included in the study. Most participants were female (434, 69%), married (459, 73%), and had a median age of 38 years (interquartile range 28-50). The overall seroprevalence was 27% (171/628), with a prevalence of 33% (126/376) in Abuja and 18% (45/252) in Lagos. Based on site-specific grouped LASSO selection, enrollment in the dry season (vs. wet; aPR, 95% CI: 1.73, 1.33-2.24), reported inconsistent washing of fruits and vegetables (aPR, 95% CI: 1.45, 1.10-1.92), and a positive malaria rapid test (aPR, 95% CI: 1.48, 1.09-2.00) were independently associated with LASV seropositivity in Abuja, whereas, only a self-reported history of rhinorrhea (PR, 95% CI: 2.21, 1.31-3.72) was independently associated with Lassa seropositivity in Lagos., Conclusions: The LASV seroprevalence was comparable to that in other areas in Nigeria. Our findings corroborate those from other studies on the importance of limiting human exposure to rodents and focusing on behavioral factors such as poor hygiene practices to reduce exposure to LASV., (© 2024. The Author(s).)

Background: Zika virus infection is commonly described as a mild and self-limiting illness. However, cardiac complications were associated with acute Zika virus infection., Case Presentation: A 46-year-old woman without previous comorbidities with a 1-day history of symptoms tested positive for ZIKV by real time reverse transcriptase polymerase chain reaction (rRT-PCR). She was admitted two days after with clinical worsening, cardiac enzymes elevated, and cardiac imaging findings, and the diagnosis of myopericarditis was made. The patient was treated and presented significant clinical improvement after one year., Conclusions: Cardiac complication following ZIKV infection appears to be infrequent. Here, we report a rare case of viral myopericarditis caused by ZIKV infection., (© 2022. The Author(s).)

Background: Zika virus (ZIKV) is a mosquito-transmitted flavivirus that affects many regions of the world. Infection, in utero, causes microcephaly and later developmental and neurologic impairments. The impact of ZIKV infection on neurocognition in adults has not been well described. The objective of the study was to assess the neurocognitive impact of ZIKV infection in adult rhesus macaques., Methods: Neurocognitive assessments were performed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) via a touch screen and modified Brinkman Board before and after subcutaneous ZIKV inoculation. Immune activation markers were measured in the blood and cerebral spinal fluid (CSF) by multiplex assay and flow cytometry., Results: All animals (N = 8) had detectable ZIKV RNA in plasma at day 1 post-inoculation (PI) that peaked at day 2 PI (median 5.9, IQR 5.6-6.2 log 10 genome equivalents/mL). In all eight animals, ZIKV RNA became undetectable in plasma by day 14 PI, but persisted in lymphoid tissues. ZIKV RNA was not detected in the CSF supernatant at days 4, 8, 14 and 28 PI but was detected in the brain of 2 animals at days 8 and 28 PI. Elevations in markers of immune activation in the blood and CSF were accompanied by a reduction in accuracy and reaction speed on the CANTAB in the majority of animals., Conclusions: The co-occurrence of systemic and CSF immune perturbations and neurocognitive impairment establishes this model as useful for studying the impact of neuroinflammation on neurobehavior in rhesus macaques, as it pertains to ZIKV infection and potentially other pathogens., (© 2022. The Author(s).)

Background: The Zika virus outbreak has triggered a set of local and global actions for a rapid, effective, and timely public health response. A World Health Organization (WHO) initiative, supported by the Department of Chronic Condition Diseases and Sexually Transmitted Infections (DCCI) of the Health Surveillance Secretariat (SVS), Brazil Ministry of Health (MoH) and other public health funders, resulted in the start of the "Study on the persistence of Zika virus in body fluids of patients with ZIKV infection in Brazil - ZIKABRA study". The ZIKABRA study was designed to increase understanding of how long ZIKV persists in bodily fluids and informing best measures to prevent its transmission. Data collection began in July 2017 and the last follow up visit occurred in 06/26/2020., Methods: A framework for the ZIKABRA Cooperation initiative is provided through a description and analysis of the mechanisms, strategies and the ethos that have guided the models of international governance and technical cooperation in health for scientific exchange in the context of a public health emergency. Among the methodological strategies, we included a review of the legal documents that supported the ZIKABRA Cooperation; weekly documents produced in the meetings and working sessions; technical reports; memorandum of understanding and the research protocol., Conclusion: We highlight the importance of working in cooperation between different institutional actors to achieve more significant results than that obtained by each group working in isolation. In addition, we point out the advantages of training activities, ongoing supervision, the construction of local installed research capacity, training academic and non-academic human resources, improvement of laboratory equipment, knowledge transfer and the availability of the ZIKABRA study protocol for development of similar studies, favoring the collective construction of knowledge to provide public health emergency responses. Strategy harmonization; human resources and health services; timing and recruiting particularities and processing institutional clearance in the different sites can be mentioned as challenges in this type of initiative.

Background: Zika virus (ZIKV) has been identified in several body fluids of infected individuals. In most cases, it remained detected in blood from few days to 1 week after the onset of symptoms, and can persist longer in urine and in semen. ZIKV infection can have dramatic consequences such as microcephaly and Guillain-Barré syndrome. ZIKV sexual transmission has been documented. A better understanding of ZIKV presence and persistence across biologic compartments is needed to devise rational measures to prevent its transmission., Methods: This observational cohort study will recruit non-pregnant participants aged 18 years and above with confirmed ZIKV infection [positive reverse transcriptase-polymerase chain reaction (RT-PCR) test in blood and/or urine]: symptomatic men and women in ZIKV infection acute phase, and their symptomatic or asymptomatic household/sexual infected contacts. Specimens of blood, urine, semen, vaginal secretion/menstrual blood, rectal swab, oral fluids, tears, sweat, urine and breast milk (if applicable) will be collected at pre-established intervals and tested for ZIKV RNA presence by RT-PCR, other co-infection (dengue, Chikungunya, HIV, hepatitis B and C, syphilis), antibody response (including immunoglobulins M and G), plaque reduction neutralization test (if simultaneously positive for ZIKV and dengue), and ZIKV culture and RNA sequencing. Data on socio-demographic characteristics and comorbidities will be collected in parallel. Participants will be followed up for 12 months., Discussion: This prolonged longitudinal follow-up of ZIKV infected persons with regular biologic testing and data collection will offer a unique opportunity to investigate the presence and persistence of ZIKV in various biologic compartments, their clinical and immunological correlates as well as the possibility of ZIKV reactivation/reinfection over time. This valuable information will substantially contribute to the body of knowledge on ZIKV infection and serve as a base for the development of more effective recommendation on the prevention of ZIKV transmission., Trial Registration: NCT03106714 . Registration Date: April, 7, 2017.

The Golden Crescent region of South Asia-comprising Afghanistan, Iran, and Pakistan-is a principal global site for opium production and distribution. Over the past few decades, war, terrorism, and a shifting political landscape have facilitated an active heroin trade throughout the region. Protracted conflict has exacerbated already dire socio-economic conditions and political strife within the region and contributed to a consequent rise in opiate trafficking and addiction among the region's inhabitants. The worsening epidemic of injection drug use has paralleled the rising incidence of HIV and other blood-borne infections in the region and drawn attention to the broader implications of the growing opiate trade in the Golden Crescent. The first step in addressing drug use is to recognize that it is not a character flaw but a form of mental illness, hence warranting humane treatment of drug users. It is also recommended that the governments of the Golden Crescent countries encourage substitution of opium with licit crops and raise awareness among the general public about the perils of opium use.

The HIV pandemic persists globally and travelers are at risk for infection by the Human Immunodeficiency Virus (HIV). While HIV-focused guidelines delineate risk stratification and mitigation strategies for people in their home communities, travel issues are not addressed. In this review, direct and indirect evidence on HIV risk among travelers is explored. The burgeoning practice of employing pre-exposure prophylaxis (PrEP) with anti-retroviral therapy in the non-travel setting is introduced, as well as the more established use of post-exposure prophylaxis (PEP). Challenges in applying these lessons to travelers are discussed, and a new guidelines process is scoped and recommended.

Background: PlMERS-CoV is a coronavirus known to cause severe disease in humans, taxonomically classified under the subgenus Merbecovirus. Recent findings showed that the close relatives of MERS-CoV infecting vespertillionid bats (family Vespertillionidae), named NeoCoV and PDF-2180, use their hosts' ACE2 as their entry receptor, unlike the DPP4 receptor usage of MERS-CoV. Previous research suggests that this difference in receptor usage between these related viruses is a result of recombination. However, the precise location of the recombination breakpoints and the details of the recombination event leading to the change of receptor usage remain unclear. Methods: We used maximum likelihood-based phylogenetics and genetic similarity comparisons to characterise the evolutionary history of all complete Merbecovirus genome sequences. Recombination events were detected by multiple computational methods implemented in the recombination detection program. To verify the influence of recombination, we inferred the phylogenetic relation of the merbecovirus genomes excluding recombinant segments and that of the viruses' receptor binding domains and examined the level of congruency between the phylogenies. Finally, the geographic distribution of the genomes was inspected to identify the possible location where the recombination event occurred. Results: Similarity plot analysis and the recombination-partitioned phylogenetic inference showed that MERS-CoV is highly similar to NeoCoV (and PDF-2180) across its whole genome except for the spike-encoding region. This is confirmed to be due to recombination by confidently detecting a recombination event between the proximal ancestor of MERS-CoV and a currently unsampled merbecovirus clade. Notably, the upstream recombination breakpoint was detected in the N-terminal domain and the downstream breakpoint at the S2 subunit of spike, indicating that the acquired recombined fragment includes the receptor-binding domain. A tanglegram comparison further confirmed that the receptor binding domain-encoding region of MERS-CoV was acquired via recombination. Geographic mapping analysis on sampling sites suggests the possibility that the recombination event occurred in Africa. Conclusion: Together, our results suggest that recombination can lead to receptor switching of merbecoviruses during circulation in bats. These results are useful for future epidemiological assessments and surveillance to understand the spillover risk of bat coronaviruses to the human population. [ABSTRACT FROM AUTHOR]

Background: Timely access to outbreak related data, particularly in the early events of a spillover, is important to support evidence based control measures in response to outbreaks of zoonotic Emerging Infectious Diseases (EID). Yet, this is impeded by several barriers that need to be understood to promote timely sharing of data. Using the MERS epidemic as a model for a zoonotic EID outbreak, this study sought to provide an in-depth understanding of data sharing practices. Methods: Semi-structured interviews with 25 experts were conducted, along with Focus Group Discussions with 15 additional experts. A root-cause analysis was performed to examine the causal relationships between barriers. Enablers were mapped to the root-cause analysis to understand their influence on the barriers. Finally, root causes were placed in context of core dilemmas identified from the qualitative analysis. Findings: Eight barriers to data sharing were identified, related to collaboration, technical preparedness, regulations, and (conflict of) interests, and placed in the context of six dilemmas inherent to the multi-stakeholder collaboration required for a zoonotic outbreak response. Fourteen identified enablers showed the willingness of stakeholders to overcome or circumvent these barriers, but also indicated the inherent trial and error nature of implementing such enablers. Interpretation: Addressing the barriers requires solutions that must consider the complexity and interconnectedness of the root causes underlying them, and should consider the distinct scopes and interests of the different stakeholders. Insights provided by this study can be used to encourage data sharing practices for future outbreaks Funding: Wellcome Trust and UK Aid; EU-H2020 Societal Challenges (grant agreement no. 643476), Nederlandse Organisatie voor Wetenschappelijk Onderzoek (VI.Veni.201S.044) [ABSTRACT FROM AUTHOR]

Excessive pulmonary inflammation is the hallmark of respiratory syncytial virus (RSV) infection hindering efficacious RSV vaccine development. Yet, the vast majority of the experimental RSV vaccine studies use laboratory-adapted RSV strains that do not reflect the highly pathogenic and inflammatory nature of the virus found in clinical settings. Here, we re-evaluated the protective efficacy of the virus-like particle (VLP) vaccine co-expressing the pre-fusion (pre-F) protein and G protein with tandem repeats (Gt) reported in our previous study against the recombinant RSV rA2-line19F strain, which inflicts severe mucus production and inflammation in mice. VLP vaccine immunization elicited virus-specific serum antibody responses that mediated RSV rA2-line19F virus neutralization. VLP vaccine immunization promoted Th1 immune response development in the spleens and CD8 + T cell influx into the lungs of mice, which are essential for efficient viral clearance and dampened inflammatory response. When compared to the VLPs expressing only the pre-F antigen, those co-expressing both pre-F and Gt antigens conferred better protection in mice against rA2-line19F challenge infection. Overall, our data suggest that the pre-clinical VLP vaccine co-expressing RSV pre-F and Gt antigens can effectively protect mice against RSV strains that resemble pathogenic clinical isolates. [ABSTRACT FROM AUTHOR]

Background: The results of clinical trials should be completely and rapidly reported during public health emergencies such as COVID-19. This study aimed to examine when, and where, the results of COVID-19 clinical trials were disseminated throughout the first 18 months of the pandemic. Methods: Clinical trials for COVID-19 treatment or prevention were identified from the WHO ICTRP database. All interventional trials with a registered completion date ≤ 30 June 2021 were included. Trial results, published as preprints, journal articles, or registry results, were located using automated and manual techniques across PubMed, Google Scholar, Google, EuropePMC, CORD-19, the Cochrane COVID-19 Study Register, and clinical trial registries. Our main analysis reports the rate of dissemination overall and per route, and the time from registered completion to results using Kaplan–Meier methods, with additional subgroup and sensitivity analyses reported. Results: Overall, 1643 trials with completion dates ranging from 46 to 561 days prior to the start of results searches were included. The cumulative probability of reporting was 12.5% at 3 months from completion, 21.6% at 6 months, and 32.8% at 12 months. Trial results were most commonly disseminated in journals (n = 278 trials, 69.2%); preprints were available for 194 trials (48.3%), 86 (44.3%) of which converted to a full journal article. Trials completed earlier in the pandemic were reported more rapidly than those later in the pandemic, and those involving ivermectin were more rapidly reported than other common interventions. Results were robust to various sensitivity analyses except when considering only trials in a "completed" status on the registry, which substantially increased reporting rates. Poor trial registry data on completion status and dates limits the precision of estimates. Conclusions: COVID-19 trials saw marginal increases in reporting rates compared to standard practice; most registered trials failed to meet even the 12-month non-pandemic standard. Preprints were common, complementing journal publication; however, registries were underutilized for rapid reporting. Maintaining registry data enables accurate representation of clinical research; failing to do so undermines these registries' use for public accountability and analysis. Addressing rapid reporting and registry data quality must be emphasized at global, national, and institutional levels. [ABSTRACT FROM AUTHOR]

Background: HIV prevalence in Tanzania is still high at 4.7% among adults. Regular HIV testing is consistently advocated in the country to increase the level of awareness of HIV status, thus contributing to national HIV prevention. We report findings from three years of implementation of an HIV Test and Treat project utilizing provider-initiated and client-initiated testing and counselling (PITC and CITC). This study compared the effectiveness of PITC versus CITC in HIV case detection by the different departments of health facilities. Method: This retrospective cross-sectional study used health facility-based HIV testing data collected from adults aged 18 years and above between June 2017 – July 2019 in the Shinyanga region, Tanzania. Chi-square and logistic regression analysis were used to assess determinants of yield (HIV positivity). Results: A total of 24,802 HIV tests were performed of which 15,814 (63.8%) were by PITC and 8,987 (36.2%) by CITC. Overall HIV positivity was 5.7%, higher among CITC at 6.6% than PITC at 5.2%. TB and IPD departments had the highest HIV positivity 11.8% and 7.8% respectively. Factors associated with a positive test were testing at a department in the facility compared to CITC, first-time test, and being or having been married compared to being single. Conclusion: Success in identifying HIV + patients was highest among people visiting the clinic for HIV testing (CITC) and first-time testers. With PITC, HIV + patient detection differed between departments, suggesting divergent risk profiles of respective clients and/or divergent HIV alertness of staff. This underscores the importance of increased targeting for PITC to identify HIV + patients. [ABSTRACT FROM AUTHOR]

Background: Despite effective antiretroviral therapy (ART) coverage in other groups living with human immunodeficiency virus (HIV) in Tanzania, virologic suppression among HIV-positive children receiving ART remains unacceptably low. This study evaluated the effectiveness of a community-based intervention (Konga model) in addressing the factor contributing to low viral load suppression among children living with HIV in the Simiyu region, Tanzania. Methods: This study used a parallel cluster randomized trial. The cluster was only eligible if the health facility provided HIV care and treatment. All eligible resident children aged 2‒14 years who attended the cluster with a viral load > 1,000 cells/mm were enrolled. The intervention included three distinct activities: adherence counseling, psychosocial support, and co-morbidity screening such as tuberculosis. The evaluation was based on patient-centered viral load outcomes measured at baseline and 6 months later. Using a pre- and post-test design, we compared the means of participants in the intervention and control groups. We performed an analysis of covariance. The effect of a Konga was calculated using omega-squared. We used F-tests, with their corresponding p-values, as measures of improvement. Results: We randomly assigned 45 clusters to the treatment (15) and control (30) groups. We enrolled 82 children with amedian age of 8.8 years(interquartile range(IQR);5.5–11.2), and a baseline median viral load of 13,150 cells/mm (interquartile range (IQR);3600–59,200). After the study, both children in each group had good adherence, with children in the treatment group scoring slightly higher than those in the control group, 40 (97.56%) versus 31(75%61), respectively. At the end of the study, the difference in viral load suppression between the two groups was significant. The median viral load suppression at the end of the study was 50 cells/mm [IQR, (20–125)]. After adjusting for the viral load before the intervention, the effect size of the Konga intervention explained 4% (95% confidence interval [0%, 14.1%]) of the viral load variation at the end of the intervention. Conclusion: The Konga model demonstrated significant positive effects that improved viral load suppression. We recommend implementing the Konga model trial in other regions to improve the consistency of results. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) is a leading cause of respiratory disease in young children. A number of mathematical models have been used to assess the cost-effectiveness of RSV prevention strategies, but these have not been designed for ease of use by multidisciplinary teams working in low-income and middle-income countries (LMICs). Methods: We describe the UNIVAC decision-support model (a proportionate outcomes static cohort model) and its approach to exploring the potential cost-effectiveness of two RSV prevention strategies: a single-dose maternal vaccine and a single-dose long-lasting monoclonal antibody (mAb) for infants. We identified model input parameters for 133 LMICs using evidence from the literature and selected national datasets. We calculated the potential cost-effectiveness of each RSV prevention strategy (compared to nothing and to each other) over the lifetimes of all children born in the year 2025 and compared our results to a separate model published by PATH. We ran sensitivity and scenario analyses to identify the inputs with the largest influence on the cost-effectiveness results. Results: Our illustrative results assuming base case input assumptions for maternal vaccination ($3.50 per dose, 69% efficacy, 6 months protection) and infant mAb ($3.50 per dose, 77% efficacy, 5 months protection) showed that both interventions were cost-saving compared to status quo in around one-third of 133 LMICs, and had a cost per DALY averted below 0.5 times the national GDP per capita in the remaining LMICs. UNIVAC generated similar results to a separate model published by PATH. Cost-effectiveness results were most sensitive to changes in the price, efficacy and duration of protection of each strategy, and the rate (and cost) of RSV hospital admissions. Conclusions: Forthcoming RSV interventions (maternal vaccines and infant mAbs) are worth serious consideration in LMICs, but there is a good deal of uncertainty around several influential inputs, including intervention price, efficacy, and duration of protection. The UNIVAC decision-support model provides a framework for country teams to build consensus on data inputs, explore scenarios, and strengthen the local ownership and policy-relevance of results. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) is among the leading childhood causes of viral pneumonia worldwide. Establishing RSV-associated morbidity and mortality is important in informing the development, delivery strategies, and evaluation of interventions. Methods: Using data collected during 2010–2018 from base regions (population-based surveillance studies in western Kenya and the Kilifi Health and Demographic Surveillance Study), we estimated age-specific rates of acute respiratory illness (ARI), severe acute respiratory illness (SARI—defined as hospitalization with cough or difficulty breathing with onset within the past 10 days), and SARI-associated deaths. We extrapolated the rates from the base regions to other regions of Kenya, while adjusting for risk factors of ARI and healthcare seeking behavior, and finally applied the proportions of RSV-positive cases identified from various sentinel and study facilities to the rates to obtain regional age-specific rates of RSV-associated outpatient and non-medically attended ARI and hospitalized SARI and severe ARI that was not hospitalized (non-hospitalized SARI). We applied age-specific RSV case fatality ratios to SARI to obtain estimates of RSV-associated in- and out-of-hospital deaths. Results: Among Kenyan children aged < 5 years, the estimated annual incidence of outpatient and non-medically attended RSV-associated ARI was 206 (95% credible interval, CI; 186–229) and 226 (95% CI; 204–252) per 1000 children, respectively. The estimated annual rates of hospitalized and non-hospitalized RSV-associated SARI were 349 (95% CI; 303–404) and 1077 (95% CI; 934–1247) per 100,000 children respectively. The estimated annual number of in- and out-of-hospital deaths associated with RSV infection in Kenya were 539 (95% CI; 420–779) and 1921 (95% CI; 1495–2774), respectively. Children aged < 6 months had the highest burden of RSV-associated severe disease: 2075 (95% CI; 1818–2394) and 44 (95% CI 25–71) cases per 100,000 children for hospitalized SARI and in-hospital deaths, respectively. Conclusions: Our findings suggest a substantial disease burden due to RSV infection, particularly among younger children. Prioritizing development and use of maternal vaccines and affordable long-lasting monoclonal antibodies could help reduce this burden. [ABSTRACT FROM AUTHOR]

Bronchiolitis is an acute respiratory illness that is the leading cause of hospitalization in young children. This document aims to update the consensus document published in 2014 to provide guidance on the current best practices for managing bronchiolitis in infants. The document addresses care in both hospitals and primary care. The diagnosis of bronchiolitis is based on the clinical history and physical examination. The mainstays of management are largely supportive, consisting of fluid management and respiratory support. Evidence suggests no benefit with the use of salbutamol, glucocorticosteroids and antibiotics with potential risk of harm. Because of the lack of effective treatment, the reduction of morbidity must rely on preventive measures. De-implementation of non-evidence-based interventions is a major goal, and educational interventions for clinicians should be carried out to promote high-value care of infants with bronchiolitis. Well-prepared implementation strategies to standardize care and improve the quality of care are needed to promote adherence to guidelines and discourage non-evidence-based attitudes. In parallel, parents' education will help reduce patient pressure and contribute to inappropriate prescriptions. Infants with pre-existing risk factors (i.e., prematurity, bronchopulmonary dysplasia, congenital heart diseases, immunodeficiency, neuromuscular diseases, cystic fibrosis, Down syndrome) present a significant risk of severe bronchiolitis and should be carefully assessed. This revised document, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of acute bronchiolitis. [ABSTRACT FROM AUTHOR]

Background: Little information is available on the costs of respiratory syncytial virus (RSV) in Vietnam or other low- and middle-income countries. Our study estimated the costs of LRTIs associated with RSV infection among children in southern Vietnam. Methods: We conducted a prospective cohort study evaluating household and societal costs associated with LRTIs stratified by RSV status and severity among children under 2 years old who sought care at a major pediatric referral hospital in southern Vietnam. Enrollment periods were September 2019–December 2019, October 2020–June 2021 and October 2021–December 2021. RSV status was confirmed by a validated RT-PCR assay. RSV rapid detection antigen (RDA) test performance was also evaluated. Data on resource utilization, direct medical and non-medical costs, and indirect costs were collected from billing records and supplemented by patient-level questionnaires. All costs are reported in 2022 US dollars. Results: 536 children were enrolled in the study, with a median age of 7 months (interquartile range [IQR] 3–12). This included 210 (39.2%) children from the outpatient department, 318 children (59.3%) from the inpatient respiratory department (RD), and 8 children (1.5%) from the intensive care unit (ICU). Nearly 20% (105/536) were RSV positive: 3.9 percent (21/536) from the outpatient department, 15.7% (84/536) from the RD, and none from the ICU. The median total cost associated with LRTI per patient was US$52 (IQR 32–86) for outpatients and US$184 (IQR 109–287) for RD inpatients. For RSV-associated LRTIs, the median total cost per infection episode per patient was US$52 (IQR 32–85) for outpatients and US$165 (IQR 95–249) for RD inpatients. Total out-of-pocket costs of one non-ICU admission of RSV-associated LRTI ranged from 32%-70% of the monthly minimum wage per person (US$160) in Ho Chi Minh City. The sensitivity and the specificity of RSV RDA test were 88.2% (95% CI 63.6–98.5%) and 100% (95% CI 93.3–100%), respectively. Conclusion: These are the first data reporting the substantial economic burden of RSV-associated illness in young children in Vietnam. This study informs policymakers in planning health care resources and highlights the urgency of RSV disease prevention. [ABSTRACT FROM AUTHOR]

Introduction: Incident syphilis leads to changes in plasma HIV-1 RNA and CD4 + T-cell level in people with HIV (PWH) with viraemia. Its effect in PWH on suppressive antiretroviral therapy (ART) is less clear. Methods: PWH on suppressive ART (plasma HIV-1 RNA < 50copies/mL) followed at the Queen Elizabeth Hospital, Hong Kong, China were regularly screened for syphilis. Their plasma HIV-1 RNA, CD4 + and CD8 + T-cell, and total lymphocyte levels before syphilis, during syphilis, and after successful treatment were compared. Results: Between 2005 and 2020, 288 syphilis episodes from 180 individuals were identified; 287 episodes were related to male, with a median age of 41 at diagnosis; 221 (77%) were syphilis re-infection. The rates of plasma HIV-1 suppression were statistically unchanged across the time-points (97% pre-syphilis, 98% during syphilis, and 99% post-treatment). Total lymphocyte, CD4+ and CD8+ T-cell levels decreased during incident syphilis (p<0.01), and rebounded post-treatment (p<0.01). VDRL titre was associated with declines in CD4+ T-cell (p=0.045), CD8+ T-cell (p=0.004), and total lymphocyte levels (p=0.021). Pre-syphilis CD4/CD8 ratio was associated with increases in CD8+ T-cell (p=0.001) and total lymphocyte levels (p=0.046) during syphilis. Syphilis re-infection was associated with an increase in total lymphocyte level (p=0.037). In the multivariable analysis, only pre-syphilis CD4/CD8 ratio was independently associated with increases in CD8+ T-cell (p=0.014) and total lymphocyte levels (p=0.039) during syphilis. Conclusions: Among virally-suppressed PWH, total lymphocyte, CD4+, and CD8+ T-cell levels declined during incident syphilis but rebounded post-treatment. The status of plasma HIV suppression was unaffected by syphilis. [ABSTRACT FROM AUTHOR]

Since its discovery in the 1990s, the DNA vaccine has been of great interest because of its ability to elicit both humoral and cellular immune responses while showing relative advantages regarding producibility, stability and storage. However, when applied to human subjects, inadequate immunogenicity remains as the greatest challenge for the practical use of DNA vaccines. In this study, we generated a DNA vaccine Δ42PD1-P24 encoding a fusion protein comprised of the HIV-1 Gag p24 antigen and the extracellular domain of murine Δ42PD1, a novel endogenous Toll-like receptor 4 (TLR4) agonist. Using a mouse model, we found that Δ42PD1-P24 DNA vaccine elicited a higher antibody response and an increased number of IFN-γ-producing CD4 and CD8 T cells. Moreover, mice with Δ42PD1-P24 DNA vaccination were protected from a subcutaneous challenge with murine mesothelioma cells expressing the HIV-1 p24 antigen. Importantly, the Δ42PD1-mediated enhancement of immune responses was not observed in TLR4 knockout mice. Collectively, these data demonstrate that the immunogenicity and efficacy of DNA vaccines could be improved by the fusion of the extracellular domain of Δ42PD1 to target the immunogen to dendritic cells. [ABSTRACT FROM AUTHOR]

Background: Edo State Surveillance Unit observed the emergence of a disease with "no clear-cut-diagnosis", which affected peri-urban Local Government Areas (LGAs) from September 6 to November 1, 2018. On notification, the Nigeria Centre for Disease Control deployed a Rapid Response Team (RRT) to support outbreak investigation and response activities in the State. This study describes the epidemiology of and response to a large yellow fever (YF) outbreak in Edo State.Methods: A cross-sectional descriptive outbreak investigation of YF outbreak in Edo State. A suspected case of YF was defined as "Any person residing in Edo State with acute onset of fever and jaundice appearing within 14 days of onset of the first symptoms from September 2018 to January 2019". Our response involved active case search in health facilities and communities, retrospective review of patients' records, rapid risk assessment, entomological survey, rapid YF vaccination coverage assessment, blood sample collection, case management and risk communication. Descriptive data analysis using percentages, proportions, frequencies were made.Results: A total of 209 suspected cases were line-listed. Sixty-seven (67) confirmed in 12 LGAs with 15 deaths [Case fatality rate (CFR 22.4%)]. Among confirmed cases, median age was 24.8, (range 64 (1-64) years; Fifty-one (76.1%) were males; and only 13 (19.4%) had a history of YF vaccination. Vaccination coverage survey involving 241 children revealed low YF vaccine uptake, with 44.6% providing routine immunisation cards for sighting. Risk of YF transmission was 71.4%. Presence of Aedes with high-larval indices (House Index ≥5% and/or Breteau Index ≥20) were established in all the seven locations visited. YF reactive mass vaccination campaign was implemented.Conclusion: Edo State is one of the states in Nigeria with the highest burden of yellow fever. More males were affected among the confirmed. Major symptoms include fever, jaundice, weakness, and bleeding. Majority of surveillance performance indicators were above target. There is a high risk of transmission of the disease in the state. Low yellow fever vaccination coverage, and presence of yellow fever vectors (Ae.aegypti, Ae.albopictus and Ae.simpsoni) are responsible for cases in affected communities. Enhanced surveillance, improved laboratory sample management, reactive vaccination campaign, improved yellow fever case management and increased risk communication/awareness are very important mitigation strategies to be sustained in Edo state to prevent further spread and mortality from yellow fever. [ABSTRACT FROM AUTHOR]

Background: With the emergence and spread of SARS-CoV-2 variants, genomic epidemiology and surveillance have proven invaluable tools for variant tracking. Here, we analyzed SARS-CoV-2 samples collected from personnel located at the US/NATO bases across Afghanistan. Results: Sequencing and phylogenetic analyses revealed at least 16 independent introductions of SARS-CoV-2 into four of these relatively isolated compounds during April and May 2021, including multiple introductions of Alpha and Delta variants. Four of the introductions resulted in sustained spread of the virus within, and in two cases between, the compounds. Three of these outbreaks, one Delta and two Alpha, occurred simultaneously. Conclusions: Even in rigorously controlled and segregated environments, SARS-CoV-2 introduction and spread may occur frequently. [ABSTRACT FROM AUTHOR]

Background: Zika virus (ZIKV) and dengue virus (DENV) cause microcephaly and dengue hemorrhagic fever, respectively, leading to severe problems. No effective antiviral agents are approved against infections of these flaviviruses, calling for the need to develop potent therapeutics. We previously identified gossypol as an effective inhibitor against ZIKV and DENV infections, but this compound is toxic and not suitable for in vivo treatment. Results: In this study, we showed that gossypol derivative ST087010 exhibited potent and broad-spectrum in vitro inhibitory activity against infections of at least ten ZIKV strains isolated from different hosts, time periods, and countries, as well as DENV-1-4 serotypes, and significantly reduced cytotoxicity compared to gossypol. It presented broad-spectrum in vivo protective efficacy, protecting ZIKV-infected Ifnar1−/− mice from lethal challenge, with increased survival and reduced weight loss. Ifnar1−/− mice treated with this gossypol derivative decreased viral titers in various tissues, including the brain and testis, after infection with ZIKV at different human isolates. Moreover, ST087010 potently blocked ZIKV vertical transmission in pregnant Ifnar1−/− mice, preventing ZIKV-caused fetal death, and it was safe for pregnant mice and their pups. It also protected DENV-2-challenged Ifnar1−/− mice against viral replication by reducing the viral titers in the brain, kidney, heart, and sera. Conclusions: Overall, our data indicate the potential for further development of this gossypol derivative as an effective and safe broad-spectrum therapeutic agent to treat ZIKV and DENV diseases. [ABSTRACT FROM AUTHOR]

Background: Lower respiratory tract infection (LRTI) is an important cause of morbidity and mortality in infants and young children. However, the etiological role of viruses and the timing of developing LRTI are not well defined.Methods: We analyzed the data of a prospective cohort study in the Philippines as a birth cohort. We detected LRTI among children who visited healthcare facilities with respiratory symptom, and collected nasopharyngeal swabs for virus detection. We analyzed the incidence rates (IRs) and cumulative proportion of LRTI and severe LRTI by age group and each virus detected.Results: A total of 350 LRTI episodes were observed from 473 child-years yielded from 419 children. The IRs of LRTI were 70.8, 70.7, and 80.8 per 100 child-years for 0-5, 6-11, and 12-23 months of age, respectively. By 12 months of age, 45% of children developed LRTI at least once. Rhinovirus and respiratory syncytial virus were the most frequently detected viruses in all age groups. However, the IRs of influenza virus were low especially at 0-5 months of age.Conclusions: We identified various patterns of age-specific IRs of LRTI and severe LRTI for different viruses, which should be considered to establish more effective interventions including vaccinations. [ABSTRACT FROM AUTHOR]

Background: Percutaneous transluminal coronary angioplasty (PTCA) balloon catheters must withstand high pressures required for the lesion treatment, pushing loads during insertion, and pulling loads during withdrawal. These loads pose a challenge especially for polymeric tubular shafts with small cross sections. In order to enable new design innovations and to better understand the mechanics of current catheter technologies, the tensile properties of polyamide (PA) 12 were investigated. PA 12 dog bone specimens and medical PA 12 tubes were either stored at ambient temperature and humidity or conditioned in water, and subjected to tensile loads at different temperatures. In addition, the effect on the tensile properties of the necking process, a forming process to reduce the wall thickness of the tubes, was determined.Results: The tested tubes showed a reduction in both Young's Modulus (- 41.5%) and yield stress (- 29.2%) compared to standardized specimens. Furthermore, an increase in temperature and water absorption softens the material and reduces the mechanical properties like the Young's Modulus and the yield stress. It was found that the material strengthens during the necking process. Likely due to the orientation of the polymers chain molecules in load direction (Rösler et al., 2007), the Young's Modulus of the material could be increased by 43.5%. Furthermore, the absence of a yield point after necking allows for a greater loading capacity of the material without unstable neck growth. Besides the strengthening, the ultimate strain is reduced by 50%. This indicates that the necking process induces plastic deformation.Conclusion: The investigation showed that the environmental conditions like temperature and humidity can influence mechanical properties. It could also be shown that pre-forming processes such as necking can enhance the mechanical properties, such as the Young's Modulus, while reducing the wall thickness. These findings suggest possible further development of catheters with a small cross section and higher mechanical strength and highlight the importance to account for the targeted operating temperature during the design process. [ABSTRACT FROM AUTHOR]

Over recent years, the research community has been increasingly using preprint servers to share manuscripts that are not yet peer-reviewed. Even if it enables quick dissemination of research findings, this practice raises several challenges in publication ethics and integrity. In particular, preprints have become an important source of information for stakeholders interested in COVID19 research developments, including traditional media, social media, and policy makers. Despite caveats about their nature, many users can still confuse pre-prints with peer-reviewed manuscripts. If unconfirmed but already widely shared first-draft results later prove wrong or misinterpreted, it can be very difficult to "unlearn" what we thought was true. Complexity further increases if unconfirmed findings have been used to inform guidelines. To help achieve a balance between early access to research findings and its negative consequences, we formulated five recommendations: (a) consensus should be sought on a term clearer than 'pre-print', such as 'Unrefereed manuscript', "Manuscript awaiting peer review" or ''Non-reviewed manuscript"; (b) Caveats about unrefereed manuscripts should be prominent on their first page, and each page should include a red watermark stating 'Caution-Not Peer Reviewed'; (c) pre-print authors should certify that their manuscript will be submitted to a peer-review journal, and should regularly update the manuscript status; (d) high level consultations should be convened, to formulate clear principles and policies for the publication and dissemination of non-peer reviewed research results; (e) in the longer term, an international initiative to certify servers that comply with good practices could be envisaged. [ABSTRACT FROM AUTHOR]

Background: Zika virus (ZIKV) has been declared a public health emergency that requires development of an effective vaccine, as it might represent an international threat. Methods: Here, two novel DNA-based (pVAXzenv) and fowlpox-based (FPzenv) recombinant putative vaccine candidates were constructed that contained the cPrME genes of ZIKV. The env gene inserted into the fowlpox vector was verified for correct transgene expression by Western blotting and by immunofluorescence in different cell lines. The production of virus-like particles as a result of env gene expression was also demonstrated by electron microscopy. BALB/c mice were immunosuppressed with dexamethasone and immunized following a prime–boost strategy in a heterologous protocol where pVAXzenv was followed by FPzenv, to evaluate the immunogenicity of the Env protein. The mice underwent a challenge with an epidemic ZIKV after the last boost. Results: These data show that the ZIKV Env protein was correctly expressed in both normal human lung fibroblasts (MRC-5 cells) and green monkey kidney (Vero) cells infected with FPzenv, and that the transgene expression lasted for more than 2 weeks. After mucosal administration of FPzenv, the immunized mice showed specific and significantly higher humoral responses compared to the control mice. However, virus neutralizing antibodies were not detected using plaque reduction assays. Conclusions: Although BALB/c mice appear to be an adequate model for ZIKV infection, as it mimics the natural mild infection in human beings, inadequate immune suppression seemed to occur by dexamethasone and different immune suppression strategies should be applied before challenge to reveal any protection of the mice. [ABSTRACT FROM AUTHOR]

Background: Cataract surgeries can improve mental health outcomes. However, previous studies have not investigated whether the time interval between cataract surgeries for 2 eyes affects mental health outcomes.Methods: We used the whole-population National Health Insurance (NHI) claims data from Taiwan to conduct a cohort study. Patients who received cataract surgeries for both eyes were identified (n = 585,422). The mental health inpatient and outpatient consultations received by these patients were analyzed, with different time intervals (< 3, 3 to 6, 6 to 12, and > 12 months) between the surgeries. Negative binominal regression was performed to estimate the interaction of the first eye surgery with the time interval.Results: The number of mental health consultations was lowest among patients with a time interval of < 3 months (1.783-1.743, P < .001), and a negative dose response effect was observed, such that a longer time interval corresponded to a lower reduction in the number of mental health consultations. For patients with a time interval of > 12 months, the predicted number of mental health consultations increased from 1.674 to 1.796 (P < .001).Conclusions: Given a patient expected to receive surgeries for both eyes within 1 year, scheduling both surgeries within a short time interval may be beneficial for maximizing the effects of cataract surgery in reducing the number of mental health consultations. [ABSTRACT FROM AUTHOR]

Background: When a new or re-emergent pathogen, such as SARS-CoV-2, causes a major outbreak, rapid access to pertinent research findings is crucial for planning strategies and decision making. We researched whether the speed of sharing research results in the COVID-19 epidemic was higher than the SARS and Ebola epidemics. We also researched whether there is any difference in the most frequent topics investigated before and after the COVID-19, SARS, and Ebola epidemics started.Methods: We used PubMed database search tools to determine the time-period it took for the number of articles to rise after the epidemics started and the most frequent topics assigned to the articles.Results: The main results were, first, the rise in the number of articles occurred 6 weeks after the COVID-19 epidemic started whereas, this rise occurred 4 months after the SARS and 7 months after the Ebola epidemics started. Second, etiology, statistics & numerical data, and epidemiology were the three most frequent topics investigated in the COVID-19 epidemic. However, etiology, microbiology, and genetics in the SARS epidemic, and statistics & numerical data, epidemiology, and prevention & control in the Ebola epidemic were more frequently studied compared with other topics. Third, some topics were studied more frequently after the epidemics started.Conclusions: The speed of sharing results in the COVID-19 epidemic was much higher than the SARS and Ebola epidemics, and that there is a difference in the most frequent articles' topics investigated in these three epidemics. Due to the value of time in controlling epidemics spread, the study highlights the necessity of defining more solutions for rapidly providing pertinent research findings in fighting against the next public health emergency. [ABSTRACT FROM AUTHOR]

Background: In 1918 an unknown infectious agent spread around the world infecting over one-third of the general population and killing almost 50 million people. Many countries were at war, the First World War. Since Spain was a neutral country and Spanish press could report about the infection without censorship, this condition is commonly remembered as "Spanish influenza". This review examines several aspects during the 1918 influenza pandemic to bring out evidences which might be useful to imagine the possible magnitude of the present coronavirus disease 2019 (COVID-19).Methods: In the first part of this review we will examine the origin of the SARS-Coronavirus-2 and 1918 Spanish Influenza Virus and the role played by host and environment in its diffusion. We will also include in our analysis an evaluation of different approaches utilized to restrain the spread of pandemic and to treat infected patients. In the second part, we will try to imagine the magnitude of the present COVID-19 pandemic and the possible measures able to restrain in the present environment its spread.Results: Several factors characterize the outcome in a viral pandemic infection. They include the complete knowledge of the virus, the complete knowledge of the host and of the environment where the host lives and the pandemic develops.Conclusion: By comparing the situation seen in 1918 with the current one, we are now in a more favourable position. The experience of the past teaches us that their success is linked to a rapid, constant and lasting application. Then, rather than coercion, awareness of the need to observe such prevention measures works better. [ABSTRACT FROM AUTHOR]

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new type of coronavirus that causes the Coronavirus Disease 2019 (COVID-19), which has been the most challenging pandemic in this century. Considering its high mortality and rapid spread, an effective vaccine is urgently needed to control this pandemic. As a result, the academia, industry, and government sectors are working tightly together to develop and test a variety of vaccines at an unprecedented pace. In this review, we outline the essential coronavirus biological characteristics that are important for vaccine design. In addition, we summarize key takeaways from previous vaccination studies of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), highlighting the pros and cons of each immunization strategy. Finally, based on these prior vaccination experiences, we discuss recent progress and potential challenges of COVID-19 vaccine development. [ABSTRACT FROM AUTHOR]

Background: The outbreak of coronavirus disease 2019 (COVID-19) has caused a public catastrophe and global concern. The main symptoms of COVID-19 are fever, cough, myalgia, fatigue and lower respiratory tract infection signs. Almost all populations are susceptible to the virus, and the basic reproduction number (R0) is 2.8–3.9. The fight against COVID-19 should have two aspects: one is the treatment of infected patients, and the other is the mobilization of the society to avoid the spread of the virus. The treatment of patients includes supportive treatment, antiviral treatment, and oxygen therapy. For patients with severe acute respiratory distress syndrome (ARDS), extracorporeal membrane oxygenation (ECMO) and circulatory support are recommended. Plasma therapy and traditional Chinese medicine have also achieved good outcomes. This review is intended to summarize the research on this new coronavirus, to analyze the similarities and differences between COVID-19 and previous outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and to provide guidance regarding new methods of prevention, diagnosis and clinical treatment based on autodock simulations. Methods: This review compares the multifaceted characteristics of the three coronaviruses including COVID-19, SARS and MERS. Our researchers take the COVID-19, SARS, and MERS as key words and search literatures in the Pubmed database. We compare them horizontally and vertically which respectively means concluding the individual characteristics of each coronavirus and comparing the similarities and differences between the three coronaviruses. Results: We searched for studies on each outbreak and their solutions and found that the main biological differences among SARS-CoV-2, SARS-CoV and MERS-CoV are in ORF1a and the sequence of gene spike coding protein-S. We also found that the types and severity of clinical symptoms vary, which means that the diagnosis and nursing measures also require differentiation. In addition to the common route of transmission including airborne transmission, these three viruses have their own unique routes of transmission such as fecal-oral route of transmission COVID-19. Conclusions: In evolutionary history, these three coronaviruses have some similar biological features as well as some different mutational characteristics. Their receptors and routes of transmission are not all the same, which makes them different in clinical features and treatments. We discovered through the autodock simulations that Met124 plays a key role in the efficiency of drugs targeting ACE2, such as remdesivir, chloroquine, ciclesonide and niclosamide, and may be a potential target in COVID-19. [ABSTRACT FROM AUTHOR]

On March 11, 2020, the World Health Organization declared the worldwide spread of the infectious disease COVID-19, caused by a new strain of coronavirus, SARS-CoV-2, as a pandemic. Like in all other infectious diseases, the host immune system plays a key role in our defense against SARS-CoV-2 infection. However, viruses are able to evade the immune attack and proliferate and, in susceptible individuals, cause severe inflammatory response known as cytokine storm, particularly in the lungs. The advancement in our understanding of the mechanisms underlying the host immune responses promises to facilitate the development of approaches for prevention or treatment of diseases. Components of immune system, such as antibodies, can also be used to develop sensitive and specific diagnostic methods as well as novel therapeutic agents. In this review, we summarize our knowledge about how the host mounts immune responses to infection by SARS-CoV-2. We also describe the diagnostic methods being used for COVID-19 identification and summarize the current status of various therapeutic strategies, including vaccination, being considered for treatment of the disease. [ABSTRACT FROM AUTHOR]

Background: The emergence of Zika virus (ZV) in tropical and subtropical areas of the world has created an urgent need for vaccines against ZV. However, approved vaccines that prevent ZV infection are not available. To develop an effective vaccine against ZV infection, a lipidated form of ZV envelope protein domain III that possesses an intrinsic adjuvant property was rationally designed. Our goal was to examine the immunogenicity of recombinant lipidated ZV envelope protein domain III (rLZE3) and evaluate its potential as a vaccine candidate against ZV. Methods: Recombinant ZV envelope protein domain III (rZE3) and rLZE3 were prepared with an Escherichia coli-based system. Dendritic cell surface marker expression and cytokine production upon stimulation were analyzed to evaluate the function of rLZE3. Neutralizing antibody capacities were evaluated using focus reduction neutralization tests after immunization. To investigate the protective immunity in immunized mice, serum samples collected from immunized mice were adoptively transferred into AG129 mice, and then viremia levels and survival times were examined after ZV challenge. Results: rLZE3 alone but not rZE3 alone efficiently activated dendritic cells in vitro and was taken up by dendritic cells in vivo. Immunization of C57BL/6 mice with rLZE3 alone (without exogenous adjuvant) could induce ZV-specific neutralizing antibody responses. Furthermore, serum samples obtained from rLZE3-immunized mice provided protection as indicated by a reduction in viremia levels and prolongation of survival times after ZV challenge. Conclusion: These results indicate that rLZE3 is an excellent vaccine candidate and has great potential that should be evaluated in further preclinical studies. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) frequently causes acute lower respiratory infection in children under 5, representing a high burden in Gavi-eligible countries (mostly low-income and lower-middle-income). Since multiple RSV interventions, including vaccines and monoclonal antibody (mAb) candidates, are under development, we aim to evaluate the key drivers of the cost-effectiveness of maternal vaccination and infant mAb for 72 Gavi countries.Methods: A static Multi-Country Model Application for RSV Cost-Effectiveness poLicy (MCMARCEL) was developed to follow RSV-related events monthly from birth until 5 years of age. MCMARCEL was parameterised using country- and age-specific demographic, epidemiological, and cost data. The interventions' level and duration of effectiveness were guided by the World Health Organization's preferred product characteristics and other literature. Maternal vaccination and mAb were assumed to require single-dose administration at prices assumed to align with other Gavi-subsidised technologies. The effectiveness and the prices of the interventions were simultaneously varied in extensive scenario analyses. Disability-adjusted life years (DALYs) were the primary health outcomes for cost-effectiveness, integrated with probabilistic sensitivity analyses and Expected Value of Partially Perfect Information analysis.Results: The RSV-associated disease burden among children in these 72 countries is estimated at an average of 20.8 million cases, 1.8 million hospital admissions, 40 thousand deaths, 1.2 million discounted DALYs, and US$611 million discounted direct costs. Strategy 'mAb' is more effective due to its assumed longer duration of protection versus maternal vaccination, but it was also assumed to be more expensive. Given all parameterised uncertainty, the optimal strategy of choice tends to change for increasing willingness to pay (WTP) values per DALY averted from the current situation to maternal vaccination (at WTP > US$1000) to mAB (at WTP > US$3500). The age-specific proportions of cases that are hospitalised and/or die cause most of the uncertainty in the choice of optimal strategy. Results are broadly similar across countries.Conclusions: Both the maternal and mAb strategies need to be competitively priced to be judged as relatively cost-effective. Information on the level and duration of protection is crucial, but also more and better disease burden evidence-especially on RSV-attributable hospitalisation and death rates-is needed to support policy choices when novel RSV products become available. [ABSTRACT FROM AUTHOR]

Background: Age-related macular degeneration (AMD) represents the leading cause of visual impairment in the aging population. The goal of this study was to identify aberrantly-methylated, differentially-expressed genes (MDEGs) in AMD and explore the involved pathways via integrated bioinformatics analysis.Methods: Data from expression profile GSE29801 and methylation profile GSE102952 were obtained from the Gene Expression Omnibus database. We analyzed differentially-methylated genes and differentially-expressed genes using R software. Functional enrichment and protein-protein interaction (PPI) network analysis were performed using the R package and Search Tool for the Retrieval of Interacting Genes online database. Hub genes were identified using Cytoscape.Results: In total, 827 and 592 genes showed high and low expression, respectively, in GSE29801; 4117 hyper-methylated genes and 511 hypo-methylated genes were detected in GSE102952. Based on overlap, we categorized 153 genes as hyper-methylated, low-expression genes (Hyper-LGs) and 24 genes as hypo-methylated, high-expression genes (Hypo-HGs). Four Hyper-LGs (CKB, PPP3CA, TGFB2, SOCS2) overlapped with AMD risk genes in the Public Health Genomics and Precision Health Knowledge Base. KEGG pathway enrichment analysis indicated that Hypo-HGs were enriched in the calcium signaling pathway, whereas Hyper-LGs were enriched in sphingolipid metabolism. In GO analysis, Hypo-HGs were enriched in fibroblast migration, membrane raft, and coenzyme binding, among others. Hyper-LGs were enriched in mRNA transport, nuclear speck, and DNA binding, among others. In PPI network analysis, 23 nodes and two edges were established from Hypo-HGs, and 151 nodes and 73 edges were established from Hyper-LGs. Hub genes (DHX9, MAPT, PAX6) showed the greatest overlap.Conclusion: This study revealed potentially aberrantly MDEGs and pathways in AMD, which might improve the understanding of this disease. [ABSTRACT FROM AUTHOR]

Background: Host proteases have been shown to play important roles in many viral activities such as entry, uncoating, viral protein production and disease induction. Therefore, these cellular proteases are putative targets for the development of antivirals that inhibit their activity. Host proteases have been described to play essential roles in Ebola, HCV, HIV and influenza, such that specific protease inhibitors are able to reduce infection. RSV utilizes a host protease in its replication cycle but its potential as antiviral target is unknown. Therefore, we evaluated the effect of protease inhibitors on RSV infection. Methods: To measure the sensitivity of RSV infection to protease inhibitors, cells were infected with RSV and incubated for 18 h in the presence or absence of the inhibitors. Cells were fixed, stained and studied using fluorescence microscopy. Results: Several protease inhibitors, representing different classes of proteases (AEBSF, Pepstatin A, E-64, TPCK, PMSF and aprotinin), were tested for inhibitory effects on an RSV A2 infection of HEp-2 cells. Different treatment durations, ranging from 1 h prior to inoculation and continuing for 18 h during the assay, were evaluated. Of all the inhibitors tested, AEBSF and TPCK significantly decreased RSV infection. To ascertain that the observed effect of AEBSF was not a specific feature related to HEp-2 cells, A549 and BEAS-2B cells were also used. Similar to HEp-2, an almost complete block in the number of RSV infected cells after 18 h of incubation was observed and the effect was dose-dependent. To gain insight into the mechanism of this inhibition, AEBSF treatment was applied during different phases of an infection cycle (pre-, peri- and post-inoculation treatment). The results from these experiments indicate that AEBSF is mainly active during the early entry phase of RSV. The inhibitory effect was also observed with other RSV isolates A1998/3–2 and A2000/3–4, suggesting that this is a general feature of RSV. Conclusion: RSV infection can be inhibited by broad serine protease inhibitors, AEBSF and TPCK. We confirmed that AEBSF inhibition is independent of the cell line used or RSV strain. The time point at which treatment with the inhibitor was most potent, was found to coincide with the expected moment of entry of the virion with the host cell. [ABSTRACT FROM AUTHOR]

Background: Systematic adaptation of evidence-informed interventions that increase retention in care and improve adherence to antiretroviral therapy (ART) are essential to ending the HIV epidemic in rural sub-Saharan Africa. We selected and adapted an adherence support worker intervention employed in Malawi for use by traditional healers in rural Mozambique. Given the levels of trust and dependence previously expressed by persons living with HIV (PLHIV) for traditional medicine, we adapted the program to engage traditional healers within the allopathic health system.Methods: Adaption followed a theoretically driven approach to intervention adaption: the Assessment-Decision-Administration-Production-Topical Experts-Integration-Training-Testing (ADAPT-ITT) model. Three rounds of performance feedback, based on theater presentations of the adapted intervention for stakeholders and idea generation, were completed with 12 groups from March to July 2016 to develop the final model. We offered healer support to 180 newly diagnosed HIV-infected patients.Results: Traditional healers were an acceptable group of community health workers to assist with patient adherence and retention. Traditional healers, clinicians, and interested community members suggested novel strategies to tailor the adherence support worker intervention, revealing a local culture of HIV denialism, aversion to the health system, and dislike of healthcare providers, as well as a preference for traditional treatments. Proposed changes to the intervention included modifications to the training language and topics, expanded community-based activities to support acceptability of an HIV diagnosis and to facilitate partner disclosure, and accompaniment to the health facility by healers to encourage delivery of respectful clinical care. PLHIV, healers, and clinicians deemed the intervention socially acceptable during focus groups. We subsequently recruited 180 newly diagnosed HIV-infected patients into the program: 170 (94%) accepted.Conclusions: Systematic translation of interventions, even between regions with similar social and economic environments, is an important first step to successful program implementation. Efforts previously limited to community health workers can be tailored for use by traditional healers-an underutilized and often maligned health workforce. It proved feasible to use theater-based performances to demonstrate delivery of the intervention in low-literacy populations, generating discussions about social norms, community concerns, and the merits of an acceptable strategy to improve retention and adherence to ART. [ABSTRACT FROM AUTHOR]

Background: Enteric parasitic infection among human immunodeficiency virus (HIV) patients has been a significant health problem in developing countries like Nepal. This study was undertaken to access the burden of enteric parasites among HIV patients and its association with their immune status. Methods: A cross-sectional study, involving 112 HIV sero-positive patients was conducted in Tribhuvan University Teaching Hospital, Public Health Research Laboratory, Kathmandu, Nepal from July 2011 to June 2012. The fecal samples were processed by direct-smear technique, in both normal saline solution and 1 % iodine solution as well as modified acid fast staining (Kinyoun's method) after formalin ether concentration and Sheather's sucrose flotation for the identification of enteric parasites. Results: Infection with one or more parasite was seen in 33.9 % (n = 38) of the cases enrolled in the study, with the parasite prevalence rate of 41.1 % (n = 46). Literacy (OR = 1.9, 95 % CI 0.9-4.3) and CD4 T-cell count <200 (OR = 2.5, 95 % CI 1.1-5.7) were found to be associated with enteric parasite infection. Similarly, CD4 T-cell count <200 was found to be associated with opportunistic parasitic infection (OR = 3.2, 95 % CI 1.2-7.8). Among opportunistic parasites, Giardia duodenalis was the most common (28.3 %, n = 13) one. Multi-parasitism was observed in six patients (15.8 %). Conclusion: Enteric parasitic infections are common in HIV-infected people. The poor immune status as indicated by low CD4 T-cell count may account for higher risk of both opportunistic and non-opportunistic enteric parasitic infection. [ABSTRACT FROM AUTHOR]

Background: Provider-initiated HIV testing and counselling (PITC) is promoted as a means to increase HIV case finding. We assessed the effectiveness of PITC to increase HIV testing rate and HIV case finding among outpatients in Rwandan health facilities (HF).Methods: PITC was introduced in six HFs in 2009-2010. HIV testing rate and case finding were compared between phase 1 (pre-PITC) and phase 3 (PITC period) for outpatient-department (OPD) attendees only, and for OPD and voluntary counseling & testing (VCT) departments combined.Results: Out of 26,367 adult OPD attendees in phase 1, 4.7% were tested and out of 29,864 attendees in phase 3, 17.0% were tested (p < 0.001). The proportion of HIV cases diagnosed was 0.25% (67/26,367) in phase 1 and 0.46% (136/29864) in phase 3 (p < 0.001). In multivariable analysis, both testing rate and case finding were significantly higher in phase 3 for OPD attendees. In phase 1 most of the HIV testing was done in VCT departments rather than at the OPD (78.6% vs 21.4% respectively); in phase 3 this was reversed (40.0% vs 60.0%; p < 0.001). In a combined analysis of VCT and OPD attendees, testing rate increased from 18.7% in phase 1 to 25.4% in phase 3, but case finding did not increase. In multivariable analysis, testing rate was significantly higher in phase 3 (OR 1.67; 95% CI 1.60-1.73), but case finding remained stable (OR 1.09; 95% CI 0.93-1.27).Conclusion: PITC led to a shift of HIV testing from VCT department to the OPD, a higher testing rate, but no additional HIV case finding. [ABSTRACT FROM AUTHOR]

Background: Helminths/HIV co-infections are very common in developing countries, especially in Africa. The effect of overlapping distribution of HIV and helminths becomes important because concomitant infection may exacerbate disease outcome of HIV infection. The study aimed at determining the effect of deworming on the immune status of helminth/HIV coinfected Pre-ART HIV patients attending three health institutions in Southern Ethiopia. Methods: 97 HIV-positive Pre-ART individuals were observed into 2 groups on the basis of helminth co-infection and no infection. Out of these, 66 study participants were helminths/HIV co-infected and the remaining 31 study participants were helminths (-)/HIV (+) control. Helminth/HIV co-infected participants CD4+ T-cell count was done at baseline, after 15 weeks and 6 months after antihelminthics treatment. Data were analyzed using SPSS version 16. Results: Ascaris lumbricoides was the highest prevalent soil transmitted helminths in Pre-ART individuals in this study. CD4+ T-cell count in the Ascaris lumricoides/HIV co-infected was significantly higher (P = 0.05) and (P < 0.05) after 15 weeks and 6 months post-antihelminthics treatment respectively. Also, after antihelminthic therapy, the CD4+ T-cell count significantly increased (P < 0.005) in all treated helminth infections. Conclusions: The study showed that treatment of ascariasis had a significant effect on CD4+ T-cell count increase in the treated Pre-ART Ascaris lumbricoides/HIV co-infected individuals; whereas the same positive effect was not evident for other intestinal helminth parasites detected in the study. In conclusion, this finding on Ascaris lumbricoides-specific nature of immune interaction in helminth/HIV co-infection may partly explain the inconsistent reports on the role of intestinal helminths on progression of HIV infection to AIDS. Therefore, a well-designed longitudinal study on helminth species-specific HIV/helminth co-infection will be needed to fully establish the possible benefits of deworming in intestinal helminth/HIV co-infection. [ABSTRACT FROM AUTHOR]

Background Helminth infections as well as structural alternations in the long-terminal repeat (LTR) regions of HIV-1 are known to contribute to elevated HIV RNA level and enhance HIV-1 diseases progression. However, the impact of helminths infections on the occurrences of triple NF-κB and genetic variability in LTR region of HIV-1C isolates is not known. We aimed to examine the presence of genetic variability in the LTR region of HIV-1C isolates during chronic HIV-helminth co-infection. Methods HIV-1C infected Ethiopians with (n = 22) and without (n = 20) helminth infection were included. The LTR region of HIV was amplified and sequenced. Sequences were aligned with reference set from the Los Alamos HIV database. Phylogenetic analysis and frequency of polymorphic changes was performed by the neighbour-joining method using Geneious Basic software. Results All LTR sequences from patients with or without of helminth co-infection clustered with HIV-1 subtype C with two distinct subclusters (C and C'). The enhancer element was found to have three copies of 10-base pair binding sites for NF-?Bs which is an evidence for predominance of triple NF-κB sites (94%) in HIV-1C isolates irrespective of helminths coinfection and subclusters. Moreover, irrespective of helminth co-infection and C and C' subclusters high sequences similarity in LTR was observed. There was no significant difference in plasma HIV RNA level between HIV-1 C and C' subclusters. Conclusions Despite the small sample size, the predominance of triple NF-?B binding sites and high sequence similarities in LTR region irrespective of helminths infection suggest the natural occurrence of the three NF-κB binding sites in HIV-1C isolates without the influence of secondary infection. Thus, the higher HIV-1C viraemia in helminth co-infected individuals is more likely a result of immune activation rather than LTR sequence variation. Moreover, the lack of significant difference in plasma HIV RNA level between HIV-1 C and C' subcluster may show the lack of functional differences among the two groups. [ABSTRACT FROM AUTHOR]

Background Efficacy of statins has been extensively studied, with much less information reported on their unintended effects. Evidence from randomized controlled trials (RCTs) on unintended effects is often insufficient to support hypotheses generated from observational studies. We aimed to systematically assess unintended effects of statins from observational studies in general populations with comparison of the findings where possible with those derived from randomized trials. Methods Medline (1998 to January 2012, week 3) and Embase (1998 to 2012, week 6) were searched using the standard BMJ Cohort studies filter. The search was supplemented with reference lists of all identified studies and contact with experts in the field. We included prospective studies with a sample size larger than 1,000 participants, case control (of any size) and routine health service linkage studies of over at least one year duration. Studies in subgroups of patients or follow-up of patient case series were excluded, as well as hospital-based cohort studies. Results Ninety studies were identified, reporting on 48 different unintended effects. Statins were associated with lower risks of dementia and cognitive impairment, venous thrombo- embolism, fractures and pneumonia, but these findings were attenuated in analyses restricted to higher quality studies (respectively: OR 0.74 (95% CI 0.62 to 0.87); OR 0.92 (95% CI 0.81 to 1.03); OR 0.97 (95% CI 0.88 to 1.05); OR 0.92 (95% CI 0.83 to 1.02)); and marked heterogeneity of effects across studies remained. Statin use was not related to any increased risk of depression, common eye diseases, renal disorders or arthritis. There was evidence of an increased risk of myopathy, raised liver enzymes and diabetes (respectively: OR 2.63 (95% CI 1.50 to 4.61); OR 1.54 (95% CI 1.47 to 1.62); OR 1.31 (95% CI 0.99 to 1.73)). Conclusions Our systematic review and meta-analyses indicate that high quality observational data can provide relevant evidence on unintended effects of statins to add to the evidence from RCTs. The absolute excess risk of the observed harmful unintended effects of statins is very small compared to the beneficial effects of statins on major cardiovascular events. [ABSTRACT FROM AUTHOR]

Background: It has been suggested that the proliferative capacity of cells from individuals with HIV or both HIV and helminth infections is attenuated and cytokine production is dysregulated. This study describes peripheral blood mononuclear cell proliferation capacity and cytokine profile from individuals with HIV or both HIV and helminth infections in South Africa. Methods: Forty HIV-infected and 22 HIV-uninfected participants were randomly selected and stratified into different helminth infection phenotypes by egg excretion and Ascaris lumbricoides specific –immunoglobulin-E (IgE) levels. Five day cell cultures of participants, unstimulated or stimulated with Phytohaemaglutinnin, Streptokinase, HIV-1 p24 and Ascaris lumbricoides worm antigens were stained with monoclonal antibody-fluorochrome conjugates (Ki67-FITC and CTLA-APC-4). Percentage expression of Ki67 and CTLA-4 was measured to determine cell proliferation and regulation, respectively. Culture supernatants were analysed for the expression of 13 cytokines using the Bioplex (BioRad) system. Kruskal Wallis was used to test for differences in variables between helminth infected subgroups who were either having eggs in stool and high IgE (egg+IgEhi); or eggs in stool and low IgE (egg+IgElo); or no eggs in stool and high IgE (egg-IgEhi) and those without helminth infection (egg-IgElo). Results: Individuals excreting eggs in stool with high serum IgE (egg+IgEhi phenotype) had potent mitogen responses but consistently produced low, but statistically non-significant antigen–specific (HIV-1 p24 (p = 0.41) and Ascaris (p = 0.19) and recall antigen (Streptokinase; p = 0.31) Ki67 responses. The group also had reduced type 1 cytokines. Individuals excreting eggs in stool with low serum IgE( egg+IgElo phenotype) had a more favourable antiviral profile, characterized by higher IFNγ, IL-2, lower IL-4 and higher IL-10 production. Conclusion: The findings suggest that dual HIV/helminth infection with egg excretion and/or high Ascaris IgE phenotye may be linked with poor proliferative capacity and deleterious cytokine profile with regards to HIV control. [ABSTRACT FROM AUTHOR]

Background Malaria is associated with an increase in HIV viral load and a fall in CD4-cell count. Conversely, HIV infection disrupts the acquired immune responses to malaria and the efficacy of antimalarial drugs. This study was carried out in five Ghanaian hospitals to estimate the prevalence of clinically confirmed malaria among HIV patients by evaluating their hospital records. Methods This retrospective descriptive cross sectional study reviewed and collected data on malaria, using Case Record Forms from HIV patients' folders in five hospitals in Ghana. Results There were 933 patients records made up of 272 (29.2%) males and 661 (70.8%) females. Majority of the patients were aged between 21-40 (63.6%) years and the rest were between the ages 1-20 (2.8%) years, 41-60 (31.6%) years and 61-80 (2.1%) years of age. A total of 38.1% (355/933) of the patients were clinically suspected of having clinical malaria. Of these 339 (95.5%) were referred to the laboratory for confirmation of the diagnosis of malaria. Only 4.4% (15/339) of patients tested were confirmed as cases of malaria among the patients that were clinically suspected of having malaria and subsequently confirmed. Fever, was not significantly associated with a confirmed diagnosis of malaria [OR = 3.11, 95% CI: (0.63, 15.37), P = 0.142]. Conclusions There was a 4.4% prevalence of confirmed malaria and 38.1% of presumptively diagnosed malaria from the case records of HIV patients from the selected hospitals in Ghana. [ABSTRACT FROM AUTHOR]

Background: Although the Centres for disease Control and Prevention (CDC) recommends empiric treatment for schistosomiasis and strongyloidiasis (prevalent but treatable parasitic infections) in some refugee groups it is unclear if these guidelines should be extended to non-refugee immigrants from endemic areas. We aimed to assess seroprevalence of, and risk factors for, positive schistosomiasis and strongyloides serology in HIV-infected patients from endemic areas attending a European Infectious Diseases clinic. Methods: In a prospective cohort study, HIV-infected patients from helminth endemic areas underwent clinical assessment and blood draw for schistosomiasis and strongyloides serology, routine haematology and inflammatory markers (ESR and CRP). Between-group differences were analyzed by Wilcoxin Signed Rank and Fisher's t tests as appropriate. Results: Ninety HIV-infected patients (mean [standard deviation (SD)] age 34 [6] years, 29% male) were recruited from May 2008 to June 2009. Nine (10%) subjects tested positive for helminth infections. Seven tested positive for schistosomiasis (8%) while two tested positive for strongyloides (2%). Seropositive subjects were more likely to have higher eosinophil counts (mean [SD]) (0.3 [0.3] vs. 0.15 [0.2] x103cells/cm, P = 0.021) with a trend towards lower CD4+ T-cell counts (mean [SD]) (280 [218] vs. 395 [217] cells/mm3, P = 0.08). Conclusion: The high prevalence of helminth infections (10%) in asymptomatic HIV infected adults identified in this study supports routine screening of immigrants from helminth endemic areas or with exposure history. [ABSTRACT FROM AUTHOR]

The article presents a research in which the researchers developed a mathematical model to test the hypothesis that viral factors contribute to the variation of the effect of co-infection and introduce variation among individuals. As reported, the model developed by the researchers describe the dynamics of HIV and malaria infections, and the researchers used the model to examine the effect of variations in the viral replicative capacity on the viral load (VL) burden generated by coinfection.

The article focuses on the research article presented by Diego F Cuadros and colleagues on the impact of variable heterosexual penile-vaginal transmission rate on the dynamics of HIV in sub-Saharan Africa. It mentions that mathematical sexual network model has been created to analyze the co-infection effects caused by other infectious diseases including, herpes simplex virus type-2, gonorrhea and malaria.