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Background COVID-19, caused by SARS-CoV-2 has become the most threatening issue to all populations around the world. It is, directly and indirectly, affecting all of us and thus, is an emerging topic dealt in global health. To avoid the infection, various studies have been done and are still ongoing. COVID-19 cases are reported all over the globe, and among the millions of cases, genetic similarity may be seen. The genetical common features seen within confirmed cases may help outline the tendency of infection and degree severity of the disease. Here, we reviewed multiple papers on SNPs related to SARS-CoV-2 infection and analyzed their results. Methods The PubMed databases were searched for papers discussing SNPs associated with SARS-CoV-2 infection and severity. Clinical studies with human patients and statistically showing the relevance of the SNP with virus infection were included. Quality Assessment of all papers was done with Newcastle Ottawa Scale. Results In the analysis, 21 full-text literature out of 2956 screened titles and abstracts, including 63,496 cases, were included. All were human-based clinical studies, some based on certain regions gathered patient data and some based on big databases obtained online. ACE2, TMPRSS2, and IFITM3 are the genes mentioned most frequently that are related to SARS-CoV-2 infection. 20 out of 21 studies mentioned one or more of those genes. The relevant genes according to SNPs were also analyzed. rs12252-C, rs143936283, rs2285666, rs41303171, and rs35803318 are the SNPs that were mentioned at least twice in two different studies. Conclusions We found that ACE2, TMPRSS2, and IFITM3 are the major genes that are involved in SARS-CoV-2 infection. The mentioned SNPs were all related to one or more of the above-mentioned genes. There were discussions on certain SNPs that increased the infection and severity to certain groups more than the others. However, as there is limited follow-up and data due to a shortage of time history of the disease, studies may be limited.

BackgroundA simple filter paper method was developed for, the transport and storage of monoclonal antibodies (Mabs) at room temperature or -20°C after spotting on filter paper, for subsequent serotyping of outer membrane antigens ofN.meningitidisby dot-blot ELISA.MethodsMonoclonal antibodies (Mabs) were spotted within a 0.5–1 cm diameter area of Whatman grade 903 paper, which were stored individually at room temperature or at -20°C. These MAbs were stored and analyzed after periods of one week, 4 weeks, 12 months, or 13 years in the case of frozen Mab aliquots, or after 4 weeks at -20°C or at room temperature (RT) in the case of Mabs dried on filter paper strips. Assays were performed in parallel using dot-blot ELISA. In addition to the MAbs specific for serotyping class 1, 2 or 3, we used a larger number of Mabs for polysaccharides, lipooligosaccharides (LOS), class 5 and cross-reactive antigens for native outer membrane ofN.meningitidis. The Mabs dried on filter paper were eluted with phosphate-buffered saline (PBS) containing 0.2% gelatin.ResultsMabs of the isotypes IgG and IgM dried on filter papers were not affected by duration of storage. The detection by serotyping Mabs was generally consistent for dried filter paper MAb samples stored frozen for over 1 year at -20°C, and although decreased reactive antibody titers were found after storage, this did not interfere with the specificity of the Mabs used after 13 years as dry spots on filter paper.ConclusionThe use of filter paper is an inexpensive and convenient method for collecting, storing, and transporting Mab samples for serotyping studies. In addition, the samples occupy little space and can be readily transported without freezing. The efficiency of using immunoglobulin G (IgG) or M (IgM) eluted was found to be consistent with measurement of IgG or IgM titers in most corresponding, ascites Mabs stored frozen for over 1 year. The application of meningococcal typing methods and designations depend on the question being asked.

Background The reproducibilty of dengue IgM and IgG ELISA was studied in serum and filter paper blood spots from Vietnamese febrile patients. Methods 781 pairs of acute (t0) and convalescent sera, obtained after three weeks (t3) and 161 corresponding pairs of filter paper blood spots were tested with ELISA for dengue IgG and IgM. 74 serum pairs were tested again in another laboratory with similar methods, after a mean of 252 days. Results Cases were classified as no dengue (10 %), past dengue (55%) acute primary (7%) or secondary (28%) dengue. Significant differences between the two laboratories' results were found leading to different diagnostic classification (kappa 0.46, p < 0.001). Filter paper results correlated poorly to serum values, being more variable and lower with a mean (95% CI) difference of 0.82 (0.36 to 1.28) for IgMt3, 0.94 (0.51 to 1.37) for IgGt0 and 0.26 (-0.20 to 0.71) for IgGt3. This also led to differences in diagnostic classification (kappa value 0.44, p < 0.001) The duration of storage of frozen serum and dried filter papers, sealed in nylon bags in an air-conditioned room, had no significant effect on the ELISA results. Conclusion Dengue virus IgG antibodies in serum and filter papers was not affected by duration of storage, but was subject to inter-laboratory variability. Dengue virus IgM antibodies measured in serum reconstituted from blood spots on filter papers were lower than in serum, in particular in the acute phase of disease. Therefore this method limits its value for diagnostic confirmation of individual patients with dengue virus infections. However the detection of dengue virus IgG antibodies eluted from filter paper can be used for sero-prevalence cross sectional studies.

Background The global expansion of dengue (DENV), chikungunya (CHIKV), and Zika viruses (ZIKV) is having a serious impact on public health. Because these arboviruses are transmitted by the same mosquito species and co-circulate in the same area, a sensitive diagnostic assay that detects them together, with discrimination, is needed. Methods We present here a diagnostics panel based on reverse transcription-PCR amplification of viral RNA and an xMap Luminex architecture involving direct hybridization of PCRamplicons and virus-specific probes. Two DNA innovations (“artificially expanded genetic information systems”, AEGIS, and “self-avoiding molecular recognition systems”, SAMRS) increase the hybridization sensitivity on Luminex microspheres and PCR specificity of the multiplex assay compared to the standard approach (standard nucleotides). Results The diagnostics panel detects, if they are present, these viruses with a resolution of 20 genome equivalents (DENV1), or 10 (DENV3–4, CHIKV) and 80 (DENV2, ZIKV) genome equivalents per assay. It identifies ZIKV, CHIKV and DENV RNAs in a single infected mosquito, in mosquito pools comprised of 5 to 50 individuals, and mosquito saliva (ZIKV, CHIKV, and DENV2). Infected mosquitoes and saliva were also collected on a cationic surface (Q-paper), which binds mosquito and viral nucleic acids electrostatically. All samples from infected mosquitoes displayed only target-specific signals; signals from non-infected samples were at background levels. Conclusions Our results provide an efficient and multiplex tool that may be used for surveillance of emerging mosquito-borne pathogens which aids targeted mosquito control in areas at high risk for transmission. Electronic supplementary material The online version of this article (10.1186/s12879-019-3998-z) contains supplementary material, which is available to authorized users.

Background Environmental cleanliness is one of the contributing factors for surgical site infections in the operating rooms (ORs). To decrease environmental contamination, pulsed xenon ultraviolet (PX-UV), an easy and safe no-touch disinfection system, is employed in several hospital environments. The positive effect of this technology on environmental decontamination has been observed in patient rooms and ORs during the end-of-day cleaning but so far, no study explored its feasibility between surgical cases in the OR. Methods In this study, 5 high-touch surfaces in 30 ORs were sampled after manual cleaning and after PX-UV intervention mimicking between-case cleaning to avoid the disruption of the ORs’ normal flow. The efficacy of a 1-min, 2-min, and 8-min cycle were tested by measuring the surfaces’ contaminants by quantitative cultures using Tryptic Soy Agar contact plates. Results We showed that combining standard between-case manual cleaning of surfaces with a 2-min cycle of disinfection using a portable xenon pulsed ultraviolet light germicidal device eliminated at least 70% more bacterial load after manual cleaning. Conclusions This study showed the proof of efficacy of a 2-min cycle of PX-UV in ORs in eliminating bacterial contaminants. This method will allow a short time for room turnover and a potential reduction of pathogen transmission to patients and possibly surgical site infections.

Background Flexible endoscopes undergo repeated rounds of patient-use and reprocessing. Some evidence indicates that there is an accumulation or build-up of organic material that occurs over time in endoscope channels. This "buildup biofilm" (BBF) develops as a result of cyclical exposure to wet and dry phases during usage and reprocessing. This study investigated whether the BBF matrix represents a greater challenge to disinfectant efficacy and microbial eradication than traditional biofilm (TBF), which forms when a surface is constantly bathed in fluid. Methods Using the MBEC (Minimum Biofilm Eradication Concentration) system, a unique modelling approach was developed to evaluate microbial survival in BBF formed by repetitive cycles of drying, disinfectant exposure and re-exposure to the test organism. This model mimics the cumulative effect of the reprocessing protocol on flexible endoscopes. Glutaraldehyde (GLUT) and accelerated hydrogen peroxide (AHP) were evaluated to assess the killing of microbes in TBF and BBF. Results The data showed that the combination of an organic matrix and aldehyde disinfection quickly produced a protective BBF that facilitated high levels of organism survival. In cross-linked BBF formed under high nutrient conditions the maximum colony forming units (CFU) reached ~6 Log10 CFU/peg. However, if an oxidizing agent was used for disinfection and if organic levels were kept low, organism survival did not occur. A key finding was that once established, the microbial load of BBF formed by GLUT exposure had a faster rate of accumulation than in TBF. The rate of biofilm survival post high-level disinfection (HLD) determined by the maximum Log10CFU/initial Log10CFU for E. faecalis and P. aeruginosa in BBF was 10 and 8.6 respectively; significantly different compared to a survival rate in TBF of ~2 for each organism. Data from indirect outgrowth testing demonstrated for the first time that there is organism survival in the matrix. Both TBF and BBF had surviving organisms when GLUT was used. For AHP survival was seen less frequently in BBF than in TBF. Conclusion This BBF model demonstrated for the first time that survival of a wide range of microorganisms does occur in BBF, with significantly more rapid outgrowth compared to TBF. This is most pronounced when GLUT is used compared to AHP. The data supports the need for meticulous cleaning of reprocessed endoscopes since the presence of organic material and microorganisms prevents effective disinfection when GLUT and AHP are used. However, cross-linking agents like GLUT are not as effective when there is BBF. The data from the MBEC model of BBF suggest that for flexible endoscopes that are repeatedly used and reprocessed, the assurance of effective high-level disinfection may decrease if BBF develops within the channels.

Background Tuberculosis (TB) remains a leading cause of death worldwide, with 98% of cases occurring in low- and middle-income countries (LMICs). The only vaccine licenced for the prevention of TB has limited protection for adolescents, adults and vulnerable populations. A safe and effective vaccine for all populations at risk is imperative to achieve global elimination of TB. We aimed to systematically review the efficacy and safety of TB vaccine candidates in late-phase clinical trials conducted in LMICs. Methods Medline, Embase, CENTRAL, PubMed, Clinicaltrials.gov and Greylit.org were searched in June 2021 to identify phase 2 or later clinical randomised controlled trials that report the efficacy or safety (adverse events) of TB vaccine candidates with participants of any age living in an LMIC. TB vaccine candidates listed in the 2020 WHO Global TB Report were eligible for inclusion aside from BCG revaccination. Trials were excluded if all participants had active TB at baseline. Two reviewers independently assessed papers for eligibility, and for bias and quality using the Risk of Bias 2 tool and GRADE guidelines, respectively. We report efficacy rates and frequencies of adverse events from each included trial where available and qualitatively synthesise the findings. Results Thirteen papers representing eleven trials met our inclusion criteria. Seven vaccine candidates were reviewed across seven countries: M72/AS01, RUTI, VPM1002, H56:IC31, MTBVAC, DAR-901 and ID93 + GLA-SE. Two trials reported on efficacy: an efficacy rate of 54% (95% CI 11.5, 76.2) was reported for M72/AS01 in adults with latent TB and 3% (95% CI -13.9, 17.7) for DAR-901 in healthy adolescents. However, the latter trial was underpowered. All vaccine candidates had comparable occurrences of adverse events between treatment arms and demonstrated acceptable safety profiles; though, RUTI resulted in one serious complication in a person living with HIV. M72/AS01 was the only vaccine considered safe across a diverse group of people including people living with HIV or latent TB and healthy infants and adolescents. Conclusion Further efficacy trials for M72/AS01 are warranted to include additional populations at risk where safety has been demonstrated. Further safety trials are needed for the remaining vaccine candidates to confirm safety in vulnerable populations.

Background Despite reports of malaria and coronavirus diseases 2019 (COVID-19) co-infection, malaria-endemic regions have so far recorded fewer cases of COVID-19 and deaths from COVID-19, indicating a probable protection from the poor outcome of COVID-19 by malaria. On the contrary, other evidence suggests that malaria might contribute to the death caused by COVID-19. Hence, this paper reviewed existing evidence hypothesizing poor outcome or protection of COVID-19 patients when co-infected with malaria. Methods PRISMA guidelines for systematic review were employed in this study. Published articles from December 2019 to May 2021on COVID-19 and malaria co-infection and outcome were systematically searched in relevant and accessible databases following a pre-defined strategy. Studies involving human, in vivo animal studies, and in vitro studies were included. Results Twenty three (23) studies were included in the review out of the 3866 records identified in the selected scientific databases. Nine (9) papers reported on co-infection of COVID-19 and malaria. Five (5) papers provided information about synergism of malaria and COVID-19 poor prognosis, 2 papers reported on syndemic of COVID-19 and malaria intervention, and 7 studies indicated that malaria protects individuals from COVID-19. Conclusions Low incidence of COVID-19 in malaria-endemic regions supports the hypothesis that COVID-19 poor prognosis is prevented by malaria. Although further studies are required to ascertain this hypothesis, cross-immunity and common immunodominant isotopes provide strong evidence to support this hypothesis. Also, increase in co-inhibitory receptors and atypical memory B cells indicate synergy between COVID-19 and malaria outcome, though, more studies are required to make a definite conclusion., Highlights Low incidence and mortality rate of COVID-19 in malaria endemic regionsThere have been reports of malaria and COVID-19 co-infectionMalaria could be the link for the reported low incidence of COVID-19 in AfricaCross immunity and common immunodominant epitopes between Malaria and COVID-19, and antimalaria drugs could be the reason for observed low fatality and incidence rate of COVID-19 in malaria endemic regions.Malaria infection and deaths could increase amid the COVID-19 pandemic due to interrupted malaria control interventions.

Background Individual-based models (IBMs) are useful to simulate events subject to stochasticity and/or heterogeneity, and have become well established to model the potential (re)emergence of pathogens (e.g., pandemic influenza, bioterrorism). Individual heterogeneity at the host and pathogen level is increasingly documented to influence transmission of endemic diseases and it is well understood that the final stages of elimination strategies for vaccine-preventable childhood diseases (e.g., polio, measles) are subject to stochasticity. Even so it appears IBMs for both these phenomena are not well established. We review a decade of IBM publications aiming to obtain insights in their advantages, pitfalls and rationale for use and to make recommendations facilitating knowledge transfer within and across disciplines. Methods We systematically identified publications in Web of Science and PubMed from 2006-2015 based on title/abstract/keywords screening (and full-text if necessary) to retrieve topics, modeling purposes and general specifications. We extracted detailed modeling features from papers on established vaccine-preventable childhood diseases based on full-text screening. Results We identified 698 papers, which applied an IBM for infectious disease transmission, and listed these in a reference database, describing their general characteristics. The diversity of disease-topics and overall publication frequency have increased over time (38 to 115 annual publications from 2006 to 2015). The inclusion of intervention strategies (8 to 52) and economic consequences (1 to 20) are increasing, to the detriment of purely theoretical explorations. Unfortunately, terminology used to describe IBMs is inconsistent and ambiguous. We retrieved 24 studies on a vaccine-preventable childhood disease (covering 7 different diseases), with publication frequency increasing from the first such study published in 2008. IBMs have been useful to explore heterogeneous between- and within-host interactions, but combined applications are still sparse. The amount of missing information on model characteristics and study design is remarkable. Conclusions IBMs are suited to combine heterogeneous within- and between-host interactions, which offers many opportunities, especially to analyze targeted interventions for endemic infections. We advocate the exchange of (open-source) platforms and stress the need for consistent “branding”. Using (existing) conventions and reporting protocols would stimulate cross-fertilization between research groups and fields, and ultimately policy making in decades to come. Electronic supplementary material The online version of this article (doi:10.1186/s12879-017-2699-8) contains supplementary material, which is available to authorized users.

Background The 2014–2016 Ebola epidemic in West Africa was the largest Ebola epidemic to date. Contact tracing was a core surveillance activity. Challenges with paper-based contact tracing systems include incomplete identification of contacts, delays in communication and response, loss of contact lists, inadequate data collection and transcription errors. The aim of this study was to design and evaluate an electronic system for tracing contacts of Ebola cases in Port Loko District, Sierra Leone, and to compare this with the existing paper-based system. The electronic system featured data capture using a smartphone application, linked to an alert system to notify the District Ebola Response Centre of symptomatic contacts. Methods The intervention was a customised three-tier smartphone application developed using Dimagi’s CommCare platform known as the Ebola Contact Tracing application (ECT app). Eligible study participants were all 26 Contact Tracing Coordinators (CTCs) and 86 Contact Tracers (CTs) working in the 11 Chiefdoms of Port Loko District during the study period (April–August 2015). Case detection was from 13th April to 17th July 2015. The CTCs and their CTs were provided with smartphones installed with the ECT app which was used to conduct contact tracing activities. Completeness and timeliness of contact tracing using the app were compared with data from April 13th-June 7th 2015, when the standard paper-based system was used. Results For 25 laboratory-confirmed cases for whom paper-based contact tracing was conducted, data for only 39% of 408 contacts were returned to the District, and data were often incomplete. For 16 cases for whom app-based contact tracing was conducted, 63% of 556 contacts were recorded as having been visited on the app, and the median recorded duration from case confirmation to first contact visit was 70 h. Conclusion There were considerable challenges to conducting high-quality contact tracing in this setting using either the paper-based or the app-based system. However, the study demonstrated that it was possible to implement mobile health (mHealth) in this emergency setting. The app had the benefits of improved data completeness, storage and accuracy, but the challenges of using an app in this setting and epidemic context were substantial.

Background Although the use of technology viz. mobile phones, personalised digital assistants, smartphones, notebook and tablets to monitor health and health care (mHealth) is mushrooming, only small, localised studies have described their use as a data collection tool. This paper describes the complexity, functionality and feasibility of mHealth for large scale surveillance at national and sub-national levels in South Africa, a high HIV-prevalence setting. Methods In 2010, 2011–12 and 2012–13 three nationally representative surveys were conducted amongst infants attending 580 facilities across all 51 districts, within all nine provinces of South Africa, to monitor the effectiveness of the programme to prevent mother-to-child transmission of HIV (PMTCT). In all three surveys a technical protocol and iterative system for mobile data collection was developed. In 2012–13 the system included automated folders to store information about upcoming interviews. Paper questionnaires were used as a back-up, in case of mHealth failure. These included written instructions per question on limits, skips and compulsory questions. Data collectors were trained on both systems. Results In the 2010, 2011–12 and 2012–2013 surveys respectively, data from 10,554, 10,071, and 10,536 interviews, and approximately 186 variables per survey were successfully uploaded to 151 mobile phones collecting data from 580 health facilities in 51 districts, across all nine provinces of South Africa. A technician, costing approximately U$D20 000 p.a. was appointed to support field-based staff. Two percent of data were gathered using paper- questionnaires. The time needed for mHealth interviews was approximately 1,5 times less than the time needed for paper questionnaires 30–45 min versus approximately 120 min (including 60–70 min for the interview with an additional 45 min for data capture). In 2012–13, 1172 data errors were identified via the web-based console. There was a four-week delay in resolving data errors from paper-based surveys compared with a 3-day turnaround time following direct capture on mobile phones. Conclusion Our experiences demonstrate the feasibility of using mHealth during large-scale national surveys, in the presence of a supportive data management team. mHealth systems reduced data collection time by almost 1.5 times, thus reduced data collector costs and time needed for data management.

Background South Africa (SA) has expanded efforts to reduce mother-to-child transmission of HIV (MTCT) to less than 2% at six weeks after birth and to less than 5% at 18 months postpartum by 2016. Despite improved antiretroviral regimens and coverage between 2001 and 2016, there is little data on infant HIV drug resistance. This paper tracks the prevalence of HIV drug resistance patterns amongst HIV infected infants from three nationally representative studies that assessed the effectiveness of national programs to prevent MTCT (PMTCT). The first study was conducted in 2010 (under the dual therapy PMTCT policy), the second from 2011 to 12 (PMTCT Option A policy) and the third from 2012 to 13 (PMTCT Option A policy). From 2010 to 2013, infant non-nucleoside reverse transcriptase inhibitor (NNRTI) exposure increased from single dose to daily throughout breastfeeding; maternal nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI exposure increased with initiation of NNRTI-and NRTI- containing triple antiretroviral therapy (ART) earlier in gestation and at higher CD4 cell counts. Methods Three nationally representative surveys were conducted in 2010, 2011–12 and 2012–13. During the surveys, mothers with known, unknown, or no exposure to antiretrovirals for PMTCT and their infants were included, and MTCT was measured. For this paper, infant dried blood spots (iDBS) from HIV PCR positive infants aged 4–8 weeks, with consent for additional iDBS testing, were analysed for HIV drug resistance at the National Institute of Communicable Diseases (NICD), SA, using an in-house assay validated by the Centers for Disease Control and Prevention (CDC). Total viral nucleic acid was extracted from 2 spots and amplified by nested PCR to generate a ~ 1 kb amplicon that was sequenced using Sanger sequencing technologies. Sequence assembly and editing was performed using RECall v3. Results Overall, HIV-1 drug resistance was detected in 51% (95% Confidence interval (CI) [45–58%]) of HIV PCR positive infants, 37% (95% CI [28–47%]) in 2010, 64% (95% CI [53–74%]) in 2011 and 63% (95% CI [47–77%]) in 2012 (p Conclusions These data demonstrate increasing NNRTI resistance amongst newly-diagnosed infants in a high HIV prevalence setting where maternal ART coverage increased across the years, starting earlier in gestation and at higher CD4 cell counts. This is worrying as lifelong maternal ART coverage for HIV positive pregnant and lactating women is increasing. Also of concern is that resistant virus was detected in HIV positive infants whose mothers were not exposed to ARVs, raising questions about circulating resistant virus. Numbers in this group were too small to assess trends over the three years.

Background Although several researches have reported the connection between the transforming growth factor-beta 1 (TGF-β1) gene polymorphisms and chronic hepatitis C virus (HCV) infection, the conclusions of these studies were not always consistent. Here, this paper proposed a meta-analysis to evaluate whether the TGF-ß1 gene polymorphisms, −509C/T (rs1800469), codon 10 T/C (rs1982073) and codon 25G/C (rs1800471), were associated with chronic HCV infection. Methods The summary odds ratios (ORs) of chronic HCV infected patients and controls with all SNPs were obtained by adaptive fixed or random effect model. A series of statistical tools were employed to guarantee the accuracy of related pooling ORs, including the Hardy-Weinberg equilibrium (HWE) test, sensitivity analysis and publication bias test. Results This paper analyzed 18 case-control studies in 17 articles which totally contains 2718 chronic HCV infection cases corresponding to 1964 controls. The results of the meta-analysis indicated that the −509C/T polymorphism effected an increased risk of chronic HCV infection in all gene models. More specifically by ethnicity stratification, the Egyptians shared the similar association with the above overall study. Moreover, the meta-fusion of healthy control studies showed that − 509 T allele carriers (TT + TA) had nearly 2.00 and 3.36 fold higher risk of chronic HCV infection in the total and Egyptian populations, respectively (OR = 2.004, 95% CI = 1.138–3.528, P = 0.016; OR = 3.363, 95% CI = 1.477–7.655, P = 0.004, respectively). However, our meta-analysis did not find any significant association between the codon 10 T/C or codon 25G/C polymorphisms and chronic HCV infection. Conclusions Our results suggested that the TGF-ß1–509C/T polymorphism may effect an increased risk of chronic HCV infection, especially in Egyptian population. Electronic supplementary material The online version of this article (10.1186/s12879-019-4390-8) contains supplementary material, which is available to authorized users.

Background Internalized HIV stigma is a public health concern as it can compromise HIV prevention, care and treatment. This paper has two aims. First, it highlights the urgent need for research evidence on internalized HIV stigma based on critical knowledge gaps. Here, critical knowledge gaps were identified based on most up-to-date systematic review-level evidence on internalized stigma related to HIV and mental health difficulties. Secondly, the paper calls for a shift in focus of internalized HIV stigma research, one that moves beyond psychological frameworks to integrate social, structural and intersectional conceptualizations of stigma. This part of the paper reviews the evolution of stigma theory since Goffman’s 1963 seminal work - which defined stigma - to present. Main text Despite studies consistently suggesting that internalized HIV stigma is more prevalent than enacted stigma, there is little evidence of well-established programs to address it. In addition to this, considerable gaps in basic knowledge about the drivers of internalized HIV stigma hamper the development of an evidence-based response to the problem. The limited intervention and epidemiological research on the topic treats internalized HIV stigma as a purely psychological phenomenon. The second part of the paper provides arguments for studying internalized HIV stigma as a function of social and structural forces: (1) Individual-level interventions for internalized HIV stigma are rooted in out-dated theoretical assumptions; (2) From an ethics point of view, it could be argued that individual-level interventions rely on a victim-centric approach to a public health problem; (3) Social and structural approaches to internalized HIV stigma must be explored due to the high opportunity cost associated with small-scale individual-level interventions. Conclusions Critical gaps in intervention and epidemiological research in internalized HIV stigma remain. There has been an absence of a shared, sound theoretical understanding of internalized HIV stigma as a manifestation of social and structural factors. This commentary sought to stimulate a dialogue to remedy this absence. Future research should take into account ethical considerations, the evolution of stigma theory over the past five decades, intersectionality and opportunity cost when framing hypotheses, developing theories of change and designing interventions.

Background Though home-based human immunodeficiency virus (HIV) counseling and testing (HBHCT) is implemented in many sub-Saharan African countries as part of their HIV programs, linkage to HIV care remains a challenge. The purpose of this study is to test an intervention to enhance linkage to HIV care and improve HIV viral suppression among individuals testing HIV positive during HBHCT in rural Uganda. Methods The PATH (Providing Access To HIV Care)/Ekkubo Study is a cluster-randomized controlled trial which compares the efficacy of an enhanced linkage to HIV care intervention vs. standard-of-care (paper-based referrals) at achieving individual and population-level HIV viral suppression, and intermediate outcomes of linkage to care, receipt of opportunistic infection prophylaxis, and antiretroviral therapy initiation following HBHCT. Approximately 600 men and women aged 18-59 who test HIV positive during district-wide HBHCT in rural Uganda will be enrolled in this study. Villages (clusters) are pair matched by population size and then randomly assigned to the intervention or standard-of-care arm. Study teams visit households and participants complete a baseline questionnaire, receive HIV counseling and testing, and have blood drawn for HIV viral load and CD4 testing. At baseline, standard-of-care arm participants receive referrals to HIV care including a paper-based referral and then receive their CD4 results via home visit 2 weeks later. Intervention arm participants receive an intervention counseling session at baseline, up to three follow-up counseling sessions at home, and a booster session at the HIV clinic if they present for care. These sessions each last approximately 30 min and consist of counseling to help clients: identify and reduce barriers to HIV care engagement, disclose their HIV status, identify a treatment supporter, and overcome HIV-related stigma through links to social support resources in the community. Participants in both arms complete interviewer-administered questionnaires at six and 12 months follow-up, HIV viral load and CD4 testing at 12 months follow-up, and allow access to their medical records. Discussion The findings of this study can inform the integration of a potentially cost-effective approach to improving rates of linkage to care and HIV viral suppression in HBHCT. If effective, this intervention can improve treatment outcomes, reduce mortality, and through its effect on individual and population-level HIV viral load, and decrease HIV incidence. Trial registration NCT02545673

Background: Over the past few decades, numerous forecasting methods have been proposed in the field of epidemic forecasting. Such methods can be classified into different categories such as deterministic vs. probabilistic, comparative methods vs. generative methods, and so on. In some of the more popular comparative methods, researchers compare observed epidemiological data from early stages of an outbreak with the output of proposed models to forecast the future trend and prevalence of the pandemic. A significant problem in this area is the lack of standard well-defined evaluation measures to select the best algorithm among different ones, as well as for selecting the best possible configuration for a particular algorithm. Results: In this paper, we present an evaluation framework which allows for combining different features, error measures, and ranking schema to evaluate forecasts. We describe the various epidemic features (Epi-features) included to characterize the output of forecasting methods and provide suitable error measures that could be used to evaluate the accuracy of the methods with respect to these Epi-features. We focus on long-term predictions rather than short-term forecasting and demonstrate the utility of the framework by evaluating six forecasting methods for predicting influenza in the United States. Our results demonstrate that different error measures lead to different rankings even for a single Epi-feature. Further, our experimental analyses show that no single method dominates the rest in predicting all Epi-features, when evaluated across error measures. As an alternative, we provide various consensus ranking schema that summarizes individual rankings, thus accounting for different error measures. We believe that a comprehensive evaluation framework, as presented in this paper, will add value to the computational epidemiology community., Submitted to BMC infectious disease Journal, 2016. Accepted in 2017

Background Zika, dengue, and chikungunya are three mosquito-borne viruses having overlapping transmission vectors. They cause diseases having similar symptoms in human patients, but requiring different immediate management steps. Therefore, rapid (< one hour) discrimination of these three viruses in patient samples and trapped mosquitoes is needed. The need for speed precludes any assay that requires complex up-front sample preparation, such as extraction of nucleic acids from the sample. Also precluded in robust point-of-sampling assays is downstream release of the amplicon mixture, as this risks contamination of future samples that will give false positives. Methods Procedures are reported that directly test urine and plasma (for patient diagnostics) or crushed mosquito carcasses (for environmental surveillance). Carcasses are captured on paper samples carrying quaternary ammonium groups (Q-paper), which may be directly introduced into the assay. To avoid the time and instrumentation requirements of PCR, the procedure uses loop-mediated isothermal amplification (LAMP). Downstream detection is done in sealed tubes, with dTTP-dUTP mixtures in the LAMP with a thermolabile uracil DNA glycosylase (UDG); this offers a second mechanism to prevent forward contamination. Reverse transcription LAMP (RT-LAMP) reagents are distributed dry without requiring a continuous chain of refrigeration. Results The tests detect viral RNA in unprocessed urine and other biological samples, distinguishing Zika, chikungunya, and dengue in urine and in mosquitoes infected with live Zika and chikungunya viruses. The limits of detection (LODs) are ~0.71 pfu equivalent viral RNAs for Zika, ~1.22 pfu equivalent viral RNAs for dengue, and ~38 copies of chikungunya viral RNA. A handheld, battery-powered device with an orange filter was constructed to visualize the output. Preliminary data showed that this architecture, working with pre-prepared tubes holding lyophilized reagent/enzyme mixtures and shipped without a chain of refrigeration, also worked with human plasma samples to detect chikungunya and dengue in Pune, India. Conclusions A kit, complete with a visualization device, is now available for point-of-sampling detection of Zika, chikungunya, and dengue. The assay output is read in ca. 30 min by visualizing (human eye) three-color coded fluorescence signals. Assay in dried format allows it to be run in low-resource environments. Electronic supplementary material The online version of this article (doi:10.1186/s12879-017-2382-0) contains supplementary material, which is available to authorized users.

Hospitalization; Influenza; Prevention Hospitalització; Grip; Prevenció Hospitalización; Gripe; Prevención Having a proper understanding of the impact of influenza is a fundamental step towards improved preventive action. This paper reviews findings from the Burden of Acute Respiratory Infections study on the burden of influenza in Iberia, and its potential underestimation, and proposes specific measures to lessen influenza’s impact. The BARI study was funded by Sanofi.

Background Balamuthia granulomatous amoebic encephalitis (GAE) is a peculiar parasitic infectious disease of the central nervous system, about 39% of the infected Balamuthia GAE patients were found to be immunocompromised and is extremely rare clinically. The presence of trophozoites in diseased tissue is an important basis for pathological diagnosis of GAE. Balamuthia GAE is a rare and highly fatal infection for which there is no effective treatment plan in clinical practice. Case presentation This paper reports clinical data from a patient with Balamuthia GAE to improve physician understanding of the disease and diagnostic accuracy of imaging and reduce misdiagnosis. A 61-year-old male poultry farmer presented with moderate swelling pain in the right frontoparietal region without obvious inducement three weeks ago. Head computed tomography(CT) and magnetic resonance imaging(MRI) revealed a space-occupying lesion in the right frontal lobe. Intially clinical imaging diagnosed it as a high-grade astrocytoma. The pathological diagnosis of the lesion was inflammatory granulomatous lesions with extensive necrosis, suggesting amoeba infection. The pathogen detected by metagenomic next-generation sequencing (mNGS) is Balamuthia mandrillaris, the final pathological diagnosis was Balamuthia GAE. Conclusion When a head MRI shows irregular or annular enhancement, clinicians should not blindly diagnose common diseases such as brain tumors. Although Balamuthia GAE accounts for only a small proportion of intracranial infections, it should be considered in the differential diagnosis.

Introduction Bacterial vaginosis (BV) is the most common vaginal dysbiosis among women of reproductive age. Micronutrient deficiencies, including vitamin D deficiency, can increase the risk of BV. The findings of previous studies regarding the relationship between vitamin D deficiency and BV were conflicting. Therefore, this study aimed to evaluate the association between BV and serum level of 25-hydroxy vitamin D. Materials and methods This case-control study was conducted in Gonabad County in 2021. One hundred and twenty-five confirmed BV cases and 125 controls who were matched based on age and intercourse frequency (maximum difference of two days per week) enrolled in the study. Data collection was performed using a demographic and reproductive data questionnaire and a checklist for recording Whiff test results, serum 25-hydroxy vitamin D level, litmus paper observation, and microscopic findings (clue cells). Serum level of vitamin D was evaluated based on enzyme-linked immunoassay method (Monobind kit) from 0.5 ml venous blood drawn from each participant. The conditional logistic regression model was used to analyze data. Results The BV cases had significantly lower 25-hydroxy vitamin D serum levels than controls. The odds of BV increased with vitamin D deficiency (Adjusted odds ratio (AOR): 4.34, 95% confidence interval (CI): 1.39–13.4, p = 0.011, FDR q-value = 0.051), vitamin D insufficiency (AOR: 3.65, 95% CI: 1.23–10.85; p = 0.020; FDR q-value = 0.053), cigarette/hookah smoking (AOR: 3.65, 95% CI: 1.23, 10.85; p = 0.020; FDR q-value = 0.053) and lower age at first intercourse (AOR: 1.16, 95% CI: 1.05, 1.28; p = 0.004; FDR q-value = 0.048). The odds of BV was 0.80 and 0.78 times lower in participants who had coitus interruptus (AOR: 0.20, 95% CI: 0.06, 0.63; p = 0.006; FDR q-value = 0.048) and condom use (AOR: 0.28, 95% CI: 0.10, 0.79; p = 0.016; FDR q-value = 0.051), respectively, compared to participants who did not use contraceptives. Conclusion These findings suggested that lower serum vitamin D levels were associated with an increased risk of developing BV. However, further studies are needed to confirm the results of the present study.

Background Paracoccidioidomycosis, a chronic granulomatous fungal disease caused by Paracoccidioides brasiliensis yeast cells affects mainly rural workers, albeit recently cases in immunosuppressed individuals has been reported. Protective immune response against P. brasiliensis is dependent on the activity of helper T cells especially IFN-γ-producing Th1 cells. It has been proposed that Paracoccidioides brasiliensis is able to modulate the immune response towards a permissive state and that the thymus plays a major role in it. Methods In this paper, we show that acute infection of BALB/c mice with P. brasiliensis virulent isolate (Pb18) might cause alterations in the thymic environment as well as the prohibitive TCR-expressing T cells in the spleens. Results After seven days of infection, we found yeast cells on the thymic stroma, the thymic epithelial cells (TEC) were altered regarding their spatial-orientation and inflammatory mediators gene expression was increased. Likewise, thymocytes (differentiating T cells) presented higher migratory ability in ex vivo experiments. Notwithstanding, P. brasiliensis-infected mice showed an increased frequency of prohibitive TCR-expressing T cells in the spleens, suggesting that the selection processes that occur in the thymus may be compromised during the acute infection. Conclusion In this paper, for the first time, we show that acute infection with Paracoccidioides brasiliensis yeast cells promotes thymic alterations leading to a defective repertoire of peripheral T cells. The data presented here may represent new mechanisms by which P. brasiliensis subverts the immune response towards the chronic infection observed in humans. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1561-8) contains supplementary material, which is available to authorized users.

Background During the last decade the resistance rate of urinary Escherichia coli (E. coli) to fluoroquinolones such as ciprofloxacin has increased. Systematic reviews of studies investigating ciprofloxacin resistance in community- and hospital-acquired E. coli urinary tract infections (UTI) are absent. This study systematically reviewed the literature and where appropriate, meta-analysed studies investigating ciprofloxacin resistance in community- and hospital-acquired E. coli UTIs. Methods Observational studies published between 2004 and 2014 were identified through Medline, PubMed, Embase, Cochrane, Scopus and Cinahl searches. Overall and sub-group pooled estimates of ciprofloxacin resistance were evaluated using DerSimonian-Laird random-effects models. The I2 statistic was calculated to demonstrate the degree of heterogeneity. Risk of bias among included studies was also investigated. Results Of the identified 1134 papers, 53 were eligible for inclusion, providing 54 studies for analysis with one paper presenting both community and hospital studies. Compared to the community setting, resistance to ciprofloxacin was significantly higher in the hospital setting (pooled resistance 0.38, 95 % CI 0.36-0.41 versus 0.27, 95 % CI 0.24-0.31 in community-acquired UTIs, P

Background Extensive parasitic diseases epidemiology in Zhejiang province has not been carried out since the second national survey in 2004. Therefore, dynamics in prevalence and infection pattern of the major intestinal parasites should be explored. Methods The distribution of three parasites including soil-transmitted helminths (STH), intestinal protozoa and C. sinensis in Zhejiang from 2014 to 2015 were explored. Kato-Katz technique was used for STH and C. sinensis detection, whereas transparent adhesive paper anal swab was used for pinworm detection, and iodine smear was used for protozoa detection. A questionnaire survey on alimentary habits and sanitary behaviors was conducted in half of the studied counties. Results This study recruited 23,552 participants: 19,935 from rural and 3617 from urban area. Overall prevalence of intestinal helminth infections was 1.80%. In this study, seven helminth species were identified including A. duodenale, N. americanus, Trichuris trichiura, Ascaris lumbricoides, C. sinensis, Fasciolopsis buski and pinworm. The average prevalence of STH infection was 1.71%: 1.94% in rural and 0.44% in urban area. Hookworm was the most prevalent infection at 1.58%: 1.79% in rural and 0.44% in urban area. Prevalence varied considerably in the studied counties. Prevalence was highest in Yongkang county at 10.25%. Only 2.79% of children from rural area were infected with pinworm. A proportion of 0.40% of rural participants were infected with protozoa, whereas Endolimax nana was the most prevalent at 0.23%. C. sinensis showed infection only in one man. Awareness on C. sinensis was 24.47% in rural and 45.96% in urban area, respectively. Conclusions Prevalence of STH and protozoa infections declined considerably whereas C. sinensis infections remained few in Zhejiang province compared with the prevalence reported in previous large scale surveys (19.56% for national STH infection in 2004, 18.66% and 4.57% for provincial STH and protozoa infection, respectively in 1999). The findings of this study showed that hookworm, mainly N. americanus remained a parasitic threat to population health, mainly in the central and western Zhejiang. Therefore, more health education regarding fertilization and farming habits is necessary in rural areas. The awareness concerning hookworm infection should be reinforced.

Background In the past decade, Brazil has significantly reduced the prevalence of schistosomiasis through a combined effort of early treatment of infected people, expansion of basic sanitation infrastructure and educational measures. Despite these efforts, in some areas, prevalence of schistosomiasis exceeds 20% of the school population, who lack knowledge of the risks of the disease. Action can be taken in schools to empower this population about their health condition. This paper describes the role of the teacher as a multiplier of knowledge about schistosomiasis and proposes two different approaches to training these teachers. Methods This study used mixed methods to evaluate training of teachers and educational intervention with those teachers’ pupils. Two training courses, each with 40 h of face-to-face activity, were offered to 19 teachers, using two different but complementary approaches, based on theoretical references and specific educational strategies: Critical Pedagogical Approach (Training Course I, held in 2013) and Creative Play Approach (Training Course II, held in 2014).The courses included classroom activities, laboratory and field work. After the training, the teachers conducted activities on schistosomiasis with their pupils. These activities involved constructing educational materials and cultural productions. The pupils’ knowledge about the disease was evaluated before the activities and 12 months later. The teachers’ acceptance and perceptions were assessed through structured interviews and subsequent thematic analysis. The Shistosoma mansoni infection status of teachers and their students was also assessed using the Kato Katz stool test. Results The parasitological study showed 31.6% of the teachers and 21.4% of the pupils to be positive for S. mansoni. The teachers’ knowledge of important aspects of schistosomiasis transmission and prevention was fragmented and incorrect prior to the training. The teachers’ knowledge changed significantly after the training and they were strongly accepting of the pedagogical methods used during the training. The level of their pupils’ knowledge about the disease had increased significantly (p 0.05). Conclusions The results of this study underline the importance of schools and teachers as partners in controlling and eliminating schistosomiasis. Teacher training on the disease significantly increases their pupils’ knowledge, reflecting empowerment with regard to local health conditions.

Background The potential impact of an influenza pandemic can be assessed by calculating a set of transmissibility parameters, the most important being the reproduction number (R), which is defined as the average number of secondary cases generated per typical infectious case. Methods We conducted a systematic review to summarize published estimates of R for pandemic or seasonal influenza and for novel influenza viruses (e.g. H5N1). We retained and summarized papers that estimated R for pandemic or seasonal influenza or for human infections with novel influenza viruses. Results The search yielded 567 papers. Ninety-one papers were retained, and an additional twenty papers were identified from the references of the retained papers. Twenty-four studies reported 51 R values for the 1918 pandemic. The median R value for 1918 was 1.80 (interquartile range [IQR]: 1.47–2.27). Six studies reported seven 1957 pandemic R values. The median R value for 1957 was 1.65 (IQR: 1.53–1.70). Four studies reported seven 1968 pandemic R values. The median R value for 1968 was 1.80 (IQR: 1.56–1.85). Fifty-seven studies reported 78 2009 pandemic R values. The median R value for 2009 was 1.46 (IQR: 1.30–1.70) and was similar across the two waves of illness: 1.46 for the first wave and 1.48 for the second wave. Twenty-four studies reported 47 seasonal epidemic R values. The median R value for seasonal influenza was 1.28 (IQR: 1.19–1.37). Four studies reported six novel influenza R values. Four out of six R values were

The EuroSIDA observational cohort study was initiated in 1993 by Jens Lundgren (Copenhagen HIV Programme) and Andrew Phillips (University College London) as the successor of the AIDS in Europe Study, with the main objective of assessing the impact of antiretroviral drugs on outcomes for the general population of HIV-infected patients living in Europe. As of April 2014 EuroSIDA included 18,786 patients followed at 111 hospitals in 34 European countries plus Argentina and Israel. Since its inception, EuroSIDA has provided data published in 202 papers in peer-reviewed journals, among them 14 papers on hepatitis C virus (HCV) co-infection [1-14] . As the HIV epidemic has evolved and the incidence of AIDS has decreased, the focus of EuroSIDA has shifted to addressing the research questions most pertinent to the clinical care of Europeans living with HIV on a long-term basis. With more than a quarter of all EuroSIDA patients positive for antibodies to HCV, and with growing concern about the burden of liver-related disease and death, hepatitis C research has come to play an increasingly important role in EuroSIDA in recent years. This article will describe key characteristics of the HIV/HCV co-infected population in EuroSIDA, and summarize the most important EuroSIDA co-infection studies.

Background Pneumonia and diarrhea are leading causes of death for children under five (U5). It is challenging to estimate the total number of deaths and cause-specific mortality fractions. Two major efforts, one led by the Institute for Health Metrics and Evaluation (IHME) and the other led by the World Health Organization (WHO)/Child Health Epidemiology Reference Group (CHERG) created estimates for the burden of disease due to these two syndromes, yet their estimates differed greatly for 2010. Methods This paper discusses three main drivers of the differences: data sources, data processing, and covariates used for modelling. The paper discusses differences in the model assumptions for etiology-specific estimates and presents recommendations for improving future models. Results IHME’s Global Burden of Disease (GBD) 2010 study estimated 6.8 million U5 deaths compared to 7.6 million U5 deaths from CHERG. The proportional differences between the pneumonia and diarrhea burden estimates from the two groups are much larger; GBD 2010 estimated 0.847 million and CHERG estimated 1.396 million due to pneumonia. Compared to CHERG, GBD 2010 used broader inclusion criteria for verbal autopsy and vital registration data. GBD 2010 and CHERG used different data processing procedures and therefore attributed the causes of neonatal death differently. The major difference in pneumonia etiologies modeling approach was the inclusion of observational study data; GBD 2010 included observational studies. CHERG relied on vaccine efficacy studies. Discussion Greater transparency in modeling methods and more timely access to data sources are needed. In October 2013, the Bill & Melinda Gates Foundation (BMGF) hosted an expert meeting to examine possible approaches for better estimation. The group recommended examining the impact of data by systematically excluding sources in their models. GBD 2.0 will use a counterfactual approach for estimating mortality from pathogens due to specific etiologies to overcome bias of the methods used in GBD 2010 going forward. Electronic supplementary material The online version of this article (doi:10.1186/s12879-014-0728-4) contains supplementary material, which is available to authorized users.

Background Cedecea neteri is a gram-negative, oxidase-negative bacillus, a rare pathogen. Few reports are emerging globally about its antimicrobial resistance pattern especially in immunocompromised individuals with comorbidities. Case presentation In this paper, we report the first case of C. neteri causing urinary tract infection in a pregnant woman at a specialty care hospital in the Northern Emirates of Ras al Khaimah, UAE. Discussion and conclusion C. neteri is a rare and unusual pathogen, unlike routine gram-negative urinary tract pathogens from the family of Enterobacteriaceae and therefore may be missed or misidentified by routine laboratories using conventional microbiology identification techniques. Hence, Cedecea infections may be under-reported. Physicians and microbiology technicians must be aware of such a rare pathogen, as most of the isolates are multi-drug-resistant and require combined antibiotic treatment with beta-lactamase inhibitors and hence pose a treatment challenge especially in immunocompromised patients with comorbidities. In recent years, it has been reported as an emerging opportunistic pathogen.

Coronavirus disease 2019 (COVID-19) continues to constitute an international public health emergency. Vaccination is a prospective approach to control this pandemic. However, apprehension about the safety of vaccines is a major obstacle to vaccination. Amongst health professionals, one evident concern is the risk of antibody-dependent enhancement (ADE), which may increase the severity of COVID-19. To explore whether ADE occurs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and increase confidence in the safety of vaccination, we conducted a meta-analysis to investigate the relationship between post-immune infection and disease severity from a population perspective. Databases, including PubMed, EMBASE, Chinese National Knowledge Infrastructure, SinoMed, Scopus, Science Direct, and Cochrane Library, were searched for articles on SARS-CoV-2 reinfection published until 25 October 2021. The papers were reviewed for methodological quality, and a random effects model was used to analyse the results. Heterogeneity was assessed using the I2 statistic. Publication bias was evaluated using a funnel plot and Egger’s test. Eleven studies were included in the final meta-analysis. The pooled results indicated that initial infection and vaccination were protective factors against severe COVID-19 during post-immune infection (OR = 0.55, 95%CI = 0.31–0.98). A subgroup (post-immune infection after natural infection or vaccination) analysis showed similar results. Primary SARS-CoV-2 infection and vaccination provide adequate protection against severe clinical symptoms after post-immune infection. This finding demonstrates that SARS-CoV-2 may not trigger ADE at the population level.