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Side effects are a common concern of current and potential HIV pre-exposure prophylaxis (PrEP) users, potentially leading to missed doses. We examined the relationship between reported side effects and adherence in the Ontario PrEP Cohort Study (ON-PrEP). In total, 600 predominantly gay (87.3%), White (65.8%), and male (95.0%) participants completed questionnaires assessing the presence and severity of five side effect categories (nausea, diarrhea, headache, abdominal pain, and "other") as well as their adherence to daily PrEP (any missed doses in the previous 4 days). In total, 175 participants (29%) ever reported experiencing side effects: most commonly diarrhea (7.5% of study visits), and most were of mild severity. Lower incomes (p = 0.01), identifying as bisexual (p = 0.04), and baseline concern about side effects (p < 0.001) were associated with ever reporting side effects. The odds of reporting any side effects decreased by a factor of 0.44 (95% confidence interval 0.25–0.80) with each additional year of PrEP use, however 1 in 10 participants still reported side effects after 1 year of use. The odds of reporting optimal adherence were 0.48 (0.28–0.83) times lower for participants reporting any side effects, 0.67 (0.51–0.89) times lower per additional side effect category reported, and 0.78 (0.65–0.97) times lower per incremental increase in side effect severity ratings. We found some evidence of interaction between side effect measures and duration of PrEP use, suggesting that these relationships were stronger for participants taking PrEP for longer. Clinicians should make efforts to ascertain patients' experience of side effects and consider risk counseling and alternative PrEP regimens to promote adherence. [ABSTRACT FROM AUTHOR]

Background: Hepatitis-E virus (HEV), an etiologic agent of acute inflammatory liver disease, is a significant cause of morbidity and mortality in South Asia. HEV is considered endemic in Nepal; but data on population-level infection transmission is sparse. Methods: We conducted a longitudinal serosurvey in central Nepal to assess HEV exposure. At each visit, capillary blood samples were collected and analyzed for the presence of anti-HEV IgG antibodies. The study took place between February 2019 and April 2021, with up to 4 visits per participant approximately 6 months apart. Results: We collected 2513 samples from 923 participants aged 0–25 years, finding a seroprevalence of 4.8% and a seroincidence rate of 10.9 per 1000 person-years. Young adults and individuals consuming surface water faced the highest incidence of infection. Geospatial analysis identified potential HEV clusters, suggesting a need for targeted interventions. Significance: Our findings demonstrate that HEV is endemic in Nepal and that the risk of infection increases with age. Author summary: Hepatitis-E virus (HEV) is an infectious cause of acute liver disease and is primarily transmitted through contaminated food and water. It has emerged as a leading cause of acute clinical hepatitis in South Asia. Pregnant women face the highest risk of complications and mortality. To better understand the impact of HEV in Nepal, we conducted a two-year cohort study in the Kathmandu Valley region. We collected dried blood spots from participants every 6 months and tested the samples to detect past and new infections of HEV. Our study, involving 923 individuals, revealed that 4.8% had IgG antibodies against HEV, indicating past exposure. Each year, about 11 in 1000 people between the ages of 1 and 25 years are newly exposed to the virus. The highest infection rates were among young adults and those using untreated surface water. Our study mapped the distribution of HEV, identifying specific areas with higher infection rates. [ABSTRACT FROM AUTHOR]

Auto-brewery syndrome is a rare condition in which fungi in the gut cause endogenous alcohol fermentation. This can lead to symptoms of alcohol intoxication even without consuming alcohol. A 50-year-old woman with recurrent presentations of alcohol intoxication despite not drinking alcohol was diagnosed with auto-brewery syndrome. She was treated with antifungal therapy and a low-carbohydrate diet, which resolved her symptoms. The diagnosis of auto-brewery syndrome can be challenging and delayed, but awareness of this condition is important for proper diagnosis and management. [Extracted from the article]

Understanding how emerging infectious diseases spread within and between countries is essential to contain future pandemics. Spread to new areas requires connectivity between one or more sources and a suitable local environment, but how these two factors interact at different stages of disease emergence remains largely unknown. Further, no analytical framework exists to examine their roles. Here we develop a dynamic modelling approach for infectious diseases that explicitly models both connectivity via human movement and environmental suitability interactions. We apply it to better understand recently observed (1995-2019) patterns as well as predict past unobserved (1983-2000) and future (2020-2039) spread of dengue in Mexico and Brazil. We find that these models can accurately reconstruct long-term spread pathways, determine historical origins, and identify specific routes of invasion. We find early dengue invasion is more heavily influenced by environmental factors, resulting in patchy non-contiguous spread, while short and long-distance connectivity becomes more important in later stages. Our results have immediate practical applications for forecasting and containing the spread of dengue and emergence of new serotypes. Given current and future trends in human mobility, climate, and zoonotic spillover, understanding the interplay between connectivity and environmental suitability will be increasingly necessary to contain emerging and re-emerging pathogens. Here, using a dynamic modelling approach, the authors find that the spread of dengue through Mexico and Brazil is shaped by specific interactions between human mobility, climate, and the environment. Their models can also be applied to predict future spread in these geographic areas. [ABSTRACT FROM AUTHOR]

Background: Environmental surveillance, using detection of Salmonella Typhi DNA, has emerged as a potentially useful tool to identify typhoid-endemic settings; however, it is relatively costly and requires molecular diagnostic capacity. We sought to determine whether S. Typhi bacteriophages are abundant in water sources in a typhoid-endemic setting, using low-cost assays. Methodology: We collected drinking and surface water samples from urban, peri-urban and rural areas in 4 regions of Nepal. We performed a double agar overlay with S. Typhi to assess the presence of bacteriophages. We isolated and tested phages against multiple strains to assess their host range. We performed whole genome sequencing of isolated phages, and generated phylogenies using conserved genes. Findings: S. Typhi-specific bacteriophages were detected in 54.9% (198/361) of river and 6.3% (1/16) drinking water samples from the Kathmandu Valley and Kavrepalanchok. Water samples collected within or downstream of population-dense areas were more likely to be positive (72.6%, 193/266) than those collected upstream from population centers (5.3%, 5/95) (p=0.005). In urban Biratnagar and rural Dolakha, where typhoid incidence is low, only 6.7% (1/15, Biratnagar) and 0% (0/16, Dolakha) river water samples contained phages. All S. Typhi phages were unable to infect other Salmonella and non-Salmonella strains, nor a Vi-knockout S. Typhi strain. Representative strains from S. Typhi lineages were variably susceptible to the isolated phages. Phylogenetic analysis showed that S. Typhi phages belonged to the class Caudoviricetes and clustered in three distinct groups. Conclusions: S. Typhi bacteriophages were highly abundant in surface waters of typhoid-endemic communities but rarely detected in low typhoid burden communities. Bacteriophages recovered were specific for S. Typhi and required Vi polysaccharide for infection. Screening small volumes of water with simple, low-cost (~$2) plaque assays enables detection of S. Typhi phages and should be further evaluated as a scalable tool for typhoid environmental surveillance. Author summary: Typhoid fever is a major health issue in low- and middle-income countries, causing illness and death. The World Health Organization recommends the use of typhoid-conjugate vaccines to combat its spread. However, limited data on typhoid prevalence in these countries hinders effective vaccination programs. Environmental surveillance, which involves detecting Salmonella Typhi DNA in the environment, has emerged as a method to identify high-risk areas for typhoid transmission. Nevertheless, this approach is costly and requires infrastructure often unavailable in many communities. To address this, we conducted a study in Nepal to explore a low-cost and sustainable typhoid surveillance method. We examined typhoid bacteriophages in surface and drinking water across communities with varying population densities and typhoid burdens. Phages were easily detectable in communities with high typhoid burdens but less prevalent in areas with lower burdens. The isolated phages exhibited specificity for S. Typhi and were effective against different bacterial strains in Nepal. This study demonstrates that phage-based assays can be a simple and affordable tool for typhoid environmental surveillance. This method can help identify areas that require vaccination prioritization and interventions for clean water and sanitation. By utilizing phage-based assays, health authorities can better understand typhoid transmission and implement targeted control measures. [ABSTRACT FROM AUTHOR]

Schistosomiasis is a neglected tropical disease affecting over 150 million people. Hotspots of Schistosoma transmission—communities where infection prevalence does not decline adequately with mass drug administration—present a key challenge in eliminating schistosomiasis. Current approaches to identify hotspots require evaluation 2–5 y after a baseline survey and subsequent mass drug administration. Here, we develop statistical models to predict hotspots at baseline prior to treatment comparing three common hotspot definitions, using epidemiologic, survey-based, and remote sensing data. In a reanalysis of randomized trials in 589 communities in five endemic countries, a regression model predicts whether Schistosoma mansoni infection prevalence will exceed the WHO threshold of 10% in year 5 (“prevalence hotspot”) with 86% sensitivity, 74% specificity, and 93% negative predictive value (NPV; assuming 30% hotspot prevalence), and a regression model for Schistosoma haematobium achieves 90% sensitivity, 90% specificity, and 96% NPV. A random forest model predicts whether S. mansoni moderate and heavy infection prevalence will exceed a public health goal of 1% in year 5 (“intensity hotspot”) with 92% sensitivity, 79% specificity, and 96% NPV, and a boosted trees model for S. haematobium achieves 77% sensitivity, 95% specificity, and 91% NPV. Baseline prevalence is a top predictor in all models. Prediction is less accurate in countries not represented in training data and for a third hotspot definition based on relative prevalence reduction over time (“persistent hotspot”). These models may be a tool to prioritize high-risk communities for more frequent surveillance or intervention against schistosomiasis, but prediction of hotspots remains a challenge. [ABSTRACT FROM AUTHOR]

We report a cluster of clade I monkeypox virus infections linked to sexual contact in the Democratic Republic of the Congo. Case investigations resulted in 5 reverse transcription PCR-confirmed infections; genome sequencing suggest they belonged to the same transmission chain. This finding demonstrates that mpox transmission through sexual contact extends beyond clade IIb. [ABSTRACT FROM AUTHOR]

Introduction: Salmonella Typhi and Salmonella Paratyphi, fecal-oral transmitted bacterium, have temporally and geographically heterogeneous pathways of transmission. Previous work in Kathmandu, Nepal implicated stone waterspouts as a dominant transmission pathway after 77% of samples tested positive for Salmonella Typhi and 70% for Salmonella Paratyphi. Due to a falling water table, these spouts no longer provide drinking water, but typhoid fever persists, and the question of the disease's dominant pathway of transmission remains unanswered. Methods: We used environmental surveillance to detect Salmonella Typhi and Salmonella Paratyphi A DNA from potential sources of transmission. We collected 370, 1L drinking water samples from a population-based random sample of households in the Kathmandu and Kavre Districts of Nepal between February and October 2019. Between November 2019 and July 2021, we collected 380, 50mL river water samples from 19 sentinel sites on a monthly interval along the rivers leading through the Kathmandu and Kavre Districts. We processed drinking water samples using a single qPCR and processed river water samples using differential centrifugation and qPCR at 0 and after 16 hours of liquid culture enrichment. A 3-cycle threshold (Ct) decrease of Salmonella Typhi or Salmonella Paratyphi, pre- and post-enrichment, was used as evidence of growth. We also performed structured observations of human-environment interactions to understand pathways of potential exposure. Results: Among 370 drinking water samples, Salmonella Typhi was detected in 7 samples (1.8%) and Salmonella Paratyphi A was detected in 4 (1.0%) samples. Among 380 river water samples, Salmonella Typhi was detected in 171 (45%) and Salmonella Paratyphi A was detected in 152 (42%) samples. Samples located upstream of the Kathmandu city center were positive for Salmonella Typhi 12% of the time while samples from locations in and downstream were positive 58% and 67% of the time respectively. Individuals were observed bathing, washing clothes, and washing vegetables in the rivers. Implications: These results suggest that drinking water was not the dominant pathway of transmission of Salmonella Typhi and Salmonella Paratyphi A in the Kathmandu Valley in 2019. The high degree of river water contamination and its use for washing vegetables raises the possibility that river systems represent an important source of typhoid exposure in Kathmandu. Author summary: Understanding the dominant route of transmission of a pathogen is important for designing and implementing effective control strategies. Salmonella Typhi and Paratyphi A, which cause enteric fever, infect approximately 10 million people and cause over 100,000 deaths annually. In the Kathmandu Valley, prior work suggested ancient stone spouts used for drinking water were often contaminated and driving transmission of the diseases. However, many of these spouts no longer function, and people are still getting sick, suggesting other possible dominant pathways for enteric fever transmission. We tested drinking water from households in this area as well as local river water and found that only 7 drinking water samples were positive for Salmonella Typhi and 4 were positive for Salmonella Paratyphi A. We also tested river water and found many samples (>40%) tested positive for these bacteria. River water samples were not often positive upstream of Kathmandu city center (12% positive for Salmonella Typhi) but were often positive within the city center (58% positive for Salmonella Typhi) and in rural areas up to 10 km downstream of the city (67% positive for Salmonella Typhi). During sample collection, individuals were observed interacting with rivers by walking in them, washing clothes and washing vegetables for sale in markets. This study shows that drinking water may not be a primary driver of enteric fever transmission in the Kathmandu Valley, but that sewage contaminated river water may be a way disease transmits into the wider population. [ABSTRACT FROM AUTHOR]

Appearance- and performance-enhancing supplements (APES) may be associated with liver and renal toxicity, but use is often under-reported. This study describes the use and safety of APES among gay, bisexual, and other men-who-have-sex with men (gbMSM) attending an urban HIV pre-exposure prophylaxis (PrEP) clinic. A cross-sectional study was conducted between February 2018 to September 2018 to assess APES usage in gbMSM taking daily tenofovir disoproxil fumarate/emtricitabine for PrEP. Renal and liver function were assessed from electronic medical records. Among 50 participants (98% male, median 32 years, 52% White, on PrEP for a median 4.4 years), 72% reported lifetime APES use, with 52% currently using APES (median 1.5 products/person) and 28% never used APES. The most common products included whey protein, creatine supplements and anabolic steroids. The primary reason for APES use was to increase muscle mass. Three (12%) current APES users had elevated serum creatinine (stage 1) versus zero (0%) in the non-APES group. Two (8%) current APES users experienced grade 3–4 ALT/AST elevations versus zero (0%) in the non-APES group. APES usage among gbMSM taking PrEP was high and may be associated with liver/renal lab abnormalities. Increased awareness of APES use and potential toxicity is encouraged to enhance safety. [ABSTRACT FROM AUTHOR]

Background Toxoplasmic encephalitis (TE) is an opportunistic infection of people with human immunodeficiency virus (HIV) or other causes of immunosuppression. Guideline-recommended treatments for TE are pyrimethamine and sulfadiazine (P-S) or pyrimethamine and clindamycin (P-C); however, a substantial price increase has limited access to pyrimethamine. Consequently, some centers have transitioned to trimethoprim-sulfamethoxazole (TMP-SMX), an inexpensive alternative treatment. We aimed to review the evidence on the efficacy and safety of pyrimethamine-containing therapies vs TMP-SMX. Methods We searched for and included randomized controlled trials (RCTs) and observational studies of TE treatments, regardless of HIV status. Data for each therapy were pooled by meta-analysis to assess the proportions of patients who experienced clinical and radiologic responses to treatment, all-cause mortality, and discontinuation due to toxicity. Sensitivity analyses limited to RCTs directly compared therapies. Results We identified 6 RCTs/dose-escalation studies and 26 single-arm/observational studies. Identified studies included only persons with HIV, and most predated modern antiretroviral treatment. Pooled proportions of clinical and radiologic response and mortality were not significantly different between TMP-SMX and pyrimethamine-containing regimens (P >.05). Treatment discontinuation due to toxicity was significantly lower in TMP-SMX (7.3%; 95% confidence interval [CI], 4.7–11.4; I2 = 0.0%) vs P-S (30.5%; 95% CI, 27.1–34.2; I2 = 0.0%; P <.01) or P-C (13.7%; 95% CI, 9.8–18.8; I2 = 32.0%; P =.031). These results were consistent in analyses restricted to RCT data. Conclusions TMP-SMX appears to be as effective and safer than pyrimethamine-containing regimens for TE. These findings support modern RCTs comparing TMP-SMX to pyrimethamine-based therapies and a revisiting of the guidelines. [ABSTRACT FROM AUTHOR]

Background A multi-country outbreak caused by monkeypox virus (MPXV) has been unfolding across endemic and non-endemic countries since May 2022. Throughout April and May 2022, Nigeria reported 31 MPXV cases, of which 11 were confirmed via testing. In May 2022, three internationally exported cases of MPXV, presumed to have originated in Nigeria, were reported, suggesting that a larger than reported outbreak might be occurring in the country. Methods We used previously established methods to estimate the true size of the MPXV outbreak in Nigeria. We estimated the incidence rate of exported MPXV cases among all outbound international air travellers from Nigeria during the time period of April and May 2022, using forecasted air traveller volumes. We then applied this incidence rate to the entire population of Nigeria during April and May 2022 assuming that the rate of infection was the same in Nigeria for both travellers and the resident population. Information on the subset of population that were considered to be travellers was obtained from the United Nations World Tourism Organization (UNWTO). Results We estimated that there were approximately 4000 (N  = 4013; 95% CI: 828–11 728) active cases of MPXV in Nigeria in April and May 2022. This is approximately 360-fold greater than the confirmed number and approximately 130-fold greater than the reported number of cases in Nigeria. Conclusion Our findings suggest that a larger outbreak than is appreciated may be ongoing in Nigeria. The observed international spread of MPXV offers important insights into the scale of the epidemic at its origin, where clinical detection and disease surveillance may be limited. These findings highlight the need to expand and support clinical, laboratory, and public health capacity to enable earlier detection of epidemics of international significance. [ABSTRACT FROM AUTHOR]

In the natural history of infection, symptoms begin 3-4 weeks after exposure, but detectable sero-conversion with the appearance of anti-HCV IgG antibodies occurs around 8-11 weeks for most people.[3] Therefore, a negative anti-HCV antibody test early in the course of acute hepatitis does not rule out acute HCV infection. Acute infection with hepatitis C virus (HCV) is a cause of severe acute hepatitis. In acute HCV infection, testing by polymerase chain reaction (PCR) returns positive results, but results from tests of anti-HCV antibodies are typically negative for several weeks after exposure. Some public health laboratories allow for HCV PCR testing only if the anti-HCV antibody test result is positive, which can make diagnosing acute HCV infection challenging. [Extracted from the article]

In recent months, more studies are emerging regarding how various nations and regions fared during the initial two years of the COVID-19 pandemic. Canada is cited as an example of a country that had performed reasonably well versus other countries with comparable infrastructures and health care systems (Razek et al., 2022). The reason is largely attributed to a combination of several public health measures coupled with widespread vaccination uptake, as a result of a country-wide vaccination campaign. This paper is based on a keynote talk given at the Autumn 2021 CJRES Annual Conference, by Dr. Isaac I. Bogoch. Dr Bogoch is an Associate Professor in the Department of Medicine at the University of Toronto, and an Infectious Diseases Consultant in the Division of Infectious Diseases at the Toronto General Hospital. Dr. Bogoch was a member of Ontario's Vaccine Distribution Taskforce, which helped guide vaccine policy during the initial rollout of COVID-19 vaccines between December 2020 through August 2021. Dr. Bogoch explains the unique vaccine policy in the Province of Ontario and in particular the social innovation around prioritising the most vulnerable and disadvantaged neighbourhoods first, thus leading to an important intra-regional social policy view of vaccine efforts on the path beyond the 'emergency phase' of the COVID-19 pandemic. What is clearly obvious from his presentation is the heightened role of urban geography tools and techniques and intra-regional policy in vaccine equity efforts. Policy lessons learned in Ontario may help us sort out future urban, social, economic, epidemiologic and public health challenges and their sometimes-complex intersections in regions, economy and society. The following is an edited transcript from Dr. Bogoch's talk. [ABSTRACT FROM AUTHOR]

Background: Gay, bisexual, and other men-who-have-sex-with-men (GBMSM) continue to be disproportionately affected by Human Immunodeficiency Virus (HIV). Although HIV pre-exposure prophylaxis (PrEP) offers an effective means of reducing incident HIV among this population, the HIV-preventive success of oral-based PrEP is contingent upon regimen adherence. Elevated rates of alcohol-, substance use-, and mental health-related issues among GBMSM potentially hinder PrEP-taking efforts, however the evidence for this remains mixed. Accordingly, the present study entailed a comprehensive qualitative investigation to explore PrEP-prescribed GBMSM's perceptions surrounding the influence of alcohol, substance use, and mental health on PrEP adherence.Methods: PrEP-prescribed GBMSM (age ≥ 18 years; prescribed PrEP for ≥ 3 months) were recruited from two PrEP-delivery clinics in Toronto, Canada for focus groups as part of the formative phase of an alcohol-, substance use-, and mental health-focused randomized controlled intervention trial. Focus group discussions qualitatively explored perceived strengths and barriers associated with adherence to PrEP treatment; with an emphasis on alcohol, substance use, and mental health concerns. Condom use among PrEP-prescribed GBMSM within the context of these concerns was also discussed.Results: A total of five focus groups involving 35 GBMSM were conducted (4-10/group; mean age = 42.4; white = 71.4%). Although participants themselves generally reported successfully adhering to their PrEP regimens-resulting from a strong, underlying motivation for self-care-they recognized the detrimental impact that alcohol, substance use, and mental health had on adherence among their peers. In this regard, alcohol and substances were perceived as detracting from adherence only when consumption was excessive or temporally linked to PrEP dosing. Pronounced mental health issues (e.g., severe depression) were also seen as hindering adherence, although these effects were nuanced and perceived as person-dependent. Alcohol and substances were linked to condomless sex, regardless of PrEP use, and PrEP was therefore viewed as an HIV-protective 'safety net.'Conclusions: Overall, findings suggest that PrEP adherence can often be successfully achieved in the presence of alcohol-, substance use-, and mental health-related issues. Augmenting self-care, and addressing pronounced addictions- and mental health-related concerns, may enhance PrEP treatment among GBMSM. [ABSTRACT FROM AUTHOR]

We aimed to determine whether early public health interventions in 2020 mitigated the association of sociodemographic and clinical risk factors with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a population-based cohort study of all adults in Ontario, Canada who underwent testing for SARS-CoV-2 through December 31, 2020. The outcome was laboratory-confirmed SARS-CoV-2 infection, determined by reverse transcription polymerase chain reaction testing. Adjusted odds ratios (ORs) were determined for sociodemographic and clinical risk factors before and after the first-wave peak of the pandemic to assess for changes in effect sizes. Among 3,167,753 community-dwelling individuals, 142,814 (4.5%) tested positive. The association between age and SARS-CoV-2 infection risk varied over time (P-interaction < 0.0001). Prior to the first-wave peak, SARS-CoV-2 infection increased with age whereas this association reversed thereafter. Risk factors that persisted included male sex, residing in lower income neighborhoods, residing in more racially/ethnically diverse communities, immigration to Canada, hypertension, and diabetes. While there was a reduction in infection rates after mid-April 2020, there was less impact in regions with higher racial/ethnic diversity. Immediately following the initial peak, individuals living in the most racially/ethnically diverse communities with 2, 3, or ≥ 4 risk factors had ORs of 1.89, 3.07, and 4.73-fold higher for SARS-CoV-2 infection compared to lower risk individuals in their community (all P < 0.0001). In the latter half of 2020, this disparity persisted with corresponding ORs of 1.66, 2.48, and 3.70-fold higher, respectively. In the least racially/ethnically diverse communities, there was little/no gradient in infection rates across risk strata. Further efforts are necessary to reduce the risk of SARS-CoV-2 infection among the highest risk individuals residing in the most racially/ethnically diverse communities. [ABSTRACT FROM AUTHOR]

The article discusses the highly pathogenic avian influenza (HPAI) H5N1 virus, which is spread globally by wild birds. The virus has caused outbreaks among poultry farms and backyard flocks, as well as die-offs among wild birds. While there have been no reported human cases of H5N1 acquired in Canada, nearly 900 human cases have been reported globally since 2003, with a case fatality rate of 52%. The article emphasizes the importance of clinicians asking about animal exposures in people presenting with influenza-like illness and highlights the need for early identification of patients with exposure histories. Currently, there is no vaccine for human use in Canada, but Oseltamivir is recommended for treatment and prophylaxis of HPAI infection. [Extracted from the article]

The article discusses the concept of postexposure prophylaxis-in-pocket (PIP), which is an HIV prevention method for individuals with infrequent exposure to the virus. Clinicians are advised to proactively identify eligible individuals and provide them with a 28-day supply of guideline-approved PEP regimens before potential exposure. After a potential exposure, individuals should self-initiate PIP as soon as possible and seek follow-up testing. PIP fills a gap in HIV prevention between traditional PEP and pre-exposure prophylaxis (PrEP), and it can be particularly beneficial for individuals with higher risk factors or limited access to urgent care. The article suggests that advance prescription and procurement of PIP can help alleviate barriers to accessing care and medications. [Extracted from the article]

Patients admitted to the ICU with critical COVID-19 often require prolonged periods of mechanical ventilation. Difficulty weaning, lack of progress, and clinical deterioration are commonly encountered. These conditions should prompt a thorough evaluation for persistent or untreated manifestations of COVID-19, as well as complications from COVID-19 and its various treatments. Inflammation may persist and lead to fibroproliferative changes in the lungs. Infectious complications may arise including bacterial superinfection in the earlier stages of disease. Use of immunosuppressants may lead to the dissemination of latent infections, and to opportunistic infections. Venous thromboembolic disease is common, as are certain neurologic manifestations of COVID-19 including delirium and stroke. High levels of ventilatory support may lead to ventilator-induced injury to the lungs and diaphragm. We present diagnostic and therapeutic considerations for the mechanically ventilated patient with COVID-19 who shows persistent or worsening signs of critical illness, and we offer an approach to treating this complex but common scenario. [ABSTRACT FROM AUTHOR]

Background: Enteric parasites are endemic in many of the countries from which refugees originate. Clinical guidelines vary in approaches to screening for and treating intestinal parasites in refugee receiving countries. This study aims to investigate the prevalence and species of intestinal parasites identified in stool ova and parasite (O&P) specimens in a sample of newly arrived refugees in Toronto, Canada.Methods: We conducted a retrospective chart review of 1042 refugee patients rostered at a specialized primary care clinic in Toronto from December 2011 to September 2016. Patients who completed recommended stool O&P analyses were included. Basic sociodemographic and clinical variables and results of stool O&P were examined.Results: 419 patients (40.2%) had a stool O&P positive for any protozoan or helminth species. Sixty-nine patients (6.6%) had clinically significant parasite species (excluding B hominis, D fragilis, and E dispar, given their lower risk for causing symptoms/complications): 2.3% had clinically significant protozoans and 4.2% had helminths on stool analysis.Conclusion: Given the relatively low prevalence of clinically significant parasites identified, our findings do not support universal screening for enteric parasites with stool O&P among refugee claimants/asylum seekers. However, stool analysis should be considered in certain clinical situations, as part of a more tailored approach. [ABSTRACT FROM AUTHOR]

Background: Limitations in laboratory diagnostic capacity impact population surveillance of COVID-19. It is currently unknown whether participatory surveillance tools for COVID-19 correspond to government-reported case trends longitudinally and if it can be used as an adjunct to laboratory testing. The primary objective of this study was to determine whether self-reported COVID-19-like illness reflected laboratory-confirmed COVID-19 case trends in Ontario Canada. Methods: We retrospectively analyzed longitudinal self-reported symptoms data collected using an online tool–Outbreaks Near Me (ONM)–from April 20th, 2020, to March 7th, 2021 in Ontario, Canada. We measured the correlation between COVID-like illness among respondents and the weekly number of PCR-confirmed COVID-19 cases and provincial test positivity. We explored contemporaneous changes in other respiratory viruses, as well as the demographic characteristics of respondents to provide context for our findings. Results: Between 3,849–11,185 individuals responded to the symptom survey each week. No correlations were seen been self-reported CLI and either cases or test positivity. Strong positive correlations were seen between CLI and both cases and test positivity before a previously documented rise in rhinovirus/enterovirus in fall 2020. Compared to participatory surveillance respondents, a higher proportion of COVID-19 cases in Ontario consistently came from low-income, racialized and immigrant areas of the province- these groups were less well represented among survey respondents. Interpretation: Although digital surveillance systems are low-cost tools that have been useful to signal the onset of viral outbreaks, in this longitudinal comparison of self-reported COVID-like illness to Ontario COVID-19 case data we did not find this to be the case. Seasonal respiratory virus transmission and population coverage may explain this discrepancy. [ABSTRACT FROM AUTHOR]

Scientists across disciplines, policymakers, and journalists have voiced frustration at the unprecedented polarization and misinformation around coronavirus disease 2019 (COVID-19) pandemic. Several false dichotomies have been used to polarize debates while oversimplifying complex issues. In this comprehensive narrative review, we deconstruct six common COVID-19 false dichotomies, address the evidence on these topics, identify insights relevant to effective pandemic responses, and highlight knowledge gaps and uncertainties. The topics of this review are: 1) Health and lives vs. economy and livelihoods, 2) Indefinite lockdown vs. unlimited reopening, 3) Symptomatic vs. asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, 4) Droplet vs. aerosol transmission of SARS-CoV-2, 5) Masks for all vs. no masking, and 6) SARS-CoV-2 reinfection vs. no reinfection. We discuss the importance of multidisciplinary integration (health, social, and physical sciences), multilayered approaches to reducing risk ("Emmentaler cheese model"), harm reduction, smart masking, relaxation of interventions, and context-sensitive policymaking for COVID-19 response plans. We also address the challenges in understanding the broad clinical presentation of COVID-19, SARS-CoV-2 transmission, and SARS-CoV-2 reinfection. These key issues of science and public health policy have been presented as false dichotomies during the pandemic. However, they are hardly binary, simple, or uniform, and therefore should not be framed as polar extremes. We urge a nuanced understanding of the science and caution against black-or-white messaging, all-or-nothing guidance, and one-size-fits-all approaches. There is a need for meaningful public health communication and science-informed policies that recognize shades of gray, uncertainties, local context, and social determinants of health. [ABSTRACT FROM AUTHOR]

Background: Aggressive non-pharmaceutical interventions (NPIs) may reduce transmission of SARS-CoV-2. The extent to which these interventions are successful in stopping the spread have not been characterized in countries with distinct socioeconomic groups. We compared the effects of a partial lockdown on disease transmission among Kuwaitis (P1) and non-Kuwaitis (P2) living in Kuwait.Methods: We fit a modified metapopulation SEIR transmission model to reported cases stratified by two groups to estimate the impact of a partial lockdown on the effective reproduction number ([Formula: see text]). We estimated the basic reproduction number ([Formula: see text]) for the transmission in each group and simulated the potential trajectories of an outbreak from the first recorded case of community transmission until 12 days after the partial lockdown. We estimated [Formula: see text] values of both groups before and after the partial curfew, simulated the effect of these values on the epidemic curves and explored a range of cross-transmission scenarios.Results: We estimate [Formula: see text] at 1·08 (95% CI: 1·00-1·26) for P1 and 2·36 (2·03-2·71) for P2. On March 22nd, [Formula: see text] for P1 and P2 are estimated at 1·19 (1·04-1·34) and 1·75 (1·26-2·11) respectively. After the partial curfew had taken effect, [Formula: see text] for P1 dropped modestly to 1·05 (0·82-1·26) but almost doubled for P2 to 2·89 (2·30-3·70). Our simulated epidemic trajectories show that the partial curfew measure greatly reduced and delayed the height of the peak in P1, yet significantly elevated and hastened the peak in P2. Modest cross-transmission between P1 and P2 greatly elevated the height of the peak in P1 and brought it forward in time closer to the peak of P2.Conclusion: Our results indicate and quantify how the same lockdown intervention can accentuate disease transmission in some subpopulations while potentially controlling it in others. Any such control may further become compromised in the presence of cross-transmission between subpopulations. Future interventions and policies need to be sensitive to socioeconomic and health disparities. [ABSTRACT FROM AUTHOR]

Although antigen tests are not perfect as diagnostic tests, they are a helpful and currently underutilized public health screening tool in Canada's COVID-19 response. More meaningful than test accuracy is the extent to which rapid antigen testing identifies cases of COVID-19 during the infectious period and whether ongoing transmission is reduced. With this context and goal, test sensitivity of rapid antigen tests compared with testing using reverse transcription-polymerase chain reaction (RT-PCR) is only 1 important characteristic, and a sole focus on sensitivity is misguided. [Extracted from the article]

Pre-exposure prophylaxis (PrEP) is traditionally prescribed by HIV specialist physicians. Given finite specialist resources, there is a need to scale up PrEP delivery by decentralizing services via other healthcare professionals. We aimed to assess the feasibility of delivering PrEP to men who have sex with men (MSM) through primary care physicians and sexual health clinic nurses. We piloted a multi-component, implementation and dissemination research program to increase provision of PrEP through primary care physicians and sexual health clinic nurses in Toronto, Canada. Community-based organizations (CBOs) provided prospective participants with information cards that contained links to an online module on engaging providers in a conversation about PrEP. In our patient-initiated continuing medical education (PICME) strategy, participants saw their family doctors and gave them the card, which also contained a link to a Continuing Medical Education module. In the nurse-led strategy, participants visited one of two participating clinics to obtain PrEP. We administered an optional online questionnaire to patients and providers at baseline and six months. CBOs distributed 3043 cards. At least 339 men accessed the online module and 196 completed baseline questionnaires. Most (55%) intended to visit nurses while 21% intended to consult their physicians. Among 45 men completing follow-up questionnaires at 6 months, 31% reported bringing cards to their physicians and obtaining PrEP through them; sexual health clinics delivered PrEP to 244 patients. Participants who went through the PICME approach reported no changes in relationships with their providers. Nurses showed fidelity to PrEP prescribing guidelines. Nurse-led PrEP and patient-initiated continuing medical education (PICME) for primary care physicians are feasible strategies to increase PrEP uptake. Nurse-led PrEP delivery was preferred by most patients. [ABSTRACT FROM AUTHOR]

Background: Although HIV pre-exposure prophylaxis (PrEP) substantially diminishes the likelihood of HIV acquisition, poor adherence can decrease the HIV-protective benefits of PrEP. The present investigation sought to identify the extent to which alcohol consumption, substance use, and depression were linked to PrEP nonadherence among gay, bisexual, and other men-who-have-sex-with-men (gbMSM).Methods: gbMSM (age ≥ 18, prescribed PrEP for ≥3 months) were recruited from two clinics in Toronto, Canada for an e-survey assessing demographics; PrEP nonadherence (4-day PrEP-focused ACTG assessment); hazardous and harmful alcohol use (AUDIT scores of 8-15 and 16+, respectively); moderate/high risk substance use (NIDA M-ASSIST scores > 4); depression (CESD-10 scores ≥10); and other PrEP-relevant factors. The primary outcome, PrEP nonadherence, entailed missing one or more PrEP doses over the past 4 days. A linear-by-linear test of association assessed whether increasing severity of alcohol use (i.e., based on AUDIT categories) was linked to a greater occurrence of PrEP nonadherence. Univariate logistic regression was employed to determine factors associated with PrEP nonadherence, and factors demonstrating univariate associations at the p < .10 significance level were included in a multivariate logistic regression model. Additive and interactive effects involving key significant factors were assessed through logistic regression to evaluate potential syndemic-focused associations.Results: A total of 141 gbMSM (Mean age = 37.9, white = 63.1%) completed the e-survey. Hazardous/harmful drinking (31.9%), moderate/high risk substance use (43.3%), and depression (23.7%) were common; and one in five participants (19.9%) reported PrEP nonadherence. Increasing alcohol use level was significantly associated with a greater likelihood of nonadherence (i.e., 15.6, 25.0, and 44.4% of low-risk, hazardous, and harmful drinkers reported nonadherence, respectively (χ2(1) = 4.79, p = .029)). Multivariate logistic regression demonstrated that harmful alcohol use (AOR = 6.72, 95%CI = 1.49-30.33, p = .013) and moderate/high risk cocaine use (AOR = 3.11, 95%CI = 1.01-9.59, p = .049) independently predicted nonadherence. Furthermore, an additive association emerged, wherein the likelihood of PrEP nonadherence was highest among those who were hazardous/harmful drinkers and moderate/high risk cocaine users (OR = 2.25, 95%CI = 1.19-4.25, p = .013). Depression was not associated with nonadherence.Conclusions: Findings highlight the need to integrate alcohol- and substance-focused initiatives into PrEP care for gbMSM. Such initiatives, in turn, may help improve PrEP adherence and reduce the potential for HIV acquisition among this group. [ABSTRACT FROM AUTHOR]

Background Enteric fever can lead to prolonged hospital stays, clinical complications, and death. The Surveillance for Enteric Fever in Asia Project (SEAP), a prospective surveillance study, characterized the burden of enteric fever, including illness severity, in selected settings in Bangladesh, Nepal, and Pakistan. We assessed disease severity, including hospitalization, clinical complications, and death among SEAP participants. Methods We analyzed clinical and laboratory data from blood culture–confirmed enteric fever cases enrolled in SEAP hospitals and associated network laboratories from September 2016 to September 2019. We used hospitalization and duration of hospital stay as proxies for severity. We conducted a follow-up interview 6 weeks after enrollment to ascertain final outcomes. Results Of the 8705 blood culture-confirmed enteric fever cases enrolled, we identified 6 deaths (case-fatality ratio,.07%; 95% CI,.01–.13%), 2 from Nepal, 4 from Pakistan, and none from Bangladesh. Overall, 1.7% (90/5205) of patients recruited from SEAP hospitals experienced a clinical complication (Bangladesh, 0.6% [18/3032]; Nepal, 2.3% [12/531]; Pakistan, 3.7% [60/1642]). The most identified complications were hepatitis (n = 36), septic shock (n = 22), and pulmonary complications/pneumonia (n = 13). Across countries, 32% (2804/8669) of patients with hospitalization data available were hospitalized (Bangladesh, 27% [1295/4868]; Nepal, 29% [455/1595]; Pakistan, 48% [1054/2206]), with a median hospital stay of 5 days (IQR, 3–7). Conclusions While defined clinical complications and deaths were uncommon at the SEAP sites, the high proportion of hospitalizations and prolonged hospital stays highlight illness severity and the need for enteric fever control measures, including the use of typhoid conjugate vaccines. [ABSTRACT FROM AUTHOR]

Background Antibiotic use prior to seeking care at a hospital may reduce the sensitivity of blood culture for enteric fever, with implications for both clinical care and surveillance. The Surveillance for Enteric Fever in Asia Project (SEAP) is a prospective study of enteric fever incidence in Nepal, Bangladesh, and Pakistan. Nested within SEAP, we evaluated the accuracy of self-reported antibiotic use and investigated the association between antibiotic use and blood culture positivity. Methods Between November 2016 and April 2019, we collected urine samples among a subset of SEAP participants to test for antibiotic use prior to the hospital visit using an antibacterial activity assay. All participants were asked about recent antibiotic use and had a blood culture performed. We used mixed-effect logit models to evaluate the effect of antimicrobial use on blood culture positivity, adjusted for markers of disease severity. Results We enrolled 2939 patients with suspected enteric fever. Antibiotics were detected in 39% (1145/2939) of urine samples. The correlation between measured and reported antibiotic use was modest (κ = 0.72). After adjusting for disease severity, patients with antibiotics in their urine were slightly more likely to be blood culture positive for enteric fever; however, the effect was not statistically significant (prevalence ratio, 1.22 [95% confidence interval,.99–1.50]). Conclusions The reliability of self-reported prior antibiotic use was modest among individuals presenting with fever to tertiary hospitals. While antibiotics are likely to reduce the sensitivity of blood culture, our findings indicate that there is still considerable value in performing blood culture for individuals reporting antibiotic use. [ABSTRACT FROM AUTHOR]

Background Blood culture is the current standard for diagnosing bacteremic illnesses, yet it is not clear how physicians in many low- and middle-income countries utilize blood culture for diagnostic purposes and to inform treatment decisions. Methods We screened suspected enteric fever cases from 6 hospitals in Bangladesh, Nepal, and Pakistan, and enrolled patients if blood culture was prescribed by the treating physician. We used generalized additive regression models to analyze the probability of receiving blood culture by age, and linear regression models to analyze changes by month to the proportion of febrile cases prescribed a blood culture compared with the burden of febrile illness, stratified by hospital. We used logistic regression to analyze predictors for receiving antibiotics empirically. We descriptively reviewed changes in antibiotic therapy by susceptibility patterns and coverage, stratified by country. Results We screened 30 809 outpatients resulting in 1819 enteric fever cases; 1935 additional cases were enrolled from other hospital locations. Younger outpatients were less likely to receive a blood culture. The association between the number of febrile outpatients and the proportion prescribed blood culture varied by hospital. Antibiotics prescribed empirically were associated with severity and provisional diagnoses, but 31% (1147/3754) of enteric fever cases were not covered by initial therapy; this was highest in Pakistan (50%) as many isolates were resistant to cephalosporins, which were commonly prescribed empirically. Conclusions Understanding hospital-level communication between laboratories and physicians may improve patient care and timeliness of appropriate antibiotics, which is important considering the rise of antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Background Characterizing healthcare-seeking patterns for acute febrile illness is critical for generating population-based enteric fever incidence estimates from facility-based surveillance data. Methods We used a hybrid model in the Surveillance for Enteric Fever in Asia Project (SEAP) to assess incidence of enteric fever at 6 study hospitals in 3 countries. We recruited individuals presenting to the hospitals and obtained blood cultures to evaluate for enteric fever. For this analysis, we undertook cluster random household surveys in Dhaka, Bangladesh (2 sites); Karachi, Pakistan; Kathmandu, Nepal; and Kavrepalanchok, Nepal between January 2017 and February 2019, to ascertain care-seeking behavior for individuals with 1) fever for ≥3 consecutive days within the past 8 weeks; or 2) fever resulting in hospitalization within the past year. We also collected data about disease severity and household demographics and assets. We used mixed-effect multivariable logistic regression models to identify determinants of healthcare seeking at study hospitals and determinants of culture-confirmed enteric fever. Results We enrolled 31 841 households (53 926 children) in Bangladesh, 25 510 households (84 196 children and adults) in Nepal, and 21 310 households (108 031 children and adults) in Pakistan. Children <5 years were most likely to be taken to the study hospitals for febrile illness at all sites. Household wealth was positively correlated with healthcare seeking in 4 of 5 study sites, and at least one marker of disease severity was positively associated with healthcare seeking in 3 of 5 catchment areas. Wealth and disease severity were variably predictive of blood culture-confirmed enteric fever. Conclusions Age, household wealth, and disease severity are important determinants of healthcare seeking for acute febrile illness and enteric fever risk in these communities, and should be incorporated into estimation models for enteric fever incidence. [ABSTRACT FROM AUTHOR]

Background Typhoid fever is endemic in the urban Kathmandu Valley of Nepal; however, there have been no population-based studies of typhoid outside of this community in the past 3 decades. Whether typhoid immunization should be prioritized in periurban and rural communities has been unclear. Methods We performed population-based surveillance for enteric fever in 1 urban catchment (Kathmandu) and 1 periurban and rural catchment (Kavrepalanchok) as part of the Surveillance for Enteric Fever in Asia Project (SEAP). We recruited individuals presenting to outpatient and emergency departments at 2 study hospitals with suspected enteric fever and performed blood cultures. Additionally, we conducted a household survey in each catchment area to characterize care seeking for febrile illness. We evaluated spatial heterogeneity in febrile illness, care seeking, and enteric fever incidence. Results Between September 2016 and September 2019, we enrolled 5736 participants with suspected enteric fever at 2 study hospitals. Among these, 304 (5.3%) were culture positive for Salmonella Typhi (249 [81.9%]) or Paratyphi A (55 [18.1%]). Adjusted typhoid incidence in Kathmandu was 484 per 100 000 person-years and in Kavrepalanchok was 615 per 100 000 person-years. While all geographic areas for which estimates could be made had incidence >200 per 100 000 person-years, we observed spatial heterogeneity with up to 10-fold variation in incidence between communities. Conclusions In urban, periurban, and rural communities in and around Kathmandu, we measured a high but heterogenous incidence of typhoid. These findings provide some support for the introduction of conjugate vaccines in Nepal, including outside urban areas, alongside other measures to prevent enteric fever. [ABSTRACT FROM AUTHOR]

Background Implementation of population-based surveys is resource intensive and logistically demanding, especially in areas with rapidly changing demographics and incomplete or no enumeration of the underlying population and their residences. To remove the need for pre-enumeration and to simplify field logistics for the population healthcare utilization survey used for the Surveillance for Enteric Fever in Asia Project in Nepal, we incorporated a geographic information system–based geosurvey and field mapping system into a single-stage cluster sampling approach. Methods A survey was administered to ascertain healthcare-seeking behavior in individuals with recent suspected enteric fever. Catchment areas were based on residential addresses of enteric fever patients using study facilities; clusters were randomly selected from digitally created grids using available satellite images and all households within clusters were offered enrollment. A tablet-compatible geosurvey and mapping system that allowed for data-syncing and use in areas without cellular data was created using the ArcGIS suite of software. Results Between January 2017 and November 2018, we surveyed 25 521 households in Nepal (16 769 in urban Kathmandu and 8752 in periurban Kavrepalanchok), representing 84 202 individuals. Overall, the survey participation rate was 90.9%, with geographic heterogeneity in participation rates within each catchment area. Areas with higher average household wealth had lower participation rates. Conclusion A geographic information system–based geosurvey and field mapping system allowed creation of a virtual household map at the same time as survey administration, enabling a single-stage cluster sampling method to assess healthcare utilization in Nepal for the Surveillance for Enteric Fever in Asia Project. This system removed the need for pre-enumeration of households in sampling areas, simplified logistics and could be replicated in future community surveys. [ABSTRACT FROM AUTHOR]

Background Enteric fever, a bacterial infection caused by Salmonella enterica serotypes Typhi and Paratyphi A, frequently presents as a nonlocalizing febrile illness that is difficult to distinguish from other infectious causes of fever. Blood culture is not widely available in endemic settings and, even when available, results can take up to 5 days. We evaluated the diagnostic performance of clinical features, including both reported symptoms and clinical signs, of enteric fever among patients participating in the Surveillance for Enteric Fever in Asia Project (SEAP), a 3-year surveillance study in Bangladesh, Nepal, and Pakistan. Methods Outpatients presenting with ≥3 consecutive days of reported fever and inpatients with clinically suspected enteric fever from all 6 SEAP study hospitals were eligible to participate. We evaluated the diagnostic performance of select clinical features against blood culture results among outpatients using mixed-effect regression models with a random effect for study site hospital. We also compared the clinical features of S. Typhi to S. Paratyphi A among both outpatients and inpatients. Results We enrolled 20 899 outpatients, of whom 2116 (10.1%) had positive blood cultures for S. Typhi and 297 (1.4%) had positive cultures for S. Paratyphi A. The sensitivity of absence of cough was the highest among all evaluated features, at 65.5% (95% confidence interval [CI], 55.0–74.7), followed by measured fever at presentation at 59.0% (95% CI, 51.6–65.9) and being unable to complete normal activities for 3 or more days at 51.0% (95% CI, 23.8–77.6). A combined case definition of 3 or more consecutive days of reported fever and 1 or more of the following (a) either the absence of cough, (b) fever at presentation, or (c) 3 or more consecutive days of being unable to conduct usual activity--yielded a sensitivity of 94.6% (95% CI, 93.4–95.5) and specificity of 13.6% (95% CI, 9.8–17.5). Conclusions Clinical features do not accurately distinguish blood culture–confirmed enteric fever from other febrile syndromes. Rapid, affordable, and accurate diagnostics are urgently needed, particularly in settings with limited or no blood culture capacity. [ABSTRACT FROM AUTHOR]

Background: Syndromic surveillance through web or phone-based polling has been used to track the course of infectious diseases worldwide. Our study objective was to describe the characteristics, symptoms, and self-reported testing rates of respondents in three different COVID-19 symptom surveys in Canada. Methods: This was a cross-sectional study using three distinct Canada-wide web-based surveys, and phone polling in Ontario. All three sources contained self-reported information on COVID-19 symptoms and testing. In addition to describing respondent characteristics, we examined symptom frequency and the testing rate among the symptomatic, as well as rates of symptoms and testing across respondent groups. Results: We found that over March- April 2020, 1.6% of respondents experienced a symptom on the day of their survey, 15% of Ontario households had a symptom in the previous week, and 44% of Canada-wide respondents had a symptom in the previous month. Across the three surveys, SARS-CoV-2-testing was reported in 2–9% of symptomatic responses. Women, younger and middle-aged adults (versus older adults) and Indigenous/First nations/Inuit/Métis were more likely to report at least one symptom, and visible minorities were more likely to report the combination of fever with cough or shortness of breath. Interpretation: The low rate of testing among those reporting symptoms suggests significant opportunity to expand testing among community-dwelling residents of Canada. Syndromic surveillance data can supplement public health reports and provide much-needed context to gauge the adequacy of SARS-CoV-2 testing rates. [ABSTRACT FROM AUTHOR]