Ramadan fasting outcome among high-risk patients.

BACKGROUND: There is a growing literature on guidelines regarding Ramadan fasting for chronic kidney disease (CKD) patients. However, most studies only consider the impact of fasting on renal function. This study additionally aims to assess factors influencing Ramadan fasting in patients with CKD. METHOD: This is a prospective before and after cohort study. CKD patients were counseled regarding fasting and followed-up post-Ramadan for renal function status, actual fasting behavior, and other relevant outcomes. RESULTS: Of the 360 patients who attended the pre-Ramadan consultation, 306 were reachable after Ramadan of whom 55.3% were female. Of these 306 67.1% reported that they had fasted, 4.9% had attempted to fast but stopped, and 28% did not fast at all. Of these 74 has a post-fasting kidney test. Of the patients, 68.1% had stage 3A CKD, 21.7% had stage 3B, 7.9% stage 4, and only 2% stage 5. Of those who fasted, 11.1% had a drop in Glomerular Filtration Rate (eGFR) of 20% or more. Those who did not fast (16.7%) presented a similar drop. Conversely, among the few who attempted to fast and had to stop, half showed a drop in eGFR of more than 20%. In linear regression, fasting was not associated with post-Ramadan eGFR, when controlling for age and baseline eGRF. There were 17 (5.6%) significant events, including one death. More significant events occurred among the group who fasted some of Ramadan days, 26.7% of the subjects experienced an adverse event-while 4.7% of the group who did not fast had a significant adverse event compared to 4.4% among those who fasted all Ramadan. CONCLUSION: Fasting was not a significant determining factor in renal function deterioration in the study's population, nor did it have any significant association with adverse events.

Mapping and characterising areas with high levels of HIV transmission in sub-Saharan Africa: A geospatial analysis of national survey data.

BACKGROUND: In the generalised epidemics of sub-Saharan Africa (SSA), human immunodeficiency virus (HIV) prevalence shows patterns of clustered micro-epidemics. We mapped and characterised these high-prevalence areas for young adults (15-29 years of age), as a proxy for areas with high levels of transmission, for 7 countries in Eastern and Southern Africa: Kenya, Malawi, Mozambique, Tanzania, Uganda, Zambia, and Zimbabwe. METHODS AND FINDINGS: We used geolocated survey data from the most recent United States Agency for International Development (USAID) demographic and health surveys (DHSs) and AIDS indicator surveys (AISs) (collected between 2008-2009 and 2015-2016), which included about 113,000 adults-of which there were about 53,000 young adults (27,000 women, 28,000 men)-from over 3,500 sample locations. First, ordinary kriging was applied to predict HIV prevalence at unmeasured locations. Second, we explored to what extent behavioural, socioeconomic, and environmental factors explain HIV prevalence at the individual- and sample-location level, by developing a series of multilevel multivariable logistic regression models and geospatially visualising unexplained model heterogeneity. National-level HIV prevalence for young adults ranged from 2.2% in Tanzania to 7.7% in Mozambique. However, at the subnational level, we found areas with prevalence among young adults as high as 11% or 15% alternating with areas with prevalence between 0% and 2%, suggesting the existence of areas with high levels of transmission Overall, 15.6% of heterogeneity could be explained by an interplay of known behavioural, socioeconomic, and environmental factors. Maps of the interpolated random effect estimates show that environmental variables, representing indicators of economic activity, were most powerful in explaining high-prevalence areas. Main study limitations were the inability to infer causality due to the cross-sectional nature of the surveys and the likely under-sampling of key populations in the surveys. CONCLUSIONS: We found that, among young adults, micro-epidemics of relatively high HIV prevalence alternate with areas of very low prevalence, clearly illustrating the existence of areas with high levels of transmission. These areas are partially characterised by high economic activity, relatively high socioeconomic status, and risky sexual behaviour. Localised HIV prevention interventions specifically tailored to the populations at risk will be essential to curb transmission. More fine-scale geospatial mapping of key populations,-such as sex workers and migrant populations-could help us further understand the drivers of these areas with high levels of transmission and help us determine how they fuel the generalised epidemics in SSA.

Trends and Predictors of Syphilis Prevalence in the General Population: Global Pooled Analyses of 1103 Prevalence Measures Including 136 Million Syphilis Tests.

Background: This study assessed levels, trends, and associations of observed syphilis prevalence in the general adult population using global pooled analyses. Methods: A standardized database of syphilis prevalence was compiled by pooling systematically gathered data. Random-effects meta-analyses and meta-regressions were conducted using data from the period 1990-2016 to estimate pooled measures and assess predictors and trends. Countries were classified by World Health Organization region. Sensitivity analyses were conducted. Results: The database included 1103 prevalence measures from 136 million syphilis tests across 154 countries (85% from women in antenatal care). Global pooled mean prevalence (weighted by region population size) was 1.11% (95% confidence interval [CI], .99-1.22). Prevalence predictors were region, diagnostic assay, sample size, and calendar year interacting with region. Compared to the African Region, the adjusted odds ratio (AOR) was 0.42 (95% CI, .33-.54) for the Region of the Americas, 0.13 (95% CI, .09-.19) for the Eastern Mediterranean Region, 0.05 (95% CI, .03-.07) for the European Region, 0.21 (95% CI, .16-.28) for the South-East Asia Region, and 0.41 (95% CI, .32-.53) for the Western Pacific Region. Treponema pallidum hemagglutination assay (TPHA) only or rapid plasma reagin (RPR) only, compared with dual RPR/TPHA diagnosis, produced higher prevalence (AOR >1.26), as did smaller sample-size studies (<500 persons) (AOR >2.16). Prevalence declined in all regions; the annual AORs ranged from 0.84 (95% CI, .79-.90) in the Eastern Mediterranean to 0.97 (95% CI, .97-1.01) in the Western Pacific. The pooled mean male-to-female prevalence ratio was 1.00 (95% CI, .89-1.13). Sensitivity analyses confirmed robustness of results. Conclusions: Syphilis prevalence has declined globally over the past 3 decades. Large differences in prevalence persist among regions, with the African Region consistently the most affected.

HIV and herpes simplex virus type 2 epidemiological synergy: misguided observational evidence? A modelling study.

OBJECTIVES: To investigate whether observational studies of HIV and herpes simplex virus type 2 (HSV-2) infections have the capacity to assess the HIV/HSV-2 epidemiological synergy. METHODS: An individual-based Monte Carlo model was used to simulate HIV/HSV-2 epidemics in two scenarios: no HIV/HSV-2 biological interaction and HSV-2 seropositivity enhancing HIV acquisition. Cross-sectional observational studies were simulated by sampling individuals from the population to assess resulting crude and adjusted ORs of the HIV/HSV-2 association. Meta-analyses were conducted to estimate the pooled mean ORs. Impact of under-reporting of sexual behaviour and miscapture of high-risk individuals was assessed through sensitivity analyses. RESULTS: Assuming no HIV/HSV-2 biological interaction, the crude HIV/HSV-2 OR ranged between 1.38 and 9.93, with a pooled mean of 6.45 (95% CI 5.81 to 7.17). Adjustment for the number of sexual partners over last year, over lifetime and for both partner numbers simultaneously reduced the mean OR to 5.45 (95% CI 4.90 to 6.06), 3.70 (95% CI 3.32 to 4.12) and 3.54 (95% CI 3.17 to 3.94), respectively. Assuming HIV/HSV-2 biological interaction, the crude OR ranged between 3.44 and 9.95, with a pooled mean of 8.05 (95% CI 7.14 to 9.07). The adjustments reduced the mean OR to 7.00 (95% CI 6.21 to 7.90), 3.76 (95% CI 3.32 to 4.25) and 3.68 (95% CI 3.25 to 4.17), respectively. Under-reporting of partners reduced the confounder-adjustment effects. Miscapture of high-risk individuals considerably lowered the estimated ORs. CONCLUSIONS: It is difficult to control for sexual-behaviour confounding in observational studies. The observed HIV/HSV-2 association appears more consistent with two infections sharing the same mode of transmission, rather than with HSV-2 enhancing HIV acquisition.

Measuring sexual behaviour in Malawi: a triangulation of three data collection instruments.

BACKGROUND: There is a need for valid approaches to measure sexual interactions to assess the impact of behavioural interventions and to predict the impact of behaviour changes. Different methods of asking about sexual behaviour often yield conflicting answers and men often report higher levels of heterosexual activity than women. To better understand self-reported sexual behaviour data and how best to collect it, we analyzed data collected as part of a larger project (ST IMPACTS) on the social and behavioural impact of introducing community-level HIV self-testing (HIVST) with counseling (semi-supervised with pre- and generic post-test counseling provided on delivery or collection of test kits) in an urban Malawian setting. METHODS: Information on sexual behaviour was collected from HIV self-testers over a three-month period. Three different methods were used: retrospective face-to-face interviews (FTFI); audio computer assisted self-interviews (ACASI) and a prospective coital diary. Both retrospective instruments were used before and after the three-month study period. Frequency and cross-tabulation, as well as scatterplots, were used for exploratory analyses. Chi-square tests were used to test for differences in proportions. Spearman's correlation coefficient was used to explore associations between both continuous and ordinal variables and Wilcoxon's paired sample and Mann-Whitney test was used to test for differences in such variables or between variables. RESULTS: There was reasonable agreement between the two retrospective methods although both yielded inconsistent answers e.g. with lower reported numbers of life-time sexual partners at the end than at the beginning of the study period. The diary method elicited higher reported levels of sex with multiple partners than both retrospective instruments which may be due to inadequate recall. Over the study period 37.4% of men and 19.7% of women reported multiple sexual partners using the diary. There was no clear relationship between reported sexual behaviour and HIV status (prevalence 9.6%). CONCLUSIONS: Diaries may therefore have higher validity for sensitive behaviour reporting and thus be the preferred method in similar African contexts in measuring sexual behaviours.

Estimating prevalence trends in adult gonorrhoea and syphilis in low- and middle-income countries with the Spectrum-STI model: results for Zimbabwe and Morocco from 1995 to 2016.

OBJECTIVE: To develop a tool for estimating national trends in adult prevalence of sexually transmitted infections by low- and middle-income countries, using standardised, routinely collected programme indicator data. METHODS: The Spectrum-STI model fits time trends in the prevalence of active syphilis through logistic regression on prevalence data from antenatal clinic-based surveys, routine antenatal screening and general population surveys where available, weighting data by their national coverage and representativeness. Gonorrhoea prevalence was fitted as a moving average on population surveys (from the country, neighbouring countries and historic regional estimates), with trends informed additionally by urethral discharge case reports, where these were considered to have reasonably stable completeness. Prevalence data were adjusted for diagnostic test performance, high-risk populations not sampled, urban/rural and male/female prevalence ratios, using WHO's assumptions from latest global and regional-level estimations. Uncertainty intervals were obtained by bootstrap resampling. RESULTS: Estimated syphilis prevalence (in men and women) declined from 1.9% (95% CI 1.1% to 3.4%) in 2000 to 1.5% (1.3% to 1.8%) in 2016 in Zimbabwe, and from 1.5% (0.76% to 1.9%) to 0.55% (0.30% to 0.93%) in Morocco. At these time points, gonorrhoea estimates for women aged 15-49 years were 2.5% (95% CI 1.1% to 4.6%) and 3.8% (1.8% to 6.7%) in Zimbabwe; and 0.6% (0.3% to 1.1%) and 0.36% (0.1% to 1.0%) in Morocco, with male gonorrhoea prevalences 14% lower than female prevalence. CONCLUSIONS: This epidemiological framework facilitates data review, validation and strategic analysis, prioritisation of data collection needs and surveillance strengthening by national experts. We estimated ongoing syphilis declines in both Zimbabwe and Morocco. For gonorrhoea, time trends were less certain, lacking recent population-based surveys.

Trends in Adult Chlamydia and Gonorrhea Prevalence, Incidence and Urethral Discharge Case Reporting in Morocco over 1995-2015-Estimates Using the Spectrum-Sexually Transmitted Infection Model.

BACKGROUND: Evolving health priorities and resource constraints mean that countries require data on sexually transmitted infections (STI) trends to inform program planning and resource allocation. METHODS: The Spectrum modeling tool estimated prevalence and incidence of gonorrhea and chlamydia in Morocco's 15- to 49-year-old population, based on prevalence surveys. Incident cases, broken down between symptomatic and asymptomatic, and treated versus untreated, were compared with urethral discharge (UD) case reports, to estimate reporting completeness among treated UD cases. RESULTS: Gonorrhea prevalence was estimated at 0.37% (95% confidence interval [CI], 0.14-1.0%) in women and 0.32% (0.12-0.87%) in men in 2015; chlamydia prevalences were 3.8% (95% CI, 2.1-6.4%) and 3.0% (95% CI, 1.7-5.1%). Corresponding estimated numbers of new cases in women and men in 2015 were 79,598 (95% CI, 23,918-256,206) and 112,013 (95% CI, 28,700-307,433) for gonorrhea, and 291,908 (95% CI, 161,064-524,270) and 314,032 (95% CI, 186,076-559,133) for chlamydia. Gonorrhea and chlamydia prevalence had declined by an estimated 41% and 27%, respectively, over 1995 to 2015. Prevalence declines probably related to improved STI treatment coverage, and decreasing risk behaviors. Reporting completeness among treated UD cases was estimated at 46% to 77% in 2015. Reported UD cases corresponded to 13% of all estimated (symptomatic and asymptomatic) gonorrhea and chlamydia cases. CONCLUSIONS: STI declines and improvements in treatment coverage are consistent with Morocco's introduction of syndromic management in 2000, scale-up of prevention, and declining human immunodeficiency virus incidence. While gonorrhea is four-fold more common as cause of clinical UD cases than chlamydia, Morocco continues to suffer a large, untreated burden of chlamydia. Reliable monitoring of both STIs requires new periodic surveys and/or novel forms of affordable surveillance beyond high-risk populations.

Respiratory Virus-Associated Severe Acute Respiratory Illness and Viral Clustering in Malawian Children in a Setting With a High Prevalence of HIV Infection, Malaria, and Malnutrition.

BACKGROUND: We used data from 4 years of pediatric severe acute respiratory illness (SARI) sentinel surveillance in Blantyre, Malawi, to identify factors associated with clinical severity and coviral clustering. METHODS: From January 2011 to December 2014, 2363 children aged 3 months to 14 years presenting to the hospital with SARI were enrolled. Nasopharyngeal aspirates were tested for influenza virus and other respiratory viruses. We assessed risk factors for clinical severity and conducted clustering analysis to identify viral clusters in children with viral codetection. RESULTS: Hospital-attended influenza virus-positive SARI incidence was 2.0 cases per 10 000 children annually; it was highest among children aged <1 year (6.3 cases per 10 000), and human immunodeficiency virus (HIV)-infected children aged 5-9 years (6.0 cases per 10 000). A total of 605 SARI cases (26.8%) had warning signs, which were positively associated with HIV infection (adjusted risk ratio [aRR], 2.4; 95% confidence interval [CI], 1.4-3.9), respiratory syncytial virus infection (aRR, 1.9; 95% CI, 1.3-3.0) and rainy season (aRR, 2.4; 95% CI, 1.6-3.8). We identified 6 coviral clusters; 1 cluster was associated with SARI with warning signs. CONCLUSIONS: Influenza vaccination may benefit young children and HIV-infected children in this setting. Viral clustering may be associated with SARI severity; its assessment should be included in routine SARI surveillance.

Repeat Use of Post-exposure Prophylaxis for HIV Among Nairobi-Based Female Sex Workers Following Sexual Exposure.

As ART-based prevention becomes available, effectively targeting these interventions to key populations such as female sex workers (FSW) will be critical. In this study we analyze patterns of repeated post-exposure prophylaxis (PEP) access in the context of a large FSW program in Nairobi. During close to 6000 person-years of follow-up, 20 % of participants (n = 1119) requested PEP at least once and 3.7 % requested PEP more than once. Repeat PEP users were younger, had a higher casual partner volume, and were more likely to use condoms with casual and regular partners, have a regular partner, and test for HIV prior to enrolment. Barriers to PEP included stigma, side effects, and lack of knowledge, suggesting repeated promotion may be required for higher rates of uptake. A small subset of FSW, potentially those with heightened risk perception, showed a higher frequency of PEP use; these individuals may be most amenable to rollout of pre-exposure prophylaxis.

The rise and fall of HIV in high-prevalence countries: a challenge for mathematical modeling.

Several countries with generalized, high-prevalence HIV epidemics, mostly in sub-Saharan Africa, have experienced rapid declines in transmission. These HIV epidemics, often with rapid onsets, have generally been attributed to a combination of factors related to high-risk sexual behavior. The subsequent declines in these countries began prior to widespread therapy or implementation of any other major biomedical prevention. This change has been construed as evidence of behavior change, often on the basis of mathematical models, but direct evidence for behavior changes that would explain these declines is limited. Here, we look at the structure of current models and argue that the common "fixed risk per sexual contact" assumption favors the conclusion of substantial behavior changes. We argue that this assumption ignores reported non-linearities between exposure and risk. Taking this into account, we propose that some of the decline in HIV transmission may be part of the natural dynamics of the epidemic, and that several factors that have traditionally been ignored by modelers for lack of precise quantitative estimates may well hold the key to understanding epidemiologic trends.

Risk Factors for HIV Acquisition in a Prospective Nairobi-Based Female Sex Worker Cohort.

With two million new HIV infections annually, ongoing investigations of risk factors for HIV acquisition is critical to guide ongoing HIV prevention efforts. We conducted a prospective cohort analysis of HIV uninfected female sex workers enrolled at an HIV prevention clinic in Nairobi (n = 1640). In the initially HIV uninfected cohort (70 %), we observed 34 HIV infections during 1514 person-years of follow-up, i.e. an annual incidence of 2.2 % (95 % CI 1.6-3.1 %). In multivariable Cox Proportional Hazard analysis, HIV acquisition was associated with a shorter baseline duration of sex work (aHR 0.76, 95 % CI 0.63-0.91), minimum charge/sex act (aHR 2.74, 0.82-9.15, for low vs. intermediate; aHR 5.70, 1.96-16.59, for high vs. intermediate), N. gonorrhoeae infection (aAHR 5.89, 95 % CI 2.03-17.08), sex with casual clients during menses (aHR 6.19, 95 % CI 2.58-14.84), Depo Provera use (aHR 5.12, 95 % CI 1.98-13.22), and estimated number of annual unprotected regular partner contacts (aHR 1.004, 95 % CI 1.001-1.006). Risk profiling based on baseline predictors suggested that substantial heterogeneity in HIV risk is evident, even within a key population. These data highlight several risk factors for HIV acquisition that could help to re-focus HIV prevention messages.

High HIV risk in a cohort of male sex workers from Nairobi, Kenya.

OBJECTIVES: Men who have sex with men (MSM) are at high risk of HIV-1 acquisition and transmission, yet there remains limited data in the African context, and for men who sell sex to men (MSM SW) in particular. METHODS: We enrolled 507 male sex workers in a Nairobi-based prospective cohort study during 2009-2012. All participants were offered HIV/STI screening, counselling and completed a baseline questionnaire. RESULTS: Baseline HIV prevalence was 40.0% (95% CI 35.8% to 44.3%). Prevalent HIV infection was associated with age, less postsecondary education, marijuana use, fewer female partners and lower rates of prior HIV testing. Most participants (73%) reported at least two of insertive anal, receptive anal and insertive vaginal sex in the past 3 months. Vaginal sex was reported by 37% of participants, and exclusive MSM status was associated with higher HIV rates. Condom use was infrequent, with approximately one-third reporting 100% condom use during anal sex. HIV incidence was 10.9 per 100 person-years (95% CI 7.4 to 15.6). Predictors of HIV risk included history of urethral discharge (aHR 0.29, 95% CI 0.08 to 0.98, p=0.046), condom use during receptive anal sex (aHR 0.05, 95% CI 0.01 to 0.41, p=0.006) and frequency of sex with male partners (aHR 1.33/sex act, 95% CI 1.01 to 1.75, p=0.04). CONCLUSIONS: HIV prevalence and incidence were extremely high in Nairobi MSM SW; a combination of interventions including increasing condom use, pre-exposure prophylaxis and access to effective treatment is urgently needed to decrease HIV transmission in this key population.

The individualistic fallacy, ecological studies and instrumental variables: a causal interpretation.

The validity of ecological studies in epidemiology for inferring causal relationships has been widely challenged as observed associations could be biased by the Ecological Fallacy. We reconsider the important design components of ecological studies, and discuss the conditions that may lead to spurious associations. Ecological associations are useful and valid when the ecological exposures can be interpreted as Instrumental Variables. A suitable example may be a time series analysis of environmental pollution (e.g. particulate matter with an aerodynamic diameter of <10 micrometres; PM10) and health outcomes (e.g. hospital admissions for acute myocardial infarction) as environmental pollution levels are a cause of individual exposure levels and not just an aggregate measurement. Ecological exposures may also be employed in situations (perhaps rare) where individual exposures are known but their associations with health outcomes are confounded by unknown or unquantifiable factors. Ecological associations have a notorious reputation in epidemiology and individualistic associations are considered superior to ecological associations because of the "ecological fallacy". We have argued that this is incorrect in situations in which ecological or aggregate exposures can serve as an instrumental variable and associations between individual exposure and outcome are likely to be confounded by unmeasured variables.

Half of the Emirati population has abnormal red cell parameters: challenges for standards and screening guidelines.

In populations with high prevalences of iron deficiency and thalassemia trait, many apparently healthy individuals have abnormal erythroid parameters, which may cause diagnostic problems in clinical practice. We studied the prevalence and causes of red cell parameter values outside their reference ranges in 394 healthy individuals of Bedouin Arab origin, who had complete blood counts (CBCs), hemoglobin (Hb) analyses and serum ferritin tests done. Their mean age ± standard deviation (SD) was 24.8 ± 4.9 years and 51.8% were females. Overall, 53.0% (209/394) had low Hb, MCV or MCH or high RDW. Anemia was present in 27.0% (55/204) of the women and 3.0% (6/190) of the men. Overall prevalence of MCV < 80.0 fL was 45.0% (176/394) and MCH < 27.0 pg was 48.0% (190/394); RDW > 14.0% was found in 21.0% (43/204) of women and 7.0% (14/190) of men. Of the women, 16.0% had iron deficiency anemia (33/204) and 65.0% had ferritin values of < 30.0 µg/L (133/204). The estimated prevalence of α-thalassemia (α-thal) trait in men was 32.0% (60/190) and that of ß-thalassemia (ß-thal) trait in both sexes was 3.0% (12/394). In conclusion, half of the healthy Emirati population have abnormal CBC values. For clinical purposes, they require reference standards for red cells that are derived from their own population. Screening of women for iron deficiency is justified due to a high prevalence of iron deficiency.

Hepatitis C risk score as a tool to identify individuals with HCV infection: a demonstration and cross-sectional epidemiological study in Egypt.

OBJECTIVES: Hepatitis C virus (HCV) infection poses a global health challenge. By the end of 2021, the WHO estimated that less than a quarter of global HCV infections had been diagnosed. There is a need for a public health tool that can facilitate the identification of people with HCV infection and link them to testing and treatment, and that can be customised for each country. METHODS: We derived and validated a risk score to identify people with HCV in Egypt and demonstrated its utility. Using data from the 2008 and 2014 Egypt Demographic and Health Surveys, two risk scores were constructed through multivariable logistic regression analysis. A range of diagnostic metrics was then calculated to evaluate the performance of these scores. RESULTS: The 2008 and 2014 risk scores exhibited similar dependencies on sex, age and type of place of residence. Both risk scores demonstrated high and similar areas under the curve of 0.77 (95% CI: 0.76 to 0.78) and 0.78 (95% CI: 0.77 to 0.80), respectively. For the 2008 risk score, sensitivity was 73.7% (95% CI: 71.5% to 75.9%), specificity was 68.5% (95% CI: 67.5% to 69.4%), positive predictive value (PPV) was 27.8% (95% CI: 26.4% to 29.2%) and negative predictive value (NPV) was 94.1% (95% CI: 93.5% to 94.6%). For the 2014 risk score, sensitivity was 64.0% (95% CI: 61.5% to 66.6%), specificity was 78.2% (95% CI: 77.5% to 78.9%), PPV was 22.2% (95% CI: 20.9% to 23.5%) and NPV was 95.7% (95% CI: 95.4% to 96.1%). Each score was validated by applying it to a different survey database than the one used to derive it. CONCLUSIONS: Implementation of HCV risk scores is an effective strategy to identify carriers of HCV infection and to link them to testing and treatment at low cost to national programmes.

Hybrid immunity from severe acute respiratory syndrome coronavirus 2 infection and vaccination in Canadian adults: A cohort study.

Background: Few national-level studies have evaluated the impact of 'hybrid' immunity (vaccination coupled with recovery from infection) from the Omicron variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: From May 2020 to December 2022, we conducted serial assessments (each of ~4000-9000 adults) examining SARS-CoV-2 antibodies within a mostly representative Canadian cohort drawn from a national online polling platform. Adults, most of whom were vaccinated, reported viral test-confirmed infections and mailed self-collected dried blood spots (DBSs) to a central lab. Samples underwent highly sensitive and specific antibody assays to spike and nucleocapsid protein antigens, the latter triggered only by infection. We estimated cumulative SARS-CoV-2 incidence prior to the Omicron period and during the BA.1/1.1 and BA.2/5 waves. We assessed changes in antibody levels and in age-specific active immunity levels. Results: Spike levels were higher in infected than in uninfected adults, regardless of vaccination doses. Among adults vaccinated at least thrice and infected more than 6 months earlier, spike levels fell notably and continuously for the 9-month post-vaccination. In contrast, among adults infected within 6 months, spike levels declined gradually. Declines were similar by sex, age group, and ethnicity. Recent vaccination attenuated declines in spike levels from older infections. In a convenience sample, spike antibody and cellular responses were correlated. Near the end of 2022, about 35% of adults above age 60 had their last vaccine dose more than 6 months ago, and about 25% remained uninfected. The cumulative incidence of SARS-CoV-2 infection rose from 13% (95% confidence interval 11-14%) before omicron to 78% (76-80%) by December 2022, equating to 25 million infected adults cumulatively. However, the coronavirus disease 2019 (COVID-19) weekly death rate during the BA.2/5 waves was less than half of that during the BA.1/1.1 wave, implying a protective role for hybrid immunity. Conclusions: Strategies to maintain population-level hybrid immunity require up-to-date vaccination coverage, including among those recovering from infection. Population-based, self-collected DBSs are a practicable biological surveillance platform. Funding: Funding was provided by the COVID-19 Immunity Task Force, Canadian Institutes of Health Research, Pfizer Global Medical Grants, and St. Michael's Hospital Foundation. PJ and ACG are funded by the Canada Research Chairs Program.

Prediction of the origin of French Legionella pneumophila strains using a mixed-genome microarray.

BACKGROUND: Legionella is a water and soil bacterium that can infect humans, causing a pneumonia known as Legionnaires' disease. The pneumonia is almost exclusively caused by the species L. pneumophila, of which serogroup 1 is responsible for 90% of patients. Within serogroup 1, large differences in prevalence in clinical isolates have been described. A recent study, using a Dutch Legionella strain collection, identified five virulence associated markers. In our study, we verify whether these five Dutch markers can predict the patient or environmental origin of a French Legionella strain collection. In addition, we identify new potential virulence markers and verify whether these can predict better. A total of 219 French patient isolates and environmental strains were compared using a mixed-genome micro-array. The micro-array data were analysed to identify predictive markers, using a Random Forest algorithm combined with a logistic regression model. The sequences of the identified markers were compared with eleven known Legionella genomes, using BlastN and BlastX; the functionality for each of the predictive markers was checked in the literature. RESULTS: The five Dutch markers insufficiently predicted the patient or environmental origin of the French Legionella strains. Subsequent analyses identified four predictive markers for the French collection that were used for the logistic regression model. This model showed a negative predictive value of 91%. Three of the French markers differed from the Dutch markers, one showed considerable overlap and was found in one of the Legionella genomes (Lorraine strain). This marker encodes for a structural toxin protein RtxA, described for L. pneumophila as a factor involved in virulence and entry in both human cells and amoebae. CONCLUSIONS: The combination of a mixed-genome micro-array and statistical analysis using a Random Forest algorithm has identified virulence markers in a consistent way. The Lorraine strain and related Dutch and French Legionella strains contain a marker that encodes a RtxA protein which probably is involved in the increased prevalence in clinical isolates. The current set of predictive markers is insufficient to justify its use as a reliable test in the public health field in France. Our results suggest that genetic differences in Legionella strains exist between geographically distinct entities. It may be necessary to develop region-specific mixed-genome microarrays that are constantly adapted and updated.

Vitamin D deficiency among healthy adolescents in Al Ain, United Arab Emirates.

BACKGROUND: Although vitamin D deficiency has been studied in various adult populations, there are few data on the prevalence of this nutritional deficiency among healthy adolescents in the United Arab Emirates (UAE). This study was conducted to determine the prevalence of vitamin D deficiency and to examine its correlates in adolescents aged 15 to 18 years. METHODS: This was a cross-sectional study in urban schools. Healthy adolescents (N=315) from a sample of 8 schools were randomly selected from the 142 schools in Al Ain, Abu Dhabi Emirate. Outcomes measured included serum concentrations of 25-hydroxy vitamin D (25OHD), plasma lipids, blood sugar, blood pressure and anthropometric data, nutrition and lifestyle variables. RESULTS: Fourty-one participants (19.7%) were vitamin D deficient (serum 25OHD level ≤15 ng/mL [≤37.5 nmol/L]. Using a cutoff level of 25(OH) D of ≤20 ng/ml [≤50 nmol/l] 143 participants (45.4%) were vitamin D insufficient. Overall 65.1% of study participants were either vitamin D deficient or insufficient. The prevalence of vitamin D deficiency varied between boys (10%) and girls (28%). In a final multivariate model, serum 25(OH) D concentrations were inversely correlated with female gender, consumption of fast food per week, and body mass index and positively correlated with physical activity scores after adjustment for age. CONCLUSIONS: Vitamin D deficiency and insufficiency were highly prevalent in adolescents, and more common in girls.