Estimating epidemiologic dynamics from cross-sectional viral load distributions.
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ABSTRACT:
SUBMITTER: Hay JA
PROVIDER: S-EPMC7885940 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionAiming to reach UNAIDS 90-90-90 targets, nearly all sub-Saharan African countries have expanded antiretroviral therapy (ART) to all people living with HIV (PLWH) (Treat All). Few published data exist on viral load testing and viral suppression under Treat All in this region. We assessed proportions of patients with available viral load test results and who were virally suppressed, as well as factors associated with viral suppression, among PLWH in 10 Rwandan health centres after Treat All implementation.MethodsCross-sectional study during 2018 of adults (?15 years) engaged in HIV care at 10 Rwandan health centres. Outcomes were being on ART (available ART initiation date in the study database, with no ART discontinuation prior to 1 January 2018), retained on ART (?2 post-ART health centre visits ?90 days apart during 2018), available viral load test results (viral load measured in 2018 and available in study database) and virally suppressed (most recent 2018 viral load <200 copies/mL). We used modified Poisson regression models accounting for clustering by health centre to determine factors associated with being virally suppressed.ResultsOf 12,238 patients, 7050 (58%) were female and 1028 (8%) were aged 15 to 24 years. Nearly all patients (11,933; 97%) were on ART, of whom 11,198 (94%) were retained on ART. Among patients retained on ART, 10,200 (91%) had available viral load results; of these 9331 (91%) were virally suppressed. Viral suppression was less likely among patients aged 15 to 24 compared to >49 years (adjusted prevalence ratio (aPR): 0.83, 95% CI 0.76 to 0.90 and those with pre-ART CD4 counts of <200 compared to ?500 cells/mm3 (aPR: 0.92, 95% CI 0.90 to 0.93). There was no statistically significant difference in viral suppression among patients who entered after Treat All implementation compared to those who enrolled before 2010 (aPR 0.98, 95% CI 0.94 to 1.03).ConclusionsIn this large cohort of Rwandan PLWH receiving HIV care after Treat All implementation, patients in study health centres have surpassed the third UNAIDS 90-90-90 target. To ensure all PLWH fully benefit from ART, additional efforts should focus on improving ART adherence among younger persons.
| S-EPMC7293767 | biostudies-literature
Project description:BackgroundDescribing the SARS-CoV-2 viral-load distribution in different patient groups and age categories.MethodsAll results from first nasopharyngeal (NP) and oropharyngeal (OP) swabs from unique patients tested via SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) collected between 1 January and 1 December 2020 predominantly in the Public Health Services regions Kennemerland and Hollands Noorden, province of North Holland, the Netherlands, were included in this study. SARS-CoV-2 PCR crossing-point (Cp)-values were used to estimate viral loads.ResultsIn total, 278 455 unique patients were tested, of whom 9.1% (n = 25.374) were SARS-CoV-2-positive. PCRs performed by Public Health Services (n = 211 914), in which sampling and inclusion were uniform, revealed a clear relation between age and SARS-CoV-2 viral load, with especially children aged <12 years showing lower viral loads than adults (β: -0.03, 95% confidence interval: -0.03 to -0.02, p < 0.001), independently of sex and/or symptom duration. Interestingly, the median Cp-values between the >79- and <12-year-old populations differed by more than four PCR cycles, suggesting an ∼16-fold difference in viral load. In addition, the proportion of children aged <12 years with a low load (Cp-value >30) was higher compared with other patients (31.1% vs 17.2%, p-value < 0.001).ConclusionsIn patients tested by Public Health Services, SARS-CoV-2 viral load increases with age. Further studies should elucidate whether the lower viral load in children is indeed related to their suggested limited role in SARS-CoV-2 transmission. Moreover, as rapid antigen tests are less sensitive than PCR, these results suggest that SARS-CoV-2 antigen tests have lower sensitivity in children than in adults.
| S-EPMC8499942 | biostudies-literature
Project description:BackgroundHIV incidence is the best measure of treatment-programme effectiveness, but its measurement is difficult and expensive. The concept of community viral load as a modifiable driver of new HIV infections has attracted substantial attention. We set out to compare several measures of community viral load and antiretroviral therapy (ART) coverage as correlates of HIV incidence in high-risk populations.MethodsWe analysed data from a sample of people who inject drugs and men who have sex with men, who were participants of the baseline assessment of a cluster-randomised trial in progress across 22 cities in India (ClinicalTrials.gov number NCT01686750). We recruited the study population by use of respondent-driven sampling and did the baseline assessment at 27 community-based sites (12 for men who have sex with men and 15 for people who inject drugs). We estimated HIV incidence with a multiassay algorithm and calculated five community-based measures of HIV control: mean log10 HIV RNA in participants with HIV in a community either engaged in care (in-care viral load), aware of their status but not necessarily in care (aware viral load), or all HIV-positive individuals whether they were aware, in care, or not (population viral load); participants with HIV in a community with HIV RNA more than 150 copies per mL (prevalence of viraemia); and the proportion of participants with HIV who self-reported ART use in the previous 30 days (population ART coverage). All participants were tested for HIV, with additional testing in HIV-positive individuals. We assessed correlations between the measures and HIV incidence with Spearman correlation coefficients and linear regression analysis.FindingsBetween Oct 1, 2012, and Dec 19, 2013, we recruited 26,503 participants, 12,022 men who have sex with men and 14,481 people who inject drugs. Median incidence of HIV was 0·87% (IQR 0·40-1·17) in men who have sex with men and 1·43% (0·60-4·00) in people who inject drugs. Prevalence of viraemia was more strongly correlated with HIV incidence (correlation 0·81, 95% CI 0·62-0·91; p<0·0001) than all other measures, although correlation was significant with aware viral load (0·59, 0·27-0·79; p=0·001), population viral load (0·51, 0·16-0·74; p=0·007), and population ART coverage (-0·54, -0·76 to -0·20; p=0·004). In-care viral load was not correlated with HIV incidence (0·29, -0·10 to 0·60; p=0·14). With regression analysis, we estimated that to reduce HIV incidence by 1 percentage point in a community, prevalence of viraemia would need to be reduced by 4·34%, and ART use in HIV-positive individuals would need to increase by 19·5%.InterpretationPrevalence of viraemia had the strongest correlation with HIV incidence in this sample and might be a useful measure of the effectiveness of a treatment programme.FundingUS National Institutes of Health, Elton John AIDS Foundation.
| S-EPMC4863069 | biostudies-literature
Project description:The development of new approaches to cholera control relies on an accurate understanding of cholera epidemiology. However, most information on cholera incidence lacks laboratory confirmation and instead relies on surveillance systems reporting medically attended acute watery diarrhea. If recent infections could be identified using serological markers, cross-sectional serosurveys would offer an alternative approach to measuring incidence. Here, we used 1569 serologic samples from a cohort of cholera cases and their uninfected contacts in Bangladesh to train machine learning models to identify recent Vibrio cholerae O1 infections. We found that an individual's antibody profile contains information on the timing of V. cholerae O1 infections in the previous year. Our models using six serological markers accurately identified individuals in the Bangladesh cohort infected within the last year [cross-validated area under the curve (AUC), 93.4%; 95% confidence interval (CI), 92.1 to 94.7%], with a marginal performance decrease using models based on two markers (cross-validated AUC, 91.0%; 95% CI, 89.2 to 92.7%). We validated the performance of the two-marker model on data from a cohort of North American volunteers challenged with V. cholerae O1 (AUC range, 88.4 to 98.4%). In simulated serosurveys, our models accurately estimated annual incidence in both endemic and epidemic settings, even with sample sizes as small as 500 and annual incidence as low as two infections per 1000 individuals. Cross-sectional serosurveys may be a viable approach to estimating cholera incidence.
| S-EPMC6430585 | biostudies-literature
Project description:Transmission of COVID-19 from people without symptoms confounds societal mitigation strategies. From April to June 2020, we tested nasopharyngeal swabs by RT-qPCR from 15,514 staff and 16,966 residents of nursing homes and assisted living facilities in Massachusetts. Cycle threshold (Ct) distributions were very similar between populations with (N = 739) and without (N = 2179) symptoms at the time of sampling (mean Ct 25.7 versus 26.4, ranges 12-38). However, as local cases waned, those without symptoms shifted towards higher Ct. With such similar viral load distributions, existing testing modalities should perform comparably regardless of symptoms, contingent upon time since infection.
| S-EPMC8420626 | biostudies-literature
Project description:To assess the accuracy of the South African National Health Laboratory Services (NHLS) corporate data warehouse (CDW) using a novel data cross-matching method.Adults (?18?years) on antiretroviral therapy (ART) who visited a hospital-based HIV clinic in Durban from March to June 2012 were included. We matched patient identifiers, CD4 and viral load (VL) records from the HIV clinic's electronic record with the NHLS CDW according to a set of matching criteria for patient identifiers, test values and test dates. We calculated the matching rates for patient identifiers, CD4 and VL records, and an overall matching rate.NHLS returned records for 3498 (89.6%) of the 3906 individuals requested. Using our computer algorithm, we confidently matched 3278 patients (83.9% of the total request). Considering less than confident matches as well, and then manually reviewing questionable matches using only patient identifiers, only nine (0.3% of records returned by NHLS) of the suggested matches were judged incorrect.We developed a data cross-matching method to evaluate national laboratory data and were able to match almost 9 of 10 patients with data we expected to find in the NHLS CDW. We found few questionable matches, suggesting that manual review of records returned was not essential. As the number of patients initiating ART in South Africa grows, maintaining a comprehensive and accurate national data repository is of critical importance, since it may serve as a valuable tool to evaluate the effectiveness of the country's HIV care system. This study helps validate the use of NHLS CDW data in future research on South Africa's HIV care system and may inform analyses in similar settings with national laboratory systems.
| S-EPMC6112393 | biostudies-other
Project description:We conducted a multicentre cross sectional observational study of laboratory, public health and hospitalisation data for PCR-confirmed COVID-19 cases within the New Zealand Northern Region, between 12 February and 8 June 2020. The aim of this study was to describe population level SARS-CoV-2 upper respiratory tract (URT) viral load dynamics by stratifying positivity rates and polymerase chain reaction (PCR) cycle threshold (Ct) values of URT samples from COVID-19 cases by days since symptom onset, and to explore utility of Ct values in determining length of time post-infection and thus potential infectivity. Of 123,124 samples tested for SARS-CoV-2 by PCR, 579 samples (407 positive and 172 negative) from 368 symptomatic non-hospitalised individuals with PCR-confirmed infection were included. Sample positivity rate was 61.5% (8/13) for pre-symptomatic samples, rising to 93.2% (317/340) for samples collected during the purported symptomatic infectious period (days 0-10 post-symptom onset), and dropping to 36.3% (82/226) for post-infectious period samples (day 11 onwards). URT viral load peaked shortly after symptom onset, with median Ct values ranging 20.00-29.99 until 15 days post-symptom onset, and >30.00 after this time. Of samples with a Ct value of <20.00, 96.1% were collected during the symptomatic infectious period. However, of samples with a Ct value ≥30.00 and ≥35.00, 46.9% and 18.5%, respectively, were also collected during the symptomatic infectious period. The findings of this study indicate that at or soon after symptom onset represents the optimum time to test for SARS-CoV-2 in the URT, with median Ct values suggesting the useful testing window extends until around 15 days post-symptom onset. In asymptomatic individuals or those with unknown dates of symptom onset, Ct values <20.00 imply recent onset/potential infectivity, but Ct values ≥30.00 or ≥35.00 do not exclude recent onset/potential infectivity. Individual sample Ct values should not be used as an absolute marker of length of time post-infection or to exclude infectivity where date of symptom onset is unavailable.
| S-EPMC7980174 | biostudies-literature
Project description:mRNA microarray profiling was performed on healthy gingival biopsies from nonhuman primates (NHPs) (between 3 and 23 years old, and periodontitis gingival biopsies from NHPs (12-22 years old)
2014-10-15 | E-MTAB-1977 | biostudies-arrayexpress
Project description:Dengue is a vector-borne viral disease of humans that endemically circulates in many tropical and subtropical regions worldwide. Infection with dengue can result in a range of disease outcomes. A considerable amount of research has sought to improve our understanding of this variation in disease outcomes and to identify predictors of severe disease. Contributing to this research, patterns of viral load in dengue infected patients have been quantified, with analyses indicating that peak viral load levels, rates of viral load decline, and time to peak viremia are useful predictors of severe disease. Here, we take a complementary approach to understanding patterns of clinical manifestation and inter-individual variation in viral load dynamics. Specifically, we statistically fit mathematical within-host models of dengue to individual-level viral load data to test virological and immunological hypotheses explaining inter-individual variation in dengue viral load. We choose between alternative models using model selection criteria to determine which hypotheses are best supported by the data. We first show that the cellular immune response plays an important role in regulating viral load in secondary dengue infections. We then provide statistical support for the process of antibody-dependent enhancement (but not original antigenic sin) in the development of severe disease in secondary dengue infections. Finally, we show statistical support for serotype-specific differences in viral infectivity rates, with infectivity rates of dengue serotypes 2 and 3 exceeding those of serotype 1. These results contribute to our understanding of dengue viral load patterns and their relationship to the development of severe dengue disease. They further have implications for understanding how dengue transmissibility may depend on the immune status of infected individuals and the identity of the infecting serotype.
| S-EPMC5113863 | biostudies-literature
Project description:Relationships between viral load, severity of illness, and transmissibility of virus are fundamental to understanding pathogenesis and devising better therapeutic and prevention strategies for COVID-19. Here we present within-host modelling of viral load dynamics observed in the upper respiratory tract (URT), drawing upon 2172 serial measurements from 605 subjects, collected from 17 different studies. We developed a mechanistic model to describe viral load dynamics and host response and contrast this with simpler mixed-effects regression analysis of peak viral load and its subsequent decline. We observed wide variation in URT viral load between individuals, over 5 orders of magnitude, at any given point in time since symptom onset. This variation was not explained by age, sex, or severity of illness, and these variables were not associated with the modelled early or late phases of immune-mediated control of viral load. We explored the application of the mechanistic model to identify measured immune responses associated with the control of the viral load. Neutralising antibodies correlated strongly with modelled immune-mediated control of viral load amongst subjects who produced neutralising antibodies. Our models can be used to identify host and viral factors which control URT viral load dynamics, informing future treatment and transmission blocking interventions.
| S-EPMC8755404 | biostudies-literature