Asymptomatic Members Research Articles

Asymptomatic Malaria Reservoirs in Honduras: A Challenge for Elimination.

Efforts on a global scale for combating malaria have achieved substantial progress over the past twenty years. Two Central American nations have accomplished their goal of eliminating malaria: El Salvador and Belize. Honduras has decreased the incidence of malaria and now reports fewer than 4000 malaria cases annually, aspiring to reach elimination by 2030. To accomplish this goal, it is essential to assess the existing strategies employed for malaria control and to address the task of incorporating novel intervention strategies to identify asymptomatic reservoirs. A survey for detecting asymptomatic cases was carried out in the community of Kaukira, in Gracias a Dios, Honduras, focusing on malaria transmission during 2023. Asymptomatic community members were recruited as participants, malaria screening was performed through a rapid diagnostic test in situ, and a blood sample was collected on filter paper. Highly sensitive molecular assays based on photo-induced electron transfer PCR (PET-PCR) were performed to detect the two species of Plasmodium circulating in Honduras: Plasmodium vivax and Plasmodium falciparum. In addition, the identification of the parasite species was verified by amplifying three genetic markers (Pvmsp3α, Pvmsp3ß, and Pfmsp1). A total of 138 participants were recruited, mostly adult women. All individuals tested negative on the rapid diagnostic test. Positive results for malaria were detected by PET-PCR in 17 samples (12.3%). Most samples (12 out of 17) were amplified with a Ct value between 37 and 42, indicating very low parasitemias. Out of the 17 samples, 16 of them also showed amplification in the species assays. There were nine cases of P. falciparum infections and seven cases of P. vivax infections that were further confirmed by nested PCR (nPCR) of Pvmsp3 and Pfmsp1. Parasitemias ranged from 100 p/μL to less than 0.25 p/μL. One sample showed mixed infection. The existence of asymptomatic malaria reservoirs in Honduras can contribute to disease transmission and pose a challenge that may hinder elimination efforts, requiring public health authorities to modify surveillance strategies to identify the disease and treat this population accordingly.

The impact of family screening in patients with Wilson’s disease from the Republic of Moldova

Introduction. Wilson’s disease (WD) is a rare genetic disease with autosomal recessive transmission, thus screening of all family members of newly diagnosed patients is recommended. Therefore, we aimed to analyze the proband’s family members to detect asymptomatic cases and early treatment initiation. Material and methods. There were retrospectively evaluated 12 families, between 2008 - 2023. The Leipzig Scoring System was used to assess the diagnosis. Genetic testing was performed in all cases by the Sanger sequencing method, examining exons with a high and moderate frequency of mutations. Results. All patients were of Caucasian origin, and originally from Moldova. No patient reported consanguineous relationships. In 9 families, first-degree relatives were tested - parents and siblings, in the other 3 cases only their descendants were evaluated. In 6/12 cases: both parents were healthy carriers; in the other 3 families, one parent was a healthy carrier, but the other parent had not been tested. Among siblings, 4 healthy carriers and 2 healthy siblings were identified. 7 new family members with WD were identified in 5/12 families. 6 patients were asymptomatic, and 1 - was symptomatic. The most frequent mutations detected were p.H1069Q and p.G1341D, both as compound heterozygous and homozygous recessive. A rare mutation has been detected. Discussions. Genetic counseling is important for the family of the patient with Wilson’s disease, as the evaluation of first-degree relatives is recommended by all international guidelines. First-degree relatives include the proband’s siblings, as well as the proband’s offspring and parents. It is also important to assess distant relatives, especially in more isolated areas. Although it is an autosomal recessive disorder, systemic family screening is recommended, as cases of paradoxical transmission are recorded. The c.2292C>T variant, identified in one patient, represents a rare mutation that, when occurring in combination with another pathogenic mutation or a homozygous state, can cause WD. Conclusions. Family screening greatly influences identifying asymptomatic members with Wilson’s disease. Genetic testing is very important in differentiating healthy carriers from asymptomatic members, especially when deciding treatment tactics.

Insulin-like growth factor binding protein-2 in at-risk adults and autopsy-confirmed Alzheimer brains.

Insulin, insulin-like growth factors (IGF) and their receptors are highly expressed in the adult hippocampus. Thus, disturbances in the insulin-IGF signalling pathway may account for the selective vulnerability of the hippocampus to nascent Alzheimer's disease (AD) pathology. In the present study, we examined the predominant IGF-binding protein in the CSF, IGFBP2. CSF was collected from 109 asymptomatic members of the parental history-positive PREVENT-AD cohort. CSF levels of IGFBP2, core AD and synaptic biomarkers were measured using proximity extension assay, ELISA and mass spectrometry. Cortical amyloid-beta (Aβ) and tau deposition were examined using 18F-NAV4694 and flortaucipir. Cognitive assessments were performed during up to 8 years of follow-up, using the Repeatable Battery for the Assessment of Neuropsychological Status. T1-weighted structural MRI scans were acquired, and neuroimaging analyses were performed on pre-specified temporal and parietal brain regions. Next, in an independent cohort, we allocated 241 dementia-free ADNI-1 participants into four stages of AD progression based on the biomarkers CSF Aβ42 and total-tau (t-tau). In this analysis, differences in CSF and plasma IGFBP2 levels were examined across the pathological stages. Finally, IGFBP2 mRNA and protein levels were examined in the frontal cortex of 55 autopsy-confirmed AD and 31 control brains from the Quebec Founder Population (QFP) cohort, a unique population isolated from Eastern Canada. CSF IGFBP2 progressively increased over 5 years in asymptomatic PREVENT-AD participants. Baseline CSF IGFBP2 was positively correlated with CSF AD biomarkers and synaptic biomarkers, and negatively correlated with longitudinal changes in delayed memory (P = 0.024) and visuospatial abilities (P = 0.019). CSF IGFBP2 was negatively correlated at a trend-level with entorhinal cortex volume (P = 0.082) and cortical thickness in the piriform (P = 0.039), inferior temporal (P = 0.008), middle temporal (P = 0.014) and precuneus (P = 0.033) regions. In ADNI-1, CSF (P = 0.009) and plasma (P = 0.001) IGFBP2 were significantly elevated in Stage 2 [CSF Aβ(+)/t-tau(+)]. In survival analyses in ADNI-1, elevated plasma IGFBP2 was associated with a greater rate of AD conversion (hazard ratio = 1.62, P = 0.021). In the QFP cohort, IGFBP2 mRNA was reduced (P = 0.049); however, IGFBP2 protein levels did not differ in the frontal cortex of autopsy-confirmed AD brains (P = 0.462). Nascent AD pathology may induce an upregulation in IGFBP2 in asymptomatic individuals. CSF and plasma IGFBP2 may be valuable markers for identifying CSF Aβ(+)/t-tau(+) individuals and those with a greater risk of AD conversion.

Analysis of contact tracing data showed contribution of asymptomatic and non-severe infections to the maintenance of SARS-CoV-2 transmission in Senegal

During the COVID-19 pandemic in Senegal, contact tracing was done to identify transmission clusters, their analysis allowed to understand their dynamics and evolution. In this study, we used information from the surveillance data and phone interviews to construct, represent and analyze COVID-19 transmission clusters from March 2, 2020, to May 31, 2021. In total, 114,040 samples were tested and 2153 transmission clusters identified. A maximum of 7 generations of secondary infections were noted. Clusters had an average of 29.58 members and 7.63 infected among them; their average duration was 27.95 days. Most of the clusters (77.3%) are concentrated in Dakar, capital city of Senegal. The 29 cases identified as super-spreaders, i.e., the indexes that had the most positive contacts, showed few symptoms or were asymptomatic. Deepest transmission clusters are those with the highest percentage of asymptomatic members. The correlation between proportion of asymptomatic and degree of transmission clusters showed that asymptomatic strongly contributed to the continuity of transmission within clusters. During this pandemic, all the efforts towards epidemiological investigations, active case-contact detection, allowed to identify in a short delay growing clusters and help response teams to mitigate the spread of the disease.

Phenotypic heterogeneity in family members of patients with retinitis pigmentosa.

To describe the phenotypic variations in family members of patients with retinitis pigmentosa (RP) with different modes of inheritance and to assess the ocular abnormalities in RP families. A descriptive analysis of three types of inheritance of RP was carried out, where 64 family members were examined at a tertiary eye care center, South India. They underwent comprehensive eye examination, fundus photography, fundus autofluorescence (FAF), full-field electroretinogram (FFERG), and spectral domain optical coherence tomography (SD-OCT). Analysis was performed between mild and severe forms of abnormalities to delineate retinal structural and functional defects in RP families. The mean age was 38.55 ± 17.95 years. Males were 48.4%. In autosomal recessive and X-linked recessive groups, 74.2% and 77.3%, respectively, were asymptomatic, whereas in autosomal dominant group, 27.3% were asymptomatic. The proportion of the cases with abnormalities in all three groups was higher on ERG (59.6%), followed by OCT (57.5%), visual acuity (43.7%), peripheral FAF (23.5%), and macular FAF (11.8%). However, these abnormalities and the clinical pictures of the family members had no statistical difference across the three groups of inheritance. Structural and functional retinal alterations were noted in four out of five asymptomatic members, suggesting the need for careful screening of RP families and the pressing need for pre-test (genetic) counseling.

Case-control investigation of invasive Salmonella disease in Malawi reveals no evidence of environmental or animal transmission of invasive strains, and supports human to human transmission.

Invasive Salmonella infections cause significant morbidity and mortality in Sub-Saharan Africa. However, the routes of transmission are uncertain. We conducted a case-control study of index-case and geographically-matched control households in Blantyre, Malawi, sampling Salmonella isolates from index cases, healthy people, animals, and the household environment. Sixty index cases of human invasive Salmonella infection were recruited (March 2015-Oct 2016). Twenty-eight invasive Non-Typhoidal Salmonella (iNTS) disease and 32 typhoid patients consented to household sampling. Each index-case household was geographically matched to a control household. Extensive microbiological sampling included stool sampling from healthy household members, stool or rectal swabs from household-associated animals and boot-sock sampling of the household environment. 1203 samples from 120 households, yielded 43 non-Typhoidal Salmonella (NTS) isolates from 25 households (overall sample positivity 3.6%). In the 28 iNTS patients, disease was caused by 3 STs of Salmonella Typhimurium, mainly ST313. In contrast, the isolates from households spanned 15 sequence types (STs). Two S. Typhimurium isolates from index cases closely matched isolates from their respective asymptomatic household members (2 and 3 SNP differences respectively). Despite the recovery of a diverse range of NTS, there was no overlap between the STs causing iNTS disease with any environmental or animal isolates. The finding of NTS strains from index cases that matched household members, coupled with lack of related animal or environmental isolates, supports a hypothesis of human to human transmission of iNTS infections in the household. The breadth of NTS strains found in animals and the household environment demonstrated the robustness of NTS sampling and culture methodology, and suggests a diverse ecology of Salmonella in this setting. Healthy typhoid (S. Typhi) carrier state was not detected. The lack of S. Typhi isolates from the household environment suggests that further methodological development is needed to culture S. Typhi from the environment.

New pathogenic variants of ALMS1 gene in two Chinese families with Alström Syndrome.

PurposeAlström Syndrome (AS) is an autosomal recessive hereditary disease with the characteristics of multiorgan dysfunction. Due to the heterogeneity of clinical manifestations of AS, genetic testing is crucial for the diagnosis of AS. Herein, we used whole-exome sequencing (WES) to determine the genetic causes and characterize the clinical features of three affected patients in two Chinese families with Alström Syndrome.Materials and methodsThree affected patients (initially diagnosed as achromatopsia). and five asymptomatic members were recruited for both genetic and clinical tests. The complete ophthalmic examinations and systemic examinations were performed on all participants. Whole exome sequencing (WES) was performed for mutation detection. The silico analysis was also applied to predict the pathogenesis of identified pathogenic variants.ResultsIn family 1, the proband showed low vision, hyperopia, photophobia, nystagmus, and total color blindness. DNA analysis revealed that she carried a compound heterozygote with two novel pathogenic variants in the ALMS1 gene NM_015120.4:c.10379del (NP_055935.4:p.(Asp2252Tyr)) and NM_015120.4:c.11641_11642del (NP_055935.4:p.(Val3881ThrfsTer11)). Further systemic examinations showed short stature, acanthosis nigricans, and sensorineural hearing loss. In family 2, two affected siblings presented the low vision, hyperopia, photophobia, nystagmus, and total color blindness. DNA analysis revealed that they carried a same compound heterozygote with two novel pathogenic variants in the ALMS1 gene NM_015120.4:c.10379del (NP_055935.4:p.(Asn3460IlefsTer49)), NM_015120.4:c.10819C > T (NP_055935.4:p.(Arg3607Trp)). Further systemic examinations showed obesity and mild abnormalities of lipid metabolism. According to the genetic testing results and further systemic analysis, the three affected patients were finally diagnosed as Alström Syndrome (AS).ConclusionsWe found two new compound heterozygous pathogenic variants of the ALMS1 gene and determined the diagnosis as Alström Syndrome in three patients of two Chinese families. Our study extends the genotypic and phenotypic spectrums for ALMS1 -AS and emphasizes the importance of gene testing in assisting the clinical diagnosis for cases with phenotypic diversities, which would help the AS patients with early diagnosis and treatment to reduce future systemic damage.

Development and psychometric evaluation of the Aversion to Bowel Cancer Screening Scale.

Avoidance of colorectal cancer (CRC) screening is well documented with emotional barriers deterring screening intention and uptake. However, the assessment of such aversion is limited by the available instruments focusing on siloed emotions or screening procedures, limiting relevance to the complete process of decision-making in the CRC context. To address this gap, psychometric properties of the newly developed Aversion to Bowel Cancer Screening Scale (ABCSS) were assessed using data from 640 CRC screening eligible asymptomatic community members. Item review and piloting reduced 179 items to the initial 29-item scale. Using a holdout sample technique, exploratory and confirmatory factor analysis, reliability and validity checks were conducted. A three-factor model (Fecal Occult Blood Test [FOBT] Aversion, Colonoscopy Aversion and Health Conscientiousness) with 21 items was identified. Analyses of the 21-item ABCSS indicated excellent reliabilities for the scale and subscales (α = .91 to .95). Correlations with relevant existing measures, intention and behaviour indicated good construct validity. The ABCSS is a valid measure of aversion to CRC screening for asymptomatic community members facing the decision to undertake CRC screening. This instrument may provide a more comprehensive understanding of the decision-making process for CRC screening.

Gargle pool PCR testing in a hospital during medium and high SARS-CoV-2 incidence

BackgroundHospitals need to be protected from SARS-CoV-2 infections to protect vulnerable patients. Thus, a safe, efficient, and cost-effective SARS-CoV-2 testing system for hospitals, in addition to standard hygiene measures and vaccination of staff, is necessary. Here we report on the feasibility and performance of a pool real-time reverse-transcriptase polymerase-chain-reaction (rRT-PCR) test system at, medium and high incidence.MethodsWe implemented a testing concept based on gargling at home and pooling of samples in the hospital before PCR testing in the laboratory. We used two PCR systems (point of care and standard 96-well plate system) to adapt to challenges in the hospital setting and respond to a rising incidence in the Omicron wave.FindingsDuring our 10-week study period, we performed 697 pool PCRs (8793 tests in total) and identified 65 asymptomatic staff members by pool PCR and 94 symptomatic staff members by positive individual PCR. Virus loads in those detected by pool testing were significantly lower (P<0.001). The test system remained workable even during the peak of the Omicron wave and no outbreaks occurred in any specific area of the hospital during the study period. Unvaccinated individuals were over-represented in the positively tested (37% vs 22% positive tests, P=0.04). The test procedure was well accepted by a majority of the hospital staff (84%).ConclusionRepeated gargle pool rRT-PCR testing can be implemented quickly in hospitals and is an effective, easily adaptable and well-accepted test system for hospitals, even during phases with very high infection rates.

Normative Values of the Nasal Obstruction Symptom Evaluation Scale.

Background: The Nasal Obstruction Symptom Evaluation (NOSE) scale is widely used by clinicians in evaluation of nasal airway obstruction (NAO). Objective: To determine normative values for the NOSE scale among both symptomatic and asymptomatic members of the general U.S. population. Methods: A survey of NAO symptoms in adults of age 18 years and older was performed. The distribution of NOSE scores among the general population was estimated. Influence of features including age, gender, race, location, and symptomatology on NOSE scores was evaluated. Results: Surveys were completed by 2333 participants. Mean NOSE score was 11 (standard deviation [SD] 11) in the asymptomatic, and 28 (SD 22) in the symptomatic population (p < 0.0001). Increasing age was associated with an increase in scores until 45 years, after which it was associated with decreasing scores. No significant differences were found related to other investigated demographics. Conclusions: Normative ranges for the NOSE scale are established, and are largely consistent with values in the existing literature. NOSE scores do not appear to be influenced by gender, race, or geography, although age should be considered in their interpretation.

Genetic insight into Birt\u2013Hogg\u2013Dub\xe9 syndrome in Indian patients reveals novel mutations at FLCN

BackgroundBirt-Hogg-Dubé syndrome (BHDS) is a rare monogenic condition mostly associated with germline mutations at FLCN. It is characterized by either one or more manifestations of primary spontaneous pneumothorax (PSP), skin fibrofolliculomas and renal carcinoma (chromophobe). Here, we comprehensively studied the mutational background of 31 clinically diagnosed BHDS patients and their 74 asymptomatic related members from 15 Indian families.ResultsTargeted amplicon next-generation sequencing (NGS) and Sanger sequencing of FLCN in patients and asymptomatic members revealed a total of 76 variants. Among these variants, six different types of pathogenic FLCN mutations were detected in 26 patients and some asymptomatic family members. Two of the variants were novel mutations: an 11-nucleotide deletion (c.1150_1160delGTCCAGTCAGC) and a splice acceptor mutation (c.1301-1G > A). Two variants were Clinvar reported pathogenic mutations: a stop-gain (c.634C > T) and a 4-nucleotide duplication (c.1329_1332dupAGCC). Two known variants were: hotspot deletion (c.1285delC) and a splice donor mutation (c.1300 + 1G > A). FLCN mutations could not be detected in patients and asymptomatic members from 5 families. All these mutations greatly affected the protein stability and FLCN-FNIP2 interaction as observed by molecular docking method. Family-based association study inferred pathogenic FLCN mutations are significantly associated with BHDS.ConclusionSix pathogenic FLCN mutations were detected in patients from 10 families out of 15 families in the cohort. Therefore, genetic screening is necessary to validate the clinical diagnosis. The pathogenic mutations at FLCN affects the protein–protein interaction, which plays key roles in various metabolic pathways. Since, pathogenic mutations could not be detected in exonic regions of FLCN in 5 families, whole genome sequencing is necessary to detect all mutations at FLCN and/or any undescribed gene/s that may also be implicated in BHDS.

COVID-19 Infection among Elite Football Players: A Nationwide Prospective Cohort Study.

Little is known about the risk of COVID-19 infection among footballers. We aimed to investigate the incidence and characteristics of COVID-19 infection among footballers. In total, 480 football players of Super League Greece and 420 staff members participated in a prospective cohort study, which took place from May 2020 to May 2021. Nasopharyngeal swabs were collected from footballers and staff members weekly. All samples (n = 43,975) collected were tested using the reverse transcriptase polymerase chain reaction (RT-PCR) test for the detection of “SARS-CoV-2”. In total, 190 positive cases (130 among professional football players and 60 among staff) were recorded. Out of the 190 cases that turned positive, 64 (34%) cases were considered as symptomatic, and 126 (66%) cases were asymptomatic. The incidence rate of a positive test result for footballers was 0.57% (confidence interval (CI) 0.48–0.68%) and for staff members it was 0.27% (CI 0.20%, 0.34%), respectively. Footballers recorded a twofold increased risk of COVID-19 infection in comparison to staff members (relative risk = 2.16; 95% CI = 1.59–2.93; p-value < 0.001). No significant transmission events were observed during the follow-up period. We found a low incidence of COVID-19 infection among professional footballers over a long follow-up period. Furthermore, the implementation of a weekly diagnostic testing (RT-PCR) was critical to break the transmission chain of COVID-19, especially among asymptomatic football players and staff members.

SARS-CoV-2 Delta and Omicron Variants Surge in Curitiba, Southern Brazil, and Its Impact on Overall COVID-19 Lethality

Screening efforts and genomic surveillance are essential tools to evaluate the course of the COVID-19 pandemic and assist the public healthcare system in dealing with an increasing number of infections. For the analysis of COVID-19 cases scenarios in Curitiba, Paraná, Brazil, we performed a diagnosis of positive cases, coupled with genotyping, for symptomatic and asymptomatic members of the Federal University of Paraná. We achieved over 1000 samples using RT-qPCR for diagnosis. The posterior genotyping allowed us to observe differences in the spread of strains in Curitiba, Brazil. The Delta variant was not associated with an infection wave, whereas the rapid Omicron variant spread became dominant in less than one month. We also evaluated the general vaccination coverage in the state, observing a striking reduction in lethality correlated to the vaccinated fraction of the population; although lower lethality rates were not much affected by the Omicron variant wave, the same effect was not translated in the number of infections. In summary, our results provide a general overview of the pandemic’s course in Paraná State and how there was reduction in lethality after a combination of multiple infection waves and a large-scale vaccination program.

Household transmission of SARS-CoV-2 from unvaccinated asymptomatic and symptomatic household members with confirmed SARS-CoV-2 infection: an antibody-surveillance study.

Background:Household transmission contributes to SARS-CoV-2 spread, but the role of children in transmission is unclear. We conducted a study that included symptomatic and asymptomatic children and adults exposed to SARS-CoV-2 in their households with the objective of determining how SARS-CoV-2 is transmitted within households.Methods:In this case-ascertained antibody-surveillance study, we enrolled households in Ottawa, Ontario, in which at least 1 household member had tested positive for SARS-CoV-2 on reverse transcription polymerase chain reaction testing. The enrolment period was September 2020 to March 2021. Potentially eligible participants were identified if they had tested positive for SARS-CoV-2 at an academic emergency department or affiliated testing centre; people who learned about the study through the media could also self-identify for participation. At least 2 participants were required for a household to be eligible for study participation, and at least 1 enrolled participant per household had to be a child (age < 18 yr). Enzyme-linked immunosorbent assays were used to evaluate SARS-CoV-2-specific IgA, IgM and IgG against the spike-trimer and nucleocapsid protein. The primary outcome was household secondary attack rate, defined as the proportion of household contacts positive for SARS-CoV-2 antibody among the total number of household contacts participating in the study. We performed descriptive statistics at both the individual and household levels. To estimate and compare outcomes between patient subgroups, and to examine predictors of household transmission, we fitted a series of multivariable logistic regression with robust standard errors to account for clustering of individuals within households.Results:We enrolled 695 participants from 180 households: 180 index participants (74 children, 106 adults) and 515 of their household contacts (266 children, 249 adults). A total of 487 household contacts (94.6%) (246 children, 241 adults) had SARS-CoV-2 antibody testing, of whom 239 had a positive result (secondary attack rate 49.1%, 95% confidence interval [CI] 42.9%–55.3%). Eighty-eight (36.8%, 95% CI 29.3%–43.2%) of the 239 were asymptomatic; asymptomatic rates were similar for children (51/130 [39.2%, 95% CI 30.7%–48.5%]) and adults (37/115 [32.2%, 95% CI 24.2%–41.4%]) (odds ratio [OR] 1.3, 95% CI 0.8–2.1). Adults were more likely than children to transmit SARS-CoV-2 (OR 2.2, 95% CI 1.3–3.6). The odds of transmission from asymptomatic (OR 0.6, 95% CI 0.2–1.4) versus symptomatic (OR 0.9, 95% CI 0.6–1.4) index participants to household contacts was uncertain. Predictors of household transmission included household density (number of people per bedroom), relationship to index participant and number of cases in the household.Interpretation:The rate of SARS-CoV-2 transmission within households was nearly 50% during the study period, and children were an important source of spread. The findings suggest that children are an important driver of the COVID-19 pandemic; this should inform public health policy.

On an optimal testing strategy for workplace settings operating during the COVID-19 pandemic.

High quality daily testing for the presence of the SARS-CoV-2 in workplace settings has become part of the standard and mandatory protection measures implemented widely in response to the current pandemic. Such tests are often limited to a small fraction of the attending personnel due to cost considerations, limited availability and processing capabilities and the often cumbersome requirements of the test itself. A maximally efficient use of such an important and frequently scarce resource is clearly required. We here present an optimal testing strategy which minimises the presence of pre-symptomatic and asymptomatic infected members of the population in a workplace setting, derived under a series of simplifying statistical assumptions. These assumptions however, retain many of the generalities of the problem and yield robust results, as verified through a number of numerical simulations. We show that reduction in overall infected-person-days, IPD, by significant percentages can be achieved, for fixed numbers of tests per day of 5% and 10% of the population, of 30% and 50% in the IPD numbers, respectively.

SARS-CoV-2 surveillance in households with and without asthmatic/allergic children: The Human Epidemiology and Response to SARS-CoV-2 study (HEROS)

Whether children and people with asthma and allergic diseases are at increased risk for SARS-CoV-2 infection is not known. Neither is their role in household transmission. Biweekly nasal sample collections and weekly surveys were conducted to identify incident SARS-CoV-2 infections among children (<13 years) and teenagers (13-21 years) enrolled in asthma/allergic disease focused cohorts, and their household members, from May 2020-February 2021. Probability of subject/household infections and household transmissions were calculated using time-to-event analyses, and factors associated with infection and transmission risk using regression analyses. Household (N=1,394) and subject (N=4,142) SARS-CoV-2 infection probability was 25.8% and 14.0%, respectively, and was similar for children (14.0%,CI:8.0-19.6%), teenagers (12.1%,CI:8.2-15.9%), and adults (14.0%,CI:9.5-18.4%). Infections were symptomatic in 24.5% of children, 41.2% of teenagers, and 62.5% of adults. Exposure to both symptomatic (aHR=87.39,CI:58.02-131.63) and asymptomatic (aHR=27.80,CI:17.16–45.03) infected household members was a risk factor for infection. Food allergy was associated with decreased infection risk (aHR=0.50,CI:0.32-0.81), but asthma was not (aHR=1.04,CI:0.73-1.46). Household infection risk was associated with attending in-person school (aHR=1.67,CI:1.09-2.57). Household secondary attack rate was 57.7%. Decreased risk of household transmission was associated with teen age, lower BMI, and lower viral load. Asthma does not increase risk of SARS-CoV-2 infection, while food allergy is protective. SARS-CoV-2 infection risk in children is similar to that of teenagers and adults. SARS-CoV-2 transmission risk and secondary attack rate is much higher than previously estimated in households with children, likely driven by the high frequency of asymptomatic childhood infections.

Village health workers as health diplomats: negotiating health and study participation in a malaria elimination trial in The Gambia

BackgroundAlthough many success stories exist of Village Health Workers (VHWs) improving primary health care, critiques remain about the medicalisation of their roles in disease-specific interventions. VHWs are placed at the bottom of the health system hierarchy as cheap and low-skilled volunteers, irrespective of their highly valued social and political status within communities. In this paper, we shed light on the political role VHWs play and investigate how this shapes their social and medical roles, including their influence on community participation.MethodThe study was carried out within the context of a malaria elimination trial implemented in rural villages in the North Bank of The Gambia between 2016 and 2018. The trial aimed to reduce malaria prevalence by treating malaria index cases and their potentially asymptomatic compound members, in which VHWs took an active role advocating their community and the intervention, mobilising the population, and distributing antimalarial drugs. Mixed-methods research was used to collect and analyse data through qualitative interviews, group discussions, observations, and quantitative surveys.Results and discussionWe explored the emic logic of participation in a malaria elimination trial and found that VHWs played a pivotal role in representing their community and negotiating with the Medical Research Council to bring benefits (e.g. biomedical care service) to the community. We highlight this representative role of VHWs as ‘health diplomats’, valued and appreciated by community members, and potentially increasing community participation in the trial. We argue that VHWs aspire to be politically present and be part of the key decision-makers in the community through their health diplomat role.ConclusionIt is thus likely that in the context of rural Gambia, supporting VHWs beyond medical roles, in their social and political roles, would contribute to the improved performance of VHWs and to enhanced community participation in activities the community perceive as beneficial.

POSC98 A Model to Evaluate the Cost-Effectiveness of a Highly-Sensitive Rapid Diagnostic Test for Malaria in a Community Setting in Uganda

Malaria remains a major cause of morbidity in Uganda, despite the presence of effective and low-cost interventions such as artemisinin-based combination therapy (ACT) and sulfadoxine/pyrimethamine (SP). This is largely attributed to the prevalence of asymptomatic low-density infections that often go undetected and hence untreated. A new generation of highly-sensitive rapid diagnostic tests (HS-RDTs) has been shown to detect asymptomatic low-density infections, offering a potential tool to help move Uganda towards Malaria elimination. A pragmatic literature review informed the conceptualisation and structuring of a cost-effectiveness model to evaluate use of the HS-RDT compared with conventional diagnostic tests (c-RDT) in three patient cohorts – febrile patients presenting at community health facilities, pregnant women attending ante-natal clinics, and asymptomatic household members of febrile children aged <5. A decision tree model will be used for the analysis to compare clinical (DALY) and cost outcomes, with patients entering the model at diagnosis stage. Clinical inputs, direct and indirect costs (including testing, treatment, disease management and mortality) are sourced from local publications. Prevalence, rapid diagnostic test (RDT) sensitivity and false positive rates will be based on data from a community based observational study in Mpigi District, Uganda. Results from the observational study and model outputs, will be used to test the hypothesis that the higher detection rate using HS-RDT translates into a larger number of asymptomatic malaria cases detected in all three patient cohorts, leading to clinical and cost benefits. Targeting and treating asymptomatic infections is also anticipated to help reduce the asymptomatic Malaria reservoir, thereby contributing towards the goal of Malaria elimination. One way sensitivity analysis will be conducted to test model sensitivity to key inputs. A limitation of this approach is that the model is not a dynamic transmission model and does not therefore model long-term consequences and seasonal effects.

The Multi-Compartment SI(RD) Model with Regime Switching: An Application to COVID-19 Pandemic

We study—with existence and unicity results—a variant of the SIR model for an infectious disease incorporating both the possibility of a death outcome—in a short period of time—and a regime switch that can account for the mitigation measures used to control the spreading of the infections, such as a total lockdown. This model is parametrised by three parameters: the basic reproduction number, the mortality rate of the infected, and the duration of the disease. We discuss a particular example of application to Portuguese COVID-19 data in two short periods just after the start of the epidemic in 4 March 2020, with the first two cases dated that day. We propose a simple and effective method for the estimation of the main parameters of the disease, namely, the basic reproduction number and the mortality rate of the infected. We correct these estimated values to take into account the asymptomatic non-diagnosed members of the population. We compare the outcome of the model in the cases of the existence, or not, of a regime switch, and under three different scenarios, with a remarkable agreement between model and data deaths in the case of our basis scenario. In a final short remark, we deal with the existence of symmetries for the proposed model.

Screening for SARS-CoV-2 infection in asymptomatic individuals using the Panbio COVID-19 antigen rapid test (Abbott) compared with RT-PCR: a prospective cohort study

BackgroundAntigen-based point-of-care tests for identification of SARS-CoV-2 may markedly enhance effectiveness of population-based controlling strategies. Previous studies have demonstrated >70% sensitivity and high specificity compared with reverse transcriptase real-time PCR...