Within-household Transmission Research Articles

MERS-CoV exposure and risk factors for MERS-CoV ELISA seropositivity among members of livestock-owning households in southern Jordan: a population based cross-sectional study

Although dromedary camels (Camelus dromedarius) are known to be the host reservoir for MERS-CoV, the virus causing Middle East respiratory syndrome (MERS), zoonotic transmission pathways and camel subpopulations posing highest transmission risk are poorly understood. Extensively managed herds, ubiquitous across the Arabian Peninsula, present a major potential source of primary infection. In this study we aimed to address key knowledge gaps regarding MERS epidemiology among high-risk communities associated with such herds, which is essential information for effective control strategies. We did a cross-sectional study between Sept 27, 2017, and Oct 11, 2018, among members of livestock-owning households in southern Jordan (Aqaba East, Aqaba West, Ma'an East, and Ma'an West regions), with random selection of households (house and tent dwellings) from Ministry of Agriculture lists via computer-generated randomisation lists. Household visits were done, with questionnaires administered to household members regarding potential risk factors for MERS-CoV exposure in the past 6months and blood samples and nasal and oral swabs collected, alongside physical examination data including blood pressure and blood glucose. Children younger than 5years and individuals without capacity to provide informed consent were excluded. Serum was tested for IgG antibodies to MERS-CoV spike protein (S1 subunit) and nucleocapsid (N) protein with in-house indirect ELISAs, and viral RNA was detected in nasal and oral samples by RT-PCR. The primary outcome was evidence of MERS-CoV exposure (ascertained by seropositive status on S1 or NELISAs, or a positive swab sample on RT-PCR); secondary outcomes were potential associations between possible risk factors and seropositive status. RT-PCR data were to be presented descriptively. Seroprevalence estimates were obtained at the individual and household levels, and associations between hypothetical risk factors and seropositive status were assessed with use of mixed-effects logistic regression. We sampled 879household members (median age 27years [IQR 16-44]; 471 [54%] males and 408 [46%] females) from 204households. 72 (8%) household members were seropositive on S1 ELISA (n=25, 3%) or NELISA (n=52,6%). No positive nasal or oral swab samples were identified on RT-PCR. Within-household clustering was identified for seropositivity on S1 ELISA (intraclass correlation coefficient 0·88 [0·35-0·96]) but not NELISA (0·00 [0·00-0·27]). On multivariable analysis, S1 ELISA seropositivity was associated with frequently (≥weekly) interacting with young (age<1year) camels (adjusted odds ratio [ORadj] 3·85 [95% CI 1·41-11·61], p=0·011), with frequent kissing and petting (ORadj 4·56 [1·55-15·42], p=0·0074), and frequent feeding and watering (ORadj 4·97 [1·80-15·29], p=0·0027) of young camels identified as risk activities. Attending camel races (ORadj 3·73 [1·11-12·47], p=0·029), frequently feeding and watering camels of any age (ORadj 3·18 [1·12-10·84], p=0·040), and elevated blood glucose (>150mg/dL; ORadj 4·59[1·23-18·36], p=0·021) were also associated with S1 ELISA seropositivity. Among individuals without history of camel contact, S1 ELISA seropositivity was associated with sharing a household with an S1 ELISA-positive household member (ORadj 8·92 [1·06-92·99], p=0·044), and with sharing a household with an S1 ELISA-positive household member with history of camel contact (ORadj 24·74 [2·72-306·14], p=0·0050). NELISA seropositivity was associated with age (categorical, p=0·0069), a household owning a young camel (age <18months; ORadj 1·98 [1·02-4·09], p=0·043), and frequently feeding and watering camels of any age (ORadj 1·98 [1·09-3·69]; p=0·025). The study findings highlight the importance of effective MERS-CoV surveillance and control strategies among camel-owning communities in Jordan and the Arabian Peninsula. Juvenile dromedaries pose increased risk for zoonotic MERS-CoV transmission and should be prioritised for vaccination once such vaccines become available. Among high-risk communities, vaccination strategies should prioritise camel-owning households, particularly individuals engaged in camel husbandry or racing, and household members who are older or diabetic, with evidence to suggest secondary within-household transmission. UK Medical Research Council and US National Institute of Allergy and Infectious Diseases.

Tuberculin skin test surveys and the Annual Risk of Tuberculous Infection in school children in Northern KwaZulu-Natal.

Tuberculin skin test surveys in primary school children can be used to quantify Mycobacterium tuberculosis transmission at community level. KwaZulu-Natal province, South Africa, is home to 11.5 million people and suffers a burden of tuberculosis disease that is among the highest in the world. The last tuberculin survey in the province was undertaken in 1979. We performed a tuberculin skin test survey nested within a demographic and health household surveillance programme in Northern KwaZulu-Natal. We enrolled children aged between six and eight years of age attending primary schools in this community. Mixture analysis was used to determine tuberculin skin test thresholds and the Annual Risk of Tuberculous Infection derived from age at testing and infection prevalence. The Community Infection Ratio, a measure of the relative importance of within-household and community transmission, was calculated from data on tuberculin positivity disaggregated by household tuberculosis contact. Between June and December 2013, we obtained tuberculin skin test results on 1240 children. Mixture analysis proved unstable, suggesting two potential thresholds for test positivity. Using a threshold of ≥10mm or treating all non zero reactions as positive yielded estimates of the Annual Risk of Tuberculous Infection of 1.7% (1.4-2.1%) or 2.4% (2.0-3.0%). Using the same thresholds and including children reported to be receiving TB treatment as cases, resulted in estimates of 2.0% (1.6-2.5%) or 2.7% (2.2-3.3%). The Community Infection Ratio was 0.58 (0.33-1.01). The force of infection in this community is lower than that observed in Western Cape province, South Africa, but higher than that observed in community settings in most other parts of the world. Children in this community are commonly infected with Mycobacterium tuberculosis outside the home. Interventions to interrupt transmission are urgently needed.

COVID-19 infections in English schools and the households of students and staff 2020-21: a self-controlled case-series analysis.

The role of children and staff in SARS-CoV-2 transmission outside and within households is still not fully understood when large numbers are in regular, frequent contact in schools. We used the self-controlled case-series method during the alpha- and delta-dominant periods to explore the incidence of infection in periods around a household member infection, relative to periods without household infection, in a cohort of primary and secondary English schoolchildren and staff from November 2020 to July 2021. We found the relative incidence of infection in students and staff was highest in the 1-7 days following household infection, remaining high up to 14 days after, with risk also elevated in the 6--12 days before household infection. Younger students had a higher relative incidence following household infection, suggesting household transmission may play a more prominent role compared with older students. The relative incidence was also higher among students in the alpha variant dominant period. This analysis suggests SARS-CoV2 infection in children, young people and staff at English schools were more likely to be associated with within-household transmission than from outside the household, but that a small increased risk of seeding from outside is observed.

Estimation of introduction and transmission rates of SARS-CoV-2 in a prospective household study.

Household studies provide an efficient means to study transmission of infectious diseases, enabling estimation of susceptibility and infectivity by person-type. A main inclusion criterion in such studies is usually the presence of an infected person. This precludes estimation of the hazards of pathogen introduction into the household. Here we estimate age- and time-dependent household introduction hazards together with within household transmission rates using data from a prospective household-based study in the Netherlands. A total of 307 households containing 1,209 persons were included from August 2020 until March 2021. Follow-up of households took place between August 2020 and August 2021 with maximal follow-up per household mostly limited to 161 days. Almost 1 out of 5 households (59/307) had evidence of an introduction of SARS-CoV-2. We estimate introduction hazards and within-household transmission rates in our study population with penalized splines and stochastic epidemic models, respectively. The estimated hazard of introduction of SARS-CoV-2 in the households was lower for children (0-12 years) than for adults (relative hazard: 0.62; 95%CrI: 0.34-1.0). Estimated introduction hazards peaked in mid October 2020, mid December 2020, and mid April 2021, preceding peaks in hospital admissions by 1-2 weeks. Best fitting transmission models included increased infectivity of children relative to adults and adolescents, such that the estimated child-to-child transmission probability (0.62; 95%CrI: 0.40-0.81) was considerably higher than the adult-to-adult transmission probability (0.12; 95%CrI: 0.057-0.19). Scenario analyses indicate that vaccination of adults can strongly reduce household infection attack rates and that adding adolescent vaccination offers limited added benefit.

Effects of Mitigation and Control Policies in Realistic Epidemic Models Accounting for Household Transmission Dynamics.

Compartmental infectious disease (ID) models are often used to evaluate nonpharmaceutical interventions (NPIs) and vaccines. Such models rarely separate within-household and community transmission, potentially introducing biases in situations in which multiple transmission routes exist. We formulated an approach that incorporates household structure into ID models, extending the work of House and Keeling. We developed a multicompartment susceptible-exposed-infectious-recovered-susceptible-vaccinated (MC-SEIRSV) modeling framework, allowing nonexponentially distributed duration in exposed and infectious compartments, that tracks within-household and community transmission. We simulated epidemics that varied by community and household transmission rates, waning immunity rate, household size (3 or 5 members), and numbers of exposed and infectious compartments (1-3 each). We calibrated otherwise identical models without household structure to the early phase of each parameter combination's epidemic curve. We compared each model pair in terms of epidemic forecasts and predicted NPI and vaccine impacts on the timing and magnitude of the epidemic peak and its total size. Meta-analytic regressions characterized the relationship between household structure inclusion and the size and direction of biases. Otherwise similar models with and without household structure produced equivalent early epidemic curves. However, forecasts from models without household structure were biased. Without intervention, they were upward biased on peak size and total epidemic size, with biases also depending on the number of exposed and infectious compartments. Model-estimated NPI effects of a 60% reduction in community contacts on peak time and size were systematically overestimated without household structure. Biases were smaller with a 20% reduction NPI. Because vaccination affected both community and household transmission, their biases were smaller. ID models without household structure can produce biased outcomes in settings in which within-household and community transmission differ. Infectious disease models rarely separate household transmission from community transmission. The pace of household transmission may differ from community transmission, depends on household size, and can accelerate epidemic growth.Many infectious disease models assume exponential duration distributions for infected states. However, the duration of most infections is not exponentially distributed, and distributional choice alters modeled epidemic dynamics and intervention effectiveness.We propose a mathematical framework for household and community transmission that allows for nonexponential duration times and a suite of interventions and quantified the effect of accounting for household transmission by varying household size and duration distributions of infected states on modeled epidemic dynamics.Failure to include household structure induces biases in the modeled overall course of an epidemic and the effects of interventions delivered differentially in community settings. Epidemic dynamics are faster and more intense in populations with larger household sizes and for diseases with nonexponentially distributed infectious durations. Modelers should consider explicitly incorporating household structure to quantify the effects of non-pharmaceutical interventions (e.g., shelter-in-place).

Contribution of cats and dogs to SARS-CoV-2 transmission in households.

SARS-CoV-2 is known to jump across species. The occurrence of transmission in households between humans and companion animals has been shown, but the contribution of companion animals to the overall transmission within a household is unknown. The basic reproduction number (R0) is an important indicator to quantify transmission. For a pathogen with multiple host species, such as SARS-CoV-2, the basic reproduction number needs to be calculated from the partial reproduction numbers for each combination of host species. In this study, the basic and partial reproduction numbers for SARS-CoV-2 were estimated by reanalyzing a survey of Dutch households with dogs and cats and minimally one SARS-CoV-2-infected human. For households with cats, a clear correlation between the number of cats and the basic reproduction number (Spearman's correlation: p 0.40, p-value: 1.4 × 10-5) was identified, while for dogs, the correlation was smaller and not significant (Spearman's correlation: p 0.12, p-value: 0.21). Partial reproduction numbers from cats or dogs to humans were 0.3 (0.0-2.0) and 0.3 (0.0-3.5) and from humans to cats or dogs were 0.6 (0.4-0.8) and 0.6 (0.4-0.9). Thus, the estimations of within-household transmission indicated the likelihood of transmission from these companion animals to humans and vice versa, but the observational nature of this study limited the ability to establish conclusive evidence. This study's findings support the advice provided during the pandemic to COVID-19 patients to maintain distance from companion animals as a precautionary measure and given the possibility of transmission, although there is an overall relatively limited impact on the pandemic when compared to human-to-human transmission.

Smart Thermometer–Based Participatory Surveillance to Discern the Role of Children in Household Viral Transmission During the COVID-19 Pandemic

Children's role in spreading virus during the COVID-19 pandemic is yet to be elucidated, and measuring household transmission traditionally requires contact tracing. To discern children's role in household viral transmission during the pandemic when enveloped viruses were at historic lows and the predominance of viral illnesses were attributed to COVID-19. This cohort study of a voluntary US cohort tracked data from participatory surveillance using commercially available thermometers with a companion smartphone app from October 2019 to October 2022. Eligible participants were individuals with temperature measurements in households with multiple members between October 2019 and October 2022 who opted into data sharing. Proportion of household transmissions with a pediatric index case and changes in transmissions during school breaks were assessed using app and thermometer data. A total of 862 577 individuals from 320 073 households with multiple participants (462 000 female [53.6%] and 463 368 adults [53.7%]) were included. The number of febrile episodes forecast new COVID-19 cases. Within-household transmission was inferred in 54 506 (15.4%) febrile episodes and increased from the fourth pandemic period, March to July 2021 (3263 of 32 294 [10.1%]) to the Omicron BA.1/BA.2 wave (16 516 of 94 316 [17.5%]; P < .001). Among 38 787 transmissions in 166 170 households with adults and children, a median (IQR) 70.4% (61.4%-77.6%) had a pediatric index case; proportions fluctuated weekly from 36.9% to 84.6%. A pediatric index case was 0.6 to 0.8 times less frequent during typical school breaks. The winter break decrease was from 68.4% (95% CI, 57.1%-77.8%) to 41.7% (95% CI, 34.3%-49.5%) at the end of 2020 (P < .001). At the beginning of 2022, it dropped from 80.3% (95% CI, 75.1%-84.6%) to 54.5% (95% CI, 51.3%-57.7%) (P < .001). During summer breaks, rates dropped from 81.4% (95% CI, 74.0%-87.1%) to 62.5% (95% CI, 56.3%-68.3%) by August 2021 (P = .02) and from 83.8% (95% CI, 79.2%-87.5) to 62.8% (95% CI, 57.1%-68.1%) by July 2022 (P < .001). These patterns persisted over 2 school years. In this cohort study using participatory surveillance to measure within-household transmission at a national scale, we discerned an important role for children in the spread of viral infection within households during the COVID-19 pandemic, heightened when schools were in session, supporting a role for school attendance in COVID-19 spread.

Staphylococcal diversity in atopic dermatitis from an individual to a global scale

Atopic dermatitis (AD) is a multifactorial, chronic relapsing disease associated with genetic and environmental factors. Among skin microbes, Staphylococcus aureus and Staphylococcus epidermidis are associated with AD, but how genetic variability and staphylococcal strains shape the disease remains unclear. We investigated the skin microbiome of an AD cohort (n= 54) as part of a prospective natural history study using shotgun metagenomic and whole genome sequencing, which we analyzed alongside publicly available data (n= 473). AD status and global geographical regions exhibited associations with strains and genomic loci of S.aureus and S.epidermidis. In addition, antibiotic prescribing patterns and within-household transmission between siblings shaped colonizing strains. Comparative genomics determined that S.aureus AD strains were enriched in virulence factors, whereas S.epidermidis AD strains varied in genes involved in interspecies interactions and metabolism. In both species, staphylococcal interspecies genetic transfer shaped gene content. These findings reflect the staphylococcal genomic diversity and dynamics associated with AD.

Risk Factors, Temporal Dependence, and Seasonality of Human Extended-Spectrum β-Lactamases-Producing Escherichia coli and Klebsiella pneumoniae Colonization in Malawi: A Longitudinal Model-Based Approach.

Sub-Saharan Africa has the highest estimated death rate attributable to antimicrobial resistance, especially from extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E). However, the dynamics of human colonization in the community with ESBL-E are not well described. Inadequate water, sanitation, and hygiene infrastructure and associated behaviors are believed to play an important role in transmission of ESBL-E, and an improved understanding of the temporal dynamics of within-household transmission could help inform the design of future policies. In this 18-month study, using microbiological data and household surveys, we built a multivariable hierarchical harmonic logistic regression model to identify risk factors for colonization with ESBL-producing Escherichia coli and Klebsiella pneumoniae, reflecting household structure and temporal correlation of colonization status. Being male was associated with a lower risk of colonization with ESBL-producing E. coli (odds ratio [OR], 0.786; credible interval [CrI], .678-.910), whereas the use of a tube well or a borehole was associated with an increased risk (OR, 1.550; CrI, 1.003-2.394). For ESBL-producing K. pneumoniae, recent antibiotic exposure increased risk of colonization (OR, 1.281; CrI, 1.049-1.565), whereas sharing plates decreased that risk (OR, 0.672; CrI, .460-.980). Finally, the temporal correlation range of 8 to 11 weeks provided evidence that within-household transmission occurs within this time frame. We describe different risks for colonization with different enteric bacterial species. Our findings suggest interventions to reduce transmission targeted at the household level need to focus on improving water, sanitation, and hygiene infrastructure and associated behaviors, whereas at the community level, they should focus on both environmental hygiene and antibiotic stewardship.

Evidence of cat-to-human transmission of Staphylococcus felis.

Introduction. Staphylococcus felis is a coagulase-negative staphylococcal species that is commonly isolated from healthy cats. Like other commensal staphylococci, S. felis can cause opportunistic infections, e.g. otitis externa, skin and urinary tract infections, in cats.Gap Statement. Several studies have reported within-household transmission between humans and pets and human infections caused by coagulase-positive staphylococci. However, human infections with coagulase-negative staphylococci of zoonotic origin are relatively rare.Methodology. Culture of a surgical site infection in a 58-year-old woman who underwent a laminectomy revealed dominant growth of S. felis. The three cats owned by the patient were sampled to investigate potential within-household transmission. S. felis isolates were sequenced to investigate the relatedness of the isolates and to look for virulence factors and host specific genes.Results. All cats were colonized with S. felis. Comparative genomics of the isolates showed that each cat was colonized with a distinct genotype. The patient's isolate clustered with isolates of one of the cats. Sequence analysis of the studied isolates together with 29 publicly available S. felis genomes detected putative virulence factors that can be crucial in potential interspecies transmission.Conclusion. The current case is the first reported human infection caused by S. felis and highlights the zoonotic potential of this bacterial species. Evidence of cat-to-human transmission was shown by comparative genomics of isolates from the patient with isolates of her cats.

Detection and Molecular Characterization of the SARS-CoV-2 Delta Variant and the Specific Immune Response in Companion Animals in Switzerland.

In human beings, there are five reported variants of concern of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). However, in contrast to human beings, descriptions of infections of animals with specific variants are still rare. The aim of this study is to systematically investigate SARS-CoV-2 infections in companion animals in close contact with SARS-CoV-2-positive owners ("COVID-19 households") with a focus on the Delta variant. Samples, obtained from companion animals and their owners were analyzed using a real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and next-generation sequencing (NGS). Animals were also tested for antibodies and neutralizing activity against SARS-CoV-2. Eleven cats and three dogs in nine COVID-19-positive households were RT-qPCR and/or serologically positive for the SARS-CoV-2 Delta variant. For seven animals, the genetic sequence could be determined. The animals were infected by one of the pangolin lineages B.1.617.2, AY.4, AY.43 and AY.129 and between zero and three single-nucleotide polymorphisms (SNPs) were detected between the viral genomes of animals and their owners, indicating within-household transmission between animal and owner and in multi-pet households also between the animals. NGS data identified SNPs that occur at a higher frequency in the viral sequences of companion animals than in viral sequences of humans, as well as SNPs, which were exclusively found in the animals investigated in the current study and not in their owners. In conclusion, our study is the first to describe the SARS-CoV-2 Delta variant transmission to animals in Switzerland and provides the first-ever description of Delta-variant pangolin lineages AY.129 and AY.4 in animals. Our results reinforce the need of a One Health approach in the monitoring of SARS-CoV-2 in animals.

Within-Household Transmission of Chikungunya Virus During an Outbreak in Cambodia

Within-Household Transmission of Chikungunya Virus During an Outbreak in Cambodia

A four-generation family transmission chain of COVID-19 along the China-Myanmar border in October to November 2021.

Foreign imported patients and within-household transmission have been the focus and difficulty of coronavirus disease 2019 (COVID-19) prevention and control, which has also posed challenges to border areas' management. However, household transmission caused by foreign imported cases has not been reported in China's border areas. This study aimed to reveal a clear family clustering transmission chain of COVID-19 caused by contact with Myanmar refugees along the China-Myanmar border during an outbreak in October to November 2021. During the outbreak, detailed epidemiological investigations were conducted on confirmed patients with COVID-19 and their close contacts in daily activities. Patients were immediately transported to a designated hospital for treatment and quarantine, and their close contacts were quarantined at designated sites. Regular nucleic acid testing and SARS-CoV-2 antibody testing were provided to them. A clear four-generation family clustering transmission involving five patients with COVID-19 was found along the China-Myanmar border. The index case (Patient A) was infected by brief conversations with Myanmar refugees across border fences during work. His wife (Patient B) and 9-month-old daughter (Patient C) were second-generation cases infected by daily contact with him. His 2-year-old daughter (Patient D) was the third-generation case infected by her mother and sister during quarantine in the same room and then transmitted the virus to her grandmother (Patient E, the fourth-generation case) who looked after her after Patients B and C were diagnosed and transported to the hospital. The household secondary attack rate was 80.0%, the average latent period was 4 days, and the generation time was 3 days. Ten of 942 close contacts (1.1%) of this family had positive IgM antibody during the medical observation period. In total 73.9% (696/942) of them were positive for IgG antibody and 8.3% (58/696) had IgG levels over 20 S/CO (optical density of the sample/cut-off value of the reagent). This typical transmission chain indicated that it is essential to strengthen COVID-19 prevention and control in border areas, and explore more effective children care approaches in quarantine sites.

Effect of Inactivated SARS-CoV-2 Vaccines and ChAdOx1 nCoV-19 Vaccination to Prevent COVID-19 in Thai Households (VacPrevent trial)

ObjectivesSARS-CoV-2 is primarily transmitted within households, with massive healthcare system burdens. The role of inactivated vaccines and ChAdOx1 nCoV-19 vaccination in the prevention of within-household transmission remains unknown.MethodsThis observational case-control study tracked 408 SARS-CoV-2 polymerase chain reaction–confirmed index cases from April to September 2021. This study aimed to prove the benefit of inactivated and ChAdOx1 nCoV-19 vaccinated index cases in preventing within-household transmissibility.ResultsA total of 1178 household contacts were investigated. A total of 231 index cases were vaccinated with inactivated or ChAdOx1 nCoV-19 vaccine, and 177 were unvaccinated. The vaccinated index cases exhibited a 7.8% risk reduction in household transmission. There was no difference in the secondary attack rate of 50.77% in unvaccinated cases compared with 46.81% in vaccinated index cases (P-value = 0.177). Those who completed the two-dose SARS-CoV-2 vaccination demonstrated a 93% reduction in household transmissibility within 14-90 days. The effectiveness for preventing household transmission was 26.09%. The 87% reduced risk of household transmissibility was observed among those who wore masks.ConclusionThe completed two-dose SARS-CoV-2 inactivated and ChAdOx1 nCoV-19 vaccination within 14-90 days among index cases demonstrated benefits in preventing within-household transmissibility. Implementing high-efficacy vaccination and an appropriate booster dose can prevent household transmission.

The potential impact of co-residence structures on socio-demographic inequalities in COVID-19 mortality

During the COVID-19 pandemic, confinement measures were adopted across the world to limit the spread of the virus. In France, these measures were applied between March 17 and May 10. Using high-quality population census data and focusing on co-residence structures on French territory, this article analyzes how co-residence patterns unevenly put different socio-demographic groups at risk of being infected and dying from COVID-19. The research ambition is to quantify the possible impact of co-residence structures heterogeneity on socio-economic inequalities in mortality stemming from within-household transmission of the virus. Using a simulation approach, the article highlights the existence of theoretical pronounced inequalities of vulnerability to COVID-19 related to cohabitation structures as well as a reversal of the social gradient of vulnerability when the age of the infected person increases. Among young age categories, infection is simulated to lead to more deaths in the less educated or foreign-born populations. Among the older ones, the inverse holds with infections having a greater potential to provoke deaths through the transmission of the virus within households headed by a highly educated or a native-born person. Demographic patterns such as the cohabitation of multiple generations and the survival of both partners of a couple help to explain these results. Even though inter-generational co-residence and large households are more common among the lower educated and foreign born in general, the higher educated are more likely to still live with their partner at higher ages.

SARS-CoV-2 Antibody Dynamics, Within-Household Transmission and the Impact of Contact Tracing from Community-Wide Serological Testing in the Italian Municipality of Vo’

Background: In February and Mach 2020, two mass swab testing campaigns conducted in Vo’, Italy demonstrated the extent of asymptomatic SARS-CoV-2 infection and the feasibility of epidemic suppression. Methods: We tested 86% of the Vo’ population (2,602 subjects) in May with three immuno-assays detecting antibodies against the spike (S) and nucleocapsid (N) antigens, a neutralisation assay and Polymerase Chain Reaction (PCR). Subjects testing positive to PCR in February/March or a serological assay in May were tested again in November. Findings: Combining the results obtained with the three assays, we estimate a seroprevalence of 3.5% (95% Credible Interval (CrI) 2.8%-4.3%) in May. In November, all assays showed a reduction in antibody titres, though 98.8% (95% Confidence Interval (CI) 93.7%-100.0%) of sera still reacted against at least one antigen. Conversely, 18.6% (95% CI 11.0%-28.5%) showed a marked increase of antibody or viral neutralisation reactivity between May and November, linked to documented or likely re-exposures. We found significant differences in the magnitude and persistence of the antibody response by age group but not by symptom occurrence, hospitalisation, or sex. Analysis of the serostatus of 1,118 households indicated a 27.3% (95% CrI 19.2%-34.6%) probability of SARS-CoV-2 transmission among household members and that 81.8% (95% CrI 55.9%-95.2%) of transmission could be attributed to 20% of infections. Contact tracing correctly identified 44% of the infected subjects and had limited impact on the epidemic. Interpretation: We find evidence of antibody persistence up to nine months post infection. Different assays provided significantly different seroprevalence estimates, making it challenging to compare seroprevalence estimates globally. Due to the high population susceptibility and the limited impact of contact tracing, rigorous testing and improvements in contact tracing are essential to control SARS-CoV-2. Funding: Veneto Region, Medical Research Council, Wellcome Trust, Royal Society, University of Padua, UK National Institute for Health Research. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The first and second serosurveys of the Vo' population were approved by the Ethics Committee for Clinical Research of the province of Padova.

Incidence, household transmission, and neutralizing antibody seroprevalence of Coronavirus Disease 2019 in Egypt: Results of a community-based cohort.

SARS-CoV-2 virus is transmitted in closed settings to people in contact with COVID-19 patients such as healthcare workers and household contacts. However, household person-to-person transmission studies are limited. Households participating in an ongoing cohort study of influenza incidence and prevalence in rural Egypt were followed. Baseline enrollment was done from August 2015 to March 2017. The study protocol was amended in April 2020 to allow COVID-19 incidence and seroprevalence studies. A total of 290 households including 1598 participants were enrolled and followed from April to October 2020 in four study sites. When a participant showed respiratory illness symptoms, a serum sample and a nasal and an oropharyngeal swab were obtained. Swabs were tested by RT-PCR for SARS-CoV-2 infection. If positive, the subject was followed and swabs collected on days three, six, nine, and 14 after the first swab day and a serum sample obtained on day 14. All subjects residing with the index case were swabbed following the same sampling schedule. Sera were collected from cohort participants in October 2020 to assess seroprevalence. Swabs were tested by RT-PCR. Sera were tested by Microneutralization Assay to measure the neutralizing antibody titer. Incidence of COVID-19, household secondary attack rate, and seroprevalence in the cohort were determined. The incidence of COVID-19 was 6.9% and the household secondary attack rate was 89.8%. Transmission within households occurred within two-days of confirming the index case. Infections were asymptomatic or mild with symptoms resolving within 10 days. The majority developed a neutralizing antibody titer by day 14 post onset. The overall seroprevalence among cohort participants was 34.8%. These results suggest that within-household transmission is high in Egypt. Asymptomatic or mild illness is common. Most infections seroconvert and have a durable neutralizing antibody titer.

Dynamics of COVID-19 under social distancing measures are driven by transmission network structure.

In the absence of pharmaceutical interventions, social distancing is being used worldwide to curb the spread of COVID-19. The impact of these measures has been inconsistent, with some regions rapidly nearing disease elimination and others seeing delayed peaks or nearly flat epidemic curves. Here we build a stochastic epidemic model to examine the effects of COVID-19 clinical progression and transmission network structure on the outcomes of social distancing interventions. Our simulations show that long delays between the adoption of control measures and observed declines in cases, hospitalizations, and deaths occur in many scenarios. We find that the strength of within-household transmission is a critical determinant of success, governing the timing and size of the epidemic peak, the rate of decline, individual risks of infection, and the success of partial relaxation measures. The structure of residual external connections, driven by workforce participation and essential businesses, interacts to determine outcomes. We suggest limited conditions under which the formation of household “bubbles” can be safe. These findings can improve future predictions of the timescale and efficacy of interventions needed to control second waves of COVID-19 as well as other similar outbreaks, and highlight the need for better quantification and control of household transmission.

Prenatal and early-life exposure to the Great Chinese Famine increased the risk of tuberculosis in adulthood across two generations

Global food security is a major driver of population health, and food system collapse may have complex and long-lasting effects on health outcomes. We examined the effect of prenatal exposure to the Great Chinese Famine (1958-1962)-the largest famine in human history-on pulmonary tuberculosis (PTB) across consecutive generations in a major center of ongoing transmission in China. We analyzed >1 million PTB cases diagnosed between 2005 and 2018 in Sichuan Province using age-period-cohort analysis and mixed-effects metaregression to estimate the effect of the famine on PTB risk in the directly affected birth cohort (F1) and their likely offspring (F2). The analysis was repeated on certain sexually transmitted and blood-borne infections (STBBI) to explore potential mechanisms of the intergenerational effects. A substantial burden of active PTB in the exposed F1 cohort and their offspring was attributable to the Great Chinese Famine, with more than 12,000 famine-attributable active PTB cases (>1.23% of all cases reported between 2005 and 2018). An interquartile range increase in famine intensity resulted in a 6.53% (95% confidence interval [CI]: 1.19-12.14%) increase in the ratio of observed to expected incidence rate (incidence rate ratio, IRR) in the absence of famine in F1, and an 8.32% (95% CI: 0.59-16.6%) increase in F2 IRR. Increased risk of STBBI was also observed in F2. Prenatal and early-life exposure to malnutrition may increase the risk of active PTB in the exposed generation and their offspring, with the intergenerational effect potentially due to both within-household transmission and increases in host susceptibility.

Hand hygiene improvement or antibiotic restriction to control the household transmission of extended-spectrum \u03b2-lactamase-producing Escherichia coli: a mathematical modelling study

BackgroundThe best strategy to control ESBL-producing Escherichia coli (ESBL-EC) spread in the community is lacking.MethodsWe developed an individual-based transmission model to evaluate the impact of hand hygiene (HH) improvement and reduction in antibiotic use on the within-household transmission of ESBL-EC. We used data from the literature and incorporated key elements of ESBL-EC transmission such as the frequency and nature of contacts among household members, antibiotic use in the community and hand hygiene behaviour. We introduced in a household a single ESBL-EC colonised person and simulated the transmission dynamics of ESBL-EC over a one-year time horizon.ResultsThe probability of ESBL-EC transmission depended on the household composition and the profile of the initial carrier. In the two-person household, the probability of ESBL-EC transmission was 5.3% (95% CI 5.0–5.6) or 6.6% (6.3–6.9) when the index person was a woman or a man, respectively. In a four-person household, the probability of transmission varied from 61.4% (60.9–62.0) to 68.8% (68.3–69.3) and was the highest when the index patient was the baby. Improving HH by 50% reduced the probability of transmission by 33–62%. Antibiotic restriction by 50% reduced the transmission by 2–6%.ConclusionsThe transmission of ESBL-EC is frequent in households and especially those with a baby. Antibiotic reduction had little impact on ESBL-EC. Improvement of hygiene in the community could help prevent transmission of ESBL-EC.