Circulation of multidrug-resistant bacteria (MRB) in healthcare facilities is a major public health problem. These settings have been greatly impacted by the Coronavirus Disease 2019 (COVID-19) ...pandemic, notably due to surges in COVID-19 caseloads and the implementation of infection control measures. We sought to evaluate how such collateral impacts of COVID-19 impacted the nosocomial spread of MRB in an early pandemic context.
We developed a mathematical model in which Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and MRB cocirculate among patients and staff in a theoretical hospital population. Responses to COVID-19 were captured mechanistically via a range of parameters that reflect impacts of SARS-CoV-2 outbreaks on factors relevant for pathogen transmission. COVID-19 responses include both "policy responses" willingly enacted to limit SARS-CoV-2 transmission (e.g., universal masking, patient lockdown, and reinforced hand hygiene) and "caseload responses" unwillingly resulting from surges in COVID-19 caseloads (e.g., abandonment of antibiotic stewardship, disorganization of infection control programmes, and extended length of stay for COVID-19 patients). We conducted 2 main sets of model simulations, in which we quantified impacts of SARS-CoV-2 outbreaks on MRB colonization incidence and antibiotic resistance rates (the share of colonization due to antibiotic-resistant versus antibiotic-sensitive strains). The first set of simulations represents diverse MRB and nosocomial environments, accounting for high levels of heterogeneity across bacterial parameters (e.g., rates of transmission, antibiotic sensitivity, and colonization prevalence among newly admitted patients) and hospital parameters (e.g., rates of interindividual contact, antibiotic exposure, and patient admission/discharge). On average, COVID-19 control policies coincided with MRB prevention, including 28.2% 95% uncertainty interval: 2.5%, 60.2% fewer incident cases of patient MRB colonization. Conversely, surges in COVID-19 caseloads favoured MRB transmission, resulting in a 13.8% -3.5%, 77.0% increase in colonization incidence and a 10.4% 0.2%, 46.9% increase in antibiotic resistance rates in the absence of concomitant COVID-19 control policies. When COVID-19 policy responses and caseload responses were combined, MRB colonization incidence decreased by 24.2% -7.8%, 59.3%, while resistance rates increased by 2.9% -5.4%, 23.2%. Impacts of COVID-19 responses varied across patients and staff and their respective routes of pathogen acquisition. The second set of simulations was tailored to specific hospital wards and nosocomial bacteria (methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase producing Escherichia coli). Consequences of nosocomial SARS-CoV-2 outbreaks were found to be highly context specific, with impacts depending on the specific ward and bacteria evaluated. In particular, SARS-CoV-2 outbreaks significantly impacted patient MRB colonization only in settings with high underlying risk of bacterial transmission. Yet across settings and species, antibiotic resistance burden was reduced in facilities with timelier implementation of effective COVID-19 control policies.
Our model suggests that surges in nosocomial SARS-CoV-2 transmission generate selection for the spread of antibiotic-resistant bacteria. Timely implementation of efficient COVID-19 control measures thus has 2-fold benefits, preventing the transmission of both SARS-CoV-2 and MRB, and highlighting antibiotic resistance control as a collateral benefit of pandemic preparedness.
Why some individuals develop AIDS rapidly whereas others remain healthy without treatment for many years remains a central question of HIV research. An evolutionary perspective reveals an apparent ...conflict between two levels of selection on the virus. On the one hand, there is rapid evolution of the virus in the host, and on the other, new observations indicate the existence of virus factors that affect the virulence of infection whose influence persists over years in infected individuals and across transmission events. Here, we review recent evidence that shows that viral genetic factors play a larger role in modulating disease severity than anticipated. We propose conceptual models that reconcile adaptive evolution at both levels of selection. Evolutionary analysis provides new insight into HIV pathogenesis.
Outbreaks of SARS-CoV-2 infection frequently occur in hospitals. Preventing nosocomial infection requires insight into hospital transmission. However, estimates of the basic reproduction number (R
) ...in care facilities are lacking. Analyzing a closely monitored SARS-CoV-2 outbreak in a hospital in early 2020, we estimated the patient-to-patient transmission rate and R
. We developed a model for SARS-CoV-2 nosocomial transmission that accounts for stochastic effects and undetected infections and fit it to patient test results. The model formalizes changes in testing capacity over time, and accounts for evolving PCR sensitivity at different stages of infection. R
estimates varied considerably across wards, ranging from 3 to 15 in different wards. During the outbreak, the hospital introduced a contact precautions policy. Our results strongly support a reduction in the hospital-level R
after this policy was implemented, from 8.7 to 1.3, corresponding to a policy efficacy of 85% and demonstrating the effectiveness of nonpharmaceutical interventions.
Healthcare facilities are vulnerable to SARS-CoV-2 introductions and subsequent nosocomial outbreaks. Antigen rapid diagnostic testing (Ag-RDT) is widely used for population screening, but its health ...and economic benefits as a reactive response to local surges in outbreak risk are unclear. We simulate SARS-CoV-2 transmission in a long-term care hospital with varying COVID-19 containment measures in place (social distancing, face masks, vaccination). Across scenarios, nosocomial incidence is reduced by up to 40-47% (range of means) with routine symptomatic RT-PCR testing, 59-63% with the addition of a timely round of Ag-RDT screening, and 69-75% with well-timed two-round screening. For the latter, a delay of 4-5 days between the two screening rounds is optimal for transmission prevention. Screening efficacy varies depending on test sensitivity, test type, subpopulations targeted, and community incidence. Efficiency, however, varies primarily depending on underlying outbreak risk, with health-economic benefits scaling by orders of magnitude depending on the COVID-19 containment measures in place.
Drug resistant HIV is a major threat to the long-term efficacy of antiretroviral treatment. Around 10% of ART-naïve patients in Europe are infected with drug-resistant HIV type 1. Hence it is ...important to understand the dynamics of transmitted drug resistance evolution. Thanks to routinely performed drug resistance tests, HIV sequence data is increasingly available and can be used to reconstruct the phylogenetic relationship among viral lineages. In this study we employ a phylodynamic approach to quantify the fitness costs of major resistance mutations in the Swiss HIV cohort. The viral phylogeny reflects the transmission tree, which we model using stochastic birth-death-sampling processes with two types: hosts infected by a sensitive or resistant strain. This allows quantification of fitness cost as the ratio between transmission rates of hosts infected by drug resistant strains and transmission rates of hosts infected by drug sensitive strains. The resistance mutations 41L, 67N, 70R, 184V, 210W, 215D, 215S and 219Q (nRTI-related) and 103N, 108I, 138A, 181C, 190A (NNRTI-related) in the reverse trancriptase and the 90M mutation in the protease gene are included in this study. Among the considered resistance mutations, only the 90M mutation in the protease gene was found to have significantly higher fitness than the drug sensitive strains. The following mutations associated with resistance to reverse transcriptase inhibitors were found to be less fit than the sensitive strains: 67N, 70R, 184V, 219Q. The highest posterior density intervals of the transmission ratios for the remaining resistance mutations included in this study all included 1, suggesting that these mutations do not have a significant effect on viral transmissibility within the Swiss HIV cohort. These patterns are consistent with alternative measures of the fitness cost of resistance mutations. Overall, we have developed and validated a novel phylodynamic approach to estimate the transmission fitness cost of drug resistance mutations.
KwaZulu-Natal, one of South Africa's three malaria endemic provinces, is nearing malaria elimination, reporting fewer than 100 locally-acquired cases annually since 2010. Despite sustained ...implementation of essential interventions, including annual indoor residual spraying, prompt case detection using malaria rapid diagnostics tests and treatment with effective artemisinin-based combination therapy, low-level focal transmission persists in the province. This malaria prevalence and entomological survey was therefore undertaken to identify the drivers of this residual transmission.
Malaria prevalence as well as malaria knowledge, attitudes and practices among community members and mobile migrant populations within uMkhanyakude district, KwaZulu-Natal were assessed during a community-based malaria prevalence survey. All consenting participants were tested for malaria by both conventional and highly-sensitive falciparum-specific rapid diagnostic tests. Finger-prick filter-paper blood spots were also collected from all participants for downstream parasite genotyping analysis. Entomological investigations were conducted around the surveyed households, with potential breeding sites geolocated and larvae collected for species identification and insecticide susceptibility testing. A random selection of households were assessed for indoor residual spray quality by cone bioassay.
A low malaria prevalence was confirmed in the study area, with only 2% (67/2979) of the participants found to be malaria positive by both conventional and highly-sensitive falciparum-specific rapid diagnostic tests. Malaria prevalence however differed markedly between the border market and community (p < 0001), with the majority of the detected malaria carriers (65/67) identified as asymptomatic Mozambican nationals transiting through the informal border market from Mozambique to economic hubs within South Africa. Genomic analysis of the malaria isolates revealed a high degree of heterozygosity and limited genetic relatedness between the isolates supporting the hypothesis of limited local malaria transmission within the province. New potential vector breeding sites, potential vector populations with reduced insecticide susceptibility and areas with sub-optimal vector intervention coverage were identified during the entomological investigations.
If KwaZulu-Natal is to successfully halt local malaria transmission and prevent the re-introduction of malaria, greater efforts need to be placed on detecting and treating malaria carriers at both formal and informal border crossings with transmission blocking anti-malarials, while ensuring optimal coverage of vector control interventions is achieved.
In 2014, inactivated poliovirus vaccine (IPV) campaigns were implemented in Nigeria and Pakistan after clinical trials showed that IPV boosts intestinal immunity in children previously given oral ...poliovirus vaccine (OPV). We estimated the effect of these campaigns by using surveillance data collected during January 2014-April 2016. In Nigeria, campaigns with IPV and trivalent OPV (tOPV) substantially reduced the incidence of poliomyelitis caused by circulating serotype-2 vaccine-derived poliovirus (incidence rate ratio IRR 0.17 for 90 days after vs. 90 days before campaigns, 95% CI 0.04-0.78) and the prevalence of virus in environmental samples (prevalence ratio PR 0.16, 95% CI 0.02-1.33). Campaigns with tOPV alone resulted in similar reductions (IRR 0.59, 95% CI 0.18-1.97; PR 0.45, 95% CI 0.21-0.95). In Pakistan, the effect of IPV+tOPV campaigns on wild-type poliovirus was not significant. Results suggest that administration of IPV alongside OPV can decrease poliovirus transmission if high vaccine coverage is achieved.
The transmission risk of SARS-CoV-2 within hospitals can exceed that in the general community because of more frequent close proximity interactions (CPIs). However, epidemic risk across wards is ...still poorly described. We measured CPIs directly using wearable sensors given to all present in a clinical ward over a 36-h period, across 15 wards in three hospitals in April-June 2020. Data were collected from 2114 participants and combined with a simple transmission model describing the arrival of a single index case to the ward to estimate the risk of an outbreak. Estimated epidemic risk ranged four-fold, from 0.12 secondary infections per day in an adult emergency to 0.49 per day in general paediatrics. The risk presented by an index case in a patient varied 20-fold across wards. Using simulation, we assessed the potential impact on outbreak risk of targeting the most connected individuals for prevention. We found that targeting those with the highest cumulative contact hours was most impactful (20% reduction for 5% of the population targeted), and on average resources were better spent targeting patients. This study reveals patterns of interactions between individuals in hospital during a pandemic and opens new routes for research into airborne nosocomial risk.
Recent data shows that HIV-1 is characterised by variation in viral virulence factors that is heritable between infections, which suggests that viral virulence can be naturally selected at the ...population level. A trade-off between transmissibility and duration of infection appears to favour viruses of intermediate virulence. We developed a mathematical model to simulate the dynamics of putative viral genotypes that differ in their virulence. As a proxy for virulence, we use set-point viral load (SPVL), which is the steady density of viral particles in blood during asymptomatic infection. Mutation, the dependency of survival and transmissibility on SPVL, and host effects were incorporated into the model. The model was fitted to data to estimate unknown parameters, and was found to fit existing data well. The maximum likelihood estimates of the parameters produced a model in which SPVL converged from any initial conditions to observed values within 100-150 years of first emergence of HIV-1. We estimated the 1) host effect and 2) the extent to which the viral virulence genotype mutates from one infection to the next, and found a trade-off between these two parameters in explaining the variation in SPVL. The model confirms that evolution of virulence towards intermediate levels is sufficiently rapid for it to have happened in the early stages of the HIV epidemic, and confirms that existing viral loads are nearly optimal given the assumed constraints on evolution. The model provides a useful framework under which to examine the future evolution of HIV-1 virulence.
As surveillance is a key strategy for malaria elimination in South Africa, ensuring strong surveillance systems is a National Department of Health priority. Historically, real time tracking of case ...trends and reporting within 24 h-a requirement in South Africa's National surveillance guidelines-has not been possible. To enhance surveillance and response efficiency, a mobile surveillance tool, MalariaConnect, was developed using Unstructured Supplementary Service Data (USSD) technology. It was rolled out in health facilities in malaria endemic areas of South Africa to provide 24-h reporting of malaria cases.
To evaluate the efficiency of the mobile tool to detect an outbreak data were extracted from the paper based and MalariaConnect reporting systems in Bushbuckridge from 1 January to 18 June 2017. These data were subject to time series analyses to determine if MalariaConnect provided sufficient data reliably to detect increasing case trends reported through the paper system. The Chi squared test was used to determine goodness of fit between the following indicator data generated using MalariaConnect and paper reporting systems: timeliness, completeness, and precision.
MalariaConnect adequately tracked case trends reported through the paper system. Timeliness of reporting increased significantly using MalariaConnect with 0.63 days to notification compared to 5.65 days using the paper-system (p < 0.05). The completeness of reporting was significantly higher for the paper system (100% completion; p < 0.05), compared to confirmed MalariaConnect cases (61%). There was a moderate association between data precision and the reporting system (p < 0.05). MalariaConnect provided an effective way of reliably and accurately identifying the onset of the malaria outbreak in Bushbuckridge.
Timeliness significantly improved using MalariaConnect and in a malaria elimination setting, can be used to markedly improve case investigation and response activities within the recommended 72-h period. Although data completeness and precision were lower compared to paper reporting, MalariaConnect data can be used to trigger outbreak responses.
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