A novel strategy based on genomics and specific PCR reveals how a multidrug resistant Mycobacterium tuberculosis strain became prevalent in Equatorial Guinea 15 years after its emergence.

OBJECTIVE: Molecular epidemiology techniques in tuberculosis (TB) can identify high-risk strains that are actively transmitted. We aimed to implement a novel strategy to optimize the identification and control of multidrug-resistant (MDR) TB in a specific population. METHODS: We developed a strain-specific PCR tailored from whole genome sequencing (WGS) data to track a specific MDR prevalent strain in Equatorial Guinea (EG-MDR). RESULTS: The PCR was applied prospectively on remnants of GeneXpert reaction mixtures owing to the lack of culture facilities in Equatorial Guinea. In 147 (93%) of 158 cases, we were able to differentiate between infection by the EG-MDR strain or by any other strain and found that 44% of all rifampicin-resistant TB cases were infected by EG-MDR. We also analysed 93 isolates obtained from Equatorial Guinea 15 years ago, before MDR-TB had become the problem it is today. We found that two of the scarce historical MDR cases were infected by EG-MDR. WGS revealed low variability-six single nucleotide polymorphisms acquired by this strain over 15 years-likely because of the lack in the country of a specific program to treat MDR-TB. CONCLUSIONS: Our novel strategy, which integrated WGS analysis and strain-specific PCRs, represents a low-cost, rapid and transferable strategy that allowed a prospective efficient survey and fast historical analysis of MDR-TB in a population

Inadequate use of antibiotics in the covid-19 era: effectiveness of antibiotic therapy

Background: Since December 2019, the COVID-19 pandemic has changed the concept of medicine. This work aims to analyze the use of antibiotics in patients admitted to the hospital due to SARS-CoV-2 infection. Methods: This work analyzes the use and effectiveness of antibiotics in hospitalized patients with COVID-19 based on data from the SEMI-COVID-19 registry, an initiative to generate knowledge about this disease using data from electronic medical records. Our primary endpoint was all-cause in-hospital mortality according to antibiotic use. The secondary endpoint was the effect of macrolides on mortality. Results: Of 13, 932 patients, antibiotics were used in 12, 238. The overall death rate was 20.7% and higher among those taking antibiotics (87.8%). Higher mortality was observed with use of all antibiotics (OR 1.40, 95% CI 1.21–1.62; p <.001) except macrolides, which had a higher survival rate (OR 0.70, 95% CI 0.64–0.76; p <.001). The decision to start antibiotics was influenced by presence of increased inflammatory markers and any kind of infiltrate on an x-ray. Patients receiving antibiotics required respiratory support and were transferred to intensive care units more often. Conclusions: Bacterial co-infection was uncommon among COVID-19 patients, yet use of antibiotics was high. There is insufficient evidence to support widespread use of empiric antibiotics in these patients. Most may not require empiric treatment and if they do, there is promising evidence regarding azithromycin as a potential COVID-19 treatment. © 2021, The Author(s)

Health Services Utilization, Work Absenteeism and Costs of Pandemic Influenza A (H1N1) 2009 in Spain: A Multicenter-Longitudinal Study

Background: The aim of this study was to estimate healthcare resource utilization, work absenteeism and cost per patient with pandemic influenza (H1N1)2009, from its beginning to March 2010, in Spain. We also estimated the economic impact on healthcare services. Methods and Findings: Longitudinal, descriptive,multicenter study of in- and outpatients with confirmed diagnosis of influenza A (H1N1) in Spain. Temporal distribution of cases was comparable to that in Spain. Information of healthcare and social resources used from one week before admission (inpatient) or index-medical visit (outpatient) until recovery was gathered. Unit cost was imputed to utilization frequency for the monetary valuation of use. Mean cost per patient was calculated. A sensitivity analysis was conducted, and variables correlated with cost per patient were identified. Economic impact on the healthcare system was estimated using healthcare costs per patient and both, the reported number of confirmed and clinical cases in Spain. 172 inpatients and 224 outpatients were included. Less than 10% were over 65 years old and more than 50% had previous comorbidities. 12.8% of inpatients were admitted to the Intensive Care Unit. Mean length of hospital stay of patients not requiring critical care was 5 days (SD =4.4). All working-inpatients and 91.7% working-outpatients went on sick leave. On average, work absenteeism was 30.5 days (SD=20.7) for the first ones and 9 days (SD= 6.3) for the latest. Caregivers of 21.7% of inpatients and 8.5% of outpatients also had work absenteeism during 10.7 and 4.1 days on average respectively. Mean cost was J6,236/inpatient (CI95%=1,384-14,623) and J940/outpatient (CI95% =66-3,064). The healthcare economic burden of patients with confirmed influenza was J144,773,577 (IC95% 13,753,043-383,467,535). More than 86% of expenditures were a result of outpatients" utilization. Conclusion: Cost per H1N1-patient did not defer much from seasonal influenza estimates. Hospitalizations and work absenteeism represented the highest cost per patient

Risk factors for severe outcomes following 2009 influenza A (H1N1) infection: a global pooled analysis

Background Since the start of the 2009 influenza A pandemic (H1N1pdm), the World Health Organization and its member states have gathered information to characterize the clinical severity of H1N1pdm infection and to assist policy makers to determine risk groups for targeted control measures. Methods and Findings Data were collected on approximately 70,000 laboratory-confirmed hospitalized H1N1pdm patients, 9,700 patients admitted to intensive care units (ICUs), and 2,500 deaths reported between 1 April 2009 and 1 January 2010 from 19 countries or administrative regions—Argentina, Australia, Canada, Chile, China, France, Germany, Hong Kong SAR, Japan, Madagascar, Mexico, the Netherlands, New Zealand, Singapore, South Africa, Spain, Thailand, the United States, and the United Kingdom—to characterize and compare the distribution of risk factors among H1N1pdm patients at three levels of severity: hospitalizations, ICU admissions, and deaths. The median age of patients increased with severity of disease. The highest per capita risk of hospitalization was among patients <5 y and 5–14 y (relative risk [RR] = 3.3 and 3.2, respectively, compared to the general population), whereas the highest risk of death per capita was in the age groups 50–64 y and ≥65 y (RR = 1.5 and 1.6, respectively, compared to the general population). Similarly, the ratio of H1N1pdm deaths to hospitalizations increased with age and was the highest in the ≥65-y-old age group, indicating that while infection rates have been observed to be very low in the oldest age group, risk of death in those over the age of 64 y who became infected was higher than in younger groups. The proportion of H1N1pdm patients with one or more reported chronic conditions increased with severity (median = 31.1%, 52.3%, and 61.8% of hospitalized, ICU-admitted, and fatal H1N1pdm cases, respectively). With the exception of the risk factors asthma, pregnancy, and obesity, the proportion of patients with each risk factor increased with severity level. For all levels of severity, pregnant women in their third trimester consistently accounted for the majority of the total of pregnant women. Our findings suggest that morbid obesity might be a risk factor for ICU admission and fatal outcome (RR = 36.3). Conclusions Our results demonstrate that risk factors for severe H1N1pdm infection are similar to those for seasonal influenza, with some notable differences, such as younger age groups and obesity, and reinforce the need to identify and protect groups at highest risk of severe outcomes

A novel strategy based on genomics and specific PCR reveals how a multidrug resistant Mycobacterium tuberculosis strain became prevalent in Equatorial Guinea 15 years after its emergence.

OBJECTIVE: Molecular epidemiology techniques in tuberculosis (TB) can identify high-risk strains that are actively transmitted. We aimed to implement a novel strategy to optimize the identification and control of multidrug-resistant (MDR) TB in a specific population. METHODS: We developed a strain-specific PCR tailored from whole genome sequencing (WGS) data to track a specific MDR prevalent strain in Equatorial Guinea (EG-MDR). RESULTS: The PCR was applied prospectively on remnants of GeneXpert reaction mixtures owing to the lack of culture facilities in Equatorial Guinea. In 147 (93%) of 158 cases, we were able to differentiate between infection by the EG-MDR strain or by any other strain and found that 44% of all rifampicin-resistant TB cases were infected by EG-MDR. We also analysed 93 isolates obtained from Equatorial Guinea 15 years ago, before MDR-TB had become the problem it is today. We found that two of the scarce historical MDR cases were infected by EG-MDR. WGS revealed low variability-six single nucleotide polymorphisms acquired by this strain over 15 years-likely because of the lack in the country of a specific program to treat MDR-TB. CONCLUSIONS: Our novel strategy, which integrated WGS analysis and strain-specific PCRs, represents a low-cost, rapid and transferable strategy that allowed a prospective efficient survey and fast historical analysis of MDR-TB in a population

Agent-Based Methods for Simulation of Epidemics with a Low Number of Infected Persons

Part 1: Information & Communication Technology-EurAsia Conference 2014, ICT-EurAsia 2014International audienceModeling of infectious diseases with a low number of infections is a task that often arises since most real epidemics affect only a small fraction of the population. Agent-based methods simulate individuals and their behavior. When the model is simulated, the epidemic automatically arises without being explicitly defined. Surprisingly, it is not easy to produce such epidemics with small infection numbers. Instead, it needs model improvements to accomplish that task. In this paper, we show different extensions, addressing the person’s behavior, the pathogen’s behavior and the environmental impacts. It turns out that the discussed improvements have different consequences. Hence, they need to be used deliberately to overcome modeling issues of a specific epidemic in an appropriate and valid way. Even more, these improvements address the underlying behavior of epidemics and hence have the ability to provide a deeper insight into the real spreading process of a disease

Different transmission patterns in the early stages of the influenza A(H1N1)v pandemic: a comparative analysis of 12 European countries.

Following the emergence of a novel strain of influenza A(H1N1) in Mexico and the United States in April 2009, its epidemiology in Europe during the summer was limited to sporadic and localised outbreaks. Only the United Kingdom experienced widespread transmission declining with school holidays in late July. Using statistical modelling where applicable we explored the following causes that could explain this surprising difference in transmission dynamics: extinction by chance, differences in the susceptibility profile, age distribution of the imported cases, differences in contact patterns, mitigation strategies, school holidays and weather patterns. No single factor was able to explain the differences sufficiently. Hence an additive mixed model was used to model the country-specific weekly estimates of the effective reproductive number using the extinction probability, school holidays and weather patterns as explanatory variables. The average extinction probability, its trend and the trend in absolute humidity were found to be significantly negatively correlated with the effective reproduction number - although they could only explain about 3% of the variability in the model. By comparing the initial epidemiology of influenza A (H1N1) across different European countries, our analysis was able to uncover a possible role for the timing of importations (extinction probability), mixing patterns and the absolute humidity as underlying factors. However, much uncertainty remains. With better information on the role of these epidemiological factors, the control of influenza could be improved