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Weekly Digest: Internationally imported cases and internal spread of COVID-19; Racial/ethnic disparities in hospitalization and mortality in patients with COVID-19 in New York City; Antibiotic treatment of common infections – evidence to support shorter duration; A pharmacist-led antibiotic stewardship intervention in South Africa.

COVID-19

Effect of internationally imported cases on internal spread of COVID-19. In a modelling study examining the impact of international travel on the spread of COVID-19 within a given country, researchers showed that heavy travel restrictions may benefit early in a pandemic, or after control of the pandemic is achieved, when there is little to no local transmission, or when the number of COVID-19 cases is on the brink of growing exponentially (i.e., an Rt between 0.95 to 1.05). However, little impact was predicted for countries close to tipping points for exponential growth. With estimated 2020 travel volumes, imported cases in September 2020, accounted for no more than 10% of total incidence in 125 countries  and less than 1% in 44 countries, 22 of which had epidemic growth rates past the tipping point of exponential growth. Thus, heavy travel restrictions in September 2020 were not beneficial for countries with high local transmission, but in countries such as New Zealand and China, where the total incidence of cases was similar to the number of imported cases, travel restrictions would go far to prevent a second wave. [The Lancet]

Assessment of racial/ethnic disparities in hospitalization and mortality in patients with COVID-19 in New York City. A cohort study involving 9722 patients from over 260 outpatient practices and 4 acute care hospitals in New York City revealed that Black (odds ratio [OR], 1.3; 95% CI, 1.2 to 1.6)  and Hispanic (OR, 1.5; 95% CI, 1.3 to 1.7) patients were more likely than White patients to test positive for COVID-19. However, following hospitalization, severe disease (OR, 0.6; 95% CI, 0.4 to 0.8) and mortality (hazard ratio, 0.7; 95% CI, 0.6 to 0.9) among Black patients was lower than among White patients. The findings led the authors to suggest that the disproportionately higher out-of-hospital COVID-19 mortality among Black individuals may be attributed to neighborhood characteristics or existing cultural determinants and that given adequate access to healthcare, Black and Hispanic communities are not inherently more susceptible to having poor outcomes. [JAMA]

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. The ChAdOx1 nCoV-19 vaccine was developed at Oxford University by AstraZeneca and consists of a replication-deficient chimpanzee adenoviral vector containing the SARS-CoV-2 surface glycoprotein antigen gene. Between April 25 and Nov 4, 2020, 23,848 participants over 18 years of age were enrolled and 11,363 were included in this interim report. Participants were assigned 1:1 to a control group receiving a placebo or the intervention group receiving two doses of the vaccine. A subset of participants age 18-55 received half a dose for the first dose, whereas the group that received two standard doses included adults 56-69 years old. For those who received two standard doses, efficacy was 62.1% (95%CI 41.0 to 5.7) and for those receiving a low dose followed by a standard dose the efficacy was 90% (95%CI 67.4 to 97.0). Overall efficacy across both groups was 70.4% (95%CI 54.8–80.6). Eighty-four adverse events occurred in the intervention group compared to 91 in the control group. The acceptable safety profile and its efficacy  against symptomatic COVID-19, support regulatory submissions for conditional or emergency use of ChAdOx1 nCoV-19. Furthermore, its storage conditions (2–8°C), make it particularly suitable for global distribution. [The Lancet]

Development and dissemination of infectious disease dynamic transmission models during the COVID-19 pandemic: what can we learn from other pathogens and how can we move forward? Researchers explained disease modelling, including mechanism and statistical models, and considered the benefits and pitfalls of modelling efforts in light of the COVID-19 pandemic by providing an overview of how modelling has been used in past outbreaks such as Malaria, HIV, Rubella, and Ebola. Successful aspects of these examples included having clear policy questions and extensive epidemiological data, quantifying uncertainty, grounding results in context, and good communication between modelers, clinicians, and policy makers. Authors discussed how past efforts could inform the COVID-19 response, emphasizing the importance of adapting models with changing policy needs and new understanding of disease dynamics, as well as communicating their specific utility and limitations. [The Lancet Digital Health]

Evaluation of Rooming-in Practice for Neonates Born to Mothers With Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Italy. Researchers in Italy conducted a  prospective, multicenter study where mothers and infants in six COVID-19 maternity centers in Lombardy, were followed for up to 20 days from March 19 to May 2, 2020. Among 62 neonates born to 61 mothers with SARS-CoV-2, no neonate tested positive for SARS-CoV-2 on nasopharyngeal swab at birth.  Mothers and infants were encouraged to practice rooming-in and breastfeeding under a standardized protocol to minimize the risk of viral transmission and 95% of infants were breastfed. During the study period, only one of the infants (1.6%; 95% CI, 0% to 8.7%) was diagnosed as having SARS-CoV-2, leading the authors to suggest that rooming-in and breastfeeding can be practiced in women with SARS-CoV-2 who are able to care for their infants. [JAMA Pediatrics]

Drug Resistance and Global Health

Antibiotic treatment of common infections: more evidence to support shorter durations. Guidelines on antibiotic treatment durations are meant to reliably cure the majority of individuals, including those with mild infections. However, increasing evidence is indicating that many infections can be treated safely with antibiotics for shorter durations than those traditionally recommended. A review of randomized controlled trials (RCTs) from the last 5 years assessing short and long antibiotic treatment durations for common infections showed that in several studies, shorter treatment for urinary tract infections (7 days vs. 14 days), respiratory tract infections (5-7 days vs. 10 days), and intraabdominal infection (4 days vs. 7-10 days), was not inferior to the longer traditional durations.  While the authors recognized that clinical experience in the treatment of individual patients is important in deciding on longer treatment duration in certain cases, they suggested that for many uncomplicated infections, compelling evidence supports shorter course of antibiotics. [Current Opinion in Infectious Diseases]

Preferences regarding antibiotic treatment and the role of antibiotic resistance: A discrete choice experiment. Researchers in Sweden conducted a discrete choice experiment, where  a questionnaire, with hypothetical but realistic choices sets was administered to 415 study participants, in an effort to identify preferences of the Swedish public regarding antibiotic treatment and the relative weight of antibiotic resistance in their treatment choices. The study found that attributes such as cost, side effects and antibiotic resistance were potential drivers of antibiotic use. Among the 378 eligible participants that completed the questionnaire, 68% and 64,6% answered correctly two questions on the use of antibiotics, however, only 6.1% and 29.1% gave correct answers on two questions on antibiotic resistance. For younger respondents, contribution to antibiotic resistance was the most important attribute in their choice of antibiotic treatments, highlighting that individual responsibility for antibiotic resistance in clinical and societal communication has the potential to affect personal decision making. [International Journal of Antimicrobial Agents].

Effectiveness of seasonal malaria chemoprevention at scale in west and central Africa: an observational study. An observational study assessed coverage, effectiveness, safety, feasibility, drug resistance, and cost-effectiveness of a seasonal malaria chemoprevention (SMC) campaign in children younger than 5 years old in 7 African countries during the high malaria transmission season in 2015 (76.4% coverage) and 2016 (74.8% coverage).  The campaign was effective in reducing malaria morbidity and mortality during the high transmission season; the number of in hospital malaria deaths was reduced by 42.4% (95% CI 5.9 to 64.7) in Burkina Faso and 56.6% (28.9 to 73.5) in The Gambia and the estimated reduction in confirmed malaria cases at the outpatient setting ranged from 25.5% (95% CI 6.1 to 40.9) in Nigeria to 55.2% (42.0 to 65.3) in The Gambia.  Additionally, markers of resistance to sulfadoxine–pyrimethamine and amodiaquine remained uncommon. Beneficial and cost effective SMC campaigns (US$3.63 for four monthly treatments per child), need to be expanded to ‘hard to reach’ communities in order to mitigate malaria burden during the high transmission months. [The Lancet]

Infectious disease team review using antibiotic switch and discharge criteria shortens the duration of intravenous antibiotic: a single-center cluster-randomized controlled trial in Thailand. A cluster-randomized controlled trial was conducted in eight general medical wards at a hospital in Thailand during January–October 2019, to determine whether infectious disease (ID) team review using antibiotic switch and discharge criteria would result in shortening of the duration of intravenous antibiotic  and length of hospital stay (LOS). The trial reported no significant difference between intervention and controls for median duration of intravenous antibiotic  therapy (7 vs 7 days) and LOS (9 vs 10 days). However, a significantly shorter duration of intravenous antibiotic  was observed in a subgroup of patients without sepsis in the intervention group when measured by days of therapy (7 vs 8 days, P = 0.027) and defined daily dose (7 vs 9, P = 0.017). The authors concluded that additional studies are needed to determine whether faster culture turnaround time or advanced testing will reduce the duration of IV antibiotic therapy. [Open Forum Infectious Diseases]

A pharmacist-led prospective antibiotic stewardship intervention improves compliance to community-acquired pneumonia guidelines in 39 public and private hospitals across South Africa. In a multi-center, prospective, cohort study involving adult patients with community-acquired pneumonia (CAP) hospitalised between July 2017 and July 2018 in 39 hospitals in South Africa, a CAP bundle consisting of seven process measures (diagnostic and antibiotic stewardship) was developed and pharmacists were recruited to audit compliance and provide feedback. Following intervention, overall CAP bundle compliance improved from 47.8% to 53.6% (95% CI 4.1 to 7.5, P <0.0001), diagnostic stewardship compliance improved from 49.1% to 54.6% (95% CI 3.3 to 7.7, P < 0.0001) and stewardship process measures increased from 45.3% to 51.6% (95% CI 4·0-8·6, P<0·0001).  Non-specialised pharmacists in public and private hospitals implemented stewardship interventions and improved compliance to South African CAP guidelines, implying that upskilling and a shared learning stewardship model may benefit LMIC countries.[International Journal of Antimicrobial Agents]

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