Understanding the Potential Impact of Different Drug Properties On SARS-CoV-2 Transmission and Disease Burden: A Modelling Analysis

Background The public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. Methods Using a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. Results The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R=1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics. Conclusions Advances in the treatment of COVID-19 to date have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority

Understanding the potential impact of different drug properties on SARS-CoV-2 transmission and disease burden : a modelling analysis

Q1Q1Background The unprecedented public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. Methods and Findings develop a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care to explore the potential public-health impact of a range of different potential therapeutics, under a range of different scenarios varying: i) healthcare capacity, ii) epidemic trajectories; and iii) drug efficacy in the absence of supportive care. In each case, the outcome of interest was the number of COVID-19 deaths averted in scenarios with the therapeutic compared to scenarios without. We find the impact of drugs like dexamethasone (which are delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in highincome countries but only 8% in low-income countries (assuming R=1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics. Conclusions There is a global asymmetry in who is likely to benefit from advances in the treatment of COVID-19 to date, which have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics that can feasibly be delivered to those earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priorityRevista Internacional - Indexad

Rickettsiosis in Southeast Asia: Summary for international travellers during the COVID-19 pandemic

Rickettsiosis is an important cause of febrile illness among travellers visiting Southeast Asia (SEA). The true incidence of rickettsiosis is underestimated; however, murine typhus and scrub typhus are widely distributed across SEA. Among travellers visiting SEA, scrub typhus was mostly reported from Thailand, whereas murine typhus was frequently found in Indonesia. Although most cases are self-limited or present with mild symptoms, a few cases with severe clinical manifestations have been reported. Doxycycline remains the key treatment of rickettsiosis. Some travellers, such as backpackers, trekkers, or cave explorers, are at a higher risk for rickettsiosis than others. Therefore, in resource-limited conditions, empirical treatment should be considered in these travellers. The coronavirus disease 2019 (COVID-19) pandemic has contributed to difficulty in the diagnosis of rickettsiosis because of the clinical similarities between these diseases. In addition, physical distancing mandated by COVID-19 management guidelines limits accurate physical examination, resulting in misdiagnosis and delayed treatment of rickettsiosis. This review summarises the characteristics of murine typhus and scrub typhus, describes travel-associated rickettsiosis, and discusses the impact of the COVID-19 pandemic on rickettsiosi

Rickettsiosis in Southeast Asia: Summary for international travellers during the COVID-19 pandemic

Rickettsiosis is an important cause of febrile illness among travellers visiting Southeast Asia (SEA). The true incidence of rickettsiosis is underestimated; however, murine typhus and scrub typhus are widely distributed across SEA. Among travellers visiting SEA, scrub typhus was mostly reported from Thailand, whereas murine typhus was frequently found in Indonesia. Although most cases are self-limited or present with mild symptoms, a few cases with severe clinical manifestations have been reported. Doxycycline remains the key treatment of rickettsiosis. Some travellers, such as backpackers, trekkers, or cave explorers, are at a higher risk for rickettsiosis than others. Therefore, in resource-limited conditions, empirical treatment should be considered in these travellers. The coronavirus disease 2019 (COVID-19) pandemic has contributed to difficulty in the diagnosis of rickettsiosis because of the clinical similarities between these diseases. In addition, physical distancing mandated by COVID-19 management guidelines limits accurate physical examination, resulting in misdiagnosis and delayed treatment of rickettsiosis. This review summarises the characteristics of murine typhus and scrub typhus, describes travel-associated rickettsiosis, and discusses the impact of the COVID-19 pandemic on rickettsiosi

Effectiveness and safety of polymyxin B for the treatment of infections caused by extensively drug-resistant Gram-negative bacteria in Thailand

Thundon Ngamprasertchai,1 Adhiratha Boonyasiri,2 Lantharita Charoenpong,3 Sireethorn Nimitvilai,4 Narisorn Lorchirachoonkul,5 Luksame Wattanamongkonsil,2 Visanu Thamlikitkul6 1Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; 2Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; 3Division of Medicine, Chaophraya Yommarat Hospital, Suphanburi, Thailand; 4Division of Medicine, Nakhornpathom Hospital, Nakhornpathom, Thailand; 5Division of Medicine, Ratchaburi Hospital, Ratchaburi, Thailand; 6Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand Background: Colistimethate sodium (colistin) has been used in the treatment of infections caused by extensively drug-resistant (XDR) Gram-negative bacteria in Thailand over the past decade, with a mortality rate of 50% and a nephrotoxicity rate of 40%. Polymyxin B has not been available in Thailand. We conducted a Phase II clinical study to determine the effectiveness and safety of polymyxin B, compared with colistin, for the treatment of XDR Gram-negative bacterial infections in Thai patients.Methods: A total of 73 adult patients hospitalized at four participating tertiary care hospitals from January 2015 to December 2015 who had infections caused by XDR Gram-negative bacteria and had to receive colistin were enrolled in the study. Polymyxin B (100 mg/day) was administered intravenously every 12 hours for 7–14 days.Results: Most of the patients were older males with comorbidities who had received antibiotics, particularly carbapenems, prior to receiving polymyxin B. More than half of the patients had pneumonia, and 51.5% of the infections were caused by XDR Acinetobacter baumannii, which was susceptible to colistin. Good clinical responses at the end of treatment were observed in 78.1% of cases, the overall 28-day mortality rate from all causes was 28.7%, the microbiological clearance of the targeted bacteria after therapy was 56.2% and nephrotoxicity occurred in 24.7% of cases. Neurotoxicity relating to reversible numbness was observed in two cases.Conclusion: Polymyxin B seems to be effective and safe for the treatment of XDR Gram-negative bacterial infections. Polymyxin B should be considered as an alternative to colistin for treatment of infections caused by XDR Gram-negative bacteria in Thai adult patients, especially those at risk of nephrotoxicity. Keywords: mortality, acute kidney injury, Acinetobacter baumanni

Mortality in Thai nursing homes based on antimicrobial-resistant Enterobacterales carriage and COVID-19 lockdown timing: a prospective cohort study

Antimicrobial-resistant Enterobacterales carriage and the coronavirus disease 2019 (COVID-19) lockdown measures may impact the incidence all-cause mortality rate among nursing home residents. To determine the all-cause mortality rate in the presence/absence of antimicrobial-resistant Enterobacterales carriage and the incidence all-cause mortality rate before and during COVID-19 pandemic lockdown, this prospective closed-cohort study was conducted at various types of nursing homes in Bangkok, Thailand, from June 2020 to December 2021. The elderly residents included 142 participants (aged ≥60 years) living in nursing homes ≥3 months, who did not have terminal illnesses. Time-to-event analyses with Cox proportional hazards models and stratified log-rank tests were used. The all-cause mortality rate was 18%, and the incidence all-cause mortality rate was 0.59/1000 person-days in residents who had antimicrobial-resistant Enterobacterales carriage at baseline. Meanwhile, the incidence all-cause mortality rate among noncarriage was 0.17/1000 person-days. The mortality incidence rate of carriage was three times higher than residents who were noncarriage without statistical significance (HR 3.2; 95% CI 0.74, 13.83). Residents in nonprofit nursing homes had a higher mortality rate than those in for-profit nursing homes (OR 9.24; 95% CI 2.14, 39.86). The incidence mortality rate during and before lockdown were 0.62 and 0.30, respectively. Effective infection-control policies akin to hospital-based systems should be endorsed in all types of nursing homes. To limit the interruption of long-term chronic care, COVID-19 prevention should be individualized to nursing home

Understanding the potential impact of different drug properties on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and disease burden: a modelling analysis

Background The public health impact of the coronavirus disease 2019 (COVID-19) pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. Methods Using a mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. Results The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R = 1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalization) could have much greater benefits, particularly in resource-poor settings facing large epidemics. Conclusions Advances in the treatment of COVID-19 to date have been focused on hospitalized-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority

Understanding the Potential Impact of Different Drug Properties On SARS-CoV-2 Transmission and Disease Burden: A Modelling Analysis

Background The public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. Methods Using a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. Results The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R=1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics. Conclusions Advances in the treatment of COVID-19 to date have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority