The Emergence of Travel-related Infections in Critical Care Units

Several tropical or geographically confined infectious diseases may lead to organ failure requiring management in an intensive care unit (ICU), both in endemic low- and middle-income countries where ICU facilities are increasingly being developed and in (nonendemic) high-income countries through an increase in international travel and migration. The ICU physician must know which of these diseases may be encountered and how to recognize, differentiate, and treat them. The four historically most prevalent "tropical” diseases (malaria, enteric fever, dengue, and rickettsiosis) can present with single or multiple organ failure in a very similar manner, which makes differentiation based solely on clinical signs very difficult. Specific but frequently subtle symptoms should be considered and related to the travel history of the patient, the geographic distribution of these diseases, and the incubation period. In the future, ICU physicians may also be more frequently confronted with rare but frequently lethal diseases, such as Ebola and other viral hemorrhagic fevers, leptospirosis, and yellow fever. No one could have foreseen the worldwide 2019–up to now coronavirus disease 2019 (COVID-19) crisis caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was initially spread by travel too. In addition, the actual pandemic due to SARS-CoV-2 reminds us of the actual and potential threat of (re)-emerging pathogens. If left untreated or when treated with a delay, many travel-related diseases remain an important cause of morbidity and even mortality, even when high-quality critical care is provided. Awareness and a high index of suspicion of these diseases is a key skill for the ICU physicians of today and tomorrow to develop.

The Emergence of Travel-related Infections in Critical Care Units.

Several tropical or geographically confined infectious diseases may lead to organ failure requiring management in an intensive care unit (ICU), both in endemic low- and middle-income countries where ICU facilities are increasingly being developed and in (nonendemic) high-income countries through an increase in international travel and migration. The ICU physician must know which of these diseases may be encountered and how to recognize, differentiate, and treat them. The four historically most prevalent "tropical" diseases (malaria, enteric fever, dengue, and rickettsiosis) can present with single or multiple organ failure in a very similar manner, which makes differentiation based solely on clinical signs very difficult. Specific but frequently subtle symptoms should be considered and related to the travel history of the patient, the geographic distribution of these diseases, and the incubation period. In the future, ICU physicians may also be more frequently confronted with rare but frequently lethal diseases, such as Ebola and other viral hemorrhagic fevers, leptospirosis, and yellow fever. No one could have foreseen the worldwide 2019-up to now coronavirus disease 2019 (COVID-19) crisis caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was initially spread by travel too. In addition, the actual pandemic due to SARS-CoV-2 reminds us of the actual and potential threat of (re)-emerging pathogens. If left untreated or when treated with a delay, many travel-related diseases remain an important cause of morbidity and even mortality, even when high-quality critical care is provided. Awareness and a high index of suspicion of these diseases is a key skill for the ICU physicians of today and tomorrow to develop.

Availability of oral antivirals against SARS-CoV-2 infection and the requirement for an ethical prescribing approach.

The first two oral antivirals, molnupiravir and nirmatrelvir-ritonavir, are now becoming available in many countries. These medicines will be indicated to treat mild-to-moderate COVID-19 in non-hospitalised patients who are at high risk of progressing to severe COVID-19. These antivirals should be prescribed within 5 days of symptom onset, and after SARS-CoV-2 infection has been confirmed. However, the availability of these antivirals will be scarce for some time due to manufacturing constraints. Each country should establish a policy on the conditions under which these antivirals can be prescribed. Such a policy should be based on the fulfilment of five ethical elements: transparency, relevance, appeals, enforcement, and fairness. Following the principles of distributive justice, molnupiravir and nirmatrelvir-ritonavir should be prescribed according to a hierarchy of predicted efficacy, ideally on the basis of an evidence-based scoring system. The placebo-controlled randomised trials that supported the temporary authorisation of these two antivirals were conducted in unvaccinated patients with COVID-19, so an evidence-based prescription practice would only use these drugs for unvaccinated patients until further data become available. However, in the countries that authorised these antivirals in 2021 (the UK and the USA), both vaccinated and unvaccinated patients meeting particular requirements have access to these antivirals. Due to the complexity of prioritisation, national health authorities should start issuing their draft policies as soon as possible and these policies should be regularly updated. The effectiveness of these antivirals against the omicron variant of SARS-CoV-2 must be urgently assessed. Once implemented, molnupiravir and nirmatrelvir-ritonavir must show their effectiveness and safety in the real world, and health systems must be adequately adapted for the correct use of these antivirals.

Low-dose hydroxychloroquine therapy and mortality in hospitalised patients with COVID-19: a nationwide observational study of 8075 participants.

Hydroxychloroquine (HCQ) has been largely used and investigated as therapy for COVID-19 across various settings at a total dose usually ranging from 2400 mg to 9600 mg. In Belgium, off-label use of low-dose HCQ (total 2400 mg over 5 days) was recommended for hospitalised patients with COVID-19. We conducted a retrospective analysis of in-hospital mortality in the Belgian national COVID-19 hospital surveillance data. Patients treated either with HCQ monotherapy and supportive care (HCQ group) were compared with patients treated with supportive care only (no-HCQ group) using a competing risks proportional hazards regression with discharge alive as competing risk, adjusted for demographic and clinical features with robust standard errors. Of 8075 patients with complete discharge data on 24 May 2020 and diagnosed before 1 May 2020, 4542 received HCQ in monotherapy and 3533 were in the no-HCQ group. Death was reported in 804/4542 (17.7%) and 957/3533 (27.1%), respectively. In the multivariable analysis, mortality was lower in the HCQ group compared with the no-HCQ group [adjusted hazard ratio (aHR) = 0.684, 95% confidence interval (CI) 0.617-0.758]. Compared with the no-HCQ group, mortality in the HCQ group was reduced both in patients diagnosed ≤5 days (n = 3975) and >5 days (n = 3487) after symptom onset [aHR = 0.701 (95% CI 0.617-0.796) and aHR = 0.647 (95% CI 0.525-0.797), respectively]. Compared with supportive care only, low-dose HCQ monotherapy was independently associated with lower mortality in hospitalised patients with COVID-19 diagnosed and treated early or later after symptom onset.

Chloroquine and Hydroxychloroquine for the Prevention or Treatment of COVID-19 in Africa: Caution for Inappropriate Off-label Use in Healthcare Settings.

The novel severe acute respiratory syndrome-coronavirus-2 pandemic has spread to Africa, where nearly all countries have reported laboratory-confirmed cases of novel coronavirus disease (COVID-19). Although there are ongoing clinical trials of repurposed and investigational antiviral and immune-based therapies, there are as yet no scientifically proven, clinically effective pharmacological treatments for COVID-19. Among the repurposed drugs, the commonly used antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) have become the focus of global scientific, media, and political attention despite a lack of randomized clinical trials supporting their efficacy. Chloroquine has been used worldwide for about 75 years and is listed by the WHO as an essential medicine to treat malaria. Hydroxychloroquine is mainly used as a therapy for autoimmune diseases. However, the efficacy and safety of CQ/HCQ for the treatment of COVID-19 remains to be defined. Indiscriminate promotion and widespread use of CQ/HCQ have led to extensive shortages, self-treatment, and fatal overdoses. Shortages and increased market prices leave all countries vulnerable to substandard and falsified medical products, and safety issues are especially concerning for Africa because of its healthcare system limitations. Much needed in Africa is a cross-continental collaborative network for coordinated production, distribution, and post-marketing surveillance aligned to low-cost distribution of any approved COVID-19 drug; this would ideally be piggybacked on existing global aid efforts. Meanwhile, African countries should strongly consider implementing prescription monitoring schemes to ensure that any off-label CQ/HCQ use is appropriate and beneficial during this pandemic.