Showing posts with label favipiravir. Show all posts
Showing posts with label favipiravir. Show all posts

Monday, June 1, 2026

First reported case of #Andes #hantavirus cardiopulmonary syndrome treated with a combination of #favipiravir, #ribavirin, icatibant and baricitinib

 

ABSTRACT

Objectives

To describe the first documented case of Andes virus (ANDV) hantavirus cardiopulmonary syndrome (HCPS) in Spain and the first worldwide use of a therapeutic regime including two antivirals (favipiravir and ribavirin) and two host-directed drugs (baricitinib and icatibant).

Methods

A 69-year-old Spanish man, repatriated following a multinational ANDV outbreak aboard a cruise ship, was managed in a high-level isolation unit. Diagnosis was established by RT-PCR and serology while he was still asymptomatic as part of protocol-driven screening. Under compassionate-use authorisation and written informed consent, the patient received ribavirin (initially intravenous, then switched to oral on day +4), oral favipiravir, subcutaneous icatibant, and oral baricitinib, with serial clinical, laboratory, and radiological monitoring.

Results

Hypoxaemia, bilateral B-lines, thrombocytopenia, lymphopenia, and hyponatraemia developed within 24 hours after diagnosis. The combination regimen was initiated on day 0, and baricitinib was added on day +1, coinciding with the need for high-flow nasal oxygen. Sustained clinical, laboratory, and radiological recovery occurred from day +2 onwards, without progression to invasive ventilation or vasopressors. Mild diarrhoea attributed to ribavirin led to its discontinuation on day +5, shortly after the IV-to-oral switch. Severe recurrent diarrhoea on day +8, attributed to favipiravir, prompted its withdrawal before completion of the planned 10-day course; baricitinib was completed on day +10.

Conclusions

This sentinel case of imported HCPS in non-endemic Europe was managed with, to our knowledge, the first reported combined antiviral and host-directed regimen for this syndrome and the first reported use of favipiravir in a patient with hantavirus infection. The favourable outcome supports prospective evaluation of antiviral combinations and adjunctive immunomodulation within international preparedness protocols.

Source: 


Link: https://www.clinicalmicrobiologyandinfection.org/article/S1198-743X(26)00310-1/fulltext

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Monday, May 18, 2026

#UK Health Security Agency #update on the #hantavirus #outbreak (May 18 '26): a batch of #Favipiravir antiviral drug arrived from #Japan

 


    The UK continues to work with international health agencies and governments around the world to understand and respond to the Hantavirus outbreak. 

    We would like to thank the Ministry of Health, Labour and Welfare of Japan, and the government of Japan, who have supplied doses of the antiviral medicine favipiravir (FAVI) to support the UK’s preparedness and response to Hantavirus. 

    This collaboration reflects the spirit of the UK and Japan public health partnership which includes a Memorandum of Cooperation between the Ministry of Health, Labour and Welfare and the UK Health Security Agency (UKHSA).  

    UKHSA accepted delivery of the medicine over the weekend, bolstering treatment supplies in the event that cases of Hantavirus are confirmed here. 

    The risk of wider transmission of Hantavirus in the UK has not changed and remains very low but this is an important part of our preparedness and defence against the outbreak.


    Health Minister Sharon Hodgson said:

    ''It is great to see countries working together in real, practical ways to protect people’s health. I would like to thank our counterparts in Japan for their supply of these vital medicines, which will support our preparedness and ongoing response to Hantavirus. The UK and Japan share a strong and longstanding relationship, and this contribution is a positive example of how working closely together helps keep people safe from health threats around the world.


    Chris Lewis, Director of Global Health Protection at UKHSA, said:

    ''The collaboration between the UK and Japan during the hantavirus outbreak demonstrates the vital role of international partnerships in detecting, preventing, and responding to global health threats. This joint effort builds on a long-standing public health partnership between the UK and Japan and we thank them for this contribution to the UK response.

Source: 


Link: https://www.gov.uk/government/news/ukhsa-update-on-the-hantavirus-cruise-ship-outbreak

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Monday, May 11, 2026

Technical note for disembarkation and onward #management of #passengers and crew in context of an #Andes virus-associated cluster MV Hondius cruise ship - Interim #guidance 8 May 2026 (WHO, edited)

 


Introduction

-- This technical note is intended for public health authorities, port health authorities, and partner agencies involved in the disembarkation, onward travel, monitoring, and follow-up of passengers and crew associated with the MV Hondius event.


Communication

-- Managed by: National health authorities / public health and medical evaluation team / risk communication specialists

-- Effective risk communication is essential to support the safe and orderly disembarkation and onward management of passengers and crew, and to maintain public trust during an evolving public health event

-- Member States should ensure that communication activities are coordinated, timely, and aligned with operational measures described in this technical note. 

-- Passengers and crew should receive clear, consistent and timely information before, during and after disembarkation, including explanations about public health measures, what to expect at each step, and next steps. 

-- Further considerations on risk communication are available in Annex 1.



1. Upon Arrival

Ship regulations

-- Managed by: Ship captain

• The required documentation should be provided to port health authorities, including the valid Ship Sanitation Certificate and the Ship Declaration of Health (or Maritime Declaration of Health).

• The ship should comply with the public health measures recommended by port health authorities, including for measures that need to be applied on board as well as during disembarkation, or medical evacuation.

• The ship captain should notify port health authorities of any person that meets the suspect case definition as assessed by physicians on board.


Communication to passengers and crew members

-- Managed by: captain / evaluation team / crew / communications officer

• Clearly communicate the steps that will be implemented.

• Inform that the disembarkation and onward travel of passengers and crew are being managed through coordinated and controlled public health measures, and that the risk to the general public remains very low.

• Communication should be reassuring yet vigilant, noting that people who have been exposed may still be at risk of developing symptoms and highlighting the importance of recognizing and reporting symptoms early.


2. Upon disembarkation

-- Managed by: national authorities

- Considering the attention attracted by this event, national authorities should ensure arrangements for security and media management in the port receiving the ship.


Management of passengers with symptoms prior to disembarkation

-- Managed by: medical team on board / national health authorities at the port of call

• Duly equipped ambulances should be pre-positioned at the port.

• If a suspected case is identified prior to the arrival of the ship, their medical evacuation to designated health facilities on-shore should be facilitated first, prior to disembarkation of passengers and crew.

• A designated trained team should be able to provide immediate care and ensure the safe and timely transfer to designated health facilities equipped to provide the appropriate level of safe and quality care.

• Any member of the medical team at the port of disembarkation, including ambulance crews, should apply standard and transmission-based precautions when attending cases.

    Perform hand hygiene before putting on personal protective equipment (PPE).

    Put on PPE items including eye protection, respirator (e.g. N95, FPP2), gown, and gloves before assessing, and transferring the case to a designated health facility on shore.

    PPE should be removed once patient transfer has been completed, and hand hygiene performed after removal of PPE items. PPE should be managed as infectious waste.

• Ensure patients use a respiratory (e.g. N95, FPP2) during the transfer.

• Transport of patients should be carefully planned to ensure those sending the patient and receiving them are fully informed and prepared.

• See Annex 2 and 3 for further information.


Steps for disembarkation for passengers and crew members

-- Managed by: national health authorities at the port of call.

• Provide guidance to the crew on organizing the order of disembarkation (e.g. prioritizing passengers according to their location on the ship, followed by crew members, including instructions on how to wear a respirator).

• Staggering the disembarkation of passengers may be considered to ensure safe and efficient disembarkation. Individuals should disembark one by one from the ship.

• Respirators (N95, FPP2) should be provided prior to disembarkation to all passengers and crew members, under the assumption that it cannot be ruled out if contacts are symptomatic until they have been screened.

• All passengers and crew members disembarking should wear a well-fitted respirator{1} prior to disembarkation and until screening is undertaken.

• Individuals should ideally carry minimal hand luggage, with the remaining luggage handled separately by the ship’s company.

• Transport (ideally facilitated through boats or coach) should be available and ready to transport individuals to the onward location. Windows should be kept open for ventilation.


Screening area for passengers and crew members

-- Managed by: national health authorities at the port of call.

• National health authorities will define the best location to organize the screening of disembarking passengers and crew. It may be organized while passengers and crew are exiting the boat one by one or in a designated screening area on shore.

• Screening area(s) should be organized in a dedicated, pre-identified location in the port area, preferably outdoors but allowing for privacy, and with seats (distanced at least one meter apart), access to dedicated bathroom facilities, hand hygiene products and drinking water available in the waiting area.

• If indoors, the room should be well-ventilated (open windows), large enough to maintain distancing of at least one meter between people, have separate entrance and exits with one-way flow to maintain distancing and crowd control, and have provision for personal comfort i.e., toilets, seating (one meter apart), supply of individual water, and waste facilities.

• Toilet and rest facilities should be separate from those for reception and assessment staff.

• Administration and support staff should be allocated to ensure compliance with public health recommendations and are advised to wear medical masks, with access to hand hygiene facilities (soap and water or alcohol-based hand solutions).

• The screening area should ensure that at least one meter distance between the screener and the passenger/crew member is maintained. Temperature checks should be undertaken with non-touch thermometers.

• Respirators, masks and hand hygiene stations should be available in the screening area.

• Adequate environmental cleaning and disinfection of surfaces and shared equipment in the screening area should be performed between screenings.

• Equipped ambulances and their staff should be prepositioned prior to disembarkation, in case a medical evacuation is needed.


Screening and evaluation of passengers and crew members at disembarking

-- Managed by: national health authorities / evaluation team

Note: a team on the ship is currently assessing passengers and crew for exposure and health status. Coordination among this team and the evaluation team at disembarkation is strongly encouraged.

• In coordination with the ship, data on exposures should be examined to facilitate rapid exposure assessments.

• All passengers and crew should be provided with clear information including why measures are in place, what happens next (monitoring, travel, contact points), what symptoms to watch out for, and who to immediately contact 24/7 if any symptom develops.

• Investigation and medical teams should be mindful of the high-stress environment experienced by the passengers and crew and ensure empathy when conducting screening.

• All passengers and crew members are advised to wear a well-fitted respirator (e.g. FFP2, N95) while being assessed by port health authorities.

• During assessment, passengers and crew members will be checked for fever with non-touch thermometers, evaluated for their exposure and any symptoms they might have or have had.

• The above procedures shall be conducted by trained medical teams.

• During evaluation, any passenger or crew member with symptoms compatible with the suspected case definition (see Management of contacts of Andes virus (ANDV) cases from the MV Hondius cruise ship) should be managed as described in the next section.

• Health personnel conducting screening should apply standard IPC precautions, including:

    Perform hand hygiene before and after the screening of contacts.

    Use of gloves if touching travelers and when handling potentially contaminated materials.

    Health personnel are advised to wear a medical mask and eye protection during screening of passengers and crew members at disembarking.

    Medical masks should be disposed of if they become soiled or wet.

    Adequate quantities of PPE items and hand hygiene material should be available in the evaluation area.

• Ideally, those disembarking should be pre-cleared by immigration authorities to avoid the need for contact with immigration staff. If they must pass through immigration, they should do so after screening, and immigration staff should wear a medical mask and have access to hand hygiene facilities (soap and water or alcohol-based hand solutions).


Management of passengers or crew members with symptoms identified at the time of screening

-- Managed by: national health authorities

• During evaluation, if a person presents symptoms compatible with ANDV infection (see case definition in Management of contacts of Andes virus (ANDV) cases from the MV Hondius cruise ship), the medical team should:

    Practice hand hygiene and ensure adequate PPE as described above and in annex 3.

    Isolate the patient in a designated area with a dedicated bathroom and dedicated linen/personal items while transfer for evacuation is organized.

    Initiate the medical evacuation of the person to a designated health facility as indicated above.

    PPE must be changed between patients, and hand hygiene should be performed before putting on PPE, and after removing PPE.

• When transferring, ensure the patient wears a respirator and the health worker wears PPE (eye protection, respirator (e.g. N95, FPP2), gown, gloves).

• Initial symptomatic treatment should be initiated for symptom control and if needed, any supportive care intervention, i.e. oxygen if hypoxemic. A monitoring plan should be put into place to ensure any clinical deterioration is noted in a timely fashion.

• See Annex 2 and 3 for further information.


Mental health and psychosocial support (MHPSS) for passengers and crew members

-- Managed by: MHPSS team, national health authorities.

• Mental health and psychosocial support should be considered for passengers and crew disembarking, as this situation may have generated significant stress in some.

• The availability of psychosocial support could help address anxiety or distress associated with the disembarkation process and perceived health risks.


Management of passenger and crew luggage and belongings

-- Managed by: conveyance operator / competent authorities

• Luggage will be handled after disembarkation by the conveyance operator, in collaboration with competent authorities.

• Passengers and crew members will be able to take their luggage back after screening is completed, in accordance with the protocols established by the competent authorities.


3. After disembarking

Onward travel of asymptomatic passengers and crew members

-- Managed by: national health authorities in country of repatriation

- For further guidance, see Management of contacts of Andes virus (ANDV) cases from the MV Hondius cruise ship.

- Asymptomatic passengers may travel following repatriation from the Canary Islands, provided that

- they have completed the active monitoring and in designated facility or home quarantine. Which includes:

• Public health authorities should conduct daily follow-up for 42 days after disembarkation, during which time the passenger should be advised to avoid contact with other persons through remaining in a designated facilities or at home, depending on national guidelines and capacities. 

• Follow-up may occur by telephone, messaging, telehealth, or in person.

• Passengers who are healthcare workers should refrain from returning to work for designated period.

• Passengers should avoid contact with other household members, and where possible and remain in a separate room.

• In case social interactions are unavoidable, passenger should wear a FFP2 or N95 respirator, practice physical distancing, and observe regular hand hygiene.

• All travel, nationally and internationally, should be discouraged for 42 days.

• Movement of the passenger out of the jurisdiction of public health authorities in charge of their follow-up may be allowed for life-threatening or humanitarian reasons, provided that arrangements are made with the public health authorities in the jurisdiction at destination, including internationally through IHR channels.

• During daily follow-up, any symptoms: temperature, fever, fatigue or malaise, muscle ache, headache, gastrointestinal symptoms, respiratory symptoms, should be promptly reported using a contact follow-up form.

• Any passengers developing symptoms compatible with hantavirus infection should be promptly isolated, clinically evaluated and tested.

• Passengers should receive:

    Written information on symptoms to look out for.

    Emergency contact numbers.

    Instructions regarding healthcare seeking and testing.


Crew management

-- Managed by: cruise operator / competent authorities

• Medical care, including public health preventive measures, for crew members should be provided in accordance with the Maritime Labour Convention, 2006, as amended (MLC, 2006)

• Crew members should not resume duty on another ship until they complete the active monitoring and in designated facility or home quarantine (as above)


Management of deceased persons confirmed for ANDV infection on the ship

-- Managed: national authorities at port of call.

- Transmission of ANDV from deceased persons has not been documented, and viral load decreases before terminal illness; however, other respiratory pathogens (e.g., tuberculosis) have been transmitted from human remains. Thus, as exposure to bodily fluids and respiratory secretions may occur during handling of remains, standard IPC precautions should be applied when managing deceased suspected, probable, or confirmed cases.

• Personnel handling remains should apply standard IPC precautions and wear appropriate PPE, including gloves, gown, medical mask, and eye protection where exposure to bodily fluids or respiratory secretions is possible.

• Hand hygiene should be performed before and after PPE use and after contact with the body or contaminated materials.

• Unnecessary manipulation of the body and aerosol-generating procedures should be avoided.

• The body should be placed in a leak-proof body bag if needed and handled according to national procedures.

• Environmental cleaning and disinfection of potentially contaminated surfaces and equipment should be performed using appropriate disinfectants.

• International repatriation of remains may proceed according to national and international regulations.


Ship disinfection

-- Managed by conveyance operator and competent authorities

• The ship should be inspected for rodents, cleaned, disinfected and appropriate rodent control measures implemented, as appropriate, in accordance with the Integrated Management Plan of the Ship and WHO guidance, and as per advice of the competent authority.

• The ship shall cease to be regarded as affected when the competent authority is satisfied with the measures implemented, and there are no conditions on board that could constitute a public health risk.

• Staff involved in sanitary procedures on board the ship should wear adequate PPE (including eye protection, respirator, gown, and gloves).


Plans for updating

-- WHO continues to monitor the situation closely for any changes that may affect this interim guidance. 

-- Should any factors change, WHO will issue a further update. 

-- Otherwise, this interim guidance will expire one year after the date of publication.


References

1. World Health Organization. International Health Regulations (2005) – As amended in 2014, 2022 and 2024. https://apps.who.int/gb/bd/pdf_files/IHR_2014-2022-2024-en.pdf

2. World Health Organization. WHO Guideline on Contact Tracing; 2025. https://www.who.int/publications/i/item/9789240102965

3. World Health Organization. Handbook for Management of Public Health Events on Board Ships; 2016. https://www.who.int/publications/i/item/handbook-for-management-of-public-health-events-on-board-ships

4. World Health Organization. Vector Surveillance and Control at Ports, Airports, and Ground Crossings; 2016. https://www.who.int/publications/i/item/vector-surveillance-and-control-at-ports-airports-and-ground-crossings

5. World Health Organization. Guide to Ship Sanitation. 3rd edition; 2011. https://www.who.int/publications/i/item/9789241546690

6. World Health Organization. Handbook for inspection of ships and issuance of ship sanitation certificates; 2011. https://www.who.int/publications/i/item/handbook-for-inspection-of-ships-and-issuance-of-ship-sanitation-certificates

7. World Health Organization. Considerations for strengthening international information sharing for tracing and managing infectious disease cases and contact persons: Interim Guidance; 2026. https://www.who.int/southeastasia/internal-publications-detail/sewhe09022601

8. World Health Organization. World Health Organization. A decision framework for effective, equitable and context-specific public health and social measures during public health emergencies: decision navigator.

9. EU Healthy Sailing. Evidence-based guidelines for the specificities and needs of medical operations in expedition passenger ships. 2026

10. WHO and ICRC. Basic Emergency Care. Approach to the acutely ill and injured. 2018. https://www.who.int/publications/i/item/basic-emergency-care-approach-to-the-acutely-ill-and-injured


Annex 1. Risk communication

-- Effective risk communication is essential to support the safe, orderly, and dignified disembarkation and onward management of passengers and crew members, and to maintain public trust during an evolving public health event. 

-- Member States should ensure that communication activities are coordinated, timely, and aligned with operational measures described in this technical note.

• Ensure that passengers and crew receive clear, consistent and timely information before, during and after disembarkation, including explanations of public health measures, what to expect and next steps.

• Ensure communication materials are available in the relevant languages of passengers and crew and in accessible formats.

• Communicate clearly that the disembarkation and onward return of passengers and crew are being conducted through coordinated and controlled public health procedures, and that the risk to the wider public remains low.

• Communication should be reassuring yet vigilant, noting that people who have been exposed may still be at risk of developing symptoms and highlighting the importance of recognizing and reporting symptoms early.

• Acknowledge openly what is known and what remains uncertain, that investigations are ongoing and that recommendations may be updated as new epidemiological or laboratory evidence becomes available.

• Explain that changes in guidance reflect standard precautionary public health practice.

• Provide passengers and crew with written and verbal information on symptoms to monitor, duration, procedures if symptoms develop and contact details for public health authorities responsible for follow-up.

• Promote early reporting of symptoms and cooperation with monitoring arrangements and any other public health measure advised while traveling home.

• Ensure communication materials and briefings emphasize respect for the dignity, privacy and rights of passengers and crew and explicitly discourage stigma, discrimination, or blame.

• Ensure that communication at points of entry (ports, airports, transit hubs) is coordinated across agencies and consistent in messaging to avoid confusion or contradictory messages.

• Provide host communities, transit authorities, and destination countries with clear public information on the rationale for measures in place, what to expect, and what actions are not required.

• Establish clear channels for two-way communication, allowing passengers and crew to ask questions, raise concerns, and seek clarification throughout disembarkation and onward management.

• Monitor public perceptions, media coverage, and misinformation related to the event and adapt communication content and tone as needed, in coordination with WHO and relevant partners.


Annex 2. IPC for healthcare workers caring for suspected or confirmed cases

• Suspected, probable or confirmed cases must be isolated in single rooms (one room per case).

• In addition to standard precautions, implement transmission-based precautions when providing care to suspected or confirmed cases.

• Those providing care should wear personal protective equipment prior to entering the isolation room.

    Perform hand hygiene before donning PPE.

    PPE items include: eye protection, respirator (e.g. N95, FPP2), gown, gloves when providing direct patient care.

    PPE should be removed and appropriately disposed of when exiting the isolation room, and hand hygiene must be performed after removal of PPE items.

• Ensure adequate indoor ventilation.

• Routine environmental cleaning and disinfection should be performed using regular disinfectants.

• Medical waste and used linen should be handled as per existing procedures.

• When transferring, ensure the patient wears a respirator and the healthcare worker wears PPE (eye protection, respirator (e.g. N95, FPP2), gown, gloves).

• Transport of patients should be carefully planned to ensure sending/receiving ends are fully informed and prepared.


Annex 3. Considerations on clinical management of suspected and confirmed patients

-- Medical management of a person with suspected, probable or confirmed hantavirus infection should be structured through standard protocols using appropriate PPE (see above), including:

• Severity-based triage of the condition using clinical and physiological measures (see WHO Basic Emergency Care).

• Systematic assessment, and rapid emergency action to address problems in Airway, Breathing, Circulation, Disability [ABCDE].

• Establishing a diagnosis is a priority (PCR and serology testing), but all patients should be managed according to the severity of disease. Outbreak case definitions are not a substitute for clinical judgment.

• High-quality and anticipatory supportive care should be provided.

    Oxygen and availability of respiratory support should be prioritised.

    * Deterioration after the prodromal phase can be precipitous (over hours). Anticipatory actions should include careful monitoring and ensuring proximity to intensive care facilities for cardiovascular support, mechanical ventilation, and ideally extracorporeal membrane oxygenation.

    * Shock should be treated according to existing clinical guidelines for sepsis.

    * Ensure monitoring of vital signs and renal function (through clinical and biochemical assays). Investigation and monitoring of platelet count and proteinuria should be in place as these provide early insight into adverse prognosis, and imminent acute kidney injury respectively.

    * There are no proven antiviral treatments for hantavirus. Off-label use of favipiravir, remdesivir and other existing drugs have been used. Such use must be accompanied by detailed clinical data capture under monitored use. Mechanistically, remdesivir is less favourable compared with favipiravir due to its relatively reduced action against segmented viruses such as hantavirus).

• Direct evidence related to the use of corticosteroids in hantavirus infection for pulmonary or renal syndromes is limited. A single randomized controlled trial of patients with Andes virus hantaviral infection with cardiopulmonary syndrome in Chile did not demonstrate a benefit from high dose corticosteroid treatment but was underpowered to detect a moderate difference between arms.

• Routine antibiotic administration is not indicated for known hantavirus disease. However, for those presenting with symptoms of acute respiratory infection, bacterial infection must be considered. Suspicion of superadded bacterial infection is also an indication for antibiotic treatment based on clinical assessment.


Annex 4. Considerations on laboratory diagnosis

NOTE. Further information on laboratory diagnosis will be provided in a separate document and will cover additional aspects.

• Laboratory diagnosis of hantavirus infection relies on either molecular detection of viral RNA and serological detection of antibodies, with the choice depending on the interval between symptom onset and sample collection.

• By the time symptoms develop, viremia is often already at or near its peak, and both IgM and IgG antibodies may be detectable. IgM levels begin to decline over the following weeks and typically disappear within about three months, whereas IgG appears slightly later and may remain elevated for many years.

• For molecular detection, whole blood is recommended, while serum and blood clot can also be used. Serum is the preferred specimen for serology, although plasma from whole blood is also acceptable. Samples should be collected in sterile plastic tubes with screw caps.


Testing of suspected cases

• Suspected cases should be tested using an Andes virus–specific RT-PCR protocol, as outlined in reference laboratory procedures posted on the WHO EIS Platform and in the WHO Disease Outbreak News. In the absence of Andes virus-specific RT-PCR, a pan-hantavirus PCR can be used, and sequencing should be performed to confirm Andes virus.

• Molecular detection by RT-PCR, whether conventional or real-time, can confirm infection at any point during the acute phase, up to approximately ten days after symptom onset.

• If a sample has been collected more than 10 days after onset, a negative RT-PCR result in a properly collected and preserved sample, only rules out infection when serological testing is also negative, provided that enough time since last exposure has elapsed to allow development of anti-Andes virus specific antibodies.

• Positive cases without an epidemiological link to a confirmed or probable case should be systematically sequenced.


Testing of asymptomatic contacts for research purposes

• Routine testing of asymptomatic contacts is not mandatory for public health purposes.

• Regular (e.g. weekly) RT-PCR testing of asymptomatic contacts, on specimens such as blood, saliva, oral swabs and nasopharyngeal swabs, could be considered for research purposes to better understand virus shedding and transmission dynamics.

• However, testing should NOT be used to determine the end of the follow-up period, which remains fixed at 42 days after last exposure regardless of test results.

• When testing capacity is limited, symptomatic contacts must always be prioritised for diagnostic testing because they are more likely to be infected and require timely clinical evaluation.

• Serological testing at the beginning and end of the follow-up period may also be considered to ascertain serological status of contacts.

© World Health Organization 2026. Some rights reserved. This work is available under the CC BY-NC-SA 3.0 IGO license.

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{1} The recommendation for contacts to wear a well-fitted respirator (N95, FFP2) until screening is undertaken is a precautionary source control measure aimed at reducing the risk of onward transmission from individuals who might be symptomatic and pre-symptomatic.

Source: 


Link: https://www.who.int/publications/m/item/who-technical-note-for-the-disembarkation-and-onward-management-of-passengers-and-crew-in-the-context-of-an-andes-virus-associated-cluster-mv-hondius-cruise-ship

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Monday, May 4, 2026

#Niclosamide Inhibits the #Replication of Highly Pathogenic Avian #Influenza #H5Nx Viruses and Antiviral-Resistant #Mutants

 


Highlights

• Niclosamide blocks the replication of highly pathogenic avian influenza H5 viruses

• Niclosamide is effective against H5 viruses with antiviral-resistant substitutions

• Niclosamide has potential as host-targeting anti-influenza drug


Abstract

The recurrent spillover of highly pathogenic avian influenza (HPAI) H5 viruses into humans represents a major public health concern that is exacerbated by the emergence of drug-resistant viral variants. Host-targeting antiviral approaches, including drug repurposing, offer a promising alternative to conventional virus-directed therapeutics. Here, we evaluated the antiviral activity of niclosamide, an FDA-approved anthelmintic drug, against four HPAI A(H5Nx) viruses, two A(H5N1), one A(H5N6), and one A(H5N8), recently isolated from human cases. Niclosamide inhibited all four viruses in plaque reduction assays with MDCK cells, with low inhibitory concentration 50% (IC50) values (0.68–1.40 μM) and minimal cytotoxicity at effective concentrations. These values were more potent than the IC50 values observed for the RdRp inhibitor favipiravir. Niclosamide treatment plus either baloxavir marboxil or favipiravir resulted in additive or near-additive interactions, as indicated by synergy scores of ±10. Importantly, niclosamide retained antiviral activity against HPAI A(H5Nx) viruses bearing resistance-associated amino acid substitutions (i.e., PA-I38T, baloxavir resistance and PB1-K229R, favipiravir resistance), consistent with its host-directed mechanism of action. Although there are barriers to be overcome such as a narrow therapeutic window, largely attributable to its poor bioavailability and some cytotoxicity, our findings suggest niclosamide has potential as a host-targeting therapeutic option against emerging zoonotic influenza viruses, particularly in settings involving antiviral-resistant escape mutants.

Source: 


Link: https://www.sciencedirect.com/science/article/pii/S016635422600080X?via%3Dihub

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Thursday, April 30, 2026

#Antiviral treatment for #influenza

 


Abstract

Seasonal influenza is a widespread acute respiratory infection that causes significant illness and death worldwide. Two major antiviral classes are neuraminidase inhibitors (NAIs) and polymerase inhibitors. NAIs, including oseltamivir, zanamivir, peramivir and laninamivir, block viral release, while polymerase inhibitors such as baloxavir disrupt viral RNA replication. Early administration within 48 h of symptom onset reduces illness duration, severity and complications, particularly in high-risk groups. Oseltamivir is the most widely studied NAI, demonstrating reduced viral shedding, faster symptom resolution and lower complication rates, though gastrointestinal side effects are common. Higher doses generally do not improve outcomes compared to standard dosing. Zanamivir is more effective against influenza B and is inhibitory for most influenza A viruses resistant to oseltamivir, but the inhaled formulation is less suitable for patients with severe illness or airway disease. Intravenous (IV) zanamivir is approved for hospitalized influenza patients in some countries. Peramivir offers IV treatment options, while laninamivir is mainly used in Japan. Baloxavir shows superior viral load reduction and comparable symptom relief to oseltamivir in outpatients, though resistance variants can emerge. Favipiravir and newer polymerase inhibitors are under investigation. Combination therapies may enhance recovery, with limited evidence. Overall, timely antiviral use is critical to reducing influenza’s burden.


This article is part of the Theo Murphy meeting issue ‘Evaluating anti-infective drugs’.

Source: 


Link: https://royalsocietypublishing.org/rstb/article/381/1949/20240344/481548/Antiviral-treatment-for-influenza

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Wednesday, March 18, 2026

Optimal Dose and #Safety of Intravenous #Favipiravir in Hospitalized Patients With #COVID19: A Dose-Escalating, Randomized Controlled Phase Ib Study

 


Abstract

AGILE (NCT04746183) is a Phase Ib/IIa platform, evaluating candidates to treat COVID-19. Candidate Specific Trial 6 evaluated the safety and optimal dose of a novel intravenous formulation of favipiravir in a dose-escalating, open-label, randomized, controlled, Bayesian adaptive Phase Ib trial. Hospitalized adults with PCR-confirmed SARS-CoV-2 infection, within 14 days of symptomatic COVID-19 were randomized 2:1 in groups of 6 (n = 4 favipiravir, n = 2 standard of care) to ascending doses of intravenous favipiravir twice daily (b.i.d.) for 7 days or standard of care. Clinical data, safety evaluations, virology and pharmacokinetic samples were collected. The primary outcome was safety. Secondary outcomes included clinical, pharmacokinetic and virological endpoints. Twenty-four participants enrolled between September 10, 2022 and November 1, 2023 [10/24 female; median age 74 years (range 52–93)]. Favipiravir was well tolerated despite a high background rate of unrelated adverse events. No dose limiting toxicities were observed, with a model-predicted dose limiting toxicity risk of 16.8% and probability of unacceptable toxicity of 2.7% at the highest dose level. No serious adverse events were deemed related to favipiravir but an expected association with asymptomatic, transient hyperuricemia was observed. Favipiravir exposures increased disproportionally to dose with significant accumulation in plasma, but with marked variability between participants within each cohort. This novel formulation of favipiravir was safe at sustained high doses that reached pre-specified pharmacokinetic targets in a study group with frailty and complex health profiles. We consider doses up to 2,400 mg b.i.d. to be safe for further evaluation.


Study Highlights

-- WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

- Pre-clinical studies of favipiravir describe broad spectrum antiviral activity, positioning it as a therapeutic candidate for many RNA viruses. An oral formulation of favipiravir has been widely studied as a treatment for COVID-19 in clinical trials. Pharmacokinetic modeling suggests the doses used in many of these trials may not have reached effective plasma concentrations.

-- WHAT QUESTION DID THIS STUDY ADDRESS?

- Was a novel intravenous formulation of favipiravir safe and well tolerated in patients hospitalized with COVID-19? Were pre-specified pharmacokinetic parameters met at doses modeled to be effective for the treatment of COVID-19?

-- WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

- We demonstrate that high doses of intravenous favipiravir are safe and well tolerated in a frail and co-morbid population who are likely to be eligible for antiviral treatment but are often excluded from early phase clinical trials. We characterize the pharmacokinetic profile of intravenous favipiravir at high doses and recommend an optimal dose to be used in future Phase II studies.

-- HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

- There is an ongoing unmet need for antivirals to effectively treat COVID-19; however, the significance of these safety and pharmacokinetic data go beyond COVID-19. High doses of favipiravir have a use case against RNA viruses with pandemic potential including viral hemorrhagic fevers and pandemic influenza. The intravenous formulation may be particularly relevant in severely unwell patients for whom oral dosing is not possible or in whom GI absorption is affected. The pharmacokinetic characterization from this study will be used to inform doses for use against a range of significant pathogens. Early phase clinical trials of IV favipiravir in Crimean-Congo Haemorrhagic Fever are ongoing.

Source: 


Link: https://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.70261

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Monday, February 23, 2026

#SARS-CoV-2 Error Catastrophe Under #Molnupiravir: #Mutagenic Enhancement Enables Viral #Persistence with Impaired Fitness

 


Abstract

Molnupiravir induces mutations that render severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication-competent through error catastrophe mechanisms. Previous studies showed no resistant virus emergence during prolonged molnupiravir treatment, with no resistant variants reported. However, these approaches were limited by genetic uniformity at passage initiation. To investigate viral population dynamics under enhanced genetic diversity, we employed mutagenic pre-treatment using 5-fluorouracil (5-FU) and favipiravir to generate diverse quasi-species populations before molnupiravir selection pressure. Viral populations were treated with stepwise increasing molnupiravir concentrations (10 μM ⟶ 25 μM ⟶ 40 μM) over ten serial passages. Viral detectability, plaque morphology, and mutation accumulation were analyzed using molecular and sequencing approaches. Only high-concentration favipiravir (1000 μM) pre-treatment maintained detectable viral RNA through ten passages under 40 μM molnupiravir, while favipiravir (500 μM) and 5-FU groups became undetectable after passage 6. Surviving populations formed extremely small plaques with markedly reduced replication capacity. Next-generation sequencing revealed extensive mutation accumulation across viral proteins, including polymerase proteins. Individual viable virus isolation was unsuccessful, and large-scale propagation could not be achieved. These findings demonstrate apparent survival rather than true resistance to molnupiravir, characterized by severely compromised viral fitness.

Source: 


Link: https://www.mdpi.com/1999-4915/18/2/273

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Friday, February 20, 2026

#Baloxavir outperforms #oseltamivir, #favipiravir, and #amantadine in treating lethal #influenza #H5N1 HA clade 2.3.4.4b #infection in #mice

 


Abstract

Intercontinental spread of highly pathogenic avian influenza A(H5N1) viruses poses significant pandemic risks and necessitates strong protective countermeasures. We evaluated the therapeutic efficacy of the neuraminidase inhibitor oseltamivir, the polymerase inhibitors baloxavir and favipiravir, and an ion-channel blocker amantadine, against severe influenza A(H5N1) virus infection in female BALB/c mice. Baloxavir (≥10 mg/kg, 1 dose) fully protected mice from death, significantly reduced virus respiratory replication, and prevented neuroinvasion. Oseltamivir (≥100 mg/kg/day for 5 days) provided limited survival benefits, reduced lung titers but failed to prevent viral neuroinvasion. Favipiravir (≥100 mg/kg/day for 5 days) provided partial protection, although did not reduce viral titers in lungs and brain. Amantadine provided no benefits. Although all drugs inhibited A(H5N1) viruses in vitro, in vivo correlations did not extend beyond baloxavir. Our results indicate that baloxavir is the most reliable treatment to address both respiratory replication and systemic spread of contemporary A(H5N1) viruses in mice and should be considered in pandemic planning.

Source: 


Link: https://www.nature.com/articles/s41467-026-69721-5

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Thursday, February 5, 2026

Post-exposure #prophylaxis with #favipiravir among #household close contacts to confirmed #COVID19 cases: A cluster-randomized trial (PEPfavi)

 


Abstract

Background

Household transmission of SARS-CoV-2 remains a key driver of community spread, with secondary attack rates in Thai households reaching approximately 50 %. There is limited evidence supporting the efficacy of antiviral post-exposure prophylaxis (PEP) in this context.

Methods

The phase 2/3, open-label, (1:1) cluster-randomized controlled trial in Thailand, 168 household close contacts from 76 index cases were enrolled to receive either favipiravir-PEP (FPV-PEP) (1600–2000 mg/day for 7 days) or usual care. The efficacy of FPV-PEP was investigated in preventing SARS-CoV-2 infection after contact with index cases.

Results

The incidence of confirmed SARS-CoV-2 infection was lower in the FPV-PEP group than in the usual care group (7.32 % vs. 14.47 %), although the difference was not statistically significant. A trend toward fewer early positive rapid diagnostic test results on day 3 was observed in the FPV-PEP group. Symptom development was less frequent among FPV-PEP recipients, with fewer cases of fever, rhinorrhea, and myalgia. A significantly higher probability of remaining asymptomatic and delayed symptom onset was observed in the FPV-PEP group. No participants developed severe COVID-19 or required hospitalization.

Conclusion

FPV-PEP was associated with a lower incidence of fever, rhinorrhea, and myalgia among household contacts. While a reduction in secondary transmission was observed, it did not reach statistical significance. Further large-scale studies are warranted to clarify its role in preventing household transmission.

Source: 


Link: https://www.sciencedirect.com/science/article/pii/S1876034126000225?via%3Dihub

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Tuesday, September 2, 2025

#Placental transfer of #medications to treat #COVID19, #molnupiravir, #favipiravir and #nirmatrelvir/ritonavir, in the ex vivo human cotyledon model

 


Abstract

Objectives

There have been few studies in pregnant women of medications that are used to reduce severe complications from COVID-19 infection. Currently, nirmatrelvir/ritonavir (Paxlovid) is recommended by the National Institutes for Health to treat non-hospitalized pregnant patients with mild-to-moderate COVID-19 illness. The aim of this study was to determine the transplacental passage of molnupiravir, nirmatrelvir/ritonavir and favipiravir utilizing an ex vivo placental perfusion model.

Methods

Human placental cotyledons were continuously perfused in a double open circuit. The study molecules and antipyrine, a marker of placental viability, were dissolved in the maternal solution. The experiment was conducted over 90 minutes, and every 5 minutes, samples of the maternal solution and fetal exchange solutions were collected for analysis. We calculated the concentrations of study molecules, fetal transfer ratios and the clearance indexes to determine placental transfer.

Results

Of 18 placentas analysed, 14 were validated by antipyrine transfer. Nirmatrelvir alone had low placental transfer, with a fetal transfer ratio of 0.025. Its placenta transfer increased in the presence of ritonavir, with a fetal transfer ratio of 0.06. The molnupiravir metabolite, β-D-N-4-hydroxycytidine (EIDD 1931), showed low placental transfer, with an average fetal transfer ratio of 0.04. By contrast, favipiravir crossed the placenta with an average fetal transfer ratio of 0.425.

Conclusions

Placental transfer was high for the nucleoside analogue favipiravir, while it was low for molnupiravir and low for the protease inhibitor nirmatrelvir but increased by ritonavir. Clinical data are required to confirm the placental transfer and determine the safety of COVID antivirals in pregnancy.

Source: Journal of Antimicrobial Chemotherapy, https://academic.oup.com/jac/advance-article-abstract/doi/10.1093/jac/dkaf302/8245204?redirectedFrom=fulltext

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Tuesday, May 13, 2025

Dose response comparison of #Nipah virus #strains #Malaysia and #Bangladesh in #hamsters exposed by the intranasal or intraperitoneal route

Abstract

Nipah virus, a zoonotic pathogen, can cause debilitating disease and death in humans. Currently, countermeasures are limited, with several in various stages of testing but none yet FDA-approved for human use. Evaluation of countermeasure candidates requires safety testing in humans, as well as efficacy testing against lethal challenge in animal models. Herein, we describe the characterization and comparison of the intraperitoneal and intranasal Syrian golden hamster models for Nipah virus strains Malaysia and Bangladesh. Overall, the intraperitoneal route of exposure resulted in a more consistent lethal outcome, regardless of virus strain. Therefore, the IP model was subsequently used to evaluate the use of Favipiravir as a potential positive control for future studies investigating NiV countermeasures. In contrast to prior reported results regarding Favipiravir in Nipah virus-infected hamsters, Favipiravir was only fifty percent effective at preventing death following lethal challenge, regardless of Nipah virus strain. The data suggest that Favipiravir is only partially protective against Nipah virus in hamsters, and, thus, would likely not be an ideal candidate as a positive control in future efficacy studies.

Source: PLoS One, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0318912

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Tuesday, April 1, 2025

#PA and #PAX: two key #proteins from segment 3 of the #influenza viruses

Abstract

In recent years, the influenza viruses have posed an increasingly severe threat to public health. It is essential to analyze the virulence and pathogenesis of influenza viruses to prevent and control them, as well as create antiviral drugs. Previous studies have revealed that influenza virus segment 3 codes for not only the PA protein but also a novel protein, PA-X. PA protein is one subunit of the polymerase of influenza viruses and plays a critical role in its life cycle. PA presented endonuclease activity, the transcription and replication of the viral genome, viral virulence, protein degradation, and host immune response by interacting with viral proteins, including PB2, PB1, and host factors, including ANP32A, CHD6, HAX1, hCLE, HDAC6, MCM complex. PA mutations were involved in the viral replication, pathogenicity, and transmission of influenza viruses in poultry, mammals, and humans. PA-X is an open reading frame generated by +1 ribosomal code shift at the N-terminal amino acids of segment 3 and possesses the shutoff activity of host gene expression, regulating the host immune response, viral virulence and transmission. Therefore, PA is one ideal target for the development of antiviral drugs against influenza viruses. Baloxavir marboxil (BXM) and Favipiravir are two very effective anti-influenza virus drugs targeting the PA endonuclease domain of influenza A viruses. In this review, we summarized the structures, viral replication, virulent determinants and transmission, host factors, innate immunity, and antiviral drugs involved in PA and PA-X. The information is of great value for underlying the mechanism of viral replication and developing novel effective strategies to prevent and control influenza infection and the pandemic.

Source: Frontiers in Cellucal and Infection Microbiology, https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1560250/full

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