#Influenza at the #human - #animal #interface - Summary and #risk #assessment, from 26 August to 29 September 2025 (#WHO, edited)

 

New human cases {1,2}: 

-- From 26 August to 29 September 2025, based on reporting date, the detection of influenza A(H5) in one human, influenza A(H5N1) in one human, influenza A(H9N2) in eight humans and an influenza A(H1N1) variant ((H1N1)v) virus in one human were reported officially.  

Circulation of influenza viruses with zoonotic potential in animals: 

-- High pathogenicity avian influenza (HPAI) events in poultry and non-poultry animal species continue to be reported to the World Organisation for Animal Health (WOAH).{3} 

-- The Food and Agriculture Organization of the United Nations (FAO) also provides a global update on avian influenza viruses with pandemic potential.{4} 

Risk assessment {5}: 

-- Sustained human to human transmission has not been reported from these events. 

-- Based on information available at the time of this risk assessment update, the overall public health risk from currently known influenza A viruses detected at the human-animal interface has not changed and remains low. 

-- The occurrence of sustained human-to-human transmission of these viruses is currently considered unlikely. 

-- Although human infections with viruses of animal origin are infrequent, they are not unexpected at the human-animal interface.  

Risk management: 

-- Candidate vaccine viruses (CVVs) for zoonotic influenza viruses for pandemic preparedness purposes were reviewed and updated at the September 2025 WHO consultation on influenza vaccine composition for use in the southern hemisphere 2026 influenza season. 

-- A detailed summary of zoonotic influenza viruses characterized since February 2025 is published here and updated CVVs lists are published here. 

IHR compliance: 

-- All human infections caused by a new influenza subtype are required to be reported under the International Health Regulations (IHR).{6} 

-- This includes any influenza A virus that has demonstrated the capacity to infect a human and its haemagglutinin (HA) gene (or protein) is not a mutated form of those, i.e. A(H1) or A(H3), circulating widely in the human population. 

-- Information from these notifications is critical to inform risk assessments for influenza at the human-animal interface.

Avian influenza viruses in humans 

Current situation:  

-- Since the last risk assessment of 25 August 2025, one laboratory-confirmed human case of A(H5) infection was detected in Bangladesh, and one laboratory-confirmed human case of A(H5N1) virus infection was detected in Cambodia. 

A(H5), Bangladesh 

-- On 19 August 2025, Bangladesh notified WHO of one laboratory-confirmed human infection with avian influenza A(H5) virus in a boy in Sylhet Division. 

-- The case developed fever and cough on 27 July and was admitted to hospital on 1 August. 

-- Oropharyngeal and nasopharyngeal swabs collected on 4 August and tested at the Virology Laboratory of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) and the Institute of Epidemiology, Disease Control & Research (IEDCR) tested positive for influenza A(H5) virus by reverse transcription-polymerase chain reaction (RT-PCR) on 14 August.

-- Subtyping for the N-type was pending at the time of notification. 

-- The case was detected through the Hospital-Based Influenza Surveillance (HBIS) platform. The case was discharged on 7 August.  

-- A seven-member multidisciplinary team, comprising physicians, epidemiologists, an anthropologist, and a technologist, was deployed on 15 August to conduct an investigation. 

-- The child had no history of travel and no reported exposure to backyard poultry, however the family purchased chickens from a local market in the days preceding the child’s illness. 

-- All samples collected from contacts tested negative for influenza A(H5) virus. 

-- Samples collected poultry at two markets that were frequently visited by the family of the case tested positive for influenza A(H5) virus.  

-- This is the 12th human case of avian influenza A(H5) reported to WHO from Bangladesh and the fourth in 2025. Where the genetic sequence data is available, the viruses from the human cases thus far are identified as clade 2.3.2.1a viruses. 

A(H5N1), Cambodia 

-- On 9 September 2025, Cambodia notified WHO of a laboratory-confirmed human infection with avian influenza A(H5N1) in a girl from Takeo Province. 

-- The case, with no known underlying medical conditions, had an onset of fever, cough and dyspnea on 1 September and was admitted to hospital on 5 September. Nasopharyngeal and oropharyngeal swabs collected on 7 September tested positive for avian influenza A(H5N1) at the National Institute of Public Health (NIPH) RT-PCR. 

-- Laboratory results were confirmed by the Institut Pasteur du Cambodge, National Influenza Center (NIC) on 8 September. 

-- Treatment with oseltamivir was initiated on 7 September.   

-- As part of the response, active case finding identified 10 close contacts and two villagers presenting with influenza-like illness (ILI). 

-- All nasopharyngeal and oropharyngeal samples collected from close contacts, symptomatic villagers and health workers tested negative for influenza A(H5N1) virus. 

-- A week before symptom onset, approximately 10 to 20 sick or dead chickens were observed at the case’s residence and at a neighbouring house. 

-- The case prepared and cooked sick/dead chickens. Samples collected from chickens and a duck in the village during the investigation tested positive for A(H5N1).

-- Sixteen human infections with A(H5N1) viruses have been confirmed in Cambodia in 2025 and eight of these have been fatal. All these cases in 2025 had exposure to domestic birds or their environments. In some cases, the domestic birds were reported to be sick or dead. Where the information is available, the genetic sequence data from the viruses from the human cases closely matches that from recent local animal viruses and are identified as clade 2.3.2.1e viruses. 

-- From the information available thus far on these recent human cases, there is no indication of human-to-human transmission of the A(H5N1) viruses.  

-- According to reports received by WOAH, various influenza A(H5) subtypes continue to be detected in wild and domestic birds in Africa, the Americas, Asia and Europe. 

-- Infections in non-human mammals are also reported, including in marine and land mammals.{7} 

-- A list of bird and mammalian species affected by HPAI A(H5) viruses is maintained by FAO.{8}

Risk Assessment for avian influenza A(H5) viruses:  

1. What is the current global public health risk of additional human cases of infection with avian influenza A(H5) viruses?  

-- Most human infections so far have been in people exposed to A(H5) viruses, for example, through contact with infected poultry or contaminated environments, including live poultry markets, and occasionally infected mammals and contaminated environments. 

-- As long as the viruses continue to be detected in animals and related environments humans are exposed to, further human cases associated with such exposures are expected but remain unusual. 

-- The impact for public health if additional sporadic cases are detected is minimal. 

-- The current overall global public health risk of additional sporadic human cases is low. 

2. What is the likelihood of sustained human-to-human transmission of avian influenza A(H5) viruses related to the events above?  

-- No sustained human-to-human transmission has been identified associated with the recent reported human infections with avian influenza A(H5) viruses. 

-- There has been no reported human-to-human transmission of A(H5N1) viruses since 2007, although there may be gaps in investigations. 

-- In 2007 and the years prior, small clusters of A(H5) virus infections in humans were reported, including some involving health care workers, where limited human-to-human transmission could not be excluded; however, sustained human-to-human transmission was not reported.  

-- Current evidence suggests that influenza A(H5) viruses related to these events did not acquire the ability to efficiently transmit between people, therefore sustained human-to-human transmission is thus currently considered unlikely.  

3. What is the likelihood of international spread of avian influenza A(H5) viruses by travellers?  

-- Should infected individuals from affected areas travel internationally, their infection may be detected in another country during travel or after arrival. 

-- If this were to occur, further communitylevel spread is considered unlikely as current evidence suggests these viruses have not acquired the ability to transmit easily among humans.  

A(H9N2), China 

-- Since the last risk assessment of 25 August 2025, eight human cases of infection with A(H9N2) influenza viruses were notified to WHO from China between 5 and 8 September 2025. 

-- All but one of the cases were in children and were reported from Anhui (1), Chongqing (1), Guangdong (1), Guangxi (2), Hunan (1), Sichuan (1) and Tianjin (1). 

-- Four had onsets of symptoms in February and were retrospectively reported. Two had onsets in July and two had onsets in August. All but one had known exposure to either live poultry markets or backyard poultry. 

-- Five cases had mild illness and three cases developed pneumonia and were hospitalized and recovered. 

-- No further cases were detected among contacts of these cases.   

Risk Assessment for avian influenza A(H9N2):   

1. What is the global public health risk of additional human cases of infection with avian influenza A(H9N2) viruses?   

-- Most human cases follow exposure to the A(H9N2) virus through contact with infected poultry or contaminated environments. 

-- Most human infections of A(H9N2) to date have resulted in mild clinical illness. Since the virus is endemic in poultry in multiple countries in Africa and Asia{11}, further human cases associated with exposure to infected poultry are expected but remain unusual. 

-- The impact to public health if additional sporadic cases are detected is minimal. 

-- The overall global public health risk of additional sporadic human cases is low.  

2. What is the likelihood of sustained human-to-human transmission of avian influenza A(H9N2) viruses related to this event?   

-- At the present time, no sustained human-to-human transmission has been identified associated with the recent reported human infections with A(H9N2) viruses. 

-- Current evidence suggests that influenza A(H9N2) viruses from these cases did not acquire the ability of sustained transmission among humans, therefore sustained human-to-human transmission is thus currently considered unlikely.   

3. What is the likelihood of international spread of avian influenza A(H9N2) virus by travellers?   

-- Should infected individuals from affected areas travel internationally, their infection may be detected in another country during travel or after arrival. 

-- If this were to occur, further community level spread is considered unlikely as current evidence suggests the A(H9N2) virus subtype has not acquired the ability to transmit easily among humans.   

Swine influenza viruses in humans  

Influenza A(H1N1)v, Germany 

Since the last risk assessment of 25 August 2025, the detection of an influenza A(H1N1)v virus in a human was reported from Germany. 

-- The virus from this case was sequenced and had an HA belonging to clade 1C.2.2, similar to other 1C.2.2 viruses detected in swine in the region. 

Risk Assessment:  

1. What is the public health risk of additional human cases of infection with swine influenza viruses?  

-- Swine influenza viruses circulate in swine populations in many regions of the world. 

-- Depending on geographic location, the genetic characteristics of these viruses differ. 

-- Most human cases are exposed to swine influenza viruses through contact with infected animals or contaminated environments. 

-- Human infection tends to result in mild clinical illness in most cases. 

-- Since these viruses continue to be detected in swine populations, further human cases are expected but remain unusual. 

-- The impact to public health if additional sporadic cases are detected is minimal. The overall risk of additional sporadic human cases is low.  

2. What is the likelihood of sustained human-to-human transmission of swine influenza viruses?   

-- No sustained human-to-human transmission was identified associated with the event described above. 

-- Current evidence suggests that contemporary swine influenza viruses have not acquired the ability of sustained transmission among humans, therefore sustained human-to-human transmission is thus currently considered unlikely.  

3. What is the likelihood of international spread of swine influenza viruses by travelers?   

-- Should infected individuals from affected areas travel internationally, their infection may be detected in another country during travel or after arrival. 

-- If this were to occur, further community level spread is considered unlikely as current evidence suggests that these viruses have not acquired the ability to transmit easily among humans. 

For more information on zoonotic influenza viruses, see the report from the WHO Consultation on the Composition of Influenza Virus Vaccines for Use in the 2026 Southern Hemisphere Influenza Season that was held on 22-25 September 2025 at this link. 

Overall risk management recommendations: 

-- Surveillance and investigations 

- Due to the constantly evolving nature of influenza viruses, WHO continues to stress the importance of global strategic surveillance in animals and humans to detect virologic, epidemiologic and clinical changes associated with circulating influenza viruses that may affect human (or animal) health. 

- Continued vigilance is needed within affected and neighbouring areas to detect infections in animals and humans. 

- Close collaboration with the animal health and environment sectors is essential to understand the extent of the risk of human exposure and to prevent and control the spread of animal influenza. 

- WHO has published guidance on surveillance for human infections with avian influenza A(H5) viruses. 

- As the extent of influenza virus circulation in animals is not clear, epidemiologic and virologic surveillance and the follow-up of suspected human cases should continue systematically. 

- Guidance on investigation of non-seasonal influenza and other emerging acute respiratory diseases has been published on the WHO website. 

- Countries should increase avian influenza surveillance in domestic and wild birds, enhance surveillance for early detection in cattle populations in countries where HPAI is known to be circulating, include HPAI as a differential diagnosis in non-avian species, including cattle and other livestock populations, with high risk of exposure to HPAI viruses; monitor and investigate cases in non-avian species, including livestock, report cases of HPAI in all animal species, including unusual hosts, to WOAH and other international organizations, share genetic sequences of avian influenza viruses in publicly available databases, implement preventive and early response measures to break the HPAI transmission cycle among animals through movement restrictions of infected livestock holdings and strict biosecurity measures in all holdings, employ good production and hygiene practices when handing animal products, and protect persons in contact with suspected/infected animals.9 More guidance can be found from WOAH and FAO. 

- When there has been human exposure to a known outbreak of an influenza A virus in domestic poultry, wild birds or other animals – or when there has been an identified human case of infection with such a virus – enhanced surveillance in potentially exposed human populations becomes necessary. 

- Enhanced surveillance should consider the health care seeking behaviour of the population, and could include a range of active and passive health care and/or communitybased approaches, including: enhanced surveillance in local influenza-like illness (ILI)/SARI systems, active screening in hospitals and of groups that may be at higher occupational risk of exposure, and inclusion of other sources such as traditional healers, private practitioners and private diagnostic laboratories. 

- Vigilance for the emergence of novel influenza viruses with pandemic potential should be maintained at all times including during a non-influenza emergency. In the context of the cocirculation of SARS-CoV-2 and influenza viruses, WHO has updated and published practical guidance for integrated surveillance. 

Notifying WHO 

- All human infections caused by a new subtype of influenza virus are notifiable under the International Health Regulations (IHR, 2005).{10} State Parties to the IHR (2005) are required to immediately notify WHO of any laboratory-confirmed{11} case of a recent human infection caused by an influenza A virus with the potential to cause a pandemic{12}. 

- Evidence of illness is not required for this report. 

- WHO published the case definition for human infections with avian influenza A(H5) virus requiring notification under IHR (2005): https://www.who.int/teams/global-influenzaprogramme/avian-influenza/case-definitions. 

Virus sharing and risk assessment 

- It is critical that these influenza viruses from animals or from humans are fully characterized in appropriate animal or human health influenza reference laboratories. 

- Under WHO’s Pandemic Influenza Preparedness (PIP) Framework, Member States are expected to share influenza viruses with pandemic potential on a timely basis{13} with a WHO Collaborating Centre for influenza of GISRS. 

- The viruses are used by the public health laboratories to assess the risk of pandemic influenza and to develop candidate vaccine viruses.  

- The Tool for Influenza Pandemic Risk Assessment (TIPRA) provides an in-depth assessment of risk associated with some zoonotic influenza viruses – notably the likelihood of the virus gaining human-to-human transmissibility, and the impact should the virus gain such transmissibility. 

- TIPRA maps relative risk amongst viruses assessed using multiple elements. The results of TIPRA complement those of the risk assessment provided here, and those of prior TIPRA analyses will be published at http://www.who.int/teams/global-influenza-programme/avian-influenza/toolfor-influenza-pandemic-risk-assessment-(tipra).  

Risk reduction 

- Given the observed extent and frequency of avian influenza in poultry, wild birds and some wild and domestic mammals, the public should avoid contact with animals that are sick or dead from unknown causes, including wild animals, and should report dead birds and mammals or request their removal by contacting local wildlife or veterinary authorities.  

- Eggs, poultry meat and other poultry food products should be properly cooked and properly handled during food preparation. Due to the potential health risks to consumers, raw milk should be avoided. WHO advises consuming pasteurized milk. If pasteurized milk isn’t available, heating raw milk until it boils makes it safer for consumption. 

- WHO has published practical interim guidance to reduce the risk of infection in people exposed to avian influenza viruses. 

Trade and travellers 

- WHO advises that travellers to countries with known outbreaks of animal influenza should avoid farms, contact with animals in live animal markets, entering areas where animals may be slaughtered, or contact with any surfaces that appear to be contaminated with animal excreta. 

- Travelers should also wash their hands often with soap and water. All individuals should follow good food safety and hygiene practices.  

- WHO does not advise special traveller screening at points of entry or restrictions with regards to the current situation of influenza viruses at the human-animal interface. 

- For recommendations on safe trade in animals and related products from countries affected by these influenza viruses, refer to WOAH guidance.  

Links:  

-- WHO Human-Animal Interface web page https://www.who.int/teams/global-influenza-programme/avian-influenza 

-- WHO Influenza (Avian and other zoonotic) fact sheet https://www.who.int/news-room/fact-sheets/detail/influenza-(avian-and-other-zoonotic) 

-- WHO Protocol to investigate non-seasonal influenza and other emerging acute respiratory diseases https://www.who.int/publications/i/item/WHO-WHE-IHM-GIP-2018.2 

-- WHO Public health resource pack for countries experiencing outbreaks of influenza in animals:  https://www.who.int/publications/i/item/9789240076884 

-- Cumulative Number of Confirmed Human Cases of Avian Influenza A(H5N1) Reported to WHO  https://www.who.int/teams/global-influenza-programme/avian-influenza/avian-a-h5n1-virus 

-- Avian Influenza A(H7N9) Information https://www.who.int/teams/global-influenza-programme/avian-influenza/avian-influenza-a-(h7n9)virus 

-- World Organisation of Animal Health (WOAH) web page: Avian Influenza  https://www.woah.org/en/home/ 

-- Food and Agriculture Organization of the United Nations (FAO) webpage: Avian Influenza https://www.fao.org/animal-health/avian-flu-qa/en/ 

-- OFFLU http://www.offlu.org/ 

___

{1} This summary and assessment covers information confirmed during this period and may include information received outside of this period. 

{2} For epidemiological and virological features of human infections with animal influenza viruses not reported in this assessment, see the reports on human cases of influenza at the human-animal interface published in the Weekly Epidemiological Record here.  

{3} World Organisation for Animal Health (WOAH). Avian influenza. Global situation. Available at: https://www.woah.org/en/disease/avian-influenza/#ui-id-2. 

{4} Food and Agriculture Organization of the United Nations (FAO). Global Avian Influenza Viruses with Zoonotic Potential situation update. Available at: https://www.fao.org/animal-health/situation-updates/global-aiv-withzoonotic-potential. 

{5} World Health Organization (2012). Rapid risk assessment of acute public health events. World Health Organization. Available at: https://iris.who.int/handle/10665/70810. 

{6} World Health Organization. Case definitions for the 4 diseases requiring notification to WHO in all circumstances under the International Health Regulations (2005). Case definitions for the four diseases requiring notification in all circumstances under the International Health Regulations (2005).   

{7} World Organisation for Animal Health (WOAH). Avian influenza. Global situation. Available at: https://www.woah.org/en/disease/avian-influenza/#ui-id-2. 

{8} Food and Agriculture Organization of the United Nations. Global Avian Influenza Viruses with Zoonotic Potential situation update. Available at: https://www.fao.org/animal-health/situation-updates/global-aiv-withzoonotic-potential/bird-species-affected-by-h5nx-hpai/en. 

{9} World Organisation for Animal Health. Statement on High Pathogenicity Avian Influenza in Cattle, 6 December 2024. Available at: https://www.woah.org/en/high-pathogenicity-avian-influenza-hpai-in-cattle/. 

{10} World Health Organization. Case definitions for the four diseases requiring notification in all circumstances under the International Health Regulations (2005).    

{11} World Health Organization. Manual for the laboratory diagnosis and virological surveillance of influenza (2011). Available at: https://apps.who.int/iris/handle/10665/44518 

{12} World Health Organization. Pandemic influenza preparedness framework for the sharing of influenza viruses and access to vaccines and other benefits, 2nd edition. Available at: https://iris.who.int/handle/10665/341850 

{13} World Health Organization. Operational guidance on sharing influenza viruses with human pandemic potential (IVPP) under the Pandemic Influenza Preparedness (PIP) Framework (2017). Available at: https://apps.who.int/iris/handle/10665/259402. 

___

Source: World Health Organization, https://www.who.int/publications/m/item/influenza-at-the-human-animal-interface-summary-and-assessment--29-september-2025

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#China notified two additional #human cases of infection with #influenza A #H9N2 (HK CHP, October, 14 '25)

 

{Excerpt}

Influenza A H9N2

-- Hunan Province:

- 1) A two-year-old boy with onset on September 28, 2025. 

-- Jiangxi Province:

- 2) A 70-year-old woman with onset on September 23, 2025. 

(...)

Source: Centre for Health Protection, Hong Kong PRC SAR, https://www.chp.gov.hk/files/pdf/2025_avian_influenza_report_vol21_wk41.pdf

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#Argentina - #Influenza A #H5 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

The Official Veterinary Service was informed of dead birds and signs consistent with highly pathogenic avian influenza (HPAI) in a backyard in the province of Buenos Aires. On the same day, the suspicion was dealt with and samples were taken for testing. The samples were tested by the official laboratory and were positive for HPAI H5.

On 6th October 2025, the Official Veterinary Service was informed of two birds dead in a backyard at Azcuénaga, province of Buenos Aires. The suspicion was dealt with and samples were taken for testing. The samples were sent to the official SENASA laboratory on 7th October 2025 and on the same day, positive results were obtained for HPAI H5 clade 2.3.4.4; all the birds were killed and disposed of, and the premises was cleaned and disinfected. The affected backyard is less than 2 kilometers from the Giles River, so contact with wild birds is suspected.

Source: WOAH, https://wahis.woah.org/#/in-review/6855

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#Germany - High pathogenicity avian #influenza #H5N1 viruses (#poultry) (Inf. with) - Immediate notification

 

A geese for fattening farm in Bayern Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6879

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#Slovakia - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

Backyard flock - sudden death, apathy, torticollis, ataxia, cyanosis, haemorrhagia of inner organs

Source: WOAH, https://wahis.woah.org/#/in-review/6874

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#India - High pathogenicity avian #influenza #H5N1 viruses (#poultry) (Inf. with) - Immediate notification

{Several poultry farms in Uttar Pradesh State.}

HPAI (H5N1) was detected in a Live Bird Market from the environmental sample. Hence no cases were observed.

Source: WOAH, https://wahis.woah.org/#/in-review/6730

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#UK - High pathogenicity avian #influenza #H5N1 viruses (#poultry) (Inf. with) - Immediate notification

{Northern Ireland} Over 23k 26-week-old grandparent and parent broiler breeders' premises. Positive test for HPAI H5N1. Clinical signs presented prior to testing.

Source: WOAH, https://wahis.woah.org/#/in-review/6872

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Death of Sardanapalus, Eugene Delacroix (1827)

 

Public Domain.

Source: WikiArt, https://www.wikiart.org/en/eugene-delacroix/death-of-sardanapalus-1827-1

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H128N Substitution in the Sa #Antigenic Site of HA1 Causes Antigenic Drift Between #Eurasian Avian-like #H1N1 and 2009 #Pandemic H1N1 #Influenza Viruses

 

Abstract

The antigenic relationship between Eurasian avian-like H1N1 swine influenza viruses (EA H1N1) and human pandemic 2009 H1N1 viruses (2009/H1N1) remains a critical question for influenza surveillance and vaccine efficacy. This study systematically investigated the antigenic differences between strains A/swine/Tianjin/312/2016 (TJ312, EA H1N1) and A/Guangdong-Maonan/SWL1536/2019 (GD1536, 2009/H1N1). Cross-hemagglutination inhibition (HI) assays revealed a significant antigenic disparity, with a 16-fold reduction in heterologous versus homologous HI titers. Comparative sequence analysis identified 22 amino acid differences across the five major antigenic sites (Sa, Sb, Ca1, Ca2, and Cb) of the HA1 subunit. Using reverse genetics, a panel of mutant viruses was generated. This study revealed that a single histidine (H)-to-asparagine (N) substitution at residue 128 (H3 numbering) in the Sa antigenic site acts as a primary determinant of antigenic variation, sufficient to cause a four-fold change in HI titers and a measurable drift in antigenic distance. Structural modeling via AlphaFold3 and PyMOL software suggests that the H128N mutation may alter the local conformation of the antigenic site. It is plausible that H at position 128 could exert electrostatic repulsion with adjacent amino acids, whereas N might facilitate hydrogen bond formation with neighboring residues. These interactions would potentially lead to structural changes in the antigenic site. Our findings confirm that residue 128 is a critical molecular marker for the antigenic differentiation of EA H1N1 and 2009/H1N1 viruses. The study underscores the necessity of monitoring specific HA mutations that could reduce cross-reactivity and provides valuable insights for refining vaccine strain selection and pandemic preparedness strategies.

Source: Viruses, https://www.mdpi.com/1999-4915/17/10/1360

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#Antiviral efficacy of oral #ensitrelvir versus oral ritonavir-boosted #nirmatrelvir in #COVID19 (PLATCOV): an open-label, phase 2, randomised, controlled, adaptive trial

 

Summary

Background

Ensitrelvir is an oral antiviral treatment for COVID-19 with the same molecular target (the main protease) as ritonavir-boosted nirmatrelvir—the current oral first-line treatment. We aimed to compare the clinical antiviral effects of the two drugs.

Methods

In an open-label, phase 2, randomised, controlled, adaptive pharmacometric platform trial, low-risk adult outpatients aged 18–60 years with early symptomatic COVID-19 (<4 days of symptoms) were recruited from hospital acute respiratory infection clinics in Thailand and Laos. Patients were randomly assigned in blocks (block sizes depended on the number of interventions available) to one of eight treatment groups, including oral ensitrelvir and oral ritonavir-boosted nirmatrelvir at standard doses, both given for 5 days, and no study drug. The primary endpoint was the oropharyngeal SARS-CoV-2 viral clearance rate assessed between day 0 and day 5 in the modified intention-to-treat population (defined as patients with at least 2 days of follow-up). Patients had four oropharyngeal swabs taken on day 0 and two swabs taken daily from days 1 to 7, then on days 10 and 14. Viral clearance rates were derived under a Bayesian hierarchical linear model fitted to log10 viral densities in standardised paired oropharyngeal swab eluates taken daily over the 5 days (14 samples). An individual patient data meta-analysis of all small molecule drugs evaluated in this platform trial using published results was also performed, adjusting for temporal trends in viral clearance. This trial is registered at ClinicalTrials.gov, NCT05041907.

Findings

Between March 17, 2023, and April 21, 2024, 604 of 903 patients enrolled were concurrently assigned to the three treatment groups (ensitrelvir n=202; ritonavir-boosted nirmatrelvir n=207; no study drug n=195). Median estimated SARS-CoV-2 clearance half-lives were 5·9 h (IQR 4·0–8·6) with ensitrelvir, 5·2 h (3·8–6·6) with nirmatrelvir, and 11·6 h (8·1–14·5) with no study drug. Viral clearance following ensitrelvir was 82% faster (95% credible interval 61–104) than no study drug and 16% slower (5–25) than ritonavir-boosted nirmatrelvir. In the meta-analysis of all unblinded small molecule drugs evaluated in the platform trial, nirmatrelvir and ensitrelvir had the largest antiviral effects (1157 patients). Viral rebound occurred in 15 (7%) of 207 patients in the nirmatrelvir group and 10 (5%) of 202 in the ensitrelvir group (p=0·45).

Interpretation

Both ensitrelvir and nirmatrelvir accelerate oropharyngeal SARS-CoV-2 viral clearance. Ensitrelvir is an effective alternative to currently available antivirals in treating COVID-19. Although COVID-19 is now generally a mild disease, it still causes substantial morbidity, particularly in vulnerable groups, and new variants or other coronaviruses could still emerge with pandemic potential. Safe effective and affordable antivirals are needed, and these are best assessed initially in pharmacometric platform trials assessing viral clearance.

Funding

Wellcome Trust through the COVID-19 Therapeutics Accelerator.

Source: The Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00482-7/fulltext?rss=yes

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History of Mass Transportation: A Henschel & Son 1936 Steam Locomotive

 

By Dornicke - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=5162139

Source: Wikipedia, https://en.wikipedia.org/wiki/Henschel_%26_Son

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#Assessment of #malnutrition in preschool-aged #children by mid-upper arm circumference in the #Gaza Strip (January, 2024–August, 2025): a longitudinal, cross-sectional, surveillance study

 

Summary

Background

Since October, 2023, Palestinian children in the Gaza Strip have suffered war-induced displacement, food insecurity, malnutrition, and elevated risks of famine and mortality. In this study, we aimed to document the extent of, and patterns in, wasting malnutrition in children aged 6–59 months across the Gaza Strip between January, 2024, and August, 2025.

Methods

This longitudinal, cross-sectional, surveillance study was conducted across a total of 16 UN Relief and Works Agency for Palestine Refugees in the Near East health centres and 78 medical points established within school shelters and tent encampments across the five governorates of Gaza. Children aged 6–59 months were screened for wasting malnutrition by mid-upper arm circumference (MUAC) measurement. Children with a MUAC of less than 125 mm were enrolled into therapeutic feeding regimens. MUAC Z scores were derived from published WHO age-specific and sex-specific arm circumferential growth curves. Monthly prevalence of acute wasting (MUAC Z scores less than –2) and severe wasting (MUAC Z scores less than –3) were described by age, sex, type of screening facility, and governorate.

Findings

Between Jan 1, 2024, and Aug 15, 2025, 265 974 measurements were obtained from 219 783 uniquely identified children, with two-thirds of children screened in Khan Younis and Middle Governorates. The monthly prevalence of acute wasting ranged from 5% (34 of 722 children) to 7% (794 of 10 907) between January and June, 2024. After approximately 4 months of severe aid restrictions between September, 2024, and mid-January, 2025, the prevalence of wasting increased from 8·8% (1601 of 18 225 children) to 14·3% (1661 of 11 619), with the highest prevalence observed in Rafah (32·2%; 95 of 295) and among children aged 24–59 months (21·0%; 1366 of 6518). After a 6-week ceasefire, marked by a substantial increase in the number of aid trucks entering through territory borders, by March, 2025, the prevalence of wasting had declined to 5·5% (831 of 15 165). However, after an 11-week blockade from March to May, 2025, and continued severely restricted entry of food, water, medicines, fuel, and other essentials thereafter, by early August, 2025, 15·8% (1213 of 7668) of screened children were acutely wasted, including 3·7% (280 of 7668) severely wasted, equating to more than 54 600 children in need of therapeutic care.

Interpretation

After nearly 2 years of war and severe restrictions in humanitarian aid, tens of thousands of preschool-aged children in the Gaza Strip are suffering from preventable acute malnutrition and facing an increased risk of mortality.

Funding

UN Relief and Works Agency for Palestine Refugees in the Near East.

Source: The Lancet, https://www.sciencedirect.com/science/article/abs/pii/S0140673625018203?dgcid=rss_sd_all

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