Avian Influenza A (H5N1) Outbreak – Cambodia

Between 24 and 25 November 2023, the Ministry of Health of Cambodia notified WHO of two confirmed cases of human infection with influenza A(H5N1) from the same village in Kampot Province. Both cases were female, one in the 20-25 years age group and the other less than five years old. The first reported case visited a public hospital four days after having symptoms of fever, shortness of breath and cough. Samples were collected, which tested positive for H5N1, and the case died while in hospital. The second reported case was detected during enhanced surveillance by the public health authorities in response to the confirmation of the first reported case. The case had fever, cough and rash and is currently being treated in hospital. Epidemiological investigation shows both cases had exposure to backyard birds, which were reported to be sick, with some having died, over the prior month. The Ministry of Health’s national and sub-national rapid response teams are investigating the source of the infection and coordinating response activities, including but not limited to active surveillance for additional cases, identifying close contacts for monitoring, and conducting health education campaigns to prevent transmission in the community. In total, six cases of influenza A(H5N1) have been reported from Cambodia this year. Influenza A(H5N1) infection in humans can cause severe disease, has a high mortality rate, and is notifiable under the International Health Regulations (2005).

The Ministry of Health of Cambodia notified WHO of two confirmed human cases of influenza A (H5N1) between 24 and 25 November 2023. The cases resided in the same village in Kampot Province. Both cases were females, one in the age group of 20-25 years and the other less than 5 years old.

The first reported case developed fever, cough and shortness of breath on 19 November 2023, was treated at home for several days, and then visited a hospital on 23 November. At the hospital, samples were collected and transported to the National Institute of Public Health for testing and was subsequently confirmed as influenza A(H5N1) by RT-qPCR assays at the National Laboratory at National Institute of Public Health and reconfirmed by Institute Pasteur du Cambodge. The case was admitted and in intensive care at the hospital and passed away on 26 November 2023. The second reported case was detected during active surveillance in response to the first reported case, for additional cases with clinical presentation including fever, cough and rash. The case was transported to hospital on 25 November 2023 for testing with samples returning positive for influenza A(H5N1) by RT-qPCR assays at the National Laboratory at National Institute of Public Health and reconfirmed by at the Institute Pasteur du Cambodge. The case is currently admitted in an isolation room in the respiratory ward of the hospital and undergoing treatment. Epidemiological investigation shows both cases had exposure to backyard birds which were reported to be sick and dead, over the past month. No epidemiological linkage of these cases has yet been confirmed other than that they both resided in the same village.

Laboratory investigation shows the viruses, as indicated by phylogenetic analysis, fall within the H5 clade 2.3.2.1c with close similarity to the viruses that have been circulating in Cambodia and Southeast Asia since 2013-2014. The sequences cluster most closely with the viruses from the two human cases reported in October 2023.

Animal influenza viruses normally circulate in animals but can also infect humans. Infections in humans have primarily been acquired through direct contact with infected animals or contaminated environments. Depending on the original host, influenza A viruses can be classified as avian influenza, swine influenza, or other types of animal influenza viruses.

Avian, swine, and other animal influenza virus infections in humans may cause disease ranging from mild upper respiratory tract infection to more severe diseases and can be fatal. Conjunctivitis, gastrointestinal symptoms, encephalitis and encephalopathy have also been reported. There have also been several detections of A(H5N1) virus in asymptomatic persons but who had exposure to infected birds in the days before a sample was collected.

Laboratory tests are required to diagnose human infection with influenza. WHO periodically updates technical guidance protocols for the detection of zoonotic influenza using molecular methods, e.g. Reverse transcription polymerase chain reaction (RT-PCR). Evidence suggests that some antiviral drugs, notably neuraminidase inhibitors (oseltamivir, zanamivir), can reduce the duration of viral replication and improve prospects of survival in some cases.

The confirmed cases are the fifth and sixth cases of human infection with influenza A(H5N1) reported from Cambodia in 2023, and the fourth reported death in 2023. From 2003 until now, 62 cases of human infection with influenza A(H5N1), including 41 deaths, have been reported from Cambodia.

The Ministry of Health’s national and sub-national rapid response teams, with support from the Ministry of Agriculture, Forestry and Fisheries, and the Ministry of Environment, have initiated and coordinated the detailed investigation of the avian influenza outbreak in Kampot Province including searching for additional suspected cases and contacts, collecting and testing samples from backyard birds and conducting health education campaigns to prevent transmission in the community.

From 2003 to 27 November 2023, a total of 882 human cases of infection with influenza A(H5N1), including 461 deaths, have been reported globally from 23 countries. Almost all cases of human infection with avian influenza A(H5N1) have been linked to close contact with infected live or dead birds, or influenza A(H5N1)-contaminated environments. Based on evidence so far, the virus does not infect humans easily and spread from person-to-person appears to be unusual. Human infection can cause severe disease and has a high mortality rate. Since the virus continues to circulate in poultry, particularly in rural areas in Cambodia, the potential for further sporadic human cases can be expected.

In these two cases, while human-to-human transmission cannot be ruled out, it is likely there were separate exposures to the viruses from sick and dead chickens.

In the past, small clusters of A(H5) virus infections were reported, including those involving health care workers, but without evidence of sustained human-to-human transmission. Available epidemiological and virological evidence suggests that A(H5N1) viruses have not acquired the ability to sustain transmission among humans. Therefore, the likelihood of sustained human-to-human spread is low. Based on available information so far, WHO assesses the risk to the general population posed by this virus to be low. The risk assessment will be reviewed as needed if additional information becomes available.

Close analysis of the epidemiological situation, further characterization of the most recent influenza A(H5N1) viruses in both human and poultry populations, and serological investigations are critical to assess associated risks to public health and promptly adjust risk management measures.

There are no specific vaccines for influenza A(H5N1) in humans. However, candidate vaccines to prevent influenza A(H5) infection in humans have been developed for pandemic preparedness in some countries. WHO continues to update the list of zoonotic influenza candidate vaccine viruses (CVV) selected twice a year at the WHO consultation on influenza virus vaccine composition. The list of such CVV is available on WHO website. In addition, the genetic and antigenic characterization of contemporary zoonotic influenza viruses are published on the Global influenza programme, human-animal interface website.

This event does not change the current WHO recommendations on influenza surveillance and public health measures.

Given reports of sporadic influenza A (H5N1) cases in humans, outbreaks in mammals, the widespread circulation in birds and the constantly evolving nature of influenza viruses, WHO continues to stress the importance of global surveillance to detect and monitor virological, epidemiological, and clinical changes associated with emerging or circulating influenza viruses that may affect human (or animal) health and timely virus sharing for risk assessment.

The public should avoid contact with high-risk environments such as live animal markets/farms and live poultry, or surfaces that might be contaminated by poultry droppings. Additionally, it is recommended to maintain good hand hygiene with frequent washing or the use of alcohol-based hand sanitizer.

The general public and at-risk individuals should immediately report instances of sick or unexpected deaths in animals to veterinary authorities. Consumption of poultry or wild birds that are sick or have died unexpectedly should be avoided.

Any person who has had exposure to potentially infected birds or contaminated environments and feels unwell, should seek health care promptly and inform their healthcare provider of their possible exposure.

WHO advises against implementing any travel or trade restrictions based on the current information available on this event. WHO does not advise special traveler screening at points of entry or other restrictions due to the current situation of influenza viruses at the human-animal interface.

State Parties to the International Health Regulations (2005) are required to immediately notify WHO of any laboratory-confirmed case of a recent human infection caused by a new subtype of influenza virus. Evidence of illness is not required for this notification.

1. MOH Cambodia press release on official Facebook page of the Ministry of Health: First reported case: Press release; Second reported case: Press release
2. Global influenza programme, human-animal interface:  https://www.who.int/teams/global-influenza-programme/avian-influenza
3. Global Influenza Programme, Zoonotic influenza: candidate vaccine viruses and potency testing reagents: https://www.who.int/teams/global-influenza-programme/vaccines/who-recommendations/zoonotic-influenza-viruses-and-candidate-vaccine-viruses
4. Protocol to investigate non-seasonal influenza and other emerging acute respiratory diseases: https://www.who.int/publications-detail-redirect/WHO-WHE-IHM-GIP-2018.2
5. Summary of Key Information Practical to Countries Experiencing Outbreaks of A(H5N1) and Other Subtypes of Avian Influenza: https://apps.who.int/iris/rest/bitstreams/1031911/retrieve
6. Influenza at the human-animal interface summary and assessment, 26 January 2023 (who.int)
7. Evidence-based risk management along the livestock production and market chain: Cambodia https://www.fao.org/publications/card/en/c/CA7319EN/(link is external)
8. DON. 26 February 2023: https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON445
9. Food and Agriculture Organization of the United Nations (FAO) – Animal Production and Health division (NSAH). FAO-NSAH Animal Health Threats Update. 11 October 2023.

World Health Organization (29 November 2023). Disease Outbreak News; Avian Influenza A (H5N1) – Cambodia. Available at https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON495