Sunday, March 12, 2023

J. Trvl. Med. Research Letter: First Case of Human Infection with HPAI H5 Influenza A Virus in South America

#17,342

In early January we learned from Ecuador's Ministry of Health that they had confirmed a single human infection with clade 2.3.4.4b H5N1 in a 9 year old girl - making her the first in South America, and the 7th globally (at that time).

A little more than a week later, in WHO Update & Risk Assessment On Human H5N1 Infection - Ecuador, we got the first detailed description of the case, and the Ecuadorian Public Health response, which included:

  • Local authorities carried out epidemiological investigations and follow-up of the case’s contacts in the family, home, and health care facilities.
  • Ongoing intersectoral activities with the Ministry of Agriculture and Livestock (MAG), and the Phytosanitary and Animal Health Regulation and Control Agency (Agrocalidad) for active detection, follow-up and control of avian influenza outbreaks in the area.
  • Continuous follow-up of persons with respiratory symptoms and suspected influenza cases due to contact with poultry or/and who have been exposed to birds, among the exposed population.
  • Seasonal influenza vaccination in risk groups is ongoing according to the guidelines of the National Immunization Program.
  • The NIC is in the process of sending the patient’s samples to a WHO Collaborating Center for further characterization.
Finding only 1 case - and no evidence of infection among the patient's close contacts - the WHO's risk assessment read: Based on available information, WHO assesses the risk to the general population posed by this virus to be low.

Today we have an uncorrected proof of a research letter - soon to be published in the Journal of Travel Medicine - written by local public health officials (and others) that provides additional details on the girl's illness and treatment. 

We also learn that the Ecuadorian public health response was not quite as robust or timely as the initial WHO report might suggest. And lastly, the authors express concern over the future course and direction of this zoonotic virus. 

It is not an overly long or technical read, but I've only posted some excerpts. Follow the link to read it in its entirety. I'll have a brief postscript when you return. 

First case of human infection with highly pathogenic H5 avian influenza a virus in South America: a new zoonotic pandemic threat for 2023?

Alfredo Bruno, MSc, PhD (c), Alonzo Alfaro-Núñez, PhD, Doménica Mora, MSc, Rubén Armas, MSc, PhD (c), Maritza Olmedo, MSc, Jimmy Garcés, MSc, Greta Muñoz-López, MD, Miguel Angel Garcia-Bereguiain, PhD
Journal of Travel Medicine, taad032, https://doi.org/10.1093/jtm/taad032

In January 2023, the first case of H5N1 avian influenza infection in humans worldwide was detected in Ecuador, affecting a girl in contact with death poultry. In the context of developing countries with low sanitation for domestic poultry this represents a threat for avian flu zoonotic outbreaks with pandemic potential.

          (SNIP)

On January 9th 2023, the WHO was notified of a human infection by an avian influenza A(H5) virus in Ecuador (https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON434).
 
The patient was a 9 years old girl without comorbidities from Bolivar Province, admitted to a hospital due to severe flu symptoms in December 30th 2022. She was transferred to the ICU of a pediatric hospital on January 3rd 2023 due to complications with septic shock and pneumonia.

She received complex support antiviral treatment including oseltamivir, managing to improve her critical condition; she continues in interdisciplinary management with favorable progress.

A nasopharyngeal and a bronchoalveolar sample were collected on the 5th and 7th 54 of January 2023 and sent to the laboratory in the Ecuadorian National Institute of Public Health in Ecuador for RT56 qPCR testing with the CDC Influenza Virus Real-Time RT-PCR Panel and Influenza A/H5 (Asian Lineage) Subtyping Panel. Both samples resulted positive for FluA (Ct of 33.2 and 34.6) and H5 (Ct of 34.2 and 36.1). Samples were sent to the Center for Diseases Control and Prevention of the USA that confirmed our results.
 
According to the epidemiological investigation, the girl was in contact with backyard poultry that died without apparent cause. Moreover, several incidents of dead backyard poultry have been reported in Bolivar Province, close to the origin of H5N1 clade2.3.4.4b outbreak in Ecuador. No family members tested positive for H5 flu. This is the first reported case of human infection by avian influenza A(H5) virus in Latin America, and the first human case reported worldwide in 2023. (6)

         (SNIP) 

Despite several sequencing attempts, no viral sequences from the H5 human case in Ecuador were recovered. Due to logistic problems, the local authorities from the Ministry of Health of Ecuador sent samples for H5 diagnosis only after several days of antiviral treatment, although an outbreak alert for HPAIVs was previously declared.

Moreover, due to budget constraints, there was not an active surveillance among people exposed to infected poultry in Ecuador, and only three poultry samples has been referred to the Ecuadorian National Institute of Public Health in Ecuador for genome sequencing. 

This case shows the need to rise concern among South American health authorities to support HPAIVs genomic surveillance, as an early identification of circulating strains would assist the WHO program for HPAIVs candidate vaccine viruses. For instance, the virus circulating in South America, is grouped in the same clade with the new 2.3.4.4b candidate vaccine virus (Figure 1).

Despite the high number of poultry outbreaks declared worldwide since 2020, only seven cases of human infection with clade 2.3.4.4b virus have been reported. Nevertheless, three of these cases had a severe or fatal outcome (6). Although, there is limited evidence for mutations associated to co-speciation in mammals and no sustained human-to-human transmission has been documented, the reported mink to mink transmission of the H5N1 clade 2.3.4.4b (5) warms about the danger associated to the current viral strain circulating in South America.

We call for action about the importance of a worldwide HPAIVs genomic surveillance from a One Health perspective including poultry, wild birds and mammals, beside humans. In a scenario of weak surveillance programs and low sanitation like the reported in this study, a high risk of uncontrolled zoonotic exposure to HPAIVs may lead to the emergence of a new variant transmitted from human-to-human representing a pandemic threat. 

          (Continue . . . )

 

Although South America had been under an avian flu alert (issued by PAHO) since mid-November, this case was very nearly missed, with this patient having spent a full week in the hospital before PCR testing was undertaken, and a novel H5 flu was identified.   

A less severe (or non-hospitalized) infection would likely have gone unrecognized (and some probably already have)

This isn't just a problem for less developed nations, as the UK warned last November that their ability to detect human-to-human transmission of the virus is similarly limited. 

There is no evidence of sustained human-to-human transmission (moderate to high confidence). Subtyping surveillance in the NHS or through NHS referral to the UK Health Security Agency (UKHSA) is incomplete and could delay detection. 

There is insufficient information to assess the occurrence of limited human-to-human transmission such as transmission within households.

We only learned about the 2009 H1N1 pandemic virus after it had been circulating for weeks (perhaps months) in Mexico.  The 2019 COVID virus had at least a month's head start (probably longer) before it was known outside of China, and there is evidence it made its way to Europe long before we initially believed

So while the small number of detected H5 cases so far is reassuring, we are basically driving forward at great speed while only looking into a foggy and badly cracked rear view mirror. 

Given those limitations, we should expect some curves ahead.