---
title: "HPAI A(H5N1) Clade 2.3.4.4b Genotype B3.13 Infection in Alpacas: Experimental Findings"
id: "cdc-emerging-infectious-diseases-journal-1-experimental-highly-pathogenic-avian-influenza-a-h5n1-clade-2-3-4-4b-virus"
canonical_url: "https://medichelpline.com/clinical-feed/cdc-emerging-infectious-diseases-journal-1-experimental-highly-pathogenic-avian-influenza-a-h5n1-clade-2-3-4-4b-virus"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "CDC Emerging Infectious Diseases Journal"
source_url: "https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article"
published_at: "2026-09-16T04:00:00.000Z"
evidence_level: "Agency Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# HPAI A(H5N1) Clade 2.3.4.4b Genotype B3.13 Infection in Alpacas: Experimental Findings
## Provenance & Clinical Metadata
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- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** CDC Emerging Infectious Diseases Journal
- **Source URL:** [Original Journal Publication](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article)
- **Published At:** 2026-09-16T04:00:00.000Z
- **Evidence Rating:** Agency Feed
## Executive GIST (TL;DR)
- Experimental intranasal challenge of 6 alpacas with **HPAI A(H5N1)** clade 2.3.4.4b genotype B3.13 demonstrated that alpacas are susceptible to productive infection. - Clinical illness after inoculation was generally mild: slight fever and reduced food intake for up to 3 days postinfection. - Viral RNA and infectious virus were detected in **nasal swab** samples, indicating upper respiratory tract shedding. - Tissue analyses at 4 days postinfection found virus localized to the **nasopharyngeal tonsil** and **nasal conchae** by immunohistochemistry and RNA in situ hybridization. - Serologic responses were measured; the study confirmed productive infection though specific titers and timing details beyond seroconversion were not reported in the source abstract. - The experimental virus matched the B3.13 genotype previously detected in US field cases in alpacas and dairy cattle, supporting relevance to recent spillover events. - Authors highlight implications for livestock surveillance and biosecurity where clade 2.3.4.4b viruses circulate, noting camelids can be infected and may contribute to transmission chains. - The controlled study addresses knowledge gaps on incubation, tissue tropism, shedding, and pathogenesis in camelids but did not report extended transmission testing or broad epidemiologic outcomes in this article.
## Clinical Analysis & Structured Key Points
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Any changes will be reflected in the online version in the month the article is officially released._ #### Volume 32, Number 10—October 2026 ##### _Research_ ### Experimental Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus Infection in Alpacas, 2026 On This Page [Methods](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article) * * * [Results](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article) * * * [Discussion](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article) * * * [Suggested Citation](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article) Figures [Figure 1](https://wwwnc.cdc.gov/eid/article/32/10/26-0491-f1) * * * [Figure 2](https://wwwnc.cdc.gov/eid/article/32/10/26-0491-f2) Downloads [Appendix ](https://wwwnc.cdc.gov/eid/article/32/10/26-0491-app1.pdf) * * * [RIS [TXT - 2 KB] ](https://wwwnc.cdc.gov/eid/article/32/10/26-0491.ris) Article Metrics [Metric Details](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article) Related Articles [The Enduring Influence of Nancy J. Cox (1948–2026)](https://wwwnc.cdc.gov/eid/article/32/10/26-0830_article) * * * [Reassortment of HPAI as Driver for Spillover](https://wwwnc.cdc.gov/eid/article/32/10/26-0067_article) * * * [Seroprevalence of H5N1 Virus in Domestic Cats](https://wwwnc.cdc.gov/eid/article/32/9/26-0785_article) * * * [More articles on Influenza](https://wwwnc.cdc.gov/eid/spotlight/influenza) Jacob Schön[![Comments to Author](https://wwwnc.cdc.gov/eid/content/images/icon/email.gif)](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#comment) , Angele Breithaupt, Nico Joel Halwe, Maxi Hertel, Ann Kathrin Ahrens, Andrea Aebischer, Donata Hoffmann, and Martin Beer Author affiliation: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald, Germany (J. Schön, N.J. Halwe, A.K. Ahrens, A. Aebischer, D. Hoffman, M. Beer); Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Greifswald (A. Breithaupt, M. Hertel) [Suggested citation for this article](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#suggestedcitation) ### Abstract Highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b virus continues to spread globally and sporadically transmits from avian reservoirs to mammalian hosts. In May 2024, H5N1 infections in young goats and alpacas in the United States were reported. Nevertheless, the overall susceptibility of camelids to clade 2.3.4.4b virus remains unclear. We conducted a controlled experimental infection study in 6 alpacas, assessing clinical signs, viral shedding, tissue distribution, and serologic responses after intranasal inoculation with HPAI H5N1 genotype B3.13 virus. Observed illness was generally mild; body temperature increased slightly and food intake reduced for up to 3 days postinfection. We detected viral RNA in nasal swab samples and confirmed infectious HPAI H5N1 virus. Immunohistochemistry and RNA in situ hybridization detected virus only in the nasopharyngeal tonsil and nasal conchae at 4 days postinfection. Our findings suggest alpacas are susceptible to productive H5N1 infection, highlighting implications for livestock surveillance and biosecurity in regions with ongoing circulation. In 1996, highly pathogenic avian influenza (HPAI) H5N1 virus (goose/Guangdong/96) appeared in southern China, causing outbreaks in poultry and infecting 18 humans, 6 of whom died ([_1_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r1 "1")–[ _3_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r3 "3")). Descendants of that lineage subsequently triggered major outbreaks in poultry in Southeast Asia and Europe, including H5N1 clades 2.2 (2005–2006) and 2.3.2.1c (2010) and H5N8 clade 2.3.4.4a (2014), reflecting a global rise in HPAI virus (HPAIV) outbreaks ([_4_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r4 "4")–[ _7_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r7 "7")). In 2016, Europe experienced major HPAI H5 clade 2.3.4.4b outbreaks in wild birds and domestic poultry ([_4_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r4 "4")), followed by major outbreaks during 2020–2021 ([_7_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r7 "7") _–_[ _9_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r9 "9")); the clade then became endemic ([_10_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r10 "10")). Nevertheless, during that period, clade 2.3.4.4b virus continuously evolved; serotype H5N8 predominated in 2016, transitioning to H5N6 by 2018, and shifting to H5N1 by 2020 ([_9_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r9 "9"),[_11_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r11 "11"),[_12_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r12 "12")). Although the virus remained in the same clade as classified by homologies of the hemagglutinin (HA) segment, the genotypes changed through continuous reassortment events ([_7_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r7 "7"),[_13_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r13 "13")). In December 2021, HPAI H5N1 clade 2.3.4.4b virus spread from Europe to Canada and the United States via wild birds ([_14_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r14 "14"),[_15_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r15 "15")). Subsequently, several Eurasian H5N1 clade 2.3.4.4b virus genotypes entered North America, and lineages A1 and A3 reassorted with local low pathogenicity avian influenza viruses in migratory birds, giving rise to new H5N1 clade 2.3.4.4b genotypes like B3.13 (late 2023–early 2024) and D1.1 (September 2024) ([_15_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r15 "15"),[_16_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r16 "16")). Those viruses spread rapidly in US wild bird populations, including waterfowl, birds of prey, seabirds, shorebirds, and a wide range of common land birds; during December 2021–December 2025, a total of 17,718 wild birds tested positive ([_17_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r17 "17")). In addition, clade 2.3.4.4b virus spread to domestic livestock birds, affecting 186.18 million birds in 2,029 flocks during February 2022–January 2026 ([_18_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r18 "18")). Besides avian species, a wide range of mammals have been infected, including 683 wild mammals tested during April 2022–December 2025, mostly terrestrial carnivores feeding on H5-infected birds, including 148 red fox (_Vulpus vulpus_), 81 skunks (various species), 34 raccoons (_Procyon lotor_), 28 mountain lions (_Puma concolor_), and 18 bobcats (_Lynx rufus_) ([_19_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r19 "19")). In addition, 148 domestic cats (_Felis catus_), 110 house mice (_Mus musculus_), and 26 deer mice (_Peromyscus_ spp.) also were infected, mostly in the context of affected farms ([_19_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r19 "19")). In March 2024, H5N1 clade 2.3.4.4b genotype B3.13 virus was detected in US dairy cattle, representing the first well-documented instance of widespread HPAIV infection in bovines ([_20_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r20 "20")). That detection was accompanied by evidence of high infectious virus shedding in milk, making milk-mediated cow-to-cow transmission highly likely ([_20_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r20 "20")–[ _23_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r23 "23")). Concurrently, young goat kids co-located with infected poultry on a Minnesota farm exhibited neurologic signs and tested positive for H5N1 genotype B3.6 virus ([_24_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r24 "24"),[_25_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r25 "25")). During March 2024–May 2025, a total of 70 cases of human H5N1 infection were reported in the United States ([_26_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r26 "26")); most were associated with exposure to infected dairy cattle (41 cases) or commercial poultry (24 cases) ([_15_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r15 "15")). Among human cases, the most common reported symptoms were conjunctivitis (89%), fever (46%), and respiratory symptoms (41%) ([_26_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r26 "26")). All sequenced viruses from human cases belonged to clade 2.3.4.4b, predominantly B3.13 and D1.1 genotypes, but 1 D1.3 genotype virus also was identified ([_15_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r15 "15")). In May 2024, the US National Veterinary Services Laboratories confirmed detection of HPAI H5N1 virus from alpacas at a premises where poultry had previously tested positive ([_27_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r27 "27")). The viral genome matched the B3.13 genotype circulating in US dairy cattle and the depopulated poultry, strongly implicating environmental contamination and cross-species exposure ([_27_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r27 "27")). The alpacas shared pasture and water sources with infected poultry and ducks but initially showed no clinical signs ([_27_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r27 "27") _–_[ _29_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r29 "29")). However, on May 10, the day H5N1 virus infection was confirmed in poultry, 1 alpaca experienced spontaneous late-term abortion; 2 more aborted on May 14 and 15, and another spontaneous abortion occurred before September 2024 ([_29_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r29 "29")). By May 15, 2024, four of 18 alpacas showed clinical signs, including depression, weakness, and mild respiratory symptoms ([_29_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r29 "29")). An additional alpaca died acutely, without prior reported signs, 10 days after the first reports of influenza-like illness in poultry; a nasal swab sample collected on the day of death tested H5N1-positive, but no postmortem examination was conducted ([_29_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r29 "29")). Of the 18 adult alpacas (14 female, 4 male), only the female animals were affected ([_29_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r29 "29")). One aborted fetus was later examined, and H5N1 was confirmed in brain tissue ([_29_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r29 "29")). Ten surviving female alpacas seroconverted ([_29_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r29 "29")). Of note, alpaca milk samples tested positive for viral genome, indicating acute infection of the udder, but also later tested positive for influenza virus A–specific antibodies ([_29_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r29 "29")). On the same farm, milk from 1 llama tested positive for specific antibodies 4 months after the outbreak, and 2 of 13 yaks (both female) also seroconverted ([_29_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r29 "29")). That detection expanded the known host range of HPAI H5N1 virus and raised questions regarding its susceptibility, pathogenesis, and transmission dynamics in camelids. HPAIV H5N1 continues to pose a threat to birds and, under certain conditions, to mammalian species. Although spillover into mammals is generally rare, the recent detections in nonavian hosts have heightened concerns about cross-species transmission, adaptation, and the emergence of novel mammalian hosts ([_11_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r11 "11"),[_20_](https://wwwnc.cdc.gov/eid/article/32/10/26-0491_article#r20 "20")). Given that precedent, controlled experimental infection studies can address key knowledge gaps, including the incubation period, clinical spectrum, transmission routes, duration of viral shedding, tissue tropism, and the potential for adaptation in nonavian hosts. We report an experimental challenge study in alpacas using HPAIV H5N1 genotype B3.13, the same genotype identified in the US field case in camelids, to characterize virus kinetics, pathology, and shedd
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> [!CAUTION]
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> Always verify dosing, contraindications, and regulatory alerts against official product labeling and primary regulatory sources before clinical decision-making.