Fowl Cholera in Poultry and Game Birds: Pasteurella multocida Pathogenesis and Management

Introduction

Fowl cholera is a highly contagious bacterial disease of domestic poultry and wild birds caused by the Gram-negative coccobacillus Pasteurella multocida [1, 2]. The disease manifests in peracute, acute, and chronic forms, with mortality rates that can reach 100% in susceptible flocks [1]. P. multocida affects a broad range of avian hosts including chickens, turkeys, ducks, geese, and numerous game bird species such as pheasants and wild waterfowl [89, 90, 91]. The economic impact of fowl cholera on commercial poultry operations is substantial, driven by mortality, reduced egg production, and costs associated with treatment and prevention [3, 80]. This article provides a detailed examination of the etiological agent, pathogenesis, clinical presentation, diagnostic approaches, and management strategies for fowl cholera in poultry and game birds.

Etiology and Taxonomy

Pasteurella multocida is a nonmotile, facultatively anaerobic, bipolar-staining coccobacillus belonging to the family Pasteurellaceae [50, 79]. The species is subdivided into three subspecies: P. multocida subsp. multocida, P. multocida subsp. septica, and P. multocida subsp. gallicida [79]. Capsular serogroups (A, B, D, E, F) and lipopolysaccharide (LPS) Heddleston serovars (1 through 16) form the basis of serological classification [4, 68]. Avian isolates most commonly belong to capsular serogroups A and F, with serogroup A predominating in acute outbreaks [5, 76]. The LPS outer core biosynthesis locus exhibits significant heterogeneity, and phase variation in glycosyltransferase genes has been documented in association with outbreaks on free-range layer farms [6, 68]. Genomic profiling has revealed substantial diversity among avian isolates, with multilocus sequence typing (MLST) schemes identifying numerous sequence types (STs) with varying host associations and geographic distributions [7, 8, 85]. For example, ST20 has been identified as widespread in Australian poultry farms and may infect wild waterbirds [7].

Pathogenesis and Virulence Factors

The pathogenesis of fowl cholera involves a complex interplay of bacterial virulence factors and host immune responses. Following inhalation or ingestion, P. multocida colonizes the upper respiratory tract mucosa and subsequently invades the bloodstream, leading to septicemia [9, 48]. The bacterium expresses a polysaccharide capsule that is a critical antiphagocytic factor [10, 84]. The Fis protein regulates capsule production and expression of other virulence determinants [84]. The stringent response, mediated by the alarmone (p)ppGpp, negatively regulates hyaluronic acid capsule production, indicating a sophisticated regulatory network governing virulence [10].

Lipopolysaccharide (LPS) is a major virulence determinant and immunogen [50, 82]. The LPS outer core structure varies among strains, and specific glycosyltransferase genes (e.g., pcgD, hptE) contribute differentially to virulence in ducks [11]. Truncation of the LPS outer core can attenuate virulence while retaining immunogenicity, a strategy exploited in live vaccine development [12, 57]. The 3-deoxy-D-manno-octulosonic acid kinase activity encoded by kdkA is essential for LPS phosphorylation and full virulence in chickens [82].

The P. multocida toxin (PMT) is a potent mitogenic toxin that constitutively activates heterotrimeric G proteins, leading to dysregulation of cellular signaling pathways [13]. While PMT is primarily associated with atrophic rhinitis in swine, its role in avian disease is less clear, and many avian isolates lack the toxA gene [13]. Other important virulence factors include filamentous hemagglutinin (FhaB), which mediates adherence to host cells [14, 73, 87]. However, the fhaB1 gene is not involved with avian fowl cholera pathogenesis in turkey poults, suggesting functional redundancy or host-specific roles [14]. Outer membrane proteins such as OmpH and PlpE are immunogenic and contribute to protective immunity [15, 45, 75]. The hyaD gene, involved in hyaluronic acid synthesis, contributes to virulence in avian P. multocida [16]. The ptfA gene encodes a type 4 fimbrial subunit important for adherence [54, 81]. The PhoP/PhoQ two-component regulatory system is also required for full virulence [60].

Host Range and Epidemiology

Fowl cholera affects a wide range of domestic and wild avian species. In commercial poultry, turkeys are particularly susceptible, with outbreaks causing significant mortality [17, 2, 18]. Chickens, including broilers, layers, and slow-growing breeds, are also commonly affected [1, 19, 20]. Ducks and geese serve as important reservoirs and can develop severe disease [21, 22, 23, 24]. Game birds such as ring-necked pheasants (Phasianus colchicus) and wild turkeys (Meleagridis gallopavo silvestris) are susceptible to infection [89, 91]. Wild waterfowl, including marine birds in the Bering Sea, experience epizootics of avian cholera [90, 92]. The disease is often associated with environmental stressors, high stocking densities, and concurrent infections [17, 25]. Coinfection with Mycoplasmoides gallisepticum has been reported to exacerbate mortality in turkeys [17]. Land cover and environmental factors may influence the occurrence of fowl cholera [25].

Clinical Signs and Pathology

The clinical presentation of fowl cholera varies with the virulence of the strain, host susceptibility, and disease form. Peracute disease is characterized by sudden death with few premonitory signs [1]. Acute fowl cholera presents with fever, depression, anorexia, mucoid or bloody diarrhea, respiratory distress, cyanosis, and swelling of the wattles and comb [1, 18]. Chronic infection may manifest as localized infections including wattle edema, conjunctivitis, sinusitis, arthritis, and torticollis due to otitis media [18].

Gross pathological findings in acute cases include petechial hemorrhages on the heart, liver, and serosal surfaces; hepatomegaly with multifocal necrotic foci; splenomegaly; and pulmonary congestion [1, 18, 48]. Fibrinous pericarditis and airsacculitis are common in chronic cases [17]. Histopathological examination reveals hepatic necrosis, fibrinoid thrombosis, and intense heterophilic and mononuclear inflammation [9, 48]. Receptor-interacting serine/threonine kinase 1 and 3 dependent inflammation (necroptosis) contributes to lung and liver injury in chickens [9, 48].

Diagnosis

Definitive diagnosis of fowl cholera requires isolation and identification of P. multocida from clinical specimens. Samples from acutely affected or freshly dead birds (liver, spleen, bone marrow, heart blood) are preferred [19, 20]. The bacterium grows on blood agar or tryptic soy agar under aerobic or microaerophilic conditions, producing characteristic small, dewdrop-like colonies [19, 20]. Gram staining reveals Gram-negative coccobacilli with bipolar staining [19].

Molecular diagnostic methods offer enhanced sensitivity and specificity. Conventional PCR targeting the kmt1 gene (species-specific) and capsular typing genes is widely used [26, 27, 76]. Loop-mediated isothermal amplification (LAMP) assays provide rapid, field-deployable detection with comparable sensitivity to PCR [27]. Real-time PCR assays enable quantification of bacterial load. Multi-locus sequence typing (MLST) and whole-genome sequencing (WGS) are employed for epidemiological investigations and outbreak tracing [7, 8, 28, 46, 69, 85]. Genomic analysis can differentiate vaccine-related fowl cholera from naturally occurring disease [29].

Serological diagnosis is performed using enzyme-linked immunosorbent assays (ELISAs) to detect antibodies against P. multocida [30, 49, 51]. In-house indirect ELISAs using whole-cell antigens or recombinant outer membrane proteins (e.g., rOmpH) have been developed for chickens and ducks [30, 49, 51]. These assays are useful for monitoring vaccine responses and flock-level exposure.

Antimicrobial susceptibility testing (AST) is critical for guiding treatment, given the emergence of multidrug-resistant strains [31, 19, 26, 20, 58]. Disk diffusion and broth microdilution methods are standard [19, 20]. Resistance genes (e.g., blaROB-1, tet genes, sul genes) are increasingly detected in avian isolates [31, 26, 32].

Differential Diagnosis

Fowl cholera must be differentiated from other causes of acute septicemia and respiratory disease in poultry. Key differentials include highly pathogenic avian influenza (HPAI), Newcastle disease, infectious coryza (Avibacterium paragallinarum), Escherichia coli septicemia, Gallibacterium anatis infection, Mycoplasma species infections, and Ornithobacterium rhinotracheale infection [17, 3, 62, 65]. The presence of characteristic wattle edema and petechial hemorrhages on the heart and liver is suggestive of fowl cholera, but laboratory confirmation is essential [1, 18].

Management and Control

Antimicrobial Therapy

Antimicrobial treatment is most effective when initiated early in the course of an outbreak. Commonly used antibiotics include tetracyclines, sulfonamides, fluoroquinolones, florfenicol, and penicillin derivatives [31, 19, 20, 33, 24]. However, antimicrobial resistance is a growing concern, and AST is strongly recommended to guide therapy [31, 19, 26, 20, 32, 58]. The pharmacokinetics of florfenicol have been characterized in healthy and P. multocida infected ducks, informing dosage regimens [24]. Veterinary prescribing practices for poultry vary, and prudent use of antimicrobials is essential to mitigate resistance development [33].

Vaccination

Vaccination is a cornerstone of fowl cholera prevention. Both inactivated (bacterin) and live attenuated vaccines are available [21, 34, 5, 35, 57]. Bacterins are typically multivalent, containing multiple serovars, and are administered parenterally [5, 35]. Adjuvants such as oil emulsions, aluminum hydroxide, and bacterial DNA enhance immunogenicity [34, 35, 86]. Live attenuated vaccines, often derived from serial passage or targeted gene deletion, can induce robust mucosal and systemic immunity [21, 57, 60]. The strain PMZ8, attenuated through serial passage in ducks, demonstrates protective efficacy [21]. Gamma-irradiated vaccines represent a novel approach, offering safety and immunogenicity in chickens [36, 37].

Recombinant subunit vaccines targeting immunogenic proteins such as OmpH, PlpE, FhaB, and PtfA are under development [38, 15, 23, 39, 53, 54, 61, 72, 73, 75, 87]. Flagellin has been used as an adjuvant to enhance the immunogenicity of a PlpE subunit vaccine [38]. Intranasal administration of recombinant OmpH induces protective immunity in chickens and ducks [23, 53, 61]. DNA vaccines encoding outer membrane proteins have also shown promise [72]. Cross-protection between serovars remains a challenge, and vaccine strains should ideally match the circulating field strains [57, 73].

Biosecurity and Management Practices

Strict biosecurity measures are essential to prevent the introduction and spread of P. multocida. These include controlling access to poultry houses, disinfecting equipment and vehicles, and preventing contact with wild birds and rodents [25, 64]. Free-range and backyard flocks are at increased risk due to environmental exposure [25, 64, 67, 78]. All-in/all-out management, proper ventilation, and reduction of stress factors (e.g., overcrowding, poor nutrition) help reduce disease incidence [3]. In game birds, surveillance and prompt removal of carcasses during epizootics are critical [89, 90, 92].

Probiotics and Alternative Approaches

Probiotics have been investigated as a non-antibiotic strategy to reduce fowl cholera mortality. Multi-strain probiotics have been shown to reduce mortality in broilers experimentally infected with P. multocida [40]. Natural byproducts, such as plant extracts, have demonstrated in vitro inhibition of P. multocida growth and alteration of host cell interactions [41, 63]. Wild Egyptian artichoke extract has been explored for its antibacterial activity against P. multocida in vitro [41].

Diagnostic Workflow

The following Mermaid diagram outlines a diagnostic decision tree for fowl cholera investigation in a poultry flock.

flowchart TD
    A[Flock mortality increase or clinical signs] --> B{Postmortem examination}
    B --> C[Gross lesions suggestive of fowl cholera]
    C --> D["Collect samples: liver, spleen, heart blood, bone marrow"]
    D --> E[Gram stain and culture on blood agar]
    E --> F[Gram-negative coccobacilli, dewdrop colonies]
    F --> G[Biochemical identification or MALDI-TOF]
    G --> H{Confirm P. multocida}
    H --> I["PCR: kmt1 gene, capsular typing"]
    I --> J[Antimicrobial susceptibility testing]
    J --> K[MLST or WGS for epidemiological typing]
    H --> L["Serology: ELISA for flock screening"]
    L --> M[Interpret results in context of vaccination history]
    K --> N[Outbreak investigation and source tracing]
    N --> O[Implement biosecurity and vaccination adjustments]

Conclusion

Fowl cholera remains a significant threat to poultry and game bird health worldwide. The pathogenesis of P. multocida is multifactorial, involving capsular polysaccharides, LPS, outer membrane proteins, and regulatory networks that coordinate virulence gene expression. Diagnosis relies on bacterial culture, molecular detection, and serological assays, with AST guiding antimicrobial therapy. Management strategies encompass biosecurity, vaccination, and prudent antimicrobial use. The emergence of multidrug-resistant strains underscores the need for continued surveillance and development of alternative control measures, including recombinant vaccines and probiotics. Genomic epidemiology provides powerful tools for understanding transmission dynamics and informing control programs.

References

[1] Miller I, Jerry C, Nguyen V et al. 100% Mortality in Commercial Slow-Growing Broiler Chickens with Acute Fowl Cholera. Avian Dis. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/40643942/

[2] Blakey J, Shivaprasad HL, Crispo M et al. Retrospective Study of Pasteurella multocida Diagnosed in Commercial Turkeys Submitted to California Animal Health and Food Safety Laboratory System; 1991-2017. Avian Dis. 2018. URL: https://pubmed.ncbi.nlm.nih.gov/31119920/

[3] Fasina YO, Suarez DL, Ritter GD et al. Unraveling frontiers in poultry health (part 1) - Mitigating economically important viral and bacterial diseases in commercial Chicken and Turkey production. Poult Sci. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/38417326/

[4] Hashish A, Johnson TJ, Ghanem M et al. Complete genome sequences of eight Pasteurella multocida isolates representing all lipopolysaccharide outer core loci. Microbiol Resour Announc. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/39365089/

[5] Semmate N, Bamouh Z, Elkarhat Z et al. Isolation and Characterization of Pasteurella multocida A from an Outbreak in Turkeys in Morocco and Vaccine Preparation and Evaluation. Avian Dis. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/40643939/

[6] Omaleki L, Blackall PJ, Cuddihy T et al. Phase variation in the glycosyltransferase genes of Pasteurella multocida associated with outbreaks of fowl cholera on free-range layer farms. Microb Genom. 2022. URL: https://pubmed.ncbi.nlm.nih.gov/35266868/

[7] Allen JL, Bushell RN, Noormohammadi AH et al. Pasteurella multocida ST20 is widespread in Australian poultry farms and may infect wild waterbirds. Vet Microbiol. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/38228079/

[8] Smith E, Miller E, Aguayo JM et al. Genomic diversity and molecular epidemiology of Pasteurella multocida. PLoS One. 2021. URL: https://pubmed.ncbi.nlm.nih.gov/33822782/

[9] Li W, Tang Q, Dai N et al. Receptor-interacting serine/threonine kinase 1- and 3-dependent inflammation induced in lungs of chicken infected with Pasteurella multocida. Sci Rep. 2020. URL: https://pubmed.ncbi.nlm.nih.gov/32286320/

[10] Smallman TR, Williams GC, Harper M et al. Genome-Wide Investigation of Pasteurella multocida Identifies the Stringent Response as a Negative Regulator of Hyaluronic Acid Capsule Production. Microbiol Spectr. 2022. URL: https://pubmed.ncbi.nlm.nih.gov/35404102/

[11] Zhao X, Shen H, Liang S et al. The lipopolysaccharide outer core transferase genes pcgD and hptE contribute differently to the virulence of Pasteurella multocida in ducks. Vet Res. 2021. URL: https://pubmed.ncbi.nlm.nih.gov/33663572/

[12] Zhao X, Yang F, Shen H et al. Immunogenicity and protection of a Pasteurella multocida strain with a truncated lipopolysaccharide outer core in ducks. Vet Res. 2022. URL: https://pubmed.ncbi.nlm.nih.gov/35236414/

[13] Kubatzky KF. Pasteurella multocida toxin - lessons learned from a mitogenic toxin. Front Immunol. 2022. URL: https://pubmed.ncbi.nlm.nih.gov/36591313/

[14] Dassanayake RP, Briggs RE, Kaplan BS et al. Pasteurella multocida filamentous hemagglutinin B1 (fhaB1) gene is not involved with avian fowl cholera pathogenesis in turkey poults. BMC Vet Res. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/40140814/

[15] Cheng LT, Chu CY, Vu-Khac H et al. Signal sequence contributes to the immunogenicity of Pasteurella multocida lipoprotein E. Poult Sci. 2023. URL: https://pubmed.ncbi.nlm.nih.gov/36423524/

[16] Gao P, Wang L, Wang S et al. The activity of hyaD contributed to the virulence of avian Pasteurella multocida. Microb Pathog. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/38960217/

[17] Gornatti-Churria CD, Jerry C, Ramsubeik S et al. High mortality in a commercial turkey flock associated with coinfection by Pasteurella multocida and Mycoplasmoides (Mycoplasma) gallisepticum. J Vet Diagn Invest. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/40996859/

[18] Blakey J, Crispo M, Bickford A et al. Fowl cholera and acute heart rupture

[19] Geda AM, Wendimu A, Lulie S et al. Molecular Detection and Antibiogram Profiling of Pasteurella multocida Isolated From Breeder Chickens Suspected of Fowl Cholera in Gondar City, Ethiopia. Int J Microbiol. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/40297765/

[20] Geda AM. Fowl Cholera in Chickens: Current Trends in Diagnosis and Phenotypic Drug Resistance in Gondar City, Ethiopia. Vet Med Int. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/39669206/

[21] Ji X, Meng Y, Yang H et al. Attenuation mechanisms and vaccine potential of the serial passage-derived Pasteurella multocida strain PMZ8 in ducks. Poult Sci. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/41747463/

[22] Xiao J, Li Y, Hu Z et al. Characterization of Pasteurella multocida isolated from ducks in China from 2017 to 2019. Microb Pathog. 2021. URL: https://pubmed.ncbi.nlm.nih.gov/34534643/

[23] Apinda N, Nambooppha B, Rittipornlertrak A et al. Protection against fowl cholera in ducks immunized with a combination vaccine containing live attenuated duck enteritis virus and recombinant outer membrane protein H of Pasteurella multocida. Avian Pathol. 2020. URL: https://pubmed.ncbi.nlm.nih.gov/31899951/

[24] Lan W, Xiao X, Jiang Y et al. Comparative pharmacokinetics of florfenicol in healthy and Pasteurella multocida-infected Gaoyou ducks. J Vet Pharmacol Ther. 2019. URL: https://pubmed.ncbi.nlm.nih.gov/30912167/

[25] Ouyang L, Campler MR, Wong S et al. Exploring the Impact of Land Cover on the Occurrence of Ornithobacteriosis and Fowl Cholera: A Case-Case Study. Animals (Basel). 2025. URL: https://pubmed.ncbi.nlm.nih.gov/39943166/

[26] El-Tarabili RM, Enany ME, Alenzi AM et al. Unveiling resistance patterns, kmt1 sequence analyses, virulence traits, and antibiotic resistance genes of multidrug-resistant Pasteurella multocida retrieved from poultry and rabbits. Sci Rep. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/39948418/

[27] Poussard M, Pant SD, Huang J et al. Comparative evaluation of PCR and loop-mediated isothermal amplification (LAMP) assays for detecting Pasteurella multocida in poultry. N Z Vet J. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/39448061/

[28] Omaleki L, Blackall PJ, Cuddihy T et al. Using genomics to understand inter- and intra- outbreak diversity of Pasteurella multocida isolates associated with fowl cholera in meat chickens. Microb Genom. 2020. URL: https://pubmed.ncbi.nlm.nih.gov/32118528/

[29] Hutcheson AR, Thompson K, Maurer JJ et al. Differentiating Vaccine-Related Fowl Cholera from Naturally Occurring Disease. Avian Dis. 2020. URL: https://pubmed.ncbi.nlm.nih.gov/33347552/

[30] Beyene D, Shite A, Getachew B. Development and optimization of in-house made indirect ELISA kit for the detection of antibodies against Pasteurella multocida in chicken. BMC Immunol. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/41724974/

[31] Miao F, Dai B, Li Z et al. Antimicrobial resistance and genomic characteristics of avian Pasteurella multocida. Poult Sci. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/41637789/

[32] Saha O, Islam MR, Rahman MS et al. First report from Bangladesh on genetic diversity of multidrug-resistant Pasteurella multocida type B:2 in fowl cholera. Vet World. 2021. URL: https://pubmed.ncbi.nlm.nih.gov/34840474/

[33] Crabb HK, Hardefeldt LY, Bailey KE et al. Survey of veterinary prescribing for poultry disease. Aust Vet J. 2019. URL: https://pubmed.ncbi.nlm.nih.gov/31359424/

[34] Chen J, Sun Y, Hu Y et al. Evaluation of the immunoprotective effect of gel 01 hydrogel inactivated vaccine against Pasteurella multocida infection in chickens. Microb Pathog. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/40934985/

[35] Ghadimipour R, Ghorbanpoor M, Gharibi D et al. Effects of Selected Adjuvants on Immunogenicity and Protectivity of Pasteurella multocida Bacterin Vaccine in Chickens. Arch Razi Inst. 2021. URL: https://pubmed.ncbi.nlm.nih.gov/35096310/

[36] Belay E, Bitew M, Ibrahim SM et al. Gamma-irradiated fowl cholera vaccines formulated with different adjuvants induced antibody response and cytokine expression in chickens. Front Immunol. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/40103817/

[37] Dessalegn B, Bitew M, Asfaw D et al. Gamma-Irradiated Fowl Cholera Mucosal Vaccine: Potential Vaccine Candidate for Safe and Effective Immunization of Chicken Against Fowl Cholera. Front Immunol. 2021. URL: https://pubmed.ncbi.nlm.nih.gov/34917086/

[38] Chung YC, Cheng LT, Chu CY et al. Flagellin Enhances the Immunogenicity of Pasteurella multocida Lipoprotein E Subunit Vaccine. Avian Dis. 2024. URL: https://pubmed.ncbi.nlm.nih.gov/39400212/

[39] Luo Q, Kong L, Dong J et al. Protection of chickens against fowl cholera by supernatant proteins of Pasteurella multocida cultured in an iron-restricted medium. Avian Pathol. 2019. URL: https://pubmed.ncbi.nlm.nih.gov/30640510/

[40] Reuben RC, Sarkar SL, Ibnat H et al. Novel multi-strain probiotics reduces Pasteurella multocida induced fowl cholera mortality in broilers. Sci Rep. 2021. URL: https://pubmed.ncbi.nlm.nih.gov/33903662/

[41] Wahdan A, Elsebai MF, Elhaig MM et al. Innovative use of wild Egyptian artichoke extract to control fowl cholera in vitro. Vet World. 2025. URL: https://pubmed.ncbi.nlm.nih.gov/40182829/

[42] Islam MA, Haque ME, Iftehimul M et al. Genomic profiling of Pasteurella multocida strains isolated from ISA Brown (Gallus gallus domesticus) in Bangladesh. Microbiol Resour Announc. 2026. URL: https://pubmed.ncbi.nlm.nih.gov/41920836/

[43] Shalaby AG, Bakry NR, El-Demerdash AS. Virulence attitude estimation of Pasteurella multocida isolates in embryonated chicken eggs. Arch Microbiol. 2021. URL: https://pubmed.ncbi.nlm.nih.gov/34554268/

[44] Kannaki TR, Priyanka E, Haunshi S. Research Note: Disease tolerance/resistance and host immune response to experimental infection with Pasteurella multocida A:1 isolate in Indian native Nicobari chicken breed. Poult Sci. 2021. URL: https://pubmed.ncbi.nlm.nih.gov/34217907/