Francisellosis (Francisella noatunensis)

Overview

What is Francisellosis (Francisella noatunensis)?

Francisellosis is a systemic, chronic, granulomatous bacterial disease of fish. It is characterised by white nodules (granulomas) in multiple organs, high morbidity, and variable mortality 2. This chapter covers the cold-water agent Francisella noatunensis, which has two subspecies:

• F. noatunensis subsp. noatunensis causes francisellosis in farmed and wild Atlantic cod (Gadus morhua) in Northern Europe, notably Norway 2.
• F. noatunensis subsp. chilensis causes francisellosis in farmed Atlantic salmon (Salmo salar) in Chile. The Chilean salmon isolates were originally classified as subsp. noatunensis, but were described as a separate subspecies in 2020 on phenotypic and genetic grounds 3.

The warm-water agent of francisellosis in tilapia (Oreochromis spp.), formerly F. noatunensis subsp. orientalis, is now a separate species, Francisella orientalis 3, and is not covered in this chapter.

In Chile, the first records of the disease date back to 1994, in Atlantic salmon farmed in lakes. The organism was initially called UA2 (unknown agent 2) and later U2 (unknown 2). The disease re-emerged in 2006, again in lake-farmed Atlantic salmon 1. The bacterium was identified as a Francisella sp. in 2007 4. In Norway, francisellosis was described as a novel systemic granulomatous disease of farmed Atlantic cod in 2006 5, although a retrospective study confirmed the disease in wild North Sea cod as early as the 1980s 2.

Clinical Signs of Francisellosis (Francisella noatunensis)

Common Signs

• Physical Signs:
  • The disease may become highly prevalent in a population before any noticeable change in fish appearance or behaviour. In severely affected fish, initial signs include emaciation, dark colouration, and raised haemorrhagic nodules 2.
  • In Atlantic salmon, affected fish show no external clinical signs. Internally, there is hepatomegaly, renomegaly, and splenomegaly, with a variable presence of white nodules in a focal to coalescing distribution. Haemorrhages in the swim bladder are occasionally seen 1.
  • In Atlantic cod, the spleen is generally enlarged, and serohaemorrhagic ascites and a thickened intestinal mucosa may be observed 2.

Gross Pathology

Internal changes are dominated by white, partly protruding nodules (granulomas) of various sizes in the spleen, kidney, and liver. Almost any other tissue may be affected, including the gill, heart, testes, musculature, brain, and eye 2. In Atlantic salmon from Chile, the following findings have been documented 1:

• Multiple white nodules in the liver, in some cases with congestion of the visceral fat.
• Haemorrhages in the swim bladder.
• Multiple focal to coalescing nodules in the spleen, some protruding from the surface and giving the organ a mulberry-like (morula) appearance.

Progression of Clinical Signs

• Chronic Course: Francisellosis usually follows a long, chronic course, particularly in cold-water species such as cod. In a cohabitation challenge at 12 °C, all cohabitant cod were infected after 38 days and all showed severe macroscopic disease after five months, yet few fish died 2.
• Impact on Fish Health: Reported mortality ranges from 5–20% in Atlantic salmon 2 6 to up to 40% in cod, although such acute mortality is rarely seen in the field. Mixed infections with other bacteria can significantly increase mortality 2.

Causes of Francisellosis (Francisella noatunensis)

Etiology

• Causative Agent: Members of the genus Francisella are non-motile, Gram-negative, strictly aerobic, facultatively intracellular coccobacilli 2 1.
• Growth Requirements: F. noatunensis is fastidious and, like all fish-pathogenic Francisella, requires cysteine. It cannot be cultured on routine media such as tryptone soya agar or blood agar without added cysteine. Isolates from both cod and salmon were recovered on cysteine heart agar with 5% ovine blood 2. Fish-pathogenic strains do not grow at 37 °C 2.
• Transmission Methods:
  • Horizontal Transmission: Transmission is mainly horizontal and closely linked to the water. Fish-to-fish contact is not necessary: cod can be infected via effluent water from tanks holding infected fish. Recovery of the bacterium from the gut of cohabitant cod suggests the faecal-oral route may be important 2.
  • Vertical Transmission: Detection of F. noatunensis in cod eggs suggests possible vertical transmission, but this has not been confirmed 2.
  • Environmental Survival: F. noatunensis enters a viable but non-culturable state in water after 16 to 30 days (at 12 °C and 8 °C, respectively), in which it was non-virulent under experimental conditions. A reservoir in aquatic protozoa has been proposed 2.

Risk Factors

• Environmental Factors: Water temperature plays a major role. In cod, infection, transmission, and mortality are low below 4 °C and increase with temperature up to about 20 °C. Salinity does not appear to be important, since the disease occurs both in marine-farmed cod and in salmon farmed in fresh water 2.
• Wild Fish Reservoirs: In Norway, F. noatunensis was detected by PCR in 7–11% of wild cod, both near and away from cod farms, although wild fish with clinical signs were rare 2.
• Host Specificity: Despite surveillance of large salmon populations farmed near infected cod farms, no clinical francisellosis in salmon has been identified in Norway, suggesting the North Atlantic strain has a greater affinity for cod 2.

Diagnosis

Diagnostic Methods

• Clinical Examination: Multi-organ white nodules provide a presumptive diagnosis, but several other bacterial diseases produce similar lesions (see Differential Diagnosis).
• Laboratory Tests:
  • Histopathology: Extensive chronic granulomatous inflammation with multiple granulomas, often dominated by hypertrophied foamy macrophages, sometimes with a necrotic core. Few or no bacteria may be visible in advanced disease 2.
  • Bacterial Culture: Culture combined with consistent gross and histological findings is the gold standard. Cysteine-enriched media are required, and isolation is easily inhibited by overgrowth of contaminating bacteria, which are common in chronic cases. Suitable incubation temperatures are about 22–25 °C 2.
  • PCR-Based Methods: Initial identification in cod and salmon relied on universal 16S rRNA PCR and sequencing. Real-time PCR assays targeting the 16S rRNA and fopA genes allow specific detection 2.

Differential Diagnosis

Several diseases produce multi-organ granulomas similar to francisellosis 2:

• Piscirickettsiosis (Salmonid Rickettsial Septicaemia (SRS)): morphologically similar and also produces granulomatous lesions, especially in salmonids.
• Atypical furunculosis (Furunculosis (Aeromonas spp.)): one of the most common systemic infections in farmed cod in Norway, macroscopically very similar to francisellosis, but readily distinguished by histology. Mixed infections with F. noatunensis are relatively common.
• Mycobacteriosis and nocardiosis: both produce visible multi-organ granulomas.

Treatment and Prevention

Treatment Options

• Antibiotics: Because the bacterium is intracellular, infection prevalence is high, the infective dose is low, and severely affected fish stop feeding, antibiotic therapy is unlikely to have a good and lasting effect on an infected population 2. For a Chilean salmon isolate, minimum inhibitory concentrations were 1.0 µg/mL for florfenicol, 0.25 µg/mL for flumequine and oxolinic acid, 0.5 µg/mL for oxytetracycline, and above 64 µg/mL for amoxicillin 2 6.

Prevention Strategies

• Vaccination: No commercial vaccine is available against F. noatunensis 7. In Norway, several trial whole-cell vaccines (bacterins) were tested in cod, both in experimental challenges and in the field, and none gave significant protection 2. Membrane vesicles from the bacterium, which had protected zebrafish in earlier trials, induced no protective immunity when tested in Atlantic cod 7. Because the disease is chronic, the usual measure of vaccine efficacy (survival of vaccinated versus unvaccinated fish) may be misleading: vaccinated fish can survive the observation period while remaining infected, with the onset of disease merely delayed 2.
• Biosecurity: Biosecurity in cod farming is demanding. In Norway there are few broodstock and juvenile facilities, sea cages allow close contact with wild fish, and there are no requirements for the quality or disinfection of intake water at facilities for marine species, no specific rules on fish movements or fallowing, and no mandatory screening programmes for infectious diseases. Until these knowledge gaps are closed, the Norwegian Veterinary Institute advises a precautionary approach to reduce the spread of infection to both farmed and wild fish 8.

Case Studies

Real-World Examples

• Notable Outbreaks:

  • Outbreaks in Lake-Farmed Atlantic Salmon (Lake Llanquihue, Chile, 2006): From June to December 2006, Atlantic salmon farmed in net cages in Lake Llanquihue suffered several simultaneous outbreaks of a chronic granulomatous disease, mainly affecting the spleen. Most farms (9 of 15) recorded a monthly accumulated mortality of 5–20%, in fish averaging 60 g (30–80 g). Affected fish were anorexic and lethargic and swam erratically at the surface. At necropsy, the liver, kidney, and spleen were enlarged, with multiple whitish foci in the liver and spleen and a congested swim bladder. Cultures on routine media (tryptone soya, blood, Mueller-Hinton, and brain heart infusion agar) were negative after eight weeks, and the bacterium grew only on cysteine-enriched Eugon agar, with colonies visible after 12 days at 18 °C. Unlike the Norwegian cod isolates, which grow at 6% NaCl, the Chilean isolates grew only at 0.4–1% NaCl, poorly at 2%, and not at 3% or above; the authors suggest this may explain why the disease in salmon has only been expressed in fresh water. Growth was best at 18–22 °C and poor below 15 °C, which may explain more cases during warmer periods 6.
  • Spread Between Cod Farms (Norway, 2004–2009): After F. noatunensis was first isolated from farmed cod in Rogaland in 2004, outbreaks were diagnosed every year, mainly in western Norway, and the bacterium was detected in farmed cod from Rogaland to Nordland (59–67°N). Genetic typing of 21 Norwegian isolates showed that most isolates from farm outbreaks belonged to only two clades, whereas each isolate from wild cod had its own profile. One clade was found at production sites in three counties, including sites stocked by the same broodfish company. The other linked two broodfish populations in Hordaland to production sites that the same company supplied. At one site in Rogaland, the same strain caused repeated outbreaks from 2004 to 2006, probably infecting each new generation of cod stocked after the first outbreak. Norwegian cod production moves fish along most of the coast and mixes populations from different broodstock companies at on-growing sites, and the authors concluded that the spread between farms was probably a result of human activity 10.

• Lessons Learned: The Chilean outbreak shows how easily francisellosis can be missed by routine bacteriology: the agent grows only on cysteine-enriched media and can take almost two weeks to appear 6 2. The Norwegian data show that a few strains, moved with live fish and possibly with offspring from infected broodstock, caused most farm outbreaks. Where no vaccine or effective treatment exists, tracing fish movements and understanding how the disease spreads are key to preventing outbreaks 10.

Data Insights

Disease Impact by Country

Norway

• Status: Francisellosis is a nationally listed disease in Norway (category F) 8.
• History: Francisellosis played a central role in the collapse of Norwegian cod farming around 2012, together with competition from wild-caught whitefish and problems with early sexual maturation 8.
• Recent Detections: Francisellosis was confirmed at one cod farming site in 2025. The report's biosecurity chapter states that the disease was found at the same site in Nordmøre in both 2024 and 2025, although its official table of listed diseases records no site in 2024. In February 2026, francisellosis was suspected at a site in Stad municipality. The disease has a smouldering course, similar to bacterial kidney disease in salmonids, and has often been present in a population for a long time by the time it is detected 8.
• Outlook: Cod farming is growing again, with 8.7 million cod stocked in 2025 (6.3 million in 2024) and about 19,700 tonnes harvested. The Norwegian Veterinary Institute describes F. noatunensis as a warm-loving pathogen that has recently re-emerged in Norwegian cod farming, and expects it to find better conditions as cod farming expands and sea temperatures rise 8.

Chile

• Freshwater Detections (2025): In national surveillance, F. noatunensis was identified in 8 positive diagnostic reports from freshwater farms (5 in Araucanía and 3 in Los Lagos), and Francisella spp. in 4 more (3 in Araucanía and 1 in Los Lagos). All were from Atlantic salmon, and the agent does not appear among the positive reports from seawater farms. These numbers are small compared with the most frequently detected agents in fresh water, such as piscine orthoreovirus (PRV) and Flavobacterium psychrophilum 9.

Research and References

Latest Research Findings

Recent studies on F. noatunensis (2025–2026) have focused on how the host immune system detects the bacterium and on the genetic regulation of the pathogen itself:

1. "TLR25 is endosomally located and responds to Francisella infection in Atlantic cod" Authors: Bjørnestad, S. A., Krokene, P., Solbakken, M. H., et al. Reference: Frontiers in Immunology, 2026; 17, 1798290. Key findings: Atlantic cod has lost the MHC II system and the cell-surface Toll-like receptors that mammals use to detect bacteria. The teleost-specific receptors TLR14 and TLR25, thought to compensate at the cell surface, were found mainly in endolysosomes, where they colocalised with internalised F. noatunensis subsp. noatunensis. Only TLR25 moved to the perinuclear region on infection and triggered up-regulation of the pro-inflammatory cytokines IL-6 and IL-18. DOI: 10.3389/fimmu.2026.1798290

2. "Exploring the regulatory landscape of non-coding RNAs in aquaculture bacterial pathogens: Piscirickettsia salmonis and Francisella noatunensis" Authors: Aliaga-Tobar, V., Arias-Carrasco, R., Isla, A., et al. Reference: Aquaculture, 2025; 594, 741356. Key findings: A comparison of 23 F. noatunensis and 77 P. salmonis genomes identified non-coding RNAs shared by both pathogens and others unique to each. Unique to F. noatunensis were two riboswitch families (flavin mononucleotide and lysine) and a small RNA at the start of the urease gene ureB that may regulate it, as a similar RNA does in Helicobacter pylori, where urease helps the bacterium survive acidic conditions. DOI: 10.1016/j.aquaculture.2024.741356

Conclusion

Francisellosis caused by F. noatunensis is a chronic, granulomatous disease that is easy to miss and hard to control. Infection can become highly prevalent before fish show any outward signs, the agent grows only on cysteine-enriched media, and the multi-organ nodules it produces resemble those of piscirickettsiosis, atypical furunculosis and mycobacteriosis, so diagnosis depends on culture, histopathology and PCR. Because the bacterium lives inside host cells and affected fish stop feeding, antibiotics are unlikely to clear an infected population, and no vaccine has yet given significant protection in cod. Prevention therefore rests on biosecurity: the Norwegian outbreaks show that a few strains, moved with live fish between farms, caused most cases.

The disease is regaining relevance. In Norway, cod farming is expanding again and francisellosis has re-emerged, with warmer seas expected to favour the pathogen. In Chile, F. noatunensis is still detected in freshwater Atlantic salmon farms, although in small numbers. Recent research has focused on basic biology, such as how cod detect the bacterium and how the pathogen regulates its genes, rather than on new vaccines or treatments, leaving control of the disease dependent on early detection and limiting the movement of infected fish.

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Last Modified: 2026-10-02

Other Bacterial Diseases

Bacterial Kidney Disease (BKD) Furunculosis (Aeromonas spp.) Moritella Viscosa Pasteurellosis Salmonid Rickettsial Septicaemia (SRS) Tenacibaculosis (Tenacibaculum spp) Vibriosis Winter Wounds Yersiniosis (enteric redmouth disease)

Citations:

[1] Godoy, M. (n.d.). Franciselosis en salmón del Atlántico (Salmo salar): Patología macroscópica. https://marcosgodoy.com/franciselosis-en-salmon-del-atlantico-salmo-salar-patologia-macroscopica/

[2] Colquhoun, D. J., & Duodu, S. (2011). Francisella infections in farmed and wild aquatic organisms. Veterinary Research, 42, 47. https://doi.org/10.1186/1297-9716-42-47

[3] Ramírez-Paredes, J. G., Larsson, P., Thompson, K. D., Penman, D. J., Busse, H.-J., Öhrman, C., Sjödin, A., Soto, E., Richards, R. H., Adams, A., & Colquhoun, D. J. (2020). Reclassification of Francisella noatunensis subsp. orientalis Ottem et al. 2009 as Francisella orientalis sp. nov., Francisella noatunensis subsp. chilensis subsp. nov. and emended description of Francisella noatunensis. International Journal of Systematic and Evolutionary Microbiology, 70(3), 2034–2048. https://doi.org/10.1099/ijsem.0.004009

[4] Birkbeck, T. H., Bordevik, M., Frøystad, M. K., & Baklien, Å. (2007). Identification of Francisella sp. from Atlantic salmon, Salmo salar L., in Chile. Journal of Fish Diseases, 30, 505–507. https://doi.org/10.1111/j.1365-2761.2007.00837.x

[5] Olsen, A. B., Mikalsen, J., Rode, M., Alfjorden, A., Hoel, E., Straum-Lie, K., Haldorsen, R., & Colquhoun, D. J. (2006). A novel systemic granulomatous inflammatory disease in farmed Atlantic cod, Gadus morhua L., associated with a bacterium belonging to the genus Francisella. Journal of Fish Diseases, 29, 307–311. https://doi.org/10.1111/j.1365-2761.2006.00714.x

[6] Bohle, H., Tapia, E., Martínez, A., Rozas, M., Figueroa, A., & Bustos, P. (2009). Francisella philomiragia, bacteria asociada con altas mortalidades en salmones del Atlántico (Salmo salar) cultivados en balsas-jaulas en el lago Llanquihue. Archivos de Medicina Veterinaria, 41(3), 237–244. https://doi.org/10.4067/S0301-732X2009000300008

[7] Mertes, V., Bekkelund, A. K., Lagos, L., Ciani, E., Colquhoun, D., Haslene-Hox, H., Sletta, H., Sørum, H., & Winther-Larsen, H. C. (2021). The use of extracellular membrane vesicles for immunization against francisellosis in Nile tilapia (Oreochromis niloticus) and Atlantic cod (Gadus morhua L.). Vaccines, 9(1), 34. https://doi.org/10.3390/vaccines9010034

[8] Moldal, T., Wiik-Nielsen, J., Oliveira, V. H. S., Svendsen, J. C., & Sommerset, I. (Eds.). (2026). Fiskehelserapporten 2025 [Norwegian Fish Health Report 2025] (Veterinærinstituttets rapportserie nr. 5a/2026; Chapter 4.4, Smitterisiko oppdrettsfisk – villfisk, and Chapter 12, Helse og velferd hos torsk i oppdrett, by K. Bjørklund, M. Gjessing, H. Nilsen, S. Patel, & K. Gismervik). Norwegian Veterinary Institute. https://www.vetinst.no/rapporter-og-publikasjoner/rapporter/2026/fiskehelserapporten-2025

[9] Servicio Nacional de Pesca y Acuicultura (SERNAPESCA). (2026). Informe con antecedentes sanitarios de agua dulce y mar, año 2025. Subdirección de Acuicultura, Departamento de Salud Animal. https://www.sernapesca.cl/app/uploads/2026/03/Informe-Situacion-Sanitaria-Salmonicultura-Ano-2025.pdf

[10] Brevik, Ø. J., Ottem, K. F., & Nylund, A. (2011). Multiple-locus, variable number of tandem repeat analysis (MLVA) of the fish-pathogen Francisella noatunensis. BMC Veterinary Research, 7, 5. https://doi.org/10.1186/1746-6148-7-5

[11] Bjørnestad, S. A., Krokene, P., Solbakken, M. H., Gosain, T. P., Jakobsen, K. S., Jentoft, S., Bakke, O., & Progida, C. (2026). TLR25 is endosomally located and responds to Francisella infection in Atlantic cod. Frontiers in Immunology, 17, 1798290. https://doi.org/10.3389/fimmu.2026.1798290

[12] Aliaga-Tobar, V., Arias-Carrasco, R., Isla, A., Santander, J., Maracaja-Coutinho, V., & Yañez, A. J. (2025). Exploring the regulatory landscape of non-coding RNAs in aquaculture bacterial pathogens: Piscirickettsia salmonis and Francisella noatunensis. Aquaculture, 594, 741356. https://doi.org/10.1016/j.aquaculture.2024.741356