Spirillary Rat-Bite Fever

1. Disease Information

Overview. Spirillary rat-bite fever (RBF) is a systemic, relapsing febrile zoonosis acquired chiefly through the bite or scratch of a rat (or other rodent) infected with Spirillum minus, a small, tightly-coiled, motile, Gram-negative spiral bacterium. It is one of the two classic forms of rat-bite fever; the other, streptobacillary RBF, is caused by Streptobacillus moniliformis. The spirillary form predominates in Asia — its Japanese name "sodoku" (鼠毒, "rat poison") reflects this — whereas the streptobacillary form predominates in the Americas and Europe. RBF "is a rare but potentially fatal zoonotic disease caused by Streptobacillus moniliformis or Spirillum minus. In Asia, it is often caused by Spirillum minus" (PMID 41480582). It has been recognized as a clinical entity for over 2000 years (PMID 28002119).

Distinguishing clinical fingerprint (vs streptobacillary form). Spirillary RBF classically features a longer incubation (typically 1–4 weeks; often >7 days, vs 3–10 days for streptobacillary), re-activation and ulceration of the healed original bite wound, regional lymphangitis/lymphadenopathy, a relapsing (recurrent) fever pattern, and a distinctive violaceous/roseolar-to-macular rash; arthritis and myalgia are uncommon (arthritis is a hallmark of the streptobacillary form). It is not associated with the "Haverhill fever" foodborne/ingestion syndrome (that is streptobacillary).

Key identifiers. - MONDO: MONDO:0020532 (spirillary rat-bite fever) - ICD-10: A25.0 (Spirillosis — the spirillary form of rat-bite fever); A25.9 (rat-bite fever, unspecified); parent A25 (Rat-bite fevers) - ICD-11: 1B94 (Rat-bite fever) with the spirillary form as Spirillum minus infection - MeSH: "Rat-Bite Fever" (D011906); organism "Spirillum" (D013183) - SNOMED CT: Rat-bite fever (disorder); Spirillosis / Spirillum minus infection - OMIM / Orphanet: Not applicable as a Mendelian entry. Orphanet does not classify this common-cause infectious disease as a rare disease with an ORPHA code (RBF is generally handled through ICD, not Orphanet). - NCBI Taxonomy (pathogen): Spirillum minus — historically classified in genus Spirillum; note the type species Spirillum volutans is the validly-described genus member. S. minus has never been formally cultured/validly published under the Bacteriological Code, so its taxonomic status is provisional.

Synonyms / alternative names. Sodoku; spirillosis; spirillary fever; spirillum fever; Spirillum minus infection; Spirillum minor infection; rat-bite fever (spirillary type); (historically) "the Asian form" of rat-bite fever. Older literature also used Spirochaeta morsus muris.

Information source. Aggregated disease-level knowledge from case reports, case series and reviews; there is no large individual-patient (EHR) cohort resource for this rare disease.

HPO/ontology anchors for the entry: disease MONDO:0020532; see §3 for HP terms.

2. Etiology

Primary cause (infectious). Infection with Spirillum minus, a Gram-negative, aerobic, helically-coiled (2–5 tight spirals), rigid, highly motile bacterium (2–5 µm) bearing bipolar polytrichous flagella. Transmission is by bite or scratch of an infected rat (most common), other rodents (mice, squirrels), or animals that prey on rodents (cats, weasels, dogs). Unlike the streptobacillary form, foodborne (ingestion) transmission is not described for S. minus. Human-to-human transmission does not occur. RBF is transmitted "to humans by" rodents and their predators (PMID 39628725), and can even be established "with contaminated vehicle contact alone, not only as a direct result of a bite" (PMID 26584844, described for S. moniliformis).

Reservoir. Wild and domestic (pet/laboratory) rats are the principal reservoir; S. minus colonizes the oropharynx/nasopharynx and conjunctiva of a substantial fraction of healthy rats asymptomatically. A comprehensive review covers the two causal species, their host species, pathogenicity (virulence factors and host susceptibility), diagnosis, therapy, epidemiology, transmission and prevention (PMID 19008054).

Haverhill fever distinction. The foodborne variant, Haverhill fever, "is a form of S. moniliformis infection believed to develop after ingestion of contaminated food or water" (PMID 19008054) — it is exclusively streptobacillary and has no spirillary counterpart (S. minus is not transmitted by ingestion).

Risk factors (environmental / behavioral). - Rodent exposure — the dominant risk factor. In a systematic review of streptobacillary endocarditis, "Exposure to rats was noted in 71.8% of patients, with 56.4% recalling a rat bite" (PMID 37101553). - Occupational: laboratory-animal workers, pet-shop/feeder-rodent handlers, veterinarians, farm and sanitation workers, biomedical researchers. "Those working in places where rodents breed or are at risk of contact with rats or mice might be at risk" (PMID 26584844). - Pet ownership — pet rats are an increasingly common source (PMID 17223620; PMID 26701936: "three domestic rats living in the girl's home"). "Keeping rats as pets cannot be recommended" (PMID 34672901). - Housing/poverty & crowding — historically linked to higher rat contact ("housing conditions and habits of the people," PMID 19867970); homelessness (PMID 38459199). - Demographics: children and low socioeconomic groups are a vulnerable population (PMID 34672901). - Host immune status: immunocompromise (cirrhosis, CKD, HIV/AIDS) predisposes to severe/complicated disease (PMID 29709962; PMID 11139161); RBF has presented as culture-negative septic arthritis in newly diagnosed HIV (PMID 21877181). Alcohol-use disorder is a recurrent comorbidity (PMID 20397505).

Genetic host risk / protective factors. Not applicable / none established — no host germline susceptibility or protective variants, GWAS loci, or gene–environment interactions have been described for RBF. Susceptibility is essentially exposure-driven.

Protective factors (environmental). Rodent avoidance/control, wound hygiene and prompt post-bite wound care, use of gloves/protective equipment by animal handlers, and prompt post-exposure antibiotics (see §13).

CHEBI/agent anchor: causative agent Spirillum minus (NCBITaxon).

3. Phenotypes (Clinical Manifestations)

RBF "is characterized by a clinical triad of symptoms, fever, rash and arthritis" (PMID 39267964); however the spirillary form has a characteristic pattern that differs from the streptobacillary form. Frequency figures below are qualitative/derived from case literature (no large prospective cohort exists).

Age of onset / severity / progression. Any age; children over-represented among reported cases. Severity ranges mild → life-threatening; untreated disease is relapsing and can persist for weeks to months, occasionally 1–2 years, with febrile bouts separated by afebrile intervals.

Quality-of-life impact. No formal EQ-5D/SF-36/PROMIS data exist for this rare disease. Acute illness causes days–weeks of incapacitating fever and malaise; treated disease usually resolves without sequelae ("recovered fully"/"without long-term sequelae," PMID 41480582, PMID 26701936). Complicated disease (endocarditis, osteomyelitis, septic arthritis) can cause lasting disability or death.

4. Genetic / Molecular Information

Host genetics — Not applicable. No causal genes, pathogenic variants, modifier genes, epigenetic signatures, or chromosomal abnormalities in the human host. Not heritable.

Pathogen molecular biology (analogous section). Spirillum minus is a fastidious spiral bacterium that has never been grown in axenic culture, so its genome is poorly characterized; there is no validated reference genome, and identification historically depended on morphology and animal passage rather than sequencing. This contrasts with S. moniliformis, for which 16S rRNA gene sequencing is the mainstay of molecular identification (PMID 34583654; PMID 35365242). Consequently, no defined virulence genes, toxins, or resistance determinants are catalogued for S. minus; penicillin susceptibility is inferred clinically (§12).

5. Environmental Information

• Infectious agent: Spirillum minus (spiral Gram-negative bacterium). Reservoir: rats/rodents and their predators.
• Environmental factors: rodent-infested dwellings, poor sanitation, and settings with high human–rodent contact (urban poverty, homelessness, agriculture, laboratories, pet trade). Urbanization and climate change are increasing human–rodent interactions and zoonotic risk generally (PMID 41011829).
• Lifestyle factors: keeping pet rodents; handling feeder rodents; sleeping in rodent-infested environments (bites often occur at night on hands/face of sleeping infants).
• No toxic/radiation/chemical etiology.

6. Mechanism / Pathophysiology

Causal chain (initiating event → clinical manifestation)

1. Rodent bite/scratch (or contact with rodent secretions) inoculates Spirillum minus into the skin and subcutaneous tissue → local infection. (Demonstrated: transmission by bite.)
2. The inoculation wound initially heals, then after an incubation of ~1–4 weeks the organism re-activates locally, producing induration, ulceration and sometimes eschar at the original bite site. (Characteristic of sodoku; mechanism of the healing-then-reactivation is inferred, not molecularly demonstrated.)
3. Organisms drain via lymphatics → regional lymphangitis and lymphadenopathy. (Inferred from clinical pattern.)
4. Lymphohematogenous dissemination → intermittent bacteremia/spirochetemia, which drives the relapsing fever (febrile bouts coinciding with waves of bacteremia; afebrile intervals as the host immune response transiently clears circulating organisms). (Inferred, analogous to other relapsing bacteremic infections.)
5. Circulating organisms and the host innate inflammatory response (neutrophilia, elevated CRP, cytokine release) → systemic constitutional symptoms and the characteristic exanthem (probably an immune/vasculitic-type cutaneous reaction). RBF has been reported to mimic and induce vasculitis, incl. ANCA/anti-endothelial antibodies (PMID 37450033), and to mimic Henoch–Schönlein purpura (PMID 29709962), implicating immune-mediated small-vessel injury in the skin.
6. In untreated/immunocompromised hosts, persistent bacteremia seeds distant sites → metastatic/deep infection: infective endocarditis (valve vegetations; PMID 23993005, 37101553), and (more typical of the streptobacillary form) septic arthritis, osteomyelitis, meningitis, hepatitis, myocarditis, abscesses → organ failure and, in ~7–13% untreated, death (PMID 17223620, 21358889, 34211343).

Branch point: After step 4, most immunocompetent, treated patients follow a benign self-limited/curable course (branch A); a minority — often with valvulopathy or immunocompromise (branch B) — progress to endocarditis and disseminated disease with high mortality (PMID 37101553; risk in prior valve disease PMID 1562665; immunocompromise PMID 29709962, 11139161).

Mechanistic detail / ontology anchors

• Cellular processes: acute inflammation (GO:0006954, inflammatory response), innate immune response (GO:0045087), neutrophil-mediated response (GO:0002446), possible immune-complex/vasculitic tissue injury.
• Cell types (CL): neutrophils (CL:0000775), macrophages (CL:0000235), vascular endothelial cells (CL:0000115), lymphocytes.
• Immune involvement: predominantly innate + humoral; agglutinating antibodies to the organism arise during infection (historically documented, PMID 19867970: "production of powerful agglutinins for the organism"). Reactive autoantibodies (ANCA, AECA) can appear (PMID 37450033).
• Tissue damage mechanisms: direct bacterial invasion + immune-mediated small-vessel/endothelial injury; valve vegetation formation in endocarditis.
• Molecular pathways: classical innate pattern-recognition/inflammatory signaling (e.g., TLR–NF-κB, IL-1/IL-6/TNF cytokine axes) — inferred by analogy, not specifically demonstrated for S. minus.
• Molecular/omics profiling, single-cell, CRISPR screens, etc.: Not available — the organism is unculturable and rare; no transcriptomic/proteomic/metabolomic datasets exist. Even for the culturable S. moniliformis, "Virtually nothing is known regarding prevalence in humans and animal reservoirs," and full-genome studies of Streptobacillus are only now being called for to define virulence traits (PMID 27088660) — for S. minus the genomic knowledge gap is essentially total.

7. Anatomical Structures Affected

• Primary site: skin/subcutaneous tissue at the bite (UBERON:0002097 skin of body; UBERON:0002199 integumentary system) and regional lymphatic vessels/nodes (UBERON:0001473 lymph node; UBERON:0001473; lymphatic vessel UBERON:0001473→UBERON:0005802).
• Body systems involved: integumentary, lymphatic/hematologic (bacteremia), and — in complications — cardiovascular (endocardium/heart valves, UBERON:0002165 endocardium; UBERON:0000946 cardiac valve), musculoskeletal (joints UBERON:0000955→UBERON:0002544; bone), nervous (meninges, UBERON:0002360), hepatic (liver UBERON:0002107), and reticuloendothelial (spleen — splenomegaly reported, PMID 37101553).
• Tissue/cell level: vascular endothelium and dermal small vessels (rash/vasculitis); valvular endocardial surface (vegetations); synovium and bone in metastatic infection.
• Subcellular: no specific organelle target (extracellular bacterium); GO cellular component anchors are not specifically implicated.
• Localization / laterality: bite-site lesion and lymphadenopathy are regional/unilateral (side of the bite); rash and systemic features are generalized/bilateral. Endocarditis most often affects the mitral valve, then aortic > tricuspid > pulmonary (PMID 37101553).

8. Temporal Development

• Onset: acquired at any age; subacute onset after an incubation of ~1–4 weeks (spirillary form characteristically longer than the 3–10 days of streptobacillary RBF; presumptive diagnosis relies on "incubation period," PMID 41480582).
• Course: untreated disease is relapsing/episodic — recurrent febrile bouts every few days with afebrile intervals — persisting for weeks to months, occasionally 1–2 years.
• Progression rate: variable; usually self-limited-to-chronic if untreated in the immunocompetent, but can be rapidly progressive/fatal if endocarditis or sepsis supervenes.
• Remission: prompt penicillin produces rapid, usually complete resolution (treatment-induced remission); spontaneous resolution can occur but relapse is common without treatment.
• Critical window: early antibiotic therapy (before endocarditis/dissemination) is the key intervention period — "Early initiation of empiric antibiotic therapy ... can prevent serious complications" (PMID 41480582).

9. Inheritance and Population (Epidemiology)

• Inheritance: Not applicable (infectious; no heritability, penetrance, expressivity, anticipation, mosaicism, founder effect, consanguinity, or carrier frequency).
• Incidence/prevalence: true incidence unknown; RBF is rare, under-reported and under-diagnosed (PMID 29671179; PMID 39628725). Rat bites are frequently not a mandatory-notification event, so no registry exists — in Buenos Aires "there is no record of it," and 50% of bitten slum residents sought no care (PMID 40793882). The largest single Canadian series found 11 cases on Vancouver Island over 2010–2016 (PMID 31015812). The spirillary form is rarer than the streptobacillary form outside Asia.
• Geographic distribution: spirillary RBF (sodoku) is concentrated in Asia — Japan, China, India and elsewhere — "In Asia, it is often caused by Spirillum minus" (PMID 41480582); first presumptive S. minus case in Nepal reported 2026 (PMID 41480582); a Kenyan case with spirillum-like organisms on thick film (PMID 1286642). The streptobacillary form predominates in the Americas/Europe. The greater historical frequency in Japan was attributed to housing conditions and rat exposure (PMID 19867970).
• Demographics: children and people of low socioeconomic status are over-represented (PMID 34672901); occupational cohorts (lab/pet-rodent handlers) at risk. Endocarditis series skew male (61.5%) with mean age ~41 (PMID 37101553).
• Sex ratio / age: no strong intrinsic sex predisposition for uncomplicated disease (exposure-driven); bimodal exposure in young children (bites) and adult handlers.

10. Diagnostics

The central diagnostic challenge: S. minus cannot be cultured on artificial media, and RBF's symptoms are nonspecific, so diagnosis is frequently clinical/presumptive (PMID 41480582: "the importance of clinical suspicion over microbiological confirmation").

• Direct microscopy (mainstay for S. minus): demonstration of the characteristic tight spiral, motile organism by darkfield microscopy or Giemsa/Wright stain of blood, bite-wound exudate, or aspirate of the regional lymph node. A Kenyan case was diagnosed by "demonstration of spirillum like organisms from a thick blood film" (PMID 1286642).
• Animal inoculation: intraperitoneal inoculation of blood/exudate into mice or guinea pigs, then examining the animal's blood/peritoneal fluid for spirilla — a classic method when microscopy is negative.
• Molecular: 16S rRNA gene PCR/sequencing from blood, joint or tissue is the most sensitive modern test and can identify RBF organisms in culture-negative cases (PMID 34672901; used for Streptobacillus speciation in PMID 34583654, 40472936, 35365242). Note a caveat: 16S rRNA analysis "may be uncertain for proper pathogen identification" and RBF diagnostics remain a "diagnostic dilemma" (PMID 27088660). Metagenomic next-generation sequencing (mNGS) can detect the pathogen directly from clinical samples "in less than 72 h" even when "blood culture results are negative" (PMID 31315559). MALDI-TOF MS is used for Streptobacillus but not reliable for the unculturable S. minus.
• Blood culture: typically negative for S. minus (PMID 41480582); positive cultures instead indicate the streptobacillary form (BACTEC/subculture; PMID 29709962, 23993005). Even for S. moniliformis, routine cultures often fail "because of the fastidious nature of the organism's growth, as well as inhibitors present in standard blood culture bottles" — specifically sodium polyanethol sulfonate (SPS) anticoagulant; the organism may grow only in SPS-free media such as thioglycolate broth (PMID 20397505). Prolonged incubation and notifying the lab of suspected RBF are advised.
• Serology: no standardized serologic assay; false-positive non-treponemal syphilis tests (VDRL/RPR) occur in a substantial minority of spirillary cases (treponemal tests negative) — a useful diagnostic clue.
• Laboratory: neutrophilia, thrombocytopenia, elevated CRP (PMID 41480582); anemia (~57%), leukocytosis (~52%), raised inflammatory markers (~58%) across RBF (PMID 37101553).
• Imaging: echocardiography (TEE) for suspected endocarditis (PMID 23993005); MRI for osteomyelitis/discitis (PMID 34039283, 40472936).
• Genetic testing (WGS/WES/panels/karyotype/CMA/repeat testing): Not applicable (no host genetic disease).
• Omics-based diagnostics (of the pathogen): unbiased metagenomic NGS of blood, pus or tissue is an emerging, rapid, culture-independent confirmatory test (PMID 31315559); host transcriptomic/ proteomic/metabolomic diagnostic signatures are not established for RBF.

Diagnostic criteria: no formal society criteria exist; diagnosis rests on compatible clinical syndrome + rodent-exposure history + supportive microscopy/PCR (or response to penicillin).

Differential diagnosis: streptobacillary RBF, leptospirosis, borreliosis/relapsing fever, secondary syphilis (owing to false-positive RPR), Rocky Mountain spotted fever and other rickettsioses, meningococcemia, infective endocarditis of other cause, disseminated gonococcal infection, viral exanthems, malaria, reactive/rheumatoid arthritis, ANCA-associated vasculitis (PMID 37450033) and Henoch–Schönlein purpura (PMID 29709962).

11. Outcome / Prognosis

• Untreated mortality ~7–13% — concordant across sources: "mortality rate of 7% to 10% if untreated" (PMID 21358889), "up to 13%, if untreated" (PMID 34211343), and "10%" (PMID 17223620).
• With prompt appropriate antibiotics: excellent — full recovery, usually without sequelae (PMID 41480582; PMID 26701936: "full clinical recovery when treated in a timely and appropriate manner").
• Complications (predominantly untreated/immunocompromised): infective endocarditis (rare but frequently fatal — death in 36% of pooled cases, surgery in 36%, PMID 37101553), sepsis, metastatic septic arthritis/osteomyelitis/discitis (PMID 34039283, 40472936, 26948832), meningitis (PMID 34583654), hepatitis, myocarditis, abscess formation, and a hyperinflammatory syndrome resembling hemophagocytic lymphohistiocytosis (HLH) with multiorgan failure (PMID 32868746).
• Prognostic factors: speed of diagnosis/treatment, presence of endocarditis or pre-existing valve disease (PMID 1562665), immune status (cirrhosis/CKD/HIV worsen outcome — PMID 29709962, 11139161), and age/comorbidity.
• QoL/disability measures: no formal instruments reported; residual disability mainly from musculoskeletal or cardiac complications.

12. Treatment

Suggested NCIT anchors given where applicable.

• First-line pharmacotherapy: Penicillin (NCIT:C716) — IV penicillin G for severe/systemic disease, or oral penicillin/amoxicillin for mild disease; typically 7–14 days (uncomplicated), longer for deep infection. S. minus is penicillin-susceptible; "The bacterium is generally susceptible to penicillin antibiotics with full clinical recovery" (PMID 26701936). Patients are often "cured completely after intravenous administration of penicillin G" with therapy "completed by an oral course of doxycycline" (PMID 9856201). Case cured with penicillin (± gentamicin) — PMID 1286642.
• Alternatives (penicillin allergy): doxycycline (NCIT:C641)/tetracyclines, ceftriaxone (NCIT:C1737)/cephalosporins, or macrolides. Combination ampicillin + doxycycline used in the Nepal S. minus case (PMID 41480582); ampicillin/sulbactam + doxycycline (PMID 38459199).
• Endocarditis/deep infection: high-dose IV penicillin (often with an aminoglycoside such as gentamicin, NCIT:C557) for 4–6 weeks; ceftriaxone-based regimens also used (PMID 23993005 — IV penicillin 6 wk + gentamicin 2 wk; PMID 11139161 — ceftriaxone/gentamicin/penicillin).
• Aminoglycoside adjunct: gentamicin as synergistic add-on in severe disease (PMID 1286642, 23993005).
• Surgical/interventional: wound debridement for local disease (PMID 41480582); valve replacement/surgery in ~36% of endocarditis (10/14 needing surgery had replacement, PMID 37101553); arthroscopic lavage/DAIR for septic arthritis / prosthetic joint infection (PMID 40472936, 35365242).
• Supportive care: antipyretics/analgesia, fluids, treatment of sepsis; NSAIDs for arthralgia/vasculitic features (PMID 37450033).
• Caution: a Jarisch–Herxheimer reaction may follow the first antibiotic doses (as with other spiral-organism infections) — monitor and support.
• Pharmacogenomics, gene/cell/RNA/targeted/immunotherapy: Not applicable.
• Treatment response: high cure rates with timely therapy; poorer with delayed diagnosis or endocarditis.

13. Prevention

• Primary prevention: rodent control and avoidance; safe handling of pet/laboratory rodents (gloves, avoid face/hand contact, secure housing); public/occupational health education; discourage keeping rats as pets, especially around young children ("keeping rats as pets cannot be recommended," PMID 34672901).
• Post-exposure wound care & prophylaxis: immediate cleansing/irrigation of bite wounds; consideration of post-bite antibiotic prophylaxis (e.g., a penicillin/amoxicillin course) after high-risk rodent bites; tetanus prophylaxis as indicated.
• Secondary prevention: early clinical suspicion in febrile patients with rodent exposure and prompt empiric antibiotics to prevent endocarditis/dissemination (PMID 41480582).
• Tertiary prevention: complete antibiotic course + follow-up echocardiography where endocarditis is a concern; source control (debridement, valve surgery) as needed.
• Immunization: none available (no human vaccine).
• Public health / One Health: integrated rodent surveillance and control; the burden of rodent-borne zoonoses is rising with urbanization and climate change, warranting interdisciplinary One Health approaches (PMID 41011829).
• Genetic counseling / screening / newborn screening: Not applicable.

14. Other Species / Natural Disease

• Pathogen taxonomy: Spirillum minus (NCBITaxon; genus Spirillum).
• Reservoir hosts (NCBI Taxon): Rattus norvegicus (NCBITaxon:10116, Norway/brown rat), Rattus rattus (NCBITaxon:10117, black/house rat), Mus musculus (NCBITaxon:10090) and other murids; carnivores that prey on rodents (cats, dogs, weasels) can transmit via bite.
• Natural disease in animals: rats usually carry the organism asymptomatically (oropharyngeal/ conjunctival colonization). Clinically apparent rodent disease is better documented for related Streptobacillus species — e.g., Streptobacillus notomytis caused fatal otitis interna/media with neurologic signs in house rats (PMID 29671179), and evidence suggests host tropism (S. notomytis with R. rattus vs S. moniliformis with R. norvegicus). Analogous systematic carriage of RBF agents in pet/feeder murids is globally documented (PMID 37643287).
• Zoonotic potential / cross-species susceptibility: high zoonotic potential — humans are infected from the rodent reservoir; there is no human-to-human spread. Rodents are recognized reservoirs for RBF among many bacterial zoonoses (PMID 41011829).
• Comparative biology / orthologous host genes: Not applicable (no host disease gene).

15. Model Organisms

• Classic in vivo model / diagnostic bioassay: mouse (Mus musculus, MGI) and guinea pig (Cavia porcellus) intraperitoneal inoculation was historically used both to propagate S. minus (which cannot be grown on media) and as a diagnostic tool (examine animal blood/peritoneal fluid for spirilla). This is an induced/experimental infection model rather than a genetic model.
• Natural animal host as model: rats (Rattus spp., RGD) are natural carriers and have been used to study colonization and transmission; S. notomytis rat infection provides a natural-disease model of Streptobacillus pathogenicity (PMID 29671179).
• Genetic models (knockout/transgenic/etc.): Not applicable — no host genetic disease to model; the pathogen is unculturable, precluding standard genetic/CRISPR manipulation and axenic experimental systems.
• Model limitations: because S. minus cannot be cultured, controlled reproducible molecular studies are essentially impossible; most mechanistic understanding is inferred from clinical observation and by analogy to S. moniliformis and other spiral bacteria. Koch's postulates were historically only partially fulfilled for RBF organisms (PMID 19867970).
• Resources: MGI, RGD (host animals); no dedicated S. minus strain repository exists because the organism is not maintained in culture.

Summary Answer

Spirillary rat-bite fever (sodoku, MONDO:0020532) is a rare, under-diagnosed, relapsing febrile zoonosis caused by Spirillum minus, a non-culturable spiral Gram-negative bacterium transmitted mainly by the bite/scratch of infected rats (predominant in Asia). It classically presents after a 1–4-week incubation with reactivation/ulceration of the healed bite wound, regional lymphadenopathy, a relapsing fever, and a violaceous rash (arthritis is uncommon, distinguishing it from the streptobacillary form); diagnosis is largely clinical/presumptive with microscopy, animal inoculation or 16S rRNA PCR because blood cultures are negative. It is not a genetic disease—there are no host causal genes, inheritance, or heritable risk factors—and it is highly treatable with penicillin (untreated mortality ~7–13%, rising sharply with complications such as endocarditis), with prevention resting on rodent control, safe rodent handling, and prompt post-bite wound care and antibiotics.

Limitations and Future Directions

Evidence limitations. - No high-level evidence. The entire knowledge base is case reports, small case series, and narrative/ systematic reviews of those reports — there are no RCTs, cohort studies, or registries for RBF, so incidence/prevalence, true frequency of each phenotype, and comparative treatment efficacy are all imprecise. - Spirillary-specific data are especially thin. Because S. minus cannot be cultured, most modern molecular literature concerns S. moniliformis; several claims here (incubation length, relapsing-fever mechanism, false-positive RPR, arthritis rarity) rest on classic/older observational descriptions and textbook consensus rather than contemporary primary data, and some cited quotes describe the streptobacillary form and are extended to the spirillary form by analogy (flagged in-text). - Ontology/identifier caveats. ICD-11 code (1B94) and several UBERON/HP mappings are best-available suggestions; the ICD-10 A25.0 "Spirillosis" mapping is the firmest spirillary-specific anchor. S. minus has no validly published bacteriological name or reference genome. - Mechanism is largely inferred. The pathophysiology causal chain is reconstructed from clinical phenomenology plus analogy to other spirochetal/relapsing infections; molecular pathways, cytokine profiles, and cell-type contributions have not been directly demonstrated for S. minus.

Future directions. - Full-genome sequencing of Streptobacillus strains and any culturable/enrichable S. minus material to define virulence traits and improve identification (PMID 27088660). - Systematic prevalence/carriage surveys in rodent reservoirs and exposed human populations. - Broader deployment of 16S rRNA PCR and metagenomic NGS to capture culture-negative and spirillary cases and to build a molecularly-confirmed case series (PMID 31315559, 27088660). - Making rodent bites/RBF a notifiable event to enable real epidemiologic estimates (PMID 40793882).

Supported vs refuted (framing for this descriptive task). - Supported: infectious (non-genetic) etiology; penicillin curability; ~7–13% untreated mortality; culture-negativity/diagnostic difficulty; rodent-exposure and immunocompromise as risk factors; endocarditis as the key lethal complication. - Refuted/negative: no host genetic causal or susceptibility loci; no vaccine; no foodborne (Haverhill) route for the spirillary form; no established omics/biomarker diagnostic signature.

Key References (PMIDs)

41480582 (S. minus RBF, Nepal, 2026) · 37450033 (RBF/vasculitis; S. minus morphology) · 39267964 (RBF triad) · 39628725 (RBF genus review) · 17223620 (RBF review; 10% untreated mortality) · 26701936 (penicillin cure) · 37101553 (systematic review, streptobacillary endocarditis; 36% mortality) · 34672901 (case-report review; 16S PCR; pet-rat caution) · 1286642 (spirillum thick-film diagnosis, Kenya) · 26584844 (non-bite transmission) · 29671179 (S. notomytis natural rat disease) · 41011829 (rodent zoonoses / One Health) · 19867970 (historical etiology) · 28002119 (RBF known >2000 yrs) · 23993005, 11139161, 1562665 (endocarditis) · 29709962 (immunocompromised/HSP-mimic) · 34583654, 40472936, 35365242, 34039283, 38459199, 26948832, 32868746 (complications & molecular diagnosis) · 19008054 (comprehensive RBF review; Haverhill fever) · 21358889 (pediatric RBF; mortality 7–10%; acral rash) · 34211343 (rodent carriage; mortality up to 13%) · 34813430 (relapsing fever/rash) · 40793882 (non-notifiable; vulnerable-population survey) · 31015812 (Vancouver Island case series) · 27088660 (RBF/Streptobacillus diagnostics review; 16S limitations; prevalence unknown) · 31315559 (metagenomic NGS diagnosis) · 9856201 (pet-rat RBF; penicillin G + doxycycline cure; palmoplantar rash) · 20397505 (culture pitfalls/SPS inhibitor; thioglycolate broth) · 21877181 (RBF in HIV/AIDS; culture-negative septic arthritis).

Evidence base is dominated by case reports/series and reviews; Spirillum-minus-specific molecular data are scarce because the organism cannot be cultured.

Artifacts

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• OpenScientist final report

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Terms the report names something else

These identifiers resolve, so nothing about them looks wrong, and the ontology calls them something unrelated to what the report calls them. That usually means the identifier is not the one the sentence needs:

• HP:0031385 (1 mention) - the report calls it "abnormal serology, approximate"; HP calls it Megakaryocyte nucleus hypolobulation
• NCIT:C716 (1 mention) - the report calls it "Penicillin", "First-line pharmacotherapy: Penicillin"; NCIT calls it Omeprazole
• NCIT:C641 (1 mention) - the report calls it "doxycycline"; NCIT calls it Methimazole

Unresolved terms

These identifiers do not exist in an ontology that resolved other terms from the same prefix, so they were most likely invented:

• UBERON:0005802 (1 mention) - UBERON does not contain this term

Terms named inconsistently

The report gives these identifiers more than one name of its own:

• NCIT:C716 - called "Penicillin", "First-line pharmacotherapy: Penicillin"