Spirillary Rat-Bite Fever (Sodoku) — Comprehensive Disease Characterization

Disease: Spirillary Rat-Bite Fever | MONDO: MONDO:0020532 | Category: Infectious Disease Causative agent: Spirillum minus (syn. Spirillum minor) Report date: 2026-09-25

Evidence-source note. This is a bacterial zoonosis, not a genetic disorder. Sections designed for Mendelian/genetic diseases (host causal genes, pathogenic variants, inheritance, penetrance, chromosomal abnormalities, germline/somatic status) are Not applicable; where relevant, the analogous pathogen genetics/biology is provided instead. Evidence is predominantly human clinical (case reports/series, narrative and systematic reviews) with some veterinary/microbiological data. Much of the Spirillum minus-specific literature is old and observational because the organism cannot be cultured on artificial media; contemporary molecular data are sparse.

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" (41480582). It has been recognized as a clinical entity for over 2000 years (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 (39628725), and can even be established "with contaminated vehicle contact alone, not only as a direct result of a bite" (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 (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" (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" (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" (26584844). - Pet ownership — pet rats are an increasingly common source (17223620; 26701936: "three domestic rats living in the girl's home"). "Keeping rats as pets cannot be recommended" (34672901). - Housing/poverty & crowding — historically linked to higher rat contact ("housing conditions and habits of the people," 19867970); homelessness (38459199). - Demographics: children and low socioeconomic groups are a vulnerable population (34672901). - Host immune status: immunocompromise (cirrhosis, CKD, HIV/AIDS) predisposes to severe/complicated disease (29709962; 11139161); RBF has presented as culture-negative septic arthritis in newly diagnosed HIV (21877181). Alcohol-use disorder is a recurrent comorbidity (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" (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," 41480582, 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 (34583654; 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 (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 (37450033), and to mimic Henoch–Schönlein purpura (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; 23993005 37101553), and (more typical of the streptobacillary form) septic arthritis, osteomyelitis, meningitis, hepatitis, myocarditis, abscesses → organ failure and, in ~7–13% untreated, death (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 (37101553; risk in prior valve disease 1562665; immunocompromise 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, 19867970: "production of powerful agglutinins for the organism"). Reactive autoantibodies (ANCA, AECA) can appear (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 (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, 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 (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," 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" (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 (29671179; 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 (40793882). The largest single Canadian series found 11 cases on Vancouver Island over 2010–2016 (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" (41480582); first presumptive S. minus case in Nepal reported 2026 (41480582); a Kenyan case with spirillum-like organisms on thick film (1286642). The streptobacillary form predominates in the Americas/Europe. The greater historical frequency in Japan was attributed to housing conditions and rat exposure (19867970).
• Demographics: children and people of low socioeconomic status are over-represented (34672901); occupational cohorts (lab/pet-rodent handlers) at risk. Endocarditis series skew male (61.5%) with mean age ~41 (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 (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" (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 (34672901; used for Streptobacillus speciation in 34583654 40472936 35365242). Note a caveat: 16S rRNA analysis "may be uncertain for proper pathogen identification" and RBF diagnostics remain a "diagnostic dilemma" (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" (31315559). MALDI-TOF MS is used for Streptobacillus but not reliable for the unculturable S. minus.
• Blood culture: typically negative for S. minus (41480582); positive cultures instead indicate the streptobacillary form (BACTEC/subculture; 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 (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 (41480582); anemia (~57%), leukocytosis (~52%), raised inflammatory markers (~58%) across RBF (37101553).
• Imaging: echocardiography (TEE) for suspected endocarditis (23993005); MRI for osteomyelitis/discitis (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 (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 (37450033) and Henoch–Schönlein purpura (29709962).

11. Outcome / Prognosis

• Untreated mortality ~7–13% — concordant across sources: "mortality rate of 7% to 10% if untreated" (21358889), "up to 13%, if untreated" (34211343), and "10%" (17223620).
• With prompt appropriate antibiotics: excellent — full recovery, usually without sequelae (41480582; 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%, 37101553), sepsis, metastatic septic arthritis/osteomyelitis/discitis (34039283 40472936 26948832), meningitis (34583654), hepatitis, myocarditis, abscess formation, and a hyperinflammatory syndrome resembling hemophagocytic lymphohistiocytosis (HLH) with multiorgan failure (32868746).
• Prognostic factors: speed of diagnosis/treatment, presence of endocarditis or pre-existing valve disease (1562665), immune status (cirrhosis/CKD/HIV worsen outcome — 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" (26701936). Patients are often "cured completely after intravenous administration of penicillin G" with therapy "completed by an oral course of doxycycline" (9856201). Case cured with penicillin (± gentamicin) — 1286642.
• Alternatives (penicillin allergy): doxycycline (NCIT:C641)/tetracyclines, ceftriaxone (NCIT:C1737)/cephalosporins, or macrolides. Combination ampicillin + doxycycline used in the Nepal S. minus case (41480582); ampicillin/sulbactam + doxycycline (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 (23993005 — IV penicillin 6 wk + gentamicin 2 wk; 11139161 — ceftriaxone/gentamicin/penicillin).
• Aminoglycoside adjunct: gentamicin as synergistic add-on in severe disease (1286642 23993005).
• Surgical/interventional: wound debridement for local disease (41480582); valve replacement/surgery in ~36% of endocarditis (10/14 needing surgery had replacement, 37101553); arthroscopic lavage/DAIR for septic arthritis / prosthetic joint infection (40472936 35365242).
• Supportive care: antipyretics/analgesia, fluids, treatment of sepsis; NSAIDs for arthralgia/vasculitic features (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," 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 (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 (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 (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 (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 (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 (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 (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 (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 (31315559 27088660). - Making rodent bites/RBF a notifiable event to enable real epidemiologic estimates (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.