Rickettsial Diseases other than Scrub Typus

Introduction

Rickettsial diseases are a group of acute febrile illnesses caused by obligate intracellular, gram-negative coccobacilli belonging to the family Rickettsiaceae. These organisms are zoonoses transmitted to humans by arthropod vectors such as ticks, lice, fleas, and mites. Historically, these diseases have caused significant morbidity and mortality, particularly during wars and famines.

While Scrub Typhus (caused by Orientia tsutsugamushi) is a major health concern in the "Tsutsugamushi Triangle" (Asia-Pacific), other rickettsial diseases from the Spotted Fever Group and Typhus Group also contribute significantly to the burden of acute febrile illness globally and in India.

Classification

The genus Rickettsia is classically divided into two major antigenically distinct groups based on clinical features and serology:

1. Spotted Fever Group (SFG): Includes Rocky Mountain Spotted Fever, Indian Tick Typhus (Mediterranean Spotted Fever), and Rickettsialpox.
2. Typhus Group (TG): Includes Epidemic Typhus and Murine Typhus.

(Note: Q Fever, caused by Coxiella burnetii, and Ehrlichiosis are closely related but distinct entities often discussed alongside rickettsiae.)

I. Spotted Fever Group (SFG)

The Spotted Fever Group rickettsiae primarily target vascular endothelial cells, causing widespread vasculitis.

1. Rocky Mountain Spotted Fever (RMSF)

This is the prototype and most severe form of rickettsial disease in the Western Hemisphere.

• Etiology: Rickettsia rickettsii.
• Vector: Ticks (e.g., Dermacentor species, Rhipicephalus sanguineus).
• Pathophysiology: The organism infects endothelial cells, leading to increased vascular permeability, edema, and activation of inflammatory cascades. This results in microvascular leakage, hypovolemia, and end-organ ischemia.
• Clinical Features:
  • Triad: Fever, headache, and rash (seen in ~60% of children).
  • Rash: Typically appears on the 4th day. It is centripetal, starting as blanching macules on the wrists and ankles, then spreading to the trunk, palms, and soles. It evolves into petechiae and purpura.
  • Systemic: Severe myalgia (calf tenderness), edema, hypotension, and confusion.
  • Complications: Gangrene of digits/ears, pulmonary edema, ARDS, and meningoencephalitis.
  • Mortality: High if untreated (20%); reduced to <5% with therapy.

2. Indian Tick Typhus (ITT) / Mediterranean Spotted Fever (MSF)

Also known as Boutonneuse fever, this is the prevalent spotted fever in India (Maharashtra, Karnataka, Tamil Nadu).

• Etiology: Rickettsia conorii (subspecies indica is proposed for ITT).
• Vector: The brown dog tick (Rhipicephalus sanguineus).
• Reservoir: Dogs and rodents.
• Clinical Features:
  • Incubation period is 5–7 days.
  • Eschar (Tache Noire): A black necrotic crust with an erythematous rim at the tick bite site. While characteristic of MSF (present in 70% of cases), it is reportedly less common or often missed in Indian Tick Typhus.
  • Rash: Maculopapular or petechial rash involving the palms and soles.
  • Systemic: Fever, headache, and regional lymphadenopathy draining the eschar site. Complications include neurological deficits ("Kan-kapya" or ear-lobe gangrene is a local term describing microinfarcts).

3. Rickettsialpox

A mild, self-limiting disease often misdiagnosed as chickenpox.

• Etiology: Rickettsia akari.
• Vector: Mouse mite (Liponyssoides sanguineus).
• Clinical Features:
  • Characterized by a primary eschar at the mite bite site.
  • Followed by a generalized papulovesicular rash that resembles varicella but does not crust in the same manner.
  • Fever and regional lymphadenopathy are common.

II. Typhus Group (TG)

1. Epidemic Typhus (Louse-Borne Typhus)

Historically the scourge of armies and refugees, associated with overcrowding and poor hygiene.

• Etiology: Rickettsia prowazekii.
• Vector: Human body louse (Pediculus humanus corporis). Transmission occurs via scratching infected louse feces into the skin, not by the bite itself.
• Clinical Features:
  • Abrupt onset of high fever, severe intractable headache, and prostration.
  • Rash: Appears around day 5. It is centrifugal, starting on the trunk (axillary folds) and spreading to the extremities, usually sparing the face, palms, and soles (unlike RMSF).
  • CNS: Stupor, delirium, and coma are common ("typhus" means smoke/hazy, referring to the clouded sensorium).
• Recrudescence: Brill-Zinsser Disease is a milder relapse occurring years after the primary infection due to waning immunity.

2. Murine Typhus (Endemic Typhus)

A milder zoonosis distributed worldwide.

• Etiology: Rickettsia typhi.
• Vector: Rat flea (Xenopsylla cheopis).
• Reservoir: Rats (peridomestic).
• Clinical Features:
  • Similar to epidemic typhus but generally milder.
  • Triad of fever, headache, and rash is seen in about half of patients.
  • The course is usually self-limiting (12–14 days).

III. Other Related Infections

Q Fever

• Etiology: Coxiella burnetii.
• Transmission: Inhalation of aerosols from infected birth products of cattle, sheep, or goats (no arthropod vector in humans).
• Clinical Features: Presents as atypical pneumonia or hepatitis. Notably, rash is absent. Chronic Q fever can cause culture-negative endocarditis.

Ehrlichiosis and Anaplasmosis

• Agents: Ehrlichia chaffeensis (Human Monocytic Ehrlichiosis) and Anaplasma phagocytophilum (Human Granulocytic Anaplasmosis).
• Features: Tick-borne leukopenia, thrombocytopenia, and fever. Rash is less common than in rickettsial diseases.

Diagnostic Approach

1. Clinical Suspicion: Based on the triad of fever, rash, and headache, especially with a history of tick exposure or travel to endemic areas. Presence of an eschar (Tache Noire) is a vital clue for SFG (and scrub typhus).
2. Weil-Felix Test:
   • A nonspecific agglutination test using Proteus antigens.
   • OX-19 and OX-2 are positive in Spotted Fever and Typhus groups.
   • OX-K is negative (it is positive only in Scrub Typhus).
   • Note: Although widely used in resource-limited settings, it has low sensitivity and specificity.
3. Specific Serology:
   • Immunofluorescence Assay (IFA): The gold standard. Detects IgM and IgG.
   • ELISA: IgM ELISA is commercially available and useful for early diagnosis.
4. Molecular Methods: PCR on skin biopsy (eschar/rash) or blood can detect rickettsial DNA in the early stage (first week) before antibodies appear.
5. Hematology: Thrombocytopenia and elevated liver enzymes are common supportive findings.

Management

Early empiric treatment is crucial to prevent mortality, as serological confirmation is retrospective.

• Drug of Choice: Doxycycline for all ages (including children <8 years).
  • Dose: 2.2 mg/kg/dose (max 100 mg) BD orally or IV.
  • Duration: 5–7 days, or until 3 days after defervescence.
• Alternatives:
  • Chloramphenicol (risk of bone marrow suppression).
  • Azithromycin (useful in mild cases or pregnant women).
• Supportive Care: Management of fluid balance is critical to prevent pulmonary edema (due to capillary leak).

Summary Table