## Introduction

For Rocky Mountain Spotted Fever (RMSF), the overall mortality rate is 4%, despite effective antibiotic therapy (Medscape)

## Hosts

Human and animal
R. rickettsia resides principally in various species of ticks, which are considered the reservoir or natural hosts[1][2]

## Transmission / Exposure Route

Transmitted to humans by the bite of infected tick species.[3] In large surveys, the prevalence of tick infection with the pathogenic species, R. rickettsia, is less than 1 per 1000 ticks. [4] There has been evidence that aerosol dissemination and infection can be possible, as well.[5]

## Case Fatality Ratio

The mortality rate is near 20%[7], increasing age is associated with increased risk of severe disease and fatal outcome.[8] A clear age-dependent mortality was reported before 1980, with a death-to-case ratio of around 5% for patients aged less than 15 years to around 20% for those aged 60 years and older. [7][9]
The mortality rate is 20% to 30% in Brazil since 2005 [10]
A study for 114 hospitalized patients with definite or probable RMSF found the mortality rate was 14%[11]
During 1997-2002, the overall case-fatality rate was 1.4%; the rate peaked in 1998 at 2.9% and declined to 0.7% in 2001 and 2002.[12] Children < 5 years of age had a case-fatality rate (5%) that was significantly greater than the rates for age groups < 60 years of age, except for that for 40-49 years of age. [12]

2-14 days [6]

## Burden of Disease

 Year Cases (per million persons) Reference 1997-2002 2.2 Chapman et al, 2006 2002 3.8 Chapman et al, 2006

Table 1. The average annual Rocky Mountain Spotted Fever incidence from 1997 to 2002[12]

#### Symptomology

Symptoms of Rocky Mountain Spotted Fever include: Fever, Rash (occurs 2-5 days after fever, can be absent in some cases), Headache, Nausea, Vomiting, Abdominal pain (may mimic appendicitis or other causes of acute abdominal pain), Muscle pain, Lack of appetite, Conjunctival injection (red eyes).[6]

A rash usually appears on day 3 of illness, although appearance varies from day 1 in 14% of cases to day 6 or thereafter in 20%.[4] Absence of a rash altogether is reported in 9 to 12% of patients.[13][14][15][16] Initially, the rash consists of lesions 1 to 5 mm in diameter.[17]

In the most severely ill patients, rickettsial vascular damage causes potentially lethal leakage of edema fluid into the interstitial tissues and airspaces.[4] Recently, pneumonitis has been reported in 17% of patients with RMSF before they are treated.[4] Severe respiratory failure ensues in 12%.[4] Pulmonary involvement may result in cough, dyspnea, pulmonary edema, and infiltrates in chest radiographs.[4] In a study of 131 patients, 9 of 10 who required mechanical ventilation died.[14]

Another critical target is the central nervous system.[4] Involvement of the blood vessels in the brain manifests as rickettsial encephalitis, a grave prognostic indicator.[18][13][19][14][20] Clinically recognized encephalitis occurs in 26 to 28% of patients with RMSF, with signs and symptoms including confusion (28%), stupor or delirium (21 to 26%), ataxia (5 to 18%), coma (9 to 10%), and seizures (8%).[4] Coma occurs much more frequently in fatal cases (86%) than in nonfatal cases (6%).[4] As a result of rickettsial infection of blood vessels of the meninges, brain, and spinal cord, the cerebrospinal fluid contains leukocytes usually in the range of 10 to 100 per uL in 34 to 38% of patients and increased protein concentration in 30 to 35% of patients.[21][14]

Patients with severe RMSF are likely to develop acute renal failure, principally because leakage of fluid from the injured blood vessels results in a reduced fluid volume within the blood vessels.[22] Consequently, vascular perfusion of the kidneys is diminished, urine output diminishes, and metabolic wastes such as urea and creatinine accumulate in the blood.[4] In the extreme situation of hypotensive shock, renal blood flow is curtailed so extensively that renal tubular cells undergo necrosis.[22][23] Acute renal failure indicates a poor prognosis, complicates fluid and electrolyte management, and may require dialysis.[4]

The presence of gastrointestinal symptoms in RMSF correlates with infection of blood vessels in the stomach, intestines, pancreas, and liver.[24][25] The occurrence of nausea or vomiting (38 to 56%), abdominal pain (30 to 34%), and diarrhea (9 to 20%) early in the course before the onset of rash may lead to a misdiagnosis of gastroenteritis or acute surgical abdomen.[13][14][26][27][28] Patients with RMSF have undergone exploratory abdominal surgery for suspected appendicitis, acute cholecystitis, and perforated diverticulitis.[26][27][28][29][30][31][32]

## Microbiology

R. rickettsia is a small (0.2 um to 0.5 um by 0.3 um to 2.0 um), obligate, intracellular bacterium [33]

### Route: , Response: morbidity

#### beta-Poisson

$$P(response)=1-[1+dose\frac{2^{\frac{1}{a}}-1}{N^{50}} ]^{-a}$$

a = 7.77E-01
N50 = 2.13E+01
ID50 = 2.13E+01

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