Exploring the Intricacies of Rickettsiae: Unraveling the Mysteries of those Intracellular Bacterial Pathogens

Exploring the Intricacies of Rickettsiae: Unraveling the Mysteries of those Intracellular Bacterial Pathogens

 

INTRODUCTION

Rickettsiae are obligate intracellular micro organism; that’s, they will

develop solely inside cells. They’re the brokers of a number of vital

illnesses, specifically typhus, noticed fevers equivalent to Rocky Mountain

noticed fever, Q fever, anaplasmosis, and ehrlichiosis. Different much less

vital rickettsial illnesses equivalent to endemic and scrub typhus

happen primarily in growing nations. Rickettsial pox, brought about

by Rickettsia akari, is a uncommon illness present in sure densely

populated cities in the US.

Extra data relating to the medical points of

infections attributable to the organisms on this chapter is supplied

in Half IX entitled Infectious Ailments starting on web page 589.

RICKETTSIA RICKETTSII &

RICKETTSIA PROWAZEKII

Ailments

Rickettsia rickettsii causes Rocky Mountain noticed fever, a life-

threatening illness that happens primarily within the Southeastern

states, for instance, North Carolina of the US. Rickettsia

prowazekii causes epidemic typhus, additionally a life-threatening

illness that happens primarily in crowded, unsanitary dwelling condi-

tions throughout wartime.

Essential Properties

Rickettsiae are very brief rods which might be barely seen within the gentle

microscope. Structurally, their cell wall resembles that of gram-

damaging rods, however they stain poorly with the usual Gram

stain.

Rickettsiae are obligate intracellular parasites, as a result of

they’re unable to provide adequate vitality to copy

extracellularly. Subsequently, rickettsiae have to be grown in cell

tradition, embryonated eggs, or experimental animals. Rickett-

siae divide by binary fission inside the host cell, in distinction to

chlamydiae, that are additionally obligate intracellular parasites however

replicate by a particular intracellular cycle (see Chapter 25).

A number of rickettsiae, equivalent to R. rickettsii, R. prowazekii, and

Rickettsia tsutsugamushi (renamed Orientia tsutsugamushi),

possess antigens that cross-react with antigens of the OX strains

of Proteus vulgaris. The Weil-Felix check, which detects antirick-

ettsial antibodies in a affected person’s serum by agglutination of the

Proteus organisms, relies on this cross-reaction.

Transmission

Essentially the most hanging side of the life cycle of the rickettsiae is

that they’re maintained in nature in sure arthropods such

as ticks, lice, fleas, and mites and, with one exception, are trans-

mitted to people by the chunk of the arthropod. The rickettsiae

flow into broadly within the bloodstream (bacteremia), infecting pri-

marily the endothelium of the blood vessel partitions.

The exception to arthropod transmission is Coxiella burnetii,

the reason for Q fever, which is transmitted by aerosol and

inhaled into the lungs (see later). Nearly all rickettsial dis-

eases are zoonoses (i.e., they’ve an animal reservoir), with the

outstanding exception of epidemic typhus, which happens solely in

people. It happens solely in people as a result of the causative organ-

ism, R. prowazekii, is transmitted by the human physique louse. A

abstract of the vectors and reservoirs for chosen rickettsial

illnesses is offered in Desk 26–1.

The incidence of the illness is determined by the geographic dis-

tribution of the arthropod vector and on the danger of publicity,

which is enhanced by things like poor hygienic circumstances

and tenting in wooded areas. These components are mentioned later

with the person illnesses.

Pathogenesis

The standard lesion attributable to these rickettsiae is a vasculitis,

notably within the endothelial lining of the vessel wall, the place

the organism is discovered. Injury to the vessels of the pores and skin outcomes

within the attribute rash and in edema and hemorrhage brought about

by elevated capillary permeability. Vasculitis of the vessels in

the mind results in the outstanding headache.

The premise for pathogenesis by these organisms is unclear.

There may be some proof that endotoxin is concerned, which is

in accord with the character of a number of the lesions equivalent to fever,

petechiae, and thrombocytopenia, however its position has not been

confirmed. No exotoxins or cytolytic enzymes have been discovered.

Medical Findings & Epidemiology

Rocky Mountain Noticed Fever

This illness is characterised by the acute onset of nonspecific

signs (e.g., fever, extreme headache, myalgias, and prostration).

The standard rash, which seems 2 to six days later, begins with

macules that regularly progress to petechiae (Determine 26–1).

The rash normally seems first on the arms and toes after which

strikes inward to the trunk. Along with headache, different

profound central nervous system modifications equivalent to delirium

FIGURE 26–1 Rocky Mountain noticed fever. Notice widespread

petechial rash. (Reproduced from MMWR, Analysis and Administration of Tickborne

Rickettsial Ailments: Rocky Mountain Noticed Fever, Ehrlichiosis, and Anaplasmosis–

United States. March 13, 2006/55(RR04);1–27.)

and coma can happen. Disseminated intravascular coagulation,

edema, and circulatory collapse could ensue in extreme circumstances. The

analysis have to be made on medical grounds and remedy began

promptly, as a result of the laboratory analysis is delayed till an increase

in antibody titer might be noticed.

The identify of the illness is deceptive, as a result of it happens

primarily alongside the East Coast of the US (within the

southeastern states of Virginia, North Carolina, and Georgia),

the place the canine tick, Dermacentor variabilis, is situated. The identify

“Rocky Mountain noticed fever” is derived from the area in

which the illness was first discovered. Within the western United States,

it’s transmitted by the wooden tick, Dermacentor andersoni.

The tick is a vital reservoir of R. rickettsii in addition to

the vector; the organism is handed by the transovarian route

from tick to tick, and a lifetime an infection outcomes. Sure

mammals, equivalent to canines and rodents, are additionally reservoirs of the

organism. People are unintended hosts and will not be required for

the perpetuation of the organism in nature; there isn’t a person-

to-person transmission. Most circumstances happen in kids throughout

spring and early summer time, when the ticks are energetic. Rocky

Mountain noticed fever accounts for 95% of the rickettsial dis-

ease in the US; there are about 1000 circumstances per 12 months.

It may be deadly if untreated, however whether it is recognized and handled, a

immediate remedy outcomes.

Typhus

There are a number of types of typhus, specifically, louse-borne epi-

demic typhus attributable to R. prowazekii, flea-borne endemic

typhus attributable to Rickettsia typhi, chigger-borne scrub typhus

attributable to O. tsutsugamushi, and several other different fairly uncommon kinds.

Circumstances of flea-borne endemic typhus, additionally known as murine typhus,

happen in small numbers within the southern areas of California

and Texas. The next description is proscribed to epidemic

typhus, an important of the typhus group of illnesses.

Typhus begins with the sudden onset of chills, fever, headache,

and different influenzalike signs roughly 1 to three weeks

after the louse chunk happens. Between the fifth and ninth days

after the onset of signs, a maculopapular rash begins on

the trunk and spreads peripherally. The rash turns into petechial

and spreads over the whole physique however spares the face, palms, and

soles. Indicators of extreme meningoencephalitis, together with delirium

and coma, start with the rash and proceed into the second and

third weeks. In untreated circumstances, dying happens from peripheral

vascular collapse or from bacterial pneumonia.

Epidemic typhus is transmitted from individual to individual by the

human physique louse, Pediculus. When a bacteremic affected person is bit-

ten, the organism is ingested by the louse and multiplies within the

intestine epithelium. It’s excreted within the feces of the louse throughout the

act of biting the subsequent individual and autoinoculated by the individual

whereas scratching the chunk. The contaminated louse dies after just a few

weeks, and there’s no louse-to-louse transmission; due to this fact,

human an infection is an compulsory stage within the cycle. Epidemic

typhus is related to wars and poverty; at current it’s discovered

in growing nations in Africa and South America however not in

the US.

A recurrent type of epidemic typhus is known as Brill-Zinsser

illness. The indicators and signs are much like these of epi-

demic typhus however are much less extreme, of shorter length, and infrequently

deadly. Recurrences can seem so long as 50 years later and might be

precipitated by one other intercurrent illness. In the US,

the illness is seen in older individuals who had epidemic typhus

throughout World Battle II in Europe. Brill-Zinsser illness is epide-

miologically attention-grabbing; persistently contaminated sufferers can serve

as a supply of the organism ought to a louse chunk happen.

Laboratory Analysis

Laboratory analysis of rickettsial illnesses relies on serologic

evaluation relatively than isolation of the organism. Though rickett-

siae might be grown in cell tradition or embryonated eggs, it is a

hazardous process that’s not accessible in the usual medical

laboratory.

Of the serologic exams, the oblique immunofluorescence and

enzyme-linked immunosorbent assay (ELISA) exams are most

usually used. The Weil-Felix check is of historic curiosity however isn’t any

longer carried out as a result of its specificity and sensitivity are too

low. The premise of the Weil-Felix check is described later.

A fourfold or higher rise in titer between the acute and

convalescent serum samples is the most typical approach the

laboratory analysis is made. That is normally a retrospective

analysis, as a result of the convalescent pattern is obtained 2 weeks

after the acute pattern. If the medical image is typical, a single

acute-phase titer of 1:128 or higher is accepted as presumptive

proof. If the check is offered, a analysis might be made throughout

the acute part of the illness by immunofluorescence assay on

tissue obtained from the location of the petechial rash.

The Weil-Felix check relies on the cross-reaction of an

antigen current in lots of rickettsiae with the O antigen poly-

saccharide present in P. vulgaris OX-2, OX-19, and OX-Ok. The

check measures the presence of antirickettsial antibodies within the

affected person’s serum by their capability to agglutinate Proteus micro organism.

The particular rickettsial organism might be recognized by the agglu-

tination noticed with one or one other of those three completely different

strains of P. vulgaris. Nevertheless, as talked about, this check isn’t any

longer utilized in the US.

Therapy

The remedy of alternative for all rickettsial illnesses is doxycycline.

Prevention

Prevention of many of those illnesses relies on decreasing expo-

certain to the arthropod vector by sporting protecting clothes and

utilizing insect repellent. Frequent examination of the pores and skin for ticks

is vital in stopping Rocky Mountain noticed fever; the

tick have to be connected for a number of hours to transmit the illness.

There is no such thing as a vaccine towards Rocky Mountain noticed fever. Professional-

phylactic antibiotics will not be really useful within the asymptomatic

individual bitten by a tick.

Prevention of typhus relies on private hygiene and

“delousing” with DDT. A typhus vaccine containing formalin-

killed R. prowazekii organisms is efficient and helpful within the

navy throughout wartime however shouldn’t be accessible to civilians within the

United States.

COXIELLA BURNETII

Illness

Coxiella burnetii causes Q fever. Q stands for “Question”; the trigger

of this illness was a query mark (i.e., was unknown) when

the illness was first described in Australia in 1937.

Essential Properties

Coxiella burnetii has a sporelike stage that’s extremely immune to

drying, which boosts its capability to trigger an infection. It additionally has

a really low ID50, estimated to be roughly one organism.

Coxiella burnetii exists in two phases that differ of their anti-

genicity and their virulence: part I organisms are remoted from

the affected person, are virulent, and synthesize sure floor antigens,

whereas part II organisms are produced by repeated passage in

tradition, are nonvirulent, and have misplaced the flexibility to synthesize

sure floor antigens. The medical significance of part varia-

tion is that sufferers with persistent Q fever have a a lot greater

antibody titer to part I antigens than these with acute Q fever.

Transmission

Coxiella burnetii, the reason for Q fever, is transmitted by aerosol

and inhaled into the lungs. Q fever is the one rickettsial illness

that’s not transmitted to people by the chunk of an arthropod.

The vital reservoirs for human an infection are cattle, sheep,

and goats. Coxiella burnetii causes an inapparent an infection in

these reservoir hosts and is present in excessive concentrations within the

urine, feces, placental tissue, and amniotic fluid of the animals.

It’s transmitted to people by inhalation of aerosols of those

supplies.

Medical Findings & Epidemiology

Not like different rickettsial illnesses, the principle organ concerned in

Q fever is the lungs. It begins immediately with fever, extreme head-

ache, cough, and different influenzalike signs. That is all that

happens in lots of sufferers, however pneumonia ensues in about half.

Hepatitis is frequent sufficient that the mix of pneumo-

nia and hepatitis ought to recommend Q fever. A rash is uncommon, in contrast to

in many of the different rickettsial illnesses. Normally, Q fever is an

acute illness, and restoration is anticipated even within the absence of

antibiotic remedy. Not often, persistent Q fever characterised by life-

threatening endocarditis happens.

The illness happens worldwide, mainly in people whose

occupations expose them to livestock, equivalent to shepherds, abat-

toir staff, and farm employees. Ingestion of cow’s milk is

normally liable for subclinical infections relatively than illness

in people. Pasteurization of milk kills the organism.

Laboratory Analysis

Serologic exams, such because the oblique immunofluorescence assay,

are used relatively than isolation of the organism. Coxiella burnetii

might be grown in cell tradition or embryonated eggs, however it is a

hazardous process that’s not accessible in the usual clini-

cal laboratory.

Therapy

The remedy of alternative is doxycycline.

Prevention

Individuals at excessive threat of contracting Q fever, equivalent to veterinar-

ians, shepherds, abattoir employees, and laboratory personnel

uncovered to C. burnetii, ought to obtain the vaccine that consists

of the killed organism. Pasteurization of milk kills C. burnetii.

ANAPLASMA PHAGOCYTOPHILUM

Anaplasma phagocytophilum is a member of the Rickettsia

household that causes human granulocytic anaplasmosis (HGA).

Illness is endemic in northeastern and north central states

(e.g., Connecticut and Wisconsin). Distribution is much like

that of Lyme illness. Ixodes ticks are the principle vectors. Rodents

and canines are vital reservoirs. In HGA, granulocytes relatively

than mononuclear cells are contaminated, however the illness is clini-

cally indistinguishable from that attributable to Ehrlichia chaffeensis

(see later). The organism kinds an inclusion physique known as a

morula within the cytoplasm of contaminated cells. The morula, which

is formed like a mulberry, is indistinguishable from that shaped

by Ehrlichia. The analysis is made serologically by detecting

an increase in antibody titer. Doxycycline is the remedy of alternative.

This organism was previously referred to as Ehrlichia equi, and the

illness it brought about was previously referred to as human granulocytic

ehrlichiosis (HGE).

EHRLICHIA CHAFFEENSIS

Ehrlichia chaffeensis is a member of the Rickettsia household and

causes human monocytic ehrlichiosis (HME). This illness

resembles Rocky Mountain noticed fever, besides that the standard

rash normally doesn’t happen. Excessive fever, extreme headache, and

myalgias are outstanding signs. The organism is endemic in

canines and is transmitted to people by ticks, particularly the canine

tick, Dermacentor, and the Lone Star tick, Amblyomma. Ticks of

the genus Ixodes are additionally vectors. Ehrlichia chaffeensis primar-

ily infects mononuclear leukocytes and kinds attribute

morulae within the cytoplasm. (A morula is an inclusion physique that

resembles a mulberry. It consists of many E. chaffeensis cells.)

Lymphopenia, thrombocytopenia, and elevated liver enzyme

values are seen. In the US, the illness happens primar-

ily within the southern states, particularly Arkansas. The analysis is

normally made serologically by detecting an increase in antibody titer.

Doxycycline is the remedy of alternative.

SELF-ASSESSMENT QUESTIONS

1. Your affected person is a 40-year-old lady with the sudden onset of

fever to 40°C, extreme headache, and petechial rash over most of

her physique together with the palms. Blood cultures are damaging. Unfor-

tunately, regardless of antibiotics and different assist, she dies the day

after presentation. An post-mortem is carried out, and immunohisto-

chemical exams on her mind tissue reveal an an infection by Rickettsia

rickettsii. Of the next, which one is essentially the most correct?

(A) It’s possible she lives in Colorado and was bitten by a tick.

(B) It’s possible she lives in Colorado and was bitten by a mosquito.

(C) It’s possible she lives in Virginia and was bitten by a tick.

(D) It’s possible she lives in Virginia and was bitten by a flea.

(E) It’s possible she lives in Connecticut and was bitten by a mosquito.

2. Concerning Q fever, which one of many following is most correct?

(A) The causative organism is transmitted by tick chunk.

(B) The pure habitat of the causative agent is the white-footed

mouse.

(C) The analysis is made primarily by Gram stain and tradition on

chocolate agar.

(D) Occupations that predispose individuals to Q fever embrace veteri-

narians and abattoir employees.

(E) Sufferers with Q fever usually have a petechial rash involving the

palms.

ANSWERS

(1) (C)

(2) (D)

SUMMARIES OF ORGANISMS

Temporary summaries of the organisms described on this chapter

start on web page 653. Please seek the advice of these summaries for a fast

evaluation of the important materials.

PRACTICE QUESTIONS: USMLE &

COURSE EXAMINATIONS

Questions on the matters mentioned on this chapter might be discovered

within the Medical Bacteriology part of Half XIII: USMLE

(Nationwide Board) Observe Questions beginning on web page 715. Additionally

see Half XIV: USMLE (Nationwide Board) Observe Examination