RICKETTSIAL INFECTION: DIVERSITIES, DILEMMA AND CHALLENGES

RICKETTSIAL INFECTION:
DIVERSITIES, DILEMMA AND
CHALLENGES
Dr. Moniruzzaman Ahmed
Associate Professor, Dept of Medicine
MAG Osmani Medical College, Sylhet
Email: dr_zaman01217@yahoo.com

Rickettsial diseases - 4 distinct genera:
•Rickettsia, Orientia, Ehrlichia (Ehrlichia
chaffeensis, the agent of human
monocytic ecrlichiosis) and Anaplasma
(Anaplasma phagocytophilium, the
agent of human granulocytic
anaplasmosis)
•Diseases caused by Rickettsia and
Orientia species often reffered to as
rickettsioses
•Coxiella burnetii, the agent of Q fever
and Bartonella spp. were recently
removed from the order Rickettsiales
Parola P, Paddock CD, Raoult D. Tick-borne rickettsioses around the world: emerging diseases challenging old
concepts. Clin Microbiol Rev. 2005;18:719–56

RICKETTSIAL SPECIES-BIOVARS
SPOTTED FEVER GROUP RICKETTSIOSES (SFGR)
/ TICK BORN RICKETTSIAL DISEASE (TBRD)
TYPHUS GROUP (TG)
SCRUB TYPHUS GROUP

RICKETTSIA- BIOLOGY
• Small obligate intracellular parasites
• Gram-negative bacteria
• Stain poorly with Gram stain
(Giemsa)
• “Energy parasites” but not obligate,
have capacity to make ATP
• Parasite of arthropods – fleas, lice,
ticks and mites
• Reservoirs - animals, insects and
humans

From 1906 to 1910, Howard T Ricketts
isolated the pathogen and showed that
it circulated among ticks and mammals
in the wild. Tragically, this talented
rickettsiologist was affected by
epidemic typhus and died in 1910, at
the age of 39 years.
The genus Rickettsia is named after
Howard Taylor Ricketts (1871–1910),
who studied Rocky Mountain spotted
fever in the Bitterroot Valley

TRANSMISSION, PATHOGENESIS &
PATHOPHYSIOLOGY

SPOTTED FEVER GROUP RICKETTSIOSES
(SFGR)/ TICK BORN RICKETTSIAL
DISEASE(TBRD)

PROTYPICAL DISEASES
ORGANISM DISEASE DISTRIBUTION
R.Rickettsii Rocky Mountain spotted fever Western hemisphere
R. akari Rickettsialpox USA, former Soviet Union
R. conorii Boutonneuse fever, Kenya
tick typhus, Israeli tick
typhus, Mediterranean spotted
fever(MSF), Indian tick
typhus, Astrakhan tick typhus,
Marseilles fever
Mediterranean countries,
Africa, India, Southwest Asia
R. sibirica Siberian tick typhus Siberia, Mongolia, northern
China
R. australia Australian tick typhus Australia
R. japonica Oriental spotted fever Japan
(SFGR)/(TBRD)

GEOGRAPHICAL DISTRIBUTION
Update on Tick-Borne Rickettsioses around the World: a Geographic
Approach
Philippe Parola,a Christopher D. Paddock,b Cristina Socolovschi,a Marcelo B. Labruna,c Oleg Mediannikov,a Tahar Kernif,d
Mohammad Yazid Abdad,e* John Stenos,e Idir Bitam,f Pierre-Edouard Fournier,a Didier Raoulta
October 2013 Volume 26 Number 4 Clinical Microbiology Reviews p. 657–702

GEOGRAPHICAL DISTRIBUTION (South
America)
Approach

Approach
(EUROPE)

Approach

GEOGRAPHIC DISTRIBUTION
Geographic and temporal distribution of
rickettsioses is largely determined by their vectors
“One continent, one pathogenic tick-born
rickettsia” an anachronism
Prevalent throughout the world except Antarctica

Summary of prevalent Rickettsiae in Southeast
Asia,their reservoirs and vectors for disease
transmission
Rickettsiae Main reservoirs Main vectors
Typhus group
Murine typhus (R.typhi)
Rats(Rattus rattus, Rattus
norvegicus, other Rattus sp.)
Xenopsylla cheopis
Scrub typhus (O. tsutsugamushi) Rats (Rattus sp. and Bandicota sp.) Trombiculid mites (Larval stage )
Spotted fever group
R.Honei
Rats ( Rattus sp. And Bandicota
indica.)
Ixodes granulatus, Ixodes sp.,
Rhipicephalus sp.
R. felis Rats(Rattus sp) and shrews (Suncus
murinus)
Domestic cats, dogs, cows and pigs.
Ctenocephalides orientis, C. felis
felis, X. cheopis
R. Conorii subsp. indica Rats ( Rattus sp.) R. sanguineus
R. helvetica Unknown Ixodes spp
R. japonica Rats ( Rattus sp. And B. indica.) Various species of animal ticks.
Am. J. Trop. Med. Hyg., 91(3), 2014, pp. 451–460
Review Article: Rickettsial Infections in Southeast Asia: Implications for Local Populace
and Febrile Returned Travelers
Ar Kar Aung,* Denis W. Spelman, Ronan J. Murray, and Stephen Graves

Short Report: Serosurveillance of Orientia
tsutsugamushi and Rickettsia typhi in Bangladesh
Short Report: Serosurveillance of Orientia tsutsugamushi and Rickettsia typhi in Bangladesh
Rapeephan R. Maude,* Richard J. Maude, Aniruddha Ghose, M. Robed Amin, M. Belalul Islam, Mohammad Ali, M. Shafiqul Bari,
M. Ishaque Majumder, Ampai Tanganuchitcharnchai, Arjen M. Dondorp, Daniel H. Paris, Robin L. Bailey, M. Abul Faiz, Stuart D.
Blacksell, and Nicholas P. J. Day
Am. J. Trop. Med. Hyg., 91(3), 2014, pp. 580–583

A total of 155 clinically suspected
febrile patients were enrolled in
the study. Out of them, 136
(88%), 31 (23%) and 61 (43%)
were positive by Weil-Felix test,
ELISA and PCR respectively.
Out of the 61 PCR positive
products, 16 were sequenced in
Sapporo Medical University,
Japan where 13 were found to be
99.9% consistent with Rickettsia
felis.
An ongoing study in
Mymensingh Medical
College
A case series of 40
rickettsial infection in
MMCH found 60%
positive for scrub
typhus by using Weil-
Felix test
(Miah MT, Rahman S, Sarker
CN, Khan GK, Barman TK,
2007. Study on 40 cases of
Rickettsia. Mymensingh Med J
16: 85–88)

Association of tick genera and rickettsial species

CLINICAL MANIFESTATIONS
•Clinical symptoms of tick-borne SFG rickettsioses begin 4 to 10
days after a bite and typically include fever, headache, muscle
pain, rash, local lymphadenopathy, and, for most of these
diseases, a characteristic inoculation eschar at the bite site
•Life-threatening manifestations : prolonged fever, renal failure,
myocarditis, meningoencephalitis, hypotension, ARDS, multiple
organ failure

A crusty necrotic lesion with or without a surrounding
erythematous halo which suggests the location of the vector bite
ESCHAR (TACHE NOIRE)

LAR
Lymphangitis may be present
in several rickettsioses
Half of the cases of R. sibirica
subsp. mongolitimonae
infection present this sign
(rope-like lymphangitis
between the inoculation
eschar and lymphadenitis) the
infection being termed
lymphangitis-associated rick-
ettsiosis (LAR)
also present in infections
caused by R.
heilongjiangensis and R.
africae

DEBONEL / TIBOLA /SENLAT
Two dominant signs characterize
this syndrome: an inoculation eschar
and regional lymphadenopathy
The occurrence of fever and rash
is rare.
DEBONEL/TIBOLA (Dermacentor-
borne necrosis erythema
lymphadenopathy/tick-borne
lymphadenopathy), also called
SENLAT (scalp eschar and neck
lymphadenopathy after tick bite)
when the tick bite affects only the
scalp
Produced by different species of
Rickettsia. The main etiological
agent is Rickettsia slovaca

HISTORY AND HISTORICAL IMPACT OF TYPHUS
Europian history has been affected by Typhus epidemics from the the 15th through the 20th centuries, Pediculus humanus corporis
as having a more profound effect on human history than any other animal
Rickettsia prowazeki is isolated and identified by Da Rocha-Lima in 1916. Named in honor of H. T. Ricketts and L. von Prowazek,
both of whom contracted typhus in the course of their investigations and died
In 1829, the French clinician Louis clearly differentiated Typhus Fever from Typhoid Fever (Wolback et al., 1922)
Transmission of Epidemic Typhus by the body louse was first demonstrated experimentally by Nicolle and others (1909)
Early History. The first pestilence attributed to louse-borne typhus was the Athenian Plague of 430 B.C.
The Fifteen Century. An epidemic of louse-borne typhus struck the besieging army of Spanish and within a month had killed 17,000
of the original 25,000 soldiers.
The Sixteen Century. Western civilizations at that time regarded their God as a somewhat capricious tyrant, who either gave life or
took it. Having no recourse to medicine as a means of explaining their devastations, medieval man turned to spiritual and
metaphysical sources.
A number of so-called "Assize Epidemics" occurred in England at this time, most notably at Oxford in 1577 and Exeter in 1589. The
Oxford epidemic was of such import that the University there was closed for 30 years afterward.
The Seventeenth Century. In the Thirty Years War of 1618-1648 along with Plague and starvation, typhus was responsible for the
loss of 10,000,000 people in which only 350,000 men died in combat .
The Eighteenth Century. The 18th century was marred by many small epidemics of typhus
The Nineteenth Century. Napoleon Bonaparte's campaign against the Russians in 1812 Napoleon had organized his "Grande
Armee", numbering 600,000 well-seasoned troops -Only 90,000 French soldiers reached Moscow out of the original army of
600,000. The great majority, possibly as high as 300,000, had died of Epidemic Typhus and dysentery.
Epidemic Typhus had helped defeat Napoleon and end his dreams of a French-ruled world.
Typhus was endemic in Russia with some 82,000 cases a year recorded before 1914
‘Either socialism will defeat the louse’, ‘or the louse will defeat socialism’; ‘All attention to this problem comrades!’ Lenin observed
The Twentieth Century. Nicolle's proof of the transmission of typhus by body lice in 1910
Insurance Company as saying that as many as twenty-five million cases of typhus occurred during the years 1918-1922 with
upwards of three million deaths.
To dehumanise the Jews the Nazi Propaganda Minister Joseph Goebbels declared: ‘These are no longer people…The task is not
humanitarian but surgical. Steps have to be taken here, and really radical ones tool. Otherwise Europe will perish from the Jewish
disease.’

HISTORY AND HISTORICAL IMPACT OF
TYPHUS
Rickettsia prowazeki is isolated and identified by Da Rocha-
Lima in 1916. Named in honor of H. T. Ricketts and L. von
Prowazek, both of whom contracted typhus in the course of their
investigations and died
In 1829, the French clinician Louis clearly differentiated Typhus
Fever from Typhoid Fever (Wolback et al., 1922)
Transmission of Epidemic Typhus by the body louse was first
demonstrated experimentally by Nicolle and others (1909). Nicolle
received the Nobel Prize for his work on typhus in 1928.

Henrique da Rocha Lima and Stanislas von
Prowazeck

HISTORY AND HISTORICAL IMPACT OF
TYPHUS
15th
-19th
century Epidemics in Europe as a result of war,
disaster, or in prisoners
The Sixteen Century The Oxford was closed for 30 years
The Seventeenth Century. In the Thirty Years War of 1618-
1648 along with Plague and starvation, typhus was responsible for
the loss of 10,000,000 people in which only 350,000 men died in
combat
The Nineteenth Century. Only 90,000 French soldiers reached
Moscow out of the original army of 600,000. Epidemic Typhus had
helped defeat Napoleon and end his dreams of a French-ruled
world

HISTORY AND HISTORICAL
IMPACT OF TYPHUS
‘Either socialism will defeat the louse’, ‘or the louse will
defeat socialism’; ‘All attention to this problem
comrades!’ Lenin observed
To dehumanise the Jews the Nazi Propaganda
Minister Joseph Goebbels declared: ‘These are no
longer Steps have to be taken here, and really radical
ones tool. Otherwise Europe will perish from the Jewish
disease.’
End of WWII, DDT for control
Discovery of Tetracycline and Chloramphenicol in late

In German soilders had to show
delousing certificates when on leave

Neither the queens nor the kings,
the lice shaped the history of
Europe

TYPHUS
Disease
Group
Disease Agent Vector Animal
Reservoir
Geographical
Distribution
Typhus
Group
Epidemic
Typhus
Sylvatic
typhus
R.
prowazekii
Human
body
louse
Flea
Humans,
Fleas,
flying
squirells
Mountainous regions
of Africa, Asia, and
Central, north and
South America.
Murine
typhus
R. typhi Rat flea
(Xenops
ylla
cheopis)
Rats, cat,
mice
Tropical and
subtropical areas
Worldwide

EPIDEMIC TYPHUS
• Incubation period approximately 1 week
• Sudden onset of fever, chills, headache
and myalgia
• Rash after one week
– Maculopapular progressing to
petechial or hemorrhagic
– First on trunk and spreads to
extremities (centrifugal spread)
• Complications
– Myocarditis, stupor, delirium (Greek
“typhos” = smoke)
• Recovery may take months, debilitating
• Mortality rate can be high (60-70%) but
this may be because of the situation,
such as famine
Brill-Zinsser
Disease
• The rickettsia can remain latent and
reactivate months or years later, with
symptoms similar to or even identical
to the original attack of typhus,
including a maculopapular rash
• Mild illness and low mortality rate.
• Rash is rare

Rickettsia typhi - Murine or endemic typhus
• Occurs worldwide
• Vector - rat flea
– Bacteria in feces
• Reservoir - rats
– No transovarian
transmission
– Normal cycle - rat to flea to
rat
• Humans accidentally infected
• Incubation period 1 - 2 weeks
• Sudden onset of fever, chills,
headache and myalgia
• Rash in most cases begins on
trunk and spreads to
extremities (centrifugal spread)
• Mild disease - resolves even if
untreated

SCRUB TYPHUS GROUP
Antigenic
group
Disease Species Vector Animal
reservoir
Geographic
distribution
Scrub typhus Scrub typhus Orientiatsutsu
gamushi
Larval
mite(chigger)
Rodents Asia-Pacific
region from
maritime Russia
and China to
Indonesia and
North Australia to
Afghanistan
Scrub typhus Scrub Typhus Orientia chuta Unknown Unknown Dubai

Isolation of a Novel Orientia Species (O. chuto sp. nov.)
from a Patient Infected in Dubai
Leonard Izzard,1,2 Andrew Fuller,3 Stuart D. Blacksell,4,5 Daniel H. Paris,4,5 Allen L.
Richards,4,6,7
Nuntipa Aukkanit,4,5 Chelsea Nguyen,1 Ju Jiang,6 Stan Fenwick,2 Nicholas P. J. Day,4
Stephen Graves,1 and John Stenos1,2*
JOURNAL OF CLINICAL MICROBIOLOGY, Dec. 2010, p. 4404–4409 Vol. 48, No. 12

Scrub typhus
 Orientia tsutsugamushi is the causative agent & transmitted to
humans through the bite of thrombiculid mites.
 The chigger (larval) phase is the only stage that is parasitic on
animals or humans.
 First described in china 318 AD, isolated in Japan in 1930
 Disease of rural villages and suburban areas.
 Term scrub is used because of the vegetation (terrain between
woods and clearing) that harbours the vector.
 Scrub typhus is endemic in tsutsugamushi triangle which extends
from northern Japan, far eastern Russia in the north to the
Northern Australia in the south and pakistan in the west.
 Estimated 1 billion people are at risk of scrub typhus and
estimated 1 million cases occur annually.

TSUTSUGAMUSHI TRIANGLE
TSUTSUGAMUSHI TRIANGLE

Clinical features-Scrub typhus
 Incubation period - 1 to 3 weeks
 Sudden onset of fever, chills, headache and myalgia
 Maculopapular rash (spots and bumps)
 Begins on trunk and spreads to extremities (centrifugal spread)
 Commonest symptom high grade fever ,headache muscle pain
,cough, and GI symptoms
 Severe disease in 2ND
week.
Meningitis , meningo-encephalitis , deafness, pneumonia, ARDS,
MODS & myocarditis.
Reinfection & Relapses are seen due to variable immunity to
different strains
 Mortality rates variable (1-15%)

SYNDROMIC CLASSIFICATION OF
RICKETTSIOSES
Syndromic classification of rickettsioses: an approach for clinical
Practice´l
varo A. Faccini-Marti´nez a, Lara Garci´a-A´ lvarez b, Marylin Hidalgo a, Jose´ A. Oteo b,*
International Journal of Infectious Diseases 28 (2014) e126–e139

SYNDROMIC CLASSIFICATION OF
RICKETTSIOSES
Practice´
lvaro A. Faccini-Marti´nez a, Lara Garci´a-A´ lvarez b, Marylin Hidalgo a, JoseInfectious Diseases 28 (2014) e126–e139

Laboratory Diagnosis
• Serologic assays (eg, indirect immunofluorescence,
complement fixation, indirect hemagglutination, latex
fixation, enzyme immunoassay, microagglutination) are
preferable to the nonspecific and insensitive Weil-Felix
test based on the cross-reactive antigens of Proteus
vulgaris strains
• Immunofluorescence assay (IFA) is currently considered
to be the reference serological method.

• Polymerase chain reaction (PCR) to detect rickettsiae in
blood or tissue provides promise for early diagnosis.
PCR testing and immunohistochemical staining of skin
specimen obtained by performing a biopsy may help
confirm the clinical diagnosis in patients with rash.
• The swabs of eschars may be used for molecular
detection of rickettsial infections when biopsies are
difficult to perform.

A thorough history and knowledge of the distribution
of rickettsial agents and their vectors
evidence of exposure to vector
clinical features like fever, rash, eschar, headache
and myalgia
high index of suspicion are crucial factors
DIAGNOSIS

TREATMENT
Antibiotic Indication Dosage Treatment
Doxycycline (standard
treatment of
rickettsosis)
Severe rickettsioses
(including pregnant
women and children)
Ideally intravenous
Adults or
children>45kg
Adults or children>45kg;100 mg twice a day
pregnant women(last trimester):100 mg twice a
day
Children<45kg;22 mg twice a day
Continued for 3 days
after symptoms has
resolved
Macrolides(josamycin,
clarythromycin and
azithrothromycin
Option for not severe
rickettsioses in
children and pregnant
women
Josamycin:children 50 mg/kg twice a day,
pregnant women 1g/8hrly
Clarithromycin for children :15mg/kg twice a
day
Josamycin 5 days
Clarithromycin 7
days and
Azithromycin 3 days
Chloramphenicol Alternative option in
severe rickettsioses
Azithromycin in children :10 mg /kg/day in 1
dose
Adults and pregnant (first and second
trimester); 60-75 mg/kg in4 divided doses
Children12-25 mg/kg every 6 hourly
5-10 days
Practice´
lvaro A. Faccini-Marti´nez a, Lara Garci´a-A´ lvarez b, Marylin Hidalgo a, JoseInfectious Diseases 28 (2014) e126–e139

But however secure and well-
regulated civilized life may
become; bacteria, protozoa,
viruses, infected fleas, lice,
ticks, mosquitoes, and bedbugs
will always lurk in the shadows
ready to pounce when neglect,
poverty, famine, or war lets
down the defenses.
Hans Zinsser
Rats, Lice and History (1934), 13-4.

RICKETTSIAL INFECTION: DIVERSITIES, DILEMMA AND CHALLENGES

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