Case 9

History
• A female child aged 7 years from USA was taken to an
emergency department (ED) with 2 days history of fever
(102.7º F [39.3º C]), malaise, abdominal pain, nausea, and
vomiting. Viral gastroenteritis was diagnosed, and the patient
was released.

• Four days later, the patient reported at ED with persistent

fever, anorexia, irritability, photophobia, cough, diffuse
myalgias, nausea, and vomiting.
 Physical examination

• Physical examination revealed hepatosplenomegaly and

an erythematous papular rash with scattered petechiae
on the trunk, arms, legs, palms, and soles.
 Laboratory results

• WBC count of 17.4 x 109 cells/L

• Platelets 19 x 109 platelets/L

• Aspartate aminotransferase (AST) of 279 U/L

• Alanine aminotransferase (ALT) of 77 U/L

 Questions

• Why the patient presented with petechiae?

• Are these laboratory parameters normal?

• List bacterial pathogens that can cause this disease

 Case…
• In the ED, the patient was treated with intravenous (IV) doxycycline

• She had declining mental status, metabolic acidosis, and respiratory

failure; the patient died 6 days after initially seeking treatment.

• IgG antibodies reactive with R. rickettsii at a reciprocal titer of 128

were demonstrated by using an indirect immunofluorescence
antibody (IFA) assay in a serum

• Spotted fever group rickettsiae (SFGR) were detected by

immunohistochemical (IHC) staining in autopsy specimens from the
brain, skin, heart, lung, spleen, and kidney.
 Questions

• How is this disease transmitted?

• What do you think is the cause of the death?

• What additional tests can be done to diagnose

infections?

• Classify Rickettsia spp.

Rickettsia spp., Coxiella spp. and Bartonella spp.

M.M.Mirambo, PhD
Microbiology/Immunology department
Weill Bugando School of Medicine
©2019
At the end of this lecture you should be able to
know/understand:

• Different spp. of Rickettsiae

• Diseases they cause

• Mode of transmission

• Pathogenic mechanisms

• Treatment options

• Epidemiology and control

 Microbiology
▪ Small obligate intracellular organisms

▪ Once thought to be viruses

▪ Structurally similar to Gram negative bacteria

▪ Stained well with Giemsa stain

▪ Cocobacilli, short rods, cocci

 …

▪ Grown in yolk sac of embryonated eggs & culture

▪ Typhus grp in cytoplasm & spotted grp in the nucleus

▪ LPS contains proteins encoded by ompA and ompB

▪ Maintained in animal and arthropod reservoirs

▪ Transmitted by arthropod with the exception of Coxiella

spp.
1. Demacentor variabilis (American dog tick) (left)
2. Demacentor andersoni (American wood tick)(right)
Life cycle of D.variabilis and D.andersoni
3. Rhipicephallus sanguines (brown dog tick)
4. Amblyoma americanum (lone star tick)
 …

▪ Rickettsiae consist of genera Rickettsia, Orientia, Coxiella and

Ehlichia

▪ Rickettsia infect endothelial cells

▪ Lyse the phagosome membrane

▪ Based on their antigenic composition & diseases, the

Rickettsia are divided into several groups

 Pathogenesis and Immunity

• Transmission is through tick bites

• Adherence to the cell wall→ multiply in large

numbers(typhus group)

• Membrane damage (phospholipase D & hemolysin C) →

water influx (spotted fever group)

• ↑ vascular permeability

• Damage to endothelia cells (vasculitis, necrosis, thrombosis)

 Pathogenesis and Immunity
▪ Lesions are prominent on the skin but vasculitis occurs in
different organs

▪ DIC, aggregation of lymphocytes, PMN’s &MØ (typhus nodules)

in the gray matter, heart & other organs

▪ Both humoral and cell mediated immunity are important

▪ Antibody-opsonized rickettsia are phagocytosed and killed by

macrophages

▪ Delayed type hypersensitivity may develops following

Rickettsia infections
 Rocky Mountain spotted fever (RMSF)

• Rickettsia ricketsii is the main etiological agent

• Common in north and Southern America

• Symptoms include fever, headache, abdominal pain,

vomiting, muscle pain

• Rash may develop

• Disease can be fatal if not treated in first few days of

symptoms

• Doxycycline is drug of choice

 Rickettsia prowazekii
Epidemic typhus or louse-borne typhus
• Greek typhos, meaning smoky or lazy, describing the state of
mind of those affected with typhus

• Epidemic typhus has been known since the 16th century

• Transmitted by the human body louse (Pediculus humanus

corporis)

• Inhalation or contact with mucous embranes (mouth &eyes)

Pediculus humanus
 Rickettsia prowazekii…

• Epidemic typhus

• Humans are the primary reservoir for R. prowazekii

• Flying squirrels in USA

• Bacteria are found in the louse feces

• Overcrowding, unsanitary conditions as in wars, famine and

natural disasters.

• Occurs in America, Asia, central and east Africa, central &south

America
 Clinical syndromes
Epidemic typhus :
• Sudden onset of fever, chills, headache myalgia, arthralgia
• Incubation period of 8 days.
• Approximately 7 days later, maculopapular rashes, petechial
hemorrhage
• Rashes from the trunk then to extremities (centrifugal spread)
• Complications : myocarditis
• The mortality rate (60 - 70%) in some epidemics.

Brill-Zinsser disease is recrudescent epidemic typhus.

• It occurs decades after the initial infection.
 Dx
Serology:
• Indirect fluorescent antibody tests and latex
agglutination tests are available.

• Immunohistochemistry (skin scrapping)

• Ab titers usually become detectable during the

second week

• 4 folds rise in ab titters is diagnostic

 Treatment, prevention and control

• Tetracyclines and chloramphenicol

• Louse control measures can prevent infection.

• A killed typhus vaccine is available and is recommended

for use in high-risk populations

 Coxiella burnetii (Q fever)
▪ Q" stands for “query”

▪ Zoonotic (cattle,sheep, goats, dogs, cats etc.)

▪ First described in abbatoir workers

▪ Inhalation & contact with vagina mucous, urine, feces, semen of

infected animals

▪ C. burnetii infects macrophages

▪ Survives and ,multiply in the phagolysosome.

▪ The bacteria are released by lysis of the cells and phagolysosomes.

 Pathogenesis & clinical presentation
• Infection: Inhalation of airborne particles, contacts with
animal products, rarely tick borne.

• Incubation period is 2-3 weeks

• Multiplies in the lungs and is disseminated to other organs.

• Characterized by flu like illness with abrupt onset of fever,

malaise
• Headache, myaglia sometimes GI symptoms

• Pneumonia and granulomatous hepatitis in severe

infections.
• May results into acute respiratory distress syndrome
 Immunity

▪ Immune complexes may play a role in pathogenesis.

▪ Phase variation occurs in the LPS of C. burnetii.

▪ In acute disease, phase II antigen.

▪ In chronic disease , phase I and phase II antigens

▪ Cellular immunity is important

 Epidemiology
• C. burnetii is extremely stable in the environment and has
"spore-like“ structure.

• C. burnetii infects goats sheep cattle and cats.

• The organism is found in the placenta and in the feces of
infected livestock.

• The organisms persist in soil which is a focus for infection.

• C. burnetii is also passed in milk.

• Arthropods are not common vectors in human

• Ticks are a primary vector for transmission among veterinary

species.
 Clinical syndromes

• Mild and asymptomatic.

• Acute or chronic.

Acute Q fever
• Headache fever, chills ,myalgia.
• Respiratory symptoms ("atypical pneumonia").
• Hepatomegaly, splenomegaly, granulomas

Chronic Q fever
• Endocarditis generally on a damaged heart valve.
• Prognosis of chronic Q fever is not good
 Dx & Rx

Dx
• Serology.
• Antibodies to phase II
• Antibodies to both phase I and phase II antigens to
diagnose chronic disease

Treatment, prevention and control

• Tetracycline acute Q fever.
• Vaccine in some countries
 Bartonella

Microbiology
• The Bartonella are small, Gram-negative aerobic bacilli,
difficult to grow in culture media.

• They are found in many different animals.

• Some species are able to infect erythrocytes while others

simply attach to host cells.

• Transmitted by vectors eg. ticks, fleas, mosquitos, sand

flies, lice

• Opportunistic
 B. henselae - (Cat-scratch disease)
• Epidemiology
– Cat-scratch disease is acquired after exposure to cats
(scratches, bites, and possible cat fleas).

• Clinical syndromes
– The disease in usually benign, characterized by chronic
regional lymphadenopathy.

• Laboratory diagnosis
– Serological tests are available
• Treatment
– Gentamicin, ciprofloxacin,
 Recap
• Different spp. of Rickettsiae

• Diseases they cause

• Mode of transmission

• Pathogenic mechanisms

• Treatment options

• Epidemiology and control