Bloodstream: Rickettsia, Brucella, spirochaetes, babesiosis Flashcards
Properties of rickettsia
Gram negative coccobacilli Obligate intracellular Arthropod transmitting Endothelial cell parasites Characterised by fever, rash, vasculitis
Former member of rickettsia which is not an obligate intracellular parasite
Bartonella
Can be grown in freshly prepared chocolate agar
Others are not cultivable
Former members of rickettsia and rickettsia like species which are not arthropod transmitted
Coxiella
Bartonella henselae
Neo rickettsia sennetsiu
Members of rickettsia which do not localise in endothelial cells
Ehrlichia
Anaplasma
The general properties of rickettsia infections are not seen in
Q fever - rash is absent Features referred are: Fever Rash Vasculitis
Stains for rickettsia
Giemsa Giminez Castaneda Machiavello Stains basophillic bodies
Rickettsia are grown in
- Lab animal - Guinea pig
- Yolk sac of hen’s egg
- Cell lines: HeLa, Hep 2
Antigens of rickettsia
- OMP antigen:
• species specific, highly immunogenic
• can be used for vaccine and serodiagnosis - LMP antigen:
• group specific
• shared by certain strains of Proteus ➡️ Weil Felix test
Pathogenesis of rickettsial infections
- Transmission to humans by tick or mite
- Spread though lymphatics, multiply in lymph nodes and spread via bloodstream
- Attack endothelial cells
- Phagocytosis of organisms
- Intercellular survival
- Cell to cell spread
Epidemic typhus (louse-borne)
Caused by R. prowazekii
Vector: human body louse
Pediculus humanus corporis
Acute febrile disease accompanied by head ache, myalgia, eye discharge and rashes
occurring after an incubation period of 1-2 weeks.
Clinical manifestations of epidemic typhus (louse borne)
1. Rashes: Beginning on upper trunk on 5th day, then generalised Except face, palms and soles 2. Myalgia 3. Complications like: • interstitial pneumonitis • mental confusion and coma
Risk factors and endemic areas for epidemic typhus (louse-borne)
Zoonotic cycle
Where high louse population is present- unhygienic
Refugee camps, prisons, overcrowded communities
Endemic to Africa and South America
Eastern flying squirrels and their lice maintain R. prowazekii in environment
Brill-Zinsser disease
It is occurs years after acute epidemic typhus
R. prowazekii remains latent for years
Its reactivation occurs due to waning immunity, leads to sporadic infections or outbreaks
Endemic (murine or flea-borne) typhus
By R. typhi
Vector: rat flea Xenopsylla cheopsis
Rarely cat flea - Ctenocephalides felis
Common symptoms: fever, head ache, myalgia, anorexia, rashes of trunk
Symptoms similar to epidemic typhus but milder and rarely fatal
Incubation period: 1-2 weeks
Rocky Mountain Spotted fever RMSF
By Rickettsia rickettsii though the bite of Dermacentor (US) or Amblyomma (S America)
Ticks serve as vector as well as reservoir
Most fatal rickettsial disease with incubation period 4-14 days
In the Americas
More common during summer and children and men
Rocky Mountain Spotted fever RMSF clinical manifestations and complications
- Fever, headache, myalgia
- Rashes appear on extremities and trunk. Initially maculopapular later hemorrhagic
Complications: - Vascular damage, increased permeability, oedema
- Haemorrhage, disseminated intravascular coagulation
- Interstitial pneumonitis
Indian tick typhus presents similarly
Indian tick typhus
By R. conorii though tick bite Rhipicephalus sanguineus
Manifests similar to Rocky Mountain Spotted fever RMSF
Eschar is seen in 50% of cases
Disease is more severe in patients with DM, alcoholism or heart failure
Rickettsialpox
By R. akari though bite of infected mites (Liponyssoides sanguineus)
Clinically similar to other rickettsial diseases, except for:
1. Vesicular rashes (pox)
2. Eschar at bite site
3. Regional lymphadenopathy
Weil Felix test
Heterophile tube agglutination test based on antigenic cross reactivity
Less sensitivity and specificity
Alkali-stable LPS antigens of stone rickettsia are shared by Proteus
Should be done after 5-7 days
Specific antibody tests for rickettsia
- Indirect immunofluorescence assay:
• Gold standard test and reference serological test
• Antibodies appear only after 7-10 days
• Titre more than 1:64 - significant - IgM capture ELISA:
• useful in early diagnosis with good sensitivity and specificity
Non-serological tests for rickettsia
- Histological examination of rash lesion
- Isolation by cell lines
- Neil-Mooser reaction using pigs
- Molecular tests
Prevention of rickettsiosis
- Vector control measures
- Control of rodents and other animals
- Improvement of personal hygiene
No vaccine available
Neil Mooser reaction
Animal pathogenicity testing performed using Guinea pigs to separate various rickettsial species
Scrub typhus/ Chiggerosis
By Orientia tsutsugamushi though bite of mite Leptotrombidium.
The larva of mite - chigger feeds on humans
Transovarian transmission present
Classical symptoms (45%):
1. Eschar
2. Regional lymphadenopathy
3. Maculopapular rash
Non-specific early symptoms: fever, head ache, myalgia, cough and GIT symptoms
Doxycycline - DoC
Ehrlichiosis
Caused by Ehrlichia, Anaplasma and Neorickettsia through ticks usually Clinical manifestations: 1. Headache, myalgia, arthralgia 2. Cough , pharyngitis 3. Lymphadenopathy 4. Diarrhoea, nausea, abdominal pain 5. Mental status affected DoC doxycycline
Inclusions of Ehrlichiosis
They reside in phagosome, multiply to produce three stages of growth:
- Elementary body
- Initial body
- Morula
Q fever
Coxiella burnetii an obligate pleomorphic intracellular coccobacili, zoonotic Incubation period: 3-30 days Manifests as acute or chronic Q fever Diagnosis: IFA, PCR, culture Vaccine present - inactivated Q-Vax
Acute and chronic Q fever
Acute Q fever: Presents as interstitial pneumonia, hepatitis, fever, CNS involvement, pericarditis or myocarditis Doxycycline DoC Chronic Q fever: Months to years later Endocarditis Hydroxychloroquine in addition
Bartonellosis
Fastidious facultative intracellular gram negative bacteria which can invade mammalian cells and RBCs
- B. henselae - by cat
- B. quintana - by louse
- B. bacilliformis - by sandfly
Cat scratch disease
🐈
By Bartonella henselae by cats through bite or scratch (like bacillary angiomatosis)
Typical features:
1. Regional lymphadenopathy - Azithromycin
2. Painless papule at the site of cat scratch
Atypical features are hepatitis, splenetis, retinitis.
Bacillary angiomatosis
By Bartonella henselae by cats or B. quintana by louse
Angioproliferative disorder
Neurovascular lesions involving skin and other organs
Rx: erythromycin or doxycycline for 3 months
Bacillary peliosis
By Bartonella henselae by cats through bite or scratch (like cat scratch disease 🐈)
Angioproliferative disorder involving liver and spleen
Trench fever
By Batonella quintana by louse
Mild febrile illness lasting for 5 days (5-day fever)
Epidemic in trenches during WW-1
Carrion’s disease or Oroya fever
Verruga peruana
By Bartonella bacilliformis by sandfly Produces a biphasic disease: 1. Carrion’s disease or Oroya fever: Initial bacteremic systemic illness 2. Verruga peruana: Late manifestation of cutaneous vascular lesions
Brucella and brucellosis
Obligate aerobic fastidious small gram negative coccobacilli responsible for highly contagious febrile illness called brucellosis which is mainly a zoonotic disease affecting humans with occupational exposure to domestic animals and their products
They are catalase and oxidase positive
Nomen system of classification of Brucella
Members of genus Brucella are closely related and probably represent a single species
So they have been classified into nomen species
Important Brucella nomen species
- B. melitensis: usually in sheep, goat and camel
- B. abortus: cattle
- B. suis: pigs
- B. canis: dogs
Antigens of Brucella
Two major types of LPS antigens: M and A
In most biovars of B. melitensis, M is predominant
In B. abortus it is A
In B. suis it can be either
Pathogenesis of Bartonella
- Transmission
- Spread to bloodstream to organs
- Reticuloendothelial system primarily affected
- Local tissue responses:
Neutrophilic infiltration ➡️ chronic inflammation ➡️ granuloma - Intracellular survival: macrophages and monocytes
- Cell mediated response (since intracellular)
Methods of transmission of Brucella
- Direct contact M/C
- Food borne
- Air borne
- Person to person spread - rare
Brucellosis
clinical manifestations
Triad: 1. Profuse night sweats 2. Arthralgia/ arthritis 3. Hepatosplenomegaly •Typhoid like illness •Musculoskeletal symptoms •Depression and lethargy with meningitis
Nomen species of brucellosis are identified on the basis of
- Preference of animal host
- CO2 requirement and H2S production
- Tolerance to bacteriostatic dyes like basic fuchsin and thionine
- Agglutination with specific antisera
- Lysis by bacteriophages
Gold standard serological test for brucellosis
Standard agglutination test SAT
Tube agglutination test detecting antibodies against LPS antigen of B. abortus
Cannot differentiate between acute and chronic but use of 2-mercaptoethanol SAT can differentiate as 2-ME destroys IgM of acute
Treatment of brucellosis in adults
1. Standard regimen: Gentamicin for 7 days plus doxycycline for 6 weeks 2. WHO regimen: Instead of gentamicin, rifampin 3. CNS involvement: Ceftriaxone added Treatment is prolonged for 3-6 months
Treatment of brucellosis in animals
- Test and slaughter
- Vaccine:
Live attenuated vaccine using B. abortus 19 strain for cattle and B. mellitensis rev-1 strain for sheep and goat are available
Spirochaetes
Thin flexible elongated spirally coiled helical bacilli
Gram negative but endoflagella is present in periplasmic space
All spirochaetes are saprophytic except
1. Treponema: Syphilis, cutaneous lesions 2. Borrelia: Lyme’s disease, Vincent’s angina, relapsing fever 3. Leptospira interrogans: Weil’s disease
Leptospira classification
Antigenically complex
Two species containing many serovars and serogroups :
1. L. interrogans: pathogenic to various extents
2. L. biflexa: saprophytic
Leptospirosis
Andaman hemorrhagic fever
(Weil’s disease)
By Leptospira interrogans
Zoonotic mainly from rats, dogs, cattle and pigs
Direct human to human transfer does not occur
More common during monsoon 🌧 and post-monsoon period
3Rs are rodents, rainfall and rice field
Leptospirosis
risk factors and modes of transmission
Transmission: 1. Indirect contact with water, moist soil and wet surfaces contaminated with animal urine 2. Direct contact with urine, parturition products of infected animals Risk factors: 1. Lower socioeconomic status 2. Urban and rural slums 3. Rainfall and floods 4. Occupational exposure
Leptospirosis
pathogenesis
- Septicaemic phase:
Bloodstream to various organs using hyaluronidase
Vascular damage - Immune phase:
Spirochaetes disappear from blood
Ag-Ab complexes deposited
Renal colonisation and excreted in urine
Leptospirosis
clinical manifestations
Incubation period: 10 days Two distinct syndromes: 1. Mild anicteric febrile illness: Biphasic- septicemic and immune Flu like symptoms 2. Weil’s disease- Hepatorenalhemorrhagic syndrome Severe form of icteric illness
Leptospirosis
specimens taken
- CSF and blood for 1st 10 days
2. Urine for 10 to 30 days
Leptospirosis
antibody detection tests
- Genus-specific tests:
• ELISA for IgM and IgG separately
• Lepto dipstick assay: for IgM
• Immunochromatographic test: IgM and IgG separately - Serovar-specific test (Microscopic agglutination test, MAT)-gold standard
- Cross agglutination and absorption test CAAT
Leptospirosis
treatment
- Mild:
Oral doxycycline 100 mg twice a day for a week
or amoxicillin - Severe:
Penicillin 1.5 MU IV four times a day for a week
or ceftriaxone or cefotaxime
Leptospirosis
precautionary measures
1. Chemoprophylaxis with doxycycline: Short teen exposures, military training or swimming 2. Sanitation and waste disposal 3. Rodent control 4. Avoid swimming in contaminated places 5. Health education
Borrelia
Larger spirochete with lesser no of spirals
Mostly commensals on buccal or genital mucosa except
1. B. recurrentis - epidemic relapsing fever
2. B. burgdorferi - Lyme disease
3. B. vincentii - Vincent’s angina
Relapsing fever
basics and types
Recurrent episodes of fever and non-specific symptoms following exposure to insect vector carrying Borrelia
1. Epidemic RF:
B. recurrentis by louse
2. Endemic RF:
B. duttoni , B. hermsii, B. turicatae by tick
Relapsing fever
mode of transmission
- Epidemic RF:
It is introduced by crushing of human body louse (scratching) leading to deposition of spirochetes - Endemic RF:
Bite of infected tick
Relapsing fever
pathogenesis
- Transmission
- Bloodstream - bacteremia and fever
Antigenic variation:
Borrelial surface antigens undergo it
Each time new antigens are produced which can evade immune system ➡️ - Repeated bacteremia and recurrent febrile episodes
Relapsing fever
clinical manifestations
- Recurrent febrile episodes: of 3-5 days and afebrile periods of 4-14 days. Subsequent episodes are shorter
Next 2 are more common in epidemic RF: - Haemorrhages:
Petechiae, epistaxis and blood tinged sputum - Neurological:
Meningitis, seizure, focal deficits, paraplegia and psychosis
Microscopy of Borrelia
- Peripheral thick or thin smear, strained by Wright or Giemsa strain
- Direct fluorescent antibody test:
Using monoclonal antibody to identify the species - Poorly gram negative
Relapsing fever
diagnosis
- Microscopy
- Culture: blood specimen
- Serology:
• ELISA and IFA
• G1pQ assay: immunoblot assay detecting Ab - Molecular methods: real time PCR
Relapsing fever
treatment
Doxycycline or erythromycin DoC
Single dose for epidemic RF
7-10 days for endemic RF
Lyme disease or Lyme borreliosis
By Borrelia burgdorferi mostly in US
Rodents and deer (reservoirs) though tick bite
Lyme disease
clinical manifestations
- Early localised infection:
After 3-32 days, annular maculopapular lesion at tick bite - erythema migrans involving thigh and groin - Early disseminated infection:
Bloodstream to many sites - secondary annular lesions, strange, malaise, neurological abnormalities - Late persistent infection- Lyme arthritis:
Arthritis of large joint, lasting for months, refractory to treatment
Diagnosis of Lyme disease
- Isolation from skin lesions, blood or CSF
- PCR from joint fluid
- Serology:
Two test approach- ELISA then Western blot - Raised leucocytes:
PMNL in joint fluid and lymphocytes in CSF
Lyme disease
treatment
1. No CNS and CVS involvement: Oral doxycycline for adults Amoxicillin for children 14 days for skin lesions 30-60 days for arthritis 2. For CVS or CNS infection: ceftriaxone for 14-28 days
Babesiosis
Malaria-like illness seen in 🐄 and 🐑.
B. microti M/C, others are B. bovis and B. divergens.
It is similar to Plasmodium in its life cycle and pathogenesis except for:
1. Hard tick (Ixodes scapularis) is the 1° vector (definitive host)
2. There is no liver stage, sporozoites directly enter into RBC
Treatment: Arivaquone + azithromycin
Babesiosis
clinical features
Differs from falciparum malaria being 🔽 severe, 🔽 parasitemia, no cerebral involvement, less severe anemia
- No periodicity is seen in fever cycle
- The disease is more severe in splenectomised and immunocompromised patients
Babesiosis
diagnosis
Peripheral blood smear examination reveals ring forms inside RBC arranged in pair of tetrads called Maltese cross forms
They are often confused with multiple ring forms of P. falciparum, but can be differentiated by lack of pigments and lack of crescentic 🌙 gametocytes
