Engidaw Ambelu

1. RICKETTSIAL DISEASES
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2. RICKETTSIAL DISEASES…
 obligately intracellular, gram-negative coccobacilli and short bacilli,
 most are transmitted by a tick, mite, flea, or louse vector.
 Except in the case of louse-borne typhus, humans are incidental
hosts.
 Bioterrorism threats.
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3. Diseas
e
Organism Transmission Geographic
Range
Incubatio
n
Period,
Days
Duration,
Days
Rash,
%
Eschar,
%
Lymphad
enopathy
Epidem
ic
typhus
R.
prowazekii
Louse feces:
Pediculus
humanus
corporis, fleas and
lice of flying
squirrels, or
recrudescence
Worldwide 7–14 10–18 80 None
--
Murine
typhus
R. typhi Flea feces Worldwide 8-16 9-18 80 None --
Scrub
typhus
Orientia
tsutsugam
ushi
Mite bite Asia,
Australia,
Pacific
and Indian
Ocean
islands
9–18 6–21 50 35% +++
Table 1.Features of Selected Rickettsial Infections
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4. EPIDEMIC (LOUSE-BORNE) TYPHUS
ETIOLOGY
-R. prowazekii
Epidemiology
 The human body louse (Pediculus humanus corporis) acquire R. prowazekii when
they ingest blood from a rickettsemic patient. The rickettsiae multiply in the louse’s
midgut epithelial cells and are shed in its feces.
 The infected louse leaves a febrile person and deposits infected feces on its
subsequent host during its blood meal; the patient autoinoculates the organisms by
scratching.
 The louse is killed by the rickettsiae and does not pass R. prowazekii to its
offspring.
 high case–fatality ratios. 4

5. EPIDEMIC (LOUSE-BORNE) TYPHUS
Clinical Manifestations
 incubation period of ~1–2 weeks
 Abrupt onset of prostration, severe headache, and fever rising rapidly to 38.8°–40.0°C
 Myalgias are usually severe.
 A rash begins on the upper trunk, usually on the fifth day, and then becomes
generalized, involving the entire body except the face, palms, and soles.
 Initially, this rash is macular; without treatment, it becomes maculopapular,petechial,
and confluent.
 Photophobia, with considerable conjunctival injection and eye pain, is common. The
tongue may be dry, brown, and furred. Confusion and coma are common.
 Skin necrosis and gangrene of the digits as well as interstitial pneumonia may occur in
severe cases 5

6. EPIDEMIC (LOUSE-BORNE) TYPHUS
 untreated patients develop renal insufficiency and multiorgan involvement in which
neurologic manifestations are frequently prominent
Diagnosis
 Epidemic typhus is sometimes misdiagnosed as typhoid fever in tropical countries
 Serology-Wel-Felix test[using antigens prepared from p.vulgaris]
Treatment
 Doxycycline (200 mg/d, given in two divided doses) for 2-3 days is administered
orally or—if the patient is comatose or vomiting—intravenously
 Pregnant patients should be evaluated individually and treated with chloramphenicol
early in pregnancy or, if necessary, with doxycycline late in pregnancy
Prevention
 Prevention of epidemic typhus involves control of body lice. Clothes should be
changed regularly, and insecticides should be used every 6 weeks to control the
louse population
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7. ENDEMIC MURINE TYPHUS
ETIOLOGY
-R. typhi
Epidemiology
 R. typhi is maintained in mammalian host/flea cycles,with rats as the classic zoonotic
niche
 Fleas acquire R. typhi from rickettsemic rats and carry the organism throughout their life
span.
 Nonimmune rats and humans are infected when rickettsia-laden flea feces contaminate
pruritic bite lesions; less frequently, the flea bite transmits the organisms.
 Transmission can also occur via inhalation of aerosolized rickettsiae from flea feces 7

8. ENDEMIC MURINE TYPHUS…
Clinical Manifestations
 The incubation period of experimental murine typhus averages 11 days (range, 8–16
days). Headache, myalgia, arthralgia,nausea, and malaise develop 1–3 days before
onset of chills and fever.
 Nearly all patients experience nausea and vomiting early in the illness
 The duration of untreated illness averages 12 days (range, 9–18days).
 Rash is present in only 13% of patients. The initial macular rash is often detected by
careful inspection of the axilla or the inner surface of the arm. Subsequently,the rash
becomes maculopapular, involving the trunk more often than the extremities; it is
seldom petechial and rarely involves the face, palms, or soles.
 interstitial pneumonia, pulmonary edema, and pleural effusions and bibasilar rales are
the most common pulmonary sign 8

9. ENDEMIC MURINE TYPHUS…
 Less common clinical manifestations include abdominal pain, confusion, stupor,
seizures, ataxia,coma, and jaundice.
 Aemia and leukopenia early in the course, leukocytosis late in the
course, thrombocytopenia, hyponatremia, hypoalbuminemia, mildly increased serum
hepatic aminotransferases, and prerenal azotemia
 Complications can include respiratory failure, hematemesis, cerebral hemorrhage,
and hemolysis.
 Severe illness necessitates the admission to an intensive care unit
 50% suffered only nocturnal fevers,feeling well enough for active daytime play
Diagnosis
Serologic studies
Culture
PCR
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10. ENDEMIC MURINE TYPHUS…
Treatment
 doxycycline (100 mg bid orally for 7–15 days)on the basis of clinical
suspicion.
 Ciprofloxacin provides an alternativeif doxycycline is contraindicated.
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11. SCRUB TYPHUS
ETIOLOGY
O. tsutsugamush
Epidemiology
 O. tsutsugamushi differs substantially from Rickettsia
 species both genetically and in cell wall composition (i.e., it lacks lipopolysaccharidO.
tsutsugamushi is maintained by transovarial transmission in mites.
 After hatching, infected larval mites (chiggers, the only stage that feeds on a host)
inoculate organisms into the skin.
 Infected chiggers are particularly likely to be found in areas of heavy scrub vegetation
during the wet season, when mites lay eggs.
 Scrub typhus is endemic and reemerging in some areas of the world.
 Immunity wanes over 1–3 years, and the organism exhibits remarkable antigenic
diversity.
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12. SCRUB TYPHUS…
Clinical Manifestations
 Illness varies from mild and self-limiting tofatal. Incubation period 6–21 days,
 onset is characterized by fever, headache, myalgia, cough, and gastrointestinal
symptoms.
 Some patients recover spontaneously after a few days.
 The classic case description includes an eschar where the chigger has fed,
regional lymphadenopathy, and a maculopapular rash—signs that are seldom
seen in indigenous patients
 Severe cases typically manifest with encephalitis and interstitial pneumonia
due to vascular injury.
 The case-fatality rate for untreated classic cases is 7%. 12

13. SCRUB TYPHUS…
Diagnosis and Treatment
 Serologic assays (indirect fluorescent antibody,indirect immunoperoxidase, and
enzyme immunoassays) are the mainstays of laboratory diagnosis. PCR is also
effective.
 Patients are treated with doxycycline(100 mg bid orally for 7–15 days),or
azithromycin (500 mg orally for 3 days), or chloramphenicol (500 mg qid orally for
7–15 days).
Prevention???
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14. HUMAN IMMUNODEFICIENCY
VIRUS DISEASE: AIDS AND RELATED
DISORDERS
 AIDS was first recognized in the United States in the summer of 1981
 when Centers for Disease Control and Prevention (CDC) reported the
unexplained occurrence of:
- Pneumocystis jiroveci (formerlyP. carinii) pneumonia and Kaposi’s sarcoma (KS)
with or without P. jiroveci pneumonia and other opportunistic infections in previously
healthy homosexual men
 The disease was soon recognized in male and female injection drug users; in
hemophiliacs and blood transfusion recipients; among female sexual partners of
men with AIDS; and among infants born to mothers with AIDS. 14

15. HUMAN IMMUNODEFICIENCY
VIRUS DISEASE…
 In 1983, human immunodeficiency virus (HIV)was isolated from a patient with
lymphadenopathy,
 In1984 it was demonstrated clearly to be the causative agent of AIDS.
 In 1985,a sensitive enzyme-linked immunosorbent assay (ELISA) was
developed;this led to an appreciation of the scope and evolution of the HIV
epidemic in USA and other developed nations
 CDC classification system for HIV infection and AIDS categorizes people on the
basis of clinical conditions associated with HIV infection and CD4+ T lymphocyte
measurement.
 A confirmed HIV case can be classified in one of five HIV infection stages(0, 1, 2,
3, or unknown).
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16. HUMAN IMMUNODEFICIENCY
VIRUS DISEASE…
 If there was a negative HIV test within 6 months of the first HIV infection
diagnosis, the stage is 0, and remains 0 until 6 months after diagnosis.
 Advanced HIV disease(AIDS) is classified as stage 3 if one or more specific
opportunistic illness has been diagnosed. Otherwise, the stage is determined
by CD4 test results and immunologic criteria.
 If none of these criteria apply (e.g., because of missing information on CD4
test results), the stage is U (unknown).
 The definition and staging criteria of AIDS are complex and comprehensive
and established for surveillance purposes rather than for the practical care of
patients.
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17. HUMAN IMMUNODEFICIENCY
VIRUS DISEASE…
CDC Stage 3 (AIDS)-Defining Opportunistic Illnesses in HIV Infection
 Candidiasis of bronchi, trachea, or lungs,esophagus
 Cervical cancer,
 Cytomegalovirus retinitis (with loss of vision)
 Kaposi’s sarcoma
 Burkitt’s Lymphoma,
 Mycobacterium tuberculosis of any site
 Pneumocystis jirovecii (previously known as Pneumocystis carinii) pneumonia
 Toxoplasmosis of brain, onset at age >1 month
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18. HUMAN IMMUNODEFICIENCY
VIRUS DISEASE…
ETIOLOGY
 HIV is the etiologic agent of AIDS; it belongs to the family of human retroviruses
(Retroviridae) and the subfamily of lentiviruses
 The four retroviruses known to cause human disease belong to two distinct
groups: the human T lymphotropic viruses (HTLV)-1 and HTLV-2,which are
transforming retroviruses; and the human immunodeficiency viruses, HIV-1 and
HIV-2, which cause cytopathic effects either directly or indirectly
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19. HUMAN IMMUNODEFICIENCY
VIRUS DISEASE…
 HIV-1- The most common cause of HIV disease throughout the world,group M
subtype C is the most common in the world; also in Ethiopia
 Transmissiion
 mother-to-child transmissions of HIV, 23–30% before birth, 50–65%
during birth, and 12–20% via breast-feeding.
 Sexual transmission-the major way of transmission?????????
 sub-Saharan Africa is home to just 12% of the world’s population;but More
than 70% of all people with HIV infection (~25 million), and nearly 90% of all
HIV-infected children live in this region.
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20. HUMAN IMMUNODEFICIENCY
VIRUS DISEASE…
MORPHOLOGY OF HIV
 HIV virion is an icosahedral structure containing numerous external spikes formed by
the two major envelope proteins, the external gp120 and the transmembrane gp41.
REPLICATION CYCLE OF HIV
 HIV is an RNA virus whose hallmark is the reverse transcription of its genomic RNA to
DNA by the enzyme reverse transcriptase.
 The replication cycle of HIV begins with the high-affinity binding of the
 gp120 protein to its receptor on the host cell surface, the CD4 molecule
 CD4 found predominantly on a subset of T lymphocytes that are responsible for
helper function in the immune system
 CD4 is also expressed on the surface of monocytes/macrophages and
dendritic/Langerhans cells 20

21. HUMAN IMMUNODEFICIENCY
VIRUS DISEASE…
 Once it binds to CD4, the gp120 protein undergoes a conformational change that
facilitates binding to one of two major co-receptors.
 The two major co-receptors for HIV-1 are CCR5 and CXCR4
 Fusion with the host cell membrane occurs via the newly exposed gp41 molecule
penetrating the plasma membrane of the target cell and then coiling upon itself to bring
the virion and target cell together
 Following fusion, uncoating of the capsid protein shell is initiated—a step that
facilitates reverse transcription viral reverse transcriptase enzyme catalyzes the
reverse transcription of the genomic RNA into DNA, resulting in the formation of
double-stranded proviral HIVDNA.
 With activation of the cell, the viral DNA accesses the nuclear pore and is exported
from the cytoplasm to the nucleus
 Integrase binds host DNA to viral DNA 21

22. HUMAN IMMUNODEFICIENCY
VIRUS DISEASE…
 This provirus may remain transcriptionally inactive (latent) or it may manifest
varying levels of gene expression, up to active production of virus.
 Following transcription, HIV mRNA is translated into proteins that undergo
modification through glycosylation, myristoylation, phosphorylation, and
cleavage.
 viral particle is formed by the assembly of HIV proteins, enzymes, and genomic
RNA at the plasma membrane of the cells.
 Budding of the progeny virion through the lipid bilayer of the host cell membrane
is the point at which the core acquires its external envelope.
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23. HUMAN IMMUNODEFICIENCY
VIRUS DISEASE…
PATHOPHYSIOLOGY AND PATHOGENESIS
 Once infection is established,the virus replicates in lymphoid cells in the
mucosa, the submucosa, and to some extent the lymphoreticular tissues that
drain the gut tissues
 large numbers of CD4+ T cells (usually memory cells) are infected and
depleted,both by direct viral effects and by activation-associated apoptosis.
 Once virus replication reaches this threshold and virus is widely disseminated,
infection is firmly established and the process is irreversible.
 The acute burst of viremia and wide dissemination of virus in primary HIV
infection may be associated with an acute HIV syndrome,which occurs to
varying degrees in ~50% of individuals with primary infection
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24. HUMAN IMMUNODEFICIENCY
VIRUS DISEASE…
DISCUSSION
 Clinical Latency versus Microbiologic Latency
 LONG-TERM SURVIVORS AND LONG-TERM NONPROGRESSORS
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25. HUMAN IMMUNODEFICIENCY
VIRUS DISEASE…
Primary
infection
Establishment of
infection in GALT
HIV-specific
immune response
Destruction of
Immune System
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26. HUMAN IMMUNODEFICIENCY
VIRUS DISEASE…
CLINICAL MANIFESTATIONS
 The clinical consequences of HIV infection encompass a spectrum ranging from an acute syndrome associated
with primary infection to a prolonged asymptomatic state to advanced disease. It is best to regard HIV disease
as beginning at the time of primary infection and progressing through various stages.
Discussion
Opportunistic infections in HIV infected individuals
 Mycobacterium tuberculosis is the most common opportunistic infection in HIV-infected individuals
 PCP[currently- PJP]
 Toxoplasmosis
 Cryptococcosis
 Candidiasis
 Isospora belli,M.parvum etc.
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27. HUMAN IMMUNODEFICIENCY
VIRUS DISEASE…
DIAGNOSIS OF HIV INFECTION
-Rapid test
-ELISA/PCR
-OraQuick Rapid HIV-1 antibody test
Q. What is meant by ‘window period’?
LABORATORY MONITORING OF PATIENTS WITH HIV
INFECTION
-CD4
-Viral load
-Tests for drug toxicity
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28. HUMAN IMMUNODEFICIENCY
VIRUS DISEASE…
TREATMENT
ANTIRETROVIRAL THERAPY
 Test and treat approach
 Combination antiretroviral therapy (cART), also referred to as highly active
antiretroviral therapy (HAART),
 Treat opportunistic infections eg vl
 READ 4 STAGES OF HIV
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29. ACUTE VIRAL HEPATITIS
 Acute viral hepatitis is a systemic infection affecting the liver predominantly.
 Almost all cases of acute viral hepatitis are caused by one of five viral agents:
hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), the HBV-
associated delta agent or hepatitis D virus (HDV), and hepatitis E virus (HEV).
 All these human hepatitis viruses are RNA viruses, except for hepatitis B, which
is a DNA virus but replicates like a retrovirus.
 Th disease range from asymptomatic and inapparent to fulminant and fatal acute
infections common to all types, and from subclinical persistent infections to
rapidly progressive chronic liver disease with cirrhosis and even hepatocellular
carcinoma, common to the bloodborne types (HBV, HCV,and HDV).
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30. ACUTE VIRAL HEPATITIS…
Clinical manifestation
 Acute hepatitis
 Chronic hepatitis
 Complications
-CLD
-HCC
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31. ACUTE VIRAL HEPATITIS…
DIAGNOSIS
VIRAL MARKERS
-HBSAg
-Anti-HBSAg
-Anti-HBc
-Anti-Hbe
Treatment???
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32.  THANK U SO MUCH
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