INFECTIOUS PATHOLOGY

Dr Michaele, MD RII

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INFLAMMATORY RESPONSE TO INFECTIOUS
AGENTS
 The interaction between the microorganisms & the host determines the his-
tologic feature of inflammatory response
 There are 5 major histologic pattern of tissue reaction
1. Suppurative Polymorphonuclear Inflammation –
• Acute tissue damage marked by increased vascular permeability and neu-
trophilic exudation.
 The size of exudates varies in different disease
 Destruction depends on the site involved & the microbes
 eg. Pneumococcus & staphylococcus

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 INFLAMMATORY RESPONSE TO INFECTIOUS
AGENTS…
2. Mononuclear Inflammation
• Diffuse, predominantly mononuclear interstitial infiltrates are a common feature
of all chronic inflammatory processes, but when they occur acutely, they are often
a response to viruses, intracellular bacteria, or intracellular parasites.

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 INFLAMMATORY RESPONSE TO INFECTIOUS
AGENTS…
3. Cytopathic-Cytoproliferative Inflammation
• Usually produced by viruses, are characterized by damage to individual host cells,
with little or no host inflammatory response
• Some viruses replicate within cells and make viral aggregates that are visible as
inclusion bodies (e.g., CMV, adenovirus) or induce cells to fuse and form
polykaryons (e.g., measles, herpesviruses)
• Viruses can cause dysplastic changes and cancers in epithelial cells and
lymphocytes

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 INFLAMMATORY RESPONSE TO INFECTIOUS
AGENTS…
4. Necrotizing Inflammation
• C. perfringens and other organisms that secrete very strong toxins
cause such rapid and severe tissue damage that cell death is the
dominant feature
• The parasite E. histolytica causes colonic ulcers and liver abscesses
characterized by extensive tissue destruction with liquefactive necrosis
in the absence of an inflammatory infiltrate

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 INFLAMMATORY RESPONSE TO INFECTIOUS
AGENTS…
5. Chronic Inflammation and Scarring
• Final common pathway of many infections is chronic inflammation, which may lead to extensive
scarring (e.g., chronic gonococcal salpingitis)
• Some organisms that are relatively inert, the exuberant host scarring response is the major cause of
disease (e.g. the "pipe-stem" fibrosis of the liver caused by schistosomal ova or gummas of tertiary
syphilis in the liver, central nervous system, and bones)

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TUBERCULOSIS

 A communicable chronic granulomatous disease caused by Mycobacterium

tuberculosis
 Usually involves the lungs but may affect any organ or tissue in the body

 The centers of tubercular granulomas may undergo caseous necrosis

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EPIDEMIOLOGY

 Among medically and economically deprived persons, tuberculo-

sis remains a leading cause of death
 1.7 billion individuals are infected worldwide
 8 to 10 million new cases and 3 million deaths per year
 Tuberculosis flourishes wherever there is poverty, crowding, and
chronic debilitating illness

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TRANSMISSION

 Infections are acquired by airborne droplets of organisms from an

active case to a susceptible host, generated by expectora-
tion or by exposure to contaminated secretions of infected
persons
 Oropharyngeal and intestinal tuberculosis contracted by drinking
milk contaminated with Mycobacterium bovis

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TESTS

 Infection with M. tuberculosis leads to the development of de-

layed hypersensitivity
 detected by the tuberculin (Mantoux) test

 2 to 4 weeks after the infection

 intracutaneous injection of 0.1 ml of PPD induces a visible and

palpable induration (at least 5 mm in diameter) that peaks

in 48 to 72 hours

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 positive tuberculin test result signifies cell-mediated hypersensi-
tivity to tubercular antigens
 It does not differentiate between infection and disease
 false-negative reactions (or skin test anergy)

- some viral infection

- sarcoidosis, malnutrition, Hodgkin's lymphoma,
immunosuppression

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ETIOLOGY

 Mycobacteria are slender rods that are acid fast

 M. tuberculosis hominis is responsible for most cases of tubercu-
losis
 Mycobacterium bovis – oropharyngeal & intestinal
 Both species are obligate aerobes whose slow growth is retarded
by a pH lower than 6.5 and by long-chain fatty acids
 M. avium-intracellulare, are much less virulent than M. tubercu-
losis

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PATHOGENESIS

 The pathogenesis of tuberculosis in the previously unexposed

immunocompetent individual is centered on the develop-
ment of a targeted cell-mediated immunity that confers re-
sistance to the organism and results in development of
tissue hypersensitivity to tubercular antigens

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 The pathologic features of tuberculosis, such as caseat-
ing granulomas and cavitation, are the result of the de-
structive tissue hypersensitivity that is part of the
host immune response
 Once virulent strains of mycobacteria gain entry into
the macrophage endosomes , the organisms are able
to inhibit normal microbicidal responses by manipula-
tion of endosomal pH and arrest of endosomal matura-
tion

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 The end result of this "endosomal manipulation" is impairment of
effective phagolysosome formation and unhindered my-
cobacterial proliferation
 Thus, the earliest phase of primary tuberculosis (<3 weeks) in

the nonsensitized individual is characterized by bacillary pro-

liferation within the pulmonary alveolar macrophages and
airspaces

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 The development of cell-mediated immunity occurs approxi-
mately 3 weeks after exposure
 Processed mycobacterial antigens reach the draining lymph

nodes and are presented in a major histocompatibility class II

context by dendritic cell macrophages to CD4+ T cells
 Under the influence of macrophage-secreted IL-12, CD4+ T cells

of the TH1 subset are generated, capable of secreting IFN-γ (cru-

cial in activating macrophages)

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 Activated macrophages release a variety of mediators -including
secretion of TNF, which is responsible for recruitment of
monocytes, which in turn undergo activation and differentiation
into the "epithelioid histiocytes" that characterize the granulo-
matous response.

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PRIMARY TUBERCULOSIS

 The form of disease that develops in a previously unexposed,

and therefore unsensitized, person
 The source of the organism is exogenous

 About 5% of those newly infected develop significant disease

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MORPHOLOGY

 Primary tuberculosis almost always begins in the lungs

 The inhaled bacilli implant in the distal airspaces of the lower

part of the upper lobe or the upper part of the lower lobe, usu-
ally close to the pleura
 As sensitization develops, a 1 to 1.5 cm area of gray-white

inflammatory consolidation emerges, the Ghon focus

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 Tubercle bacilli, either free or within phagocytes, drain to the re-
gional nodes, which is often caseate
 This combination of parenchymal lesion and nodal involvement is

referred to as the Ghon complex

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 In approximately 95% of cases, development of cell-mediated
immunity controls the infection.
 Hence, the Ghon complex undergoes progressive fibrosis, often

followed by radiologically detectable calcification (Ranke com-

plex), and, despite seeding of other organs, no lesions de-
velop

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HISTOLOGY

 Sites of active involvement are marked by a characteristic

granulomatous inflammatory reaction that forms both
caseating and noncaseating tubercles
 The granulomas are usually enclosed within a fibroblastic rim

punctuated by lymphocytes
 Multinucleate giant cells are present in the granulomas

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 The chief implications of primary tuberculosis are
1) it induces hypersensitivity and increased resistance
2) the foci of scarring may harbor viable bacilli for years
3) uncommonly, the disease may develop without interruption
into so-called progressive primary tuberculosis

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 Progressive primary tuberculosis more often resembles an acute
bacterial pneumonia, with lower and middle lobe consolida-
tion, hilar adenopathy, and pleural effusion; cavitation is rare,
especially in persons with severe immunosuppression

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SECONDARY TUBERCULOSIS (REACTIVATION TU-
BERCULOSIS)
 Is the pattern of disease that arises in a previously sensitized
host
 It may also result from exogenous reinfection because of waning

of the protection afforded by the primary disease or because of a

large inoculum of virulent bacilli
 5% of individuals with primary disease subsequently develop

secondary tuberculosis

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 Secondary pulmonary tuberculosis is classically localized to the
apex of one or both upper lobes
 Cavitation occurs readily in the secondary form

 Secondary tuberculosis should always be an important consider-

ation in HIV-positive patients who present with pulmonary dis-

ease
 The manifestations differ depending on the degree of immunosuppression

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 For example, persons with less severe immunosuppression present with
"usual" secondary tuberculosis (apical disease with cavitation).
 On the contrary, persons with more advanced immunosuppression present
with a clinical picture that resembles progressive primary tuberculosis
(lower and middle lobe consolidation, hilar lymphadenopathy, and noncavi-
tary disease)

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 The extent of immunosuppression also determines the frequency
of extrapulmonary involvement
 Other atypical features in HIV-positive patients includes

- increased frequency of sputum-smear negativity for acid-fast

bacilli
-false-negative PPD and the lack of characteristic granulomas
in tissues, particularly in the late stages

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MORPHOLOGY

 The initial lesion is usually a small focus of consolidation within 1

to 2 cm of the apical pleura
 Such foci are sharply circumscribed, firm, gray-white to yellow

areas that have a variable amount of central caseation and pe-

ripheral fibrosis

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HISTOLOGICALLY

 The active lesions show characteristic coalescent tubercles with

central caseation.
 Localized, apical, secondary pulmonary tuberculosis may heal
with fibrosis either spontaneously or after therapy, or the
disease may progress and extend along several different
pathways:-

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 Progressive pulmonary tuberculosis
 Miliary pulmonary disease

 Pleural effusions, tuberculous empyema (accumulation of pus in

body cavities), or obliterative fibrous pleuritis may develop

 Endobronchial, endotracheal, and laryngeal tuberculosis

 Systemic miliary tuberculosis

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 Lymphadenitis - is the most frequent form of extrapulmonary
tuberculosis, usually occurring in the cervical region ("scro-
fula")
--In HIV-negative individuals, lymphadenopathy tends to be uni-
focal, but in HIV-positive persons almost always demonstrate
multifocal disease
 Intestinal tuberculosis - contracted by the drinking of contam-

inated milk was fairly common as a primary focus of tuberculosis

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 Isolated-organ tuberculosis - meninges (tuberculous menin-
gitis), kidneys (renal tuberculosis), adrenals, bones (os-
teomyelitis), and fallopian tubes (salpingitis).
 When the vertebrae are affected, the disease is referred to as
Pott’s disease
 Paraspinal "cold" abscesses in persons with this disorder may
track along the tissue planes to present as an abdominal or
pelvic mass

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CLINICAL COURSE

 Localized secondary tuberculosis may be asymptomatic

 Usually insidious in onset; there is gradual development of both systemic and
localizing symptoms
 Systemic symptoms, probably related to cytokines released by activated
macrophages (e.g., TNF and IL-1), often appear early in the course and in-
clude malaise, anorexia, weight loss, and fever

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 -- The fever is low grade and remittent (appearing late each af-
ternoon and then subsiding), and night sweats occur
 With progressive pulmonary involvement, increasing amounts of

sputum, at first mucoid and later purulent, appear

 Hemoptysis is present in about half of all cases of pulmonary

tuberculosis
 Pleuritic pain may result from extension of the infection to the

pleural surfaces

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 Extrapulmonary manifestations of tuberculosis are dependent on
the organ system involved
 The diagnosis of pulmonary disease is based in part on the his-

tory and on physical and radiographic findings of consolidation or

cavitation in the apices of the lungs.
 Ultimately, however, tubercle bacilli must be identified

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LEPROSY

 Leprosy, or Hansen disease, is a slowly progressive infection

 Cause – Mycobacterium leprae

 Affects skin & peripheral nerves resulting in disabling deformi-

ties
 Can be transmitted person to person through aerosols from le-

sions in the upper respiratory tract

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PATHOGENESIS

 M. leprae is an acid-fast, obligate intracellular organism

 Grows very poorly in culture

 Cell mediated immunity is reflected by delayed type hypersensi-

tivity reactions to dermal injections of a bacterial extract called

lepromin

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 Leprosy has 2 strikingly different patterns of disease
1. Tuberculoid leprosy
- less sever form
- have dry, scaly skin lesions that lacks sensation
- often have large, asymmetric peripheral nerve involve-
ment

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 -has a TH1 response with production of IL-12 & IFN γ
- IFN γ is critical to mobilizing an host macrophage re-
sponse
- IL-12 is important in the generation of TH2 cells

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 2. lepromatous leprosy
-more sever form
-symmetric skin thickening & nodules
-called anergic leprosy because of unresponsiveness (an-
ergy) of the host immune system
-cooler areas of skin is more affected than warmer areas

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 -damage to the nervous system comes from widespread in-
vasion of the mycobacteria into schwann cells and into endoneu-
ral & perineural
macrophages
-In advanced case, M. leprae presents in the sputum &
blood
-some people can also have an intermediate form called
borderline leprosy

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MORPHOLOGY

Tuberculoid leprosy
 Begins with localized skin lesions (flat & red) progressed to irreg-

ular shapes with indurated, elevated, hyperpigmented margins

& depressed pale center (central healing)
 Neural involvement dominates & nerves become enclosed with

in
granulomatous inflammatory reactions

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 These nerve degeneration causes skin anesthesias & skin &
muscle atrophy
 Microscopic examination, all sites of involvement disclose

granulomatous lesion

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 Lepromatous leprosy
 Involves skin, peripheral nerves, anterior chamber of the eye,

upper airways, testes, hands & feet

 Vital organs & CNS are rarely affected

 Lepromatous lesion usually contain large aggregates of lipid-

laden macrophages (lepra cells) often filled with mass of acid

fast bacilli

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 Macular, papular, or nodular lesions form on the face, ear, elbow,
wrist & knees
 The testes usually extensively involved, with destruction of

semniferous tubules lead to sterility

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SYPHILIS

 Syphilis, or lues, is a chronic venereal infection caused by the

spirochete Treponema pallidum
 African Americans affected 30 times more than whites

 T. pallidum is a fastidious spirochete whose only natural hosts

are humans
 source of infection is an active cutaneous or mucosal lesion in a

patient in the early (primary or secondary) stages of syphilis

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TRANSMISSION

 The organism is transmitted from the lesion during sexual intercourse across
minute breaks in the skin or mucous membranes of the uninfected partner
 Across the placenta from mother to fetus, particularly during the early stages
of maternal infection
 Once introduced into the body, the organisms are rapidly disseminated to dis-
tant sites by lymphatics and the bloodstream, even before the appearance
of lesions at the primary inoculation site

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 2 to 6 weeks after the initial infection, a primary lesion, termed a
chancre, appears at the point of entry
 The host mounts an immune response

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 The chancre of primary syphilis resolves spontaneously over a
period of 4 to 6 weeks and is followed in approximately 25% of
untreated patients by the development of secondary
syphilis
 Syphilis is common in HIV-infected patients

 Although disease progression is more likely, there is little evi-

dence that the clinical manifestations are more fulminant in

the setting of HIV disease

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MORPHOLOGY

 The macroscopic lesions of syphilis vary with the stage of dis-

ease
 Fundamental microscopic lesion of syphilis is a proliferative

endarteritis and an accompanying inflammatory infil-

trate rich in plasma cells
 The treponemes cause endothelial hypertrophy and proliferation,

followed by intimal fibrosis and narrowing of the vessel lu-

men

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 Spirochetes are readily demonstrable in histologic sections of
early lesions with the use of standard silver stains
 Large areas of parenchymal damage in tertiary syphilis result in

the formation of a gumma, an irregular, firm mass of necrotic

tissue surrounded by resilient connective tissue.

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 Microscopically, the gumma contains a central zone of coagula-
tion necrosis surrounded by a mixed inflammatory infiltrate
composed of lymphocytes, plasma cells, activated
macrophages (epithelioid cells), occasional giant cells, and a
peripheral zone of dense fibrous tissue.

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PRIMARY SYPHILIS

 Characterized by the presence of a chancre at the site of initial

inoculation
 The primary chancre in males is usually on the penis

 In females, multiple chancres may be present, usually in the

vagina or on the uterine cervix

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 begins as a small, firm papule, which gradually enlarges to pro-
duce a painless ulcer with well-defined, indurated margins and a
"clean," moist base
 Regional lymph nodes are often slightly enlarged and firm, but

painless
 Histologic examination of the ulcer reveals a loss of the overlying
epidermis, with epidermal hyperplasia at its periphery
 Serologic tests for syphilis are often negative during the early
stages of primary syphilis

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SECONDARY SYPHILIS

 Within approximately 2 months of resolution of the chancre, the

lesions of secondary syphilis occur
 The manifestations are varied but include a combination of gen-

eralized lymph node enlargement and a variety of mucocuta-

neous lesions
 Skin lesions are usually symmetrically distributed and may be

maculopapular, scaly, or pustular

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 Involvement of the palms of the hands and soles of the feet is
common
 In moist skin areas, such as the anogenital region, inner thighs,

and axillae, broad-based, elevated lesions termed condylomata

lata may occur
 Spirochetes are present and easily demonstrable within the

mucocutaneous lesions; they are therefore contagious

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 Lymph node enlargement is most common in the neck and
inguinal areas
 Biopsy of enlarged nodes reveals nonspecific hyperplasia of ger-
minal
centers accompanied by increased numbers of plasma cells or,
less
commonly, granulomas or neutrophils
 Less common manifestations
 hepatitis
 renal disease
 eye disease (iritis), and gastrointestinal abnormalities. 59

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• Moist areas of the skin ,such as the anogenital region, inner thighs & axillae may
have condyloma lata, which are broad-based, elevated plaques.

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TERTIARY SYPHILIS

 Develops in approximately one third of untreated patients

 This phase of syphilis is divided into three major categories:

I. Cardiovascular syphilis (syphilitic aortitis)

II. Neurosyphilis
III. benign tertiary syphilis
 Nontreponemal antibody tests may revert to negative during the
tertiary phase, although antitreponemal antibody tests remain
positive

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CONGENITAL SYPHILIS

 The likelihood of maternal transmission is greatest during the

early (primary and secondary) stages of disease
 Manifestations of congenital syphilis include stillbirth, infantile

syphilis, and late (tardive) congenital syphilis

 Among infants who are stillborn, the most common manifesta-

tions are hepatomegaly, bone abnormalities, pancreatic fibrosis,

and pneumonitis

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AMOEBIASIS

 Is a parasitic infection caused by entamoeba histolytica

 Usually contracted by ingesting water or food contaminated with

amoebic cyst
 It infects around 500 million people in developing countries

 Entamoeba histolytica is dysentery causing protozoan parasite

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RISK FACTORS

 Eating contaminated food

 Oral-anal contact

 Unhygienic conditions & poor sanitation

 Eating vegetables & fruits which have been contaminated

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PATHOGENESIS

 E. histolytica cyst is the infectious form because it is resistant to

gastric acid
 Cysts in the colonic lumen → release trophozoites→ replicate un-

der
anaerobic environment
 They cause dysentery when attached to the colonic epithelium

as they lyse colonic epithelial cells, invade glands & burrow pro-
pria

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 In asymptomatic infections the amoeba lives by eating & digest-
ing bacteria & food particles in the gut
 Disease occurs when amoeba comes in contact with the cells lin-

ing the intestine

 It then secrets the same substances it uses to digest bacteria,

which include enzymes that destroy cell membranes & pro-

teins

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MORPHOLOGY

 Amoebiasis frequently involves the cecum & ascending colon fol-

lowed by sigmoid, rectum, & appendix
 They invade in to the mucosa & sub mucosa until stopped by

muscularis
 The organism borrow vertically & then laterally to create a flask

shaped ulcer with a narrow neck & a broad base

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 The earliest amebic lesions show neutrophilic infiltrates in the
mucosa→ ulcers that contain few inflammatory cells & areas of
extensive liquefactive necrosis
 Ameboma – uncommon lesion, a granulomatous mass formed on

the wall of the colon

 Misdiagnosed as colonic tumor & may cause intestinal obstruc-

tion

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 In some pts the parasites penetrate splanchnic vessels & em-
bolize to the liver causing amebic liver abscess which can
be solitary or multiple
 It contains hemolized blood hence the name chocolate abscess
 As it enlarged, it produces pain by pressing on the liver capsule
 Rarely, amebic abscesses reach the lung & the heart by direct
extension or spread through the blood in to the kidneys &
brain

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CLINICAL MANIFESTATION

 The incubation period is from few days up to few wks, 2-4 wks
 Patient could be symptomatic or asymptomatic

 Mild diarrhea – dysentery, abdominal pain, fever, nausea, loss of

appetite
 Rarely, abscess in the liver, lung & the brain

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MALARIA

 Caused by intracellular parasite plasmodium

 Affects 300 million people & kills 1million/yr

 90% of the death occur in the sub-Saharan Africa

 Causes – plasmodium falciparum

- plasmodium vivax
- plasmodium ovale
- plasmodium malariae
-plasmodium knowelsi

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LIFE CYCLE & PATHOGENESIS

 Except P.falciparum, the other four cause mild parasitemia,

mild anemia, & rarely causes splenic rupture & nephrotic
syndrome
 Infectious stage sporozoites in salivary gland (of
mosquito)→ invade liver cells →parasites multiply
rapidly → merozoites (asexual), P. vivax & P. ovale form
latent hypnozoites → merozoites bind RBC → most
malaria parasites with in the RBC develop in to merozoites,
some parasites develop in to sexual forms called game-
tocytes
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CTD…

 P. falciparum causes more sever disease than the other plasmod-

ium species do.
 Several features of P. falciparum account for its greater patho-

genecity
 Can infect all ages of RBC
 Causes rosetting & sequestration, P. falciparum erythrocyte membrane

protein 1 (pfEMP 1)
 Stimulate production of high levels of cytokines

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MORPHOLOGY

 Parasites are present with in RBC, & there is increased phago-

cytic activity of the macrophages in the spleen
 In chronic cases, spleen became increasingly fibrotic & brittle,

with a thick capsule & fibrous trabecula

 Liver becomes progressively enlarged & pigmented.

 Kupffer cells are heavily laden with malarial pigment, parasites,

& cellular debris

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SCHISTOSOMIASIS

 Mortality due to hepatic granulomas & fibrosis

Causes
 S. mansoni

 S. japonicum & S. mekongi

 S. haematobium

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PATHOGENESIS

 Transmission by freshwater snails

 The immune response to S. mansoni & S. japonicum eggs in the
liver causes the severe pathology of schistosomiasis
 Acute schistosomiasis in humans can be a severe febrile illness
that peaks about 2 months after infection, Katayama fever

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MORPHOLOGY

 In mild S. mansoni or S. japonicum infections

 White, pinhead-sized granulomas are scattered throughout the

gut &
liver
 At the center of granuloma is the schistosome egg, which con-

tains a miracidium ( degenerate & calcifies)

 The granulomas are composed of macrophages, lymphocytes,

neutrophils, & eosinophils

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CTD…

 In sever S. mansoni or S. japonicum infections

 Inflammatory patches or pseudopolyps may form in the colon

 The surface of the liver is bumpy, whereas cut surface reveal

granulomas & a wide spread fibrous portal enlargement

without distortion of the intervening parenchyma by regen-
erative nodule

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CTD…

 In S. haematobium infections
 Bladder inflammatory patches due to massive egg deposition &

granulomas appear early, when they erode, they cause

hematuria
 The most common complications are – obstruction, hydronephro-

sis, chronic pyelonephritis

 The common cause of squamous cell carcinoma of the bladder

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TYPHOID FEVER
 Typhoid fever is a systemic disease characterized by fever and
abdominal pain and caused by dissemination of S. Typhi or
S. Paratyphi.
 Unique to humans and it is characterized by fever,

splenomegally and neutropenia.

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TRANSMISSION

 Feco-oral routes.
 Contaminated food and water.

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CARRIERS

 Convalescent carrier- for up to 6 months following infection.

 Chronic fecal & urinary carriers in association with chronic

cholecystitis & pyelonephritis respectively.

 S.mansoni & S.hematobium co-infection protract the course.

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 PATHOGENESIS
 Infection is by ingestion of 103-106 colony forming units.
 Decreased gastric acidity and loss of intestinal mucosa integrity

increases susceptibility for infection

 After crossing the epithelial lining bacteria resist intracellular

killing by the phagocytes and get disseminated throughout the

body’s reticulo endothelial organs (lymph node, spleen, liver,
bone marrow)

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 Development of hepatosplenomegaly and recruitment of more
mononuclear cells following development of specific im-
mune response
 Several weeks after colonization there will be recruitment of ad-

ditional mononuclear cells and lymphocytes into the Payer’s

patches resulting in marked enlargement and necrosis

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MORPHOLOGY
 Payer’s patches may show
-Hyperplasia in the 1st week
-Necrosis in 2nd wk.
-Ulceration in the 3rd wk.
-Healing in the 4th wk.
 Typhoid ulcers are oval & are situated longitudinally along the
long axis of the colon in contrast to transverse ulcers in Tb.

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DIAGNOSIS

 Leucopenia- 3000-4000/mm3(15%-20%)
 Blood culture-1stwk(70 -90% +ve)
 Fecal culture-2nd -3rdwk –best(75% +ve)
 Urine culture-2nd -3rdwk
 Serology-2ndwk

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CLINICAL COURSE

 Typhoid fever is protracted disease that is associated with

 Bacteremia, fever &chills during the first week.
 Wide spread reticuloendothelial involvement with rash,
abdominal pain in the 2nd week.
 Ulceration of the payer’s patches with intestinal bleeding,
Perforation & shock during the third week.

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LEISHMANIASIS

• Leishmaniasis is a chronic inflammatory disease of the skin, mucous membranes

or viscera caused by obligate intracellular, kinetoplastid (kinetoplast-containing)

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protozoan parasites transmitted through the bite of infected sandflies.
• Leishmaniasis is endemic throughout the Middle East, South Asia, Africa & Latin
America.
• It is exacerbated by HIV/AIDS.

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Pathogenesis

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• The life cycle of Leishmania involves two forms: the promastigote, which
develops & lives extracellularly in the sandfly vector & the amastigote, which
multiplies intracellularly in host macrophages.
• Mammals including rodents, dogs & foxes are reservoir of leishmania.

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• When sandflies bite infected humans or animals, macrophages harboring

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amastigotes are ingested.
• The amastigotes differentiate into promastigotes & multiply within the digestive
tract of the sandfly & migrate into the pharynx.
• When the infected sandfly bites a person, the infectious slender, flagellated
promastigotes are released into the host dermis.

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• The promastigotes are then phagocytosed by macrophages & the acidity within
the phagolysosome induces them to transform into round amastigotes that lack

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flagella but contain a single DNA–containing specialized mitochondrion called
the kinetoplast.
• Amastigotes proliferate within macrophages & dying macrophages release
progeny amastigotes which can infect additional macrophages.

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• The amastigotes spread throughout the body depending
on the Leishmania species:

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Cutaneous leishmaniasis - Leishmania major & Leishmania aethiopica
in the old world & Leishmania mexicana & Leishmania braziliensis in the new
world.

Mucocutaneous leishmaniasis - L. braziliensis

Visceral leishmaniasis - L. donovani in the old world & L. chagasi in the

new world.

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Morphology
• Leishmania species produces four different lesions in humans:-

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- Visceral leishmaniasis
- Cutaneous leishmaniasis
- Mucocutaneous leishmaniasis
- Diffuse cutaneous leishmaniasis

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Visceral leishmaniasis /Kala-azar/
• L. donovani or L. chagasi parasites invade macrophages throughout the

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mononuclear phagocyte system & cause severe systemic disease marked by
hepatosplenomegaly, lymphadenopathy, pancytopenia, fever & weight loss.
• Phagocytic cells in the spleen, bone marrow and lymph node are enlarged & filled
with leishmania.
• Hyperpigmentation of the skin of the extremities, that is why the disease is called
kala-azar or “black fever” in Hindu.

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• The overloading of phagocytic cells with parasites predispose to bacterial
superinfection.

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• Hemorrhages related to thrombocytopenia also occur.

• Splenic, bone marrow & lymph node aspirates reveal the parasites.

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Cutaneous leishmaniasis
• It is a relatively mild, localized disease consisting of ulcer(s) at the site of
exposure.
• The lesion begins as an itching papule later changes into shallow ulcer followed
by healing in 6 to 18 months.
• Microscopically, the lesion is granulomatous with few parasites.
• Diagnosis depends upon finding the parasites in the skin.

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Mucocutaneous leishmaniasis
It is caused by L. braziliensis and found only in the New World.

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• Moist ulcerating & non-ulcerating lesions develop in the larynx & at the
mucocutaneous junctions of the nasal septum, anus or vulva.

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Diffuse cutaneous leishmaniasis
• A rare form of dermal infection found in Ethiopia & other East African
countries & in central & south America.
• It begins as a single skin nodule, which continues spreading until the entire body
is covered by bizzare nodular lesions resembling lepromatous leprosy.
• The hallmark of this form of leishmaniasis is the apparent lack of host immune
response.

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Post kala-azar dermal leishmaniasis
• About 6% of patients treated for kala-azar develop skin lesions without a history
of re-exposure.

• Lesions frequently start as hypopigmented macules & subsequently nodules.

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Diagnosis
1) Pathology

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 Identification of organisms in aspirates & biopsies.
 Aspirates can be taken from cutaneous lesions in CL & in visceral leishmaniasis
from spleen, lymph node & bone marrow.
2) Serology
 rK39
 ELISA

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