Protozoan and Helminth Infections Flashcards
Normal Blood Cell Counts/ Functions
Neutrophils: 50-70% WBCs, bacterial infections
Eosinophils: 1-4% WBCs, parasitic infections, allergy
Basophils: < 1% WBCs, allergic, type 1 reactions
Lymphocytes: 30-40% WBCs, T&B cells, NK cells - T cells (CD4 and CD8 cells) - CD4 TH1 for intracellular infections/IFN-γ production, inflammatory/DTH responses - CD4 TH2 for antibody production by B cells - CD8 TC kills virus infected cells, organ transplants, tumor cells - Natural Killer (NK) Cells
Monocytes: (phagocytic, 3-5%) macrophages, alveolar macro, dendritic cells, Kupfer cells (liver), histiocytes (connective tissue), microglial cells (brain)
Malaria transmission
Transmitted by female Anopheles
mosquito
malaria incubation
Merozoite incubates and multiplies
in liver for 8-10 days
malaria RBC recepturs
RBC receptors: glycophorin A for
P. falciparum and Duffy antigen
for P. vivax
malaria pathogenesis
Invades rbcs in blood circulation,
develops into schizont in 48 hrs;
ruptures, releases glycolipid toxin
that initiates malaria cascade with
cyclic fever, chills, anemia,
diarrhea, respiratory difficulty
malaria complications
Cerebral malaria complication:
convulsion, coma, death
Invasion of red blood cells by merozoites
Merozoites transform into ring
stage in 6-12 hrs
Rings transform into trophozoites
in 12 hrs
Trophozoites transform into
schizonts in 24 hrs
Schizonts rupture to release
daughter merozoites into blood
circulation to infect new rbcs
More than one ring in singe rbc
indicates P. falciparum infection
schizont multicellular stage
Schizont ruptures to
release merozoites, glycolipid toxin, soluble antigens and cellular metabolic products
Each daughter
merozoite reinvades red blood cells
Toxin (LPS-like) and
above products induce fever, chills,
clinical features of malaria
Clinical Features Fever Chills Rigors Myalagia Diarrhea
complications of malaria
Cerebral malaria -progressive headache, neck
stiffness, convulsions
(seizures), coma
(unconsciousness) Severe anemia Hypoglycemia Lactic acidosis Splenomegaly Glomerulonephritis
malaria pathogenesis
nephrotic syndrome in P. malariae
Deposition of malaria
antigens on
glomerular membrane
surface
Damage to the
endothelial surface of
glomeruli
High protein
excretion
Low serum albumin
cerebral malaria
Caused by Plasmodium falciparum Parasite-infected rbcs migrate to cerebral capillaries Adhere to each other and to capillary endothelium by
cysteine-rich knobs Occlusion of cerebral capillaries progressive headache; neck stiffness convulsions (seizures) coma (unconsciousness) Death if untreated
Cerebral occlusion by parasite- infected rbcs, stiff neck, convulsion, coma, death
malaria, diagnosis
Dx: microscopic demonstration of merozoites and trophozoites
on Giemsa-stained thick/thin blood smars DNA-based
techniques
malaria, treatment
Wide-spread resistance to chloroquine
Primaquine to prevent dormant liver hypnozoites of P. vivax and elimination of gametocytes
Fansidar (pyrimethamine-sulfadoxine), larium (mefloquine) and
doxycyline for prophylaxis and treatment
Resistance to fansidar due to gene mutation for dihydrofolate
reductase
Halofantrine, quinine and artemisinin for treatment of
chloroquine resistant malaria
malaria control
Control: vaccine development, vector control, bednets
impregnated with mosquito repellents
malaria, new treatment approaches
Combination Drug Therapy Artemisinin-based combination therapy (ACT) Artemether-lumenfantrine (Coartem) Dihydroartemisinin-piperaquine (Artekin) Artemisinin mefloquine ACTs reduce drug resistance, but are 10 to 20
times more expensive than single drugs
other malaria complications
Explanations: Sickle cell disease -double recessive Hb gene, vaso-occlusion,
ischemia, bone pain crisis, acute chest pain,
spleen atrophy, leg ulcers, jaundice, infections
(pneumonia, cholecystitis/gallstone disease,
osteomyelitis)
Burkitt’s lymphoma (tumor of the jaw),
associated with EBV and malaria
capillary blockages in SCD and cerebral malaria
normal blood flow and sickled RBCs
adhesion of malaria -parasitized red cells to capillary endothelium in cerebral capillaries resulting in cerebral malaria
shared characteristics of cerebral malaria and SCD
Fever (cyclic, non-cyclic) Anemia, hypoferremia, hypoxia Vasocclusion (convulsion, ischemia) Splenic dysfunction Sepsis, inflammation (acute, chronic) underlie
complications of the two diseases High mortality in malaria-endemic regions
Burkitt’s lymphoma and malaria
Tumor of immature B cells
Prevalent in Central/East Africa, Papua New
Guinea in 6-14 year olds, particularly boys
Lymphoma associated with EBV and malaria
infections
EBV antigens are mitogenic for B cells
EBV nuclear antigen is prevalent in sera and
infected cells
EBV DNA is integrated into DNA of host B cell;
present in tumor cells
Malaria infection is also mitogenic for
B cells
IL-10 analogue made by EBV prevents TH1
response
Cellular oncogene (c-myc) is translocated from
chromosome 8 to chromosome 14, where it is
expressed
Malaria mitogens; EBV mitogens and oncogens
lead to B cell proliferation and development of B
cell lymphoma of the jaw and face
EBV also causes i) leukemia, Hodgin lymphoma ii)
nasophryngeal carcinoma in China and southeast
Asia; hairy oral leukoplakia, lesions of tongue/ mouth
in AIDS
pneumocystitis jirovecii infection of lung in immunocompromised
Dormant, endogenous fungal
/protozoan? asymptomatic
cyst infections in lungs of
immunocompetent hosts
Reactivated in cellular
immunocompromised
individuals (AIDS, leukemia),
immunosuppressive drugs) Multiplies in large numbers Occludes the alveoli
Causes interstitial pneumonia Treatment: Trimethoprim
sulfamethoxazole
occlusion of alveli by pneumocystis jiroveii infection
Occlusion of
alveoli by cell
debris from dead
macrophages, dead
lymphocytes and
dead P. jirovecii
cells, resulting in
apoxia and
interstitial
pneumonia
replication/rupture of toxoplasma gondii in macrophage
Organism has
predilection
for cells of
the: Lung Heart Lymphoid
organs Eye
toxoplasma clinical phases
Asymptomatic
Congenital – transplacental infection -spontaneous abortion, stillbirth, encephalitis, mental retardation, chorioretinitis, blindness
Recrudescent – reactivated infection in immunocompromised, transplants, immunosuppressive therapy - mostly neurologic complications - encephalitis, cerebral mass lesions, chorioretinitis - endocarditis - seizures, confusion, lethargy
Diagnosis and treatment of toxoplasma gondii
Diagnosis
- ELISA for specific IgM - tissue biopsy of lymph nodes, CSF, bone marrow, amniotic fluid
Treatment - pyrimethamine sulfadiazine - pyrimethamine + clindamycin
Leishmania parasites
Leishmania tropica (cutaneous ) L. aethiopica
(cutaneous
disseminated) L. braziliensis
(mucocutaneous) L. donovani (visceral) All transmitted by
Phlebotomus sandfly Macrophage
toxin destruction of epithelial layer
Leishmaniasis clinical ; aethopica
Localized cutaneous lesions cutaneous lesions, in Leishmania tropica
L. aethopica disseminated cutaneous lesions an indication of cellular immunosuppression
Leishmania braziliensis
Parasites also
transmitted by
Phlebotomus sandfly Multiplication of
protozoan parasites in
macrophages
Rupture of parasites
out of macrophages
Dissemination of
infection in
mucocutaneous layer
Visceral, systemic leishmaniasis L. donovani (kala-azar)
Initiated by insect bite Multiplication and rupture in
macrophages Dissemination by
macrophages to blood,
spleen, liver, lymph nodes Slow disease with fever,
weight loss, splenomegaly,
hepatomegaly Untreated die of liver failure
Leishmania diagnosis and treatment
Diagnosis: microscopic demonstration of
Leishmania species
amastigotes in Giemsa stained skin scrapings or lymph node, spleen or bone marrow biopsies
Disseminated cutaneous and visceral
leishmaniasis are complications of HIV infection in endemic countries
Treatment: sodium stibogluconate for all four
African and American Trypanosomiasi
African trypanosomiasis -Trypanosoma gambiense in West Africa -Trypanosoma brucei in East Africa, much more virulent American trypanosomiasis (Chagas disease) -Trypanosoma cruzi in Central and South America; destruction of Purkinje fibers and
cardiomegaly Antigenic variation in all trypanosome infections, with
consequent immune evasion and treatment
Trypanosomes in lymph node
Trypanosoma gambiense in blood
after insect inoculation
Trypanosomes migrate to the
lymph nodes, causing lymph node
enlargement/Winterbottom’s sign
and eventually to the brain
Fever, splenomegaly, severe
headache, weight loss and coma
(sleeping sickness)
Diagnosis by microscopic demo of
parasites in blood smears and CSF;
high serum parasite IgM
Treatment: pentamidine,
melarsoprol
triatoma vectors for what diseases
Triatoma (reduvid) vectors for Trypanosoma cruzi/Chaga’s Disease
Chagoma in Chaga’s disease
Chagoma/ chancres
/swellings at sites of insect
bites
Parasites introduced into
blood circulation; invade
macrophages and cardiac
muscle cells
Parasite causes myocarditis
and enlargement of
ventricles (cardiomegaly) by
destruction of Purkinje
fibers; mega-esophagus and
megacolon by destruction of
afferent nerves
Cardiomegaly by T. cruzi due to destruction of Purkinje fibers
Ventricular enlargement
to compensate for loss of
nerve conduction
Parasite also invades
mesenteric nerves of the
esophagus and colon
Lack of peritalsis leads to
esophagus and colon
enlargement
Diagnosis and Treatment : T Cruzi
Diagnosis:
- based on clinical presentations -microscopic demonstration of trypanosomes in
Giemsa stained bood smears or lymph node
biopsies; serum parasite specific IgM
Treatment: - suramin, pentamidine for acute and
melarsoprol for chronic trypanosomiasis - nifurtimox, benznidazole and allopurinol for
Chaga’s disease
Onchocerca volvulus/River blindness
Transmitted by Simulium black flies Adult worms live in subcutaneous nodules Eye disease (chorioretinitis) due to damage of eye tissues by
microfilarial migration and intense inflammatory reactions from
antigen/antibody complex depositions Migration thr’ eye tissues cause inflammation of sclera, retina
and choroid, leading to blindness Wolbachia bacteria endosymbiont also contributes to
inflammatory reactions from antigen/antibody complex
depositions Cause pruritis, hyperkeratosis, skin depigmentation, hanging
groin due to loss of skin elasticity and thickening Called river blindness- vectors live near rivers Treatable with ivermectin and doxycycline (Wolbachia bacteria) Control by reduced exposure to streams that serve as breeding
sites for black flies
Onchocerca in skin nodules
Inflammatory damages in eye tissue
Sclerosing keratitis Chorioretinis Optic atrophy All leading to river
blindness Treatment:
Ivermectin plus and
surgical removal of
encapsulated nodules
of adult worms
Lymphatic Filariasis
Caused by Wuchereria bancrofti and Brugia
malayi Transmitted by mosquitoes Adults live in lymph nodes and lymphatics of
the lower limbs Inflammatory reactions and subsequent
calcification lead to occlusion of lymphatics,
hydrocoele and enlargement of scrotum and
limbs
Diagnosis and Treatment : lymphatic filariasis
Diagnosis by demonstration of larval
microfilariae in blood smears Treatment is effective with ivermectin Vector control seems promising
Life cycle of Dracunculus medinensis
Also known as guinea worm
Mentioned in biblical accounts
Larval stages live in fresh waters
and ingested by copepods (water
fleas)
Reservoir hosts include dogs and
fur-bearing animals
Humans infected by drinking water
with infected copepods
Adults migrate, mate in
retroperitoneum
Gravid females ulcerate in
subcutaneous tissues of the lower
extremities to expel larvae into
water
Worldwide eradication by Carter
Foundation since 1976 almost
complete
D. medinensis (contd)
No drugs and vaccine for guinea worm Village doctors extract worms with a rolling twig Worm breakage can lead to severe anaphylactic reactions Drug of choice is niridazole or metronidazole for wond
treatment Control by elimination of copepods in drinking water Provision of safe drinking water
