1. Phylum

2.  Posess structures collectively known as apical complex found in sporozoite or
merozoite stages of the life cycle
 Polar rings at the anterior end, just beneath the plasma membrane
 In Toxoplasma gondii conoid lies within the polar rings
 The rhoptries located within the polar rings
 Except in Babesia subpellicular microrubules radiate from the polar rings
 These organelles probably serve as support elements and facillitate the limited
motility
 Micronemes lie parallel to the rhoptries
 Rhoptries and micronemes probably secrete proteins that alter the host cell’s
plasma membrane
 Micropores are analogous to cytostomes
 All these organelles dissapear in trophozoite stage, except of micropores, they
persist through all stages

5. MALARIA
Human Malaria is caused by one of 4 protozoan parasites:
 Plasmodium falciparum
 Plasmodium vivax
 Plasmodium ovale
 Plasmodium malariae

6.  Kingdom
 Subkingdom
 Phylum
 Class
 Subclass
 Order
Protista
Protozoa
Apicomplexa
Sporozoasida
Coccidiasina
Eucoccidiorida
Haemosporina
Plasmodiidae
Plasmodium
Falciparum, malariae,
ovale, vivax
TAXONOMY

7.  Malaria is transmitted through the bite of an
infected female Anopheles mosquito
 May be acquired congenitally from mother to the
child across the placenta
 From platelet or blood transfusions
 From the use of shared needles
Transmission

8. Scope of the Malaria Problem:Scope of the Malaria Problem:
 Malaria is the most common life-threatening infectionMalaria is the most common life-threatening infection
– 1.5 to 2.7 million deaths/yr1.5 to 2.7 million deaths/yr
– 300-500 million infections/yr300-500 million infections/yr
 ~90% of these cases occur in sub-Saharan Africa~90% of these cases occur in sub-Saharan Africa
 Two-thirds of remaining cases are concentrated in sixTwo-thirds of remaining cases are concentrated in six
countries: India, Brazil, Sri Lanka, Vietnam, Colombia,countries: India, Brazil, Sri Lanka, Vietnam, Colombia,
Solomon IslandsSolomon Islands
 most victims are children <5 yrsmost victims are children <5 yrs
 Pregnant women are also especially vulnerablePregnant women are also especially vulnerable
 The majority of P.falciparum cases imported into NorthThe majority of P.falciparum cases imported into North
America and Europe are acquired in AfricaAmerica and Europe are acquired in Africa

9.  P. Ovale is limited to tropical Africa and to discrete
areas of the Western Pacific
 Most West Africans are negative for the Duffy blood-
type, which is shown to be associated with receptor sites for
P. vivax merozoites on the RBCs
 Therefore, many West Africans are not susceptible to
infection with P. vivax
 Falciparum Malaria is confined to sub-Saharian Africa,
the Amazon region of South America, rural forested areas of
Southeast Asia and urban and rural areas of the Indian
subcontinent
 Individuals with sickle-cell trait are more resistant to
severe falciparum malaria than normal homozygotes
Epidemiology

11. Areas of Malaria Transmission and Antimalarial
Drug Resistance

12. Life cycle
 The entire life span is spent in two hosts: the insect
vector and a human host
 Only female Anopheles mosquitoes serve as vectors
 The alternation of sexual and asexual phases is a
significant feature
 The asexual phase, schizogony occurs in the human
 The sexual phase, gamogony occurs in the mosquito
 The subsequent another asexual reproductive
phase, sporogony occurs in the mosquito

13.  Infective form is the slender, elongated sporozoite
 Exoerythrocytic schizogonic phase (hepatocytes)
 Inside the hepatocyte sporozoite develops into a trophozoite
which divides several times
 This multiple fission produces thousands of merozoites
 Erythrocytic schizogonic phase
 Inside the erythrocyte, the merozoite grows to an early
trophozoite stage – the signet ring stage
 Early trophozoite develops into mature trophozoite and
undergoes multiple fission into schizonts
 Merozoites may begin schizogony anew or may become a male
microgametocyte or a female macrogametocyte
 Sexual phase occurs in the female mosquito Anopheles:
microgametocytes – microgametes, macrogametocytes –
macrogametes
 Syngamy produces a diploid zygote, ookynete, oocyst
 Oocysts rupture releasing the sporozoites into the hemocoel

14. Life Cycle

15. Liver stage
Sporozoites
Mosquito Salivary
Gland
Malaria Life Cycle
Gametocytes
Oocyst
Red Blood Cell
Cycle
Zygote

16.  P. vivax and P. ovale cause benign tertian malaria; during
schizogony 12 to 24 merozoites are produced; the rupture from
erythrocytes occurs synchronously at 48 hour interval
 P. malariae causes quartan malaria; the number of
merozoites varies from 6 to 12; merozoites rupture from the
infected cell synchronously every 72 hours
 P. falciparum causes malignant quartan malaria; the
schizonts produce 8 to 32 merozoites; rupture of merozoites
occurs at 48 to 72 hour intervals
 Merozoites of P.falciparum can infect RBCs of all ages,
whereas those of P.vivax and P.ovale infect reticulocytes and
those of P.malariae invade only older RBCs

18. Clinical manifestation
 Incubation period: 7 to 30 days
 Typical symptoms include: fever, chills, sweats,
rigors, headache, nausea and vomiting, body aches and
general malaise, mild anemia and splenomegaly
 Uncomplicated malaria
 Complicated or severe malaria is associated with
vital organ dysfunction:
 CNS (coma, seizures)
 RS (pulmonary edema, ARDS)
 GI complications
 Acute renal failure, severe anemia, metabolic
acidosis

19. Clinically Mild malariaClinically Mild malaria
 An abrupt onset of an initial 'cold stage'An abrupt onset of an initial 'cold stage'
associated with dramatic rigors in which theassociated with dramatic rigors in which the
patient visibly shakes; (10-15minutes)patient visibly shakes; (10-15minutes)
 An ensuing 'hot stage' during which theAn ensuing 'hot stage' during which the
patient may have a temperature of well overpatient may have a temperature of well over
104°F (40°C), may be restless and excitable,104°F (40°C), may be restless and excitable,
and may vomit or convulse; may have frontaland may vomit or convulse; may have frontal
headache and myalgia in limbs and back (2-6headache and myalgia in limbs and back (2-6
housr) andhousr) and
 Finally, the sweating stage, during which theFinally, the sweating stage, during which the
patient feels better and may fall asleep.patient feels better and may fall asleep.

20.  Fever occurs on alternate days with P.vivax and P.ovale
and every 3 days with P.malariae
 With falciparum malaria, fever may be asynchronous,
recurring every 36 to 48 hours
 P.falciparum is a deadly parasite, causing death as
quickly as 36 hours from the onset of symptoms in non-
immune individuals
 P.vivax is a relatively benign parasite that elicits
alternate day fever without causing mortality
 P.ovale also produces alternate day fever and is
clinically similar to vivax malaria

21. Severe MalariaSevere Malaria
 Manifestations of severe malaria include:Manifestations of severe malaria include:
 Cerebral malaria, with abnormal behavior,Cerebral malaria, with abnormal behavior,
impairment of consciousness, seizures, coma, orimpairment of consciousness, seizures, coma, or
other neurologic abnormalitiesother neurologic abnormalities
 Severe anemia due to hemolysis (destruction ofSevere anemia due to hemolysis (destruction of
erythrocytes) and dysertyhropoesiserythrocytes) and dysertyhropoesis
 HemoglobinuriaHemoglobinuria
 Pulmonary edemaPulmonary edema
 Abnormalities in blood coagulation andAbnormalities in blood coagulation and
thrombocytopeniathrombocytopenia
 Cardiovascular collapse and shockCardiovascular collapse and shock

22.  One pathological element unique to
P.falciparum is vascular obstruction
 A condition known as “blackwater fever”
often accompanies falciparum malaria
infections
 Massive lysis of erythrocytes produces high
levels of hemoglobin in urine and blood
 Fever, vomiting with blood and jaundice
also occur
 20-50 percent mortality rate due to renal
failure

23.  In the case of P.vivax and P.ovale, the development of exo-
erythrocytic forms allows the parasite to remain dormant within the
hepatocyte
 These dormant parasites are called hypnozoites and can reinitiate
the infection causing relapsing disease
 P.falciparum and P.malariae do not develop hypnozoites and do not
cause relapsing disease
 Recrudescence is the recurrence of symptoms of malaria after a
subclinical or asymptomatic level of parasitemia for a certain period of
time
 This occurs when blood stages of malaria are maintained at very low
levels after inadequate drug treatment
 All malaria species can cause recrudescence
Relapsing and recrudescence

24. Diagnosis
Thick blood films
 One or two drops of blood from a fingerprick areOne or two drops of blood from a fingerprick are
stirred in a circle on a glass slide, allowed to air dry andstirred in a circle on a glass slide, allowed to air dry and
then stained with Giemsa or Field's .then stained with Giemsa or Field's .
 With this method, the red cells lyse whereas the whiteWith this method, the red cells lyse whereas the white
cells and parasites remain intact. Parasites arecells and parasites remain intact. Parasites are
identified by recognizing both the eosinophilic nucleusidentified by recognizing both the eosinophilic nucleus
and the basophilic cytoplasm of the malarial parasite.and the basophilic cytoplasm of the malarial parasite.
Parasite density can be related to the number of whiteParasite density can be related to the number of white
cells present. This method has far greater sensitivitycells present. This method has far greater sensitivity
than the thin blood film.than the thin blood film.

25. Thin blood filmsThin blood films
 A thin film is produced by spreading aA thin film is produced by spreading a
small drop of blood across a slide usingsmall drop of blood across a slide using
the edge of a second slide, therebythe edge of a second slide, thereby
producing a monolayer of red cells.producing a monolayer of red cells.
 The thin blood film allows accurateThe thin blood film allows accurate
speciation of the parasite andspeciation of the parasite and
quantitation, in which the number ofquantitation, in which the number of
parasites is related to the number of redparasites is related to the number of red
cells present.cells present.

26.  The ring stage derives its name from signet ring-like
appearance
 With a blue-stained nucleus and a pink-stained ring of
cytoplasm
 The trophozoite is a feeding stage and contains single
nucleus with pigment granules, called hemozoin (a product
of hemoglobin digestion), located within the cytoplasm
 The schizont stage is initiated by the division of the
trophozoite nucleus
 Each individual nucleus then becomes surrounded by
parasite cytoplasm to form a merozoite

27. Recent Diagnostic TestsRecent Diagnostic Tests
 Malaria PF antigen capture tests use a monoclonalMalaria PF antigen capture tests use a monoclonal
antibody to theantibody to the P. falciparumP. falciparum and are very usefuland are very useful
tests in those who have not had malaria before .cantests in those who have not had malaria before .can
only detect the presence ofonly detect the presence of P. falciparumP. falciparum..
 The optimal test detects parasite lactateThe optimal test detects parasite lactate
dehydrogenase (pLDH) which can be distinguisheddehydrogenase (pLDH) which can be distinguished
from human LDH. This test can also distinguishfrom human LDH. This test can also distinguish
falciparumfalciparum fromfrom vivaxvivax infections.infections.
 The polymerase chain reaction is useful for makingThe polymerase chain reaction is useful for making
an accurate species diagnosis and detecting lowan accurate species diagnosis and detecting low
level parasitemiaslevel parasitemias

28.  The first known antimalarial drug was quinine – destroys the schizogonic stages,
but has little or no effect on exoerythrocytic stages or gametocytes
 A synthetic drug Atabrine dihydrochloride, which, like quinine is ineffective gainst
exoerythrocytoic stages
 Chloroquine, amodiaquine, primaquine should be administered in combination
 Chloroquine, amodiauine – effective against erythrocytic stages, primaquine –
against exoerythrocytic stages
 3 days of chloroquine, followed by a single dose of primaquine
 Fansidar, combnation of pyrimethamine andsulfadoxine – inhibits folic acid cycle
 Mefloquine - is being added to pyrimethmine-sulfadoxin combination – against
chloroquin-resistant malaria, chemoprophylaxis
 Lapdap – chlorproguanil and dapsone – effective against drug-resistant mlria
Treatment

34. Exchange transfusionExchange transfusion
 CDC recommends that exchange transfusion be stronglyCDC recommends that exchange transfusion be strongly
considered for persons with a parasite density of moreconsidered for persons with a parasite density of more
than 10% or if complications such as cerebral malaria,than 10% or if complications such as cerebral malaria,
non-volume overload pulmonary edema, or renalnon-volume overload pulmonary edema, or renal
complications exist.complications exist.
 Its beneficial effect by removing infected red cells,Its beneficial effect by removing infected red cells,
improving the rheological properties of blood, andimproving the rheological properties of blood, and
reducing toxic factors such as parasite derived toxins,reducing toxic factors such as parasite derived toxins,
harmful metabolites, and cytokines.harmful metabolites, and cytokines.

35. Prevention and control
A. Be Aware of the risk, the symptoms and
understand that malaria is a serious infection
B. Avoid mosquito Bites
C. Take Chemoprophylaxis when appropriate
D. Seek immediate Diagnosis and treatment if
they develop fever during or after travel

36. Susceptibility to Malaria
 Susceptibility conferred by the presence of Duffy
antigen
 Genetic deficiency in glucose-6-phosphate
dehydrogenase in erythrocytes (favism) creates an
inhospitable environment for the parasites
 Humans heterozygous for sickle-cell anemia
posesses a selective advantage over individuals with
normal hemoglobin
 Sickle erythrocyte membrane leaks potassium
from the infected cell
 The parasite dies

37. Vector

38. Sporogony

39. Sporozoites Liver schizonts

40. Merozoite

41. Red blood cell invasion

44. Diagnosis

45. Like most of the Apicomplexa, Toxoplasma is an obligate
intracellular parasite. Its life cycle includes two phases called the
intestinal - enteric (or enteroepithelial) and extraintestinal phases.
The intestinal phase occurs in cats only (wild as well as
domesticated cats) and produces "oocysts."
The extraintestinal phase occurs in all infected animals (including
cats) and produces "tachyzoites" and, eventually, "bradyzoites"
or "zoitocysts."
The disease toxoplasmosis can be transmitted by ingestion of
oocysts (in cat feces) or bradyzoites (in raw or undercooked meat).

46. Domestic cat and other Felidae are theDomestic cat and other Felidae are the definitive hostdefinitive host
Vertebrates areVertebrates are intermediate hostintermediate host
1. amphibians1. amphibians
2. fish2. fish
3. reptiles3. reptiles
4. all warm-blooded animals including man4. all warm-blooded animals including man
Transmission
1. Accidental ingestion of oocysts passed in cat feces through
contaminated soil or handling of cat litter
2. Ingestion of tissue cysts with raw or undercooked meat (lamb,
pork, beef), drinking unpasterized milk, contaminated water, or
unwashed fruits or vegetables
3. Transplacental transmission. Tachyzoites multiply within the
placenta and spread to the fetus.

47. In most humans infected with Toxoplasma, the disease
is asymptomatic.
However, under some conditions, toxoplasmosis can
cause serious pathology, including hepatitis, pneumonia,
blindness, and severe neurological disorders.
This is especially true in individuals whose immune
systems are compromised (e.g., AIDS patients).
Toxoplasmosis can also be transmitted transplacentally
resulting in a spontaneous abortion, a still birth, or a
child that is severely handicapped mentally and/or
physically.

48. Morphology
Oocyst – infective stage transmitted via
cat feces
Tachyzoites – infect macrophages, are
carried throughout the human body via
macrophages, causing pathology
Tissue cysts (pseudocysts) – large cyst-
like forms
Bradyzoites – slowly developing forms
within tissue cyst

49. MORPHOLOGY
The intracellular
parasites (tachyzoite)
are 3x6µ, crescent
shaped organisms that
are enclosed in a
parasite membrane to
form a cyst measuring
10-100 µ in size. Cysts
in cat feces (oocysts)
are 10-13 µ in diameter

51. A sporulated oocyst of
Toxoplasma gondii. The
oocyst contains two
sporocysts, each of which
contain four sporozoites.
Thus, they resemble the
oocysts of Isospora sp.
Only cats will produce and
pass Toxoplasma oocysts;
approximate diameter = 10
µm.

54. SYMPTOMS
Although Toxoplasma infection is common, it rarely produces
symptoms in normal individuals. Its serious consequences are limited
to pregnant women and immunodeficient hosts. Congenital infections
occur in about 1-5 per 1000 pregnancies of which 5-10% result in
miscarriage, 8-10% result in serious brain and eye damage to the
fetus, 10-13% of the babies will have visual handicaps. Although 58-
70% of infected women will give a normal birth, a small proportion
of babies will develop active retino-chorditis or mental retardation in
childhood or young adulthood.
In immunocompetent adults, toxoplasmosis, may produce flu-like
symptoms, sometimes associated with lymphadenopathy. In
immunocompromised individuals, infection results in generalized
parasitemia involvement of brain, liver, lung and other organs, and
often death.

55. TOXOPLASMOSIS IN HUMANS
1. Majority of cases are asymptomatic
2. Mild fever, myalgia, swollen glands and lymph nodes (cervical or
occipital lymphadenopathy), headache, rash, sore throat
3.Immunocompromized individuals are at greater risk: HIV patients,
Organ transplant patients, people on chemotherapy
4.Brain lesions associated with fever, headache, confusion, seizures,
abnormal neurological findings, myocarditis, pneumonitis, chorioretinitis
4. Pregnant women’s fetus are at risk if the mother acquires the
infection during gestation.
5. CDC estimates 400-4000 cases of congenital toxoplasmosis per year.
6.Blindness, hydrocephalus, microcephaly, seizures and mental
retardation are common among infants
7.Hepatosplenomegaly, rash, fever, jaundice, anemia may also be present
8.Most common pathology is chorioretinitis which may result in
strabismus and blindness

56. DIAGNOSIS
 Indirect serological test or direct detection of the organism
 ELISA, IFA, complement fixation
 PCR
 Presence of high IgM in the absence of a significant IgG
titers indicates early stages of primary infection
 A negative IgM titer is helpful for ruling out recent
infection
 Measurement of maternal and infant IgG antobodies is
critical
 An infant: maternal Ig G ratio of four or higher is
indicative of new infection
 The presence of high titers of specific IgM antibodies in the
infant’s serum is diagnostic

57. TREATMENT
Acute infections benefit from pyrimethamine or sulphadiazine.
Spiramycin is a successful alternative. Pregnant women are advised
to avoid cat litter, handle uncooked meat carefully and undercooked
meat.
Additional drugs
Sulfonamide drugs
Folinic acid
Clindamycin
Trimethoprim-sulfamethoxazole

58. Babesiosis
Causitive agent: Babesia microti
Vector: tick Ixodes dammini
Symptoms mimic mild malaria
Hemolytic anemia
Clindamycin plus quinine has been used successfully
to treat the disease