MALARIA PLASMODIUM SPP LIFE CYCLE
A. Infective cycle inside mosquito
MALARIA 1. Anopheles bites man
Leading parasitic disease than causes mortality 2. Feeds on blood with Gametocyte
worldwide 3. Forms Zygote
627,000 malaria-related deaths in 2012 4. Oocyst
Estimated 3.4B people at risk for infection 5. Mature oocyst release sporozoites
Millenium Development Goal 6 (MDG 6) goal:
Combat/ Reduce the burden of HIV/AIDS, malaria and B. Exoerythrocytic cycle - outside RBCs
other diseases 1. Anopheles mosquito bites man (injects
sporozoite)
HEMOSPORIDIA 2. Sporozoite invades parenchymal cells of the
Plasmodium spp liver then it signals the start of schizogony
- causative agent of malaria 3. Infected cells burst then release merozoites
Definitive Host
- Mosquito (Anopheles) C. Erythrocytic cycle-- inside RBCs
- Sexual stage occurs (Sporogony) 1. Merozoites infect RBCs then burst which released
Intermediate Host the merozoites
- Man 2. Some merozoites are destroyed by the immune
- Asexual stage occurs (Schizogony) system
Infective stage to mosquito: GAMETOCYTE 3. Some merozoites transform to become
Infective stage to man: SPOROZOITE Macrogametocyte (female) and Microgametocye
(male)
P. vivax P. malariae P. falciparum P. ovale
Disease Malignant Tertian Malaria
Benign Tertian Malaria Quartan Malaria Ovale Malaria
caused Blackwater Fever
RBC stage Neocytes (Young RBCs)
Old RBCs All ages of RBCs Young RBCS
infected Reticulocytes (RETICS)
Serrated (with notch or
Infected
tooth ends)
RBC Enlarged Larger than normal Remains in Normal size
with fimbriated edges
appearance
Enlarged/Comet like
8-24
possibility of Multiple Ring
# of 612 (ave 810)
Infection; Double
merozoites 12-24 (ave. 16) "rosette, daisyhead, 8
Chromatin/ Nuclear dots;
per RBC fruitpie appearance"
Applique; Accole Marginal
Forms
Shape of Crescentshaped or
Round Ovoid
gametocyte Bananashaped
Schuffner's dots Maurer's Dots
Schuffner's Dots/ James
Dots Schuffner's Dots (+) Band Cuneiform Dots
Dots
Trophozoites Stephen Christopher Dots
Pre--patent
period
sporozoite
injection to 11 15 days 3 4 weeks 11 14 days 14 26 days
detection of
parasites in the
blood
Incubation
Period
time of injection 12 20 days 18 40 days 8 15 days 11 16 days
and appearance
of signs and
symptoms
1
2
Sporozoa life cycle stages/terms 3 Stages of Paroxysms
Oocyst: results from fusion of gametes in the Sporozoa. A. Cold Stage
Infective stage in most cases: passed in host feces in - Inappropriate feeling of coldness
case of intestinal protozoans, or in blood in gut of the - Violent teeth chattering and shaking of the whole
mosquito vector in the case of Plasmodium. body
Sporozoites form in oocyst in host via mitosis (asexual - Patient may vomit and febrile convulsion may
fission) develop
Sporozoite: special term form trophozoite in - Last for 15-60 minutes after which the shivering
Sporozoans. Formed by mitosis within oocyst and ceases and hot stage or the flush phase begins
infects new host cells; hepatocytes in case of B. Hot Stage
Plasmodium. Mitosis (schizogeny) of these cells - patient becomes hot and manifest headache,
result in formation of merozoites. Merozoites can palpitations, tachypnea, epigastric, discomfort,
continue mitosis = asexual reproduction, or thirst, nausea, and vomiting
Merozoite: results from mitotic fission (schizogony) of - fever of 40-41C
sporozoites. May infect same cell type as sporozoite - skin is flushed and hot
or different host cell: RBCs causing clinical malaria in - last for 2-6 hours
the case of Plasmodium. Can also go through meiosis C. Sweating Stage
to form gametes. - defervecence, diaphoresis, profuse sweating;
Gametocyte: result of merozoite cell fission via Meiosis - temperature lowers over the next 2-4 hours and
Fusion of these results in formation of oocyst. symptoms diminished
Incubation period may range from 9 days to 3 years - Total duration of attack is 8-12 hours
depending on: The pathological processes are the result of
Parasite stain erythrocytic cycle
Dose of sporozoites inoculated The reduction in cells deformability is due to the
changes in the red blood cell cytoskeleton and the
Immune status of the host
increase in membrane stiffness and cytoplasmic
Hosts malaria chemoprophylaxis history
viscosity
PATHOLOGY In the course of invasion, electron-dense
One schizogony (asexual cycle) can produce: submembranous structures appear and enlarge
Fever These become the knobs which are important in co-
Chills adhesion
Synchronized RBC destruction They contain several proteins such as:
The interval between attacks is determined by the rosettins
length of erythrocytic cycle: riffins
P. falciparum P. ovale P. vivax P. malariae histidine-rich proteins
P. falciparum erythrocyte membrane protein 1 (most
Length adhesive)
Alternate days Alternate days
of eryth. Every 48 hrs Every 72 hrs
cycle
(48 hrs) (48 hrs) Infected RBCs also undergo altered membrane
transport mechanism
Malaria Malignant
Ovale Malaria
Benign Tertiary
Quartan Malaria The fever, febrile paroxysms, headache, various
type Tertian Malaria Malaria
aches and pains and prostration are probably the
P. malariae longest erythrocytic cycle result of cytokines at the time of schizont rupture
ANEMIA due to RBC destruction leading to large Other destructive tissue processes include:
spleen and possible joint pains increased capillary permeability, which allows fluid
Paroxysms of fever to leak into surrounding tissues
Prodromal Symptoms (WLANDS)
congestion in blood vessels resulting in tissue
infarction and necrosis
Weakness and Exhaustion
Loss of appetite In Severe forms:
Aching bones, limbs, and back impairment of consciousness
Nausea and vomiting delirium
Desire to stretch or yawn generalized convulsions are observed
Sense of chillness Severe hemolytic anemia
Cerebral malaria generally manifest with diffuse
Onset (MBED)
symmetric encephalopathy
Malaise
Other signs and symptoms include retinal
Backache
hemorrhage, bruxism and mild neck stiffness
Epigastric discomfort
Coma and death
Diarrhea
3
Altered pulmonary function which include: Most prevalent Plasmodium infection in the WORLD:
air flow obstruction P. vivax
impaired ventilation and gas transfer Most prevalent Plasmodium infection in the
increased pulmonary phagocytic activity Philippines: P. falciparum
In African children, pneumonitis from sequestered There is also a possibility of MIXED INFECTION (P.
RBC vivax + P. falciparum infections COMBINED)
In adults, pulmonary edema and Acute Pulmonary Resistant Individuals
Distress Syndrome (ARDS) Individual with Fy (a-b-) African Black Race
Patient with G-6-P-D enzyme
Malaria in Pregnancy Patient with Sickle Cell anemia (malarial growth will
Maternal death not be favored)
Maternal anemia
Intrauterine growth retardation Plasmodium spp.
Spontaneous abortion Plasmodium spp. And Duffy blood group system
Stillbirth Two receptors:
Low birthweight associated with risk for neonatal BINDING RECEPTOR found on all RBC.
death Merozoites can BIND to RBC irrespective of Duffy
phenotype
Most common complication of severe malaria in
INVASION RECEPTOR DUFFY ANTIGEN.
children:
Merozoites of P. vivax and P. knowlesii require
Cerebral malaria
Severe anemia Duffy antigen in order to invade RBC
Respiratory distress FY3 antigen receptor for P. knowlesii
Hypoglycemia FY6 antigen receptor for P. vivax
Seizures Thus, a merozoite can only BIND to RBCs of Duffy
Opisthotonos negative individuals while merozoite can BIND and
INVADE red cells of Duffy positive individuals.
Between 5-30% of children who survive cerebral
malaria develop sequelae such as: Laboratory Diagnosis
Cerebral ataxia Preparation of Blood Smear
Hemiparesis Thick and Thin Blood Smear Stained with GIEMSA
Cortical blindness THICK dehemoglobinized; utilized for SCREENING
Behavioral disturbances THIN (usually fixed with 50% methanol; utilized for
Hypotonia IDENTIFICATION PUPOSES)
Generalized spasticity Thick and thin blood smears stained with Giemsa or
Epilepsy Wrights stain (gold standard)
Blood smears may be taken anytime (every 6 to 8
P. falciparum infection is the MOST FATAL. It can hours)
lead to: QBC (Quantitative buffy coat) uses a specially
CEREBRAL MALARIA red blood cells, plasmodium prepared capillary tube coated with acridine orange.
organisms and pigments block brain vessels Malarial parasite appear as bright green and
BLACKWATER FEVER sudden massive yellow when viewed under the fluorescent
intravascular hemolysis with resultant hemoglobinuria microscope
usually leading to the formation of BLACK urine. Malaria Rapid Diagnostic test make use of
(Renal Failure) immunochromatographic methods in order to detect
Plasmodium-specific antigens in a finger-pricked
Important Notes Plasmodium species blood sample
Mode of tansmission:
Serological test:
Mosquito vector bite
Blood transfusion easier to treat, blood did not IHA (indirect hemeagglutination)
enter the liver (exoerythrocytic cycle) IFAT (indirect fluorescent antibody test)
HYPNOZOITE ELISA (Enzyme linked immunosorbent assay) but
Dormant or sleeping stage; once activated, it can cannot differentiate between current and past
release merozoites infections
Responsible for malarial RELAPSE
PCR
RELAPSE is only possible for P. vivax and P. ovale
4
Plasmodium knowlesi In recent years, rapid diagnostic tests (RDTs) that
First reported case in the Phil. was in 2006 detect particular antigens the Histidine-rich Protein II
Previously thought to be a parasite of monkeys (HRP-II) of P. falciparum. Examples of this RDT
Found in Malaysia and other parts of Southeast Asia available in the market are Parasight F marketed by
Resembles P. malariae by microscopic method Becton Dickinson and the Malaquick test
Infect erythrocytes of all ages manufactures by ICT Diagnostics, Sydney, Australia.
Depending on the morphological forms present, it may Another group of RDTs is able to detect the lactate
also resemble P. falciparum dehydrogenase (LDH) of the parasite. Unlike the HRP-
DNA extraction and nested-PCR examination is II tests, this test is able to detect all stains of
known to reveal the differences between P. faciparum Plasmodium that affect humans but cannot distinguish
and P. knowlesi between P. vivax, P. ovale and P. malariae. The test
Cross reactivity with P. vivax appears to interfere with is available in the market under the name OptiMal and
PCR testing is manufactured by Flow Laboratories, Portland,
Oregon.
Clinical features
Respiratory distress EPIDEMIOLOGY
Acute renal or multi-organ failure to shock Cases have decrease (based on 2013 report)
High in Region IV-B, Autonomous region in Mindanao
Treatment 49 out of 81 provinces are endemic to malaria
Quinine Total of 11.3 million Filipinos (14.8% of the population)
Chloroquine are at risk for the disease
Artemetherlumefantrine In the year 2000, the incidence was reported 0.48 per
Gametocytocidal drugs destroy the sexual forms in 1000. The total number of deaths due to malaria in the
the blood year was 536
Hypnozoitocidal drugs kill dormant forms in the liver More than 70% is caused by P. falciparum while less
than 30% is caused by P. vivax. P. malariae occurs in
Sporonticidal drugs inhibit the development of cocyst
less than 1% of cases, while P. ovale has been
on the gut of mosquito
reported in Palawan in 1960
Babesia microti
ENDEMIC PROVINCES + VECTORS
Commonly mistaken as P. falciparum ring form
Cagayan, Isabela, Palawan, Sulu, Tawi-tawi
To differentiate:
Lack of malarial pigment provinces with high malaria cases as of 2013.
Lack of growing trophozoites Principal vector anopheles minimus var. flavirostris
Vector of Babesia:ticks (a night biter)
Anophele litoralis is associated with malaria
transmission in the coastal areas of Mindanao,
particularly in Sulu
Anopheles maculates coexists with A. flavirostris
responsible for malaria transmission in higher
altitudes
Anopheles mangyanus prefer habitats located in the
forest fringes
PREVENTION AND CONTROL
Screening of houses
Use of mosquito nets, protective clothing and
mosquito repellants; insecticide
Wearing of light colored clothing
Fig. 2. Babesia parasites in human erythrocytes.
(a) B. divergens, Chemoprophylaxis
(b) B. venatorum, Proper vector control (environmental modification,
(c) Babesia sp. MO1 from Kentucky, biological control (larvivorous fish) chemical control
(d) B. microti,
(e) B. duncani,
(f) Babesia sp. KO1 from Korea.
(1) Paired piriforms; (2) Tetrads; (3) Ring forms.
