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MALARIA
• Clinical picture of Malaria was recognized centuries before
discovery of the pathogen, that’s why this disease was
referred to their clinical features, usually by type of the
fever.
• Tertian and quartian fever were noted, in 48h and 72h
cycles of fever
• Modern tendency is to refer to the various types of malaria
by name of the agent
• Benign tertian malaria = Vivax Malaria
• Malignant tertian Malaria = Falciparum Malaria
• Quartian Malaria = Malaria Malaria, but for the sake of
euphony, we use the old term ‘quartian malaria’ because
it’s the unique feature
• Ovale malaria was described so recently as to possess
only the name derived from P. ovale
• Human malaria is thought by some authorities to have
originated from South East Africa & then to Europe
Epidemiology
– Falciparum and Ovale Malaria are primarily disease of the
tropics
– Quartian malaria is seen in subtropic & temperate zones as
well
– Vivax is most common in all endemic areas
– Gametocytes appear in circulating blood early in the course of
vivax infection and may appear with succeeding clinical
relapses
– Gametocytes of Falciparum Malaria appear in circulating blood
approximately 10 days after onset of parasitemia & are not
infectious for mosquitoes for another 4 days
– In addition to gametocytes-induced mosquito-transmitted-
malaria, transmission by means of transfusion is also possible
– Mechanical transmission through shared syringes is seen
among IVDU
– Because sporazoites are not likely to be present in transfused
blood, relapse equally unlikely to occur with transfusion or
syringe-transfused malaria
– Congenital transmission is rare
– Various species of malaria
Relapse parasite that
= recurrence havetakes
different
placeT after complete initial clearing of the erythrocytic infection and implies re-invasion of the blood stream by p
requirements for development in mosquito host
– In cooler parts of endemic areas, development of P. falciparum
don’t take place in spring & attacks of infections caused by this
species occur mainly in hot weather of summer & early autumn
– From this characteristic seasonal appearance comes the old
name of Estival-Autumnal Malaria (in summer & autumn.
Estival = relating to, or appearing in summer)
– Immunity is relative Recrudescence = recurrence of symptoms in a patient whose blood stream infection has previously been at such a low level as not to b
& generally strain-specific
– Infants born to native parent in the regions in which Malaria is
hyperendemic are almost completely free of Malaria during first
few months of life dt passive transfer of maternal immunity
Life Cycle of Plasmodium~
 There are 2 parts to the life cycle
○ Human
○ Mosquito
 Various species of Anopheli mosquito are definitive hosts of
Malaria parasites & when female mosquito bites an infected
person, it draws into her stomach blood that may contain
male & female gametocytes
 In the mosquito, as blood T ↓, male (microgametocyte)
undergo process of maturation that results in production of
a number of microgametes
 At the same time, female (macrogametocytes) matures to
become macrogamete, after which it maybe fertilized by the
microgamete forming a zygote
 Zygote becomes elongated and active & is called an
ookinate
 Ookinate penetrates cells of the stomach wall of mosquito
& rounds up just beneath the outer covering of that organ to
become an oocyst
 Growths & development of oocyst result in production of
large numbers of slender haploid sporozoite which break
out & wander throughout body of mosquito
 Length of development cycle in mosquito depends not only
on species of plasmodium but on the particular mosquito
host & ambient T
 It ranges from 8 days (P. vivax) to 35 days (P. malariae)
 Those sporozoites that enter salivary glands of mosquito
maybe inoculated into next person bitten
 After bite of infected mosquito, sporozoite inject into blood
stream, leave the blood vascular system in 40 mins &
subsequently invade parenchymal cells of liver
 Later, development of P. falciparum and P. malariae differs
from that of P. vivax and P. ovale
 In all 4 species, asexual multiplication takes place in liver
cells but with PV and PO, a varying proportion of
sporozoites enter a resting stage before asexual
multiplication, while others undergo this multiplication w/o
delay
 Resting stage of sporozoite, also known as hypnozoite
 After period of weeks/months, reactivation of hypnozoites
initiate asexual multiplication
 Hypnozoites reactivation brings about relapses
characteristic of these species producing a wide variation in
time of relapse dt difference in latency period of hypnozoite
 Successive relapses in the same pt are the result of
infection of a number of sporozoites, each of which produce
hypnozoite of different reactivation time
 This subpopulation are grouped characteristically within a
given strain with a distinct tendency to a
○ shorter latency in strains originating from tropical
areas &
○ a longer one in those origination from temperate
& especially colder areas
 Asexual multiplication (schizogony) results in production of
thousands of tiny merozoites in each schizont
 Rupture of the infected hepatic cells release merozoite into
circulation
 In the blood stream, asexual cycle takes place within the
RBC
 The process is known as erythrocytic schizogony that
results, in 48 – 72h, in the formation of from 4 – 36 new
parasites in each infected cell
 At end of schizogonic cycle, the infected RBC rupture &
liberate merozoites which in turn infect new RBC
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 Rupture of RBC liberates products of metabolism of the
parasites & of the RBC, and it is thought that if large
numbers of RBC rupture simultaneously, volume of toxic
materials maybe sufficient to bring about a malarial
paroxysm
 Generally in the initial stage of infection, rupture of infected
cells is not synchronous
 It’s so called initial fever
Features of Primary Malaria
 Schizogony x take place in peripheral blood
 Therefore, the only stages of parasite ordinarily seen young
trophozoites & gametocytes
 Double/Triple infection of RBC are very common (high
parasitemia)
 Infected RBC which retain their original size may develop a
few irregular, dark red rod or wedge-shaped markings
known as Maurer’s dots or clefts
 In very heavy infections, schizonts maybe seen in
peripheral blood

– Fever maybe continuous or fluctuant Clinical Manifestations

– In intermittent fever characteristic for this disease, T returns to
normal 1 or > times during 24h  IP longest in quartian & shortest in PF
– Diff variants  Last few days of IP maybe marked by prodromal sx such
○ Undulant as
○ Intermittent ○ HA
○ Continuous ○ Photophobia
○ Etc ○ Msc aches & pains
– Fever peaks themselves may have a regulatory effect on ○ Anorexia
development cycle speeding up those that are out of phase ○ Nausea
– After a number of days, febrile cycle develop a 48h or 72h ○ St vomiting
periodicity  Sx seen in all types of malaria
– After few paroxysms, gametocytes appear in the RBC  Malaria paroxysms is typically ushered in with a sudden
– They are finally formed male & female gametocytes shaking chill or rigor
– They continue to circulate in blood stream & if ingested by  This may last 10-15min or longer
Anopheles mosquito, undergoes transformation to gametes
 During this stage, pt complain of extreme cold although T ↑
(gametogonia), sexual fusion & subsequent development to
at the onset & rises during period of the chill
sporozoites
 The hot stage follows the cold without respite and a pt who
was a few moments before huddled under a pile of blankets
P. vivax
now throws them off
 Skin that was pale & cyanotic in cold stage becomes
 Everywhere in endemic areas of malaria
flushed
 In blood smears from pt infected with PV, a variety of
 Pt frequently seems agitated and maybe restless,
stages in the asexual cycle of the parasite mb seen
disoriented & maybe even delirious
 Gametocytes may also be present
 Severe frontal HA & pain in limbs & back are common
 Stages in the sexual cycle that are seen depend on when
 Hot stage
blood is taken in relation to the febrile cycle
○ 2-6h in PV & PO
 Paroxysms follows the somewhat synchronous rupture of
○ 6h & > in PM
infected cells, liberating merozoites which in turn infect new
RBC ○ Longer in PF
 First few hours after paroxysms, majority of infected cells  Following hot stage, pt sweat profusely & begins to feel
contain very early forms of trophozoites (rings) better
 In blood film stained with Giemsa stain or Field’s stain,  Sweating stage lasts several hours & at its end, pt is weak
parasite appear as minute blue disk with red nucleus lying & fall asleep
in pink cytoplasm of RBC  Upon awakening, T is normal or subN
 Pt feels quite well until onset of next paroxysm
 As the cycle is not synchronous, parasites or >1 site of
 Acute splenomegaly may occur rapidly especially in non-
development are usually seen in blood smears
immune pt and may rarely result in tears of splenic capsule
(trophozoites, schizonts, merozoites & gametocytes)
& intra-abdominal bleeding requiring surgical intervention
P. ovale
Diagnosis
– Morphological feature that originally led to the
– Thick and thin blood films
establishment of PO as a separate species is the ovoid
shape of many infected RBC. – It should be noted that the 1st level of diagnosis is the
– This feature is variable presumptive differentiation of PF from the other species as the
presence of PF in non-immune pt constitutes a medical
P. malariae emergency
– CBC
- PM morphologically very similar to PV & differs only clinically with ○ Anemia
72h life cycle ○  ESR
– Liver function test
P. falciparum
– Kidney function test
 disease in tropics & subtropics
 sharply different from other malaria
 a lot of morphological differences too
Complications
 gametocytes are elongated or sausage-shaped in contrast
with spherical/ovoid gametocytes of the other species – Vivax, Ovale & Quartian malaria are generally benign
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– Majority of complications are in PF Black Water Fever

– Dt change in physiological character of RBC infected with PF,
may lt – Syndrome dt massive intravascular hemolysis & consequent
○ localized capillary obstruction, Hb-uria
○ ↓blood flow, – Almost exclusively in pt with severe PF but possible in PV &
PM
○ tissue hypoxia,
– Usually there is h(x) of previous malaria attacks & occasionally
○ infarction
of prior bouts of BWF
○ death – Onset occur generally during a paroxysm but mb w/o any
accompanying symptoms
Cerebral Malaria – Possible to miss onset of condition because Hb-uria by itself x
give rise to Sx
– Most common Cx of infection dt PF – Cause is unknown
– Frequent COD – Mb connected with auto-immune phenomenon with
– Onset mb sudden development of Ab to RBC, st accompanied by quinine action
– Mb even 1st symptom of infection! – T ↑, urine becomes dark beer colour
– Severe HA is the usual Sx, followed by – After sedimentation, divided into 2 :
○ Drowsiness ○ Lower part : dark beer
○ Confusion ○ Top part : red wine
○ Coma
– Cerebellar ataxia maybe evident Algid Malaria
– Physical symptoms of CNS involvement mb quite variable or
completely absent – Looks like shock
– CM – Rapid development of hypotension & impaired vascular
○ Precoma I (apathic pt) perfusion
○ Precoma II (active pt!) – T  rapidly
○ Coma I (x conscious,  reflexes) – Pt maybe delirious
○ Coma II (x reflexes)
Pulmonary edema
– Suspicion of Cerebral Malaria indicates prompt administration
of
– Develops rapidly in oliguria/anuria pt
○ Quinine
– Or in pt with CVS disease or dt DIC
○ Quinidine
Usually IV at first & consideration of exchange transfusion
Tropical Splenomegaly syndrome
– Sequelae
○ Cortical blindness – Spleen usually enlarges during acute attack of malaria but then
○ Hemiparesis regress to N
○ Generalized spasticity – Persistent splenomegaly is x N
○ Ceberellar ataxia – Splenomegaly of unknown cause is typical in malaria of
○ Severe hypotonia endemic area in tropics
– Called tropical splenomegaly syndrome
Anemia – Syndrome is characterized by
○ Chronic splenomegaly
– Heavy parasite load in PF is to be expected & should be ○ Marked  of serum IgM (as compared with ppl
treated with due care to prevent fluid overload & overt
from same area who do not have splenomegaly)
pulmonary edema
– Maybe also lymphatic infiltration of hepatic sinusoids
– If hematocrit <20% or hematocrit ≥5%
– Response to Anti-malaria treatment is essential to Dx
– Anemia, reticulocytosis & TCP are usual
Renal Diseases
– Only effective Rx is life-long anti-malarial suppressive Rx
– Splenectomy has been tried, but initial improvement is not
– Common in severe PF
sustained & hepatomegaly ensues
– Also in repeated PM infection esp in children
– ARF may occur in any attack of severe PF malaria
Hyperparasitemia
– Result of tubular necrosis, resulting from RBC sludging & renal
anoxia, but usually improvesas infection is brought under
control – In excess of 10 – 20% of the RBC =  mortality rate
– Nephritic syndrome dt acute GN & typical renal biopsy finding – Prompt exchange blood transfusions is life-saving
in light microscopy in PM & PF
– Proteinuria is common in attack of PF & in children associated Hypoglycemia
with massive edema & other clinical symptoms of nephrotic
syndrome – Hyperinsulinemia dt treatment with quinine or quinidine
– Renal lesions are 2° to deposition within glomeruli of circulating – Quinine shd be admin with 10% glucose in pt who are prone to
Ag-Ab complexes that may occur in chronic low-grade PM hypoglycemia
infection
– This form of nephrotic syndrome is essentially unaffected by
administration of GCS
– Treatment is not different from treatment of malaria Therapy
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– 1st effective treatment is with bark of Cinchona tree which

contains quinine
– Tree grows mainly in Peru
– Proper use of anti-malarial drugs is based on knowledge of
their effects on parasite and various stages of their life cycle
– Suppressive Rx, chemoprophylaxis attempts to destroy
parasites as they enter blood stream with small doses of drugs
effective in erythrocytic stages
– Radical cure = elimination of blood stream infection, tissue
stage & liver infection too
– 1st line is Blood Schizonticides:
○ Chloroquine
○ Metroquine
○ Quinine
○ Quinidine
○ Pyrimethamine-sulfadiazone
○ Doxocycline
○ Artemisinine
– They suppress an acute attack of malaria
– Prescribe drugs for 3days & check parasitemia every day
○ if x change  change the drug
○ if there is ↑  use this drug for full course
– PO and PV : after blood schizonticides, have to use tissue
schizonticides (Primaquine)
– We have to use gameticides too,
○ Chloroquine
○ Amodium chloroquine
X affect mature gametocides
– Primaquine is gametocidal for all species

Prevention

Awareness
Bite Prevention
Chemoprophylaxis
rapid Diagnosis and Treatment

Reduce exposure by

– Insecticides
– Larvicides
– Bed nets
– Insect repellants
– Clothes

In areas where Chloroquine-resistance was not reported =

Chloroquine 1x/week

Everywhere else = Mefloquine 1x/week

Mefloquine is CI?

– Doxycycline 1x/week
– Chloroquine 1x/week
– Treatment dose of Pancidar for use in case of fever

If patient cannot get appropriate medical care in 24h,

– Chloroquine 1x/week and daily paludrine

– Treatment dose of Pancidar