Malaria - Update

Dr.Girish Vaswani (D.N.B. med)

Consulting Physician
Bhatia hospital
Motiben Dalvi
Kothari Hospital

Plasmodium species which

infect humans
Plasmodium vivax ( B. tertian)
Plasmodium ovale ( B. tertian)
Plasmodium falciparum ( M.tertian)
Plasmodium malariae (quartian)

Malaria Life
Cycle
Life Cycle

Sporogony
Oocyst
Sporozoites
Mosquito Salivary
Gland

Zygote

Exoerythrocytic
(hepatic) cycle

Gametocytes

Erythrocytic
Cycle

Schizogony

Hypnozoites
(for P. vivax
and P. ovale)

Malaria Transmission Cycle

Exo-erythrocytic (hepatic) Cycle:
Sporozoites infect liver cells and
develop into schizonts, which release
merozoites into the blood

Sporozoires injected
into human host during
blood meal

Parasites
mature in
mosquito
midgut and
migrate to
salivary
glands

MOSQUITO

Parasite undergoes
sexual reproduction in
the mosquito

HUMAN

Some merozoites
differentiate into male or
female gametocyctes

Dormant liver stages

(hypnozoites) of P.
vivax and P. ovale
Erythrocytic Cycle:
Merozoites infect red
blood cells to form
schizonts

Components of the Malaria Life Cycle

Sporogonic cycle

Infective Period
Mosquito bites
uninfected
person
Mosquito bites
gametocytemic
person

Mosquito Vector
Parasites visible

Prepatent Period

Human Host

Symptom onset
Recovery

Incubation Period
Clinical Illness

Clinical presentation
Early symptoms

Headache
Malaise
Fatigue
Nausea
Muscular pains
Slight diarrhea
Slight fever, usually not intermittent

Could mistake for influenza or gastrointestinal

infection

Clinical presentation
Acute febrile illness, may have periodic febrile
paroxysms every 48 72 hours with
Afebrile asymptomatic intervals
Tendency to recrudesce or relapse over months to
years
Anemia, thrombocytopenia, jaundice,
hepatosplenomegaly, respiratory distress syndrome,
renal dysfunction, hypoglycemia, mental status
changes, tropical splenomegaly syndrome

Malarial Paroxysm
Can get prodrome 2-3 days before
Malaise, fever,fatigue, muscle pains, nausea, anorexia
Can mistake for influenza or gastrointestinal infection
Slight fever may worsen just prior to paroxysm

Paroxysm
Cold stage - rigors
Hot stage Max temp can reach 40-41o C, splenomegaly
easily palpable
Sweating stage
Lasts 8-12 hours, start between midnight and midday

Malarial Paroxysm
Periodicity
Days 1 and 3 for P.v., P.o., (and P.f.) - tertian
Usually persistent fever or daily paroxyms for
P.f.
Days 1 and 4 for P.m. - quartian

Differential diagnosis
At the onset of the disease it may be very difficult to
differentiate malaria from viral fevers.
Jaundice and fever is also seen in viral hepatitis and
other forms of hepatitis, cholecystitis and hepatic
abscess.
Dengue, Leptospirosis and hemolytic anemia have
the common triad of pallor, icterus and
splenomegaly.

P. Falciparum-cerebral malaria:A
symmetric encephalopathy
Whenever you see a patient who complains of
headache, vomiting, diplopia, and is disoriented,
confused or behaving abnormally then always
think MALARIA. The relatives may say that he is
always sleepy and had a few convulsions.
On examination, varying levels of consciousness
may be noted with divergent or convergent eyes,
release of primitive reflexes, hyper/hyporeflexia,
hyper/hypotonia, extensor/flexor plantars and
absent abdominals-cremasterics.
Signs of meningeal irritation may also be elicited.

Cerebral Malaria-D/D
Always rule out other causes of altered
sensorium like encephalitis, menigitis and
cerebral bleeds and infarcts.
Check for metabolic parameters and renal and
hepatic failure as other diagnosis or as
contributing to reduced alertness or
convulsions

As the disease progresses

The patient becomes more drowsy and breathless
suggesting ALI and ARDS.The O2 concentration
starts to drop and respiratory alkalosis sets in.
Eventually he may be started on mechanical
ventillation.
The kidneys start to fail and urine output lessens
signifying acute renal failure.
Shock,hypoglycemia, lactic acidosis and DIC
complete the picture of MOSF.

Chronic malaria - tropical

splenomegaly

Anorexia, nausea, vomiting, weight loss

Symptoms due to anemia pancytopenia
Abdominal pain
Abdominal lump
Splenic rupture

Tropical splenomegaly

Patient from endemic area

Many attacks of malaria in childhood
Moderate to massive hepatosplenomegaly
Smear negative for parasites
Malarial antibodies positive
Parasites in bone marrow
Hypersplenism

Tropical splenomegaly diff

diagnosis

Kala-azar
Portal hypertension hepatic, extrahepatic
Myeloproliferative diseases
Lymphomas
CLL

Chronic complications of malaria

Tropical splenomegaly with or without
hypersplenism is very common.
Immunological complications like nephrotic
syndrome and a predisposition to Burkitts
lymphoma have also been reported.

Diagnosis - malaria
A high index of suspicion is required and a
history of visit to a malarious tract should always
be sought by direct questioning of the patient or
accompanying persons.A history of recent blood
transfusion may point to an iatrogenic mode of
spread of malaria.
Thick and Thin smears should always be examined
and indirect evidence of malaria by demonstrating
hemolytic jaundice should be performed.

Other tests
Generally the complete blood counts and platelets
counts are of little benefit in the diagnosis but aid
in assessing the severity and complications of the
ongoing infection.
PfHRP2 dipstick or card test: monoclonal ab
captures the parasite antigens. Only for falciparum
malaria.
LDH dipstick or card test

Drugs used to treat Malaria-First

group

CHQ, Amiodaquine
Quinine, Quinidine
Mefloquine, Halofantrine
Lumefantrine

First group-adverse reactions

GI disturbances-nausea, vomiting, diarrhoea and
erosive or hemorrhagic gastritis with abdominal
pain and hematemisis at times.
Cardiovascular instability- Prolonged QTc
ventricular tachyarrythmia and hypotension
CNS-disorientation, abn behaviour, seizure
Metabolic- hypoglycemia
ALWAYS CHECK K, MG, SUGAR before
starting

Drugs used to treat malaria

Doxy, Tetra pregnancy, children, hepatic
Sulfadoxine-Pyrimethamine sulfa allergy,
renal failure
Artemisin derivatives - safe

Drugs used to treat Malariaothers

Clindamycin
Azithromycin
Proguanil
Dapsone
Primaquine

How to select antimalarials

Type of malaria vivax or falciparum?
Sensitive or resistant
Associated renal or liver damage
Associated metabolic-electrolyte imbalances
Pregnancy, weight
Drug reactions
Oral therapy possible?

Intravenous anti-malarial
therapy- Indications
Presence of vomiting
Inability to start oral therapy may also be due
to altered mental alertness and seizures.
Patients who are intubated and on
ventillators.
Those who are critically ill.

Intra-venous therapy
Chloroquine: intravenous 10 mg/kg max
600mg over 6-8 hrs followed by 15mg/kg
max 900mg over next 24 hrs as slow
infusion.
Quinine : intravenous 20mg/kg over 4 hrs;
then 10mg/kg(max 600mg)three times a
day.

Intra-venous therapy-severe
f.malaria
Artesunate 2.4mg/kg stat; followed by 2.4mg/kg at
12 hrs, 24hrs and then daily. OR
Artemether 3.2mg/kg stat im; then 1.6mg/kg od im.
PLUS
Add quinine 20mg salt/kg over 4 hrs; followed by
10mg/kg over 2-8 hrs slow infusion thrice a day.
PLUS
Doxy 100mg bd / tetra 250mg (4mg/kg) qds

Oral therapy-CHQ sensitive

malaria
Chloroquine 10mgbase/kg stat followed by
5mg/kg at 12, 24 and 36 hrs.
OR
Chloroquine 10mg/kg stat; then 10mg/kg at
24hrs and 5mg/kg at 48 hrs.
OR
Amodiaquine 10mg base/kg od x 3 days

Oral therapy-sensitive f.malaria

Sulfadoxine-pyrimethamine 25mg/kg (max
1500mg of sulfadoxine) single dose
PLUS
Artesunate 4mg/kg od x 3 days
OR
Amodiaquine/CHQ plus artesunate

Multidrug resistant malaria

Mefloquine 8mg base/kg orally od for 3 days,
or 15mg/kg and then 10mg/kg next day
PLUS
Artemether-lumefantrine (1.5/9mg/kg bid) or
artesunate 4mg/kg od for 3 days

Multidrug resistant malaria- 2

line

nd

Doxy 100mg bd (3mg/kg x 7 days)

Artesunate 2mg/kg od or quinine 10mg/kg tds
PLUS
1 drug of the following:
Tetra 250mg qds (4mg/kg qid x 7 days)
Clindamycin 10mg/kg bd x 7 days or
atovoquone-proguanil 20/8 mg/kg od x 3
days

Other supportive therapy

Maintain acid-base balance

Maintain blood sugar
Add folvite for hemolysis
Blood transfusions
Exchange transfusion

DISEASES SPREAD BY
MOSQUITOS

MALARIA
DENGUE FEVER
YELLOW FEVER
VIRAL ENCEPHALITIS
VIRAL HEMORRHAGIC FEVERS

Malaria

Malaria (contd)

Avoid mosquitoes by taking protective measures.

Use protective clothing: long sleeved shirts/pants.
Use DEET repellant.
Use bed netting if rural or if locked windows not available.
Prophylactic medications when indicated are widely used based
on CDC recommendations for intended destinations.

chemoprophylaxis
Chloroquine 5mg base/kg (max 300 mg) once a
week. Begin 1-2 weeks before travel, during stay
and continue till 4 weeks after returning from
malarious area.
Mefloquine 5mg salt/kg (max 250 mg) once a
week. Regime same as above.
Atovoquone/proguanil (250/100mg) 1 tab for travel
to resistant malarious area beginning 1-2 days
before travel and taken daily during stay and ctd till
1 week after return from malarious area.

Travel in Chloroquine Resistant areas

Atovaquone/proguanil (Malarone)
250 mg atovaquone and 100 mg proguanil hydrochloride.
Begin 1-2 days before travel and continue daily for 7 days
after leaving the area..
Daily, at the same time each day .
Contraindicated in persons with severe renal impairment
Contraindicated in children <5 kg, pregnant women, and
women breastfeeding.
Side effects- abdominal pain, nausea, vomiting, and
headache

Congenital malaria
Transplacental infection
Can be all 4 species
Commonly P.v. and P.f. in endemic areas
P.m. infections in nonendemic areas due to long persistence of species

Neonate can be diagnosed with parasitemia within 7 days of

birth or longer if no other risk factors for malaria (mosquito
exposure, blood transfusion)
Fever, irritability, feeding problems, anemia,
hepatosplenomegaly, and jaundice
Be mindful of this problem even if mother has not been in
malarious area for years before delivery