This document provides an overview of malaria, including its definition, causative organisms, life cycle, signs and symptoms, risk factors, complications, diagnosis, and treatment. Malaria is caused by protozoan parasites of the genus Plasmodium and transmitted via mosquito bites. It presents with fever, chills, and flu-like symptoms. Risk factors include living in endemic areas and pregnancy. Complications can include severe anemia, renal failure, liver dysfunction, and death if falciparum malaria is not treated. Diagnosis involves examining blood smears under a microscope. Treatment depends on the parasitic species but generally involves antimalarial medications like chloroquine or artemesinin combination therapies.

1. Presented by : PRIYANKA K
1st Pharm D (PB)
Shree devi college of pharmacy
Mangalore

2.  Definition
 Epidemology
 Life cycle
 Signs and symptoms
 Clinical presentation
 Risk factors
 Complication
 Diagnosis
 Treatment
 Malaria in pregnancy
 Prevention
 Case study.

3. DEFINITION
Malaria is an infectious disease caused by protozoan parasites of genus plasmodium that can
be transmitted by the bite of the Anoheles mosquito or by a contaminated needle or
transfusion.
CAUSATIVE ORGANISM
P. falciparum( the most common and dangerous)
P. viva
P. ovale
P. malaria
P. knowlesi

4.  The WHO estimates that in 2010 there were 219 million cases of malaria
resulting in 660,000 deaths.
 Others have estimated the no. of cases at between 350 and 550 million for
falciparum malaria and deaths in 2010 at 1.24 - 1.0 million deaths in 1990.
 The majority of cases occur in children under 15 years old.
 P. vivax and P. ovale causes relapsing malaria.
 P falciparum is found in the tropical region and causes the most severe and
fatal disease.
 P. vivax is the most common cause of malaria and is found insubtroical and
temperate areas of the world.
 P. ovale is the least common malarial species .

6. The life cycle of malaria parasite consists of following phases:
 Sexual cycle : in female anopheles mosquito, definitive host
 Asexual cycle: in human, as intermediate host.
 Sporozoites are the sexual form of the parasite.
 When the infected female anopheles mosquito bites the human then
the sporozoites enter the human along with the saliva of the
mosquito.
 Within 30min they enter the parenchymal cells of the lier, where
during next 10 - 14 days, they undergo pre-erythrocytic stages of
development and multiplication.

7.  Following mitotic replication of its nucleus, the parasite is termed as
schizont.
 Atlast the parasites rupture the liver cell and merozites are released
 The merozoites from the liver cell then bind to or enter the RBC and
further develops into trophozoites.
 The mulitplication here results to Erythrocytic schizont.
 Some merozoites of erythrocytic schizony develop into male and
female gametocytes known as microgamates and macrogamates.
 They are sexual form and are found in peripheral blood.

8.  Some of the sporozoites also, on entering into the liver cells, do not
undergo asexual multiplication but enter into a resting phase called
hypnozoite
 The sexual cycle of malaria parasites actually starts in the human
host by the formation of gametocytes which are then transferred to
mosquito for further develoment.
 In the midgut of the mosqito, one microgametocyte develops into 4
to 8 thread like filamentous structures named microgamates.
 From one microgamate only one microgamate is formed

9.  The fertilization occurs, and the gamate is known as zygote.
 The zygote matures into an ookinete and it further develops into an
oocyts.
 An oocyts mature and it increases in size and a large no of
sporozoites develop inside it.
 The oocyts rupture and releases sporozoites in the body cavity of
mosquito.
 The sporozoites are distributed to different organs of the mosquito
and they have a special predilection for salivary glands.
 The mosquito is now capable of transmitting the infection to man.

10. SPECIES INCUBATION PERIOD (LIVER CYCLE)
P. falciparum 7-14 days
P. vivax 12-17 days (withrelapse upto 3 yrs)
P. ovale 9-18 days (with relapse upto 20 yrs)
P. malaria 13-40 days.

12. Initial Presentation
 Nonspecific fever, chills, rigors, diaphoresis, malaise, vomiting
 Orthostatic hypotension
 Electrolyte abnormalities
Erythrocytic Phase
 Prodrome: Headache, anorexia, malaise, fatigue, myalgias
 Nonspecific complaints such as abdominal pain, diarrhea, chest pain, and arthralgias
Paroxysm: High fever, chills, and rigor
 Cold phase: Feeling of intense cold , vigorous shivering , lasts 15- 60 min, Severe
pallor, cyanosis of the lips and nail bed, and cutis anserina (“goose flesh”)
 Hot phase: intense heat ,Fever between 40.5◦C (104.9◦F) and 41◦C (105.8◦F), dry
burning skin, throbbing headache , last 2-6 hours.

13.  Sweating phase:
o Follows hot phase by 2–6 hours , profuse sweating, decline temperature, exhausted and weak
sleep
o Fever resolves
o Marked fatigue and drowsiness, warm, dry skin, tachycardia, cough, severe headache, nausea,
vomiting, abdominal pain, diarrhea, and delirium
o Lactic acidosis and hypoglycemia (with falciparum malaria)
 Anemia
 Splenomegaly
P. falciparum Infections
Hypoglycemia, acute renal failure, pulmonary edema, severe anemia, thrombocytopenia, high-
output heart failure, cerebral congestion, seizures and coma, and adult respiratory syndrome

14.  Living or traveling in a region where malaria is present.
 Travelling to area where malaria is common:
- without taking medicine to prevent malaria.
- being outdoors, especially in rural areas.
- not taking steps to protect yourself from mosquito bites.
 pregnant women.
 Children under 5yrs of age.
 Patients with HIV/AIDS.

15.  Anaemia – It results from the obligatory destruction of rbc containing
parasites at merogony. The shortened survival of rbc from which parasites
have been extracted by the spleen, and accelerated destruction of non-
parasitized rbc all compound by bone marrow dyserythropoeisis. In severe
malaria anaemia develops rapidly because of the rapid haemolysis of rbc
and decline in the haematocrit.
 Renal failure – There is renal vasoconstriction and hypoperfusion in severe
falciparum malaria. The renal injury in severe malaria results from acute
tubular necrosis.
 Fluid space and electrolyte changes – The general vasodilation and a
falling haemtocrit there will be increase in the plasma renin activity, anti
diuretic harmone concentration

16.  Pulmonary oedema – in malaria results from a sudden increase in
pulmonary capillary permeability ( due to of presence of sequestered rbc
and host leucocytes in pulmonary capillary endothelial dysfunction).
 Coagulopathy and thrombocytopenia – In acute malaria coagulation
cascade activity is increased with accelerated fibrinogen turnover,
consumption of antithrombin III, reduced factor XIII and increased
concentration of fibrin degradation products.
 Blackwater fever – massive intravascular haemolysis and the passage of
‘coco cola’ coloured urine. It may be associated with acute renal failure.

17.  Liver dysfunction – jaundice
 Acidosis – major cause of death in severe falciparum malaria.
 Gastrointestinal dysfunction- abdominal pain, enlarged soft, dark or black,
firable spleen.
 Hypoglycaemia
 Placental dysfunction

18.  Clinical diagnosis
 Malaria blood smear
 Fluorescent microscopy
 Antigen detection
 Serology
 Polymerase chain reaction

19.  Remains the gold standard for diagnosis.
Giemsa stain
- distinguishes between secies and life cycle stages
- parasitemia is quantifiable

21. THICK FILMS THIN FILMS
 Lysed RBCs
 Larger volume
 0.25µl blood/ 100 fields
 blood elements more concentrated
 good screening test
 positive or negative
 parasite density
 more difficult to diagnosis species.
 fixed RBCs, single layer
 smaller volume
 0.005µl blood/ 100 fields
 good species differentiation
 requires more time to read
 low density infections can be
missed.

23. ANTIGEN DETECTION
 Various test kits are available to detect antigens derived from malaria parasites.
 Such immunologic tests most often use a dipstick or cassette format, and provide results
in 2-15mins.
 These “Rapid Diagnostic Test” (RTDs) offer a useful alternative to microscopy in
situations where reliable microscopic diagnosis is not available.
 Malaria RDTs are currently used in some clinical settings and programs.
 The use of this RDT may decrease the amount of time that it takes to determine that a
patient is infected with malaria

24. MOLECULAR DIAGNOSIS
 Parasite nucleic acids are detected using polymerase chain reaction
 Although this is technique may be slightly more sensitive than smear microscopy, it is of
limited utility for the diagnosis of acutely ill patients in the standard healthcare setting.
 PCR is most useful for confirming the species of malarial parasite after the diagnosis has
been established by either smear microscopy or RDT.
SEROLOGY
 Serology detects antibioties against malaria parasites, using either indirect
immunofluorescence or enzyme- linked immuno- sorbent assay (ELISA).
 Serology does not detect current infection but rather measures past exposure.

26.  spectrum of activity : rapid acting erythrocytic schizontic against all species of
malaria
 MOA :- Accumulates in acidic vacuole of parasite it increases ph and inhibits
heme polymerisation.
by formation CQ-heme complex it damages plasmodial membrane complex
inhibits formation of hemozoin.
dosage
 uncomplicated vivax/ ovale/ malaria: 600mg- 300mg after 8hrs, continue for
next 2days, total 25mgkg over 3days + primaquine 15mg(0.25mg/kg)daily
for 14 days
 chloroquine sensitive falciparum:- dose as above + primaquine
45mg(0.75mg) single dose
Adverse effects
 nausea, vomiting, anorexia, itching, epigastric pain, difficult in
accommodation, headache are frequent and unpleasent.

27.  toxic effects after prolonged use:
 skin eruptions, headache, blurring of vision, diplopia, confusion and
convulsion.
 haemolysis and blood dyscrasis
 discolouration of nail beds, hairs and mucoucs membrane.
 ototoxicity irreversible
 myoppathy, cardiomyopathy, peripheral neuropathy, suicidal tendency occurs
 mental confusion, convulsion and coma.
 interactions and precautions of CQ
 With Mefloquine convulsion Will occur.
 Digoxin level increases used along
 with gold and phenylbutazone dermatitis will occur.
 haemolysis occurs in G6PD deficient patients.

28.  decrease cost and safety in CQ resistance P. falciparum in certain
areas
 faster action and better tolerance then chloroquine
 Prophylactically not used because of hepatotoxicity &
agranulocytosis in certain areas can be used in clinical attacks.
Doasge:
25 - 35mg/kg for 3days (10mg/kg is given immediately following
5mg//kg after 6hrs then 5mg/kg for next 2 days)
Mechanism, uses &ADR are similar to CQ

29.  Chloroquine congener with similar mechanism.
 high efficacy, erythrocytic schizonticide with prolonged action & onset is
slow.
 Activity: chloroquine sensitive & chloroquine resistant P.falciparum
malaria
MOA :- Similar to morphological changes in the intraerythrocytic parasite of
chloroquine & quinine.
 act in cytosol of the parasite
 mechanism is unclear it can also inhibit heme polymerization forming
toxic complex with heme & damage membrane.

30.  Dosage - 25mg/kg - 1.25gm sinle or 2doses of 750& 500mg 12hr apart.
chlidren- first dose 15mg/kg→ 10mg/kg after 12h after meals with plenty of water since
its irritant
Adverse drug effect
 Dizziness, nausea, vomiting, diarrhoea, abdominal pain, sinus bradycardia & QT
prolongation.
 Safe during pregnancy but should be avoided in first trimester.
 Neuropsychiatric reactions present.
Drug interaction
Halofantrine or Quinine or Chloroquine with this drug causes QT lengthening and cardiac
arrest.

31.  Isolated from bark of chinchona tree .
MOA
 It forms heme- quinine complex.
 Inhibits polymerization of heme to hemozoin.
 Damages parasite membrane and kills it.
Dosage : 7 day course
 Loading dose : 20mg/kg IV over 4hrs diluted in 5% dextrose to prevent
hypoglycemia.
 Maintenance dose : 10mg/kg over 4hr in adults or 2hr in children every 8hr.
 Then switch over to oral 10mg/kg 8hrly
Adverse effects : affects hearing & vision cardio depressent, anti arrythmic and
hypotensive action similar to quinidine.
 On rapid IV it causes hypoglycemia.
 Toxicity : 8-10g taken in single dose may be fatal.

32.  Slow acting erythrocytic schizontocide.
 Inhibits pre erythrocytic stage of P.falciparum gametocytes prevents its development.
 It gets converted to active form cycloguanil, which inhibits plasmodial DHFRASE.
MOA: Inhibits DHFRase- thymidylate synthetase
Dosage: >200mg daily in adults & children 4weeks after leaving endemic area.
 Causal prophylaxis : 400mg proguanil+ Atovaquine 1g for 3 days in multidrug resistence.
Adverse effects : mild abdominal symptoms.
occasional stomatitis, haematuria, rashes and transient loss of hair.

33.  Radical cure : given with choloroquine.
 Only agent active against dormant hepatic forms of vivax & ovale .
 Gametocidal action against all four species of plasmodium.
MOA : not clear, its converted & produces active oxygen interfere with
plasmodial mitochondrial function.
 Resistance induced among P.vivax.
Adverse effect : haemolysis and methaemoglobinaemia commonly seen in
G6PD deficiency.
 Causes nausea, headache, epigastric pain and abdominal cramps on empty
stomach.

34.  Derived from plant Artemisia annua .
 Its sesquiterpine lactone endoperoxide, poorly soluble in oil and water-used orally/
rectally.
 Other compound :
 Dihydroartemisinin (oral)
 Artemether (oral or IM) & Artesunate (oral/rectal/IV/IM)
 Arteether – (IM) produced in India in 1990.
 Arterolone – (oral) synthetic ompound are developed.
MOA :Endoperoxide moiety produces carbon centered radicals by intramolecular
rearrangement which modify & damages malarial proteins.
High reacted free radicals inhibit plasmodial sarcoplasmic endoplasmic calcium ATPase.
Resistance decrease response & combination of drugs with different mechanism & longer
acting drugs given with these drugs in 3 days course will solve the problem.

35. Dosage 12mg of total oral dose for both children & adults in which 4mg/kg
given on first day followed by 2mg/kg for 4days.
 Parenteral : Artesunate – 120mg IV/IM on first day followed by 60mg for
next 4days by same route.
 Artemether ; 2mg/kg for 5days
 Arteether : for complicated malaria in adults IM 150mg daily.
Adverse effect: nausea, vomiting, abdominal pain, itching and drug fever.
 Headache, tinnitus, dizziness, bleeding, dark urine, ST segment changes,
QT prolongation, first degree AV block, transient reticulopenia and
leucopenia are rare.

36.  Malaria is more common in pregnancy compared to the general population.
Immuno suppression and loss of acquired immunity to malaria could be the
causes.
 Malaria in pregnancy being more severe, also turns out to be more fatal,
the mortality being double (13%) in pregnant compared to the non-
pregnant population(6.5%).
 Some anti malarials are contra indicated in pregnancy and some may cause
severe adverse effects. Therefore the treatment may become difficult,
particularly in cases of severe P.falciparum malaria.

37.  In pregnant women the morbidity due to malaria includes anaemia, fever, hypoglycemia,
cerebral malaria, pulmonary edema, puerperal sepsis and mortality can occur from severe
malaria and haemorrhage.
 The problem in the new born include low birth weight, prematurity, IUGR, malaria illness
and mortality.
 Drugs used in pregnancy:
 Proguanil with folic acid 5mg/day.
 Chloroquine in usual doses.
 Quinine in low dose- chloroquine resistant malaria
 High dose induce labour.
 Pryrimethamine + dapsone – 2nd & 3rd trimester with folinic acid.
 Chloroquine, quinine 7 proguanil safe but pyrimethamine with folic acid can be used.

39. Case study

40.  Patient name : Mr. XYZ
 Age : 26yrs
 Sex : Male
 IP No. : F34327
 Deparment: General medicine
 Date of admission: 22/09/2019
 Date of discharge: 27/09/2019

41. Chief complaints : C/o fever, vomiting, back pain, fatigue, headache ×
3days
History of present illness
H/o backpain, headache.
Past medical history:
N/K/C/o DM, HTN, BA.

42.  Past medication history: not significant
 Social history : not smoker and alcoholic
 Personal history
Diet – mixed
Sleep – adequate
B and B – loose stool
Appetite - normal
no substance abuse

43.  General physical examination:
Patient is conscious, cooperative, well oriented moderately built and
nourished
No pallor, icterus, clubbing,cyanosis, lymphadenopathy, edema
 Vital signs:
BP- 120/80 mm/Hg RR – 20bpm
TEMPERATURE – 104F PR- 80bpm
 Systemic examination
CVS - S1 S2+ CNS – NFND
RS – NVBS P/A - Soft

44. PARAMETER TEST VALUE NORMAL VALUE
Hemoglobin 12.6 14 – 18 gm/dl
RBC 4.4 4.2 – 5.6 million/cubic mm
Platelet count 110 140- 450 cubic mm
ESR 25 15 – 20 mm/hr
Bilirubin (total) 1.8 0.2 – 1.4 mg/dl
Bilirubin ( direct) 1.5 0.0 – 0.4 mg/dl
Bilirubin (indirect) 0.3 0.2 – 1.0 mg/dl

45. OTHER TEST’S
 Dengue test – negative
 Polymerase chain reaction – positive
 MP QBC – Positive (P. vivax)

46. FINAL DIAGNOSIS BY SUBJECTIVE DATAAND
OBJECTIVE DATA

47.  Releive the signs and symptoms of a disease.
 Decrease morbidity and mortality associated with the infection.
 To prevent the clinical attack of malaria (prophylatic).
 To treat the clinical attack of malaria ( clinical curative).
 To completely eradicate the parasite from the patients body ( radical curative).
 To cut down human to mosquito transmission (gametocidal).

48. Brand name Generic name Dose Freq ROA 22/0
9
23/0
9
24/0
9
25/0
9
26/0
9
27/0
9
Cap.
DOXYCYCLINE
DOXYCYCLINE 100mg BD Oral      
Tab. DOLO PARACETAMOL 650mg TDS Oral  
Tab. LARIAGO CHLOROQUINE
PHOSPHATE
600mg OD Oral      
Inj. EMESET ONDRANSETRON 4mg STAT I V   

49.  CHLOROQUINE < - > ONDANSETRON
The metabolism of ondansetron can be decreased when combined with
chloroquine.
 DOXYCYLCINE <-> CHLOROQUINE
Doxycyline may decrease the excretion rate of chloroquine which could
result in a higher serum level.

50.  Tab. LARIAGO (600mg) OD for 14days
 Tab. DOLO (650mg) STAT
 Cap. DOXYCYCLINE (100mg) BD for 7days
 Review after 14days.

51. ABOUT THE DISEASE AND LIFESTYLE
 Research your destination to learn about any malaria risk.
Consult a health practitioner to determine if you need antimalarial medication for your trip and take
as presecribed.
Prevent mosquito bite: use a repellent containing 20 – 30% DEET or 20% Picaridin.
Wear neutral coloured clothing.
Avoid scented soaps.
Sleep under a permethrin – treated bed net.