This document discusses management issues related to malaria. It begins by noting that malaria is a major killer worldwide, with approximately one million deaths per year. It then describes the typical clinical presentations and incubation periods of different malaria species. It discusses unusual presentations, complications like cerebral malaria and acute renal failure, and common errors in diagnosis. The document concludes by outlining general principles of malaria management, including drug therapy options and their dosages. Key recommendations include quinine or artesunate-based combinations for treating falciparum malaria due to widespread drug resistance.

1. Management Issues in Malaria
Dr Rajesh Deshwal, MD, FHM
Consultant in Internal Medicine and HIV Medicine
Military Hospital, Agra Cantonment, India

2. Major killer of mankind
Most important parasitic disease
Approximately one million die each year

3. Usual Clinical Presentations in Malaria

4. Incubation Period
P. vivax 18-40 Days
P. falciparum 9-14 days

5. Cold stage, onset occurs with
• Lassitude
• Headache,often severe
• Nausea followed by vomiting
• Chilly sensation followed by rigors
• Skin feels cold; later it becomes hot
• Parasite is usually demonstrable in the blood
• Pulse rapid and may be weak

6. Hot Stage
Patient feels hot
Skin is hot and dry to touch
Headache is intense but nausea diminishes
Pulse is full and respiration rapid

7. Sweating stage
Profuse sweating
Body temperature drops rapidly to normal
Skin is cool and moist
Pulse rate becomes slower
Patient feels relieved and often falls asleep

8. Followed by afebrile interval of 48-72 hours hence
typical malarial fever is usually observed on
alternate days

9. Latent period
The patient is usually free of symptoms but
in P. vivax hypnozoites persist in the liver and
in P. falciparum infection, following
inadequate treatment parasites persist in
the blood

10. Recrudescence
It is a renewed manifestation of infection within
days or weeks
It is a result of continued survival or presence in the
blood of asexual forms of parasite because of no
treatment or inadequate treatment

11. Relapse
It is the result from maturation of hypnozoites in
the liver with liberation of merozoites in to the
blood
It varies according to the species and even according
to the group or strain
It can occur even three years after the primary
infection

12. Peripheral smear
Essential for the confirmation of the diagnosis of
malaria
Confirming the species of parasite present in the
blood
Thick film is reliable in searching for parasite
Thin is valuable for identification of species

13. Rapid Diagnostic Tests(RDT)
- PfHRP2
- PMA-aldolase
- pLDH

14. Pattern of fever
May be irregular or continuous
When more than two breeds of parasites are
involved daily paroxysms may be observed
The pattern may be varied by use of antipyretics and
chemoprophylaxis

16. UNUSUAL PRESENTATIONS OF
MALARIA

17. Uncomplicated malaria in adult and older
patients may present with following symptoms:
Bodyache, headache and no fever
Throat pain, bodyache and mild fever
Severe headache
Diarrhoea, jaundice, urticaria
Pain in epigastrium

18. Uncomplicated malaria in children may
present with following symptoms:
Vomiting, cough, urticaria
No rhinitis and clear throat
Child becomes irritable, crying and not looking
healthy

20. Causes of fever where malaria is likely to
be confused are:
- URTI
- UTI
- Influenza
- Dengue
- Typhoid and paratyphoid fever
- Tuberculosis
- Amoebic liver abscess
- Brain abscess, endocarditis

21. When malaria is associated with Jaundice
Viral Hepatitis
Leptospirosis
Cholangiohepatitis
The most important step in diagnosis is to think of
the possibility that malaria may be the cause of
patient’s illness

22. Anaemia
Anaemia is an inevitable consequence of malaria,
because of the great proportion of erythrocytes
which became parasitized in malarial infection
Release of more malaria antigens result into marked
immunohaemolytic anaemia
Growth of parasite within erythrocyte leads to
consistent drop in the haematocrit level which leads
to shortening of the life span of RBC even in the
absence of overt infection

23. It is more common and more marked in
children than in adults
Malaria may be the cause of sudden and
catastrophic fall in Hb% in pregnant women
Remember
In any illness with or without fever sudden or
persistent fall in Hb%, think of malaria first

24. Jaundice
Jaundice with palpable liver and spleen is common finding in
falciparum malaria
Degree of icterus correlates well with the amount of
haemolysis
Clinical signs of hepatic failure are rarely seen
Raised serum bilirubin, SGPT, SGOT level in the liver profile
study is also observed in malaria
Bile pigment in the urine usually increased during the malaria
Remember
Fever in the presence of jaundice suggest malaria rather than
viral hepatitis in which the fever has usually resolved by the
time jaundice develops

25. Gastro intestinal involvement
Vomiting is a common feature of severe malaria
particularly in children
Diarrhoea in case of malaria may be seen as a result
from necrosis and damage to the intestinal wall
Sweating, vomiting and diarrhoea may combine to
produce dehydration
Remember : Any GIT symptoms can be caused by
malaria, but a blood film to exclude malaria should
always be taken

26. SEVERE COMPLICATED MALARIA

29. Cerebral Malaria
Any manifestation of cerebral dysfunction in a
patient with malaria is evident of cerebral malaria
Occurs particularly when nonimmune persons have
remained untreated for 3 to 7 days after the
development of primary fever
Patient’s condition may deteriorate rapidly with
increasing headache and drowsiness which later
merge into confusion and coma
Inspite of treatment given the condition may
deteriorate further into deep coma

30. When the coma is light, patient may be able to talk
and answer questions, although later patient will have
no recollection of having done so
In severe infections, delirium and coma may develop
suddenly and may even occur early during the course
of the febrile illness
Patients with cerebral malaria may present with
convulsions, hallucinations and a state of agitation
Hyperpyrexia is not unusual, focal neurological
deficits and signs of meningeal irritation are rare
CSF is usually normal on examination

31. Acute renal failure
Malaria with associated dehydration and hypotension may lead
to oliguria, anuria, and ultimately acute renal failure
Intravascular haemolysis and secondary infection may further
aggravate the situation
A reduction in urine output 400 ml or less per day indicate
renal failure
Raised blood urea and serum creatinine
If effective treatment not employed may reach high levels
Remember
A careful clue in the early watch on a urinary out put and
raised blood urea and serum creatinine is a good diagnosis of
ARF due to malaria

32. PULMONARY MANIFESTATIONS IN
MALARIA
Malaria may present with signs and symptoms
suggestive of respiratory disease like pneumonia,
bronchial asthma, bronchitis and more grave ARDS
Most commonest presentation are fever with or
without chills, cough with expectoration or dry
cough, chest pain and dyspnea
Haemoptysis is uncommon

33. Hepatomegaly and splenomegaly are for less clinical
observation. Drop in haematocrit level, but no
specific abnormality trends seen in total or
differential leucocyte count
Peripheral blood film examination reveals the type of
malaria
If not treated in time ARDS is the most common
complication in pulmonary manifestations and where
management is extremely difficult and prognosis is
also poor

34. Pulmonary edema
This could be a grave and fatal complication due to P.
falciparum Malaria
The pathogenesis of this condition remains unclear
The first indication of pulmonary edema is cough
usually dry, difficulty in breathing, tightness in the
chest
Dyspnoea may increase rapidly in severity

35. The respiratory rate goes up - crepitations may
appear
Haemoptysis is usually absent
Serious signs such as frothing from the mouth,
cyanosis, convulsions, deterioration in the level of
consciousness may lead to grave complication like
ARDS
Remember
Incidence of respiratory manifestations in malaria
are far more than described in the literature.
Suspicion of malaria should be kept and peripheral
smear examination help in decreasing morbidity and
mortality

36. Hypoglycaemia
It is a quite frequent observation in malaria
It may contribute to the neurological disturbances
In pregnant woman suffering from malaria
hypoglycaemia appears to be a common clinical
observation

37. It may present during early convalescence or patient
receiving 5% dextrose during treatment, not because
of liver glycogen depletion or starvation but due to
glucose consumption by the malaria, and stimulation
of insulin secretion by quinine
Remember
Any patient with symptoms of hypoglycaemia may be
misdiagnosed as a case of cerebral malaria
Glucometer is a more powerful tool in visit bag or in a
clinic than stethoscope

38. CIRCULATORY COLLAPSE
Marked hypotension where systolic BP less than 80
mm of Hg in supine position
Cold clammy, cyanotic skin
Constricted peripheral vessels may occur in severe
falciparum malaria
Circulatory collapse may occur suddenly if it is
associated with severe dehydration, gram negative
septicaemia and massive GI haemorrhage
This grave emergency in past was also known as
‘Algid Malaria’

39. Urticaria as an allergic manifestation
Sinusitis
Occasionally retinal and sub conjunctival
haemorrhage may also present as an unusual
presentation in malaria

42. Common errors in diagnosis
Failure to do a malarial blood film (Thick and thin
smear)
Failure to take a detail history e.g. travel history,
previous malarial infection
Misjudgement of severity of the disease
False parasitological diagnosis
Missed hypoglycaemia
Missed diagnosis e.g. influenza, viral hepatitis,
typhoid fever
Failure to perform fundoscopic examination to rule
out presence of retinal haemorrhage

43. MANAGEMENT OF MALARIA

44. General Principle
If parasitiological confirmation of malaria is not
readily available, a blood film should be made and the
treatment started on the basis of clinical
presentation
In severe malaria, anti malarial therapy must be
given Intravenously or Intramuscularly, oral
treatment should be substituted as early as possible
Doses must be calculated in on a mg/kg of body
weight. It is important to weigh the patient, this is
particularly important for children

45. Do not confuse the doses of salt and base. Quinine
doses are prescribed as salt (10 mg of salt 8.3 mg of
base). Chloroquine and mefloquine are prescribed as
a base
Good nursing care is vital
Maintain adequate fluid balance, to avoid
overhydration or underhydration
Initial check of blood glucose is vital
Frequent monitoring for hypoglycaemia are important
Frequent monitoring of the therapeutic response is
important

46. Anaemia
Keep haemoglobin level above 7 gm per cent
If required a slow transfusion of 5 ml-10 ml/kg pcv
or 10-20 ml/kg whole blood may be given
In children with severe anaemia with associated
tachycardia inj. frusemide (1-2 mg/kg) may be given
Administer appropriate anti malarial therapy with
proper dosage calculation
Supplement iron and folic acid during convalescent
period is helpful

47. Pulmonary oedema
It may be caused by fluid overload, so careful fluid
management is vital
Along with strict control of fluid intake propped
patient at an angle of 45⁰
Maintain CVP
Give high concentration of oxygen by any convenient
method
IV frusemide (40-120 mg) should be tried first, if
CVP does not fall use other vasodilators in well
equipped ICU
If required fluid can be removed by dialysis

48. HYPOGLYCAEMIA
Prompt IV glucose is essential and life saving
Pregnant woman with malaria closely monitor both,
hypoglycaemia and foetal distress
50% glucose (up to 1.0 ml/kg) followed by IV infusion
of 10-20% dextrose should be given
The possible recurrence of hypoglycaemia, when
patient on IV quinine should be kept in mind

49. Hyper pyrexia and associated management
Cooling by fanning, tepid lukewarm water sponging
Use appropriate antipyretic
Pneumonia, urinary tract infection, typhoid fever
should be treated with appropriate antibiotics
Be careful in using nephrotoxic drugs such as
sulphonamides, aminoglycosides and tetracycline if
there is renal insufficiency or hepatotoxic antibiotic
in case of complicated jaundice or altered LFT

50. Acute renal failure
It is because of haemoglobinaemia may lead to
oliguria and ARF
Continue appropriate anti malarial treatment
Maintain haematocrit level above 20% or 7 gm
Correct fluid and electrolyte deficit
Treatment of hypotension and shock is of vital
importance

51. If oliguria (below 400 ml/24 hrs.) is present
preventive measure for the development of ARF
should be instituted
Patient with G6PD deficiency should be screened
carefully
ARF demands skillful management hence refer
patient to a well equipped centre, because these
patient may require peritoneal/hemo-dialysis

52. DRUG THERAPY
Quinine
Still it is a drug of choice for the treatment for
severe and complicated malaria
It should always be given by rate controlled infusion
never by bolus IV injection
Switch on to oral administration as early as possible
Common side effect are tinnitus, hearing loss,
nausea, uneasiness, restlessness and blurring of
vision
Serious CVS and neurological toxicity is rare

53. Hypoglycaemia is the most frequent adverse side
effect
IM injection of quinine is not recommended
In suspected quinine poisoning activated charcoal
given orally or by nasogastric tube accelerates
elimination
Dosage Schedule : Dose 10 mg salt/kg Infusion
Volume : 10 ml/kg if pt is normally hydrated. 20
ml/kg if pt is dehydrated.5 ml/kg. if the pt. is
overhydrated
Infusion time : 2.5 hours. Infusion interval : 8 hours

54. CHLOROQUINE
Chloroquine is still the more widely prescribed drug
in the tropics
It should always be given by slow rate controlled IV
infusion, and never by bolus injection
Oral therapy should be substituted as early as
possible
Side effects include headache, nausea, vomiting,
uneasiness, blurred vision, hypotension and pruritis

55. Dosage Schedule
Dose 5 mg. base/kg
Infusion Volume : 10 ml/kg Infusion Time 4.6 hours
Infusion interval 8 hours
IM chloroquine injection may be given as 5 mg
base/kg in two divided doses of 2.5 mg/kg in the
gluteal region at an interval of one hour and repeated
every 12 hours, never to be given in single dose
Avoid in infants and in children

61. Falciparum resistance
across India

62. Recommended Combinations
1. Artemether + Lumefantrine (Lumether)
2. Artesunate (3 days) + Amodiaquine
3. Artesunate (3 days) + Mefloquine
4. Artesunate (3 days) + SP
5. Amodiaquine + SP (as interim option)

63. Mefloquine
Chemically related to quinine
It is a long acting schizontocide
It is effective against multidrug resistant parasite
Single oral dose is sufficient to effect cure
Dose 20 mg to 25 mg/kg taken as a single dose
Side effect may include GI upset, dizziness, fatigue,
asymptomatic bradycardia and occasionally acute
psychosis

64. Artemisine (Artesunate)
It is ancient Chinese herbal medicine
Artesunate is a semisynthetic derivative of
artemisine
Dose
IV /IM 2.4 mg/kg and 1.2 mg/kg after 12 hrs and
then daily for 5 days
Oral : 100-200mg initially then 100 mg daily for 4-5
days

65. Side effect : GI upset
Relatively safe drug

68. Arteether
It is an artemisinin derivative
It has a ‘reserve status’ in WHO essential drug,
means it should be reserved for multi drug resistant
malaria
So far no significant toxicity or drug resistance to
these compound has been reported
Compliance of patient is excellent
Cost of therapy is comparable to other second line
antimalarial drugs
Dose : 150 mg deep IM once daily on three
consecutive days

69. Combinations not recommended
1. Chloroquine based combinations (e.g CQ + SP; CQ +
Artesunate)
2. Artesunate (single dose) + SP
3. Chloproguanil-Dapsone (LapDap)

70. What to give in pregnancy ?
• In 1st trimester
• Quinine + Clindamycin 7 days
• In 2nd and 3rd trimesters
• Any ACT combination as per rec. or
• Artesunate + Clindamycin 7 days or
• Quinine + Clindamycin 7 days
• Lactating women same ACT

72. PRESUMPTIVE TREATMENT
(Before the result of the smear is known)
It is given to all fever cases or cases with history of
fever during the preceding 15 days immediately
after the blood smear is collected and also to fever
cases where blood smears are not collected
Chloroquine base Day 1, 10 mg/kg (600 mg adult)
Primaquine Day 1, 0.75 mg/kg (45 mg adult)
Chloroquine base Day 2, 10 mg/kg (600 mg adult)
Chloroquine base Day 3, 5 mg/kg (300 mg adult)

73. G6 PD deficiency
It is a myth that person with G6PD deficiency are
more protected from P. falciparum malaria
They suffer more frequently from P. vivax malaria
Intravascular haemolysis may occur in G6PD
deficient person, due to action of anti malarial drugs
on older erythrocytes
As a physician one should be careful of G6PD
deficiency in certain ethnic group e.g. Parsi, Khatri,
Sindhis
Primaquine can produce massive haemolysis and may
cause severe anaemia, and renal failure

74. RADICAL TREATMENT
(All microscopically positive cases)
All microscopically positive cases of malaria
are to be given radical treatment with
Primaquine for its anti-relapse properties

75. CHEMOPROPHYLAXIS
Chloroquine-sensitiveP.falciparum :Chloroquine :
300 mg base once weekly. Start 1 week before
exposure
Chloroquine-resistant P.falciparum
a)Mefloquine 250 mg base once weekly. Start 1
week before exposure
b)Doxycycline 100 mg daily. Start 2 days before
exposure
c)Chloroquine 300 mg base weekly. Start 1 week
before exposure plus Proguanil 200 mg daily.
Start 2 days before exposure

76. TAKE HOME MESSAGE
Malaria continues to be major killer of Mankind
Approximately one million die each year of malaria
around the globe
We must take note of changing pattern of malaria
The malaria prone areas are now the metro cities and
urban India
Newer development of ‘Resistant Malaria’ has to be
kept in mind

77. REFERENCES
1. Gilles HM, Warrell DA. Brace Chwatt’s Essential Malariology.
Third Edition. Plates: 1, 2, 3, 4, 6, 25 Pg. 44. 3 rd ed.
2. The Clinical Management of Acute Malaria. WHO regional
publications. South East Asia - Series No. 9. Pgs. 19, 27, 37, 46,
47, 50, 51, 54, 68.
3. Management of severe and complicated malaria practical
handbook. HM Gilles WHO Geneva. Pg. 20, 35, 46. 2 nd ed.
4. A closer look at Malaria’ General Practitioners’ Association
Surat Publication. Pg. 67, 68.
5. Guidelines for Diagnosis and Treatment of Malaria in India
2011.