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Management Issues in Malaria



Dr Rajesh Deshwal, MD, FHM
Consultant in Internal Medicine and HIV Medicine
Military Hospital, Agra Cantonment, India
Major killer of mankind
Most important parasitic disease
Approximately one million die each year
Usual Clinical Presentations in Malaria
Incubation Period

P. vivax 18-40 Days

P. falciparum 9-14 days
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
Hot Stage

Patient feels hot

Skin is hot and dry to touch

Headache is intense but nausea diminishes

Pulse is full and respiration rapid
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
Followed by afebrile interval of 48-72 hours hence
typical malarial fever is usually observed on
alternate days
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
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
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
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
Rapid Diagnostic Tests(RDT)
- PfHRP2
- PMA-aldolase
- pLDH
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
Management issues in malaria
UNUSUAL PRESENTATIONS OF
MALARIA
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
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
Management issues in malaria
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
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
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
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
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
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
SEVERE COMPLICATED MALARIA
Management issues in malaria
Management issues in malaria
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
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
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
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
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
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
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
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
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
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’
Urticaria as an allergic manifestation

Sinusitis

Occasionally retinal and sub conjunctival
haemorrhage may also present as an unusual
presentation in malaria
Management issues in malaria
Management issues in malaria
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
MANAGEMENT OF MALARIA
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
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
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
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
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
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
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
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
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
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
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
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
Management issues in malaria
Management issues in malaria
Management issues in malaria
Management issues in malaria
Management issues in malaria
Falciparum resistance
across India
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)
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
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
Side effect : GI upset

Relatively safe drug
Management issues in malaria
Management issues in malaria
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
Combinations not recommended


 1.   Chloroquine based combinations (e.g CQ + SP; CQ +
      Artesunate)
 2.   Artesunate (single dose) + SP
 3.   Chloproguanil-Dapsone (LapDap)
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
Management issues in malaria
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)
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
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
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
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
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.
Management issues in malaria

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Management issues in malaria

  • 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
  • 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
  • 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
  • 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
  • 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
  • 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.