2. Questions of Learning Unit

8/9/2019 2. Questions of Learning Unit

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The diagnosis & management of Malaria: Learners Guide

Revised by: Md. Baha Uddin (ISMC-03)::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::8

QUESTIONS OF LEARNING UNIT-01:

1. What is the rough percentage of Uncomplicated Malaria (UM) cases amongst total outpatientcases? How do you rank it comparing with other common illness?

2. What anti-malarial drugs are commonly prescribed for UM? Do the patients take adequate doseof anti-malarial drugs for adequate treatment? Ifno what are the possible causes?

3. Severe Malaria SM can present with many complications in your place of worka. How many (roughly) of your SM patients had anti-malarials before development of

complications?b. What complications are more common?c. What complications are more serious?d. What complications lead to fatal outcome usually?e. How many deaths are due to SM per month (roughly)?f. Do you believe that most of the patients in your locality brought to the health

facility? Ifno what are the possible cause?g. Do many deaths occur at home before reaching to the health facility in your working

place? Ifyes, state why?4. How do you rankSM as a cause of severe illness compared to other cause of severe illness like

ARI, AWD, CVD, and AMI etc?5. What anti-malarials are used to treat SM cases in your place of work? Do you think they are

effective? Ifno, state why?6. What other drugs (other than anti-malarials) are being used for treatment ofSM?7. Do most of the SM patients come late in your health facility? Ifyes,what are the possible reasons

for delayed attendance/referral?8. What are the major constrains for optimal and satisfactory treatment ofSM in your place of

work? What are the suggestions to overcome those?9. What diagnostic facilities are available in your place of work? Are these sufficient to manage SM?

LEARNING UNIT -02:Case definition of Malaria

It has been evident from several studies that Chloroquineis resistant to P. falciparummalaria tothe extent ranging from 40%-70% in many areas ofSouth East Asia includingBangladesh. The casedetection of Uncomplicated Malaria (UM) based on clinical ground was not successful in the controlof malaria. Moreover indiscriminate use of ineffective Chloroquine partly contributed to failure ofmalaria control.

The previous case definition of Uncomplicated Malaria (UM). Treatment failure malaria(TFM) and Severe Malaria (SM) which was an operational one based on treatment policy has beenchanged due to availability of new evidence on resistance ofP. falciparumto Chloroquine& emergenceof Multi Drug Resistant (MDR) strains ofP. falciparum.

Learning Objectives

By theend of thisunityoushould beable to:Understand the new case definition of malariaKnow about the treatment policy of different types of Malaria


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Thus new case definition is made to ensure proper case detection of malaria & there by toensure appropriate & effective management to decrease the malaria burden.

CASE DEFINITION OF MALARIA ARE AS FOLLOWS:

1. Uncomplicated Malaria Confirmed (UMC)-a. Fever or History of fever within last 48 Hours.b. Absence of convincing evidence of any other Febrile illness,c. High index of suspicion, endemic zone, susceptibility population, transmission

season andd. Diagnosis is confirmed by Blood Slide Examination (BSE) or Rapid Diagnostic Test

(RDT) Positive for Plasmodiumfalciparum.

2. Uncomplicated Malaria Presumptive (UMP)-In absence of Microscopy or RDT, UMP is

a. Fever or History of fever within last 48 Hours.b. Absence of convincing evidence of any other Febrile illness,c. High index of suspicion, endemic zone, susceptibility population, transmission

season etc.

3. Severe Malaria (SM)-a. Fever or History of fever within last 48 Hours.b. With one or more of the following features of severity

i. A change of behavior, confusion & drowsiness,ii. Altered consciousness & coma (cerebral malaria),iii. Generalized convulsion >2 episodes in 24 hours,iv. Hypoglycaemia (


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MALARIATREATMENT REGIMENThe malaria treatment regimen as per case definitions are as follows:1. Uncomplicated Malaria Confirmed (UMC)-The drug should be depending on the species which are as follows:

For P. falciparum Infection:

Artemethur + Lumefantrin combination (Coartem)-24 Tabs in divided dosagesfor adults(3 days).Or

Qunine for 7 days. (Alternative in specific and special situations)

OrQuinine for 7 days + Tetracycline 7 days (Q7+T7) or Quinine 7 days +Doxycycline 7 days (Q7+D7) may be second line.

Rationale of Anti-Malarial combination treatment

a. To improve therapeutic efficacy,b. To delay the emergence of resistancec. To prevent transmission (as coartem has gametocidal effect).

For P. vivax infection-Chloroquine 3 days + primaquine 14 days (CQ7+PQ14)

Tab. Chloroquine (150mg base)1st day- 10mg/kg2nd day- 10mg/kg3rd day- 5mg/Kg (i.e. - 4+4+2 Tablet)

2. Uncomplicated Malaria Presumptive (UMP)-The drug should be Chloroquine-03 days

Drug Day Weight in Kg

3-5 6-9 10-19 20-29 30-39 40-49 50+

ChloroquineTab. 150mg

base

Day-1 0.5 1 1.5 2 3 4Day-2 0.5 1 1.5 2 3 4Day-3 0.5 1 1.5 2 2 2

But all efforts should be made for confirming the diagnosis as soon as possible by BSE orRDT. If BSE/RDT is positive, treatment should be started in the line of UMC.

3. Severe Malaria (SM)Objectives:1. The primary objective of treating severe malaria is to save life.2. Secondary objectives are to prevent recrudescence, transmission or emergence of

resistance.3. In the treatment of severe malaria in pregnancy, saving mothers life is primary objective.The drugshould be:

IVQuinine drip/IM Quinine followed by oral Quinine for 7 days.IM Artemether or IV Artesunate will be used in selected cases.

Specialsituations are-a. Pregnancy in 1st trimester b. Children


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Leaning ObjectivesBy theend of this unityoushould beable to:

Define what is severe malaria.Identify the high risk groups likely to get severe malaria]Diagnosis severe malaria

Appropriate the importance of early treatment

IM Quinine / Rectal Artesunate may be used as pre-hospital treatment in thecommunity. Immediate referral should be made to the nearest health facility whereparenteral treatment is available. There is insufficient evidence to recommended one anti-malarial over other forsevere malaria.

LEARNING UNIT -03:Severe Malaria

What is severe malaria?Severe malaria is falciparum malaria that is sufficiently serious to be an immediate threat to

life. It is a medical emergency. A patient having sign symptoms of severe malaria should behospitalized immediately. Diagnosis is definite if there are asexual forms ofPlasmodium falciparumon ablood film/and or Rapid Diagnostic Test, (RDT) for P. falciparumpositive and the patient has any ofthe following:

- A change of behavior, confusion & drowsiness,- Altered consciousness & coma (cerebral malaria),- Generalized convulsion >2 episodes in 24 hours,- Hypoglycaemia (


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Any infection with P. falciparum can become severe if treatment is delayed or inadequate.However, people who have been repeatedly exposed to malaria develop partial immunity & are lesslikely to experience severe malaria. Those people who are at risk are as follows:

- Children in areas of high endemicity especially those aged from six months to six years.- People of all ages in areas of low endemicity,- Travelers from areas where there is little or no malaria when they go into malarious areas;

this may involve travel within a single country or between countries,- People returning to highly endemic areas after a few years absence,- Indigenous pregnant women, especially those in their first pregnancy,- Migrant people to high endemic area.

Why does severe malaria need special attention?Because:

Severe malaria is common cause of voidable death, Correct early treatment & careful nursing can greatly improve the outcome, Antimalarial drugs should, if possible, be given parenterally under close supervision, Treatment should preferably in hospital, Treatments which are not recognized by national malaria treatment guideline should

be avoided.

How severe malaria is diagnosed?Consider the possibility of severe malaria in patients with any of the clinical features and/ or

syndromes listed above, even if the illness did not start with typical malaria symptoms.

A common reason for death in severe malaria is that the diagnosis is not thought ofimmediately in patient presenting with one of the complications.

Most patients will also have fever but this is not invariable.

Ideally a blood film should be done to demonstrate the presence of P. falciparum asexualparasites. But remember:

Getting a blood film done must not be allowed to delay the start of treatmentunduly.

Occasionally blood films may be negative even though the patient is suffering fromsevere malaria. Blood films be repeated every 6 hourly, if clinical features stronglysuggest severe malaria; treatment may be started even if films are negative.

Positive blood film does not prove always that malaria is the cause of the severeillness. Consider & look for other possibilities as well.

Rapid diagnostic test (RDT) for P. falciparum with sign/ or symptoms of severemanifestation is also considered as diagnosis of severe malaria. But remember:

y RDT may be positive due to prior malarial illness,y A blood film is the Gold Standard,y Clinical judgment is the priority where the positive RDT is a strong adjuvant to

diagnosis,

y RDT is particularly helpful in patients with prior anti-malarial use & cases coming tohospital in odd hours.

You should read carefully the next section of this module the session

to which it relates.


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LEARNING UNIT -04:Pathophysiology of severe falciparum malaria:

Working as a small group, read carefully the following unit, remember that while some of thefactors & theories are established, others remain speculative.

Discuss with colleagues first, then in plenary, what you have read. Consider therelevance of the Pathophysiology in determining the appropriate treatments.

Mechanism of malarialdisease: The possible effects of malarial infection cover an enormous range, from completelyasymptomatic infection to fatal severe disease. Many factors are believed to influence the clinicalmanifestations of infection: some of these factors are known beyond, while others remainspeculative. They include:

Factorsknown to influence theseverity of disease in a malaria infection: The species of parasite P. falciparumusually causes severe & complicated malaria but it also

(more commonly) causes mild or asymptomatic disease.Severe disease due to Vivax I hasbeen reported.

The immunity of the individual. Adults who have lived all their life in an endemic area areless susceptible to severe disease than:

Adults who visit an endemic area for the first time, Young children living in the same endemic area. Pregnant women are more

susceptible, perhaps because of altered immunity. The use effective antimalarial drugs either as prophylaxis or early in the course of the

malarial illness. The degree of parasite drug-resistance that prevails locally. Some genetically inherited conditions in the human host eg.Sickle cell trait, which reduce

the risk of a P. falciparuminfection leading to severe disease.

Factors that may affect theseverity of illness (but we do notyet know forcertain) The particular strain ofP. falciparum is some strains more virulent than others? There is

evidence to suggest that this is so, but no proof. The age at which first infection takes place. Perhaps very infections in the first 3 months of

life, when maternal antibodies still convey some protection against parasite proliferation ordisease- cause gradual immunization with less risk of severe disease.

The intensity of transmission: if transmission is very intense, first infections in infants willtend to occur very early in life. There is evidence that the pattern & severity of disease inchildren differs according to the local transmission pattern.

Other differences between people; some abnormal hemoglobins in their heterozygote stateeg. HbS & red cell abnormalities ( and thalassemia G6-PD deficiency, ovalocytosis) as well

Leaning ObjectivesBy theend of thisunityoushould beable to:

Describe the mechanism believed to be responsible for the

main complications of malaria.Show how an understanding of the mechanism of thedisease can help to determine appropriate treatment.


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as some tissue (HLA) types in some areas seem to make individuals less susceptible to severedisease.

Other infections or circumstances that might impair immunity. The extent of the individual response to an infection eg. The rate & degree of production of

cytokines such as tumour necrosis factor(TNF). The number of spotozoites injected by the mosquito (or by several mosquitos).

Mechanism of mild (uncomplicated illness)All species of malaria parasites can cause of fever with its associated symptoms (shivering,

headache, myalgia, rigors). There is now little doubt that fever is caused not directly by the parasitesbut by host substances known as cytokines. These are secreted by host cells (marcophages,endothelial & other cells) in response to parasites or red cell materials released when the schizontruptures. Fever is in itself not a bad thing & it may be beneficial, because we know that a highertemperature suppresses parasite growth & also accelerates host immune mechanism eg. Abproduction.

Possible mechanism of severe disease1. Cytokines:

It is possible but still not proven, that cytokines, if produced to excess may cause severedisease in addition to fever.One cytokine known to be secreted by the individual in responseto malaria is TNF. Large quantities of TNF circulate in severe malaria, especially in fatalcases & we know that TNF is capable of causing many of symptoms, signs & complicationsthat are typical of severe malaria e.g. Coma, Hypoglycemia, Acidosis, Anemia &Respiratory distress syndrome (inshort- ARCH).

2. Sequestration:In falciparum malaria, a consistent pathological feature is the sequestration of red blood cellscontaining maturing parasites (schizonts; large trophozoites) in deep capillaries & venules.This phenomenon is observed in many different organs & tissues including the brain, lung,heart, bone marrow & gut. It seems likely but is not proven that sequestration is in some way

responsible for certain complications such as altered consciousness & acidosis.

If sequestration is important in causing severe disease , how does it do so? It is unlikely thatsequestration actually blocks blood vessels so that blood flow is reduced or stopped. Ifsequestration had this effect, we would expect most people who recover from malarial comato have persisting brain damage but this is not so. Most survivors recover fully.

a. Alternatively sequestered parasites, which we know to be highly metabolicallyactive, may use up vital substances such asglucose, oxygen, and so that these are notavailable to host cells e.g. brain cells. The parasites may produces waste mattere.g. lactate or toxins e.g. free iron, toxic oxygen radicals that are directly injuriousto host tissues.

b. Another alternative theory is that sequestration serves to concentrate schizonts in vital tissues. Rupture of schizonts may then stimulate the release of largequantities of cytokines locally which could then have a powerful local effect evenif cytokine levels in the general circulation are not particularly high.

c. In vitro, a parasitised cell may attract an unparasitised cell, which adheres to thesurface of the parasitized cell forming a rosette. There is not yet any convincingevidence that rosettes play an important part in pathogenesis in vivo.

3. Raised intracranial pressure:Children with cerebral malaria commonly have a high opening pressure of the cerebrospinalfluid, indicating raised pressure in brain & spinal column. The cause of raised intracranial


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pressure is not clear. It is not due to cerebral edema, although this may occasionally developas a terminal event. Intracranial pressure may sometimes be high because of the

a. Increased mass of red cells sequestered in the brain, orb. Dilatation of vessels in the brain in response to locally generated cytokines.

Raised intracranial pressure is not the cause of coma / death in the majority of cases . It may,however, play a part of pathogenesis or affect the course of the disease in ways that are not

yet understood.

Other mechanism of some specific complicationsy Anemia: Anemia is partly due to the destruction of all red cells that contain parasites. Several othermechanisms may accelerate the development of anemia: non-parasitised red cells are destroyed morequickly than normal during malarial illness & bone marrow does not functioning adequately. Anemiais worsened if ther is abnormal bleeding, intravascular haemolysis, renal failure, hypersplenism.y Pulmonary edemaPulmonary edema may result from excessive fluid replacement by intravenous infusion, especially ifthere is renal failure. Respiratory distress syndrome appears to be due to a direct effect of parasitessequestered in the lungs, possibly through release of cytokines.y Renal failureRenal failure is acute tubular necrosis. It is therefore fully reversible if the patient is kept alive e.g. byperitoneal dialysis for long enough usually 2-3 weeks. Renal failure is most likely to develop if therehas been a period of low blood pressure or shock.y HypoglycemiaHypoglycemia may be due to

a. Impaired gluconeognesis in the liver,b. May result from the fact that maturing parasites consume large quantities of glucose from

plasma,c. In children hypoglycemia may develop during any period of fasting & it therefore

complicates much childhood illness in addition to malaria.

d. Another mechanism: most commonly but not only seen in pregnant women, may developduring the course of treatment with quinine or quinidine. These drugs stimulate the pancreasto secrete insulin, which may lead to hypoglycemia.

y AcidosisAcidosis is probably due to a relative shortage of oxygen in tissues occupied by parasites. This lackof oxygen forces tissues to get their energy by other biochemical pathways not dependent on O2: asa result of this is the release of lactic acid, leading to metabolic acidosis (anaerobic).

LEARNING UNIT -05:Guidelines for diagnosis & assessment of sever malaria:

You should read carefully the next section of this module the session to which it relates.

Leaning ObjectivesBy theend of thisunityoushould beable to:

Record a complete history from the patient/ relatives.Conduct a physical examination of the patient looking forsignificant signs.Request the most urgent tests necessary for the diagnosis &management of severe disease.


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The history:Malaria may be confused with a wide variety of disease syndromes; a careful history may provide afirm basis of differentiation

The patients/ relatives should be carefully questioned in order to gain information that is of great

value in establishing a diagnosis.A complete history has two aims;

To look for clues to possible diagnosis other than malaria, To assess the severity of malaria & of any of its complications.

In the course of taking a complete history, pay special attention to:

Table: 01Geographical history Residence & travel within and / or outside the countryDrugs taken Anti malarials & other drugs:

Prior to illness For this illness

Symptoms: their duration &time course

y Fever, chills, rigor, these may have proceeded later developments,y Change of behavior: relatives or guardians must be specifically

asked about this-it may not be obvious to you,

y Drowsiness or deteriorating level of consciousness,y Convulsions, when, how many? Try to distinguish from

unconsciousness, chill & rigor for which the same word is used inmany languages,

y Very dark urine,y Breathlessness,y Inability to eat or drink, to talk, stands or walks. These indicate

the need for admission to hospital.Previous illness & treatment Any recent febrile illness may be important. The current sickness may

be a relapse e.g. typhoid or a complication of an infectious disease e.g.post-measles encephalitis, cerebral abscess after pneumonia,meningitis after otitis media.

Remember that sickle cell anemia crisis may resemble malaria & maybe triggered by malaria, a history of previous episodes or diagnosismay be helpful.

Diabetes may complicate the clinical picture & will require specialattention in a patient with malaria.

Previous blood transfusions When?y Hepatitis may resemble malaria,y Malaria itself may be transmitted by transfusion.

Is the patient pregnant? A pregnant patient is at special risk both from malaria & from its drugtreatment,

Other illness in the family? An identified illness in a close relatives or contact may suggest analternative diagnosis- e.g. meningococcal meningitis, measles, mumps,chicken pox, typhoid fever, tuberculosis.


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There may be other clues in the history- e.g. a dog bite in a patient with rabies, head injury in apatient developing a subdural hematomas, drug overdose, and chronic alcoholism.

This outline suggests some common points requiring emphasis. Much other useful information mayfrom a complete history.

The physical examination:Like the history, the complete examination aims at,

y Identifying other possible diagnosis &y Assessing the severity of malaria & any of its complications.

Pointers to an alternative diagnosisThese examples are quoted because they are commonly neglected:

Table: 02In all patients Inchildren

y Rash: rare in malaria, may suggest typhus,typhoid, measles, & arbovirus infection,

relapsing fever, chicken fever, leptospirosisor meningococcaemia.

y Neck stiffness: note that absence of this doesnot exclude meningitis & some children withsevere malaria have neck stiffness (as part ofgeneralized hypertonicity in some patientswith cerebral malaria).

y Sepsis: look for signs of sepsis in any limb ororgan.

y Enlarged lymph nodes: trypanosomiasis,tuberculosis & many other possibilities.

y Eardrums: acute or chronic otitis media.y Buccal mucosa: kopliks spots of prodromal

measles,y Pharynx: tonsillitis, diphtheria,y Bulging fontanelle: suggests meningitis (small

child)

y Shallow, rapid breathing with nasal flare: maysuggest acute respiratory infection (ARI) orpneumonia (but remember that somepatients with severe malaria haveabnormalities of breathing).

Clinical features indicating severe malaria:Each of the clinical features and/ or syndromes listed on page 8-9, that define malaria as severe orcomplicated may be suspected on the basis of clinical assessment (history & physical signs).

Behavioral changes:May include confusion, delirium, agitation, somnolence, hallucinations psychosis.

Differential diagnosis: typhoid, drug or alcohol intoxication, hypoglycaemia of any cause,encephalitis (including rabis), metabolic failure e.g. hepatic failure, renal failure, & heat stroke.

Coma (cerebral malaria):Cerebral malaria may be defined as unrousable coma in falciparum malaria . However every patient ofmalaria with altered sensorial should be managed as cerebral malaria until proved otherwise.

Coma may be moderate or profound, gradual or sudden inset. Coma is usual sequelae of aconvulsion of any cause, but if due only to convulsion; consciousness is usually resorted within a fewminutes to few hours.

Neurological manifestation:one or several of the following neurological manifestations may bepresent:


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1. Diffuse symmetrical encephalopathy. Focal neurological signs are rare,2. Focal or generalized convulsions,3. Muscle tone may be increased or decreased,4. Tendon reflexes are variable; planter reflex may be flexor or extensors,5. Tooth grinding (bruxism) may be observed,6. Motor abnormalities such as decebrate rigidity & decorticate rigidity (arms flexes

& legs stretched) may be present,7. Mild neck stiffness may occur, but frank signs of meningitis in the form of neck

rigidity, positive Kernigs & photophobia are rare. However in suspected casesmeningitis should be ruled out by doing a lumbar puncture examination.

Differential diagnosis:all conditions listed under behavioral changes above.

Convulsions:Relative may describe what they believe were convulsions, occurring before the patient came to theclinic/ hospital. Ask a person who witnessed the event & request details including movements ofhands & face, biting of tongue, incontinence.Sometimes any loss of consciousness or even drowsinessis described by the same words used for convulsions.

HypoglycemiaMay manifest as altered behavior, loss of consciousness, convulsions or simply vague symptoms ornone.Sweating & cold, clammy skin may be present but are not invariable.

Acidosis:There is deep (not necessarily) breathing. This is not dependable sign, as the breathing pattern may beobscured by other influences- e.g. depression or excitation of respiratory center in the brain stem,pulmonary edema or chest infection. In may be possible to detect acidotic factor (sweet smell).

Other breathingdifficulties:The breathing pattern in severe malaria is influenced by many factors-

Central effects, resulting from disease in the brain. These include irregular breathing.Cheyne-stokes breathing & noisy or stertorous breathing.

Acidaemia- causing deep respiration,

Infection- aspiration pneumonia, causing labored breathing, High fever- causes rapid breathing, Pulmonary edema- causes rapid breathing with crackles heard on auscultation & in severe

cases, pink frothy sputum & central cyanosis (tongue). Heart failure, which may complicate severe malaria, featured with hepatomegaly, gallop

rhythm & pulmonary edema. Respiratory distress syndrome- indistinguishable from pulmonary edema, but in the absence

of fluid overload.

Acute renal failure:

Mortality is significantly higher in patients of cerebral malaria when associated

with other complications such as ARF, ARDS etc. Therefore cerebral malariapatients with multiple complications should be referred to facilities of

intensive care if available.


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This is detected by the monitoring of urine output. If there is persist oliguria (volume ofurine produced is less than 17ml/hour in an adult or less than 0.3ml/kg/hour in a child, despiteadequate correction of dehydration or hypotension), then renal failure is present or imminent.Hiccup is the indicator of advanced renal failure.

Severe anemia:Properly diagnosed by measuring haematocrit or Hb level.Suggestive sign is severe pallor of

mucosa (especially tongue). Severe anemia may cause heart failure (breathlessness, enlarged liver,gallop rhythm, pulmonary edema), or altered consciousness.

Shock:There is low blood pressure, a feeble pulse & impaired tissue perfusion with cold , clammy

skin & peripheral cyanosis (nail beds, lips).

Hemoglobinuria:The urine is dark, tests are strongly positive for blood (Hb) but contain no red blood cells on

microscopy, plasma may also dark due to hemoglobin freed from red cells.

Jaundice:Best detected on sclerae of eyes. This is quite commonly seen in severe malaria, but signs ofhepatic failure are rare.Jaundice in malaria occurs concomitantly with fever (unlike jaundice due tohepatitis)

Bleeding tendency: There may be spontaneous bleeding from gums or in the skin or prolonged bleeding at

venepuncture sites. Best tested by measuring the bleeding time (pierce earlobe with lancet, mopevery 15 seconds with filter-paper, in normal circumstances bleeding will be stopped within 2minutes).

Extreme weakness:The patient cannot sit or stand without help from others. There may be many contributing

causes. In children it may be presented by inability to eat.

Assessing the coma score: A score is based on the patients ability to move & speak in response to commands &

painful stimuli. In infants who have not yet acquired speech, you can assess the cry & the childsability to watch its mothers face & also the response to pain.You may grade coma according to oneof the following scales (tables03 & 04).

The Glasgow coma scale (Table03) is suitable for adults & for the older children.

For the children aged 9months to 12 years, the modified Blantyre score (Table04), may be used.

Measurement of coma in younger infants is difficult. It is best to describe how the child responds toa standard painful stimulus.

Table-03 (Glasgow Coma Scale)Site Symptoms Score

y Eyes open Spontaneously 4


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To speechTo painNever

32

1

y Best verbal response OrientatedConfusedInappropriate words

Incomprehensible soundsNone

543

21

y Best motor response Obeys commandsLocalizes painFlexion to pain:

WithdrawalAbnormal

Extension to painNone

65

432

1 Total 15

To obtain the Glasgow coma scale, obtain the score for each section, then add the three figures to

obtain the total.

Table-04: The modified Glasgow coma scale (The Blantyre coma Scale)Site Symptoms Score

Eyes movements Directed e.g. follows mothers faceNot directed

10

Verbal response Appropriate cryMoan or inappropriate cryNone

210

Best motor response Localizes painful stimuli1W

ithdraws limb from pain2Nonspecific or absent of response

21

0

Total

1) Press your knuckles firmly on the patients sternum,2) Press firmly on patients thumbnail bed with the side of a horizontal pencil.

These scales can be used repeatedly to assess improvement or deterioration.

Laboratory investigations:1. Thick & thin blood film for malaria parasites,12. Rapid Diagnostic Test (RDT) for P. falciparummalaria2.3. Blood glucose in any patient with altered consciousness, confusion, and convulsion. This is

the best done using a stix method. The test requires one finger-prick blood & the resultcan be read within 1-2 minutes, either by eye or more accurately by reflectance meter.

4. Haematocrit,5. Lumbar puncture to exclude meningitis. Meningitis cannot be diagnosed without a lumbar

puncture. Neck stiffness may be absent in meningitis, especially in children & after aconvulsion, some patients with malaria have neck retraction or optisthotonos, withoutmeningitis. A clear cerebro-spinal fluid should be examined microscopically for cells, since a


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fluid may look clear with up to 300cells/mm3. Do not wait for the cell count result if this willtake more than a few minutes.

With these results you should initiate immediate treatment without waiting for other test results.

1. For complete reference onhow to prepare thick & thin blood films, staining techniques &examination ofblood films for malarial parasites: BasicMalaria Microscopy, Part 1:Learners guide, Part 2: Tutors guide.Geneva, World HealthOrganization, 1994. See annex 1

2. For details of RDTSee Annex 2Discovery of parasitaemia can quickly confirm clinical suspicion of malaria, but in patient withsymptoms & sign compatible with severe disease, a therapeutic trial of parenteral anti-malarial drugis justified, even if the initial blood film is negative. This applies to both immune & non-immuneperson.

Antibiotics in appropriate doses should be given to cover the possibility of bacterial meningitis, ifCSF is inconclusive or for control of other unrecognized infections.

Other laboratory investigations if possible:These are not essential to management, but if available may be helpful or of prognostic usefulness.

1. Plasma creatinine: Urea is an alternative, but there is no need to measure both as creatinine ismore useful.

2. Electrolytes, these may occasionally reveal a correctable abnormalities such ashyponatraemia. Both creatinine & electrolytes are of most value when acute renal failurethreatens or develops.

3. Full blood cell count & differential count of WBCs sometimes these may indicates thepossibility of an additional diagnosis e.g. gross Eosinophilia or complications e.g. profoundthrombocytopenia.

4. Chest X-Ray may identify pulmonary edema, respiratory distress syndrome or lobarconsolidation (pneumonia).

5. Blood culture because septicaemia may complicate severe malaria & cause shock orunresolving fever.

6. Liver function test.7. Blood gases analysis, pH & anion gap, Acidaemia is an indicator of severe disease, in both

conscious & unconscious patients.8. Plasma & cerebro-spinal fluid lactate concentrations. These are raised in lactic acidosis; high

levels are associated with a poor prognosis.


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Investigations & Management:Some investigations will be equally or more valuable if repeated during the course of

treatment, according to clinical indicators e.g. blood glucose for deepening coma or convulsions,

creatinine & electrolytes if renal failure is suspected, chest X-Ray for possible pulmonary edema orrespiratory distress syndrome. Some tests nearly always need repeating at intervals: Blood films ,Haematocrit, Hemoglobin concentration estimations etc.

LEARNING UNIT -07:

The management of severe & complicated malaria:

Poor Prognostic Indicator:A. Clinical indicators-

a. Age under 3 yearsb. Deep comac. Witnessed or reported convulsionsd. Absent of corneal reflexese. Decerebrate rigidityf. Clinical signs of organ dysfunctions (renal failure, pulmonary edema.

B.Laboratory indicators-a. Hyperparasitaemia (>5% in hyper-endemic area)b. Peripheral schizontaemia,c. Peripheral leukocytosis,d. PCV less than 15%,e. Hb% 3mg/dl,j. High CSF lactate >6 mmol/l,k. More than 3 fold increased liver enzymes,l. Increased plasma 5-Nucleotidase,m.Low anti-thrombin III levels.

Leaning Objectives

By theend of this unityoushould beable to:

Provide urgent treatment to the severely ill patient.Provide maintenance treatment throughout the period ofillness.

Arrange for regular monitoring & appropriate actions asnecessary.

You should read carefully the next section of this module thesession to which it relates.


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How is severe & complicated malaria managed?Under ideal conditions the severely ill patient, especially comatose, should be managed in

Intensive Care Unit (ICU). This is not possible in most endemic areas. In such conditions the nurseassures the role of the intensive care unit monitoring system. Thus the nurse must be appropriatelytrained up to high level optimal skill to assure the essential role in patient management.

Clinical assessment & Urgent treatment & General measures-y Clear & maintain the airways,y Maintain the breathing,y Circulation assessed,y Position semi prone or on side,y Establish an intravenous infusion by a canula,y Weight the patient or weight estimated to calculate dose,y Measure blood glucose & correct the hypoglycaemia (


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Continuing treatment:This calls for close co-operation between medical & nursing staff. Responsibility for various

observations must be allocated according to availability & expertise of personnel. Proper nursingcare of the unconscious patient is of utmost importance in patients with cerebral malaria.

You should have a record chart on which the important complications of the patients illness aresummarized, treatment is prescribed & all important observation is recorded at suitable intervals.

A sample chart is provided (Table-06) make our own modification to this chart according to local

facilities & experience.

Stipulate how frequently observations should be made: this will depend on the particularcircumstances of each patient & the severity, stage & the complications of illness. For example,blood glucose should be checked hourly in a comatose pregnant woman receiving intravenousquinine, but less frequently in a man whose condition is steadily improving.

Observations should be aimed at: Controlling & monitoring the delivery of drugs & infusion fluids. Detecting the development of complications of malaria. Detect the toxic effects of drugs being given. Document the patients recovery/ clinical illness.

Specific Anti-malarialChemotherapy In Severe Malaria: There are currently five parenteral drug treatments which are recommended for severe

malaria: Quinine, Artesunate, Artemether, Artemotil, Quinidine. All patients of severe malariashould be treated with parenteral Quinine or artemesinin degivatives due to presence of widespreadchloroquine resistance in South East Asia.s

Treatments which are not recommended:y Corticosteroids,y Other anti-inflammatory agents,y Other agents given for cerebral edema (urea, invert sugar)y Low2 molecular weight dextran,y Epinephrine (adrenaline).y Heparin,y Epoprostenol (PGI2),y Pentoxifylline (oxepentifylline),y Hyperbarie oxygen,y Cyclosporine (cyclosporine A),y Hyper immune serum,y Iron chelating agents,y Dichloroacetate,y Anti tumor necrosis factor anti body (anti TNF antibody)


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Table-05Anti-malarial chemotherapy of severe falciparum malaria in adults & children:Quinine:

Loading dose: quinine dihydrochloride20 mg salt/kg of body weight by infusionover 4 hours, in 5% dextrose saline (5-10

ml/kg of body weight depending on thepatients overall fluid balance). Maintenance dose: 8-12 hours after the

start of the loading dose, given amaintenance dose of quinine 10mgsalt/kg of body weight dextrose salinediluted as above over 4 hours. Thismaintenance dose should be repeatedevery 8-12 hours, calculated from thebeginning of the previous infusion, untilthe patient can take oral medication.

Oral Quinine:Q

uinine sulphate 10mgsalt/ kg, 8 hourly to complete a 7 dayscourse of treatment.

Artemesinin Derivatives

Artesunate: 2.4 mg/ kg (loadingdose) IV, followed by 1.2 mg/kg at12 hours then 1.2 mg/kg daily for 6

days, if the patient is able to swallow,the daily dose can be given orally.

Artemether: 3.2 mg/kg (loadingdose) IM followed by1.6 mg/kg dailyfor 5 days. If the patient can swallow,the daily dose can be given orally.

Arteether: 150 mg once a day bydeep intramuscular injection for 3consecutive days in adults.

y Artemesenin derivatives are safe, effective, have a wider therapeutic window, can beadministered intramuscularly & should be considered a safer alternative to quinine.

y The choice of oral medication will be governed by drug availability & sensitivity of theparasites. The following may be used: Quinine tablets10 mg/kg of body weight, every 8 hours, to complete 7 days of

treatment or single dose of sulfadoxine/ pyrimethamine (Fansider) following ashorter course of quinine. Shorter course include the schedule of quinine

10mg/kg for 9 oral dose followed by single oral dose of fansider. Chloroquine is ineffective in severe falciparum malaria.There is no evidence that combining with an artemesenin derivatives provides any

additional benefit & it adds potential toxicity. This is not recommended.

Some important points to note in relation to table -05:1. In areas with a significant degree of quinine resistance add an oral course of tetracycline

250mg four times a day for 7 days, as soon as the patient can swallow. It is unnecessary &dangerous to give tetracycline intravenously. Tetracycline is contraindicated for childrenunder 8 years & pregnant women. As an alternative, Mefloquine could be given as indicatedin foot note B to table-04.

2. In patients requiring more than 48 hours of parenteral therapy, reduce the quinine or quininemaintenance dose by one-third to one-half (i.e. 5-7 mg salt/kg of body weight every 8-12hourly.

3. Total daily doses of intravenous quinine are as follows:Adults:

Day 0 (first day of treatment): 30-4- mg salt/kg of body weight. Day1: 30 mg salt/kg of body weight. Day 2 & subsequent days: 15-21 mg salt/kg of body weight.

Children:


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Day 0: 30-40 mg salt/kg of body weight. Day1: 20 mg salt/kg of body weight. Day 2 & subsequent days: 10-14 mg salt/kg of body weight.

It is unusual to have to continue intravenous infusions of quinine for more than 4-5 days . Inchildren the infusion can usually be stopped after 1-2 days.

4. If it is more convenient, quinine may be given by continous infusion. (Infusion rates shouldnot exceed 5 mg per kg of body weight per hour).

5. A loading dose should not be used if the patient received quinine or quinidine within thepreceding 24 hours or mefloquine within the preceding 7 days.

6. If for some reason quinine cannot be administered by infusion, quinine dihydrochlorode canbe given in the same dose by intramuscular in the anterior thigh. The dose of quinine shouldbe divided between two sites- half the dose in each anterior thigh (not the buttock) . Ifpossible, for intramuscular use, quinine should be diluted in sterile normal saline to aconcentration of 60 mg/ml.

7. Quinine should never be given by intravenenous injection.8. The objective of a loading dose is to provide therapeutic blood concentration as early as

possible in the course of treatment without overshoot to toxic level. The loading dose is

unnecessary if the patient has received more than 40 mg/kg of quinine in the previous 2days.9. As pre-treatment is common in the tropics & the patients history may be unreliable there is

often concern that administration of a loading dose may cause cumulative toxicity. Inpractice this is rare, so if in doubt the loading dose should be given.

10.If there is no clinical improvement after 48 hours of parenteral therapy, the maintenancedose of parenteral quinine should be reduced by one-third to one half (i.e. 5-7 mg quininesalt/kg).

11.The patient who had developed severe malaria despite treatment with Mefloquine should begiven, the loading dose of quinine unless the last dose of Mefloquine was administeredwithin the previous 12 hours.

An example of a chart for recording regular observations during treatment of severe malaria isshown above. This could be modified to suite particular circumstances. Clinical notes should also bekept separately. Frequency of observations should be according to clinical need.

The following table indicates some of the important observations duringtreatment & their complications:

Table-07:Regularobservations

Possible abnormality Appropriate actions

ClinicalBreathing Increased rate or difficulty Review urine & fluid balance. Assesslung, heart, live4r size. Chest X-Rayif available. If pulmonary edema isdemonstrated, or seems likely,treatment prop up 450,O2 diuretics,stop IV fluid, incubate, Haemofilter.

An uncomplicated P. falciparum malaria patient may progress tosevere & complicated state if not treated early & appropriately.


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Temperature >390 C (core)

If temperature remains high orrises despite 24 hours of anti-malaria therapy.

Give paracetamol (rectal or oral) ifnot given within past 4 hours. Tepidsponge & faming- get relatives tohelp with this.Reconsider your diagnosis, whilecontinuing treatment.

Bl

ood pressure Falls:


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Follow up treatment of severe malaria: Quinine or Artesunate.

Pre-referral treatment options: Either IM Quinine or Rectal Artesunate when available.

Management of severe malaria in epidemic situations: repeated injection byQuinine may notbe feasible. Diagnosis by Rapid Diagnostic Test. Artemether IM injection is preferable.

Special clinical features & management of severe malaria inpregnancy:

Woman developing malaria during 2nd & 3rd trimester of pregnancy or post-partum period isat higher risk of developing severe complications than non-pregnant women . Mortality is 2-10 timeshigher than non-pregnant patients. The clinical manifestations of malaria in pregnancy may varygreatly according to their level of immunity. Non-immune pregnant women are more likely todevelop cerebral & other complications, particularly hypoglycemia & acute pulmonary edema. Theyhave an increased risk of abortion (in severe malaria), still birth, premature delivery & low infantbirth weight. Uterine contractions may be induced, the frequency & intensity of which appear to berelated to the height of fever. Role of early Caesarian section for viable live foetus is unproven but is

recommended by many authorities. Obstetric advice should be sought at an early stage & thepaediatrician alerted & blood glucose checked frequently. Anti-malarial drugs should be given in fulldoses. Artesunate or Artemether are preferred over quinine (except in 1st trimester) because quinineis associated with recurrent hypoglycaemia.Associated infections occur: Pneumonia & urinary tract infections are common.

Clinical features of importance:Hypoglycaemia:

y May be present as initial presentation,y May occur after quinine infusions and usually recurrent,y It is commonly asymptomatic,y May be associated with fetal distress & in severe cases with lactic acidosis & high mortality.Pulmonary edema:y May present as initial presentation,y May develop suddenly & unexpectedly.y May be develop immediately after childbirth.

Anemia:

y Associated with peri-natal mortality, morbidity & increased risk of fetal maternal postpartumhaemorrhage,

y Women who go into labour when severely anaemic or fluid overloaded may developpulmonary edema after separation of the placenta,

Management:

y Pregnant women with severe malaria should be transferred to an intensive care unit forcarefully monitoring because of the higher risks involved.

y Treat hypoglycaemia as described earlier.y If volume overload conditions develop, treat as described earlier.y Monitoring of uterine contractions & fetal heart rate may reveal asymptomatic labor & fetal

tachycardia, bradycardia or late deceleration in relation to uterine contractions indicatingfetal distress.

y Once labor has started, fetal or maternal distress may indicate the need to shorten thesecond stage by forceps or vacuum extraction or caesarian section.


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Anti-malarial drugs:Quinine in the doses advocated for the treatment of life-threatening malaria is safer in

pregnancy. It has been shown that the initial intravenous infusion ofQuinine in women who aremore than 30 weeks pregnant is not associated with uterine stimulation or fetal distress. Its majoradverse effect is hypoglycaemia.Artesunate &Artemethershould not be used in first trimester of pregnancy.

Table-08:Common errors in the management of severe malaria:

Daley in starting anti-malaria therapy,Dosage not correctly calculated,Inappropriate route or schedule of drug administration &/or,Failure to elicit a history of recent chemotherapy and/orUnjustified cessation of treatment,Failure to control the rate of intravenous infusion and/ or,Failure to prevent cumulative effect of anti-malarial drugs,Failure to recognize & treat severe anemia,Failure to look for & correct hypoglycemia,

Failure to recognize & manage pulmonary edema, aspiration pneumonia & metabolicacidosis,Delay in starting peritoneal or haemodialysis,Inadequate nursing care,Error in fluid & electrolyte replacement,Use of an inappropriate drug,Unjustified withholding of an anti-malarial drug,Failure to switch patients from parenteral to oral therapy as soon they can take oralmedication,Unnecessary continuation of chemotherapy beyond the recommended length of treatment,Unnecessary endotracheal intubation,

Use of potentially dangerous ancillary therapies,Failure to review anti-malarial treatment in a patient whose condition is deteriorating.

LEARNING UNIT -08:Assessment of recovery and referral:

How doyou assess the patients recovery?

Leaning Objectives

By theend of this unityoushould beable to:Assess the extent to which the patient has recovered.Record any residual sequelae.

Arrange for follow up.Write a summary of the events & out-come.Appropriate referral.


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This is an extension of previous learning unit.Your records & observations will provide someindications of patient recovery-e.g. falling temperature (should fall by 48 hours). Falling parasitecount (should fall by 72 hours) & an improving coma score (should be assessed 4 hourly).In addition, also record the patients ability to:

y Drinky Eaty Talk

y Sity Standy Walk

When a patient has recovered, assess for possible sequelae of the disease or the treatment. Inparticular you should perform the followings:

A neurologicalexamination:It is assumed that the Glasgow coma scale follows up is being done .

Especially assess functional capacity in holding & using objects, ability to feed, gait & posture. Try todetermine whether the patient can do the things that he or she was able to do before the illnessbegan. For a young child this requires asking parents or guardians about the childs previousactivities.

Assess vision &hearing:Use the best available methods. Repeated examination of the fundus oculi may be preferred

to assess retinal haemorrhages. You can use simple bedside measures, especially for infants &children (e.g does the child turn its head towards a noise? Does the child watch the mother whenshe moves?) Use audiometry & vision charts if these are available.

Repeat Haematocrit & blood films:Ideally these should be repeated on the 7th & 14th day after recovery and again one month

later. Monitor reticulocyte response. Also make sure that on the 7th day the Hb is not continuing tofall. If so there may be another cause of anemia that needs to be looked for . By day the 14th fullrecovery should have occurred.

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2. Questions of Learning Unit