Malaria clinical features

MALARIA

Clinical features and diagnosis

EPIDEMIOLOGY

Malaria is a major public health problem Malaria is the fifth most common infectious

cause of mortality 3.3 billion ( half of world’s population ) are at

risk of malaria in 109 countries In 2009 Cases-225 million deaths -7.81 million

www.searo.who.int

DISEASE BURDEN IN SOUTH EAST ASIA REGION

Out of 11 countries of the Region 10 countries

are malaria endemic

15% of the global reported confirmed cases

and 2.7% of the global mortality.

In southeast Asia region India accounts for 80%

of cases

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INDIA

80.5% of the population lives in malaria risk areas

In 2010 15.9 million cases were reported No of deaths- 1023

nvbdcp.gov.in

KSCH DATA(2010-2011)

Total no of slides examined -7092

Total no of positives- 336

P vivax-291

P falciparum-45

Deaths- 10

CLINICAL FEATURES

Children are asymptomatic during the initial phase– the incubation period

P falciparum ---- 9-14 days P vivax---- 12-17 days P ovale---- 16-18 days P malariae--- 18-40 days Prolonged in p vivax, partial immunity

and incomplete chemoprophylaxis.

PRODROMAL SYMPTOMS

Headache Fatigue Anorexia Myalgia Pain in joints Chest and abdominal pain

CLINICAL FEATURES (CONT..)

The classic presentation is paroxysms of fever alternating with periods of

fatigue but otherwise relative wellness

CLINICAL FEATURES (CONT…)

Fever is the cardinal symptom of malaria Febrile paroxysms associated with rigors ,

headache, myalgia , back pain, abdominal pain, nausea and vomiting.

Paroxysms coincide with rupture of schizonts P vivax: every 48 hours( benign tertian

malaria) P falciparum and mixed infections: no

periodicity or less appparent.

PRESENTATION

Fever 96% Chills 96% Headache 79% Muscle Pain 60% Palpable liver 33% Palpable Spleen 28% Nausea or vomiting 23% Abdominal pain/diarrhea 6%

(According to the working group of WHO,2001)

On the basis of severity malaria can be classified as

uncomplicated complicated

UNCOMPLICATED MALARIA

Uncomplicated malaria is defined as symptomatic malaria without signs of severity or evidence (clinical or laboratory) of vital organ dysfunction.

The signs and symptoms of uncomplicated malaria are nonspecific.

Malaria is usually suspected clinically on the basis of fever or a history of fever.

Guidelines for the treatment of malaria – 2nd edition World Health Organization, 2010

COMPLICATED OR SEVERE MALARIA

In a patient with P. falciparum parasitaemia presence of certain clinical features or laboratory parameters classify the patient as severe or complicated malaria

COMPLICATED MALARIA (CONT..)

Clinical features

Impaired consciousness or unrousable coma

prostration

Failure to feed

Multiple convulsions (more than 2 episodes in

24 h)

Deep breathing, respiratory distress

COMPLICATED MALARIA (CONT..)

Clinical features (cont..) Circulatory collapse or shock, systolic blood

pressure < 70 mm Hg in adults and < 50 mm Hg in children

Clinical jaundice ( serum bil > 3 mg/dl) plus evidence of other vital organ dysfunction

Haemoglobinuria Abnormal spontaneous bleeding Pulmonary oedema (radiological)

COMPLICATED MALARIA (CONT…)

Laboratory parameters

Hypoglycemia (blood glucose < 2.2 mmol/l or < 40 mg/dl)

Metabolic acidosis (plasma bicarbonate < 15 mmol/l)

Severe normocytic anaemia (Hb < 5 g/dl)

Haemoglobinuria

Hyperparasitaemia (> 2%in low intensity transmission areas or >

5% in ar eas of high stable malaria transmission intensity)

Hyperlactataemia (lactate > 5 mmol/l)

Renal impairment (serum creatinine 3 mg/dl)

CLINICAL PROFILE OF SEVERE MALARIA IN INDIACharacteristics Frequency(46) Mortality

Cerebral malaria 76% 22%

Severe anemia 34% 56%

Hypoglycemia 21% 40%

Jaundice 15% 57%

Renal failure 8% 75%

Blackwater fever 6% 66%

Algid malaria 4% 50%

Indian Pediatrics 2003; 40:939-945 

CEREBRAL MALARIA

Cerebral malaria is the most severe

neurological complication of

Plasmodium falciparum

It is a major cause of acute non-

traumatic encephalopathy in tropical

countries

CEREBRAL MALARIA (CONT..)

Clinical syndrome characterised by Coma (inability to localise a painful

stimulus) at least 1 h after termination of a seizure or correction of hypoglycaemia

Detection of asexual forms of P falciparum malaria parasites on peripheral blood smears, and exclusion of other causes

WHO. Severe falciparum malaria. Trans R Soc Trop Med Hyg 2000

CEREBRAL MALARIA (CONT...)

Seizures Seizures are commonly reported and occur in

over 60% of children causes of seizures In children not associated with fever at the

time of the seizure or electrolyte disturbances. Sequestration of infected erythrocytes Parasite-derived toxins Immune mechanisms

CEREBRAL MALARIA (CONT..)

Coma Cerebral malaria is a diffuse encephalopathy

characterised by coma and bilateral slowing on Electroencephalography

coma is potentially reversible. Brainstem signs Changes in pupillary size and reaction Disorders of conjugate gaze and eye movements. Abnormal respiratory patterns (such as

hyperventilatory, ataxic, and periodic breathing) posture (decerebrate, decorticate, or opisthotonic

posturing), and motor abnormalities of tone and reflexes

CEREBRAL MALARIA (CONT..)

Cerebral malaria should be considered in the differential diagnosis of any patient who has a febrile illness with impaired consciousness who lives in or has recently travelled to malaria endemic areas

The mortality rate in children is about 20%, and most deaths happen within 24 h of admission.

CEREBRAL MALARIA

Clinical feature Children (African) Adults

Onset Rapid Insidious

Seizures More common (in 80%)

In 20 %

Neurological signs

Brainstem signs, raised ICP,retinal changes

Symmetrical upper motor neuron signs

Mortality 18.6% 20%

Sequelae 11% <5%

Lancet Neurol 2005; 4: 827–40

NEUROLOGICAL SEQUELAE

Hemiplegia

Cortical blindness

Aphasia

Ataxia

Cognitive impairment

Richard Idro ,Lancet Neurol 2005; 4: 827–40

MALARIAL RETINOPATHY

Common in children with cerebral malaria(60%) and may be related to pathological changes

Malarial retinopathy consists of four main components: retinal whitening, vessel changes(whitening of retinal vessels), retinal hemorrhages, and papilledema

Bad prognostic indicator

Lancet Neurol 2005; 4: 827–40

ANEMIA OF MALARIA

• Hemoglobin less than 8 g/dl, which is equivalent to a hematocrit of less than 24% in a parasitemic individual

Abdalla S, Weatherall D, Wickramasinghe SN and Hughes M (1980). The anaemia of P. falciparum malaria. Br. J. Haematol. 46: 171

• World Health Organization has defined severe malarial anemia (SMA) as a hemoglobin less than 5 g/dL or a hematocrit less than 15% seen in the context of malaria but without specifying parasitemia .

WHO (2000). Severe falciparum malaria. Trans. R. Soc. Trop. Med. Hyg. 94: Suppl. 1.

PANCYTOPENIA

Pancytopenia can occur in both falciparum and vivax infections.

Can be due to microangiopathic hemolytic anemia, hypersplenism

Few cases due to bone marrow suppression have and hemophagocytosis have been reported

J Fam Community Med. 2009;16:71-73

HEPATIC DYSFUNCTION

In patients with severe malarial infestation, the incidence of jaundice is reported to be around 2.5%

Transient abnormalities of liver enzymes are most commonly seen

If serum bil > 3 mg/dl---- severe malaria Hepatic encephalopathy is almost never

seen. Bhalla A J Postgrad Med 2006 Oct-

Dec;52(4):315-20.

RENAL FAILURE

• In P. falciparum malaria, acute renal failure may develop in 0.1-0.6% of the patients

Defined as Urine output <400 ml/24 hours in adults (<12 ml/kg/24 hours in children) and a serum creatinine >265 µmol/l (> 3.0 mg/dl) despite adequate volume repletion

Renal failure is rare in children• High mortality (upto 45%)

Indian Academy of Clinical Medicine Vol. 3, No. 2 April-June 2002

RENAL FAILURE CONTD..

The vulnerable group of patients are: with high parasitaemia with deep jaundice with prolonged dehydration patients receiving NSAIDs Manifests as ATN ,renal cortical

necrosis never develops

METABOLIC ACIDOSIS

Venous lactate concentration at 4 hours after

admission to hospital is the BEST PROGNOSTIC

INDICATOR in severe malaria. (>5mmol/l has

bad prognosis)

This may result form renal failure, but more

commonly there is a primary lactic acidosis

Trans R Soc Trop Med Hyg. 1994 Jan-Feb;88(1):67-

73.

HYPOGLYCEMIA

Hypoglycemia occurs in 30% of children

Hypoglycemia is a sign of poor prognosis

with a mortality rate as high as 40%.

PULMONARY EDEMA/ADULT RESPIRATORYDISTRESS SYNDROME (ARDS)

May develop even after several days of

antimalarial therapy

Mortality >80%

P VIVAX…. NEGLECTED AND NOT BENIGN

In recent years, complicated and even

fatal cases of malaria due to P. vivax

have been increasingly reported

COMPLICATIONS OF P VIVAXCONTD..

Severe anemia Acute respiratory distress syndrome (ARDS) Incidence is less in children compared adults

Coma Malnutrition Splenic rupture Thrombocytopenia Acute renal failure and shock mortality rate - 1.6% among hospitalized patients

Trends in Parasitology Vol.25 No.5

DIAGNOSIS

Symptom-based (clinical) diagnosis

Not possible to accurately diagnose malaria using

any one set of clinical criteria

Microscopy

Microscopy of stained thick and thin blood smears

remains the gold standard for confirmation of

diagnosis of malaria.

DIAGNOSIS(CONT..)

In profound anemia ---parasite --often absent

malaria pigment in polymorphonuclear leukocytes and monocytes-- malaria

If more than 5% of PNM contains visible pigment it denotes poor prognosis.

Recommendations and IAP plan of action indian pediatrics volume 42 november 2005

EXAMINATION OF BLOOD FILM

A minimum of 100 fields should be

examined before concluding the slide

to be negative.

Samples may be examined for at least

three consecutive days where clinical

suspicion of malaria persists.

ADVANTAGE OF MICROSCOPY

Advantages of microscopy are: The sensitivity is high. It is possible to

detect malaria parasites at low densities.

It also helps to quantify the parasite load.

It is possible to distinguish the various species of malaria parasite and their different stages

WHO Expert Committee on Malaria. Twentieth report. Geneva, World Health Organization, 2000

DIAGNOSIS (CONT..)

Rapid diagnostic tests are immunochromatographic tests that detect parasite-specific antigens in a finger-prick blood sample

WHO recommends that such tests should have a sensitivity of > 95% in detecting plasmodia at densities of more than 100 parasites per μl of blood

DIAGNOSIS RDT..

Current tests are based on the detection of histidine-rich protein 2 (HRP2), (specific for P. Falciparum)

pan-specific or species-specific Plasmodium lactate dehydrogenase (pLDH)

pan-specific aldolase Commercially available kit can detect

falciparum, vivax and other malaria but cannot differentiate ovale and malarie malaria.

DIAGNOSIS RDT..

HRP-II tests can remain positive for 7-14 days following malaria treatment even when blood doesn't show parasitemia by microscopy

p LDH is produced by only viable parasite so the tests detecting this antigen becomes negative within 3-5 days of treatment

ADVANTAGES OF RDTS IN COMPARISON TOMICROSCOPY simple, straight forward ,less time

consuming, requiring no special equipment or skill/training

They can detect P. falciparum infection even when the parasite is sequestered

This test can exclude mixed falciparum and vivax malaria where the former may not be evident microscopically

DISADVANTAGE OF RDTS IN COMPARISONTO MICROSCOPY

RDTs that target HRP-II of P. Falciparum is unsuitable for assessment of treatment failure and monitoring of drug resistance.

They do not quantify the parasite load so they do not have prognostic value

DISADVANTAGES RDT CONT...

Under optimal conditions an expert microscopist can detect even 5-10 parasite per μl of blood, detection threshold of RDTs are 40- 60 parasite per μl of blood

Currently, available RDT kits are required

to be stored up to or under 30ºC