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
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 www.searo.who.int
India 80.5% of the population lives in malaria risk areas In 2010
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 isusually 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. falciparumparasitaemia 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 areas of high stable malaria transmission intensity) Hyperlactataemia (lactate > 5 mmol/l) Renal impairment (serum creatinine 3 mg/dl)
Clinical profile of Severe malaria in India 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.
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.
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 Neurol2005; 4: 827–40
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.
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 indianpediatrics 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 lactatedehydrogenase (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. Falciparumis 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