Management of Complicated MalariaFORMATINTRODUCTIONAETIOLOGY/EPIDEMIOLOGYDIFFERENTIAL DIAGNOSESPATHOPHYSIOLOGYMANAGEMENTCONCLUSIONBIBLIOGRAPHY
Management of ComplicatedMalaria INTRODUCTION Complicated malaria Increasing Rates of malaria infection- refers to any clinical presentation requiring WHY? parenteral treatment. POOR CONTROL- drug-resistant strains of parasites (e.g. chloroquine Severe malaria refers to those patients whose resistance) presentation meets the strict Increasing international WHO case definition of severe disease as indicated travel/Immunity in Table 1 Delays in diagnosis or treatment.
Management of ComplicatedMalariaAETIOLOGY/EPIDEMIOLOGY Of the four species of malarial parasites that commonly cause infection in man, P. Of all cases of falciparum malaria, around falciparum is responsible for virtually all the 10% can be classified as severe, severe cases and deaths. among which the mortality is 10% (i.e. 1% of all cases) but may rise to as The other species, P. vivax, P. ovale and P. high as 50% (of case definition severe malariae, cause mainly a febrile illness and cases). Any form of complicated or only rarely lead to severe disease. severe malaria must therefore be regarded as a life-threatening medical Falciparum malaria remains a major cause emergency. of morbidity and mortality worldwide. The annual clinical caseload may well be over 500 million, leading to between 1 and 3 million deaths, mainly among young children . More than 90% of these deaths occur in sub-Saharan Africa.
Management of ComplicatedMalariaPATHOPHYSIOLOGY Altered consciousness or coma. It is believed that coma or alteration of the level of consciousness is caused by sequestration of infected RBCs in the brain. • Hypoglycaemia This is as a result of impaired production or release of glucose in the liver and increased utilization in the tissues. Hypoglycaemia may also result from reduced intake or use of drugs such as quinine.
Management of ComplicatedMalaria Convulsions - sequestration of infected RBCs in the brain - severe accompanying metabolic disorders e.g. Hyponatraemia. • Raised intracranial pressure The cause of this is not exactly known but has been noted present from time to time during the illness and may be due to increased mass of red blood cells sequestered in the brain, or because of dilatation of vessels in the brain in response to locally generated cytokines. Raised intracranial pressure is not the primary cause of coma or death in a majority of cases. • Anaemia This is partly due to the destruction of red cells that contain parasites. Several other mechanisms may accelerate the development of anaemia. These include destruction of non-parasitised red blood cells, bone marrow suppression, intravascular haemolysis, abnormal bleeding and renal failure
Management of ComplicatedMalaria Acidosis Probably due to a relative shortage of oxygen in tissues occupied by sequestered parasites. This shortage of oxygen is made worse by hypovolaemia and/or severe anaemia as both of these conditions may impair the supply of oxygen to tissues. This lack of oxygen in tissues forces the tissues to get their energy by other biochemical pathways not dependent on oxygen. The result of this is the release of lactic acid, leading to metabolic acidosis. There is evidence that drugs containing salicylates e.g. Aspirin often given to lower fever may exacerbate this metabolic acidosis. • Acute renal failure Acute tubular necrosis is a common complication in adults, but it is rarely seen in children. It is fully reversible if the patient is kept alive e.g. by peritoneal dialysis, for a period ranging from a few days to 3 weeks. Renal
Management of ComplicatedMalaria • Pulmonary oedema and Adult respiratory distress syndrome (ARDS) -Pulmonary oedema (non-cardiogenic) may result from excessive fluid replacement by intravenous (iv) fluids especially if there is renal failure. - Adult respiratory distress syndrome (ARDS) appears to be due to a direct effect of parasites sequestered in the lungs, possibly through release of cytokines. Both of these complications are usually found in children in endemic areas. • Haemoglobinuria - rapid breakdown of red blood cells in the circulation (massive intravascular haemolysis).
Jaundice Jaundice is more common in adults than children and is due to haemolysis and partly to liver dysfunction. • Shock -Inadequate cardiac output and poor tissue perfusion. In some patients it may occur concurrently with bacteraemia. • Platelets In P. falciparum malaria, the platelet count is typically low. Nevertheless, spontaneous bleeding is rare in both children and adults. When it develops it results from disseminated intravascular coagulopathy (DIC).
Management of ComplicatedMalariaINVESTIGATIONS Blood - THICK/THIN films/Rapid Antigen Test - P. falciparum malaria with possibly hyperparasitaemia. Thin films, which are a monolayer of red cells dried and fixed with methanol, can provide valuable clinical information: a- The intensity of infection or parasitaemia (usually measured as the percentage of red cells infected). Parasitaemia does not always correlate with disease severity, higher parasitaemias = special consideration for parenteral Rx. + = 1–10 per 100 thick fields. ++ = 11-100 per 100 thick fields. +++ = 1–10 per thick field. ++++ = >10 per thick field.
Management of ComplicatedMalaria b- Parasite maturity The presence of more mature ring forms, trophozoites containing pigment or schizonts in the peripheral blood film is associated with a worse prognosis than in those patients with only small immature ring forms . c- Neutrophils containing malarial pigment (hemozoin) The presence of malarial pigment in peripheral blood polymorphs reflects prolonged infection and a large sequestered parasite burden. The finding of ≥5% of polymorphs containing hemozoin is associated with a poorer prognosis . d- Monitoring the effect of treatment Peripheral blood films should be carefully examined at least once daily in complicated and severe malaria. An initial increase in parasitaemia is not uncommon during the first 18–24 h of treatment and paradoxically, may be of favourable prognostic significance.
Management of ComplicatedMalaria Blood - Hypoglycaemia - RBS Acidosis i.e metabolic acidosis- Blood gases Hyperlacticaemia Severe normocytic anaemia packed cell volume < 15%, Hb < 5 gldl). - FBC Renal impairment, as indicated by abnormal creatinine and urea levels. – BUE & Cr Urine - Haemoglobinuria (BLACK WATER FEVER – ?quinine,artemisinin, ? Haemoglobinopathies-G6PD LP- CSF to exclude meningitis/ meningoencephalitis
Management of ComplicatedMalaria TREATMENTSUPPORTIVE THERAPY HYDRATION MONITORING GLYCAEMIC CONTROL PARENTERAL MEDICATION- Cinchona alkaloids (eg. quinine) +/- clindamycin/doxycycline/tetracycline (recrudecense prevention) Artemisinin derivatives *** EXCHANGE Transfusion CARE OF THE UNCONSCIOUS
Management of ComplicatedMalaria HYDRATION MONITORING: Input-output chart Electrolytes : Na, K, Ca, Mg, Phosphate
Management of ComplicatedMalaria GLYCAEMIC CONTROL: FBS/RBS monitoring – regularly esp. in the unconscious. Quinine IV Dextrose infusionNB: Irreversible neuroglycopenia
Management of ComplicatedMalaria Cinchona Alkaloids : Quinine/quinidine Ideally ICU/HDU supervision Narrow therapeutic index : Cardiac arrhythmias Hypotension Hypoglycaemia Prolongation of QTc Interval on ECGLoading dose: 20mg/kg over 4 hrsMaintenance dose: 10 mg/kg over 4 hrs 8 hrly till parasitaemia< 1%
Management of ComplicatedMalaria ARTEMISININ DERIVATIVES: Artesunate (water soluble - iv) Arthemeter (fat soluble – im)- more rapid parasite clearance (active on the immature parasite forms)- safer and simpler to administer.- reduce mortality in adults by over a third (35%) in complicated and severe malaria when compared to intravenous quinine (15% as opposed to 22%) (P = 0.0002).- fewer episodes of hypoglycaemia than quinine.- Reassuringly, the effects of artesunate were greatest in patients with hyperparasitaemia.- Artesunate has a limited shelf life.- The dose is 2.4 mg kg−1 IV, followed by the same dose at 12 and 24 h, then once daily until the patient is able to take artesunate (2 mg kg−1 per day) per os
Management of ComplicatedMalaria CARE OF THE UNCONSCIOUS: Frequent turning in bed NG feeding Eye and oral care Toileting needs Seizure chart
Management of ComplicatedMalaria CONCLUSION: Falciparum malaria is potentially life-threatening. Blood film microscopy is the gold-standard for diagnosis of malaria. Parenteral treatment is required in severe / complicated malaria. Artemisinin derivatives are safer and more effective than the cinchona alkaloids. Prompt and adequate treatment are essential to survival.
Management of Complicated Malaria -References New Perspectives - Malaria Diagnosis : REPORT OF A JOINT WHO/USAID INFORMAL CONSULTATION 25–27 OCTOBER 1999 p 11 At http://www.wpro.who.int/NR/rdonlyres/3DC6B7D7-711F-4F63-8FF9-A70DBA99DB7E/0/NewPersectives.pdf Castelli F, Carosi G. Diagnosis of malaria infection In Castelli F, Carosi G ed Handbook of malaria infection in the tropics. Organissazione per la cooperazione sanitaria internazionale 1997 pp 114 http://www.med-chem.com/procedures/DetofPara.pdf http://www.btinternet.com/~ukneqas.parasitologyscheme/Blood_Scheme/ Warhurst DC, William J Laboratory diagnosis of malaria ACP Broadsheet No 148 J Clin Path 1996;49:533-8 Jacek Skarbinski et al. Effect of Malaria Rapid Diagnostic Tests on the Management of Uncomplicated Malaria with Artemether- Lumefantrine in Kenya: A Cluster Randomized Trial Am. J. Trop. Med. Hyg., 80(6), 2009, pp. 919-926 Available at http://www.ajtmh.org/cgi/content/abstract/80/6/919?etoc Snow RW, Guerra CA, Noor AM et al. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature 2005;434:214–17. CrossRefMedline ↵ Bell D, Winstanley P. Current issues in the treatment of uncomplicated malaria in Africa. Br Med Bull 2004;71:29–43. Abstract/FREE Full Text ↵ WHO. Severe falciparum malaria. World Health Organization, Communicable Diseases Cluster. Trans R Soc Trop Med Hyg 2000;94(Suppl. 1):S1–90. MedlineWeb of Science ter Kuile F, White NJ, Holloway P et al. Plasmodium falciparum: in vitro studies of the pharmacodynamic properties of drugs used for the treatment of severe malaria. Exp Parasitol 1993;76:85–95. Dondorp A, Nosten F, Stepniewska K et al. Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet