Relapse and recrudescence It is the disease’s potential for long persistence.Relapse P. vivax (more important in Asia) and P. ovale( Africa). Primaquine will eradicate hypnozoites in over 80% of cases, but if not given relapse occur in more than 50% of cases.Recrudescence Applies to a recurrence of malaria from surviving blood merozoites. Due to failure of treatment to eliminate the asexual erythrocytic parasites. Recrudescence is characteristic of P. falciparum infection but lesser in other malaria. Go to slide 38
Severe MalariaDeath from acute P. vivax, P. ovale, or P. malariaeinfection is very rare, following ruptured spleentraumatic or spontaneous).Falciparum malaria is a potentially lethal infectionwith rapid progression to severe disease.Young children present with cerebral malaria in less than one dayRare in malnourished children, strike healthiestpeople.
WHO definition of severe malaria (clinical) 1. Cerebral malaria with unrousable coma persisting at least 30 minutes after generalized convulsions. 2. Severe anaemia. 3. Renal failure . 4. Pulmonary oedema or adult respiratory distress syndrome. 5. Hypoglycemia 5. Circulatory collapse or shock-hypotension ( Algid Malaria ) 6. Spontaneous bleeding from gums, nose, gastrointestinal tract etc. and/or substantial laboratory evidence of DIC. 8. Repeated generalized convulsions, more than two in 24 hours despite cooling. 9. Acidaemia. 10 .Macroscopic haemoglobinuria. One or more of the above features in the presence of asexual parasitaemia define severe falciparum malaria.
Cerebral MalariaDefined strictly as unrousable coma ( no response topainful stimuli) in falciparum malaria.The most prominent feature of severe malaria.The onset of coma may be sudden after generalizedseizure, or gradual.Extreme agitation is poor prognostic sign.Prodromal history, usually several days in adult and6 - 12 hours in children, with history of convulsions.
.On examination Severe Malaria Cont.1. Patient febrile and unrousable.2. Passive resistance to hand flexion.3. Patient usually warm, dry, well perfused peripherally.4. The clinical features are of symmetrical encephalitis. Gaze is usually normal or divergent. Go to slide 39 Untreated cerebral malaria is fatal and the overall mortality of treated malaria 15% in children, 20 % in adults and 50% in pregnancy. Other manifestation of CNS dysfunction: Delirium and brief reactive psychosis. Cerebellar syndrome: Cerebellar ataxia (Defective muscular control resulting in irregular and jerky movements)
AnaemiaNormocytic anaemia ( Hct <15% or Hb <5 g/dl)).It is a big problem in children, may lead to highoutput cardiac failure and sudden death. Acute renal FailureA common complication of malaria in adults living inareas of low or unstable transmission.Associated with haemoglobinuria in patients withmassive haemolysis ( B. W. F. )
Metabolic AcidosisMay result from renal failure in adults, but usuallythere is a primary ( type B) lactic acidosis. Blackwater feverDue inadequate quinine treatment.In the first half of the twentieth century mortality ratewas high, half of which is due renal failure.Today, the mortality is much lower.Mortality is highest when associated with severemalaria or other vital organs dysfunction.
Acute Pulmonary oedemaIt is one of the form of adult respiratory distresssyndrome.Result from sudden increase in pulmonary capillarypermeability.Hyperventilation or kussmaul’s breathing is a poorPrognostic sign in malaria. It is associated withmetabolic acidosis, pulmonary oedema or pneumonia.May develop at any time in severe falciparum malaria, itis common in pregnant women.
Algid Malaria (Hypotension)Patient with severe disease may develop suddenhypotension and become shocked. This is called‘algid malaria’Shock usually responds temporary to saline infusionand inotropes, but pulmonary oedema may develop iftoo much salt is given.Overall mortality is high.
HypoglycemiaEither asymptomatic in severely ill patient. Orpresent as a further deterioration in the level of coma.Whole blood glucose less than 2.2 mmol/l or 40 mg/dl.Occur in 8% of adults and 30% of children.In pregnant women with quinine-induced hypoglycemia: 1. The clinical features are usually evident. 2. Patient respond dramatically to glucose.
Malaria In ChildrenSevere falciparum malaria is rare in infancy, but of high mortality.Majority present with fever and malaise, respondrapidly to antimalarial treatment.In young children the progression of falciparummalaria can be rapid.General seizures are more common in P. falciparum
Severe malariaManifestations: - Coma. - Convulsion ( <3-year age group). - Lactic acidosis. - Hypoglycemia and - Severe anaemia.Rare in older children.Intense transmission areas: Profound anaemia, (1-3 years ).Less stable transmission areas : predominantly Cerebralmalaria.Children tolerate anti-malarial drugs better than adults,resolve more quickly.
A 3-year-old Gambian girl with cerebral Malaria and opisthotonosA 6-year-old Thai boywith cerebral Malaria.His father was admittedat the same day withcerebral Malaria - bothsurvive
Malaria in PregnancyA. In areas of intense Transmission The principle impact of falciparum malaria in pregnancy are : 1. An increased incidence of anaemia. 2. Reduction in birth weight of babies born to primigravidae. Despite intense sequestration of parasites in placenta the mother is usually asymptomatic.
B. In areas of less transmission If pregnant women develop severe malaria: 1. Fetal loss is common, Abortion, premature labor. 2. Maternal mortality is also high. 3. Pulmonary oedema and hypoglycemia are particular complication. The mortality of cerebral malaria in pregnancy is high. Congenital Malaria Rare, even the risk of symptomatic malaria is low (<1%). More common in non-immune mothers than highly immune ones. Babies present with anaemia, jaundice, and splenomegaly.
DIAGNOSIS There are no diagnostic clinical features of malaria except fore the regular paroxysm with virtual asymptomatic interval in endemic regions. In endemic areas , in any febrile illness, malaria should be excluded.Blood smear: Malaria is diagnosed by microscopic examination of thick (parasites) and thin (species) blood films stained by any Romanovskys stain. The red cells in the tail of the film should be examined under oil immersion. The level of parasitaemia is expressed as the number of parasitized RBCs among 1000 cells and this figure is converted to the number of parasitized RBCs per l.
Other Techniques • Quantitative Buffy Coat (QBC) Technique Blood samples are taken into a specialized capillary tube containing acridine orange stain and a float. Under high centrifugal forces (14000) the infected RBCs, which have a higher buoyant density than uninfected RBCs, become concentrated around the float. The acridine orange fluorescence from malaria parasites can be visualized under ordinary microscope.
Chronic complications of Malaria Hyperactive Malarial splenomegallyWidely known as Tropical splenomegally Syndrome.Occurs in areas of intense transmission , throughout thetropics, the highest incidence is in Papua New Guinea.Chronic or repeated infections lead to an abnormalimmune response, characterized by: 1. Gross splenomegaly, with normal architecture. 2. Lymphocytic infiltration of hepatic sinusoids with Kupffer cell hyperplasia (Hepatomegally).
In many cases no malaria parasite in peripheral blood.Treatment Splenectomy is only recommended if there is failure of prophylaxis given for at least 6 months and there is severe hypersplenism. Quartan Malarial Nephropathy Chronic or repeated infection with P. malariae may cause soluble immune-complex injury to the renal glomeruli, resulting in the nephrotic syndrome in children. Subendothelial deposits of complement and immuno- globulines , often P. malariae antigens.
TreatmentAim of treatment 1. Causal or true prophylaxis: Use of drugs that can act on tissue stages in the liver ( Tissue Schizontocidal drugs). 2. Radical cure ( Anti-relapse): Use of drugs that can act on latent forms in the liver (Hypnozoitocidal drugs). 3. Temporary cure (Clinical cure) & Suppressant treatment: That is a drug given as prophylactic, but acts through eliminating the erythrocytic forms as they invade the RBCs; no action being exerted on P. E. forms. 4. Control: Gametocidal drugs.
Antimalarial drugsAntimalarial drugs are more toxic than antibacterials, but withrare serious adverse effectsFall in three broad groups 1.The quinoline-related compounds: ( inhibit Haem polymerization): - Quinine. - Quinidine. - Chloroquine - Amodiaquine. - Mefloquine. - Halofantrine - Primaquine. 2.The antifols: ( interfere with folic acid synthesis): - Pyrimethamine. - Proguanil. - Chlorproguanil. - Trimethoprim. 3. The artemisinin compounds: ( involve oxidative damage): - Artemisinin. - Artemether. - Artesunate.
Several antibacterial drugs have antiplasmodialactivity, although slow , can be used in combination withother antimalarial drugs: - Sulfonamides - sulphones . - The tetracyclines. - The macrolides.Tetracycline, in multi-drug-resistant parasites.Antimalarial treatment must usually providetherapeutic drug concentration for 7 days to effect a cure in non immune subjects.In semi-immune subjects the host defense collaboratewith the antimalarial treatment to eradicate residual parasites, and a short course of treatment is effective.
P. VivaxAdult treatment.Based on Chloroquine tablets containing 150mg base. Day 1 4 tablets (600mg base) or 10 mg/kg first dose. 2 tablets (300mg base) or 5 mg/kg 6-8 hours later. Day 2 2 tablets (300mg base) or 5 mg/kg. Day 3 2 tablets (300mg base) or 5 mg/kg. Next 14 days primaquine 2 tablets (each tablet contains 7.5mg base daily with food ).
P .falciparum.Uncomplicated malaria (where patients can take oral therapy) can usually be treated effectively with one of three regimens:1. Quinine sulphate 10 mg salt/kg 8 hourly for seven days plus doxycycline 100 mg daily for 7 days. Tetracycline (4mg/kg daily for seven days) or the combination drug FansidarTM (25mg/kg sulfadoxine plus 1.25mg/kg pyrimethamine as a single dose) can be given as less expensive alternatives to doxycycline.2. MalaroneTM (atovaquone 250 mg plus proguanil 100 mg) 4 tablets daily for three consecutive days. This combination therapy is relatively new and appears to be very effective but it is also very expensive.3. Mefloquine (LariumTM) given as 15 mg/kg in a divided dose followed by 10 mg/kg the following day. Antipyretic and antiemetic agents may need to be given prior to mefloquine administration to reduce the risk of vomiting..
Severe malariaIn patients who have not received quinine in the previous 48 hours, one of two regimens can be used:1. Quinine dihydrochloride 20 mg salt/kg base given i.v. in 5% w/v dextrose or normal saline as a once-only 4 hour infusion followed, 4 hours later, by quinine dihydrochloride 10 mg salt/kg base 4-hour infusions, 8 hourly.2. Where a syringe pump or other accurate infusion device is available, quinine dihydrochloride 7 mg salt/kg base over 30 minutes followed immediately by quinine dihydrochloride 10 mg salt/kg base over 4 hours then, starting 4 hours later, quinine dihydrochloride 10 mg salt/kg base as 4 hour infusions, 8 hourly.