Malaria - Update : Malaria - Update Dr.Girish Vaswani (D.N.B. med)
Kothari Hospital Plasmodium species which infect humans : Plasmodium species which infect humans Plasmodium vivax ( B. tertian)
Plasmodium ovale ( B. tertian)
Plasmodium falciparum ( M.tertian)
Plasmodium malariae (quartian) Slide 3: Exo-
(hepatic) cycle Malaria Life Cycle
Life Cycle Schizogony Sporogony Malaria Transmission Cycle : Malaria Transmission Cycle Parasite undergoes sexual reproduction in the mosquito Some merozoites differentiate into male or female gametocyctes Erythrocytic Cycle: Merozoites infect red blood cells to form schizonts Dormant liver stages (hypnozoites) of P. vivax and P. ovale Exo-erythrocytic (hepatic) Cycle: Sporozoites infect liver cells and develop into schizonts, which release merozoites into the blood MOSQUITO HUMAN Sporozoires injected into human host during blood meal Parasites mature in mosquito midgut and migrate to salivary glands Components of the Malaria Life Cycle : Components of the Malaria Life Cycle Mosquito Vector Human Host Sporogonic cycle Infective Period Mosquito bites
person Mosquito bites
person Prepatent Period Incubation Period Clinical Illness Parasites visible Recovery Symptom onset Clinical presentation : Clinical presentation Early symptoms
Slight fever, usually not intermittent
Could mistake for influenza or gastrointestinal infection Clinical presentation : Clinical presentation Acute febrile illness, may have periodic febrile paroxysms every 48 – 72 hours with
Afebrile asymptomatic intervals
Tendency to recrudesce or relapse over months to years
Anemia, thrombocytopenia, jaundice, hepatosplenomegaly, respiratory distress syndrome, renal dysfunction, hypoglycemia, mental status changes, tropical splenomegaly syndrome Malarial Paroxysm : Malarial Paroxysm Can get prodrome 2-3 days before
Malaise, fever,fatigue, muscle pains, nausea, anorexia
Can mistake for influenza or gastrointestinal infection
Slight fever may worsen just prior to paroxysm
Cold stage - rigors
Hot stage – Max temp can reach 40-41o C, splenomegaly easily palpable
Lasts 8-12 hours, start between midnight and midday Malarial Paroxysm : Malarial Paroxysm Periodicity
Days 1 and 3 for P.v., P.o., (and P.f.) - tertian
Usually persistent fever or daily paroxyms for P.f.
Days 1 and 4 for P.m. - quartian Differential diagnosis : Differential diagnosis At the onset of the disease it may be very difficult to differentiate malaria from viral fevers.
Jaundice and fever is also seen in viral hepatitis and other forms of hepatitis, cholecystitis and hepatic abscess.
Dengue, Leptospirosis and hemolytic anemia have the common triad of pallor, icterus and splenomegaly. P. Falciparum-cerebral malaria:A symmetric encephalopathy : P. Falciparum-cerebral malaria:A symmetric encephalopathy Whenever you see a patient who complains of headache, vomiting, diplopia, and is disoriented, confused or behaving abnormally then always think MALARIA. The relatives may say that he is always sleepy and had a few convulsions.
On examination, varying levels of consciousness may be noted with divergent or convergent eyes, release of primitive reflexes, hyper/hyporeflexia, hyper/hypotonia, extensor/flexor plantars and absent abdominals-cremasterics.
Signs of meningeal irritation may also be elicited. Cerebral Malaria-D/D : Cerebral Malaria-D/D Always rule out other causes of altered sensorium like encephalitis, menigitis and cerebral bleeds and infarcts.
Check for metabolic parameters and renal and hepatic failure as other diagnosis or as contributing to reduced alertness or convulsions As the disease progresses : As the disease progresses The patient becomes more drowsy and breathless suggesting ALI and ARDS.The O2 concentration starts to drop and respiratory alkalosis sets in. Eventually he may be started on mechanical ventillation.
The kidneys start to fail and urine output lessens signifying acute renal failure.
Shock,hypoglycemia, lactic acidosis and DIC complete the picture of MOSF. Chronic malaria - tropical splenomegaly : Chronic malaria - tropical splenomegaly Anorexia, nausea, vomiting, weight loss
Symptoms due to anemia – pancytopenia
Splenic rupture Tropical splenomegaly : Tropical splenomegaly Patient from endemic area
Many attacks of malaria in childhood
Moderate to massive hepatosplenomegaly
Smear negative for parasites
Malarial antibodies positive
Parasites in bone marrow
Hypersplenism Tropical splenomegaly – diff diagnosis : Tropical splenomegaly – diff diagnosis Kala-azar
Portal hypertension – hepatic, extrahepatic
CLL Chronic complications of malaria : Chronic complications of malaria Tropical splenomegaly with or without hypersplenism is very common.
Immunological complications like nephrotic syndrome and a predisposition to Burkitt’s lymphoma have also been reported. Diagnosis - malaria : Diagnosis - malaria A high index of suspicion is required and a history of visit to a malarious tract should always be sought by direct questioning of the patient or accompanying persons.A history of recent blood transfusion may point to an iatrogenic mode of spread of malaria.
Thick and Thin smears should always be examined and indirect evidence of malaria by demonstrating hemolytic jaundice should be performed. Other tests : Other tests Generally the complete blood counts and platelets counts are of little benefit in the diagnosis but aid in assessing the severity and complications of the ongoing infection.
PfHRP2 dipstick or card test: monoclonal ab captures the parasite antigens. Only for falciparum malaria.
LDH dipstick or card test Drugs used to treat Malaria-First group : Drugs used to treat Malaria-First group CHQ, Amiodaquine
Lumefantrine First group-adverse reactions : First group-adverse reactions GI disturbances-nausea, vomiting, diarrhoea and
erosive or hemorrhagic gastritis with abdominal pain and hematemisis at times.
Cardiovascular instability- Prolonged QTc ventricular tachyarrythmia and hypotension
CNS-disorientation, abn behaviour, seizure
ALWAYS CHECK – K, MG, SUGAR before starting Drugs used to treat malaria : Drugs used to treat malaria Doxy, Tetra – pregnancy, children, hepatic
Sulfadoxine-Pyrimethamine – sulfa allergy, renal failure
Artemisin derivatives - safe Drugs used to treat Malaria-others : Drugs used to treat Malaria-others Clindamycin
Primaquine How to select antimalarials : How to select antimalarials Type of malaria – vivax or falciparum?
Sensitive or resistant
Associated renal or liver damage
Associated metabolic-electrolyte imbalances
Oral therapy possible? Intravenous anti-malarial therapy- Indications : Intravenous anti-malarial therapy- Indications Presence of vomiting
Inability to start oral therapy may also be due to altered mental alertness and seizures.
Patients who are intubated and on ventillators.
Those who are critically ill. Intra-venous therapy : Intra-venous therapy Chloroquine: intravenous 10 mg/kg max 600mg over 6-8 hrs followed by 15mg/kg max 900mg over next 24 hrs as slow infusion.
Quinine : intravenous 20mg/kg over 4 hrs; then 10mg/kg(max 600mg)three times a day. Intra-venous therapy-severe f.malaria : Intra-venous therapy-severe f.malaria Artesunate 2.4mg/kg stat; followed by 2.4mg/kg at 12 hrs, 24hrs and then daily. OR
Artemether 3.2mg/kg stat im; then 1.6mg/kg od im.
Add quinine 20mg salt/kg over 4 hrs; followed by 10mg/kg over 2-8 hrs slow infusion thrice a day.
Doxy 100mg bd / tetra 250mg (4mg/kg) qds Oral therapy-CHQ sensitive malaria : Oral therapy-CHQ sensitive malaria Chloroquine 10mgbase/kg stat followed by 5mg/kg at 12, 24 and 36 hrs.
Chloroquine 10mg/kg stat; then 10mg/kg at 24hrs and 5mg/kg at 48 hrs.
Amodiaquine 10mg base/kg od x 3 days Oral therapy-sensitive f.malaria : Oral therapy-sensitive f.malaria Sulfadoxine-pyrimethamine 25mg/kg (max 1500mg of sulfadoxine) single dose
Artesunate 4mg/kg od x 3 days
Amodiaquine/CHQ plus artesunate Multidrug resistant malaria : Multidrug resistant malaria Mefloquine 8mg base/kg orally od for 3 days, or 15mg/kg and then 10mg/kg next day
Artemether-lumefantrine (1.5/9mg/kg bid) or artesunate 4mg/kg od for 3 days Multidrug resistant malaria- 2nd line : Multidrug resistant malaria- 2nd line Doxy 100mg bd (3mg/kg x 7 days)
Artesunate 2mg/kg od or quinine 10mg/kg tds
1 drug of the following:
Tetra 250mg qds (4mg/kg qid x 7 days)
Clindamycin 10mg/kg bd x 7 days or atovoquone-proguanil 20/8 mg/kg od x 3 days Other supportive therapy : Other supportive therapy Maintain acid-base balance
Maintain blood sugar
Add folvite for hemolysis
Exchange transfusion DISEASES SPREAD BY MOSQUITOS : DISEASES SPREAD BY MOSQUITOS MALARIA
VIRAL HEMORRHAGIC FEVERS Malaria : Malaria Malaria (cont’d) : Malaria (cont’d) Avoid mosquitoes by taking protective measures.
Use protective clothing: long sleeved shirts/pants.
Use DEET repellant.
Use bed netting if rural or if locked windows not available.
Prophylactic medications when indicated are widely used based on CDC recommendations for intended destinations. chemoprophylaxis : chemoprophylaxis Chloroquine 5mg base/kg (max 300 mg) once a week. Begin 1-2 weeks before travel, during stay and continue till 4 weeks after returning from malarious area.
Mefloquine 5mg salt/kg (max 250 mg) once a week. Regime same as above.
Atovoquone/proguanil (250/100mg) 1 tab for travel to resistant malarious area beginning 1-2 days before travel and taken daily during stay and ctd till 1 week after return from malarious area. Travel in Chloroquine Resistant areas : Travel in Chloroquine Resistant areas Atovaquone/proguanil (Malarone)
250 mg atovaquone and 100 mg proguanil hydrochloride.
Begin 1-2 days before travel and continue daily for 7 days after leaving the area..
Daily, at the same time each day .
Contraindicated in persons with severe renal impairment
Contraindicated in children <5 kg, pregnant women, and women breastfeeding.
Side effects- abdominal pain, nausea, vomiting, and headache Congenital malaria : Congenital malaria Transplacental infection
Can be all 4 species
Commonly P.v. and P.f. in endemic areas
P.m. infections in nonendemic areas due to long persistence of species
Neonate can be diagnosed with parasitemia within 7 days of birth or longer if no other risk factors for malaria (mosquito exposure, blood transfusion)
Fever, irritability, feeding problems, anemia, hepatosplenomegaly, and jaundice
Be mindful of this problem even if mother has not been in malarious area for years before delivery