Malaria - Update

Dr.Girish Vaswani (D.N.B. med)

Consulting Physician

Bhatia hospital

Motiben Dalvi

Kothari Hospital

Plasmodium species which infect humans

Plasmodium vivax ( B. tertian)

Plasmodium ovale ( B. tertian)

Plasmodium falciparum ( M.tertian)

Plasmodium malariae (quartian)

Exo-erythrocytic (hepatic) cycle

Sporozoites

Mosquito Salivary Gland

Malaria Life CycleLife Cycle

Gametocytes

Oocyst

Erythrocytic Cycle

Zygote

Schizogony

Sporogony

Hypnozoites(for P. vivax and P. ovale)

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

Mosquito Vector

Human Host

Sporogonic cycle

Infective Period

Mosquito bitesgametocytemic person

Mosquito bitesuninfected person

Prepatent Period

Incubation Period

Clinical Illness

Parasites visible

Recovery

Symptom onset

Clinical presentation

• Early symptoms– Headache– Malaise– Fatigue– Nausea– Muscular pains– Slight diarrhea– Slight fever, usually not intermittent

• Could mistake for influenza or gastrointestinal infection

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

• 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

• Paroxysm– Cold stage - rigors– Hot stage – Max temp can reach 40-41o C,

splenomegaly easily palpable– Sweating stage – Lasts 8-12 hours, start between midnight and midday

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

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

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

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

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

• Anorexia, nausea, vomiting, weight loss

• Symptoms due to anemia – pancytopenia

• Abdominal pain

• Abdominal lump

• Splenic rupture

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

• Kala-azar

• Portal hypertension – hepatic, extrahepatic

• Myeloproliferative diseases

• Lymphomas

• CLL

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

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

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

• CHQ, Amiodaquine

• Quinine, Quinidine

• Mefloquine, Halofantrine

• Lumefantrine

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, seizureMetabolic- hypoglycemia

ALWAYS CHECK – K, MG, SUGAR before starting

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

• Clindamycin

• Azithromycin

• Proguanil

• Dapsone

• Primaquine

How to select antimalarials

Type of malaria – vivax or falciparum?

Sensitive or resistant

Associated renal or liver damage

Associated metabolic-electrolyte imbalances

Pregnancy, weight

Drug reactions

Oral therapy possible?

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

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

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.

PLUS

Add quinine 20mg salt/kg over 4 hrs; followed by 10mg/kg over 2-8 hrs slow infusion thrice a day.

PLUS

Doxy 100mg bd / tetra 250mg (4mg/kg) qds

Oral therapy-CHQ sensitive malaria

Chloroquine 10mgbase/kg stat followed by 5mg/kg at 12, 24 and 36 hrs.

OR

Chloroquine 10mg/kg stat; then 10mg/kg at 24hrs and 5mg/kg at 48 hrs.

OR

Amodiaquine 10mg base/kg od x 3 days

Oral therapy-sensitive f.malaria

Sulfadoxine-pyrimethamine 25mg/kg (max 1500mg of sulfadoxine) single dose

PLUS

Artesunate 4mg/kg od x 3 days

OR

Amodiaquine/CHQ plus artesunate

Multidrug resistant malaria

Mefloquine 8mg base/kg orally od for 3 days, or 15mg/kg and then 10mg/kg next day

PLUS

Artemether-lumefantrine (1.5/9mg/kg bid) or artesunate 4mg/kg od for 3 days

Multidrug resistant malaria- 2nd line

Doxy 100mg bd (3mg/kg x 7 days)Artesunate 2mg/kg od or quinine 10mg/kg tds PLUS1 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

• Maintain acid-base balance

• Maintain blood sugar

• Add folvite for hemolysis

• Blood transfusions

• Exchange transfusion

DISEASES SPREAD BY MOSQUITOS

• MALARIA

• DENGUE FEVER

• YELLOW FEVER

• VIRAL ENCEPHALITIS

• VIRAL HEMORRHAGIC FEVERS

MalariaMalaria

Malaria (cont’d)Malaria (cont’d)• Avoid mosquitoes by taking protective measures.Avoid mosquitoes by taking protective measures.

• Use protective clothing: long sleeved shirts/pants.Use protective clothing: long sleeved shirts/pants.

• Use DEET repellant.Use DEET repellant.

• Use bed netting if rural or if locked windows not available.Use bed netting if rural or if locked windows not available.

• Prophylactic medications when indicated are widely used based Prophylactic medications when indicated are widely used based on CDC recommendations for intended destinations.on CDC recommendations for intended destinations.

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 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• 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