Malaria

Chapter 1 – Malaria

v History

· History of being @ malaria endemic area à ~ ↑ Px’s recall.

· Determine!: Px’s immune status, age, pregnan’, allergy, current medical conditions & medications.

· (Typic’) Sympt’ after few weeks post-infection.

· Px’s immunity & previous expos’ malaria affect symptomatology & incubat’ period.

· Each Plasmodium species has typic’ incub’ period.

· Virtual’, all Px present w/ headache.

· Clinical sympt’ also include: cough, fatigue, malaise, shaking chills, arthralgia, & myalgia.

· Paroxysm of fever¸ shaking chill, & sweats (per 48-72 hours) depending on species.

§ Classic: begin w/ period of chills & shivers (for 1-2 hours); then, high fever; finally, excess’ diaphoresis à ↓ed body temperat’ to ≤ normal.

§ Px (espec’ @ early infect’) Ø present w/ classic paroxysm, but ~ + several low fever spikes a day.

§ Periodicity of fever (due to cyclic RBC lysis as trophozoites complete their cycle in RBC per 2-3 days) related to species (Ø reliable for diagnos’):

· P falciparum (maligna), P vivax (benign), P ovale (benign) (Tertian Fever): 48 hours, oft’ Ø seen @ P falciparum infect’.

· P malaria (Quartan Fever): 72 hours, Ø apparent @ initial infect’ due to multiple broods emerg’ in bloodstream.

() Cyclic Fever pattern is rare.

· Less common malarial sympt’: anorex’ & lethargy, nausea & emesis, diarrh’, & jaundice.

· P vivax infec’ @ temperate area of India ~ cause sympt’ up to 6-12 months after Px left endemic area. P vivax & P ovale ~ relapse after longer period due to hypnozoite stage in liver.

· P malaria Ø hypnozoite stage, but ~’ve prolong’ asympt’ erythrocyt’ infec’ à sympt’ years post-leaving endemic area.

· P knowlesi can cause severe ill’ & death in humans.

§ Normally only found @ long-tailed- (Macaca fascicularis) & pigtail-macaque monkey (M nemestrina).

§ Microscopic’: similar to P malaria.

§ Suspect’ @ severely ill Px w/:

o  History of being @ forested area of SouthEast Asia & South America.

o  Microscop’ (+) P malaria.

§ Diagnos’ ~ confirm’ via Polymerase Chain Reaction (PCR) assay test method.

v Physic’ Exam’

· No spec’, ~ as flulike ill’ w/ fever, headache, malaise, fatig’, & myalgia.

· (Some) Diarrhea & other GI sympt’.

· Splenomega’ ~ (+).

· Immune Px ~ asympt’ or mild’ anemic.

· Nonimmune Px ~ very ill quick’.

· Severe malaria (main’ involv’ P falciparum). Death due to spleen rupture’s been found @ non-P falciparum.

· Severe malaria manifest’: cerebral malaria, +++ anemia, respirat’ sympt’, renal fail’.

· (@ Child) Short’ malaria course, oft’ into severe malaria quick’.

More like’ present w/ hypoglyc’, convuls’, +++ anemia, & sudden death.

Much less like’ (+) renal fail’, pulmon’ edema, or jaundice.

o          Cerebral malaria

§ Almost always by P falciparum.

§ Coma ~ (+), can usu’ be differ’ from postictal state second’ to generalized seizures if Px Ø conscious after 30 minutes à determine: is it due to hypoglyc’, Prolong’ postictal unrespons’, or CNS infection? (@ Comatose malaria Px, hypoglyc’, prolong’ postictal unrespons’, & CNS infect’ should be excluded)

o          Severe Anemia

§ Multifactorial (usu’ relat’ to P falciparum), due to:

o  (@ Nonimmune Px) ~ loss of infected RBCs

o  Inappropriat’ clear’of uninfected RBCs.

o  ~ bone marrow suppress’.

o          Renal Fail’

§ (Rare) Infected RBC adhere to renal cortex’s microvascul’ –(oft’)à oliguric renal fail’.

§ (Typic’) Reversible, usu’ support’ dialysis ~ needed till renal funct’ recovers.

§ (Rare) Chronic P malaria à nephrotic syndr’.

o          Respirat’ sympt’

§ ~ + metabolic acidosis & related respirat’ distress.

§ Pulmon’ edema can occur.

§ Signs of malaria hyperpneic syndr’: alar flaring, chest retract’ (intercost’ or subcost’), accessory muscle usage for breathing, or abnormally deep breathing.

v Differ’ Diagnos’

· Viral illness

· Bacteremia

· African trypanosomiasis

· Amebiasis and amebic liver abscess

· Brucellosis

· Cholera

· Collagen vascular disease

· Enteric fever

· Epidemic or louse-borne typhus

· Food-borne illness or toxin

· Hodgkin disease

· Relapsing fever

· Poliomyelitis

· Schistosomiasis (acute Katayama fever)

· Seizure disorder

· HIV infection

· Babesiosis

· Plague

· Q fever

· Viral hemorrhagic fevers

· Dengue Fever

· Encephalitis

· Gastroenteritis

· Giardiasis

· Heat exhaustion and heatstroke

· Hepatitis

· Hypothermia

· Leishmaniasis

· Mononucleosis

· Otitis media

· Pelvic inflammatory disease

· Pharyngitis

· Bacterial pneumonia

· Immunocompromised pneumonia

· Mycoplasma pneumonia

· Viral Pneumonia

· Salmonella infection

· Sinusitis

· Tetanus

· Toxoplasmosis

· Yellow fever

· Ehrlichiosis

· Infective Endocarditis

· Influenza

· Leptospirosis

· Meningitis

· Toxic Shock Syndrome

· Typhoid Fever

v Workup

· Px w/ history of being @ endemic area: malaria’s suggested by triad (thrombocytopenia, ↑ed Lactate Dehydrogenase (LDH), & atypic’ lymphocyt’) à prompt malarial smear.

· (General) Blood culture should be drawn from febrile Px. Px from tropical area ~ (+) > 1 infec’.

· (25% cases, oft’ more + @ young child) ↓ed Hemoglobin.

· (50-68% cases) Thrombocytopenia.

· (50% cases) abnorm’ liver funct’.

· Monitor renal function, electrolyte (espec’ Na⁺), and hemolysis-suggesting parameter (haptoglobin, LDH, reticulocyte count).

· Rapid HIV test if indicated.

· (<5% cases) ↑ed WBC à if (+) leukositosis à broader differ’ diagnos’.

· Assess Px’s G6PD level before usage, if medicat’ w/ primaquine (primaquine can (+) +++ hemolytic in Px w/ low G6PD)!

· If Px (+) cerebral malaria: exclude hypoglyc’-induced mental-altera’ by measuring blood glucose 1stly! IV quinine à hypoglyc’à Monitor blood glucose if (+) quinine usage.

· Imagings:

§ If (+) respirat’ sympt’ à chest radiography ~ helpful.

§ If (+) CNS sympt’, head CT scan ~ (+) for excludi’ cerebral- edema or hemorrhage.

· Microhematocrit centrifugation:

§ This w/ CBC tube’s more sensitive for malaria detecti’.

§ Can’t identify Plasmodium sp.

· Fluorescent dyes/ UV indicator tests:

§ Several dyes w/ fluoresc’ microscop’ make quicker lab’ results . ~ Ø yield speciation info’.

· PCR assay

§ Specific & sensitive Plasmodium sp indentific’ @ parasitemia ≥ 10 parasites/ml blood.

· Lumbar puncture

§ To rule out bacterial meningitis if Px + mental status change, & even if (+) P falciparum @ peripher’ bloodsmear.

· Blood smear

§  To support malaria diagnos’ by indentific’ of Plasmodium sp @ bloodsmear.

§  (Rare) present w/o detectable parasitem’.

§  If no (+) alternative diagnoses @ malaria-risky Px w/ possible cerebr’ malaria (ie: unrevealing lumbar punct’ findings) à start presumptive malaria therapy & continue to take extra bloodsmear to confirm diagnosis.

§  @ reading smear: 200-300 oil immers’ (more if Px’s used prophylac’ medicat’ (~ ↓ parasitemia) recent’) fields should be exam’.

§  1 negative smear Ø exclude malaria à several more smear should be exam’ over 36-hour period.

§  Thick smear

§  3 Thick & 3 thin smears should be taken 12-24 hours apart. Highest yield of peripher’ parasit’ is @ or soon after fever spike, but smear should Ø delayed to wait for fever spike.

§  20x more sensitive > thin smear. Difficulty @ speciati’ > thin smear. Quantitative.

§  Parasitemia can be calculated based on number of infected RBCs.

§  Thin smear

§  Qualitative.

· Alternative to Blood Smear tests

§  Rapid Diagnostic Test (RDT)

§  Immunochromatograph’ (Antibody to histidine-rich protein-2 (PfHRP2), parasite LDH (pLDH), Plasmodium aldolase) w/ high specific’ & sensitiv’.

§  Some ~ indentify P falciparum @ parasitem’ < reliable microscop’ speciat’ threshold.

§  (13 Mar 2014) Only BinaxNOW RDT’s approved in U.States for malaria diagnosis.

§  91,7% sensitive, 96,7% specif’ > microscop’s (52,5% sensitive, 77% specif’).

Similar to nested PCR, w/ ↓ed time to result.

§  Antimalarial could be withheld safely from febrile child < 5 y.old if (negative) PfHRP2 RDT.

§  Less effective @ parasitemia < 100 parasite/ml blood. (Rare) (-) result @ high parasitemia. If possib’, should + 2nd type screening.

§  False positive ~ lasts ≥ 2 weeks after treatment, due to circulating antigen persistence.

§  Other tests

§  PCR assay test & Nucleic Acid Sequence-based Amplification (NASBA) (expensi’, unavailab’ @ most develop’ countr’), more sensitive > thick smear.

§  Quantitative Buffy Coat’s (QBC) as sensitive as thick smear, can’t speciate Plasmodium.

· Histolo’ Find’

Findings	P falciparum	P vivax	P ovale	P malariae
Only early forms present in peripheral blood	Yes	No	No	No
Multiply-infected RBCs	Often	Occasionally	Rare	Rare
Age of infected RBCs	RBCs of all ages	Young RBCs	Young RBCs	Old RBCs
Schüffner dots	No	Yes	Yes	No
Other features	Cells w/ thin cytoplasm, 1 or 2 chromatin dots, & applique forms.	Late trophozoites w/ pleomorphic cytoplasm.	Infected RBCs become oval, w/ tufted edges.	(+) Bandlike trophozoites

Reference:
1. http://emedicine.medscape.com/article/221134-clinical
2. http://emedicine.medscape.com/article/221134-differential
3. http://emedicine.medscape.com/article/221134-workup