Transcript Malaria - University of Massachusetts Medical School
Malaria
Richard Moriarty, MD University of Massachusetts Medical School
Objectives
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Scope of the problem The parasite The symptoms The treatment Preventive measures Questions
Malaria - worldwide
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1.5 billion live in endemic areas over 500 million infected 1-2 million deaths per year Most deaths in children < age 5 years old Caused by protozoan from Plasmodium genus Transmitted by female Anopheles mosquito
Areas of Malaria Transmission and Antimalarial Drug Resistance
Malaria in Liberia
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Leading cause of morbidity and mortality Year-long stable transmission 40% of outpatient visits 18% of inpatient deaths 21,000 deaths in <5 years of age Only 18% households have bednets Only 4% of kids get first choice med From President’s Malaria Initiative Liberia’s Malaria Operational Plan FY 2008
Life cycle of Plasmodium
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Asexual phase http://www.who.int/tdr/diseases/malaria/lifecycle.htm
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Blood Liver RBC Sexual phase
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Blood Gut of female mosquito Saliva gland http://www.wellcome.ac.uk/stellent/groups/corporatesite/@msh_publis hing_group/documents/web_document/wtd039685.swf
sporozoites
Life Cycle of Plasmodium falciparum Rosenthal P. N Engl J Med 2008;358:1829-1836
The Numbers
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70 kg person has @ 5 liters of blood = 5 x 10 3 ml = 5 x 10 6 μL times 5 x 10 6 RBCs per μL of blood = 2.5 x 10 13 RBCs 1% parasitemia= 1 in 100 iRBCs= 2.5 x 10 11 = 250 billion parasites parasites P. vivax invades predominately reticulocytes and so has a built-in ceiling, but P. falciparum can invade all ages of RBCs.
Pyrogenic density P. falciparum 10,000/uL nonimmune; 100,000/uL immune; P. vivax100/uL
David Sullivan, MD; Johns Hopkins School of Public Health
Malaria species
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Plasmodium vivax Plasmodium ovale
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Plasmodium malariae
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Plasmodium falciparum
• www.rph.wa.gov.au/malaria/diagnosis.html
Plasmodium vivax
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~43% of cases WW
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Paroxysms on a 48 hr cycle
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Relapses up to 8 years
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merozoites infect only young RBC’s
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RBC’s usually enlarged
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Schuffner’s dots
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common in temperate zones
Plasmodium malariae
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not found in contiguous distribution ~7% WW 72 hour cycle second exoerythrocytic stage not observed reactivation can occur up to 53 years post infection!
merozoites infect only old RBC’s low parasitemia
Plasmodium ovale
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rare in humans
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found in tropical S. Africa and Western Pacific
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<1% WW.
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mildest and rarest form of malaria
Plasmodium falciparum
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most pathogenic and virulent form
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common in tropics, formerly in temperate zones
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~50% WW greatest killer of humans in the tropics only one exoerythrocytic stage, no relapse merozoites invade RBC’s of all ages parasitemia very high Marginal forms; double chromatin dots
Why is P. falciparum so dangerous?
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Ability to infect all age of RBCs Higher multiplication capacity Sequestration (cytoadherance and rosetting)
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Capillary leak syndromes End organ failure
Malaria Symptoms
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Early generalized symptoms
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Malaise, myagias, headache, low grade fever Fever is not always present Repeatedly infected adults may have few symptoms Paroxysms
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Chills, nausea, emesis, intense HA, fever Severe malaria
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Prostration, shock, metabolic acidosis hypoglycemia Severe anemia, jaundice Organ failure (pulmonary edema, hemoglobinuria,etc) Cerebral malaria
Physical Findings
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Fever Tachycardia Hypotension Jaundice Pallor Splenomegaly Later, hemoglobinuria, pulmonary edema, bleeding, acute renal failure
Cerebral malaria
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Agitation Seizures Coma Cytoadherence CFR 20% Significant neurological residua
Features, Outcome of CNS Malaria in Kenyan Children
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33% of ped admissions malaria 1 st dx 47% of those had neurologic sx
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37% seizures – multiple or prolonged 20% prostration 13% impaired consciousness or coma Neuro involvement associated with met acidosis, hypoglycemia, hyperkalemia 2.8% mortality (75% of those had CNS) JAMA 2007;297:2232-2240
Malaria Diagnosis
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Clinical diagnosis is inaccurate Blood smear
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Giemsa
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Field’s Rapid tests
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HRP-2: may stay + for >7 days
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pLDH: clears quickly PCR detection of antigen in urine & saliva http://www.wpro.who.int/sites/rdt
Malaria in Pregnancy
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Increased risk of spontaneous abortion, stillbirth, pre-term birth and low birth weight Low birth weight is the single greatest risk factor associated with perinatal mortality; up to 200,000 newborn deaths/year occur in Africa due to malaria Malaria parasites can cross the placenta and cause malaria & anemia in the newborn HIV-malaria-infected women more likely for anemia, preterm birth, IUGR, infant deaths
Increased risk of HIV transmission
Differential diagnosis
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Dengue Typhoid Sepsis/bacteremia Acute schistosomiasis Yellow fever Leptospirosis African tick fever
Treatment
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Quinine
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IV, oral, rectal Quinidine
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Cinchonism: rashes, deafness, blurred vision, confusion Chloroquine – resistance common Sulfadoxine-pyrimethamine – resistance common
Treatment
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For children < age 5 years in a setting of stable high transmission, consider treating all febrile episodes if no other cause of fever Liberia’s National Malaria control Program does not support this; NMCP supports confirmatory diagnosis with RDT to encourage HCW’s to see other diagnoses when RDT’s negative
Treatment - Artemesinins
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Rapid blood schizonticide Used with other med to prevent recrudescence Recommended for P. falciparum only Dose varies with preparation Possible neurotoxicity Increasing evidence of safety during pregnancy
Artemisinin Preparations
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Artesunate Artemether Artemotil Dihydroartemisinin Rapidly eliminated Reduces parasite load by 10 8 Paired with slowly eliminated drug Allows effective treatment in 3 days Very well tolerated; few side effects Rx failure within 14 days is rare
Malaria Treatment
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Access to affordable appropriate drugs
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Chloroquine $0.20 but widespread resistance
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Fansidar widespread resistance
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Artemether-lumefantrine (Coartem) $0.90 – 2.40 (private $15)
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Artesunate-amodiaquine (ASAQ) $0.50 but limited availability
Artemisinin Combination Therapy
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Artemether / lumifantrine: Coartem Artesunate / amodiaquine: ASAQ
WHO Malaria Treatment Guidelines 2006
Treatment - supportive
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Transfusion may be lifesaving to reverse tissue hypoxia and metabolic acidosis
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Intermittent preventive treatment during pregnancy
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IPTi
Preventive Measures
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Insecticide-treated bednets Topical insecticides Indoor residual spraying Intermittent Preventive Treatment during pregnancy: sulfadoxine pyrimethamine
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Counterfeit drugs ? Vaccine
Malaria
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Low tech solutions: prevention
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Insecticide-treated bed nets
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In-house spraying Drainage Higher tech solutions
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Intermittent preventive treatment in pregnancy
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Intermittent preventive treatment in infancy Prompt evaluation of febrile illnesses Rectal quinine for acute management High tech solutions
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Drugs and vaccine
Liberia’s Goals for Malaria
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Rapid scale-up of
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ACT’s
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IPTp
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ITN’s
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IRS Expand microscopic diagnosis Use rapid tests until good microscopy $12.5 million budget
Treatment Miscellany
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Antipyretics?
What to do if an infant vomits a dose?
Transfuse at what level?
Steroids?
Anticonvulsants?
Concomitant antibiotics?
References
• WHO; Guidelines for the Treatment of Malaria; 2006 • WHO; malaria life cycle • CID; 2007;45:1446; intrarectal quinine • PRESIDENT’S MALARIA INITIATIVE; Malaria Operational Plan (MOP) LIBERIA FY 2008