Malaria & Dengue Global Health Lecture Series

Malaria & Dengue Global Health Lecture Series Julie Gutman, MD MSc Pediatric Infectious Disease 5/13/2011

What would be the most appropriate treatment for a patient presenting with malaria acquired in Haiti? n 1. Malarone n 2. Quinine + Clindamycin n 3. Chloroquine n 4. Doxycycline n 5. Mefloquine

What would be the most appropriate treatment for a patient presenting with malaria acquired in Nigeria with >5% parasitemia? n 1. Malarone n 2. Quinine + Clindamycin n 3. Chloroquine n 4. Doxycycline n 5. Mefloquine

What would be the most appropriate treatment for a patient presenting with malaria acquired in Nigeria with 2% parasitemia? n 1. Malarone n 2. Quinine + Clindamycin n 3. Chloroquine n 4. Doxycycline

Characteristic symptoms of dengue include all of the following except? 1. Fever 2. Frontal headache 3. Retro-orbital pain 4. Diarrhea 5. Maculopapular rash

A patient who contracts dengue for the first time is at high risk of DHF? n 1. True n 2. False

In a patient presenting with fever who returned from Haiti 3 weeks ago, which of the following illnesses should be considered? n 1. Dengue n 2. Malaria

Treatment with Primaquine is required for which of the following species? n 1. P. falciparum n 2. P. vivax n 3. P. malariae n 4. P. ovale n 5. P. vivax and P. ovale

Case n 7-year-old, previously healthy female, 5-day history of fever to 104 F and headache n Abdominal pain, with emesis x 5 n Denies diarrhea. Denies cough and runny nose. n The parents are from Sierra Leone, the child was born in US. n Family returned 3 days ago from a 6 week visit to Senegal. This was the child s 1 st trip abroad. n The child s symptoms started 2 days prior to return. n Her mom also complaining of fevers and emesis, the rest of family is healthy

Physical examination n Temp 38 C, HR 136, RR 22, BP 89/54, 28.1 kg n General: Awake and alert, no apparent distress. n HEENT: Scleral icterus. n Lungs: clear. n CVS: RRR. No murmurs, rubs, or gallops. n Abdomen: Soft, Liver~6 cm below costal margin. n Extremities: No edema n Skin: No rash or petechiae, no jaundice. n Neuro: Intact

Laboratory 10.75 9.9 46 CRP 7.1 28.1 ESR 46 N43, B40, L14 AST 107 ALT 112 Total bilirubin 5.5

Diagnosis?

MALARIA

Which is the most appropriate treatment for this patient who was found to have 27% parasitemia? 1. Doxycycline 2. Quinine + Doxycycline 3. Malarone 4. Quinine + Clindamycin 5. Mefloquine

Hospital Course n Started on IV quinidine + IV clindamycin n Developed hypotension; resolved with NS bolus n Tachypnea and mild hypoxia requiring 1lt O2 n CXR with pulmonary edema n Resolved w/in 24 hours n After about 24 hours of treatment, parasitemia < 1% n Switched to oral therapy n 3 days quinine and 7 days clindamycin

Malaria n Parasitic disease caused by one of 5 species of Plasmodium n P. falciparum n P. vivax n P. ovale n P. malariae n P. knowlesi n Transmitted by bite of female Anopheles mosquito

Plasmodium falciparum n Infects all stages of RBCs n Potentially fatal n Widespread drug-resistance n Chloroquine n Fansidar (SP) n Mefloquine

Plasmodium vivax n Potential for relapsing malaria n Hypnozoites remain dormant in the liver

Vectors of human malaria n > 100 species of Anopheles mosquitoes n Each species occupies a distinct ecological niche n Different species have different biting and resting behavior n Affects transmission potential n Only females bite for blood meals

Malaria Life Cycle Mosquito Oocyst Zygote Sporozoites Mosquito Salivary Gland Gametocytes Exoerythrocytic (hepatic) cycle Hypnozoites Human Erythrocytic Cycle

Current Malaria Situation n One of the most important and devastating infectious diseases in the developing world. n ~40% of the world s population is at risk n ~2.4 billion people n ~27 million U.S. residents travel each year to malarious areas n Costs Africa > US$12 million annually n Slows economic growth in Africa by 1.3% a year

Malaria Endemic Countries Hay, et al. 2009 A World Malaria Map: Plasmodium falciparum Endemicity in 2007. PLoS Med6(3): e1000048.

Global Burden of Malaria

Morbidity and Mortality n 300-500 million clinical cases annually n ~ 1 million deaths annually n 90% of deaths occur in Africa n Mostly among children under 5 years n One African child dies every 30 seconds

Chloroquine would be appropriate prophylaxis for which of the following places? 1. Brazil 2. Nigeria 3. Brazil and Thailand 4. Mexico and Haiti 5. Mexico, Haiti, and Brazil

CQ resistant Pv Antimalarial Drug Resistance chloroquine-sensitive chloroquine-resistant multiple drug-resistant

Chloroquine susceptibility n Caribbean, including Haiti n Central America west of the Panama Canal n Parts of the Middle East n Iraq n Chloroquine resistance is found in Iran, Saudi Arabia, Afghanistan, Pakistan

Clinical Presentation Uncomplicated Malaria n Symptoms n Fever, 100% n Headache, 100% n Weakness, 94% n Signs n Anemia n Thrombocytopenia n Night sweats, 91% n Arthralgias, 59% n Myalgias, 56% n Diarrhea, 13% n Abdominal cramps, 8%

Clinical Presentation Severe or Complicated Malaria n Cerebral malaria n Hyperparasitemia: parasitemia >5% n Severe anemia: Hb <5 mg/dl n Shock n Renal failure n Pulmonary edema or ARDS n DIC, thrombocytopenia n Metabolic acidosis n Hypoglycemia

Malaria infection and acquired immunity n No complete protective immunity n Repeated infection can result in resistance to severe illness n At a great cost in infant and child survival n Does not protect from primary infection/ illness n Greater risk of asymptomatic infection and gametocytemia n Pregnancy disrupts acquired immunity

How can you make a diagnosis of malaria? n 1. Blood Smear n 2. Rapid Diagnostic Tests n 3. PCR n 4. Serology n 5. All of the above

Diagnosis- Blood Smear n The gold standard n Diagnosis based on morphologic characteristics n Requires trained personnel and microscope n Thick Smear n RBCs are lysed to show the presence of parasites n Threshold of detection 5-20 parasites/ul n Thin Smear n Parasites seen within RBCs. n Better for speciation. n Threshold of detection 100 parasites/ul

Diagnosis- Rapid Diagnostic Tests n Detect presence of malaria antigen n Either Pan-malaria or Pf specific n Rapid and require little technical skill and no electricity n Take ~ 15 minutes to get a result n Less sensitive than blood smear n Threshold of detection ~ 200 parasites/ul n May remain positive for up to 3 weeks after treatment n BinaxNow- only RDT licensed in the US n P. falciparum Sensitivity 99.7%, Specificity 94.2% n P. vivax Sensitivity 93.5%, Specificity 99.8%

Diagnosis- PCR n Most sensitive test n Able to detect very low level parasitemia n Provides accurate speciation n Requires sophisticated machinery, electricity, skilled technician

Diagnosis- Serology n Detects antibodies to malaria n Remains positive after treatment for several years n Not widely used nor highly useful

Malaria Treatment: Non-falciparum n Chloroquine PLUS Primaquine n Primaquine n Eradicates liver phase (hypnozoite) in P. vivax and P. ovale infections n G6PD testing n CQ-resistant P. vivax - Oceania and S America n Mefloquine or quinine for proven resistant cases

Malaria Treatment: P. falciparum n Acquired in CQ-sensitive areas n Chloroquine alone n Acquired in CQ-resistant areas n Coartem (Artemether- Lumefantrine) n Malarone (Atovaquone- Proguanil) n Quinine + Clindamycin, doxycycline, or tetracycline n Mefloquine

Malaria Treatment: Severe Malaria n Criteria n parasite density > 5% n unable to take oral medication n evidence of complications n IV quinidine + clindamycin, doxycycline, OR tetracycline n IV artesunate (available from CDC) n Exchange transfusion n parasite density > 10% n altered mental status n renal or pulmonary complications

Chemoprophylaxis CDC Recommendations n Areas with NO chloroquine resistance n weekly chloroquine n Areas with chloroquine resistance n mefloquine weekly n doxycycline daily n Atovaquone/ proguanil daily n Long-term exposure n post exposure prophylaxis with primaquine

CDC Malaria Risk Map n http://cdc-malaria.ncsa.uiuc.edu/

DENGUE

DENGUE VIRUS n Transmitted by Aedes aegypti mosquito n domestic, day-biting n preferentially feeds on humans n ssrna positive-strand Flavivirus n 4 Serotypes (DENV 1, 2, 3, or 4) n 60-80% homology n Infection results in immunity ONLY to the infecting serotype

Importance/ Global Burden n Most important mosquito-borne viral disease affecting humans n 40% of world s population in at risk areas n 2.5 billion people n 50-100 million infections yearly n 500,000 DHF cases n 22,000 deaths, mostly among children n 2001-2005: estimated cost of US$ 440 million

Distribution

Infection in Travelers n Infection rate in febrile travelers = 2.9-8.0% n Leading cause of systemic febrile illness among travelers returning from the Caribbean, South America, South Central Asia, and Southeast Asia n Among 17,353 ill travelers in GeoSentinel network

Clinical Presentation: Break Bone Fever" n Incubation: 3-14 days n Asymptomatic infections n Self-limiting febrile illness lasting ~ 1 week n Acute onset of high fever n Frontal Headache, Retro-orbital pain n Myalgias, Arthralgias- may progress to arthritis n Nausea, vomiting n Maculopapular rash n Change in taste sensation n weakness, malaise, & anorexia may persist several weeks.

Dengue Hemorrhagic Fever (DHF) n Develops following first phase of illness n As fever subsides, patient becomes lethargic, with circulatory failure, and hemorrhage n Thrombocytopenia n Hemoconcentration n Capillary leak may result in dengue shock syndrome (DSS) n May be fatal

n Case-fatality rate ~ 5% Dengue n Can be reduced to <1% with proper treatment. n Hydration n Avoid Aspirin and NSAIDS n Dengue shock syndrome: fatality >10% n Risk factors for DHF n Prior dengue infection history of the patient n Strain of the infecting virus n Age of patient n Most fatal cases are among children and young adults.

Diagnosis n ELISA n Non-specific among the flaviviruses n West Nile, St. Louis encephalitis, Yellow Fever, Japanese encephalitis, Tick borne encephalitis, etc. n RT-PCR n Viral antigen identification in autopsy tissue samples by immunofluorescence or immunohistochemical analysis

Prevention n Insect Avoidance n DEET containing repellant n Long sleeves and pants n Light colored clothing n Permethrin treatment of clothing n Accommodations with air conditioning, window screens

What would be the most appropriate treatment for a patient presenting with malaria acquired in Haiti? n 1. Malarone n 2. Quinine + Clindamycin n 3. Chloroquine n 4. Doxycycline n 5. Mefloquine

What would be the most appropriate treatment for a patient presenting with malaria acquired in Nigeria with 8% parasitemia? n 1. Malarone n 2. Quinine + Clindamycin n 3. Chloroquine n 4. Doxycycline n 5. Mefloquine

What would be the most appropriate treatment for a patient presenting with malaria acquired in Nigeria with 2% parasitemia? n 1. Malarone n 2. Quinine + Clindamycin n 3. Chloroquine n 4. Doxycycline

Characteristic symptoms of dengue include all of the following except? 1. Fever 2. Frontal headache 3. Retro-orbital pain 4. Diarrhea 5. Maculopapular rash

A patient who contracts dengue for the first time is at high risk of DHF? n 1. True n 2. False

In a patient presenting with fever who returned from Haiti 3 weeks ago, which of the following illnesses should be considered? n 1. Dengue n 2. Malaria

Treatment with Primaquine is required for which of the following species? n 1. P. falciparum n 2. P. vivax n 3. P. malariae n 4. P. ovale n 5. P. vivax and P. ovale

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