Malaria Prevention : Malaria Prevention Mary F. Vaeth, MD, MS
Deployment Health Clinical Center
Malaria Prevention Objectives : Malaria Prevention Objectives Describe geographic distribution and risk factors for malaria
Review classification and life cycle of malaria parasite
Describe personal protective measures for malaria prevention
Discuss malaria chemoprophylaxis
Epidemiology of Malaria : Epidemiology of Malaria Global malaria
Incidence increased over 40 years
300-500 million infected annually (90% in Sub-Saharan Africa
Over 1 million deaths annually (mostly infants and children
Reasons malaria problem has worsened
Development of resistance by parasite and mosquito vector
Socioeconomic problems
Movement of nonimmune populations into malarious areas (refugees and travelers)
Malaria Endemic Countries : Malaria Endemic Countries P. falciparum (most prevalent) and P. malariae in all shaded areas
P.ovale predominant
in Sub-Saharan Africa and P. vivax
in the other areas
Centers for Disease Control and Prevention
Countries and Territories With Malarious Areas : Countries and Territories With Malarious Areas * = P. vivax risk only World Health Organization
Cause of Malaria : Cause of Malaria Cause – protozoan parasite genus Plasmodium
Vector – female Anopheles mosquito (about 60
of the 400 species)
Host - man
Species of malaria parasite -
P. falciparum
P.vivax
P. ovale
P. malariae
Transmission : Transmission Vector – Anopheles mosquito
Blood transfusion
Organ transplant
Congenital
Malaria Risk : Malaria Risk Risk varies widely between and within countries
Depends on travel itinerary (location, duration, type of travel)
Transmission is highest in Africa
Most urban areas are malaria-free except in Africa and India
Risk highest at end of rainy season
Usually restricted to altitudes below 1500 meters but can occur up to almost 3000 meters
Locations of P. falciparum Drug Resistance : Locations of P. falciparum Drug Resistance Resistance to Chloroquine has been confirmed in all areas with P. falciparum malaria except
Dominican Republic
Haiti
Central America west of former Panama Canal Zone
Egypt
Some countries in the Middle East
Locations of P. falciparum Drug Resistance (cont.) : Locations of P. falciparum Drug Resistance (cont.) Resistance to Fansidar
Widespread in Amazon River Basin area of South America
Much of Southeast Asia
Other parts of Asia
Large parts of Africa
Resistant to Mefloquine
Borders of Thailand with Myanmar (formerly Burma) and Cambodia
Western provinces of Cambodia
Eastern states of Myanmar
Locations of P. vivax Drug Resistance : Locations of P. vivax Drug Resistance Resistance to Chloroquine
Indonesia
Papua New Guinea
Declining sensitivity to Chloroquine
Brazil
Columbia
India
Myanmar (formerly Burma)
Republic of Korea
Thailand
Locations of P. malariae Drug Resistance : Locations of P. malariae Drug Resistance Resistance to Chloroquine
Indonesia
Three Stages of Malaria Parasite Life Cycle : Three Stages of Malaria Parasite Life Cycle Liver
Red blood cells
Mosquito
Life Cycle of Malaria Parasite : Life Cycle of Malaria Parasite Centers for Disease Control and Prevention Division of Parasitic Diseases
Malaria Incubation Period : Malaria Incubation Period Corresponds with liver stage of malaria parasite
P. falciparum 12 Days
P. vivax 14 Days*
P. ovale 14 Days*
P. malariae 30 Days
* May be 8 - 10 months or longer for some strains
Life Cycle of Malaria Parasite (cont.) : Life Cycle of Malaria Parasite (cont.) Infected mosquito takes blood meal and injects sporozoites into human host
Sporozoites infect liver cells, multiply and mature into schizonts that rupture and release merozoites into the bloodstream
In P. vivax and P. ovale, a dormant stage (hypnozoites) can persist in the liver and cause relapses by invading the bloodstream weeks, or even years, later
Merozoites infect red blood cells
Slide17 : Malaria Parasite in Red Blood Cells
Classic Clinical Symptoms of Malaria : Classic Clinical Symptoms of Malaria Blood stage parasites are responsible for clinical manifestations
Classical cyclic paroxysms
Cold stage: chills and shaking
Hot stage: warm, headache, vomiting
Sweating stage: weakness
Feel well for period of time, then cycle repeats itself
Life Cycle of Malaria Parasite (cont.) : Life Cycle of Malaria Parasite (cont.)
Some merozoites mature into schizonts that rupture into the bloodstream releasing more merozoites
Some merozoites differentiate into sexual cells (male and female gametocytes)
Mosquito ingests gametocytes during blood meal
Gametocytes mature and produce a fertilized egg that grows, ruptures and releases sporozoites
Sporozoites migrate to mosquito’s salivary gland waiting to be injected into a new human.
Principles of Malaria Protection : Principles of Malaria Protection Be Aware of the risk, the incubation period, and the main symptoms
Avoid Being bitten by mosquitoes, especially between dusk and dawn
Take the (Chemoprophylaxis) antimalarial drugs to suppress infection when appropriate
Seek immediate Diagnosis and treatment if a fever develops one week or more after entering an area where there is a malaria risk, and up to 1 year after departure
Personal Protective Measures (PPM) : Personal Protective Measures (PPM) Avoid malarious areas
Stay indoors from dusk to dawn in screened or air conditioned rooms
Use insect spray inside rooms, bed nets
Cover skin by wearing long sleeves, long pants
Apply DEET lotion on exposed skin
Use treated bed nets
DoD Insect Repellent System : DoD Insect Repellent System YOU NEED TO KNOW…
Dry cleaning removes permethrin from the uniform + + = MAXIMUM
PROTECTION Permethrin
On
Uniform DEET On
Exposed
Skin Properly
Worn
Uniform US Army Center for Health Promotion and Preventive Medicine
Insect Repellents For Skin And Clothing : DEET lotion NSN 6840-01-284-3982 Apply a thin coat to EXPOSED skin
One application lasts up to 12 hours Insect Repellents For Skin And Clothing Individual Dynamic Absorption Kit (IDA)
Treatment lasts for for over 50 launderings NSN 6840-01-345-0237 NSN 6840-01-278-1336 Aerosol spray can
Treatment lasts through 5-6 washes Permethrin US Army Center for Health Promotion and Preventive Medicine
Use of Bed Net While Sleeping : Use of Bed Net While Sleeping
Spray the outside of the net with permethrin
Tuck edges under cot or sleeping bag
Don’t let net touch your skin while you sleep
US Army Center for Health Promotion and Preventive Medicine
Chemoprophylaxis : Chemoprophylaxis Broad term comprising multiple strategies for the prevention of disease using medications
Primary prophylaxis
Prior to, during, and after the exposure period to prevent the initial infection
Terminal prophylaxis
At the end of the exposure period (or immediately after) to prevent relapses or delayed-onset of clinical presentations
Action of Antimalarial Drugs : Action of Antimalarial Drugs Kills parasites during multiplication phase in red blood cells
Suppresses symptoms by lowering the number of parasites in the blood; does not prevent infection
Taken long enough, eventually eliminates P. falciparum and P. malariae infection
Requires terminal prophylaxis to eliminate liver stage of P. vivax and P. ovale
Factors for Choosing Malaria Chemoprophylaxis : Factors for Choosing Malaria Chemoprophylaxis Type of malaria
Drug resistance in specific locations
History of allergic or other reaction to the anti-malarial drug of choice
Restriction based on job (e.g., mefloquine not authorized for aviators and divers)
Drugs for Primary Malaria Chemoprophylaxis : Drugs for Primary Malaria Chemoprophylaxis Chloroquine
Mefloquine (Lariam® and generic brands)
Doxycycline
Atovaquone-proguanil (Malarone®)
Schedule for Taking Primary Malaria Chemoprophylaxis : Schedule for Taking Primary Malaria Chemoprophylaxis Prior to travel, start malaria medication:
Chloroquine and mefloquine - 1 to 2 weeks
Doxycycline and atovaquone/proguanil - 1 to 2 days
Can start earlier to allow any potential adverse effects to be identified prior to travel
Most antimalarial drugs well tolerated (Minor side effects do not require stopping the drug)
Continue drug during travel and after leaving malarious area:
Chloroquine, mefloquine and doxycycline - 4 weeks
Atovaquone/proguanil - 7 days
Antimalarial Medications : Antimalarial Medications Chloroquine
Mefloquine (Lariam® and generic brands)
Doxycycline
Atovaquone-proguanil (Malarone®)
Primaquine
Chloroquine : Chloroquine Adults: 500 mg per week (300 mg base)
From 1-2 weeks before entry, during, and 4 weeks after exit from malarious area
OK in all ages, including infants, pregnant and lactating women
Overdose in children potentially fatal
Side effects: GI upset, headache, dizziness, blurred vision, insomnia and pruritis
Has been reported to exacerbate psoriasis
Occasional GI upset, recommend take with food
Drugs of Choice in Chloroquine-Resistant Areas : Drugs of Choice in Chloroquine-Resistant Areas Mefloquine (Lariam ®)
Doxycycline
Atovaquone-proguanil (Malarone®)
Mefloquine (Lariam ®) : Mefloquine (Lariam ®) Adults: 250mg per week
From 1-2 weeks before entry, during, and 4 weeks after exit from malarious area
Safe for use in 2nd and 3rd trimesters and inadvertent use in 1st trimester has not resulted in adverse effects
Safe for use in breastfeeding women, but infants must take their own separate dose of mefloquine
Mefloquine Contraindications : Mefloquine Contraindications
Known hypersensitivity to mefloquine or related compounds (e.g., quinine or quinidine)
Active depression or recent history of depression
Generalized anxiety disorder, psychosis, schizophrenia, or other major psychiatric disorders
History of seizure disorder or epilepsy
Mefloquine Cautionary Warnings : Mefloquine Cautionary Warnings
May cause psychiatric symptoms at rate of 1 per 2,000-13,000 persons
Symptoms include: anxiety, paranoia, depression, hallucinations, psychotic behavior
Rarely symptoms continue after drug is stopped
Rare cases of suicidal ideation and suicide although no relationship has been confirmed
Advise patients to discontinue medication if experience psychiatric symptoms such as excessive anxiety, depression, restlessness or confusion
Substitute alternative antimalarial medication
Lariam Medication Guide : Lariam Medication Guide Developed by the Food and Drug Administration (FDA) in cooperation with the drug’s manufacturer, Roche Pharmaceuticals
Designed to help ensure patients understand the risks of malaria, and the rare but potentially serious psychiatric adverse events associated with use of Lariam
As of July 2003, required that a Guide be given to the traveler each time that Lariam is dispensed
Copy available at http://www.fda.gov/medwatch/
SAFETY/2003/LariamMedGuide.pdf
Doxycycline : Doxycycline Adults: 100 mg per day
From 1-2 days before entry, during, and 4 weeks after exit from malarious area
GI upset, photosensitivity, vaginal yeast infections, esophageal ulceration possible
Take with sufficient liquid to transport capsule into stomach; take with food
Contraindicated in pregnancy, lactation, and in children 8 and under
Effectiveness equivalent to mefloquine and chloroquine
Atovaquone-proguanil (Malarone®) : Atovaquone-proguanil (Malarone®) Adults: 1 tablet per day (atovaquone 250mg, proguanil 100mg)
From 1-2 days before entry, during, and for 7 days after exit from malarious area
Take with food or milky drink
Adverse effects: abdominal pain, nausea, vomiting, headache
Contraindicated in children <11kg, pregnant women, women breastfeeding infants <11kg, and patients with severe renal impairment
Pregnancy and Malaria : Pregnancy and Malaria Malaria infection more severe
Increased risk for prematurity, abortion, stillbirth
Advise women who are pregnant or likely to become pregnant to avoid travel to malarious areas if possible
Chemoprophylaxis
Chloroquine is safe
Mefloquine is safe in 2nd and 3rd trimester and probably during the 1st
Don’t use primaquine, doxycycline, and atovaquone/proguanil
Terminal Prophylaxis with Primaquine : Terminal Prophylaxis with Primaquine Decreases the risk of relapses by eradicating liver stage of P. vivax and P. ovale
Taken for 14 days during last 2 weeks of 4 week post-exposure prophylaxis with chloroquine, mefloquine or doxycycline
Taken during the final 7 days of post-exposure prophylaxis with atovaquone/proguanil and for an additional 7 days or for 14 days after atovaquone/proguanil has been completed
Adults: CDC has recently increased the recommended dose from 15mg to 30 mg
Terminal Prophylaxis with Primaquine (cont.) : Terminal Prophylaxis with Primaquine (cont.) Possible GI distress; take with food
Contraindicated in pregnancy
Breastfeeding OK if infant G6PD negative
G6PD deficiency and primaquine
Inherited sex linked trait, full expression in males
More common in persons of African, Mediterranean and Asian ancestry
Primaquine causes hemolysis, more severe in Mediterranean and Canton variants
G6PD testing advisable before treatment with primaquine
Restrictions on Blood Donation : Restrictions on Blood Donation Persons who are residents of nonmalarious countries are not allowed to donate blood for 1 year after returning from a malarious area
Persons who are residents of malarious countries are not allowed to donate blood for 3 years after leaving a malarious area (Residence is > 6 months in country)
Persons who have had malaria are not allowed to donate blood for 3 years after completion of treatment for malaria
Information Sources Centers for Disease Control and Prevention : Information Sources Centers for Disease Control and Prevention Health Information for International Travel
Malaria locations and prophylaxis guidelines
http://www.cdc.gov/travel/yb
National Center for Infectious Disease, Division of Parasitic Diseases
Prophylaxis guidelines
http://www.cdc.gov/ncidod/dpd/parasites/
malaria/default.htm
Information Sources (cont.) Other Sources : Information Sources (cont.) Other Sources World Health Organization
http://www.who.int/health-topics/malaria.htm
Navy Environmental Health Center
Navy Medical Department Pocket Guide to Malaria Prevention and Control NEHC-TM PM 6250.1 (September 2000)
www-nehc.med.navy.mil/downloads/prevmed/ Malaria2000.PDF
Information Sources (cont.) Other Sources (cont.) : Information Sources (cont.) Other Sources (cont.) US Army Center for Health Promotion and Preventive Medicine
http://chppm-www.apgea.army.mil
Armed Forces Medical Intelligence Center
Malaria locations
http://mic.afmic.detrick.army.mil
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