Conduct Epidemiological Conduct Epidemiological InvestigationsInvestigations(MALARIA)(MALARIA)

EO 004.01EO 004.01

TP 2

Malaria: References

• Control of Communicable Diseases Manual, 18th Edition.• CCDR – Canadian Recommendations for the Prevention and

Treatment of Malaria Among International Travellers – 2009, Supplement June 2009, Volume 35s1 http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/09vol35/35s1/index-eng.php

• World Health Organization, International Travel Health: Country List http://www.who.int/countries/en/

• Center for Disease Control (CDC), Traveller’s Health http://wwwnc.cdc.gov/travel/

• Repellent use in the CF to prevent insect bites and associated diseases http://hr.ottawa-hull.mil.ca/health-sante/pd/pol/word/DFHP-CDCP-2008-02s-eng.doc

• Guidelines for Diving Medical Officers, Medications and Divers (2006) http://hr.ottawa-hull.mil.ca/health-sante/pd/pol/pdf/divers-plongee-medic-eng.pdf

TEACHING POINTSTEACHING POINTS

• Identification• Infectious agent• Occurrence• Reservoir• Mode of Transmission• Incubation periods• Period of Communicability• Susceptibility & resistance• Methods of Control

• Preventive Measures• Chemoprophylaxis• Glucose-6-Phosphate

Dehydrogenase deficiency (G6PD)

• Diving• Malaria risk by geographic

area• CF use of repellents

GeneralGeneral

Malaria is a life-threatening disease in many tropical and subtropical areas. It is currently endemic in over 100 countries, which are visited by more than 125 million international travellers every year.

Each year, malaria causes up to 500 million infections worldwide and approximately 1 million deaths.

Malaria*• Malaria is a blood parasite transmitted

person to person through the bite of an infected mosquito (previously bitten an infected person).

• There are 4 human subtypes with symptoms similar enough to make differentiation impossible without lab studies.– Plasmodium falciparum (the most serious);– P.vivax;– P. ovale; and– P. malariae.

Infectious agent

• Plasmodium falciparum;

• P.vivax;

• P. ovale; and

• P. malariae.

P knowleski

• Recently, P. knowlesi, a parasite of Old World monkeys, has been documented as a cause of human infections and some fatalities in Southeast Asia. Investigations are ongoing to determine the extent of its transmission to humans.

Occurrence*

• Major cause of ill health in tropical & subtropical countries;

• Causes over 1 millions deaths/year, mostly in African children;

• High transmission in:– Tropical Africa (ovale in sub-sahara Africa); – South western Pacific;– Forested areas of South America (Brazil);– South eastern Asia; and– Parts of the Indian south continent.

Reservoir

• Humans are the only important reservoir of human malaria, except with P. malariae, which is common to humans, African apes and South American monkeys.

Mode of transmission*

• Bite of an infective Female Anopheles mosquito (handout )

• Female Anopheles ingests blood containing sexual stages of the parasite (gameocytes);

• male and female gametes unite in the stomach to form ookinete which penetrates the stomach wall & forms a cyst.

• About a thousand sporozoites develop requiring 8 – 35 days;

• The sporozoites reach the salivary glands and are infective when injected into a person when the mosquito takes it’s next blood meal.

Malaria Life Cycle*

Incubation period*• The time between the infective bite and appearance

of clinical symptoms is:

– P. falciparum: 9 to 14 days;– P. vivax: 12 to 18 days (temperate areas

incubation may be 8 to 10 months);– P. ovale: 12 to 18 days; and– P. malariae: 18 to 40 days.

• Infection through transfusion, incubation usually short but could be up to 2 months.

• Suboptimum drug suppression from prophylaxis may result in prolonged incubation periods.

Period of communicability• Humans can infect mosquitoes as long as infective

gametocytes are present in the blood, varying in parasite species and response to therapy.

• Untreated or insufficiently treated patients may be a source:– Malariae: for several years;– Vivax: up to 5 years; and– Falciparum: generally not more that 1 year; and

• Transfusional transmission occurs as long as asexual forms remain in circulating blood – up to 40 years in P. malariae.

• Stored blood can remain infective for 1 month.

Susceptibility & Resistance• Susceptibility is universal except for people with

specific genetic traits.

• Tolerance or resistance is present in adults in anopheles highly endemic communities.

• Most indigenous populations of Africa show a natural resistance to P. vivax, associated to the absence of Duffy factor on their erythrocytes.

• Persons with HIV are at high risk with falciparum for severe manifestations

• What are ways to prevent the spread of malaria -or any other vector borne disease?

Methods of Control – Endemic Areas

• Use of insecticide treated mosquito nets with a fibre strength of at least 100 denier with a mesh size:

– 156 holes/in2 (about 25 holes/cm2);

Methods of Control – Endemic Areas

• Indoor residual spraying (IRS) with insecticides. Most effective where mosquitoes rest on sprayable surfaces, prior to active season.

• Coverage rates must be high;• In households, IRS is ineffective compared to

treated netting;• Pyrethroids are selected as an alternative to

DDT. Their duration of action is shorter & thus, a lesser risk to the environment.

Methods of Control – Endemic Areas*

• Control of larval stage by elimination of breeding sites:

Methods of Control – Endemic Areas

• Intermittent preventive treatment with full curative dose of an effective antimalarial drug is a highly effective measure for reducing the malaria burden among pregnant women in areas of intense P. falciparum transmission. – This is only promoted in Africa, but of limited use

else where due to widespread parasite resistance to the only drug validated for this (sulfadoxine-pyrimethamine)

Methods of Control – Endemic Areas

• In epidemic areas: surveillance should be based on weekly reporting combined with monitoring locally important factors such as meterological, environmental & human population movements.

• Confirmed case need to be distinguished from non-confirmed (probable) cases.

• Non-endemic areas: blood donors should be questioned for malaria history or travel to malarious areas.

Preventive Measures (Travellers)

The components of malaria prevention are oftendescribed as the ABCD of malaria. All travellers toareas with Malaria need to:

a) be aware of the risk of Acquiring malaria infection;

b) know how to avoid mosquito Bites;

c) take Chemoprophylaxis, as appropriate; and

d) understand the need to urgently seek medical advice for Diagnosis and treatment if they have a fever.

Exposure Assessment The travel itinerary should be reviewed and compared with

known areas of malaria transmission within a country to determine the likelihood that the traveller will be at risk of acquiring malaria. Factors to consider in determining risk of exposure include the following:

• level of endemicity in the area(s) covered by the travel itinerary;• presence of Plasmodium falciparum;• duration of exposure;• rural, periurban, urban travel;• seasonality (rainy vs dry);• night-time exposure; and• availability and likelihood of use of other interventions, e.g.,

personal protective measures.

CATMAT considers there to be minimal risk of malaria in urban centres of Southeast Asia, and Central and South America.

Early Diagnosis*

Inform travellers:• Malaria should be suspected with any fever;• Medical attention should immediately be

sought;• Traveller’s should then request a thick and

thin blood film be obtained & examined for malaria parasites;

• If initial film is negative – then repeat in 12 to 24 hours.

Insect Repellents & Clothing• DEET (N,N-diethyl-3-methyl- benzamide, also known as N,N-diethyl-

m-toluamide) remains the first choice among repellants.

• CATMAT recommends up to 30% DEET-containing products for all age groups.

• Where extended-duration formulations are unavailable, products that contain up to 35% DEET are preferred.

• if DEET and sunscreen application are both required, apply the sunscreen first, allowing skin penetration for 20 minutes, followed by DEET.

• When DEET is not permitted, consider soybean oil 2% “blocker” repellents as a third-line repellent where arthropod-borne infections present a significant risk. Picaridin (Bayrepel, KBR 3023, Autan), which is available in Europe and the United States and recommended by WHO, may be as effective as 15% to 50% DEET.

• Repellents containing citronella oil are not effective

Insect Repellents & Clothing

• Bed netting - should be intact (without tears or large holes) and be tucked in under a mattress;

• Permethrin impregnated clothing;

ChemoprophylaxisChemoprophylaxis

• Chloroquine

• Atovaquone/proguanil

• Mefloquine

• Doxycycline

• Primaquine

Chemoprophylaxis

Chloroquine or Hydroxychloroquine:

• Mechanism of action: Chloroquine is a synthetic 4-aminoquinoline, which acts against the intra-erythrocytic stage of parasite development. It interferes with the digestion of hemoglobin within the red cell and leads to toxic metabolite formation within the food vacuole of the parasite;

• Indications and efficacy: Chloroquine/hydroxychloroquine, taken once weekly, is effective for malaria prevention in travellers to areas with chloroquine-sensitive malaria;

• Chloroquine is suitable for people of all ages and for pregnant women. There is insufficient drug in breast milk to protect an infant, and therefore nursing infants should be given chloroquine (adjusted for changing weight);

• Except for its bitter taste, chloroquine is usually well tolerated.

Atovaquone/Proguanil (ATQ/PG)

Trade Name: Malarone®, Malarone® Pediatric:• Licensed in Canada for malaria chemoprophylaxis for adults and

children 11 kg and above & treatment of uncomplicated malaria in adults & children.

• Atovaquone/proguanil is a fixed drug combination of atovaquone and proguanil in a single tablet that must be taken daily.

• It can be discontinued 1 week after departing a malaria endemic area.• Indications and efficacy:

– For malaria chemoprophylaxis, atovaquone/proguanil has equal efficacy to that of doxycycline and mefloquine against chloroquine resistant falciparum malaria.

• The most frequent side effects are those of the gastrointestinal tract: 8% to 15% experience nausea, vomiting, abdominal pain or diarrhea.

MefloquineTrade Name: Lariam®, Apo-Mefloquine.

• Mefloquine is a quinoline-methanol. It is a lipophylic drug that acts on the intraerythrocytic asexual stages of parasite development.

• It is an effective chemoprophylactic and therapeutic agent against drug resistant P. falciparum. In Canada it is only recommended for chemoprophylaxis because of side effects with higher treatment doses.

• Side effects: the most frequent minor side effects reported with mefloquine use are nausea, strange vivid dreams, dizziness, mood changes, insomnia, headache and diarrhea;

Doxycycline*Doxycycline*• Doxycycline is an antimicrobial that inhibits parasite

protein synthesis• Doxycycline is effective for the prevention and

treatment of chloroquine-resistant P. falciparum. • It has been shown to have equivalent efficacy to that of

atovaquone/proguanil and mefloquine for the prevention of chloroquine-resistant P. falciparum

• Doxycycline can cause gastrointestinal upset and,rarely, esophageal ulceration, which is less likely and large amounts of fluid.

Primaquine

• recommended when the first-line agents mefloquine, doxycycline or malarone cannot be used or for treatment of P. vivax or P. ovale malaria.

• Primaquine (30 mg base daily) is an effective chemoprophylactic agent with a protective efficacy of 85% to 93% against both P. falciparum and P. vivax infections;

• Primaquine is well tolerated in people who are not G6PD deficient;

• It is given either for acute or latent stage malaria

• G6PD: Primaquine may break down the red bolld cells in patients deficient in the compound glucose-6-phosphate-dehydrogenase (G6PD). Before taking Primaquine, blood testing must be performed to determine if opatients are G6PD deficient.

Divers• CF divers on operations should take Doxycycline, followed by 7 days 'unfit

diving‘. If no side effects occur, divers can then be declared fit to dive but must be monitored for gastric upset and warned of photosensitivity.

• Mefloquine:

– CF divers are not permitted to dive on Mefloquine due to potentially serious side effects (vertigo, visual disturbances, difficulty with co-ordination, sleep disturbances, depression, hallucinations and psychosis), which may worsen under pressure.

– Members who are not CF divers & are required to take Mefloquine, should not to do recreational diving while on HLTA. Since the elimination of Mefloquine from the body is 2 to 4 weeks, there isn’t time for elimination of the drug. For most AORs, members have a choice of antimalarials.

– Mefloquine has also been associated with an increased risk of nitrogen narcosis and anxiety attacks.

• Malarone: contains both atovaquone and proguanil, both of which are known to lower the seizure threshold in individuals. Therefore, the recommendation is against diving on Malarone since a seizure at depth is not survivable.

• Summary: Doxycycline is the drug of choice for divers taking antimalarials or for members who wish to dive while on HLTA.

CF Use of Repellants• Pathogens transmitted through insect or tick bites can cause

serious disease & can be a threat to military operations around the world;

• Two important methods to prevent insect bites include:– Application of deet on exposed skin; and– The use of Permethrin-impregnated physical barriers (clothing &

bednetting).

• Use of Deet & Permethrin to prevent bites has been reviewed & approved by the Pest Management Regulatory Agency (PMRA) of Health Canada and is guided by:– the Pest Control Products Act and Regulations;– The product labels and conditions of registration;– Tresury board Directive 2-15;– CFAO 34-46; and– Canadian Occupational Health and Safety Legislation.

CF Use of Repellents

Repellent Recommendations:

1. If bites present a threat to work-related activities, e.g. distraction during critical tasks, use of permethrin on combat clothing is recommended.

2. If biting insects cannot be eliminated from sleeping areas, then treated bednetting is recommended.

3. For certain operational situations, e.g. where combats will not (or usually not) be worn, use of permethrin on other clothing might be considered, but is to have approval from D FHP.

Risk level Intervention

Disease Risk Biting Risk Topical repellent

(deet)

Treated clothing (combat)

Treated clothing (other)

Treated bednet

No to very low

No to Low No No No No

No to very low

Moderate or Higher

Yes No 1 No No 2

Low to Moderate

Low or Higher

Yes Yes No 3 Yes

High Low or Higher

Yes Yes Yes Yes

Deviations from Repellent Recommendations:

• Where the senior medical authority feels there is reason to enhance protection against insect bites and/or associated disease – he/she should do so and inform D FHP.

• A local decision to recommend reduced measures for protection against insect bites and/or associated disease is to have prior approval from D FHP.

Use of PermethrinTwo types of permethrin treatment used by the CF:a. Permethrin pouch system: (NSN 6840-01-345-0237, Cdn Reg # 28560).

– Applied by soaking clothing in a solution for several hours;– Protective effects are retained for approximately six months, after which

re-treatment is recommended; and– Use is restricted to combat clothing (e.g. CADPAT).

b. Permethrin Aerosol Spray: (NSN 6840-01-278-1336; Cdn Reg # 27930).

– Applied by spraying treatment onto clothing or bednetting;– Clothing treated with spray loses its protective effect after several

washes and must periodically be re-treated (e.g. at monthly intervals);– Bednetting treated with spray also loses its protective effect after about

one month, after which re-treatment is recommended; and– If bednetting is washed or substantially wetted, it should be retreated.

• Pouch and spray-treated clothing and spray-treated bednetting can be used in Canada and abroad.

Use of Permethrin

• Clothing or bed-netting treated with permethrin must not be dry-cleaned or the Permethrin will no longer be effective. If they are dry cleaned - the permethrin treatment needs to be reapplied;

• Use of permethrin treatments is normally restricted to military personnel;

• Use pouch treatment on combat clothing for deployments greater than 1 month;

• For deployments to a areas where disease risk is high (regardless of deployment length);

• For multiple short deployments. If treated clothing is stored in an air-tight bag (e.g. ziplock) between the short deployments, then retreatment is required after 6 months of cumulative use or 1 year after treatment, whichever comes first;

• for retreatment, when the clothing has been worn for six months since it was last treated and exposure to risk continues; and

• Use IAW the conditions of registration, set out by Health Canada. This requires application at a military facility, under appropriate supervision (e.g. Preventive Medicine Technician) and in a well-ventilated area;

Use of Permethrin

• There is no limit on the number of uniforms that can be treated per day per person.

• Whenever possible, permethrin pouch treatment of clothing should be done as close as possible to the date of deployment. If clothing is treated well in advance of the date of departure it must be stored in an airtight (e.g. ziplock) bag until deployment. Permethrin-impregnated clothing, stored in an airtight bag for up to 6 months, retains its protective effect for 6 months after it is removed from the storage bag.

Use of Permethrin• Permethrin is not to be applied to fire retardant clothing.

Individuals in an area of risk should wear permethrin treated clothing whenever fire retardant clothing is no longer required.

• Only spray treatment is authorized for:– use on bednets;– non-combat clothing;– Spray treatment is also recommended for combat clothing if

deployment is for less than 30 days; and – Permethrin spraying is to occur outdoors or a well-ventilated area.

• Permethrin can be obtained through the Base/Wing Preventive Medicine Technician IAW this policy and other recommendations made by D FHP e.g. health protection recommendations for specific deployments.

Permethrin use documentation

• A register must be maintained for permethrin and shall be retained indefinitely. It shall include:1. name and service number of person to which

product is issued/used;2. date issued; 3. treatment location: in Canada or outside Canada

(country/operation);4. treatment site (e.g. Base, Wing, overseas site);5. item (pouch or spray) and quantity issued; and6. lot number.

Use of DEET• Only topical repellents with the active ingredient deet is recommended.

Other active ingredients are not used, because they don’t perform well, are not registered in Canada and/or because there is concern about their safety.

• The current military issue repellent is 3M Ultrathon:

– (NSN 6840-01-284-3982; Canadian Registration Number 22966);– has excellent and well-documented performance against biting insects and is the

normal recommendation for deployments within or outside Canada.

• Where 3M Ultrathon is not available or where persons prefer another type of application method (e.g. pump spray), repellents containing 20% to 30% deet are recommended.

• Protection time on product label is based on a “best-case” scenario. Protection is reduced through abrasion, hot and/or wet climates, exercise, sweating, swimming. Repellent should therefore be reapplied based on need rather than label time based periods.

• Triggers for application include: user notices bites; after swimming or moderate to intense sustained exercise; or period of high risk for biting is approaching (e.g. evening through morning for malaria mosquitoes).

Malaria

Questions