2 Malaria: ReferencesControl of Communicable Diseases Manual, 18th Edition.CCDR – Canadian Recommendations for the Prevention and Treatment of Malaria Among International Travellers – 2009, Supplement June 2009, Volume 35s1World Health Organization, International Travel Health: Country ListCenter for Disease Control (CDC), Traveller’s HealthRepellent use in the CF to prevent insect bites and associated diseasesGuidelines for Diving Medical Officers, Medications and Divers (2006)
3 TEACHING POINTS Identification Infectious agent Occurrence Reservoir Mode of TransmissionIncubation periodsPeriod of CommunicabilitySusceptibility & resistanceMethods of ControlPreventive MeasuresChemoprophylaxisGlucose-6-Phosphate Dehydrogenase deficiency (G6PD)DivingMalaria risk by geographic areaCF use of repellents
4 GeneralMalaria 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.International Travel & Health, WHO 2008, chapter 7, page 146CDC, MalariaInternational travellers from non-endemic areas are at high risk of malaria and its consequences because they lack immunity.
5 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; andP. malariae.Plasmodium falciparum (the most seroius, usually present with one or more of the following: fever, chills, sweats, anoexia, nausea, lassitude, headache, muscle & joint pain, cough & diarrhea. Anaemia and/or splenomegaly often develops after some days. Without treatment the disease may progress to severe malaria, of which the most important manifestations are: acute encephalopathy (cerebral malaria), severe anemia, icterus, renal failure, hypoglycemia, respiratory distress, lactid acidosis and more rarely coagulation defects and shock. Quick treatment is essential for falciparum malaria, even in mild cases, since irreversible complications can rapidly appear. Case fatality rates among untreated children & non-immune adults can reach 10% to 40%.The other human malarias, vivax, ovale and malariae are usually not life threatening. Illness may begin with malaise & a slow rising fever for several days, followed by a shaking chill & rapidly rising temperature, headache & nausea, ending in profuse sweating. After a fever free interval, the cycle of chills, fever and sweating reoccurs daily, every other or third day. An untreated primary attack may last from 1 week to a month or longer & is accompanied by prostration, anemia and splenomegaly. True relapses may reoccur at irregular intervals for up to 5 years. Infections with P. malariae may persist for life, with or without febrile episodes.Laboratory confirmation is viewing malaria parasites in blood films.
6 Infectious agent Plasmodium falciparum; P.vivax; P. ovale; and P. malariae.All 4 are protozoan parasites with asexual & sexual phases. Mixed infections are common in endemic areas.
7 P knowleskiRecently, 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.Center for Disease Control & Prevention,
8 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; andParts of the Indian south continent.Chloroquine restistant P. Falciparum occurs in tropical portions of both hemispheres, particularly in the Amazon region, south eastern Asia, eastern Africa and more now in central & western Africa.Resistance to chloroquine: Resistance began from 2 epicentres – Columbia (South America) and Thailand (South East Asia) in early part of 1960s. Since then, resistance has been spreading world wide and reached the Indian state of Assam in 1973.Resistance to mefloquine: Sporadic cases of mefloquine resistance have been reported from Thailand and Kenya. To prevent development of resistance, it has been suggested that mefloquine should always be used in combination with another antimalarial, like pyrimethamine/ sulphadoxine.
9 ReservoirHumans are the only important reservoir of human malaria, except with P. malariae, which is common to humans, African apes and South American monkeys.
10 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.
12 Malaria Life Cycle*The malaria parasite life cycle involves two hosts. During a blood meal, a malaria-infected female anopheline mosquito inoculates sporozoites into the human host(1). Sporozoites infect liver cells. (2) and mature into schizonts. (3) which rupture and release merozoites. (4) 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, after this initial replication in the liver (exo-erythrocytic schizogony A), the parasites undergo asexual multiplication in the erythrocytes (erythrocytic schizogony B). Merozoites infect red blood cells. (5). The ring stage trophozoites mature into schizonts which rupture, releasing merozoites. (6). Some parasites differentiate into sexual erythrocytic stages (gametocytes). (7). Blood stage parasites are responsible for the clinical manifestations of the disease.
13 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; andP. 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.The period between an infective bite and detection on blood smear is:6 to 12 days for P. falciparum; 8 to 12 days for P. vivax & P.ovale; 12 to 16 days for P. malariae.Delayed primary attacks may occur in P. vivax up to 6 to 12 months after exposure.Some sporozoites of p.vivax & P. ovale become dormant in the liver (hypnozoites) that remain in hepatocytes to mature months or years later to produce relapses.Injection or transfusion of infected blood or use of contaminated needles may also transmit malaria.Congenital transmission rarely occurs however pregnant women are more vulnerable to falciparum. In low transmission areas, pregnant women are at a higher risk of severe malaria, abortion & premature delivery.
14 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; andFalciparum: generally not more that 1 year; andTransfusional 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.
15 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 manifestationsDuffy-blood-group-negative human erythrocytes, FyFy is found predominantly in African and American blacks, who are the only groups resistant to infection by P. vivax.
16 What are ways to prevent the spread of malaria -or any other vector borne disease?
17 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);
18 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.
19 Methods of Control – Endemic Areas* Control of larval stage by elimination of breeding sites:Filling & draining or increasing the speed of water in natural or artificial channels is of little use where Malaria persists today. The same goes for chemical & biological control methods applied to bodies of water. It is rarely possible to get the necessary level of coverage to reduce transmission. Nonetheless, these methods may be useful in situations such as arid, coastal, urban areas or camp locations.Education: informing people to cover areas of stagnant, still water e.g. water tanks, empty stagnant water in tires etc, which are ideal breeding grounds for the parasite and mosquito.
20 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)
21 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.
22 Preventive Measures (Travellers) The components of malaria prevention are oftendescribed as the ABCD of malaria. All travellers toareas with Malaria need to:be aware of the risk of Acquiring malaria infection;b) know how to avoid mosquito Bites;c) take Chemoprophylaxis, as appropriate; andd) understand the need to urgently seek medical advice for Diagnosis and treatment if they have a fever.
23 Exposure AssessmentThe 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; andavailability 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.
24 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.Early diagnosis and treatmentAll travellers must be informed that malaria should be suspected if unexplained fever occurs during orafter travel. Medical attention should be sought as soon as possible, and the traveller should requestthat a thick and thin blood film be immediately obtained and examined for malaria parasites. If the initial blood film is negative and the traveller remains symptomatic, then the blood film should be repeated in 12 to 24 hours. The most important factors that determine the survival of patients with P. falciparum malaria are early diagnosis and prompt initiation of appropriate treatment.
25 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 effectiveAll travellers to areas with malaria risk are advised to use personal protective measures to prevent bites from Anopheles mosquitoes. Use of effective repellents and insecticide-treated clothing, covering up exposed skin and avoidance of areas or times where/when vectors are active are also considered to be important for prevention of malaria.
26 Insect Repellents & Clothing Bed netting - should be intact (without tears or large holes) and be tucked in under a mattress;Permethrin impregnated clothing;Insecticide-Treated BednetsGiven the behaviour of malaria vectors (usually night-active), the proper use of insecticide-treatedBed-nets (ITNs) is a critical protective measure for malaria and insecticide (permethrin) impregnated clothing should be considered.Insecticide-impregnated mosquito netting substantially increases the protection afforded by the net, since arthropods may still bite through the mesh when the traveller’s skin is against it or even pass through the net if they are small enough.The mosquito net should be intact (without tears or large holes) and be tucked in under a mattress.
28 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.
29 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.Adverse effects, contraindications and precautions: Compared with other standard antimalarial regimens, the atovaquone/proguanil combination for chemoprophylaxis has demonstrated excellent safety and tolerance. The most frequent side effects are those of the gastrointestinal tract: 8% to 15% experience nausea, vomiting, abdominalpain or diarrhea.
30 Mefloquine Trade 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;Precautions for mefloquine include: those with occupations requiring fine coordination or activities in which vertigo may be life-threatening, such as flying an aircraft or women in first trimester of pregnancy should not use Mefloquine.When mefloquine is prescribed for prophylactic use, individuals should be advised that if they experience psychiatric symptoms, such as acute anxiety, depression, restlessness or confusion, these may be prodromal to more serious adverse events. The drug should be discontinued, and an alternativemedication should be substituted.
31 Doxycycline*Doxycycline is an antimicrobial that inhibits parasite protein synthesisDoxycycline 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. falciparumDoxycycline can cause gastrointestinal upset and,rarely, esophageal ulceration, which is less likely and large amounts of fluid.CCDR – Canadian Recommendations for the Prevention and Treatment of Malaria Among International Travellers – 2009, Supplement June 2009, Volume 35sTP kIt is an effective chemoprophylactic and theraputic 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;Precautions for mefloquine include: those with occupations requiring fine coordination or activities in which vertigo may be life-threatening, such as flying an aircraft or women in first trimester of pregnancy should not use Mefloquine.When mefloquine is prescribed for prophylactic use, individuals should be advised that if they experience psychiatric symptoms, such as acute anxiety, depression, restlessness or confusion, these may be prodromal to more serious adverse events. The drug should be discontinued, and an alternative medication should be substituted.
32 Primaquinerecommended 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 malariaG6PD: 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.
33 DiversCF 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.
34 CF Use of RepellantsPathogens 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; andThe 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; andCanadian Occupational Health and Safety Legislation.3. Pathogens transmitted through insect or tick bites can cause serious disease and are a threat to military operations in many areas of the world. The bites of arthropods (insects and ticks) can also be very annoying, whether or not they carry disease, and a reduction in nuisance biting is of benefit in maintaining an operational focus.4. Two important methods for preventing bites are application of deet on exposed skin and the use of permethrin-impregnated physical barriers such as clothing and bednetting.5. Use of deet and permethrin to prevent bites has been reviewed and 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; Treasury Board Directive 2-15; CFAO 34-46; and Canadian Occupational Health and Safety legislation.6. Some CF members have indicated that they are concerned about use of deet and permethrin. Background information and responses to some common questions and fears are addressed in two question and answer documents: one for health care providers at annex A; and the other at annex B for non-medical personnel. These documents (or ones containing similar information) should be made available to their respective target audience(s).
35 CF Use of Repellents Risk level Intervention Disease Risk Biting Risk Repellent Recommendations:If bites present a threat to work-related activities, e.g. distraction during critical tasks, use of permethrin on combat clothing is recommended.If biting insects cannot be eliminated from sleeping areas, then treated bednetting is recommended.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 levelInterventionDisease RiskBiting RiskTopical repellent (deet)Treated clothing (combat)Treated clothing (other)Treated bednetNo to very lowNo to LowNoModerate or HigherYesNo 1No 2Low to ModerateLow or HigherNo 3High
36 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.
37 Use of Permethrin Two types of permethrin treatment used by the CF: Permethrin pouch system: (NSN , 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; andUse is restricted to combat clothing (e.g. CADPAT).Permethrin Aerosol Spray: (NSN ; 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; andIf 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.
38 Use of PermethrinClothing 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; andUse 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;
39 Use of PermethrinThere 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.
40 Use of PermethrinPermethrin 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; andPermethrin 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.
41 Permethrin use documentation A register must be maintained for permethrin and shall be retained indefinitely. It shall include:name and service number of person to which product is issued/used;date issued;treatment location: in Canada or outside Canada (country/operation);treatment site (e.g. Base, Wing, overseas site);item (pouch or spray) and quantity issued; andlot number.
42 Use of DEETOnly 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 ; 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).