Chemoprophylaxis for Malaria By Tarik Zaher Assistant Professor

Chemoprophylaxis for Malaria By Tarik Zaher Assistant Professor of Endemic and Tropical Medicine, Zagazig University , Egypt

� Malaria is the most important parasitic disease of man. Approximately 5% of the world's population is infected. � It causes over 1 million deaths each year. � The disease is a protozoan infection of red blood cells transmitted by the bite of a bloodfeeding female anopheline mosquito.

Risk of infection � Generally, without prophylaxis, the risk of malaria is highest in sub. Saharan Africa, intermediate in South Asia, and lowest in the Americas and South-east Asia. Other considerations include: • Type of travel – backpacking versus air-conditioned, wellscreened urban hotels. • Traveller's exposure to bites, adherence with prophylaxis. • Duration of stay – the cumulative risk of contracting malaria is proportional to the length of stay in the transmission area. • Region visited. • Altitude of destination – malaria is not transmitted above 2000 m. • Season of travel – the rainy season is associated with higher transmission. �

Prevention • Awareness: recognizing the risk. • Bites by mosquitoes: prevent and avoid. • Compliance with appropriate chemoprophylaxis. • Diagnose malaria swifty and treat promptly.

Anti-mosquito measures � The use of long clothing to reduce exposed skin during biting periods (dusk through to dawn). � The use of topical repellents : DEET , picaridin ), PMD , MGK-326, MGK-264 , IR 3535 and oil of citronella. � Other repellents: mats, coils, lotions and vaporizers.

Anti-mosquito measures � Mosquito nets : most mosquito nets are made of polyester and rarely last longer than 2– 3 years under field situations. Conventional nets treated with pyrethroids such as alphacypermethrin, cyfluthrin, deltamethrin, lambda-cyhalothrin or permethrin, need to be re-treated after three washes, or at least once a year to ensure continued insecticidal effect. Longlasting insecticidal nets [LLINs] are factory-treated mosquito nets, made with netting material that has the insecticide incorporated within or bound around the fibres and the insecticide is progressively released so that the net retains the efficacy after repeated washings. The LLINs are expected to retain their effective biological activity without re-treatment for at least 20 standard washes and for three years of recommended use under field conditions.

Anti-mosquito measures � Indoor Residual Spraying : IRS is an integral component of the Global Malaria Action Plan and currently DDT, pyrethroids (Deltamethrin 2. 5% WP, Cyfluthrin 10% WP, Alphacypermethrin 5% WP and Lambdacyhalothrin 10% WP) or Malathion 25% are used in different parts of the world for this purpose. All the interior walls and ceilings as well as the underside of furniture, back of the doors and porches of permanent human dwellings

Anti-mosquito measures � Space sprays: These insecticides instantly kill the mosquitoes, but lack any residual effects. They are therefore sprayed into the air. By killing adult mosquitoes, not only bites are prevented, but breeding is also prevented, resulting in net reduction in the mosquito population. Space sprays must be repeated often, at least once every week. Pyrethroids are commonly used for this purpose.

The Mosquito Control Chain Female mosquito develops eggs, nourished with human blood Personal Protection deny the blood meal Close windows and doors to prevent entry; Protect humans against mosquito bite by using bednets (insecticide treated), mosquito repellents Eggs laid on water collections Source Reduction deny breeding ground Prevent water logging, destroy unwanted water collections, keep water containers closed

The Mosquito Control chain Eggs hatch and develop into larvae and pupae in a week Larvicides Chemical, biological Kill the larvae with larvicidal agents, Guppy or Gambusia fish or bacteria or fungi Adults can live up to 4 -10 weeks or more Insecticides Kill the adults with space sprays (for instant kill) and residual sprays (for lasting effect)

The Mosquito Control chain Adults enter the human dwellings between 5 pm and 10 pm and early morning, hide in dark corners Prevent entry Close the doors and windows at that time; clear hiding places if possible Adults bite human beings at night, maximum at 11 pm-4 am Personal protection by covering the body with clothes; use of mosquito nets and repellents.

Chemoprophylaxis � It must be remembered that no chemoprophylaxis regime provides 100% protection. � Primary Prophylaxis: Use of antimalaria drugs at recommended dosage, started 2 -20 days before departure to a malarious area and continued for the duration of stay and for 1 -4 weeks after return.

Chemoprophylaxis 1 -Causal prophylaxis: This prevents the establishment of infection in the liver by inhibiting the pre-erythrocytic schizogony. Primaquine malaron and proguanil are effective as causal prophylactic drugs. 2 -Suppressive prophylaxis: Use of blood schizonticides suppresses the blood forms of the malaria parasite and thus protects against clinical illness. However, P. vivax and P. ovale may cause relapses from the hypnozoites and to prevent this, terminal prophylaxis may be needed.

Chemoprophylaxis � Terminal Prophylaxis: Terminal prophylaxis is the administration of primaquine for two weeks after returning from travel to tackle the hypnozoites of P. vivax and P. ovale that can cause relapses of malaria.

Chemoprophylaxis � Chemoprophylaxis is NOT recommended for residents of endemic area.

Chemoprophylaxis for Long Term Travelers: Long-term travelers intending to stay for more than 1 -3 months should seek the advice of local health care professionals familiar with the management of malaria in non-immune foreigners. The risk of serious side effects associated with long term use of chloroquine and proguanil are low. However, twice yearly screening for the detection of early retinal changes should be performed in anyone who has taken 300 mg of chloroquine (as base) weekly for over five years and requires further prophylaxis. If changes are observed, an alternative regimen should be considered. Data indicate no increased risk of serious side effects with long term use of mefloquine. The risk of long term use of doxycycline are not known. These two latter drugs should be reserved for those with greatest risk of infection. �

Chemoprophylaxis � Chemoprophylaxis for Frequent Travelers: Frequent travelers such as members of the aircraft crew may reserve chemoprophylaxis for high risk areas only. They should maintain rigorous self-protection against mosquito bites and be prepared for an attack of malaria and should carry a course of antimalarials as stand-by.

Prophylaxis During Pregnancy: � Malaria infection in pregnant women may be more severe than in non-pregnant women. In addition, the risk of adverse pregnancy outcomes, including prematurity, abortion, and stillbirth, may be increased. For these reasons, and because chloroquine has not been found to have any harmful effects on the fetus when used in the recommended doses for malaria prophylaxis, pregnancy is not a contraindication to malaria prophylaxis with chloroquine or hydroxychloroquine. However, because no chemoprophylactic regimen is completely effective in areas with chloroquine resistant P. falciparum, women who are pregnant or likely to become so should avoid travel to such areas

Prophylaxis During Pregnancy: � � � Chloroquine and Proguanil are the preferred chemoprophylactic drugs against malaria in the first 3 months of pregnancy. Mefloquine can be given during the second and third trimesters if the situation demands. Mefloquine and doxycycline can be used in non-pregnant women with child bearing potential, but pregnancy should be avoided for 3 months after mefloquine use and for one week after doxycycline use. Doxycycline, a tetracycline and malarone, are generally contraindicated for malaria prophylaxis during pregnancy.

Atovaquone plus Proguanil (Malarone): Adults: Adult tablet of 250 mg atovaquone and 100 mg proguanil - 1 tab. daily � Children: Pediatric tablet of 62. 5 mg atovaquone and 25 mg proguanil: 5 -8 kg: 1/2 tablet daily >8 -10 kg: 3/4 tablet daily >10 -20 kg: 1 tablet daily >20 -30 kg: 2 tablets daily >30 -40 kg: 3 tablets daily >40 kg: 1 adult tablet daily � Daily dosing; only have to continue for 7 days after exposure; not in pregnancy and lactation �

Chloroquine: � Adults: 300 mg base once weekly � Children: 5 mg/kg base weekly; maximum 300 mg � Long-term safety known; chloroquine resistance reported from most parts of the world; except in north Iraq, south of turkey, north of syria � Not for persons with epilepsy, psoriasis or visual disturbances. � Safe in pregnancy.

Proguanil: � < 2 yrs: 50 mg/day; 2 -6 yrs: 100 mg/d 7 -9 yrs: 150 mg/day; >9 yrs: 200 mg/d � Proguanil is used in combinations. � Safe in pregnancy.

Doxycycline: � (Vibramycin 100 mg cap) � 100 mg once daily for adults. � � 1. 5 mg base/kg once daily (max. 100 mg) <25 kg or <8 yr: Not given 25 -35 kg or 8 -10 yr: 50 mg 36 -50 kg or 11 -13 yr: 75 mg >50 kg or >14 yr: 100 mg Its not used in pregnancy or lactation. �

Mefloquine: � (Lariam Tablet with 250 mg base, 274 mg salt): 250 mg base once weekly for adults � <15 kgs: 5 mg of salt/kg; 15 -19 kg: 1/4 tab/wk; 20 -30 kg: 1/2 tab/wk; 31 -45 kg: 3/4 tab/wk; >45 kg: 1 tab/wk � Avoid in psychosis and epilepsy. �

Chemoprophylaxis Regimen: � Preferably, it should be started 1 -2 weeks prior to travel to a malarious area. In addition to assuring adequate blood levels of the drug, this regimen allows for evaluation of any potential side effects. Chemoprophylaxis should continue during the stay in malarious area and for 1 -4 weeks after departure from the area.

Areas with chloroquine sensitive P. falciparum: Chloroquine Start one week before exposure, continue during exposure and for 4 weeks thereafter Areas with chloroquine resistant P. falciparum (low degree, not wide spread): Chloroquine Plus Start one week before, continue during exposure and for 4 weeks thereafter Proguanil Start 1 -2 days before, continue during exposure and for 4 weeks thereafter Areas with chloroquine resistant P. falciparum (High degree, widespread): Chloroquine Plus Proguanil As above OR Mefloquine Start 2 -3 weeks before, continue during exposure and for 4 weeks thereafter OR Doxycycline Start 2 days before, continue during exposure and for 4 weeks thereafter OR Atovaquone Plus Proguanil(Malaron) Start 2 days before, continue during exposure and for 7 days thereafter

Intermittent preventive treatment in infancy (IPTi), childhood (IPTc) and in adults (IPTa) � Following the success of IPT in pregnancy (IPTp), the strategy of providing a treatment dose of antimalarials to all infants in high transmission settings at the time of EPI immunizations (usually given at 2, 3 and 9 months of age) has been developed. The two drugs evaluated mainly have been SP and, to a much lesser extent, amodiaquine.

Mass treatment Treatment of the entire at-risk population has been used in malaria elimination. � However, when the incidence of malaria is very low, this approach is sometimes considered as a method of final elimination – particularly when the influx of malaria from elsewhere can be well controlled (e. g. islands, edges of transmission areas). Where Plasmodium vivax and P. ovale are present, primaquine 15 mg base adult dose given for 2 weeks has been used in several settings. �