Malaria remains a leading global health challenge, with an estimated 219 million clinical malaria cases and 1.24 million deaths attributed to Plasmodium falciparum infection reported annually. Malaria remains endemic in 104 countries, primarily located in Africa and Asia. Rates of international travel to malaria-endemic regions have increased drastically, with 233.6 million travelers visiting Asia and the Pacific, and 52.4 million travelers visiting Africa in 2012. Falciparum malaria remains a leading cause of acute and potentially life-threatening illness among Western travelers. With increased international travel and continued endemicity of malaria around the world, the number of travelers exposed to malaria is rising, and travelers need to be informed of effective measures to protect themselves from this potentially life-threatening disease.
There are significant risks associated with Plasmodium infection, especially with P. falciparum and Plasmodium vivax infection. Although the majority of infected individuals develop uncomplicated malaria and can be effectively managed with prompt diagnosis and treatment with appropriate anti-malarials, a subset may progress to severe disease. Severe malaria can manifest in a variety of forms, including cerebral malaria (malaria with coma and without other identifiable cause), severe malarial anemia, respiratory distress, metabolic acidosis and multi-organ failure. Life threatening infections can develop within 24 h of disease onset and, despite the use of first-line anti-malarials, fatality rates for severe malaria complications, such as cerebral malaria, remain high, at 15–30 %. Due to the risk of severe morbidity and mortality associated with malaria, prevention is a priority strategy for disease management. This review will emphasize two of the key principles for malaria prevention in travelers: bite avoidance and chemoprophylaxis, based on guidelines outlined by the World Health Organization (WHO) ‘ABCD’ approach. It is important to note that malaria prevention measures do not provide complete protection and early diagnosis is important for disease management. Physicians should inform patients of the importance of seeking prompt medical attention if they develop fever after entering a malaria-endemic area. Prophylaxis measures themselves are not without risk; therefore, in order to determine an appropriate course of action, it is important to weigh the relative risk of exposure and development of severe disease with the risk of adverse events (AEs) due to chemoprophylaxis.
Pharmacologic Treatment
There are two types of chemoprophylactic agents for the prevention of malaria: suppressive and causal. The majority of agents are suppressive and target the blood stages of malaria. This has important implications for the duration of use required for these drugs after departing malaria-endemic regions. Agents in the other category are causal in effect and target both the liver and blood stages of malaria. Currently, there are only two causal agents in use for the prevention of malaria and only one drug that can kill the dormant hypnozoites of P. vivax and P. Ovale.
Suppressive Chemoprophylaxis
Chloroquine
Chloroquine has been used continuously since its potent anti-malarial activity was recognized in the 1940s. Chloroquine is a suppressive agent that acts against intraerythrocytic parasites by inhibiting hemozoin formation. Its use is now limited due to the widespread prevalence of chloroquine-resistant P. Falciparum in most malaria-endemic regions. Chloroquine remains the drug of choice for areas with chloroquine-sensitive strains including Mexico, the Caribbean (Haiti and Dominican Republic) and parts of Central America, the Middle East and China. Chloroquine-resistant P. vivax has been reported in Indonesia, Papua New Guinea, the Solomon Islands, Burma, Vanuatu, India, and Guyana. It is recommended that travel healthcare advisors consult updated country-specific information prior to prescribing chloroquine.
The standard adult dose of chloroquine for malaria chemoprophylaxis is 300 mg base weekly, starting 1–2 weeks prior to travel and continuing for 4 weeks after travel to malaria-endemic regions. Post-travel treatment requirements can lead to treatment non-compliance, especially in short-term travelers.
Chloroquine is contraindicated in patients with epilepsy or a history of psychosis, as it may exacerbate these conditions. Precautions should be taken in patients with a known history of liver disease, alcoholism, or concurrent administration of known hepatotoxic drugs. Chloroquine may exacerbate psoriasis and should be used with precaution in patients with this underlying condition. Concomitant use of chloroquine and mefloquine is not recommended, as co-administration may increase the risk of convulsions, electrocardiogram abnormalities and/or cardiac arrest. Precautions should be used for travelers on long-term chloroquine therapy. Baseline examination and annual screening should be conducted and treatment should be discontinued if evidence of muscle weakness and ophthalmologic abnormalities (keratopathy and retinopathy) are observed. Travelers with glucose-6-phosphate dehydrogenase (G6PD) deficiencies should be monitored frequently for hemolytic anemia.
The standard chloroquine dose for malaria prophylaxis is well-tolerated, however, gastrointestinal upset is not uncommon (reported in >1 % of users). Administration with food can minimize GI symptoms. For travelers to chloroquine-resistant areas who have contraindications or intolerance to other first-line antimalarial drugs (e.g., mefloquine, atovaquone-proguanil or doxycycline), chloroquine plus proguanil combination therapy has been used as an alternative, although it has higher failure rates than the first-line drugs. The recommended adult dose of combination chloroquine–proguanil prophylaxis is 200 mg/daily proguanil and 300 mg base/weekly chloroquine, continued for 4 weeks after leaving a malarious region. Studies have not been able to conclusively show comparative efficacy relative to other first-line options and show an inferior tolerability profile compared to other antimalarials. Due to Pregnancy considerations. Chloroquine is recommended for pregnant and lactating women traveling to areas with chloroquine-sensitive P. falciparum and is an FDA Category C drug. When used at the recommended prophylaxis dose, its potential drug-related teratogenicity is low and any associated risk of drug exposure is outweighed by the significant risk of mortality and morbidity to both the mother and fetus associated with malaria. In studies conducted on children born to mothers taking therapeutic chloroquine for rheumatic disease (SLE, rheumatoid arthritis), no visual defects, adverse pregnancy outcomes, or congenital birth defects above the expected ratein a normal, unexposed population were associated with in utero chloroquine exposure at any stage of pregnancy.
Pediatric considerations. Chloroquine is recommended for pediatric travelers to areas with chloroquine sensitive strains. The recommended dose for infants and small children is 5 mg base/kg weekly. Overdose can be fatal. It is recommended to deliver the drug with food or syrup to improve palatability.
Reference:
Robyn E. Elphinstone & Sarah J. Higgins & Kevin C. Kain. Curr Treat Options Infect Dis (2014) 6:47–57