Malaria prevention—keep it simple and logical

Due to various activities—including those by the World Bank and the Bill & Melinda Gates Foundation—we are happy to see a global decrease in malaria cases. But too many still suffer and die from malaria so malaria prevention or at least to prevent deaths by malaria is of paramount importance, still. And this is not true for the indigenous population only but for travellers as well. Balancing the risk of disease with that of possible side effects of chemoprophylaxis is a difficult task which mostly leads to split decisions even in experts (as was shown in a thrilling Pro-Con debate at the CISTM14 in Quebec in May 2015). This lack of guidance left and still leaves many colleagues (including qualified travel medicine practitioners) quite puzzled—not to talk about those on target—i.e. the travellers. For sustainable guidance my deep believe is: KEEP IT SIMPLE—otherwise counselling doctors (not all of whom are experts in tropical medicine or malariology) as well as travellers will get lost in confusion for sure1 (‘The compliance is inversely proportional to the complexity of the prescription’—Haynes and Sackett 1976). Insect bite precautions (IBP) from dusk until dawn are the mainstay of malaria prophylaxis—so this is of paramount importance for each traveller going to malaria endemic areas no matter how high the risk actually is. The first crucial decision of the binary decision tree is the definition of high risk of exposure (but may consider high risk of complications in vulnerable travellers as well). Whereas some sources say that there is no method of quantifying the risk2 in other sources high risk is defined by a risk of 10:1000 in the indigenous population3 or 1:100 (or higher)/month of stay (e.g. for tropical Africa—older data: incidence of malaria per month of exposure for travellers not taking chemoprophylaxis: 15.2 per 1000 in East Africa and 24.2 per 1000 in West Africa4). Highly endemic throughout the year are most countries in tropical Africa, some islands in the Pacific Ocean and—at the moment—shrinking areas of tropical South America (to be looked up in actual malaria maps from various organizations). In these regions, the recommended strategy is chemoprophylaxis (with active compounds in addition to insect protection) —no matter how long the stay is (in some areas in West Africa the average likelihood of having an infectious bite is >1/night !5). In regions with a high annual variability of risk chemoprophylaxis (+IBP) should be limited to the high risk seasons, only. MISCONCEPTIONS DUE TO WORDING The wording “stand by therapy or treatment (SBT)” [10] always leaves me with huge discomfort and I would re-emphazise to replace it in general by the expression “emergency self treatment” or “emergency self therapy” (EST)**. The reason to push “EST” is that “stand by” might be dangerously misleading. At least it plays a critical strategy (which is not even state of the art globally) down in putting travellers to increased risk based on misconception (which is - amongst several other cases dramatically illustrated by an Austrian traveller to Lombok who died in Austria due to malaria while still having atovaqone/proguanil in his pocket). For clarification: emergency self treatment (EST) is applied by (mostly lay) people based on symptoms typical for malaria (which also means that they must know the symptoms as well as the minimal incubation period) if they have no or delayed access only to qualified medical care. The goal of this (primarily European) approach is to bridge the gap in between onset of symptoms and qualified medical care to positively impact the course of a potentially life threatening disease. By using the expression “EST” the traveller knows that this is for emergency use (i.e. dealing with a dangerous disease), done by her-/himself (which indicates self-responsibility for correct intake) as a pre-emptive treatment (i.e. highly active medical compounds which might cause side effects as well). This kind of strategy implies that the traveller needs to be trained and should get a written information on the initial symptoms (when to start the drug), the prescribed drug (i.e. how to take it: dosing, interval, duration, cofounding factors and additional aspects like impact of food on absorption and possible side effects) and what to do in case of vomiting. And most importantly to go and see a doctor as soon as possible no matter whether the symptoms improved after taking the drug since this might be due to unspecific actions of the drug, to the natural course of a disease other than malaria (e.g. a bacterial sepsis) or might camouflage partially resistant malaria parasites, respectively. Under the bottom-line if given in a correct way for the counsellor giving instructions for EST are more time consuming by far as compared to providing those for malaria chemoprophylaxis. And the action required, i.e. self-medication based on clinical symptoms is by far more difficult for the traveller. While this is adequately reflected by the wording “emergency self treatment” the expression “stand by” does not mirror this situation in any instance - thus bearing the risk of gross underestimation. To avoid any further misconceptions I propose to eliminate the term “stand by” from all official malaria literature. **IAMAT has already agreed to change all wordings accordingly. For other regions and/or seasons with moderate or low risk6 (in the actual scientific literature there are no clear data how to discriminate these both groups; the API always relates to the risk of the local population and is of limited—if any—value for travellers; regions with a high annual variability between high and low should not be addressed as ‘moderate’ just by calculating the average perennial risk) prophylaxis is limited to IBP. The additional (and frankly spoken most confusing) challenge is whether for these trips drugs for emergency self-treatment (EST) should be recommended or not: If the end of the trip to a non-high-risk region is earlier than the minimal incubation period no additional action is needed. So there is no need to carry drugs for EST, too. If the stay is longer the decision should be based on the accessibility to qualified medical care, which includes exact diagnosis and proper treatment. Proper treatment excludes over-the-counter products that might be fake or of bad quality due to production, shipping or storage. As a result qualified medical care usually is limited to hospitals and officially certified health care centres. Since as to my knowledge not even P. knowlesi (the fastest replicating plasmodial parasite) caused fatal courses of malaria within 24 h from the first (!) signs of infection and the course of disease is comparable to P. falciparum infection this time frame7 could be used for further decisions: if qualified medical services can be provided within 24 h (which is true in general for most of the travellers) no additional action is needed. So there is no need to carry drugs for EST, too. Consequently, EST should be provided only for travellers to remote areas (i.e. when qualified medical services cannot be approached within 24 h) where the malaria risk is (moderate to) low. As a summary + chemoprophylaxis in addition to insect bite prevention should be recommended for (seasonal or perennial) high risk areas (or for travellers with a high risk of complications in case of malaria) + insect bite prevention only if the trip is to regions/in seasons/under conditions with (moderate to) low risk of exposure and shorter than 6 days or for longer trips if medical care can be accessed within 24 h and + EST for longer trips to remote areas (i.e. with no access to qualified medical care within 24 h) with (moderate to) low malaria risk. Since, we are dealing with a potentially life threatening disease adherence to each detail of this decision-making process is crucial. Anyhow a scheme based on three basic decisions (risk of exposure—duration of stay—access to qualified medical care: flowchart see Figure 1) should make this complex challenge simple enough to provide satisfying and uniform guidance for counselling nurses, pharmacists and doctors and accomplish the goal to improve adherence of travellers to the recommendations given.8,9 Malaria prevention in travellers Conflict of interest: None declared.

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