This study was designed to identify whether local transmission of malaria within countries of Latin America reflected the pattern and trends of malaria acquired by travellers from ten developed countries. During 2004, twenty one PAHO countries with active malaria programs examined 6.7 million slides, of which 13% were positive for malaria, three quarters of them were speciated as P. vivax infections in an "at risk" population of 262 million [3]. The detailed information collected in Central and South American countries and presented by PAHO [3, 2, 13] provides evidence of a clear trend of declining transmission across most of the countries, most notably in Brazil, which reported a 56% decrease in the high incidence regions, attributed to malaria control programmes initiated in 2000. The total number of tourists visiting Latin America is not known precisely, but the World Tourism Organization [4] estimates there were 16 million international tourist arrivals to South America, with a 16% increase from 2003. Central America, during 2004, received 5.7 million inbound visitors, a 17% growth in arrivals over the previous year. The main country sources of imported malaria were Honduras, French Guiana, Guatemala, Mexico and Ecuador, from where there were 1,066 imported cases over five years, accounting for 64% of all imported cases from Latin America, 75% were non-falciparum malaria. There are a number of important limitations that need to be understood when reflecting on the findings. Local transmission reported to PAHO may be inconsistent and regions not reporting or not diagnosing cases may be interpreted as no malaria transmission. The imported malaria cases collected nationally use different reporting methods and are of varied quality. The denominators used in the analysis are again of different capture methods. The USA, France and the Netherlands record the number of citizens departing to a destination while in the UK samples of departing passengers are interviewed, capturing destination, duration of travel and reason for travel. The pattern of travel through the regions by western travellers is not recorded in the denominator data or through the malaria case reports, and therefore the proportion visiting high transmission regions are unknown.
Although a number of regions within Peru and Brazil have an API above 50/1000 cases/year the actual numbers of malaria cases in returning travellers is low, a total of 145 cases over five years, and in 2005, there were only 30 cases of which three were P. falciparum. Asymptomatic carriage in natives living in the Peruvian Amazon near Iquitos is estimated to be less than 10% and the entomological inoculation rate for the Amazonas region reported as 10–20 annually [18]. The small numbers of travel associated cases from Peru are unlikely to be a result of widespread use of chemoprophylaxis. Currie and colleagues [19] examined prophylaxis use in tourists departing Lima, Peru. Of the 1226 travellers interviewed, 43% were from the USA. Nearly three quarters had visited only Peru and 54% had visited a malarious region (as defined by CDC). Of these around half had taken regular chemoprophylaxis (42% atovaquone/proguanil). During that year (2003) there were 10 (six P vivax) imported malaria cases from Peru. The highest numbers of imported malaria cases, over the 5-year study period, were of P. vivax from Honduras, Guatemala, Ecuador and French Guiana. Despite an increase in local transmission in Honduras, total travel associated cases declined by 20% suggesting that there is no correlation between the two trends. The rates in US and UK travellers to the whole region (excluding Mexico) reveal a similar incidence of 0.3 and 0.8 per 10,000 visits despite an increasing volume of travel over the study (237,526 UK and 4.5 million US travellers in 2005).
Mexico had an estimated 20 million visits by US citizens in 2004. Visits to malaria endemic regions of Mexico are unknown, but are likely to be small. There was a fall in imported malaria to the U.S. from Mexico, from 30 case reports in 2000 to 14 in 2005.
Current chemoprophylaxis policies recommend prophylaxis for high risk regions [20–22], but many of these regions (as shown in Table 2 have a declining risk for indigenous populations). The inconsistency between focal high transmission areas in countries popular with western travellers and small numbers of travel associated malaria is worth exploring. Significant numbers of travellers may not be using prophylaxis during their travel and the departure lounge suggests approximately 50% of visitors will be using chemoprophylaxis. Other countries visited by significant numbers of tourists as reported by WTO in 2005 – Peru, (1.5 million) Brazil (5.4 million), Guatemala (1.3 million) had small numbers of cases and low rates of malaria. Although these countries have areas of high transmission, the major parts of these countries have no malaria transmission. It would appear that most visitors to these countries are at low or no risk of acquiring infection, whatever their journey and destination within the country.
Protection against P. vivax, disease despite using the most widely available regimens is marginal [23–25], as only the primary attack [23] is aborted. Most clinical episodes develop some months after infection when travellers have returned home and are unlikely to be missed through routine reporting systems. Severe adverse events leading to stopping medication during chemoprophylactic drug use were reported in 3–8% of users whilst mild to moderate adverse events were reported by 32%–45% of users [26]. In the 423,416 visitors from reporting countries to Peru in 2003 [4] approximately 25% (105,000 or 50% of those visiting a malarious region) visitors were using chemoprophylaxis as identified by the airport departure lounge study [19]. During that year, 10 (two P. falciparum) cases of malaria were reported in nine study countries after visiting Peru. Using the minimal proportion of users encountering adverse events from the popular prophylaxis regimens [26] an estimated 34,000 travellers would have suffered an adverse event related to chemoprophylaxis use. The risk of adverse events for visitors to Peru and other regions are likely to be significantly higher than avoided infections particularly of benign P. vivax malaria under current policy recommendations. Unless chemoprophylaxis prescribing is significantly reduced, current recommendations are likely to be causing more harm than benefit.
Policy change
Despite its limitations, this study suggests that the risk of adverse events from chemoprophylaxis is likely to be significantly higher than the risk of acquiring malaria in the most popular tourist destinations in Central and South America. Although current national and international policy focuses on chemoprophylaxis for focal, highly endemic malaria transmission regions in countries which have overall low API's, this strategy appears to provide limited benefit as travellers appear to have a low malaria attack rate and will acquire P. vivax rather than P. falciparum infection. The benefit of chemoprophylaxis in preventing the former is unclear. An alternate strategy adopted by a number of European countries, for example Switzerland [27], is to provide travellers with emergency standby treatment in case of malaria symptoms during travel. This has the benefit of dealing with a life threatening attack of falciparum malaria, but avoiding adverse events associated with excessive chemoprophylaxis. It has the disadvantage of cost, as all travellers will have to purchase therapy. Two of the highest risk countries reported by PAHO – French Guiana, and Surinam, correlated to countries where visitors were at high risk of malaria and chemoprophylaxis would be appropriate for travel to risk areas in these countries. There appears to be no clear benefit and significant potential for toxicity in recommending chemoprophylaxis for visitors to Mexico, where the highest API is less than 0.07 for local residents and 20 imported cases annually. Despite the low or falling risk of malaria, the continued use of bite prevention measures remains important as these are effective, safe and have the added benefit of reducing other vector borne diseases.