Assessing the incidence of infection with Plasmodium falciparum among international travelers.

Abstract

Abstract. Circumsporozoite (CS) antibodies, indicating plasmodial infection but not necessarily development of disease, have been shown to be reliable indicators of transmission in endemic areas. To estimate the actual rate of plasmodial infection, the prevalence of CS antibodies was investigated by an ELISA test system in a selected population of 2,131 travelers returning from areas endemic for malaria who presented to an outpatient clinic without any apparent symptom or clinical sign of malaria. Serum specimens from 104 of the investigated 2,131 patients (4.9%) were found to be positive (titer Ն 6.25 international ELISA units [IEU]). The geometric mean titer of antibody concentrations (IEU) in seropositive patients was 18.64 IEU (95% confidence interval [CI] ϭ 13.15-24.13), while it was 2.1 IEU (95% CI ϭ 1.8-2.4) in seronegative patients. A significantly above average risk for plasmodial infection could be found among travelers to East Africa (risk ratio [RR] ϭ 4.5, P Ͻ 0.001), West Africa (RR ϭ 4.5, P Ͻ 0.001), and Southern Africa (RR ϭ 3.2, P ϭ 0.015), while areas with a comparatively low risk included Central America (RR ϭ 0.86, P Ͻ 0.001 ), the Indian subcontinent (RR ϭ 0.45, P ϭ 0.015), South America (RR ϭ 0.49, P ϭ 0.091), East Asia (RR ϭ 0.68, P ϭ 0.441), West Asia (RR ϭ 0.24, P ϭ 0.099), and Southeast Asia (RR ϭ 0.69, P ϭ 0.094). The results of this study emphasize the importance of adequate malaria chemoprophylaxis in nonimmune travelers to endemic areas. By use of the described method, estimates of the true infection rate of malaria in travelers can be derived for certain areas and the value of prophylactic measures can be demonstrated.The first antigens that are presented to the immune system of a host who is infected with malaria parasites are the surface antigens of plasmodia sporozoite stages expressed shortly after inoculation by the anopheline vector. For a few hours, the immune system of the infected host may produce protective antibodies before the parasites invade liver cells and transform to merozoite stages. Antibodies to sporozoites of Plasmodium spp. are directed against a major surface antigen, the circumsporozoite (CS) protein. Therefore, the detection of significant titers of antibodies to CS protein in a person indicates previous inoculation with sporozoites, not necessarily the development of disease. The immunodominant epitope of the P. falciparum CS protein consists of highly conserved tandem repeats of amino acids (Asn-AlaAsn-Pro ϭ NANP) 1 . Several NANP repeats of variable length have been synthesized using either chemical 1 or recombinant DNA techniques, 2 and a variety of immunoassays have been tested to detect humoral immunity to P. falciparum sporozoites. 1,3 An ELISA kit using a chemically synthesized (NANP) 40 peptide is available. 3 In individuals living in endemic areas, the prevalence and level of sporozoite antibodies have been shown to correlate with the entomologic inoculation rate assessed at the same time for the same area, and the development of detectable titers ...

Prevention of Malaria in Long-term Travelers

“…*Categories of maleria risk are defined based on world regions and country-specific risk levels. 2,7,8,21,94 †The CDC currently does not recommend SBET alone or seasonal chemoprophylaxis for any malarious areas. ‡Rapid diagnostic tests for malaria could become an attractive option in occasional circumstances if technical problems are overcome.…”

“…6 Investigators using Plasmodium falciparum circumsporozoite antibody titers as a measure of malaria exposure found large variation in the proportion of seropositive travelers depending on the area visited: West Africa (22.2%), East Africa (21.8%), and southern Africa (15.4%), in contrast to Central America (4.2%), Southeast Asia (3.4%), East Asia (3.3%), South America (2.4%), and the Indian subcontinent (2.2%). 7 Recent analyses of traveler databases have found the highest risk of acquiring malaria in Africa and Oceania, an intermediate risk in South Asia, and a lower risk in Central America, Southeast Asia, and South America. 2,8 Long-term travelers, particularly occupational travelers such as miners, are at an even higher risk.…”

Evaluation of a malaria antibody enzyme immunoassay for use in blood screening

“…Consequently, exclusion of potentially infected donors is widely used to prevent transfusion transmitted malaria (Reesink 2005). Previous reports suggested that a malaria antibody test is effective in detecting malaria infection in travelers returning from overseas (Knappik et al 2002) and in non-immune visitors to endemic areas after their departure (Jelinek et al 1998, Knappik et al 2002.…”

Malaria

“…Daß solche Annahmen aufgrund des völlig anderen Risikoverhaltens von Reisenden und Einheimischen in Endemiegebieten naturgemäß nur ungenaue Näherungen sein konnten, wurde mangels besserer methodischer Möglichkeiten akzeptiert. Weltweit das höchste Malariarisiko wird für Westafrika südlich der Sahara angenommen (ca 2% aller ungeschützten Reisenden), gefolgt vom wesentlich häu-figer besuchten Ostafrika [8]. Dementsprechend werden für Reisen in diese Gegenden strikte Expositionsprophylaxe und die zusätzliche Einnahme wirksamer Chemoprophylaktika empfohlen [3,13].…”

“…Auch bei Nichtimmunen konnte gezeigt werden, daß das Transmissionsrisiko durch den Nachweis von CSP-Antikörpern geographisch unterschiedlich quantifizierbar ist [6,7,8,10]. Dabei kann eine stattgefundene Malariainfektion auch ohne anschließenden Ausbruch der Erkrankung, z.B.…”