Testing for anti-circumsporozoite and anti-blood-stage antibodies for epidemiologic assessment of Plasmodium falciparum infection in travelers.

Abstract

Abstract. The purpose of this investigation was to assess the role of serology for establishing incidences of Plasmodium falciparum malaria and of exposure to P. falciparum in epidemiologic studies of travelers using chemoprophylaxis. The design was a prospective cohort study involving 548 short-term Dutch travelers to areas endemic for P. falciparum malaria. Sera were collected before departure and, together with the medical history, 2-6 weeks after return. All sera were tested for anti-circumsporozoite (CS) antibodies by an R32tet 32 -ELISA; sera of subjects reporting febrile illness during travel or after return or with anti-CS responses were tested for anti-blood-stage antibodies by an indirect fluorescence antibody test (IFAT). Five subjects (0.9%) reported P. falciparum malaria confirmed by thick blood smear examination (documented cases) and six (1.0%) reported treatment for malaria without a documented diagnosis (presumptive cases). Conversions in the IFAT were detected in six subjects, including all five documented cases and one presumptive case. Anti-CS antibodies were detected in seven subjects (1.3%), including three documented cases and four of 442 subjects with no history of fever or malaria treatment (0.9%). Incidence rates per 1,000 person-months of travel (95% confidence interval) of infection with P. falciparum, whether or not suppressed by chemoprophylaxis, were 16.9 (8-31) for all destinations and 91.6 (33-200) for West Africa. In epidemiologic studies of P. falciparum malaria in travelers, testing for antibodies to blood stages can increase the sensitivity and specificity of case detection; testing for antibodies to sporozoites may be useful for the assessment of exposure to P. falciparum in travelers using chemoprophylaxis, but the sensitivity is limited.In most epidemiologic studies that assess risks of Plasmodium falciparum malaria or efficacies of prophylactic measures in nonimmune travelers, incidences are based retrospectively on cases of malaria that are confirmed by blood slide evaluation.

Specific antibody responses against membrane proteins of erythrocytes infected by Plasmodium falciparum of individuals briefly exposed to malaria

“…Among them, only 2% had experienced a clinical malaria attack [22]. Others have reported that travellers from malaria-free countries can develop antibody response against pre-erythrocytic [20,21] and blood stages [32] P. falciparum antigens without progressing to a symptomatic illness. Thus, the characterization of erythrocytic stage antigens specifically detected by healthy adults shortly exposed to malaria and under chemoprophylaxis could be informative to estimate individual exposure to malaria transmission, and to clarify the mechanisms involved in the development of immune responses after malaria infection.…”

“…Several blood stage antigens have been characterized, and some of them are candidates for vaccine trials (for review [18,19]). Although some studies have assessed the antibody response to pre-erythrocytic antigens in travellers [20-22], seldom data are available concerning the antibody response against blood stage antigens from non-immune healthy adults briefly exposed to malaria transmission, such as travellers or individuals living in area where malaria is under elimination.…”

Compliance with malaria chemoprophylaxis and preventative measures against mosquito bites among Dutch travellers.

“…Compliance regarding protection against mosquito bites was recorded as self-reported use and defined as having applied two or more of the four measures mentioned in the leaflet. (Cobelens et al 1997). Travel destinations were grouped into 5 regions that corresponded to the classification used by the World Health Organization (1991).…”

Update on Rapid Diagnostic Testing for Malaria

“…These methods have included malaria antigen detection using tagged monoclonal antibodies, fluorescence microscopy, flow cytometry, automated analysis of blood cells, quantitative buffy coat inspection, acridine orange staining, serology-antibody detection, molecular amplification methods, and laser desorption mass spectrometry (1,17,21,24,31,40,62,68,82,95). Remote microscopic diagnosis via telemedicine has also been evaluated, but imaging quality and infrastructure requirements pose challenges (67).…”