This study analysed the evolution of the antimalarial (P. falciparum anti-trophozoites) antibody titre in non-immune patients suffering from their first P. falciparum malaria episode, which was confirmed by a negative antibody titre in almost all of them
While there is a paucity of papers describing the natural evolution of antimalarial antibodies after a natural infection, relevant research has been done on experimental infection, often in the context of studies aimed at malaria vaccine development.
Recently, Boyle et al. interestingly compared the dynamics of anti-merozoite IgM and IgG following experimentally induced as well as natural malaria infection. The latter, differently from our study population, was mainly composed of children and adults with repeated malaria exposure. Among other interesting findings, they discovered that IgM and a long persistence in both groups, similar to that of IgG, and that IgM in particular were likely to play a protective role by blocking merozoite invasion of erythrocytes in a complement-dependent manner. They also studied a small cohort of 10 Australian returning travellers with a (self reported) first malaria episode, showing again persistence of IgM antibodies in all of them up to 6 months after the infection and no difference in the decline of the latter, compared with IgG, up to 300 days after infection.
The scope of our work was of course different. This was an non-experimental, observational study, using a commercially available anti-P. falciparum IFAT, principally aimed at finding a potential diagnostic (retrospective) role in returning travellers on one side, and at discussing the role of serology as a screening tool in transfusional medicine on the other. The antibodies detected by the test are total antibodies with no distinction between classes, and we have no element to discuss their protective role, that was not among our study objectives. In particular, we cannot state that finding a positive IFAT titre, say, at one year or two after the first (and unique) malaria episode would confer a protection in case of re-exposure, and we can only suppose that this may be partially so, in comparison with a subject with a negative titre.
To the authors’ knowledge this is the first such study published. Virtually all patients became positive during the acute malaria episode, and the positivity, after a sharp increase in titre, persisted for at least one month in the 19 patients who had a follow-up after discharge. Thus a negative test result would virtually rule out a previous P. falciparum malaria in a returning traveller with a recent (i.e. one month or less) diagnosis while traveling, while a positive test would retrospectively confirm malaria. Five patients had already a detetctable antibody titre at their first observation, four at the lowest titre of 20, and one at titre 40. One of them was a (VFR) patient from Africa (Nigeria) who reported no previous malaria history, although a past exposure might have escaped recollection. Unfortunately the last available antibody titre for this patient (at the very high value of 5120) was recorded during hospitalization and no follow-up was available. Although it has been shown that immigrants, even if with a malaria history, tend to lose their semi-immunity after a long stay abroad [11, 12], the dynamic of the antibody response in this group, after a new malaria episode, would be probably different from that in completely naïve patients.
One patient remained negative until the last observation before discharge (5 days after admission). This was a patient with an exceedingly low parasite density, and given the strong negative correlation between the parasite density and the days to positivization, had the patient had a sufficient observation time a positive antibody titre would probably eventually have appeared. This cannot be stated with certainty, though, as he was unfortunately lost to follow-up after discharge. As for the five patients who had already a positive (albeit very weak) antibody titre at their first determination, a possible explanation is a previous, unreported malaria episode, or alternatively this may represent an early positivization (at least for two of them who had both a very high parasite density on admission).
In all patients with a sufficiently long follow-up, the antibody titre reached a peak in about a couple of months and then started declining, with no case of rebound, tending to negativization. This could open interesting perspectives in transfusional medicine. Current rules tend to exclude a donor who has a positive serology, irrespective of the titre. However, a declining titre most probably indicates that malaria infection is no longer present and might be taken as sufficient to re-admit a subject to donation, best if in combination with a sensitive molecular test, and without waiting for a complete negativization that would take a comparatively long time. It is reasonable to assume that chronic carriers of a very low or undetectable parasitemia (who might represent a theoretical risk of transmission through blood donation) would maintain a high antibody titre. This is typically observed in chronic malaria infection . Subjects with a persistently high antibody titre would be automatically excluded from blood donation, moreover they might benefit from an effective antimalarial treatment, even in case of failure to detect circulating plasmodia, antigen or DNA . Of course, a change of the current policy would need more evidence to be suggested, but a periodical serologic testing might be suggested especially for donors with particularly requested blood groups, also considering that serologic tests are available at a reasonable cost.
Study limitations. The sample size, that is a convenience sample based on data availability and is constrained by the retrospective design of the study, might not be sufficient to adequately describe the antibody dynamic over time. However, this study provides a first indication of the trend of antimalarial antibodies after a first, successfully treated malaria episode in non-immune subjects.
The antibody tests were executed with a method (IFAT – BioMérieux) that is no longer available (unfortunately the fabricant has ceased production). It would be interesting to validate the results with other, commercially available (ELISA) tests with the serum specimens from the same patients that are still available in the hospital biobank.