The role of spore morphology in horizontal transmission of a microsporidium of Daphnia

The microsporidian parasite Hamiltosporidium tvaerminnensis can infect Daphnia magna both horizontally (through environmental spores) and vertically (through parthenogenetic and sexually produced eggs). The spores of H. tvaerminnensis come in three distinguishable morphologies, which are thought to have different roles in the transmission of the parasite. In this study, we examined the role of the two most common spore morphologies (i.e. oval-shaped spores and pear-shaped spores) in horizontal transmission of H. tvaerminnensis. To this end, we infected hosts with solutions consisting of either mostly oval- or mostly pear-shaped spores, and quantified infection rates, parasite-induced host mortality and mean number of parasite spores produced per host. We found that spore morphology by itself did not influence infection rates and parasite-induced host mortality. Instead, host clone and parasite isolate interacted with spore morphology in shaping infection outcome and mortality. Thus, there appear to be strong genotype-by-genotype (G × G) interactions in this system. While there is no dispute that H. tvaerminnensis can transmit both vertically and horizontally, our findings do not support theoretical predictions that different spore morphologies hold different roles in horizontal transmission of H. tvaerminnensis.

Early Curative Applications of the Aminoglycoside WR279396 on an Experimental Leishmania major-Loaded Cutaneous Site Do Not Impair the Acquisition of Immunity

ABSTRACT Topical therapy is an attractive approach for the treatment of L eishmania major cutaneous leishmaniasis (CL). WR279396, an expanded-spectrum aminoglycoside ointment, is now in phase 3 trials. Because the application of a cream is easier than the injection of pentavalent antimony, many patients with CL will likely be treated with WR279396 soon after the onset of a lesion. However, this new therapeutic approach may impair the acquisition of immunity. We evaluated the impact of early topical therapy on acquired immunity in an optimized mouse model of L. major-induced CL. The efficacy of the WR279396 ointment in this model has been established previously. Acquired immunity was defined as the absence of lesions upon reinoculation of the same parasite isolate at a different skin site. Bioluminescence-based follow-up of luciferase-expressing L. major loads was also performed. In this model, the control of L. major loads at the initial inoculation site and the acquisition of immunity are simultaneous (day 22 postinoculation). The clinical and parasitological efficacies of WR279396 applied as early as day 11 postinoculation, i.e., during the L. major multiplication phase, did not impair the acquisition of immunity to a second L. major challenge. This is reassuring from the perspective of the wide deployment of WR279396-based therapy in foci where L. major is endemic.

Antibodies to Variant Antigens on the Surfaces of Infected Erythrocytes Are Associated with Protection from Malaria in Ghanaian Children

ABSTRACT Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a variant antigen expressed on the surface of infected erythrocytes. Each parasite genome contains about 40 PfEMP1 genes, but only 1 PfEMP1 gene is expressed at a given time. PfEMP1 serves as a parasite-sequestering ligand to endothelial cells and enables the parasites to avoid splenic passage. PfEMP1 antibodies may protect from disease by inhibiting sequestration, thus facilitating the destruction of infected erythrocytes in the spleen. In this study, we have measured antibodies in Ghanaian children to a conserved region of PfEMP1 by enzyme-linked immunosorbent assay and antibodies to variant molecules on erythrocytes infected with field isolates of P. falciparum by flow cytometry. Based on close clinical monitoring, the children were grouped into those who did (susceptible) and those who did not (protected) have malaria during the season. The prevalences of antibodies to both the conserved PfEMP1 peptide and the variant epitopes were greater than 50%, and the levels of immunoglobulin G (IgG) correlated with age. The levels of antibodies to both the conserved peptide and the variant epitopes were higher in protected than in susceptible children. After correcting for the effect of age, the levels of IgG to variant antigens on a Sudanese and a Ghanaian parasite isolate remained significantly higher in protected than in susceptible children. Thus, the levels of IgG to variant antigens expressed on the surface of infected erythrocytes correlated with protection from clinical malaria. In contrast, the levels of IgG to a peptide derived from a conserved part of PfEMP1 did not correlate with protection from malaria.

Antibody Recognition of Plasmodium falciparum Erythrocyte Surface Antigens in Kenya: Evidence for Rare and Prevalent Variants

ABSTRACT Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is the name given to a family of parasite proteins that are inserted into the infected erythrocyte surface. Studies using agglutination assays have shown previously that PfEMP1 epitopes are extremely diverse. In a study in Kenya, 21 parasite isolates, including nine from children with severe malaria, were tested for agglutination by 33 pairs of plasma, 21 of which were from the corresponding children. Each plasma pair consisted of a sample taken at the time of disease (acute) and one taken 3 weeks later (convalescent). In agreement with previous studies, infection was generally followed by the induction of antibodies specific to the homologous parasite isolate. In addition however, the results show that (i) some isolates were agglutinated very frequently by heterologous plasma; (ii) unexpectedly, these frequently agglutinated isolates tended to be from individuals with severe malaria; (iii) an inverse relationship existed between the agglutination frequency of each parasite isolate in heterologous plasma and the agglutinating antibody repertoire of the homologous child at the time of disease; and (iv) A 3-month-old child apparently still carrying maternal antibodies was infected by a rarely agglutinated isolate. This child’s plasma agglutinated all isolates at the time of disease, apart from the homologous isolate. These results support the idea that preexisting anti-PfEMP1 antibodies can select the variants that are expressed during a new infection and may suggest the existence of a dominant subset of PfEMP1 variants.