Detection of naturally acquired, strain-transcending antibodies against rosetting Plasmodium falciparum strains in humans.

Strain-transcending antibodies against virulence-associated subsets of P. falciparum-infected erythrocyte surface antigens could protect children from severe malaria. However, the evidence supporting the existence of such antibodies is incomplete and inconsistent. One subset of surface antigens associated with severe malaria, rosette-mediating Plasmodium falciparum Erythrocyte Membrane Protein one (PfEMP1) variants, cause infected erythrocytes to bind to uninfected erythrocytes to form clusters of cells (rosettes) that contribute to microvascular obstruction and pathology. Here, we tested plasma from 80 individuals living in malaria-endemic regions for IgG recognition of the surface of four P. falciparum rosetting strains using flow cytometry. Broadly reactive plasma samples were then used in antibody elution experiments in which intact IgG was eluted from the surface of infected erythrocytes and transferred to heterologous rosetting strains to look for strain-transcending antibodies. We found that seroprevalence (percentage of positive plasma samples) against allopatric rosetting strains was high in adults (63%-93%) but lower in children (13%-48%). Strain-transcending antibodies were present in nine out of eleven eluted antibody experiments, with six of these recognizing multiple heterologous rosetting parasite strains. One eluate had rosette-disrupting activity against heterologous strains, suggesting PfEMP1 as the likely target of the strain-transcending antibodies. Naturally acquired strain-transcending antibodies to rosetting P. falciparum strains in humans have not been directly demonstrated previously. Their existence suggests that such antibodies could play a role in clinical protection and raises the possibility that conserved epitopes recognized by strain-transcending antibodies could be targeted therapeutically by monoclonal antibodies or vaccines.

Use of a modified SCORFAD scale to define localised reaction patterns associated with a flea burden in cats.

BACKGROUND: The SCORing Feline Allergic Dermatitis scale (SCORFAD) is a validated dermatological scale assessing reaction patterns associated with allergic dermatitis in cats. While no pathognomonic reaction pattern is recognised with flea allergy dermatitis (FAD), miliary dermatitis is more common. HYPOTHESIS/OBJECTIVE: This study aimed to document regional cutaneous reaction patterns of cats with fleas using a modified SCORFAD (mSCORFAD). ANIMALS: In total, 142 owned cats from West Central Florida enrolled over three study periods. To be included, each cat and household environment had five or more fleas on Day (D)0. MATERIALS AND METHODS: Cats were examined on D0, D7, D14, D21, D28, D44, D56 and D80. On D0 they were treated with an isoxazoline and treatment continued through the study. Ten body regions were assessed using mSCORFAD to give a regional score for each of four reaction patterns. These were compared using the Wilcoxon rank sum test. RESULTS: At D80 there was an 80% reduction in total mSCORFAD representing clinical response to ectoparasite control only. The most commonly affected region was the ventral abdomen with a mean mSCORFAD score of 1.8 (95% confidence interval = 1.5-2.1) compared with other body regions (p < 0.01). The most common reaction patterns were self-induced alopecia on the ventral abdomen and miliary dermatitis in the cervical region (p < 0.0001). CONCLUSIONS AND CLINICAL RELEVANCE: The mSCORFAD suggests that self-induced alopecia on the ventral abdomen and miliary dermatitis in the cervical region is more strongly associated with a flea burden in cats.

Comparative speed of kill provided by lotilaner (Credelio™), sarolaner (Simparica Trio™), and afoxolaner (NexGard™) to control Amblyomma americanum infestations on dogs.

BACKGROUND: Canine acaricides with rapid onset and sustained activity can reduce pathogen transmission risk and enhance pet owner experience. This randomized, complete block design, investigator-masked study compared the speed of kill of Amblyomma americanum provided by three monthly-use isoxazoline-containing products. METHODS: Eight randomized beagles per group were treated (day 0), per label, with sarolaner (combined with moxidectin and pyrantel, Simparica Trio™), afoxolaner (NexGard™), or lotilaner (Credelio™), or remained untreated. Infestations with 50 adult A. americanum were conducted on days - 7, - 2, 21, and 28, and tick counts were performed on day - 5 (for blocking), and at 4, 8, 12, 24, 48, and 72 h following treatment and subsequent infestations. Efficacy calculations were based on geometric mean live tick counts. A linear mixed model was used for between-group comparisons. RESULTS: On day 0, only lotilaner significantly reduced an A. americanum infestation by 12 h (43.3%; P = 0.002). Efficacy of lotilaner and afoxolaner at 24 h post-treatment was 95.3% and 97.6%, respectively, both significantly different from sarolaner (74%) (P = 0.002, P < 0.001, respectively). On day 21, at 12 h postinfestation, lotilaner efficacy (59.6%) was significantly different from sarolaner (0.0%) (P < 0.001) and afoxolaner (6.3%) (P < 0.001). At 24 h, lotilaner efficacy (97.4%) was significantly different (P < 0.001) from sarolaner and afoxolaner (13.6% and 14.9%, respectively). On day 28, at 12 h postinfestation, lotilaner efficacy (47.8%) was significantly different from sarolaner (17.1%) (P = 0.020) and afoxolaner (9.0%) (P = 0.006). At 24 h, lotilaner efficacy (92.3%) was significantly different from sarolaner 4.9% (P < 0.001) and afoxolaner (0.0%) (P < 0.001). Speed of kill for sarolaner and afoxolaner, but not lotilaner, significantly declined over the study period. Following reinfestation on day 28, neither sarolaner nor afoxolaner reached 90% efficacy by 48 h. By 72 h, sarolaner efficacy was 97.4% and afoxolaner efficacy was 86.3%. Only lotilaner achieved ≥ 90% efficacy by 24 h post-treatment and 24 h postinfestation on days 21 and 28. Time to ≥ 90% efficacy following new infestations consistently occurred 24-48 h earlier for lotilaner compared with sarolaner or afoxolaner. CONCLUSIONS: Credelio (lotilaner) has a more rapid onset of acaricidal activity against A. americanum than Simparica Trio (sarolaner-moxidectin-pyrantel) and NexGard (afoxolaner). Only lotilaner's speed of tick kill is sustained throughout the dosing period.

Differential burdens of blacklegged ticks (Ixodes scapularis) on sympatric rodent hosts.

In the United States, there has been a steady increase in diagnosed cases of tick-borne diseases in people, most notably Lyme disease. The pathogen that causes Lyme disease, Borrelia burgdorferi, is transmitted by the blacklegged tick (Ixodes scapularis). Several small mammals are considered key reservoirs of this pathogen and are frequently-used hosts by blacklegged ticks. However, limited studies have evaluated between-species host use by ticks. This study compared I. scapularis burdens and tick-associated pathogen presence in wild-caught Clethrionomys gapperi (southern red-backed voles) and Peromyscus spp. (white-footed mice) in forested areas where the habitat of both species overlapped. Rodent trapping data collected over two summers showed a significant difference in the average tick burden between species. Adult Peromyscus spp. had an overall mean of 4.03 ticks per capture, while adult C. gapperi had a mean of 0.47 ticks per capture. There was a significant association between B. burgdorferi infection and host species with more Peromyscus spp. positive samples than C. gapperi (65.8% and 10.2%, respectively). This work confirms significant differences in tick-host use and pathogen presence between sympatric rodent species. It is critical to understand tick-host interactions and tick distributions to develop effective and efficient tick control methods.