Microstructured Blood Vessel Surrogates Reveal Structural Tropism of Motile Malaria Parasites.

Plasmodium sporozoites, the highly motile forms of the malaria parasite, are transmitted naturally by mosquitoes and traverse the skin to find, associate with, and enter blood capillaries. Research aimed at understanding how sporozoites select blood vessels is hampered by the lack of a suitable experimental system. Arrays of uniform cylindrical pillars can be used to study small cells moving in controlled environments. Here, an array system displaying a variety of pillars with different diameters and shapes is developed in order to investigate how Plasmodium sporozoites associate to the pillars as blood vessel surrogates. Investigating the association of sporozoites to pillars in arrays displaying pillars of different diameters reveals that the crescent-shaped parasites prefer to associate with and migrate around pillars with a similar curvature. This suggests that after transmission by a mosquito, malaria parasites may use a structural tropism to recognize blood capillaries in the dermis in order to gain access to the blood stream.

Geometrical model for malaria parasite migration in structured environments.

Malaria is transmitted to vertebrates via a mosquito bite, during which rodlike and crescent-shaped parasites, called sporozoites, are injected into the skin of the host. Searching for a blood capillary to penetrate, sporozoites move quickly in locally helical trajectories, that are frequently perturbed by interactions with the extracellular environment. Here we present a theoretical analysis of the active motility of sporozoites in a structured environment. The sporozoite is modelled as a self-propelled rod with spontaneous curvature and bending rigidity. It interacts with hard obstacles through collision rules inferred from experimental observation of two-dimensional sporozoite movement in pillar arrays. Our model shows that complex motion patterns arise from the geometrical shape of the parasite and that its mechanical flexibility is crucial for stable migration patterns. Extending the model to three dimensions reveals that a bent and twisted rod can associate to cylindrical obstacles in a manner reminiscent of the association of sporozoites to blood capillaries, supporting the notion of a prominent role of cell shape during malaria transmission.

Typical and atypical pattern of pulmonary sarcoidosis at high-resolution CT: relation to clinical evolution and therapeutic procedures.

AIM: This study was done to evaluate the importance of high-resolution CT (HRCT) in defining pattern and extent of disease and establishing the clinical and therapeutic pathway in sarcoidosis. MATERIALS AND METHODS: A retrospective analysis of 56 patients with pulmonary involvement of sarcoidosis was performed. Two groups were identified: 39 patients exhibiting a typical HRCT pattern and 17 patients with an atypical pattern. Inclusion criteria were the presence of radiological documentation (HRCT) of disease, clinical and radiological follow-up of 1 year and the beginning of any therapy within 1 month from the diagnosis. RESULTS: Among subjects not receiving therapy, the comparison between the two groups showed that the radiological findings remained stable in subjects with a typical pattern, while they worsened in more than 70% of cases with atypical appearance. Therapy was more effective in patients with a typical pattern. Recurrences occurred in both groups, but more often in patients with a typical pattern. One patient not receiving treatment experienced clinical worsening. Re-evaluation of HRCT within 1 year revealed no correlation between clinical deterioration and radiological changes. CONCLUSIONS: The findings of this study suggest that persistence of the inflammatory process rather than the radiological pattern at onset is a prognostic factor for recurrence.