LifeCycle

The lifecycle of the disease starts with an arthropod (mosquito[1], Simuliidae (blackfly)[2], Tabanid(horsefly)[3], Stomoxys calcitrans(stablefly)[4], or Ceratopogonidae (biting-midge)[7][8]) as a vector of transmission first bites an infected animal and acquires the L1 stage filaria and then later bites another uninfected human at which point the L3 stage filaria escape the arthropods mouth parts, drops to the surface of the potential hosts skin and crawls into the open incision left by that arthropod. The L3 filaria will then reside in the skin for a while and transform into the L4 adult stage filaria within the new host.

In most mammals the adult filaria will produce microfilaria (L1) which will circulate in the blood where they are able to be picked up by the next insect bite. In humans however the microfilaria have not been observed to circulate or at least not in sufficient quantities for microscopic examination to help diagnose the disease.

HDRI Theory: There have however been many observations in specific case studies where the aspirated fluids from skin/tissue nodules where microfilaria [5][6] have been observed. It is believed that these microfilaria were present due to the nature of the skin/tissue nodules acting to protect the inner walled off tissues from the human immune system which would have otherwise killed off the microfilaria. HDRI hopes to determine if this is actually the case because of the immunological consequences of such an immune response could drive morbidity in several significant ways.

Because there are no circulating microfilaria in humans the specific parasites have entered a host which is an evolutionary dead end as any microfilaria will not have the chance to find a new host. This of course does not mean that the host is going to fare any better than any other host. There are likely significant stresses on the human immune system as Dirofilaria has been titled the “Masers of Immune Regulation”[9][10][11] for a reason.

While the human as a host may be a dead end as far as Dirofilaria reproduction is concerned, it is clearly not an inconsequential disease as far as the host is concerned. There is all manner of morbidity that will follow as the senescence of their immune system degrades as their immune system response is slowly eroded away over time. Dirofilaria is not a pleasant disease to have.

[1] Riahi, S. M., Yusuf, M. A., Azari-Hamidian, S., & Solgi, R. (2021). Prevalence of dirofilaria immitis in mosquitoes (diptera) – Systematic review and meta-analysis. Journal of Nematology, 53, 1–13. https://doi.org/10.21307/JOFNEM-2021-012

[2] Castillo, J. C., Reynolds, S. E., & Eleftherianos, I. (2011). Insect immune responses to nematode parasites. Trends in Parasitology, 27(12), 537–547. https://doi.org/10.1016/j.pt.2011.09.001

[3] Foil, L. D. (1989). Tabanids as vectors of disease agents. Parasitology Today, 5(3), 88–96. https://doi.org/10.1016/0169-4758(89)90009-4

[4] Baleba, S. B. S. (2021). Water immersion tolerance by larval instars of stable fly, Stomoxys calcitrans, L1758 (Diptera: Muscidae) impairs the fitness performance of their subsequent stages. BMC Ecology and Evolution, 21(1), 1–10. https://doi.org/10.1186/s12862-021-01810-z

[5] Damle, A. S., Iravane Bajaj, J. A., Khaparkhuntikar, M. N., Maher, G. T., Patil, R. V., & Microfilaria, K. (2014). Microfilaria in Human Subcutaneous Dirofilariasis : A Case Report. Journal of Clinical and Diagnostic Research, 8(3), 113–114. https://doi.org/10.5580/11b6.PARTICULARS

[6] Sulekova, L. F., Gabrielli, S., de Angelis, M., Milardi, G. L., Magnani, C., di Marco, B., Taliani, G., Cancrini, G., Angelis, M. de, Milardi, G. L., Magnani, C., Marco, B. di, Taliani, G., & Cancrini, G. (2016). Dirofilaria repens microfilariae from a human node fine-needle aspirate: A case report. BMC Infectious Diseases, 16(1), 10–14. https://doi.org/10.1186/s12879-016-1582-3

[7] Napoli, E., Panarese, R., La Russa, F., Cambera, I., Mendoza-Roldan, J., Otranto, D., & Brianti, E. (2022). Detection of Dirofilaria DNA and host blood-meal identification in Culicoides paolae biting midges. Parasitology, 149(7), 968-972. doi:10.1017/S0031182022000440

[8] Grandi, G., Živičnjak, T., & Beck, R. (2007). Pathogenesis of Dirofilaria spp. infections. In C. Genchi, L. Rinaldi, & G. Cringoli (Eds.), Dirofilaria immitis and D. repens in dog and cat and human infections (Issue February). https://www.esda.vet/media/attachments/2021/08/19/europe1.pdf p183

[9] Maizels, R. M., Balic, A., Gomez-Escobar, N., Nair, M., Taylor, M. D., & Allen, J. E. (2004). Helminth parasites – Masters of regulation. Immunological Reviews, 201, 89–116. https://doi.org/10.1111/j.0105-2896.2004.00191.x

[10] McSorley, H. J., & Maizels, R. M. (2012). Helminth infections and host immune regulation. Clinical Microbiology Reviews, 25(4), 585–608. https://doi.org/10.1128/CMR.05040-11

[11] Maizels, R. M., & Yazdanbakhsh, M. (2003). Immune regulation by helminth parasites: Cellular and molecular mechanisms. Nature Reviews Immunology, 3(9), 733–744. https://doi.org/10.1038/nri1183