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| Year : 2020 | Volume
: 10
| Issue : 1 | Page : 65-67 |
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Migratory parasites esp larva migrans and its changing patterns
| Date of Submission | 26-Feb-2020 |
| Date of Decision | 27-Feb-2020 |
| Date of Acceptance | 27-Feb-2020 |
| Date of Web Publication | 20-May-2020 |
Correspondence Address:
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/tp.TP_20_20
How to cite this article:
. Migratory parasites esp larva migrans and its changing patterns. Trop Parasitol 2020;10:65-7 |
Professor Celia Holland is currently working as Professor of Parasitology in the Department of Zoology, School of Natural Sciences, Trinity College, Dublin, Ireland. She has worked as Postdoctoral Research Fellow, in Cornell University, USA. Prof Holland is a parasitologist with a particular interest in the relative contributions of host exposure and susceptibility to parasite intensity from an epidemiological standpoint. This encompasses nutritional, immunological, genetic and behavioural characteristics of the host and aspects of its environment. She has studied these mechanisms in a number of parasite species, in both humans and other animals, in the field and the laboratory. Professor Holland has served as President of Irish Society for Parasitology, also as Secretary General European Federation of Parasitology and Director of Research, School of Natural Sciences, Trinity College. She has served as invited member of WHO Guidelines development group (GDG) – deworming and also has served as invited expert WHO advisory panel on Parasitic diseases (5 invitations). Professor Holland has received many awards as an acknowledgement for her contributions. She has received the imperial Group Studenship, University of Cambridge, Elected fellow of Trinity college, Linnean Society, Royal Irish Academy Council and also nominated as Vice president and has also received the Lifetime achievement (teaching) award, Trinity College. She has a keen interest in research and has published more 124 articles and has worked on 46 funded grants and was the Editor of Parasitiology, Cambridge journal.
1. As an eminent member of various prestigious organizations, please share your views and experiences in parasitology.
Working in parasitology and collaborating with other scientists in my field has been the joy of my life. Despite the ups and downs of seeking research funding, trying to publish good papers and other challenges, I would recommend such a career choice with great enthusiasm. Recently, I have had the honor to interact a little with Professor William C. Campbell who won the Nobel Prize for Physiology or Medicine for his work on ivermectin. He, in fact, graduated from the same Department of Zoology where I now work. He describes very well the so-called “light-bulb moment” whereby he witnessed the parasitologist, Professor J. D. Smyth, dissecting a fish and removing a tapeworm from it. From then on, as he says he was “hooked” on the subject of parasitology. I have also greatly enjoyed teaching medical parasitology to medical students with a particular focus on neglected tropical disease (NTDs). I am always pleased to find at least one student who has decided to gravitate toward being a clinician in infectious diseases. I have also had the privilege to be involved with some work for the WHO including assisting in developing guidelines for the treatment of soil-transmitted helminths. This gave me an opportunity to interact with scientists from a wide range of disciplines and from many different countries. This type of decision-making is of course complex and requires continuous evaluation as we move toward the possible elimination of such infections.
2. As Toxocara is one of your specialized areas of research, please shed some light on its current trends.
The number of publications on Toxocara and toxocariasis continues to increase including a number of important, recent reviews. This suggests that interest in this parasite remains high. However, this interest is not matched by increases in research funding. We still struggle to obtain research funding on the topic– certainly my recent attempts to secure funding on the relationship between Toxocara and brain involvement with consequent behavioral and inflammatory changes has fallen on stony ground despite, I believe, its considerable importance! In addition, as outlined in my knowledge gaps paper, we require integrated data on the epidemiology of Toxocara in humans, other animals, and in the environment in order to assess its true public health significance.
3. What are your other areas of interest in parasitology research?
I am also interested in Ascaris and having worked extensively in the field in collaboration with my colleague, Professor S. O. Asaolu. More recently, we have moved to a more experimental approach utilizing a mouse model of early infection (utilizing a susceptible and resistant strain of inbred mice to model observed predisposition in humans). I also have ecological interests, and we have recently started research on the importance of parasites in invasive species. We utilize the bank vole (invader) and the native woodmouse as our study system. This is a very useful system as it reflects the process of invasion without any control measures. (See some publications listed below).
4. Please share your work experience in cerebral toxocariasis and its link between brain involvement, behavior, and immune response.
Yes, we have explored various aspects of Toxocara brain involvement in a mouse model. We concluded that a fruitful line of inquiry is suggested by the evidence for upregulation of both pro-inflammatory and inflammatory cytokines coinciding with peak levels of Toxocara larvae in the brain. However, as of now, these changes in immune parameters have not been correlated with observed behavioral changes or defects in the same experimental animals. Therefore, if simultaneous measurements of larval number, behavior, and immune response markers could be made at a number of time points postinfection, this would greatly enhance our understanding of the implications of cerebral toxocariasis.
5. Over the past years, many invasive parasites like Toxoplasma gondii has been explored over its role in central nervous system conditions like Alzheimer's disease. Does cerebral toxocariasis have a role in neurodegenerative diseases?
We suspect that Toxocara may play a role in neurodegenerative disease but do not yet have sufficient data at present to draw a firm conclusion. My colleague, Professor Fan et al. observed BI-associated biomarkers (BIABs) associated with brain injury, including glial fibrillary acidic protein, transforming growth factor-β1, S100B, tissue transglutaminases, β amyloid precursor proteins (A β PP), and Neurofilament light chain (NF-L), and p-tau, in the brains of ICR (Institute of Cancer Research, USA) outbred Toxocara-infected mice. In addition, abnormal blood–brain barrier (BBB) permeability and cerebral injury increased over the duration of the infection, although the changes appeared to be unrelated to larval numbers in the brain.
Prof Fan et al. concluded that such observations underline an urgent need to further elucidate the link observed between enhanced BIAB expression or abnormal BBB permeability and behavioral alterations in experimental cerebral toxocariasis. He also indicated that enhanced expression of BIABs, which may be deleterious to the brain, might be explained by a ubiquitin-proteasome system (UPS) dysfunction that is unable to degrade misfolded, damaged, or unwanted proteins with the potential to form toxic aggregates in the brains of mice infected with Toxocara canis. It has been hypothesized that the presence of deposits consisting of ubiquitylated proteins in diseased neurons (found in many hereditary and sporadic neurodegenerative diseases) is suggestive of a link between pathogenesis and UPS dysfunction, e.g., in AD, and whether cerebral infection by T. canis has damaging effects that increase the risk of cerebral toxocariasis progressing to neurodegenerative disorders should not be completely disregarded.
6. Larva migrans is an underestimated problem as well as a great mimicker of many infections. What is your take on Toxocara spp. infections and its association with allergic asthma or allergic manifestations?
Toxocara infection has been linked with allergic diseases such as asthma and allergic rhinitis. However, this association is not always found depending upon the specific characteristics of the study undertaken. Whether these individuals develop asthma later in life remains controversial, and some authors have suggested that they may, in fact, be protected from atopic asthma as a result of immunoregulatory responses induced by infection.
7. Why is drug research in parasitology lagging when compared to development of antibacterial or antiviral agents?
I am not an expert on this area, but in my view, this may, in part, be a consequence of neglect, i.e., some infections may not be regarded as of comparative importance in public health terms compared with large-scale outbreaks of viral disease as we are experiencing at present. Chagas disease is an interesting example in that of the two drugs that are used to treat the disease, one has significant side effects and neither drug were developed specifically for Chagas. This has led to Peter Hotez (2017) in his recent paper on “Ten failing in global NTDs” to highlight the need to develop new drugs for the treatment of this highly debilitating disease that if left untreated, can develop into life-changing morbidities such as cardiomyopathy.
8. You have been working all over the world on various research aspects. What is your opinion on research approach in developing countries when compared to developed nations?
Having worked with excellent scientists, such as Professor S. O. Asaolu of Obafemi Awolowo University, based in Nigeria over many years, I am keenly aware of some of the obstacles that scientists working in developing countries face. Furthermore, securing funding for research based in the field in developing countries remains challenging. However, the need to support such scientists, particularly in a subject such as parasitology is absolutely essential if we are going to make the advances required, particularly in the areas of parasite control, enhanced monitoring, and the collection of high-quality epidemiological data.
9. In your opinion, what newer perspectives can be addressed in these programs for eliminating parasitic infections of zoonotic origin? Should the human programs work in co-ordination with the veterinary programs and how?
Yes, undoubtedly, we require a one health approach to tackle important zoonotic infections whereby collaboration between clinicians both medical and veterinary, public health experts, and those with expertise in environmental aspects work in tandem. This is not always easy to achieve and requires generous funding. This is something I advocated in my Toxocara knowledge gaps paper (see reference list below).
10. Please share a few words of advice for the budding scientists in the field of parasitology.
As outlined, parasitology is a wonderful subject partly because it encompasses so many aspects from molecular biology to social science and economics. Therefore, despite increased emphasis on specialization, it is possible to branch out and change as your career develops. You also have the opportunity to work on organisms that have profound impacts on human and animal health in addition to, as we increasingly realize, entire ecosystems. Also, do not shy away from working on neglected parasites as there is now an increasing focus on the so-called NTDs.
In a paper by John Janovy (2014), he stated the following “As I look over the younger generation of parasitologists, the successful ones make me think that a parasitologist is like a coyote. He or she is cunning, resourceful, adaptable, omnivorous, albeit in an intellectual sense, not easily frightened, and able to survive in seemingly hostile environments. Such coyotes are beautiful in their own way, but most of all they can, and will, “'sing” through the night, delivering elegant and insightful stories about parasitism, the most common way of life on Earth, in a language, and for reasons, that the lesser creatures simply cannot seem to understand.” [1, 2, 3, 4, 5, 6, 7, 8, 9];
 References | |  |
| 1. | Hotez PJ. Ten failings in global neglected tropical diseases control. PLoS Negl Trop Dis 2017;11:e0005896.  |
| 2. | Janovy J Jr. Why American higher education needs parasitologists. J Parasitol 2014;100:700-7. |
| 3. | Liao CW, Fan CK, Kao TC, Ji DD, Su KE, Lin YH, et al. Brain injury-associated biomarkers of TGF-beta1, S100B, GFAP, NF-L, tTG, AbetaPP, and tau were concomitantly enhanced and the UPS was impaired during acute brain injury caused by Toxocara canis in mice. BMC Infect Dis 2008;8:84. |
| 4. | Fan CK, Holland CV, Loxton K, Barghouth U. Cerebral toxocariasis: Silent progression to neurodegenerative disorders? Clin Microbiol Rev 2015;28:663-86. |
| 5. | Stuart P, Paredis L, Henttonen H, Lawton C, Ochoa Torres CA, Holland CV. The hidden faces of a biological invasion: Parasite dynamics of invaders and natives. Int J Parasitol 2020.pii: S0020-7519 (20) 30003-5. |
| 6. | Deslyper G, Holland CV, Colgan TJ, Carolan JC. The liver proteome in a mouse model for Ascaris suum resistance and susceptibility: Evidence for an altered innate immune response. Parasit Vectors 2019;12:402. |
| 7. | Deslyper G, Doherty DG, Carolan JC, Holland CV. The role of the liver in the migration of parasites of global significance. Parasit Vectors 2019;12:531. |
| 8. | Rostami A, Riahi SM, Holland CV, Taghipour A, Khalili-Fomeshi M, Fakhri Y, et al. Seroprevalence estimates for toxocariasis in people worldwide: A systematic review and meta-analysis. PLoS Negl Trop Dis 2019;13:e0007809. |
| 9. | Holland CV. Knowledge gaps in the epidemiology of Toxocara: The enigma remains. Parasitology 2017;144:81-94. |
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