One of the most interesting and fascinating biological characteristics about parasitic organisms is their life cycle. Most parasites have a very specific, complex, yet delicate life cycle. Parasites do not have a straight forward way to mature, reproduce, and survive; most parasites require of specific conditions to thrive. Some parasites require a vector to infect their host, other infect multiple hosts, and other parasites infect only one species. Some parasites reproduce sexually, other asexually, and others reproduce by both sexual and asexual means. The specificity to follow a very unique life cycle is what makes parasites’ survival so intriguing. For decades, scientists have studied life cycles in order to understand the pathogenicity, epidemiology, and biology of the parasites. One would think that by parasites following such unique paths to survive will make them easy to eradicate; and the case is partially true. Research has focused on finding weak points in the parasite’s life cycle in order to truncate its reproduction. An example is the implementation of a very simple measure to reduce transmission of Dracunculus medinensis. The life cycle of D. medinensis, also known as Guinea worm, starts when a person drinks contaminated water with D. medinensis larvae infected copepods. After ingestion, the larvae exit the copepod and migrate to the mammalian’s host intestines where the parasite matures and mates; with the female worm migrating to the skin surface where it forms a blister and upon contact with water, the worm breaks the skin releasing its larvae into the water; which are then eaten by copepods. After understanding the life cycle of this parasite it was possible to start prevention programs to provide safe water. One of the simplest, yet most successful implementation strategies in Guinea worm endemic regions was the use of net filters or cheesecloth to filter the copepods present in the water. The use of cheesecloth has been key in the reduced transmission, and close eradication, of this ancient nematode caused disease. On the other side, other parasites continue to spread and have high infection rates despite years of research on their life cycle and implementation of strategies to halt their life cycle. For example, Plasmodium spp. the causative agent of malaria, infect female mosquitoes as vectors and as intermediate hosts. Despite the use of insecticides to kill the mosquitoes, disease continues to spread and new insecticide resistant mosquitoes have emerged, thus malaria control continues to be a modern science challenge; with the use of bed nets and artemisinin the best approaches to prevent and treat malaria.

Parasitic diseases control rely on different approaches: immunization, therapeutic drugs, education, and public health. All these measures can target different points in a parasite’s life cycle, thus making the study of their biology of such importance in the control of parasitic neglected tropical diseases. On the course of this blog I will dedicate some of the entries on describing the life cycle of different parasites.

In developed countries the presence of parasitic diseases is not common. The exotic causative agents of neglected tropical diseases are only prevalent in zones in rural areas of developing countries. Unlike cancer, diabetes, and hypertension; NTDs are not part of our everyday life, so why should we care about NTDs? First of all we should care about them because we owe to our specie to thrive. These diseases affect the “world’s poorest people” which represents the most marginalized populations. Urbanization has not reach such areas and people do not enjoy from basic things we have for granted such as clean water, food, and electricity. On top of that, infections agents worsen the social situation on these areas. While improvements in the countries themselves need to take place in order to provide better living conditions in NTD endemic regions people outside these regions can dedicate their effort, time, and resources to prevent or cure NTDs. We have the necessary technology and resources to help in the biomedical advancement of therapies, drugs, and vaccines. Another reason on why we should care is to prevent the spread of these diseases to areas where they are not endemic. There have been reported cases of travelers getting infected with schistosomiasis in Europe. Also, there are reported parasitic diseases in developed countries such as neurocysticercosis, toxoplasmosis, Chagas disease, and pinworm infection.

In an era in which technology has tremendously facilitated the spread of globalization, it is impossible for us to turn the blind eye about the different issues around the world. One of the biggest obstacles developing countries face is the spread of diseases otherwise nonexistent in developed countries. These diseases have a great impact in the socioeconomic advancement of these regions and we are aware of it. Awareness about these diseases is just the first step, the next one is to take action. We can contribute to the spread of NTDs by dedicating efforts in biomedical research, support medical services in such areas, health promotion, as well as interdisciplinary cooperation with the fields of engineering and architecture to develop strong urbanization plans to improve the infrastructure in such regions. It is up to us to take action and cooperate in the elimination of NTDs.

In a distant part of Venezuela a little kid starts to have second thoughts on whether continue eating his meal after he heard his parents talking about the relative who was hospitalized after eating “bad-pork”. At the same time, over in Michigan, Tim and Jane take their puppy to the veterinarian for its first shots and deworming.  Crossing the Atlantic Ocean, in Kenya, a woman’s forearm starts to itch after washing the clothes near the river. Further North, in Germany, a physician who just returned from a trip to Turkey, notices that he has been having episodes of intermittent fever. Parasites have, still are, and will continue to co-exist with humans. Since the beginning of time, parasitic infections have affected humans. These diseases, while not a cause of high mortality, they all lead to disability, social burden, chronic disease, and may be associated with stigma.  Sadly, most parasitic infections affect the world’s poorest people.  Despite industrialization, modern medicine, and globalization, these infections are still a major cause of disease in developing countries. Two major causes by which parasitic diseases continue to cause such high burden in the world is related to their intrinsic ability to infect and evade the immune system. On the other side, these infections continue to afflict millions of people because the lack of their ability to debilitate the host and because they affect developing countries.

Parasite co-existence with humans and other hosts has been driven by mutation processes along with natural selection giving rise to new phenotypes. Parasites have evolved to develop ingenious ways to evade the immune response from the host. These mechanisms have allowed them to persist in harsh environments thus giving them the opportunity to continue with their life cycle and spread to a new host. Most parasitic infections can go unnoticed because the parasite does not elicit an immune reaction in the host. In order to survive, feed, and reproduce; parasites can evade, sabotage, or manipulate the immune system of the host. For example, parasites can invade an immune-privileged tissue such as the central nervous system or the eyes. Tachyzoites of Toxoplasma gondii are known to hide in neuroretinas causing ocular toxoplasmosis. By hiding in such tissue, the tachyzoites can evade the cells of the immune system [1]. Likewise, onchospheres from Taenia solium survive in protected places like the CNS. Most T. solium infections resolve without any obvious symptoms, but residual brains calcifications can be detected by brain CT [2]. Another way by which parasites can become “invisible” to the immune system is in the example we have learned from trypanosomes. While most protozoan microorganisms replicate inside a host’s cell, trypanosomes freely circulate in blood. Most trypanosomes die soon after they have entered blood circulation because of a strong IgM response from the host. Less than 1% of surviving trypanosomes survived because of their variable surface glycoprotein coat (VSG) which has a different epitope for the antibody already in circulation. The surviving parasites multiply and again induce a strong immune response, but then again a small number survives because of their different VSG. VSG switching leads to antigenic variation and fluctuations in parasitemia which causes cycles of intermittent fever [3]. Parasites can also actively modulate the host’s immune response. Serine proteases released from schistosoma cercariae can cleave IgE from the host and thus interfere with recognition and complement-mediated lysis [4]. Likely, trypanosomes can interfere with innate immunity. Trypanosome lytic factors (TLF) are secreted proteins found in serum which can kill trypanosomes by forming pores in the parasite’s endosomes leading to transmembrane flux of chloride ions and osmotic swelling. However, T. brucei spp. can neutralize the lytic portion of TLFs by neutralizing it with a serum resistance-associated protein or by stiffening the endosome’s lipid membrane thus making it more difficult for the TLF to insert into the membrane [5]. Another example on how parasites can modulate the immune system is in the intracellular protozoan parasite Leishmania spp. Leishmania can delay neutrophil apoptosis for up to 24 hours by inhibiting pro-caspase processing, thus the parasite will be protected from other immune system cells inside the neutrophil. Promastigote infected neutrophils will eventually die and secrete chemotactic factors, such as IL-10 and IL-12, for macrophages to engulf them. Cleverly, Leishmania promastigotes are also engulfed by the macrophages, which are their primary host cell in which they reproduce and mature into amastigotes. Ironically, the cells supposed to kill the parasite are the ones harboring it. This is possible because amastigotes can delay phagolysosome fusion and by diluting the hydrolytic enzymes below their effective level. Also, glycosylinositolphospholipd, which is a component of the amastigote’s glycocalyx can suppress the expression of nitric oxide synthase (NOS) of the macrophage, thus preventing death from reaction nitrogen species. Likely, trypanothione reductase can neutralize reactive oxygen species and NOS, thus rendering the parasite immune to killing by the macrophage [6]. Another example of immune evasion strategy is mediated by interacting with C-type lectins (CTLs). CTLs are a family of proteins that form cell surface receptors on macrophages and NK cells. These receptors mediate the first steps in adhesion of the leukocytes to the endothelium in order to permeate into the site of infection. Toxocara caniis larvae is known to secrete excretory-secreted antigens which contain a CTLs domain that is similar to the host’s CTLs. These CTLs analogs will thus bind to tissue endothelium preventing leukocyte infiltration to the site of infection [7]. Similarly, Schistosoma mansoni secretes lectins which bind to plasma components of Biomphalaria snail and act in a similar fashion as CTLs, but these bind to snail’s haemocyte surface lectins [8]. Following on Schistosoma spp. immune evasion strategies, adult worms are known to have an affinity for IgG and complement factor C3. Affinity to these molecules is mediated by the presence of IgG-Fc and C3 receptors on the surface of adult male worms. These receptor will thus render the effector molecules ineffective [9]. It is also hypothesized that these receptors may serve as a mechanism for molecular mimicry of host’s molecules. Alongside, S. mansoni schistosomula have been shown to express MHC class I molecules as well as ABO and Lewis blood antigens. Schistosomula-expressed MHC molecules are acquired from the host and not synthesized by the parasite; a possible mechanism by which this occurs is that the parasite’s cell membranes is able to fuse with the host’s cells thus antigens flow from one cell to other and are eventually expressed [10]. We have observed on different immune evasion mechanism by parasites.

Parasitic infections continue to afflict millions of people because the high social burden and morbidity caused by these diseases. Neglected tropical diseases (NTDs) have a high prevalence in developing countries, especially in rural areas. Currently, NTDs affect 1.4 billion people in 149 countries and the economic burden for these countries rises every year to billions of dollars. Surprisingly, NTDs have been around since ancient times in human history. Ancient writings have been found describing some NTDs, such as schistosomiasis, dracunculiasis, and hookworm infections. Devastatingly, these infections are known to lead to chronic conditions, disability, and even disfigurement. Chronic hookworm infection is one of the most prevalent human parasitic infections. Ancylostoma duodenale and Necator americanus are the two main species that cause hookworm disease in humans. The life cycle of both hookworms is almost identical and they are distinguished by their morphological features. Infections occurs when hookworm larvae in filariform in soil penetrate intact skin. Then, the parasite travels through the blood and lymphatic system, the heart, lungs, and it is eventually swallowed to the small intestines where it matures and starts hatching eggs that pass through feces. It is then in the intestines where adult hookworms cause the most damage to the host. By using their “teeth” they attach to mucosal surface and start feeding on blood. Infected patients then start to develop iron-deficiency anemia, abdominal pain, stunted growth, protein deficiency, and even death. Another hookworm infection caused by A. braziliense causes cutaneous larval migrans, for which like out from a sci-fi movie, larvae migrate within the skin causing an intense, itchy eruption. Linked to the symptomatology of hookworm infection, debilitating chronic infection eventually leads to socio-economic burden. It is known that hookworm infection (as well as the other of the soil-transmitted helminthes) affects cognitive and memory ability, thus infected children demonstrate reduced school performance and attendance. Also, chronically infected agricultural workers tend to have decreased productivity and thus may have difficulty keeping the family income. Current control strategies against hookworms are frequent periodic deworming with benzimidazole as well as improving sanitary disposal of human feces to break the parasite’s life cycle [11].

Parasitic infections can also lead to disability. Onchocerciasis, also known as river blindness, is caused by a filarial nematode Onchocerca volvulus. 20 to 30 million people are infected with onchocerciasis mostly in West and Central Africa. Transition and infection is caused by a blackfly which takes a blood meal in the human and injects the parasite into the skin. Microfilariae migrate in the skin of the host where they cause itching and even disfigurement. From the skin, some microfilariae may reach the eye, where they form opacities, inflammation of the sclera, cornea, iris, and retina. If untreated, these opacities become larger and eventually block light from entering the eye thus leading to impaired vision or total blindness. Also, accumulation of filariae in subcutaneous tissue leads to disfigurement. Chronic inflammation of the skin causes it to lose its elasticity thus making it look loose and aged. The socio-economic harms caused by chronic onchocerciasis are devastating. When, the head of the household becomes blind due to the infection it becomes a burden to the family income. They will not be able to work. In some villages of sub-Saharan Africa up to 10% of the population is blind from ochocerciasis thus debilitating the economy of the whole village [11]. Coupled with economic difficulties, depression in the patient and their families makes the situation more overwhelming. Resources are already lacking in such endemic areas, thus these situations make it more difficult for the population to improve their economy. An extreme case of physical disfigurement is the one caused by another filarial worm, Wucheria bancrofti, which causes lymphatic filariasis. Similarly to onchocerciasis, an insect vector is required to spread the disease, in the case of W. bancrofti a mosquito takes a blood meal and injects the larvae through the skin. Eventually, the larvae migrate and make their way through to reach the lymphatics, where they mature to adult worms that can live for up to 8 years. Now, this scenario brings us back to on the immune evasion strategies of parasites because these worms can reside on the “headquarters” of the immune system. Inside the lymphatic vessels, adult worms block the vessels (lymphangiectasia) which eventually leads to accumulation of connective tissue cells and fibers, thus enlargement of limbs. Along with continuous secretion of inflammatory cytokines and secondary bacterial infections, it leads to massive swelling and granulomatous response in the lymphatics, leading to a condition known as elephantiasis. As a result of this devastating disability and disfigurement; socioeconomic consequences arise. These infections mainly occur in young adults whom usually are agricultural workers. Forced by the diseases, these patients have to abandon their jobs. In fact, the annual loss in the country of India due to lymphatic filariasis pathology is of $842 million dollars [11]. Moreover, a deep stigma follows people with elephantiasis. Patients with these conditions are frequently perceived as lacking hygiene, being cursed, or dirty. Family fragmentation due to abandonment is also common. Inevitably, these series of events lead to depression for which in some cases patients do not seek medical treatment. Even the term elephantiasis may not be the best term to describe their condition since it falls into making a somewhat offensive analogy from their physical appearance. Altogether these conditions eventually lead to a cycle of poverty and disease. While tremendous effort has taken place in controlling these infections, they continue to spread to new geographic areas and are still a cause of high morbidity. More resources and attention must be given to parasitic diseases. It is thus important to continue funding, researching, and implementing alternatives in the treatment of these diseases. The fact that we may not be in close contact with these type of diseases should not be an excuse to forget that they exist.

REFERENCES

1. Bhopale, G.M., Pathogenesis of toxoplasmosis. Comp Immunol Microbiol Infect Dis, 2003. 26(4): p. 213-22.
2. Garcia, H.H., S. Rodriguez, and J.S. Friedland, Immunology of Taenia solium taeniasis and human cysticercosis. Parasite Immunol, 2014. 36(8): p. 388-96.
3. Namangala, B., How the African trypanosomes evade host immune killing. Parasite Immunol, 2011. 33(8): p. 430-7.
4. Aslam, A., et al., Proteases from Schistosoma mansoni cercariae cleave IgE at solvent exposed interdomain regions. Mol Immunol, 2008. 45(2): p. 567-74.
5. Pays, E., et al., The molecular arms race between African trypanosomes and humans. Nat Rev Microbiol, 2014. 12(8): p. 575-84.
6. Cecilio, P., et al., Deception and manipulation: the arms of leishmania, a successful parasite. Front Immunol, 2014. 5: p. 480.
7. Loukas, A. and R.M. Maizels, Helminth C-type lectins and host-parasite interactions. Parasitol Today, 2000. 16(8): p. 333-9.
8. van der Knaap, W.P. and E.S. Loker, Immune mechanisms in trematode-snail interactions. Parasitol Today, 1990. 6(6): p. 175-82.
9. Tarleton, R.L. and W.M. Kemp, Demonstration of IgG-Fc and C3 receptors on adult Schistosoma mansoni. J Immunol, 1981. 126(1): p. 379-84.
10. Simpson, A.J., et al., Evidence that schistosome MHC antigens are not synthesized by the parasite but are acquired from the host as intact glycoproteins. J Immunol, 1983. 131(2): p. 962-5.
11. Hotez, P.J., Forgotten People Forgotten Diseases. Second Edition ed. 2010: ASM Press.

A few months back I submitted an essay to a student competition called “How would you raise awareness of neglected tropical diseases?” hosted by Rice University’s Baker Institute for Public Policy. Luckily the essay got selected for honorable mention and got published in the Baker Institute blog. After that event I realized I should start what was proposed on such essay. That is how this blog started. Hopefully, as time goes on, this website can serve to inform, communicate, and educate people not yet familiar with NTDs and their devastating effects as well as recognize the efforts of all those people working towards solutions in preventing and treating this group of diseases.

Tropical Diseases Campaign

With the spread of globalization and the Internet, an awareness campaign has the potential to reach millions of people and educate them about neglected tropical diseases (NTDs). I propose the creation of a new campaign, called Tropical Diseases Campaign, to reach people through social media and events.

Tropical Diseases Campaign (TDC) will have a website with three main components: a YouTube channel, a blog, and a “take action” portal, with the goal of reaching as many people as possible. First, an active YouTube channel linked to the TDC website will broadcast short clips of 5–10 minutes teaching about different NTDs. Individual videos about each NTD will present and explain information in general language, and new videos will be uploaded on a regular basis. These videos will teach about various aspects of tropical diseases, including causative agents, epidemiology, clinical cases, current treatments, and preventive strategies. Viewers will be encouraged to share the video and visit the TDC website. The purpose of these short clips is to make the information accessible—people can watch the videos at any time, and the videos leave them with a message. Also, YouTube channels are popular because of the profit earned by the number of views and advertisements. The money earned from the YouTube channel can be income for the self-supporting TDC.

The blog component of TDC will be designed to invite people to share ideas, anecdotes, videos, and photos about their experiences with NTDs. The purpose of the blog is to give a voice to those who have experienced NTDs firsthand. For example, physicians, scientists, and people who live in endemic areas can all share their experiences.

The final main component of the Tropical Diseases Campaign website is the “take action” portal. This part of the website will provide links and information about volunteer opportunities to help people living in endemic areas, job positions related to treating NTDs, and research opportunities. This section will also provide information about universities that have ongoing research related to NTDs for students interested in graduate school. The “take action” portal will also include a donation option that will support people living in endemic areas.

Although there are a number of websites that provide sources and information about NTDs, few people are aware of these websites, and thus the message is not able to reach the public. The main challenge for the success of TDC is to reach a large audience and encourage them to take action.

There are three ways people can make a difference through the Tropical Diseases Campaign: 1) creating partnerships with universities, 2) selling merchandise, and 3) organizing an NTDs awareness walk. TDC can create partnerships with universities and promote student clubs that focus on NTDs awareness. Students can actively participate in the website by making videos, writing for the blog, or making donations. Another way to promote awareness of NTDs is merchandise. In fact, merchandise has played a strong role in promoting awareness of diabetes, breast cancer, and HIV/AIDS. T-shirts, bracelets, ribbons, and bumper stickers are commonly used to invite people to participate in battling these diseases. The TDC could also sell merchandise to support awareness of NTDs. Finally, organizing walks or runs can also help engage and educate people about a cause. In fact, the Making Strides Against Breast Cancer walk organized by the American Cancer Society is a powerful event that engages the community to increase awareness and raise money. The same approach can be implemented by the TDC. A Shoeless Walk a Mile event for NTD awareness could bring the community together as well as secure sponsors, in order to provide donations that will be used to treat, prevent, and research NTDs. More importantly, this event will bring media attention to reach more people who can participate in the campaign.

While this proposal may appear too broad, we need to keep in mind that no single approach will be effective in spreading awareness of NTDs. It is important to use as many resources as possible to reach people and educate them about neglected tropical diseases. Hopefully, in the near future, with the help of the TDC, these diseases will no longer be neglected.