Parasites: Biological Clocks and Rhythmicities PDF

1 BSCI 3230: BIOLOGICAL CLOCKS PARASITE RHYTHMICITY Julián F. Hillyer, Professor of Biological Sciences Vanderbilt University  Parasite Diversity 2 Protozoans Vertebrate Host...

1 BSCI 3230: BIOLOGICAL CLOCKS PARASITE RHYTHMICITY Julián F. Hillyer, Professor of Biological Sciences Vanderbilt University  Parasite Diversity 2 Protozoans Vertebrate Host Cestodes Arthropods Nematodes Trematodes 3 Parasites are ubiquitous and diverse 3 Campbell Biology 4 Parasites and humans 4  Humans are susceptible WHO, January 2023: to about 300 species of “Soil-transmitted helminth (STH) infections are helminth worms and over among the most common infections worldwide 70 species of protozoans. with an estimated 1.5 billion infected people or 24% of the world’s population.” https://www.who.int/news-room/fact-sheets/detail/soil-transmitted-helminth-infections  Parasitic diseases continue to be a leading Distribution of soil-transmitted helminth infection cause of morbidity and mortality worldwide.  Estimated worldwide prevalence: ◼ Ascaris = 15% ◼ Trichuris = 8% ◼ Hookworm = 8% 5 Parasitic diseases are often not talked about in the U.S., but they’re here! 5 6 Parasite life cycles range from 6 simple to complex 1. 3. Definitive Zoonotic Host Definitive Host Human 2. Definitive Zoonotic Host Intermediate Host(s) Intermediate Host(s)  Parasite Diversity 7 7 Protozoans Vertebrate Host Cestodes Arthropods Nematodes Trematodes 8 https://doi.org/10.1177/0748730417718904 9 https://doi.org/10.1177/0748730417718904  Case #1: Dicrocoelium dendriticum 10  “Lancet fluke”.  Pointed body.  Adult resides in the bile duct.  Can infect humans, but human infections are rare. DH 2nd IH 1st IH  Case #1: Dicrocoelium dendriticum 11  In the ant, cercariae penetrate the gut and most encyst as metacercaria in the hemocoel.  But one cercaria invades the Metacercaria subesophageal Brainworm ganglion and develops into a brainworm that alters ant behavior:  Tetania causes clamping at the tip of the grass blades in the early morning or late afternoon.  Case #1: Dicrocoelium dendriticum 12 12 ℃ 20 ℃ 25 ℃  Case #2: Filarial worms and lymphatic filariasis 13  Caused by nematodes that infect the lymphatic system.  Wuchereria bancrofti  Brugia malayi  Brugia timori  Combined, they infect ~40 million people worldwide; many are permanently incapacitated.  In its most severe form, they cause “elephantiasis”.  Adults live about 10 years. DH IH  Case #2: Filarial worms and lymphatic filariasis 14  32 of the 38 least developed countries in the world have L.F.  W. bancrofti:  Equatorial belt.  ~90% of cases.  B. malayi:  China, Korea, India, Sri Lanka, Philippines.  ~10% of cases  B. timori:  Southeast Indonesia.  Rare 15  Case #2: Filarial worms and lymphatic filariasis 16  The adults live in the lymph nodes.  The microfilaria live in the blood.  The microfilaria exhibit periodicity:  During the day, they reside in the lungs.  At night, they are in the peripheral circulation. 17  Case #2: Filarial worms and lymphatic filariasis 18 6 am 6 am  and/or the presence or absence of sheath (Fig. 3). Case #2: Filarial worms and Brugia timori (David and Edeson 1965). The adults of these parasites live in the lymphatic system, especially the lymphatic vessels and the nodes, and the mf, which are sheathed, are Different strains based on periodicity of microfilariae lymphatic filariasis found in the blood. W. bancrofti is prevalent in tropical Africa, South East Asia, Papua New Guinea, Philippines, Candelonia and Thailand. B. malayi is spread over South and South East Fig. 3 Differentiation of species of microfilariae on the basis of Threepresence genetically W. bancrofti or absence and determined or absence of B. of caudalphysiological malayi, a sheath (SH) races nuclei (CN), and exist in the presence depending on the microfilarial 19 periodicity (Sasa and Tanaka 1974; Tanaka 1981; Gupta Asia. B. timori is localized in Lesser Sunda Islands of Eastern et al. 1990; Tewari et al. 1995; Weerasooriya et al. 1998; Indonesia (WHO 1992). isShriram not yetetfully understood. al. 2002; Pichon Theand periodicity Treuil 2004). of They mf seems to are the JJ Parasit Since Parasit Dis Dis (June (June & W. 2009)bancrofti & December December 2009) 33(1&2):3–12 33(1&2):3–12 and B. malayi co-exist in many 3 be oriented to nocturnally the 24 nocturnally periodic, hours cyclesubperiodic of the host and in which the diurnally placesARTICLE REVIEW (Raina et al. 1990; Rajendran et al. 1997), their circadian subperiodic rhythmforms of (Table the host3). could act Indian In the as a cuesub-continent, to the control J P D Fig.identifi2 Mfcation to species of W. bancrofti level iscephalic showing very important space (CS), in nerve diagnosis ring of thethe both circadian parasites rhythm exist of as the mf. Whatever nocturnally be the periodic reason, forms the and the (NR), Excretory pore of (EP), and caudal nucleus (CN) mf Aasreview well as of theepidemiological complexity surveys. biology These of lymphatic speciesfilarial could be mfperiodicity appear in is thein peripheral agreement with the feeding circulation behavior at night. of the Diurnally parasites differentiated based on the measurements of various body vector mosquito (Vanamail and Ramaiah 1991; Weerasooriya subperiodic strain of W. bancrofti occurs in many islands K.characters P. Paily S. L. Hoti of P.the K. Dasmf (Table 2). et in al. 1998) South enabling Pacifi the mosquito c, French Polynesia,toThailand ingest theand mf Nicobar in large subperiodic The infective and the L3mf stageis present of theseinspecies,the peripheral by dissecting bloodout at numbers island. The by presenting mf remainthemselves in large numbers in the peripheral blood allin the the allfrom times, with a slight mosquito vectors, nocturnal can be rise. B. timori present differentiated by examining in the peripheral time with blooda peakduring theatpeak density 12–20biting timeThe hours. of the mosquito. zoonotic B. Received: 17 November 2009 / Accepted: 01 December 2009 Timor theIndian ©2009 island caudal is papillae Society for nocturnally periodic. Parasitology (Fig. 1). There are three caudal papillae, However, the mf need not be absent from malayi prevalent in Indonesia and Malaysia is nocturnally the peripheral Abstract Various hypothesis There are about have five more common, been postulated including that the endosymbiont, onWolbachia, the mechanism plays an important role blood during the rest of the period unless there are some Wuchereria bancrofti and Brugia malayi, and four less common in the survival of filarial parasites. The possibility of in vitro of microfi Table filarial 3 larial parasites infecting Different periodicity. human. Genetic analysis As strains of offiW.larial early and in as in 1951, vivo culture parasites basedHawking of filarial parasites and of microfi is also reviewed. on periodicity physiological lariae factors which govern their appearance and bancrofti populations in India showed that two strains of the Thurston demonstrated that periodic species are prevalent in the country. The adult filarial parasites Keywords Lymphatic filariasis, Parasite, Life cycle, fluctuation in the number disappearance. For example, there are several animal filariae are Periodic tissue specific inform the humanofhost filarial and their parasite embryonic Microfilariae, Distinguishing characters, Periodicity, Vector, Geographic distribution of mf was due to their accumulation stage, called microfilariae (mf), are found in the blood or susceptibility, Endosymbiont, animal models in the lungs during day such as the Litomosoides carinii and Dipetalonema viteae, Nocturnally periodic W. bancrofti Introduction skin of the host, depending upon the species of the parasite. Asia, Africa, which do Malaysia, not showPhilippines, PNG to host circadian rhythm any orientation and release to the circulating Three genetically determined physiological races exist in W. bancrofti and B. malayi, based on the microfilarial blood at night. Stimuli like body Nocturnally sub-periodic W. bancrofti are appendageless, cylindrical, non-segmented Thailand or vector feeding rhythm through mf periodicity (Reddy et al. temperature periodicity. are shown They are the nocturnally to have Nematodes periodic, nocturnally subperiodic and diurnally subperiodic forms. The effect on the periodicity of invertebrate worms possessing a body cavity and a complete Diurnally sub-periodic W.infection bancrofti tract with tri-radiate pharynx. The body is covered South Pacifi 1984), c, Andaman and still have&successful Nicobar Islands transmission. of W.of bancrofti, susceptibility mf a mosquito B. malayi, species to filarial depends on various factors, which could be genetic, B.digestive ceylonensis and Dirofilaria with a cuticle and has four main longitudinal hypodermal Nocturnally repens physiological or physical. (Hawking periodic B. malayi Survival analysis et al. of Culex 1966). chords. They are bilaterally symmetrical and have well India, China, Malaysia, Indonesia, Philippines, Japan, Korea Later, it was postulated that quinquefasciatus infected with W. bancrofti showed that developed nervous, excretory and reproductive systems, but the Nocturnally accumulation sub-periodic parasite load in the mosquito is a risk in lungs is due factor B. malayi of vector lack to greater specialized respiratory and circulatory systems. Over Malaysia, Indonesia, Philippines oxygen tension in sothe Mosquito susceptibility and host range of different survival. The extrinsic life cycle of the parasite is initiated 15,000 nematode species have been described far and when the mf are ingested by a mosquito vector during lungs during feeding on the host blood. the daymostcompared On maturity, of the infective their size vary from the smallest being 82 μm in length to tothe largest thatreaching in the over 8night meter. Mostwhen the are of the nematodes species/strains of filarial parasites L3 stage larvae migrate to the head and proboscis of the marine or fresh water and soil inhabiting, but a few of them host mosquitois under to get transmittedrest to the (Hawking mammalian host during and parasitize Clarkcrops, 1967; Hawking insects, livestock and human.et al. subsequent feeding. They develop to the adult L5 stage and 1981). However, the period of development why ofand and the longevity There are many theories on the origin of nematodes. One how mf remain in lungs during the parasites Many of the Anopheline, Mansonoid, Culex and Aedes  Case #2: Filarial worms and Wb SA Am. Samoa 4 14.77 (1.17) 0.55 (0.110) Wb TA Tahiti 10 15.75 (0.93) 0.38 (0.054) Wb TO Tonga 10** 16.24 (0.99) 0.36 (0.046) Wb WA Wallis 3 17.38 (0.91) 0.28 (0.041) lymphatic filariasis Wb NI Nicobar 7 17.92 (1.65) 0.33 (0.045) Bm MA Malaysia 20 21.89 (0.86) 0.38 (0.042) Bm PH Philippines 29 23.14 (0.48) 0.58 (0.060) * Wb: Wuchereria bancrofti; Bm: Brugia malayi. ** 10 biorhythms on the same subject during 15 months. 20 The sum (or mean) of several individual rhythms with the same period at the same time is a cosine func- tion with the same period. Geometrically, a cosine function ya,k can be rep- resented by a vector in polar coordinates V (a, k) of length a and of direction k. C. R. Biologies 327 (2004) 1087–1094 3. Hypothesis http://france.elsevier.com/direct/CRASS3/ Biological modelling / Biomodélisation Genetic determinism of parasitic circadian periodicity and subperiodicity We put forward in human the hypothesis lymphatic filariasis that the diversity ofGastonthe Pichonglobal∗ , Jean-Pierre biorhythms Treuil observed in the different Institut de recherches pourpopulations le développement (IRD), UR ofGEODES, 32, av. Henri-Varagnat,filariasis subperiodic 93143 Bondy cedex,is ruled by two France co-dominant alleles, D (for ‘day’) and d, which can Received 17 June 2004; accepted 14 September 2004 combine Presented into three biorhythm genotypes D D , D d and by Pierre Auger dd. The predominant nocturnal periodicity, assumed Fig. 2. Periodicity, subperiodicity and cycle of vectors A–B. Ob- Abstract to be genetically pure, is correctly fitted (r = 0.991) served bihourly mff relative densities (squares, with standard error), by lymphatic The larval parasites of the pantropical a cosine function filariasis exhibit y1,[dd] two types of circadian in the human bloodstream at nighttime, synchronised with their mosquito vectors. In (Fig. behaviour. 2A) Typically, with they only appear ampli- Polynesia and parts of Southeast Asia, free fitted by a cosine function (Eq. (1)). (A) Nocturnal periodic W. ban- of nocturnal vectors, they are found tude a =and 1eachand at all hours, population biorhythm differs.k peak-hour = [dd] Through = 0approach, a geometrical h (as we usual, crofti (Philippines ): curve with parameters a = 1 and k = 0 h. explain this circadian diversity by a single, dominant mutation: the clocks of individual parasites are set at midnight (ubiquitous) (B) Diurnal subperiodic W. bancrofti (Tahiti ; white squares, square or at 2 p.m. Compared to other circadian brackets genes, this mutation mustfeature be very old, asphenotypes). Theremote it is shared by four biologically other of parasites. This seniority sheds new light on several theoretical and practical aspects of vector–parasite temporal relations. To genera two el- interrupted curve, a = 0.26, k = 15.7 h), and nocturnal subperi- ementary biorhythms described by y1,[D d] and y1,[D D ] cite this article: G. Pichon, J.-P. Treuil, C. R. Biologies 327 (2004). ã 2004 Académie des sciences. Published by Elsevier SAS. All rights reserved. odic B. malayi (Philippines ; black squares, continuous curve, Résumé have unknown [D d] and [D D ] peak hours. We also a = 0.46, k = 23.1 h). C–E. Sketch of the biting cycles of main Déterminisme génétique de la périodicité et de la subpériodicité parasitaires chez la filariose lymphatique. La filariose assume that the frequencies of the three elementary vectors of filariasis. (C) Vectors of nocturnal periodic filariasis: lymphatique est pantropicale. Les larves du parasite présentent deux types de comportement circadien. Typiquement, elles genotypes follow a Hardy–Weinberg law. A popula- apparaissent seulement la nuit dans la circulation périphérique, en même temps que leurs moustiques vecteurs. En Polynésie, Anopheles and Culex. (D) Vectors of diurnal subperiodic filaria- sans vecteurs nocturnes, on les trouve à toute heure, et le biorythme diffère d’une population à l’autre. Par une approche géométrique, nous expliquons cette diversité circadienne par l’existence d’une mutation dominante : les horloges de chaque sis: Aedes mosquitoes (subgenera Stegomyia and Ochlerotatus). The tion biorhythm is the frequency-weighted sum of the parasite sont réglées à minuit (ubiquistes) ou à 14 h. Cette mutation semble très ancienne, car elle est partagée par quatre genres pattern of aggressiveness is highly variable (bars), depending on éloignés de parasites. Ce résultat jette un jour nouveau sur divers aspects des relations temporelles hôte–parasite. Pour citer cet three elementary biorhythms. It is proven that this sum article : G. Pichon, J.-P. Treuil, C. R. Biologies 327 (2004). many factors. (E) Vectors of nocturnal subperiodic filariasis: Man- ã 2004 Académie des sciences. Published by Elsevier SAS. All rights reserved. is also a cosine function, of known parameters ā and k̄: sonia mosquitoes (in swamp forests). Keywords: circadian periodicity; subperiodicity; genetics; parasite; lymphatic filariasis; mosquito vector; coevolution 21 22 Source: WHO  Case #3: Plasmodium: 23  Etiological agent of malaria.  247 million cases of malaria worldwide in 2021  Currently kills 619,000 people per year (WHO, 2021).  Prevalent in tropical regions.  Africa, South America, Southern Asia.  Five different species cause human malaria.  Case #3: Plasmodium and malaria Life cycle of 25 Plasmodium:  Heteroxenous parasite:  Definitive host: mosquito. ◼ Sexual reproduction (syngamy), then asexual replication (sporogony). ◼ Of the ~3,500 known species, only ~40 transmit human malaria.  Intermediate host: human. IH DH ◼ Asexual replication by schizogony (exoerythrocytic & erythrocytic). ◼ Formation of macrogametocytes and microgametocytes.  Case #3: Plasmodium and malaria 26  Severe anemia.  Cerebral malaria.  Acute, widespread disease of the brain.  Induces comma and seizures. ◼ Deadly in 25-50% of cases (24-72 hours).  Placental malaria.  Infection of the placenta.  Low birth weight.  Stillbirth.  Case #3: Plasmodium and malaria 27  Fever paroxysms closely follow maturation of each generation of merozoites, and rupture of the RBCs that contain them.  Host-inflammatory response.  Less synchrony in P. falciparum infection. Figure. 9.5. Correlation of fever paroxysms and merozoite  Little relief. release from erythrocytes.  Case #3: Plasmodium and malaria 28 Periodicity in multiples of 24 hours  Case #3: Plasmodium and malaria 29 There is a cost to losing periodicity with the host?  Case #3: Plasmodium and malaria 30 Food intake maintains the periodicity?  Case #3: Plasmodium and malaria 31 Intrinsic periodicity?