Canine Babesiosis
Oliver Organista, LA Canine babesiosis is a tick-borne, protozoal, haemoparasitic disease that can cause varying degrees of haemolytic anaemia, splenomegaly, thrombocytopenia and fever. It is very endemic to different parts of the world, and presents varying clinical, hematological, and pathological manifestation depending on the species and subspecies involved.1,2 There are two hosts for the transmission of Babesia spp., viz. invertebrate (tick) and vertebrate host. Dogs are one among the many targets of Babesia spp., causing canine babesiosis, and now there are clinical evidences of possible vertical transmission too. Dogs of all ages can be affected with Babesia spp., but young puppies are more commonly affected. Two Babesia parasites were thought to occur in dogs; the relatively large intra-erythrocytic piroplasm referred to as Babesia canis and a smaller parasite, known predominantly as the cause of canine babesiosis in Asia, Babesia gibsoni. B. canis has been reclassified into three separate species (B. canis, B. rosi, B. vogeli) on the basis of immunity, serological testing, vector specificity and molecular phylogeny At least 4 genetically and clinically distinct small piroplasms affect dogs which include: Babesia gibsoni–originally described in India nearly a century ago and now occurring sporadically in other parts of the world including the Australia; Babesia conradae, a piroplasm that occasionally infects dogs in California; Theileria annae, a Babesia microti-like parasite that has so far been reported only in northwest Spain, transmitted by Ixodes hexagonus ; and a fourth small piroplasm, B. (=T.) equi has also been reported in dogs in Spain.³ Prevalence of Babesiosis The incidence of canine babesiosis vary considerably from one country to another depending on the distribution of the causative parasite and their specific vectors. Table below shows the data gathered during the Questionnaire-based survey on the distribution and incidence of canine babesiosis in countries of Western Europe.5 DIAGNOSIS, SYMPTOMS, AND TREATMENT Diagnosis. In the past, babesiosis was diagnosed by seeing the parasite on a blood smear. Other diagnostic tests are becoming more readily available, including FA (fluorescent antibody) staining of the organism and ELISA (enzyme-linked immunosorbent assay) tests. A PCR (polymerase chain reaction) test is also available and is commonly used to diagnose babesiosis. The PCR test has the advantage in that it can detect all four species of Babesia. Serologic or antibody titer testing in the diagnosis of babesiosis has limitations. A positive test result is dependent on an antibody response by the infected dog, which may take up to ten days to develop. Once a dog has developed antibodies to babesiosis, they may persist for years and this must be considered when performing follow-up tests.6 Symptoms. Dogs typically present with the acute, severe form of babesiosis, which is characterized by findings such as abnormally dark urine, fever, weakness, pale mucous membranes, depression, swollen lymph nodes, and an enlarged spleen. Potential complications: Bleeding problems, a severe type of anemia that leads to jaundice, organ damage, death.7 Treatment. The FDA approved treatment for babesiosis is imidocarb diproprionate. A combination therapy of quinine, azithromycin, atovaquone, and/or clindamycin is being researched and may become more common to treat dogs within the US or Canada in the future. Clindamycin, the treatment of choice for Babesia microti, the main Babesia species that infects humans, can also be used against Babesia in dogs. Clindamycin is a readily available antibiotic and is an excellent starting point for treatment in many dogs. Your veterinarian will discuss any alternative and adjunctive treatments with you.7 TRANSMISSION AND PREVENTION OF BABESIOSIS How is dog Babesia transmitted? Transmission. In most cases, Babesia organisms are spread to dogs through the bite of an infected tick but is not likely to be transmitted until a tick is attached for 36 hours. However, some studies suggest that infected dogs with open mouth sores can pass on the infection to other dogs through a bite, and infected pregnant females can transmit babesiosis to their unborn puppies. It can also be transmitted by the needle passage of infected blood, inadvertently in the case of blood transfusion or deliberately during experimental studies. Generic Life Cycle of Babesia spp.10 Generic life cycle of Babesia spp. Sporozoites (Sz) are injected into a vertebrate host blood system, during the blood meal of an infected tick. After invasion, Sz differentiate into trophozoites (T). Trophozoites undergo asexual division into two or four merozoites (M) in the infected red blood cells. Merozoites exit the red blood cells and invade new ones. Some groups of merozoites transform into gamonts or pregamotyces (G). The process of gamogony and sporogony takes place in the tick. Gamonts ingested by a tick feeding on an infected host differentiate in the gut into gametes (called ray bodies or Strahlenkorper – (Sk)) that fuse forming a diploid zygote (Z, gamogony). Via meiosis division, zygotes give rise to motile haploid kinetes. After haploid kinetes multiply by sporogony, they penetrate the tick haemolymph and organs. The final stage of the development occurs in the salivary glands (Sg), where differentiation and multiplication occur. Kinetes transform into sporozoites that infect the vertebrate host after vector development into a subsequent life stage – larvae to nymph, nymph to adult (transstadial transmission, Ts). In large Babesia spp. kinetes also invade the tick ovaries and eggs, and infective sporozoites are formed in the salivary glands of the next generation larvae. This process is called transovarial transmission (To). Adopted and reproducted from Schnittger et al. 9 How ticks spread disease11 Ticks transmit pathogens that cause disease through the process of feeding. Depending on the tick species and its stage of life, preparing to feed can take from 10 minutes to 2 hours. When the tick finds a feeding spot, it grasps the skin and cuts into the surface. The tick then inserts its feeding tube. Many species also secrete a cement-like substance that keeps them firmly attached during the meal. The feeding tube can have barbs which help keep the tick in place. Ticks also can secrete small amounts of saliva with anesthetic properties so that the animal or person can’t feel that the tick has attached itself. If the tick is in a sheltered spot, it can go unnoticed. A tick will suck the blood slowly for several days. If the host animal has a bloodborne infection, the tick will ingest the pathogens with the blood. Small amounts of saliva from
Thyroid Function in Animals
Sushant Sadotra Introduction: The thyroid is one of the endocrine glands in vertebrates. The thyroid gland has a bilobed structure located below the larynx and overlays the trachea in animals. In different animals, Anatomical variations of the thyroid are primarily seen in the isthmus connecting the gland’s two lobes. The size of the gland approximates 0.20% of body weight. However, the size may increase due to iodine deficiency, ingestion of goitrogenic toxins, tumors, and hyperactivity of the gland, or maybe reduced to fibrotic due to hyperthyroidism. Thyroid follicles are the thyroid gland’s functional units with a spherical structure composed of an inner core of the thyroglobulin-hormone complex, colloid. The colloid is surrounded by an outer monolayer of follicular cells and acts as the storage tank of thyroid hormone. The overall size of the follicles and the shape of their follicular cells may differ due to the functional activity of the thyroid gland. The dormant follicular cells are squamous-shaped compared to the tall columnar, highly active follicular cells. Other than colloid, the thyroid C-cells are interspersed between the follicles. The thyroid C-cells are the source of the hypocalcemic hormone calcitonin that is associated with calcium metabolism. The third type of tissue embedded in the thyroid gland is the parathyroid. The parathyroid is the source of the hypercalcemic hormone parathormone. Functions of the thyroid gland: The thyroid gland functions the same in all animals. There are four primary functions of the thyroid gland in animals; trapping the iodide, synthesis of thyroid hormones, storage, and release of hormones. All these activities of the thyroid gland are usually regulated by thyroid-stimulating hormone (TSH), a pituitary hormone. Hormonogenesis and release of thyroid hormone mainly have four stages: Trapping of Iodide: The follicular cells trap the circulating I– from the blood against the concentration gradient mediated by a sodium iodide symporter (NIS) protein present on the thyroid follicular cell membrane. A trapping enzyme catalyzes the trapping process via a mode of active transport catalyzed by an ATP-dependent Na+K+-ATPase. This trapping system’s high efficiency can concentrate most blood iodine in the thyroid gland. This process is stimulated by TSH and blocked by large amounts of I– or goitrogenic agents. (Figure 1) Synthesis of Thyroid Hormones: The trapping of I- is followed by its oxidation, catalyzed by peroxidase to form a highly active free radical I*. This reaction is also stimulated by TSH and inhibited by thyrotoxic agents (thiouracils or thioureas). At the follicular cell membrane-colloid interface, highly active I* binds to thyroglobulin, a thyroidal glycoprotein of a high molecular weight of 660 kDa. I* binds to thyroglobulin at its tyrosine moieties to form monoiodotyrosine (MIT) or a diiodotyrosine (DIT). After that, the iodinated phenyl groups of the tyrosine undergo oxidative condensation resulting in the synthesis of thyroid hormones. The thyroid gland produces two active hormones: 3,5,3’-triiodothyronine (T3) and 3,5,3′,5,-tetraiodothyronine (T4). T3 is formed by the oxidative condensation of an iodinated phenyl group of one DIT to an MIT group or of one DIT to another DIT to create T4. The inner deiodination product of the T4 is the inactive hormone is 3,3′,5’-triiodothyronine (rT3). Storage of hormones: Thyroid follicular cells synthesized thyroglobulin and localized it to the cell membrane for the iodination process. Iodinated thyroglobulin, also known as a colloid, is released and stored in the lumen of the follicle. Release of hormone: TSH stimulates the release process of hormones. TSH acts at the follicular cell membrane, the second site of action for TSH. Colloid from the lumen is taken up to the follicular membrane, where they are taken in as vesicles into the follicular cells by the process of endocytosis. Lysosomes merge with these vesicles to release lysosomal proteases that hydrolyze the colloid. Hydrolyses of colloid release their T3, T4, DIT, and MIT. Microsomal tyrosine deiodinases enzymatically degrade the released DIT and MIT, and their iodine is recycled within the follicular cell. A simple diffusion process releases the T4 and T3 into circulation. Out of the total hormone released from the gland, 90% is T4, and only 10% is T3. The phenyl group of T4 may also undergo some deiodination within the gland or in the peripheral tissues to form rT3. rT3 is an inactive form of the T3 hormone. Therefore it undergoes a degradation pathway. (Figure 1) The regulation of T3 and T4 secretion starts in the hypothalamus. The thyrotropin-releasing hormone secreted from the hypothalamus acts on the pituitary gland. This stimulates TSH secretion, which ultimately acts on the thyroid gland, producing and releasing thyroid hormones. The action and disorder of Thyroid Hormones: In humans and animals, thyroid hormones play a vital role in regulating metabolic and cellular mechanisms. The mode of action can be quick in minutes or prolonged to hours or longer. Thyroid hormones in normal levels work together with other hormones like insulin (beta cells of the pancreatic islets) and growth hormone (pituitary gland) to work on protein synthesis in different cellular processes. However, thyroid hormones can be catabolic in excess (hyperthyroidism), with increased protein breakdown and gluconeogenesis. Hyperthyroidism is more common in cats middle-aged to old cats than in dogs. However, thyroid carcinoma could be a cause when it occurs in dogs. Decreased levels of thyroid hormones (hypothyroidism) cause a slower metabolic rate in animals. This disorder is most likely seen in middle-aged (4-10 Years) dogs and mid to large-size dog breeds (Doberman pinscher, Golden retriever, etc.). Also, spayed female dogs have a higher hypothyroidism risk than unspayed ones. On the contrary, naturally occurring hypothyroidism is rare in cats. Reference: Kaneko, J. J. (2008). Clinical biochemistry of domestic animals. San Diego: Academic Press. Thanas C, Ziros PG, Chartoumpekis DV, Renaud CO, Sykiotis GP. The Keap1/Nrf2 Signaling Pathway in the Thyroid—2020 Update. Antioxidants. 2020; 9(11):1082. https://doi.org/10.3390/antiox9111082 Mark E. Peterson. The Thyroid Gland in Animals. Last full review/revision Jul 2019 | Content last modified Oct 2020. MSD MANUAL Veterinary Manual, https://www.msdvetmanual.com/endocrine-system/the-thyroid-gland/the-thyroid-gland-in-animals