Human Babesiosis: An Emerging Zoonotic Disease in India
Post no 1296 Dt 28/06 /2019
Compiled & shared by-DR. RAJESH KUMAR SINGH, (LIVESTOCK & POULTRY CONSULTANT), JAMSHEDPUR, JHARKHAND,INDIA 9431309542, rajeshsinghvet@gmail.com
The arboviral and zoonotic diseases are a huge challenge in India leading to increased morbidity and mortality in humans.
Babesiosis , caused by infection with intraerythrocytic parasites of the genus Babesia , is one of the most common infections of free-living animals worldwide and is gaining increasing interest as an emerging zoonosis in humans. All Babesial parasites described to date are transmitted by Ixodid ticks to their vertebrate hosts, but the infection can spread by blood transfusion and perinatally. The parasites replicate in the vertebrate hosts’ red blood cells and are called piroplasms due to their pear-shaped appearance when within the infected host cells.Human babesiosis is caused by one of several babesial species that have distinct geographic distributions based on the presence of competent hosts.
In North America, babesiosis is caused predominantly by Babesia microti a rodent-borne piroplasm, and also occasionally by a newly recognized species, the so-called WA1 piroplasm. In Europe, babesiosis is considerably rare but more lethal; it is caused by the bovine pathogen Babesia divergens . The spectrum of disease is broad, ranging from an apparently silent infection to a fulminant, malaria-like disease resulting occasionally in death.
Without passing through pre-erythrocytic stage the Babesia parasites enter the erythrocytes and multiply resulting in rupture of the RBCs followed by infection of other RBCs.
Babesiosis is an emerging tick-borne zoonotic disease caused by obligate intra-erythrocytic protozoa of genus Babesia, which is widespread over the world. There are more than 100 species which infect several wild and domesticated animals; but only few have been confirmed as causative agents for babesiosis in humans. Babesia microti, Babesia duncani, Babesia divergens, and Babesia venatorum are the species which have been identified to cause infection in humans worldwide. B. microti is the most common species to cause infection in humans. Even though it is observed that the infection by a species varies with the geographical area. Infection of B. microti cases is common in United States; B. divergens in Europe and B. venatorum found to cause more infection in China.
The first human case of babesiosis was identified in 1957 in a Croatian herdsman. Babesiosis considered as occupational hazard for farmers, landscapers, hunters, and professionals who work in direct contact with the soil and animals. Travelers and health professionals are of more concern about babesiosis while considering the destination, duration and the risk of exposure to infection of babesiosis. Currently more than half a billion people are involved in international travel annually, movement of people and their interaction with the various environments could be a risk factor. In India the first case of babesiosis reported in 2005.
What is this parasite?
Babesia is included in the phylum Apicomplexa of the suborder Piroplasmida and family Babesiidae. They are oval, round or pyriform in shape presenting annular conformation and peripheral location, similar to the protozoa Plasmodium falciparum which complicates the diagnosis. In Plasmodium, hemozoin deposits on the ring and banana-shaped gametocytes observed which absent in Babesia spp.
Rout of infection/transmission-
Bite of Ixodes tick is the most common route infection. The previously infected Ixodes ticks, blood transfusion and congenital pathways are routes of transmission. Bite of a tick injects the sporozoites, which then penetrates into the erythrocytes directly in case of B. bovis and B. divergens; whereas, in case of B. microti initially it lodge into lymphocytes and then invade into red blood cells.
The sporozoite transform into trophozoites which then into merozoites by binary fission (merogony). During this process erythrocytic membrane breaks and released merozoites invade new cells resulting in an intra-erythrocytic cycle.
The parasitic cycle in tick
When ticks feed on blood it ingests trophozoites, merozoites and gametocytes. Only gametocytes could survive the intestinal lumen of the tick where gamogony occurs; which fuse to form diploid zygotes. These zygotes invade the digestive and undergo successive round of multiplication before emerging as haploid kinetes. The kinetes migrate by means of the hemolymph to many other organs including the ovaries, where further division occurs. After hatching of eggs kinetes migrate to the salivary gland; where they transform into multi-nucleated stages by sporogony which later forms sporozoites that are inoculated from saliva during the vector’s feeding. Period of incubation depends on the route of transmission. Following a tick bite it is up it takes up to six weeks and nine weeks following transfusion of contaminated blood. Babesiosis can be asymptomatic to life-threatening in humans. The severity of the infection may vary with age and host immune status.
Pathogen Life Cycle in Humans———
When Babesia spp. sporozoites are first injected into the human host, they target the host RBCs immediately, unlike Plasmodium spp. which are required to undergo an exoerythrocytic phase in hepatic cells. Further, infected RBCs remain circulating in peripheral blood stream, including regularly passing through the hosts’ spleen, and do not sequester to the fine capillaries of the bone marrow or organs. It is the parasite’s ability to first recognize and then invade host RBCs that is central to human babesiosis and the parasites invade RBCs using multiple complex interactions between parasite proteins and the host cell surface, which are not fully elucidated yet .Once inside the RBC, the parasite begins a cycle of maturation and growth. The early stages of the cycle are morphologically indistinguishable from Plasmodium spp., with both appearing as ring-like parasites. Replication occurs by budding, where one ring forms divides into two, often referred to as “figure eight” form. Budding may occur again, giving ride to the tetrad form know as a “Maltese Cross” . Both these morphological forms are unique to Babesia spp. and are the basis of definitive diagnosis by microscopy, especially if Plasmodium spp. are also suspected. Once the parasites have concluded division, the resulting merozoites egress from the RBCs, destroying it in the process and seek new, uninfected RBCs to invade, perpetuating the intracellular cycle of infection.
The clinical signs
The symptoms were highly nonspecific which could pertain to many other febrile infective conditions. Infected individuals develop fatigue, myalgia, and malaise followed by persistent or intermittent pattern of fever. Other commonly reported symptoms were sweating, headache, anorexia, vomiting, diarrhea, abdominal pain, joint pain, sore throat, cough, breathing difficulty, redness of eyes, dark-colored urine, depression, and emotional lability, hepatomegaly, splenomegaly, jaundice.
Diagnosis
Diagnosis of babesiosis is made from patient history, especially travel history to endemic areas, blood smear examination stained with Giemsa, for detection of intra erythrocytic pathogen. In low parasitemia molecular methods like polymerase chain reaction (PCR), DNA sequency, DNA microarray systems and serologic methods like indirect immunoflourescence (IFA) Imunoblot, immunochromatography, and ELISA (enzymelinked immunosorbent assay) may be used.
The most commonly used antibiotics are atovaquone, azithromycin, clindamycin, quinine. Supportive therapy like antipyretics, vasopressors, blood transfusion and mechanical ventilation required.
Treatment————–
Treatment for mild babesiosis is clindamycin for 7–10 days in B. divergens and B. venatorum, with the addition of quinidine or quinine for B. duncani. As the drug-related toxicity for quinine can be significant , intravenously administered quinidine is a recommended alternative . In mild B. microti infections, a 7–10-day course atovaquone plus azithromycin is the combination of choice after it was shown this is was just as effective but with fewer side effects compared with the clindamycin/quinine combination . Indeed, atovaquone plus azithromycin was successfully used to treat a B. venatorum infection in Germany , suggesting that investigation into the most effective and most tolerable treatments are necessary. It is also suggested that chronic B. microti parasite-positive but asymptomatic infection lasting more than 3 months are also treated with this same combination . However, in immunocompromised individuals or any severe case with symptoms of severe hemolysis, renal or hepatic distress, compromised respiratory function, or a parasitemia greater than 10 %, regardless of species, a 10-day course of intravenous clindamycin plus quinine coupled with exchange transfusion is the recommended course of treatment . The additive measure of exchange transfusion swiftly removes the parasitized RBCs from the host circulation, resolving any pathologies arising from anemia, such as low hematocrit and circulating toxic metabolites which released into the host’s circulatory system from the cyclical destruction of the RBCs.
Prevention is better than cure
The best preventive measure for babesiosis is to avoid exposure to tick habitats in endemic area. Efforts should be made to prevent tick bites and transmission of infections. There is no vaccine available on babesiosis.
India has witnessed a number of outbreaks of arboviral and zoonotic diseases in the last two decades. prevention and control of these diseases needs intersectoral coordination between health and veterinary sectors and involvement of epidemiologists, microbiologists, veterinary officers, entomologists, etc. Joint orientation of various sectors is needed to understand the knowledge pertaining to the source, transrnission, pathogenicity, treatment and control of zoonotic diseases.
Ref- Marathe A, Tripathi J, Handa V, Date V. Human babesiosis – A case report. Indian J Med Microbiol 2005;23:267-9
