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Veterinary Parasitology Apr 2018Canine babesiosis is a tick-borne disease caused by several Babesia spp. which have different susceptebility to anti-protozoal drugs. A few drugs and drug combinations... (Review)
Review
Canine babesiosis is a tick-borne disease caused by several Babesia spp. which have different susceptebility to anti-protozoal drugs. A few drugs and drug combinations are used in the treatment of canine babesiosis often without complete parasite elimination leaving treated dogs as carriers which could relapse with clinical disease and also transmit infection further. Although the large form canine babesial species Babesia canis, Babesia vogeli and Babesia rossi are sensitive to the aromatic diamidines imidocarb dipropionate and diminazene aceturate, small form species such as Babesia gibsoni, Babesia conradae and Babesia vulpes (Theileria annae) are relatively resistant to these drugs and are treated with the combination of the hydroxynaphthoquinone atovaquone and the antibiotic azithromycin. Azithromycin and other antibiotics that have anti-protozoal properties target the apicoplast, a relict plastid found in protozoa, and exert a delayed death effect. The triple combination of clindamycin, diminazene aceturate and imidocarb dipropionate is also effective against B. gibsoni and used to treat atovaquone-resistant strains of this species. Novel drugs and the synergistic effects of drug combinations against Babesia infection should be explored further to find new treatments for canine babesiosis.
Topics: Animals; Antiprotozoal Agents; Babesia; Babesiosis; Dog Diseases; Dogs
PubMed: 29657012
DOI: 10.1016/j.vetpar.2018.03.001 -
Clinical Microbiology Reviews Oct 2018Primary infection is usually subclinical, but cervical lymphadenopathy or ocular disease can be present in some patients. Active infection is characterized by... (Review)
Review
Primary infection is usually subclinical, but cervical lymphadenopathy or ocular disease can be present in some patients. Active infection is characterized by tachyzoites, while tissue cysts characterize latent disease. Infection in the fetus and in immunocompromised patients can cause devastating disease. The combination of pyrimethamine and sulfadiazine (pyr-sulf), targeting the active stage of the infection, is the current gold standard for treating toxoplasmosis, but failure rates remain significant. Although other regimens are available, including pyrimethamine in combination with clindamycin, atovaquone, clarithromycin, or azithromycin or monotherapy with trimethoprim-sulfamethoxazole (TMP-SMX) or atovaquone, none have been found to be superior to pyr-sulf, and no regimen is active against the latent stage of the infection. Furthermore, the efficacy of these regimens against ocular disease remains uncertain. In multiple studies, systematic screening for infection during gestation, followed by treatment with spiramycin for acute maternal infections and with pyr-sulf for those with established fetal infection, has been shown to be effective at preventing vertical transmission and minimizing the severity of congenital toxoplasmosis (CT). Despite significant progress in treating human disease, there is a strong impetus to develop novel therapeutics for both the acute and latent forms of the infection. Here we present an overview of toxoplasmosis treatment in humans and in animal models. Additional research is needed to identify novel drugs by use of innovative high-throughput screening technologies and to improve experimental models to reflect human disease. Such advances will pave the way for lead candidates to be tested in thoroughly designed clinical trials in defined patient populations.
Topics: Animals; Antiprotozoal Agents; Drug Discovery; Humans; Models, Animal; Toxoplasmosis
PubMed: 30209035
DOI: 10.1128/CMR.00057-17 -
Biology of Blood and Marrow... Sep 2018
Topics: Atovaquone; Hematopoietic Stem Cell Transplantation; Incidence
PubMed: 29909155
DOI: 10.1016/j.bbmt.2018.06.012 -
Hepatology Communications Jun 2017We report a novel association between the commonly used antimalarial medication atovaquone/proguanil and drug-induced autoimmune-like hepatitis. The patient developed...
We report a novel association between the commonly used antimalarial medication atovaquone/proguanil and drug-induced autoimmune-like hepatitis. The patient developed severe liver disease fulfilling biochemical, immunologic, and histologic criteria for the diagnosis of autoimmune hepatitis after the inadvertent rechallenge with the offending drug, which had caused self-limited hepatitic symptoms a year previously. Over a period of 18 months, the patient underwent two follow-up liver biopsies showing progressive resolution of the liver inflammation and achieved complete biochemical and immunologic remission on steroids. This remission persisted for 20 months following treatment withdrawal. : This well documented case raises awareness of the potential hepatotoxicity of atovaquone/proguanil. ( 2017;1:293-298).
PubMed: 29404460
DOI: 10.1002/hep4.1039 -
Pathogens (Basel, Switzerland) Sep 2021Babesiosis is an emerging tick-borne disease caused by apicomplexan parasites of the genus . With its increasing incidence worldwide and the risk of human-to-human... (Review)
Review
Babesiosis is an emerging tick-borne disease caused by apicomplexan parasites of the genus . With its increasing incidence worldwide and the risk of human-to-human transmission through blood transfusion, babesiosis is becoming a rising public health concern. The current arsenal for the treatment of human babesiosis is limited and consists of combinations of atovaquone and azithromycin or clindamycin and quinine. These combination therapies were not designed based on biological criteria unique to parasites, but were rather repurposed based on their well-established efficacy against other apicomplexan parasites. However, these compounds are associated with mild or severe adverse events and a rapid emergence of drug resistance, thus highlighting the need for new therapeutic strategies that are specifically tailored to parasites. Herein, we review ongoing babesiosis therapeutic and management strategies and their limitations, and further review current efforts to develop new, effective, and safer therapies for the treatment of this disease.
PubMed: 34578153
DOI: 10.3390/pathogens10091120