Tick transmission of toxoplasmosis.

Introduction: Infection with Toxoplasma gondii (T. gondii) causes the disease toxoplasmosis in humans and animals. Oral transmission alone may not explain the widespread distribution of this parasite over large species of host animals and geographic areas.Areas covered: Limited studies indicate the potential role of ticks in the distribution of T. gondii. The possibility of transmission of T. gondii has been demonstrated in Dermacentor variabilis, Dermacentor andersoni, Amblyomma americanum, Dermacentor reticulatus, Ixodes ricinus, Ixodes amblyomma, Amblyomma cajennense, Ornithodorus moubata and Haemaphysalis longicornis. Tick transmission of T. gondii, spread of ticks and pathogens by migratory birds and presence in the United States (US) of tick vectors of human and animal disease like Haemaphysalis longicornis indigenous to other parts of the world provide a possible mechanism for the widespread distribution of T. gondii, and a potentially expanding disease threat.Expert opinion: The evidence indicates that T. gondii is potentially an unrecognized tick-borne pathogen spreading toxoplasmosis, and that clinicians might consider toxoplasmosis in the differential diagnosis of tickborne diseases.

Perspective on current and emerging drugs in the treatment of acute and chronic toxoplasmosis.

No new drugs for treatment of toxoplasmosis have been approved in over 60 years, despite the burden of toxoplasmosis on human society. The small selection of effective drugs is limited by important side effects, often limiting patient use. This perspective highlights promising late-stage drug candidates in the treatment of toxoplasmosis. Presently, drugs target the tachyzoite form of the parasite Toxoplasma gondii responsible for the acute infection but do not eradicate the tissue cyst form underlying chronic infection. Pyrimethamine - the first-line and only approved drug for treatment of toxoplasmosis in the United States - inhibits parasite DNA synthesis by inhibiting dihydrofolate reductase (DHFR). Two novel DHFR inhibitors with improved potency and selectivity for parasite DHFR over human DHFR are in clinical-stage development. One of the most advanced and promising therapeutic targets, demonstrating potential to treat both acute and chronic toxoplasmosis, is the calcium-dependent protein kinase 1 (CDPK1) which plays an essential role in the intracellular replicative cycle of the parasite, and has no direct mammalian homolog. Two CDPK1 inhibitor programs have identified potent and selective lead series, demonstrating acceptable systemic and CNS exposure, and in vivo efficacy in animal models of acute and chronic infection. Physicians need a better arsenal of parasiticidal drugs for the treatment of toxoplasmosis, particularly those active against tissue cysts.

High burden and low awareness of toxoplasmosis in the United States.

Toxoplasmosis, a disease with diverse clinical manifestations, caused by infection with the Apicomplexan parasite, Toxoplasma gondii (T. gondii), is a major source of morbidity and mortality in the United States. Although toxoplasmosis prevalence and mortality have declined over the past two decades, the CDC considers this disease a neglected parasitic infection requiring public health action. Here, we overview the literature to bring attention to the prevalence of the disease in the United States, and high economic burden associated with the disease. The conclusions to be drawn are clear: there is low awareness and underestimation of the disease burden amongst healthcare professionals; a high economic burden associated with the disease; relapse rates to treatment represent additional mortality and morbidity and further costs for the healthcare system; and better treatments are necessary to combat this public health threat.

Patient and treatment pathways for toxoplasmosis in the United States: data analysis of the Vizient Health Systems Data from 2011 to 2017.

Toxoplasmosis causes substantial morbidity and mortality in the United States (US). Clinical manifestations to toxoplasmosis vary and there is limited information on incidence or treatment patterns in the US. Treatment pathways for pyrimethamine-based regimens and trimethoprim-sulfamethoxazole (TMP-SMX) for toxoplasmosis hospitalizations were investigated using the Vizient Health Systems inpatient and outpatient data. Between January 1st, 2011 and December 31st, 2017, 10,273 hospital visits from 4,736 unique patients received a primary or secondary ICD-9/ICD-10 diagnosis for toxoplasmosis. The projected annual hospital visits with a diagnosis of toxoplasmosis was 68,821, corresponding to a total annual incidence of 9,832 comprising ocular toxoplasmosis of 2,169, toxoplasmic encephalitis of 1,399, unspecified toxoplasmosis of 4,368, congenital toxoplasmosis of 381, multisystemic toxoplasmosis of 69 and other toxoplasmosis of 1,446. Only 16.3% of the study population received treatment with pyrimethamine-based regimens or TMP-SMX. Pyrimethamine-based regimens were used significantly more often than TMP-SMX in toxoplasmic encephalitis (88.7% vs 79.6%, p = 0.01), other toxoplasmosis (85.0% vs 79.2%, p = 0.04), and unspecified toxoplasmosis (87.6% vs 77.9%, p = 0.03) in hospitals with 300 beds or more. A significantly higher percentage of visits with TMP-SMX as first-line treatment switched to pyrimethamine-based regimens compared to visits initiated on pyrimethamine-based treatments (26.7% vs 4.1%, p < .001). Ocular toxoplasmosis patients receiving pyrimethamine-based therapy were more likely to be discharged home compared to TMP-SMC at rates of 72.4% and 55.2%, respectively. Our analysis of commercial insurance records suggest toxoplasmosis is undertreated. Overall, pyrimethamine-based regimens are favored over TMP-SMX, have higher rates of discharge home, and have lower switch rates.

Adverse Event Profile of Pyrimethamine-Based Therapy in Toxoplasmosis: A Systematic Review.

INTRODUCTION: Approximately a third of the population worldwide is chronically infected with Toxoplasma gondii. Pyrimethamine-based regimens are recommended for the treatment of toxoplasmosis. OBJECTIVE: The aim was to evaluate the safety profile of pyrimethamine-based treatment for the three main Toxoplasma manifestations: toxoplasmic encephalitis (TE), ocular toxoplasmosis, and congenital toxoplasmosis. METHODS: PubMed, Cochrane Library, and Google Scholar databases were searched through August 1, 2016. Randomized, observational, prospective/retrospective, and cohort studies were eligible. Thirty-one studies were included with a total of 2975 patients. Of these, 13 were in congenital toxoplasmosis (n = 929), 11 in ocular toxoplasmosis (n = 1284), and seven in TE (n = 687). Across manifestations, adverse event (AE)-related treatment discontinuation and/or change in therapy involved ≤37% of patients and occurred in >55% of studies: 100% for ocular toxoplasmosis, 57.1% for TE, and 61.5% for congenital toxoplasmosis. The most commonly observed AEs were bone marrow suppression, dermatologic, and gastrointestinal (GI). The prevalence of bone marrow suppression-related AEs was ≤50% in congenital toxoplasmosis, ≤42.7% in TE, and ≤9.0% in ocular toxoplasmosis. The frequency of GI and dermatologic AEs were ≤100 and ≤11.1%, respectively, for ocular toxoplasmosis, ≤10.7 and ≤17.9% for TE, and ≤10.8 and ≤2.1% for congenital toxoplasmosis. Steven-Johnson syndrome was reported in two patients with ocular toxoplasmosis and one with TE. CONCLUSION: The AE profile associated with pyrimethamine-based treatments differed by each manifestation of toxoplasmosis and within a given manifestation. Hematologic AEs occurred across all manifestations indicating the importance of monitoring the blood of patients administered pyrimethamine-based regimens.