Common Parasitic Infection Research Articles

Unfortunate Presentation of a Common but Forgotten Parasite Infection in the Caribbean

A 77 years old man is brought to the ER due to a 2-3 days history of altered mental status, cough and shortness of breath associated to fever and non-bloody diarrheas. A month before he had a hospitalization due to seizures, that were attributed to a left frontal meningioma. While admitted he received intravenous steroids and was discharged on dexamethasone while awaiting neurosurgical evaluation. On evaluation he was found hypotensive, tachycardic and tachypneic. His physical exam was unremarkable, although he was disoriented. He had 34% bands, thrombocytopenia, and mild elevation of liver enzymes. His eosinophil's count was normal. A Chest X ray and head CT did not show significant interval changes. He was admitted and started on broad spectrum antibiotics. Initial blood cultures were positive for S. gallolyticus, for which he was consulted for a colonoscopy. The study revealed multiple erythematous skip lesions. Tissue examination demonstrated acute colitis due to Strongyloides stercoralis. Daily treatment with weight-based oral ivermectin was started without response. His clinical course continued deteriorating, developing a widespread urticarial rash, progressive hypoxemic respiratory failure due to cytology confirmed larvae infestation and profound vasopressor-resistant shock. Despite aggressive treatment he died 14 days after admission. Strongyloidiasis is one of the most overlooked helminthic diseases. The clinical course is usually mild or asymptomatic. Subclinical infection may persist for decades since the parasite can complete the entire lifecycle within the human host. The risk of dissemination increases with impaired immunity, underlying malignancy, the administration of cytotoxic drugs, or with the use of steroids as it was in our case. The massive dissemination of the filariform larvae led to profound sepsis, respiratory failure, and death. Even though S. stercolaris is considered a tropical disease, in this globalized era, is important not to underestimate the potentially fatal outcomes of this parasitic infection if undiagnosed, this is very important when providing care to patients coming from endemic areas, and when immunosuppression or corticosteroids are considered in this population at risk. Our case exemplifies the importance of screening for Strongyloidiasis in endemic areas prior to immunosuppression and illustrates the high level of suspicion needed when dealing with an immunocompromised patient with unexplained sepsis.Figure: Colon mucosa with multiple erythematous skip lesions.Figure: Acute colitis with organism consistent with strongyloides parasites.Figure: Urticarial rash.

Viral and parasitic pathogen burden and the association with stroke in a population-based cohort.

Background Higher cumulative burden of viral and bacterial pathogens may increase the risk of stroke, but the contribution of parasitic infections in relation to cumulative pathogen burden and risk of stroke has rarely been examined. Aim To estimate the association of multiple persistent viral and parasitic infections with stroke in a representative sample of adults in the United States. Methods Serological evidence of prior infection was categorized as positive for 0-1, 2, 3, or 4-5 infections based on immunoglobulin G seropositivity to cytomegalovirus, hepatitis A virus, hepatitis B virus, Toxoplasma gondii, and Toxocara spp. in 13,904 respondents from the National Health and Nutrition Examination Survey III. Regression analysis was used to estimate the cross-sectional association between serological evidence of prior infection and history of stroke adjusting for demographic risk factors, and potential mediators of stroke. Results Age-adjusted models that included serological evidence of prior infection to cytomegalovirus, hepatitis A virus, hepatitis B virus, Toxoplasma gondii, and Toxocara spp. showed that adults in the highest serological evidence of prior infection category (4-5 infections) had a higher prevalence of stroke (5.50%, 95% confidence interval 2.44-10.46%) than those in the lowest serological evidence of prior infection categories (1.49%, 95% confidence interval 1.01-2.11%), and a trend test suggested a graded association between serological evidence of prior infection and stroke ( p = 0.02). In multivariable logistic regression models, the positive association of serological evidence of prior infection with stroke prevalence remained significant after adjustment for other significant risk factors (odds ratio = 1.4, p = 0.01) but was only significant among those aged 20-59 (odds ratio = 2.0, p = 0.005) and not among those aged 60-69 ( p = 0.78) or 70 and older ( p = 0.43). Conclusion We found support for a connection between serological evidence of prior infection to cytomegalovirus, hepatitis A virus, hepatitis B virus, Toxoplasma gondii, and Toxocara spp. and stroke among those aged 20-59. There may be a need to consider common parasitic infections in addition to viral and bacterial pathogens when calculating serological evidence of prior infection in relation to cerebrovascular disease.

Cysticercosis: Reiterating the role of cytodiagnosis.

Cysticercosis is a common parasitic infection in many Asian countries. The histopathological features of this parasitic infection are well established, however, the subtle cytological features and their importance in diagnosing this condition need more elaboration. In this case series we have reiterated the role of fine-needle aspiration cytology (FNAC) in the diagnosis of cysticercosis in clinically unsuspected cases, thereby obviating the need for a biopsy. Sixteen patients presented with palpable subcutaneous swellings. The clinical diagnosis varied from tubercular/reactive lymphadenitis, lipoma to neurofibromatosis. These patients were subjected to FNAC of the swellings. In all 16 cases, a definitive diagnosis of cysticercosis was made on FNAC on the basis of characteristic features like parasite tegument/bladder wall and occasional hooklets. Features suggestive of host reaction were also observed, which included multinucleated giant cells, mixed inflammatory infiltrate with conspicuous eosinophils, histiocytes, and palisading granulomas. These findings were correlated with histopathology and patients were followed up. We noticed spontaneous resolution of the nodules after the FNAC in six patients. The cytological diagnosis of cysticercosis is quite straightforward in cases where the actual parasitic structures are identified in the smears. However, in the absence of parasitic fragments, features suggestive of host reaction should alert the cytologist to search for the evidence of cysticercosis in the smear, which can help in early and timely diagnosis and treatment of the disease. We also postulate that injury to certain parts of the larval form during FNAC procedure would result in degeneration of the parasite.

Neonatal Central Nervous System Infection

AbstractIn this review article, neuroimaging features of common bacterial, viral, fungal, and parasitic infections of the pediatric central nervous system (CNS) are discussed. Imaging modalities used by pediatric neuroradiologists include cranial ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI). After a brief discussion of the clinical presentation of each disease entity, imaging strategies and findings are reviewed. The role of advanced neuroimaging techniques is discussed wherever appropriate.

Neurocysticercosis presenting with visual and unilateral auditory hallucinations and behavioral change: a case report

IntroductionNeurocysticercosis (NCC) is the most common parasitic infection of the central nervous system (CNS)(1)(2). It is caused by larvae stages of Taenia Solium and is the major cause of acquired epilepsy worldwide(3). Seizure disorders are common neurological manifestation(4); however, neuropsychiatric manifestations have also been reported(5,6). Humans acquire infection through ingestion of eggs of Taenia Solium from contaminated food(7). The brain immunological response towards the cysts may be responsible for the pleomorphic manifestations(8), including psychiatric symptoms that may take years before the onset of seizures(6). As a result, diagnostic confusion is common, and this often affects management and outcome.Case reportWe report a case of 30-year-old black African male who presented with a history of auditory hallucinations and behavioral changes without focal neurologic signs or symptoms. The onset of generalized tonic-clonic seizures prompted him to seek medical attention although prodromal psychiatric symptoms started about a year before the onset of seizures. MRI of the brain revealed multiple cysts involving mainly the cerebral cortex.ConclusionThis case highlights the need to exclude organic cortical pathology should in rare forms of psychiatric manifestations such unilateral auditory hallucinations and acute behavioral disturbances. Correct diagnosis and prompt management will prevent complications and usually have a favorable prognosis.Key clinical messagePleomorphic manifestations of NCC pose a challenge in diagnosis. We present a case of a 30-year old male who presented with prodromal psychiatric symptoms before the onset of generalized tonic-clonic seizures. This case highlights challenges in diagnosis though prompt management promises a favorable outcome.

Gene silencing by RNA interference in Sarcoptes scabiei: a molecular tool to identify novel therapeutic targets

BackgroundScabies is one of the most common and widespread parasitic skin infections globally, affecting a large range of mammals including humans, yet the molecular biology of Sarcoptes scabiei is astonishingly understudied. Research has been hampered primarily due to the difficulty of sampling or culturing these obligatory parasitic mites. A further and major impediment to identify and functionally analyse potential therapeutic targets from the recently emerging molecular databases is the lack of appropriate molecular tools.MethodsWe performed standard BLAST based searches of the existing S. scabiei genome databases using sequences of genes described to be involved in RNA interference in Drosophila and the mite model organism Tetranychus urticae. Experimenting with the S. scabiei mu-class glutathione S-transferase (SsGST-mu1) as a candidate gene we explored the feasibility of gene knockdown in S. scabiei by double-stranded RNA-interference (dsRNAi).ResultsWe provide here an analysis of the existing S. scabiei draft genomes, confirming the presence of a double stranded RNA (dsRNA) - mediated silencing machinery. We report for the first time experimental gene silencing by RNA interference (RNAi) in S. scabiei. Non-invasive immersion of S. scabiei in dsRNA encoding an S. scabiei glutathione S-transferase mu-class 1 enzyme (SsGST-mu1) resulted in a 35% reduction in the transcription of the target gene compared to controls.ConclusionsA series of experiments identified the optimal conditions allowing systemic experimental RNAi without detrimental side effects on mite viability. This technique can now be used to address the key questions on the fundamental aspects of mite biology and pathogenesis, and to assess the potential therapeutic benefits of silencing S. scabiei target genes.

Parkinson’s disease and Toxoplasma gondii infection: Sero-molecular assess the possible link among patients

We investigated the possible association between Parkinson's disease (PD), the second most common neurodegenerative disorder and Toxoplasma gondii infection, the most common neurotropic protozoan parasitic infection, using serological and molecular techniques. One hundred and fifteen patients with confirmed PD and 115 healthy subjects in the same age and sex distribution were enrolled in this study. Blood samples were taken from each participant and the sera was screened for anti-Toxoplasma antibodies (IgG and IgM). PCR assay was performed in duplicate using the primer pair targeting the B1 gene of Toxoplasma. Amplicons were directly sequenced to conduct the phylogenetic analysis. The prevalence of Toxoplasma infection based on IgG titer was 53% in case and 55.6% in the control groups, revealing no statistically significant association between Toxoplasma seropositivity and PD (OR=0.90; 95% CI=0.54–1.51; P=0.691). According to PCR assay, the prevalence of Toxoplasma infections was 19.3% in the case and 10.4% in control groups which the difference was statistically significant (OR=3.02; 95% CI=1.46–6.27; P=0.002). Multiple sequence alignment of Toxoplasma gondii isolates manifested a common haplotype by the identity: 93.6–100% and divergence: 0–6.7%. We concluded that T. gondii infection not only could not be a risk factor to PD, but even it could be concluded that patients with PD are in more risk to acquisition of infection. These results provide fresh insights into the ambiguous association between T. gondii infection and PD.

More Than an Association: Latent Toxoplasmosis Might Provoke a Local Oxidative Stress That Triggers the Development of Bipolar Disorder.

Introduction:Toxoplasma gondii, a common parasitic infection, has a special affinity to the brain. It has a lifelong existence without an apparent clinical disease. While the etiology of bipolar disorder (BD) remains unclear, epidemiological studies suggest a role for infections. Central nervous system is particularly susceptible to oxidative stress (OS) because of its high metabolic rate and its low levels of antioxidant defenses. OS is a contributor to the initiation and progression of many neurological illnesses. OS injury is a constantly and compelling finding associated with BD and toxoplasmosis.Aim:This cross-sectional study has investigated a possible role of toxoplasma-induced OS in the development of BD.Methods:Healthy controls and BD patients were examined for anti-Toxoplasma immunoglobulin-G (IgG) and two protein (3-nitrotyrosine) and DNA (8-hydroxy-2’ deoxyguanosine [8-OHdG]) OS markers.Results:Toxoplasma positivity was higher (40%) among BD patients compared to controls (12%). Significantly higher levels of anti-Toxoplasma IgG were detected in BD patients compared to controls. Nitrotyrosine (796.7 ± 106.28) and especially 8-OHdG (20.31 ± 8.38) were significantly higher among toxo-positive BD compared to toxo-negative BD (675.97 ± 144.19 and 7.44 ± 2.86) and healthy controls (464.02 ± 134.6 and 4.17 ± 1.43).Conclusion:These findings might indicate a role for Toxoplasma infection in the development of BD, possibly through creating a highly oxidative brain environment.

Lumbar spinal intradural neurocysticercosis: A case report.

Neurocysticercosis is a parasitic disease that results from the larvae of Taenia solium. While neurocysticercosis is considered as the most common parasitic infection of the nervous system, spinal neurocysticercosis is rare. The present case study investigated a 59-year-old woman, who was admitted to our hospital with pain in the bilateral lower limbs and urinary complaints in the form of straining of micturition with increasing frequency. Magnetic resonance imaging revealed an intradural extramedullary lesion extending from L1/2 to S1 of the spine. Subsequently, a laminectomy from L1 to S1 was performed 3 days post-presentation. Intraoperatively, a thin-walled cyst with clear fluid was identified, extending from L2 to S1. The exposed, white and mucoid cysticerci was removed completely. Which on pathological examination was identified to be cysticercosis.

Cytology Preparations of Formalin Fixative Aid Detection of Giardia in Duodenal Biopsy Samples.

Giardiasis is the most common intestinal parasitic infection in the United States. The organism elicits no, or minimal, inflammatory changes in duodenal biopsy samples, so it can be easily overlooked. We performed this study to determine whether Giardia could be isolated from the formalin fixative of biopsy samples, and to evaluate the value of fluid analysis in the assessment for potential infection. We prospectively evaluated duodenal biopsy samples from 92 patients with a clinical suspicion of giardiasis or symptoms compatible with that diagnosis (ie, diarrhea, bloating, or abdominal pain) Biopsy samples were routinely processed and stained with hematoxylin and eosin. Histologic diagnoses included giardiasis (5 cases, 4%), normal findings (64 cases, 70%), peptic injury/active duodenitis (12 cases, 13%), and intraepithelial lymphocytosis with villous blunting (10 cases, 12%). Fifteen cases (13%) showed detached degenerated epithelial cells or mucus droplets in the intervillous space that resembled Giardia. Cytology slides were prepared from formalin in the biopsy container using the standard Cytospin protocol and reviewed by a cytopathologist blinded to the biopsy findings. Cytologic evaluation revealed Giardia spp. in all 5 biopsy-proven cases, and identified an additional case that was not detected by biopsy analysis. Organisms were significantly more numerous (mean: 400 trophozoites; range, 120 to 810) and showed better morphologic features in cytology preparations compared with tissue sections (mean: 129 trophozoites; range, 37 to 253 organisms; P=0.05). Our findings suggest that cytology preparations from formalin fixative can resolve diagnostically challenging cases and even enhance Giardia detection in some cases.

Giardiasis Diagnosis and Treatment Practices Among Commercially Insured Persons in the United States.

Giardiasis, the most common enteric parasitic infection in the United States, causes an estimated 1.2 million episodes of illness annually. Published clinical recommendations include readily available Giardia-specific diagnostic testing and antiparasitic drugs. We investigated sequences of giardiasis diagnostic and treatment events using MarketScan, a large health insurance claims database. We created a longitudinal cohort of 2995 persons diagnosed with giardiasis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 007.1) from 2006 to 2010, and analyzed claims occurring 90 days before to 90 days after initial diagnosis. We evaluated differences in number and sequence of visits, diagnostic tests, and prescriptions by age group (children 1-17 years, adults 18-64 years) using χ2 tests and data visualization software. Among 2995 patients (212433 claims), 18% had a Giardia-specific test followed by or concurrent with an effective antiparasitic drug, without ineffective antibiotics. Almost two-thirds of patients had an antiparasitic and 27% had an antibiotic during the study window. Compared with children, adults more often had ≥3 visits before diagnosis (19% vs 15%; P = .02). Adults were also less likely to have a Giardia-specific diagnostic test (48% vs 58%; P < .001) and more likely to have an antibiotic prescription (28% vs 25%; P = .04). When Giardia-specific tests and antiparasitic and antibiotic prescriptions were examined, pediatric clinical event sequences most frequently began with a Giardia-specific test, whereas adult sequences most frequently began with an antiparasitic prescription. Giardiasis care infrequently follows all aspects of clinical recommendations. Multiple differences between pediatric and adult care, despite age-agnostic recommendations, suggest opportunities for provider education or tailored guidance.

A Case of Sudden Death due to Neurocysticercosis (NCC) in a Chronic Alcoholic

NCC or Neurocysticercosis is one of the clinical syndromes produced by infection with larval stage of tapeworm Taenia Solium (Pork tapeworm). It is the commonest parasitic infection affecting the central nervous system in human beings. Though seizure disorders are common in NCC in adults, sudden death is rarely reported. In our present case study one young male footpath dweller of 35 years of age and known to be a chronic alcoholic, died suddenly after a drinking bout. The dead body was sent to Kolkata police morgue for autopsy examination as a medico-legal case. Save a minor degree of cirrhotic changes in the liver, abdominal and thoracic viscera were unremarkable. Unexpectedly the brain parenchyma was found to be studded with numerous cystic lesions, which on Histopathological examination was confirmed to be the lesions of Neurocysticercosis. Cardiovascular events originating from coronary atherosclerosis are regarded worldwide as commonest cause of sudden death, more so in alcoholics. Neurological causes, particularly vascular events are not rare too. Meticulous autopsy, supported by ancillary investigations, occasionally leads an autopsy surgeon to such surprising outcomes.

K63-Linked Ubiquitination Targets Toxoplasma gondii for Endo-lysosomal Destruction in IFNγ-Stimulated Human Cells.

Toxoplasma gondii is the most common protozoan parasitic infection in man. Gamma interferon (IFNγ) activates haematopoietic and non-haematopoietic cells to kill the parasite and mediate host resistance. IFNγ-driven host resistance pathways and parasitic virulence factors are well described in mice, but a detailed understanding of pathways that kill Toxoplasma in human cells is lacking. Here we show, that contrary to the widely held belief that the Toxoplasma vacuole is non-fusogenic, in an immune-stimulated environment, the vacuole of type II Toxoplasma in human cells is able to fuse with the host endo-lysosomal machinery leading to parasite death by acidification. Similar to murine cells, we find that type II, but not type I Toxoplasma vacuoles are targeted by K63-linked ubiquitin in an IFNγ-dependent manner in non-haematopoetic primary-like human endothelial cells. Host defence proteins p62 and NDP52 are subsequently recruited to the type II vacuole in distinct, overlapping microdomains with a loss of IFNγ-dependent restriction in p62 knocked down cells. Autophagy proteins Atg16L1, GABARAP and LC3B are recruited to <10% of parasite vacuoles and show no parasite strain preference, which is consistent with inhibition and enhancement of autophagy showing no effect on parasite replication. We demonstrate that this differs from HeLa human epithelial cells, where type II Toxoplasma are restricted by non-canonical autophagy leading to growth stunting that is independent of lysosomal acidification. In contrast to mouse cells, human vacuoles do not break. In HUVEC, the ubiquitinated vacuoles are targeted for destruction in acidified LAMP1-positive endo-lysosomal compartments. Consequently, parasite death can be prevented by inhibiting host ubiquitination and endosomal acidification. Thus, K63-linked ubiquitin recognition leading to vacuolar endo-lysosomal fusion and acidification is an important, novel virulence-driven Toxoplasma human host defence pathway.

Frequency, diagnostic performance of coproantigen detection and genotyping of the Giardia among patients referred to a multi-level teaching hospital in northern India

Giardiasis, a common gastrointestinal parasitic infection in tropics, is diagnosed on stool microscopy (gold standard); however, its sensitivity is low due to intermittent fecal shedding. Coproantigen detection (ELISA) is useful but requires further evaluation. We aimed to study: (a) detection of Giardia by stool microscopy and/or coproantigen, (b) diagnostic performance of fecal antigen detection and microscopy, and c) genotypic characterization of G. lamblia using PCR specific for triose phosphate isomerase (tpi) gene. Stool samples from 2992 patients were examined by microscopy from March 2013 to March 2015 in a multi level teaching hospital in northern India. Giardia coproantigen detection was performed by ELISA in a subset of patients. Genetic characterization of G. lamblia was performed by PCR targeting tpi gene in a subset of microscopy positive stool samples. Of 2992 patients, 132 (4.4%) had Giardia by microscopy (cyst/trophozoite) and/or ELISA. ELISA was performed in 264 patients; of them, 127 were positive by microscopy. Sensitivity, specificity, positive and negative predictive values of ELISA were 91, 91, 94, and 91%, respectively, using microscopy as a gold standard. PCR was performed in 116 randomly selected samples having Giardia using tpi gene. Assemblages A and B were found among 44 (38%) and 72 (62%) patients, respectively. Assemblage B was more often associated with malnutrition and loss of appetite than A (48/72 [67%] vs. 21/44 [48%], P = 0.044 and 17/72 [24%] vs. 14/44 [32%], P = 0.019). We conclude that 4.4% of studied population had giardiasis. Fecal antigen is a useful method for diagnosis and assemblage B is the most common genotype.

Neurocysticercosis: a review on status in India, management, and current therapeutic interventions.

Tapeworms (cestodes) are segmented flatworms responsible for causing diseases that may prove fatal and difficult to treat in the absence of proper treatment and efficient drugs. Neurocysticercosis (NCC) is a common parasitic infection of the central nervous system and a major contributor to epilepsy caused by the metacestode (larva) of the human tapeworm Taenia solium, characterized by a range of pathological symptoms including epileptic seizures, headaches, and hydrocephalus. Cysticercosis is considered as a "biological imprint" of the socioeconomic development of a community in general and a country in particular. It is the single most common cause of epilepsy in the resource-poor endemic regions of the world, including most of South and Central America, India, Southeast Asia, China, and sub-Saharan Africa. A vast degree of variation in the neuropathology and clinical symptoms of NCC often makes it difficult to diagnose and manage. To add to it, emerging drug resistance to known anti-parasitic agents, together with the inability of these agents to prevent re-infection and relapse, further complicates the disease scenario. The aim of the current review was to provide the latest update on NCC with special emphasis on the Indian scenario, along with current and novel methods of diagnosis as well as scope of development for novel detection techniques, novel targets for drug development, and therapeutic interventions, as well as future challenges.

What Is New in Infectious Diseases?

The practice of infectious diseases is an ever-changing discipline. Diseases such as syphilis and tuberculosis have been with mankind for millennia, whereas conditions such as AIDS and Zika virus are relatively new maladies. A working knowledge of clinical presentations associated with Zika virus infection, syphilis, and common parasitic infections will help the primary care provider determine whom to treat and whom to refer to a specialist. Increasing the use of vaccination for influenza and pre-exposure prophylaxis for HIV infection should reduce the burden of these common diseases.

New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections.

Toxoplasma gondii, the most common parasitic infection of human brain and eye, persists across lifetimes, can progressively damage sight, and is currently incurable. New, curative medicines are needed urgently. Herein, we develop novel models to facilitate drug development: EGS strain T. gondii forms cysts in vitro that induce oocysts in cats, the gold standard criterion for cysts. These cysts highly express cytochrome b. Using these models, we envisioned, and then created, novel 4-(1H)-quinolone scaffolds that target the cytochrome bc1 complex Qi site, of which, a substituted 5,6,7,8-tetrahydroquinolin-4-one inhibits active infection (IC50, 30 nM) and cysts (IC50, 4 μM) in vitro, and in vivo (25 mg/kg), and drug resistant Plasmodium falciparum (IC50, <30 nM), with clinically relevant synergy. Mutant yeast and co-crystallographic studies demonstrate binding to the bc1 complex Qi site. Our results have direct impact on improving outcomes for those with toxoplasmosis, malaria, and ~2 billion persons chronically infected with encysted bradyzoites.

Neurocysticercosis, unusual manifestations

Neurocysticercosis is the most common parasitic infection in the central nervous system. This disease is presented when a person ingests Taenia solium eggs excreted in feces from another individual infected with taeniasis. In 50% of the cases, neurocysticercosis takes place in the brain parenchyma, and its appearance is less frequent in the posterior fossa and the spinal cord.The case of a patient with an atypical location of the parasite at the medulla oblongata, between parenchymal and spinal areas, is presented. The initial symptoms were common but its subsequent manifestations were similar to those of Bruns syndrome. Furthermore, the epidemiological profile of neurocysticercosis in Colombia, its control measures and prevention strategies were reviewed in this study.

Functional Analysis of the Rhoptry Kinome during Chronic Toxoplasma gondii Infection.

ABSTRACTToxoplasma gondii is one of the most common parasitic infections of humans worldwide. Once exposed, humans remain infected with T. gondii for life, and there are no therapeutics capable of eliminating a chronic infection. In the search for novel drug targets, T. gondii is known to contain several unique secretory organelles, one of which is called the rhoptries. Rhoptry organelles contain and secrete numerous proteins with kinase domains, but the roles of most of these kinases during infection remain unknown. In a recent mBio article, B. A. Fox et al. [mBio 7(3):e00193-16, 2016, http://dx.doi.org/10.1128/mBio.00193-16] performed a tour de force deletion analysis of 31 rhoptry kinases and examined their roles in the development of chronic infection. While rhoptry kinase deletion strains that displayed an acute infection defect also showed a reduction in chronic infection cyst burden, two rhoptry kinase deletion strains had decreased cyst burden without any change in acute virulence. These results indicate the necessity of the rhoptry kinases for the establishment and perhaps maintenance of chronic infection. They also highlight the potential of these kinases as drug targets to clear chronic infection or as candidates to generate a nonpersisting vaccine.

Common Infections in Patients Prescribed Systemic Glucocorticoids in Primary Care: A Population-Based Cohort Study.

BackgroundLittle is known about the relative risk of common bacterial, viral, fungal, and parasitic infections in the general population of individuals exposed to systemic glucocorticoids, or about the impact of glucocorticoid exposure duration and predisposing factors on this risk.Methods and FindingsThe hazard ratios of various common infections were assessed in 275,072 adults prescribed glucocorticoids orally for ≥15 d (women: 57.8%, median age: 63 [interquartile range 48–73] y) in comparison to those not prescribed glucocorticoids. For each infection, incidence rate ratios were calculated for five durations of exposure (ranging from 15–30 d to >12 mo), and risk factors were assessed. Data were extracted from The Health Improvement Network (THIN) primary care database. When compared to those with the same underlying disease but not exposed to glucocorticoids, the adjusted hazard ratios for infections with significantly higher risk in the glucocorticoid-exposed population ranged from 2.01 (95% CI 1.83–2.19; p < 0.001) for cutaneous cellulitis to 5.84 (95% CI 5.61–6.08; p < 0.001) for lower respiratory tract infection (LRTI). There was no difference in the risk of scabies, dermatophytosis and varicella. The relative increase in risk was stable over the durations of exposure, except for LRTI and local candidiasis, for which it was much higher during the first weeks of exposure. The risks of infection increased with age and were higher in those with diabetes, in those prescribed higher glucocorticoid doses, and in those with lower plasma albumin level. Most associations were also dependent on the underlying disease. A sensitivity analysis conducted on all individuals except those with asthma or chronic obstructive pulmonary disease produced similar results. Another sensitivity analysis assessing the impact of potential unmeasured confounders such as disease severity or concomitant prescription of chemotherapy suggested that it was unlikely that adjusting for these potential confounders would have radically changed the findings. Limitations of our study include the use of electronic medical records, which could have resulted in some degree of misclassification of the infectious outcomes; a possible reporting bias, as general practitioners could be more prone to record an infection in those exposed to glucocorticoids; and a low number of events for some outcomes such as scabies or varicella, which may have led to limited statistical power.ConclusionsThe relative risk of LRTI and local candidiasis is very high during the first weeks of glucocorticoid exposure. Further studies are needed to assess whether low albumin level is a risk factor for infection by itself (e.g., by being associated with a higher free glucocorticoid fraction) or whether it reflects other underlying causes of general debilitation.