Neuroradiology of infectious diseases.

PURPOSE OF REVIEW: Early diagnosis of central nervous system (CNS) infections is crucial given high morbidity and mortality. Neuroimaging in CNS infections is widely used to aid in the diagnosis, treatment and to assess the response to antibiotic and neurosurgical interventions. RECENT FINDINGS: The Infectious Diseases Society of America (IDSA) guidelines have clear recommendations for obtaining a computerized tomography of the head (CTH) prior to lumbar puncture (LP) in suspected meningitis. In the absence of indications for imaging or in aseptic meningitis, cranial imaging is of low utility. In contrast, cranial imaging is of utmost importance in the setting of encephalitis, bacterial meningitis, ventriculitis, bacterial brain abscess, subdural empyema, epidural abscess, neurobrucellosis, neurocysticercosis, and CNS tuberculosis that can aid clinicians with the differential diagnosis, source of infection (e.g., otitis, sinusitis), assessing complications of meningitis (e.g., hydrocephalus, venous sinus thrombosis, strokes), need for neurosurgical interventions and to monitor for the response of therapy. Novel imaging techniques such as fast imaging employing steady-state acquisition (FIESTA), susceptibility-weighted imaging (SWI), and chemical exchange saturation transfer (CEST) contrast are briefly discussed. SUMMARY: Though the radiological findings in CNS infections are vast, certain patterns along with clinical clues from history and examination often pave the way to early diagnosis. This review reiterates the importance of obtaining cranial imaging when necessary, and the various radiological presentations of commonly encountered CNS infections.

Toxoplasma gondii infection and its implications within the central nervous system.

Toxoplasma gondii is a parasite that infects a wide range of animals and causes zoonotic infections in humans. Although it normally only results in mild illness in healthy individuals, toxoplasmosis is a common opportunistic infection with high mortality in individuals who are immunocompromised, most commonly due to reactivation of infection in the central nervous system. In the acute phase of infection, interferon-dependent immune responses control rapid parasite expansion and mitigate acute disease symptoms. However, after dissemination the parasite differentiates into semi-dormant cysts that form within muscle cells and neurons, where they persist for life in the infected host. Control of infection in the central nervous system, a compartment of immune privilege, relies on modified immune responses that aim to balance infection control while limiting potential damage due to inflammation. In response to the activation of interferon-mediated pathways, the parasite deploys an array of effector proteins to escape immune clearance and ensure latent survival. Although these pathways are best studied in the laboratory mouse, emerging evidence points to unique mechanisms of control in human toxoplasmosis. In this Review, we explore some of these recent findings that extend our understanding for proliferation, establishment and control of toxoplasmosis in humans.

Modeling the Dose Response Relationship of Waterborne Acanthamoeba.

This study developed dose response models for determining the probability of eye or central nervous system infections from previously conducted studies using different strains of Acanthamoeba spp. The data were a result of animal experiments using mice and rats exposed corneally and intranasally to the pathogens. The corneal inoculations of Acanthamoeba isolate Ac 118 included varied amounts of Corynebacterium xerosis and were best fit by the exponential model. Virulence increased with higher levels of C. xerosis. The Acanthamoeba culbertsoni intranasal study with death as an endpoint of response was best fit by the beta-Poisson model. The HN-3 strain of A. castellanii was studied with an intranasal exposure and three different endpoints of response. For all three studies, the exponential model was the best fit. A model based on pooling data sets of the intranasal exposure and death endpoint resulted in an LD50 of 19,357 amebae. The dose response models developed in this study are an important step towards characterizing the risk associated with free-living amoeba like Acanthamoeba in drinking water distribution systems. Understanding the human health risk posed by free-living amoeba will allow for quantitative microbial risk assessments that support building design decisions to minimize opportunities for pathogen growth and survival.

The hitchhiker's guide to parasite dissemination.

Toxoplasma gondii (T. gondii) is a parasitic protist that can infect nearly all nucleated cell types and tissues of warm-blooded vertebrate hosts. T. gondii utilises a unique form of gliding motility to cross cellular barriers, enter tissues, and penetrate host cells, thus enhancing spread within an infected host. However, T. gondii also disseminates by hijacking the migratory abilities of infected leukocytes. Traditionally, this process has been viewed as a route to cross biological barriers such as the blood-brain barrier. Here, we review recent findings that challenge this view by showing that infection of monocytes downregulates the program of transendothelial migration. Instead, infection by T. gondii enhances Rho-dependent interstitial migration of monocytes and macrophages, which enhances dissemination within tissues. Collectively, the available evidence indicates that T. gondii parasites use multiple means to disseminate within the host, including enhanced motility in tissues and translocation across biological barriers.

[Infections of the central nervous system by protozoa, helminths and fungi]. / Infektionen des zentralen Nervensystems durch Protozoen, Würmer und Pilze.

A plethora of different parasites and fungi can lead to infections of the central nervous system (CNS) and cause different clinical symptoms and outcomes depending on the pathogen and the anatomic location of the infection. The diagnosis and treatment of these eukaryotic infections is challenging. The prevalence of CNS infections depends on many factors, including geographical location, living conditions, genetic background and the immune status of the individual. In Germany, infections of the CNS by fungi and parasites are rare but can lead to considerable morbidity. Some parasitic and fungal CNS infections are becoming increasingly more prevalent and clinically relevant due to the increasing number of immunocompromised people. Case fatality rates of these infections, which are difficult to diagnose and to treat, are high. This article provides an overview of a subjective selection of parasitic and fungal infections of the CNS relevant to clinical practice in Germany and presents the diagnostic and therapeutic options.

Seroprevalence of Toxoplasma gondii infection in children with central nervous system disorders in Mansoura, Egypt: a case-control study.

Background: Toxoplasma gondii is a global infection with a crucial role in the development of neurological diseases. Data concerning the association between T. gondii and neurological illnesses in Egyptian children is scarce. Methods: A case-control study was conducted on 60 patients divided into children suffering from central nervous system manifestations without apparent chromosomal anomalies (n=30) and children with Down syndrome (n=30) recruited from Mansoura University Children's Hospital, Mansoura, Egypt. A total of 30 healthy children were included as controls. Demographics and clinical data were collected from all cases and Toxoplasma immunoglobulin (Ig) M and G antibodies were assessed by enzyme-linked immunosorbent assay. Results: Anti-T. gondii IgG was the most frequent antibody detected and the highest seropositivity rates were ranked for the neurologically disabled non-syndromic children, followed by Down syndrome, compared with controls (p≤0.001). Statistically significant (p=0.05) associations were found between Toxoplasma IgG seropositivity and hydrocephalus and between Toxoplasma IgM and a history of contact with farm animals, soil and cats in children with Down syndrome. Conclusions: The association between Toxoplasma infection and neurological disorders in children should be kept in mind by paediatricians and assessment of T. gondii antibodies in early childhood is needed for timely management of afflicted patients.

Metabolic Profiling of Central Nervous System Disease in Trypanosoma brucei rhodesiense Infection.

Background: The progression of human African trypanosomiasis from the early hemolymphatic stage to the late meningoencephalitic stage is of critical diagnostic importance as it determines the choice of potentially toxic drug regimens. Current diagnostic criteria involving analysis of cerebrospinal fluid (CSF) for parasites and/or pleocytosis are sensitive, but recent evidence suggests that specificity may be poor. Methods: We used an untargeted global metabolic profiling approach for the discovery of novel candidate stage-diagnostic markers in CSF from patients infected with Trypanosoma brucei rhodesiense, using 1H nuclear magnetic resonance (NMR) spectroscopy. Results: Metabolic markers did not distinguish between early and late-stage cases but were associated with neuroinflammatory responses and the presentation of neurological disturbances. In particular, increased concentrations of 3-hydroxybutyrate and alanine and reduced concentrations of mannose and urea were discriminatory for the presentation of daytime somnolence and gait ataxia. Conclusions: CSF metabolite concentrations provide markers for neuroinflammatory responses during central nervous system (CNS) invasion by trypanosomes and are associated with the presentation of neurological disturbances independently of disease stage determined by current criteria. This suggests that applying a dichotomous-stage diagnosis on the basis of CSF pleocytosis does not accurately reflect the biological changes occurring as parasites invade the CNS and has implications for biomarker discovery strategies.

Evaluation of a TaqMan Array Card for Detection of Central Nervous System Infections.

Infections of the central nervous system (CNS) are often acute, with significant morbidity and mortality. Routine diagnosis of such infections is limited in developing countries and requires modern equipment in advanced laboratories that may be unavailable to a number of patients in sub-Saharan Africa. We developed a TaqMan array card (TAC) that detects multiple pathogens simultaneously from cerebrospinal fluid. The 21-pathogen CNS multiple-pathogen TAC (CNS-TAC) assay includes two parasites (Balamuthia mandrillaris and Acanthamoeba), six bacterial pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Mycoplasma pneumoniae, Mycobacterium tuberculosis, and Bartonella), and 13 viruses (parechovirus, dengue virus, Nipah virus, varicella-zoster virus, mumps virus, measles virus, lyssavirus, herpes simplex viruses 1 and 2, Epstein-Barr virus, enterovirus, cytomegalovirus, and chikungunya virus). The card also includes human RNase P as a nucleic acid extraction control and an internal manufacturer control, GAPDH (glyceraldehyde-3-phosphate dehydrogenase). This CNS-TAC assay can test up to eight samples for all 21 agents within 2.5 h following nucleic acid extraction. The assay was validated for linearity, limit of detection, sensitivity, and specificity by using either live viruses (dengue, mumps, and measles viruses) or nucleic acid material (Nipah and chikungunya viruses). Of 120 samples tested by individual real-time PCR, 35 were positive for eight different targets, whereas the CNS-TAC assay detected 37 positive samples across nine different targets. The CNS-TAC assays showed 85.6% sensitivity and 96.7% specificity. Therefore, the CNS-TAC assay may be useful for outbreak investigation and surveillance of suspected neurological disease.

Brain-Eating Amoebae: Predilection Sites in the Brain and Disease Outcome.

Acanthamoeba spp. and Balamuthia mandrillaris are causative agents of granulomatous amoebic encephalitis (GAE), while Naegleria fowleri causes primary amoebic meningoencephalitis (PAM). PAM is an acute infection that lasts a few days, while GAE is a chronic to subacute infection that can last up to several months. Here, we present a literature review of 86 case reports from 1968 to 2016, in order to explore the affinity of these amoebae for particular sites of the brain, diagnostic modalities, treatment options, and disease outcomes in a comparative manner.

Parelaphostrongylus tenuis Cerebrospinal Nematodiasis in a Horse with Cervical Scoliosis and Meningomyelitis.

There are reports of horses with acute onset acquired cervical scoliosis and cutaneous analgesia. The underlying dorsal gray column myelitis that produces these neurologic signs has been only presumptively attributed to migration of Parelaphostrongylus tenuis within the spinal cord. Despite previous confirmation brain by polymerase chain reaction testing, of P. tenuis within the brain of horses by polymerase chain reaction testing, genetic testing has failed to definitively identify the presence of this parasite in cases of equine myelitis. This case report provides molecular confirmation via polymerase chain reaction of P. tenuis within the cervical spinal cord of a horse with scoliosis and cutaneous analgesia.

SEROPREVALENCE OF TOXOPLASMA GONDII INFECTION AND ITS AS- SOCIATED RISK FACTORS IN NEUROPSYCHIATRIC PATIENTS IN JAZAN PROVINCE, SAUDI ARABIA.

Toxoplasma gondii has worldwide distribution in nearly one-third of the human population. It is a neurotropic protozoan parasite so a potential role of T. gondii infection for some neuropsychiatric disorders was postulated. Patients with psychiatric disorders had high toxoplasmosis se- roprevalence. Limited information about toxoplasmosis seroprevalence in psychiatric patients was known in southern area of Saudi Arabia. The current cross sectional case control study aims at determination of the prevalence of T. gondii IgG & IgM in neuropsychiatric patients in Jazan Province. A total of 162 neuropsychiatric patients from Al-Amal hospital for psychiatric health and 162 subjects without neuropsychiatric manifestations from Jazan General Hospital, Jazan City, KSA. were enrolled in the study. Psychiatric diagnosis was based on the International Classification of Diseases-10 (ICD-10 classification). Serological analysis for latent toxoplasmosis (IgG) and active toxoplasmosis (IgM) was done using Enzyme Linked Immunosorbent Assay (ELISA). Investigations for the association with socio-demographic, clinical and behavioral characteristics in psychiatric patients were also done. The serofrequency of IgG antibodies among neuropsychiatric patients was significantly higher than that of the controls (35.8% vs 14.8%) P = 0.0022. OR 3.2 with 95% CI= (1.4952 to 6.8774). However; serofrequency of toxoplasma IgM antibody between neuro-psychiatric patients and controls was not statistically significant (P > 0.05).,Bivariate and multivariate analysis for socio-demographics and possible associated risk factors showed that contact to cats and/or dogs, eating under cooked meat, and contact to soil were significantly higher in neuropsychiatric patients than controls.

VP-shunt dysfunction caused by malaria CNS infection.

INTRODUCTION: Malaria is a widespread mosquito-borne infectious disease with over 300 million cases and roughly 900 thousand deaths in 2013. Cerebral involvement of malaria causes 50 % of all infection-associated deaths, especially in children below the age of 5 years. Hydrocephalus is a medical condition with abnormal accumulation of cerebrospinal fluid in physiological cavities and ventricles. Standard treatment is the implantation of a cerebrospinal fluid shunt device. A common problem associated with shunt treatment especially in pediatric patients is infection and consecutive shunt dysfunction caused by bacteriae or high protein levels clogging the valve. In these cases, Staphylococcus aureus and Staphylococcus epidermidis are predominantly found in CSF cultures. CASE PRESENTATION: We present a case of a 2-year old boy from Saudi Arabia with a ventriculoperitoneal (VP)-shunt-dependent congenital hydrocephalus who suffered from cerebral malaria and developed consecutive shunt failure. CONCLUSION: To the best of our knowledge, shunt failure caused by malaria CNS infection with Plasmodium falciparum has not yet been reported in the literature and should be considered as a rare cause of VP-shunt failure in patients with atypical VP-shunt infections living in or traveling from endemic areas.

From the blood to the brain: avenues of eukaryotic pathogen dissemination to the central nervous system.

Infection of the central nervous system (CNS) is a significant cause of morbidity and mortality, and treatments available to combat the highly debilitating symptoms of CNS infection are limited. The mechanisms by which pathogens in the circulation overcome host immunity and breach the blood-brain barrier are active areas of investigation. In this review, we discuss recent work that has significantly advanced our understanding of the avenues of pathogen dissemination to the CNS for four eukaryotic pathogens of global health importance: Toxoplasma gondii, Plasmodium falciparum, Trypanosoma brucei, and Cryptococcus neoformans. These studies highlight the remarkable diversity of pathogen strategies for trafficking to the brain and will ultimately contribute to an improved ability to combat life-threatening CNS disease.

Canine neural angiostrongylosis: a case-control study in Sydney dogs.

OBJECTIVE: To determine the risk factors for canine neural angiostrongylosis in dogs domiciled in Sydney, Australia; geographic location, age, sex, neuter status, weight and breed were assessed. PROCEDURE: Case and matched-control dogs were selected from three veterinary clinics in Sydney. Conditional logistic regression was used to identify factors associated with disease status. A scan statistic was used to identify disease clusters. RESULTS: Age (young dogs) and neuter status (entire dogs) were independent risk factors for neural angiostrongylosis diagnosis, and diagnoses predominantly occurred during autumn, with some evidence of spatial clustering. CONCLUSIONS: Veterinarians in endemic areas should be aware of these risk factors when presented with suspect canine neural angiostrongylosis cases and also should consider advising clients of preventive treatment. Potential human health risks should be further investigated, because urban dog populations might represent a useful sentinel species for disease in humans.

Biomarkers for neural injury and infection in small animals.

Cross-sectional imaging techniques have facilitated diagnosis of central nervous system (CNS) diseases. However, there is still frequently a lack of definition of the cause of neurologic lesions, because tissue sampling from the pathologic site is often difficult and there are few clinical diagnostic tools to assist diagnosis. Biomarkers can assist in understanding the cause, diagnosis, severity, and prognosis for neural injury. Integration of conventional testing and new diagnostic techniques will overcome shortcomings in understanding infectious diseases of the CNS. Diagnostic tests may be limited by poor positive and negative predictive values, which must be recognized when interpreting test results.

Neurological trypanosomiasis in quinapyramine sulfate-treated horses--a breach of the blood-brain barrier?

Trypanosoma evansi infection typically produces wasting disease, but it can also develop into a neurological or meningoencephalitis form in equids. Trypanosomiasis in horses was treated with quinapyramine sulfate, and all the 14 infected animals were recovered clinically. After clinical recovery, four animals developed a neurological form of the disease at various intervals. Two of these animals treated with diminazene aceturate recovered temporarily. Repeated attempts failed to find the parasite in the blood or the cerebrospinal fluid (CSF), but all of the animals were positive in enzyme-linked immunosorbent assay. The calculation of the antibody index (AI) in the serum and the CSF and polymerase chain reaction (PCR) analysis of the CSF and brain tissue were carried out to confirm the neuro-infection. We found PCR and AI analyses of the CSF to be useful tools in the diagnosis of the neurological form of trypanosomiasis when the organism cannot be found in the blood or CSF. The increased albumin quotient is indicative of barrier leakage due to neuroinflammation. The biochemical changes in the CSF due to nervous system trypanosomiasis include increases in the albumin quotient, total protein, and urea nitrogen. It seems to be the first report on relapse of the nervous form of trypanosomiasis in equids even after quinapyramine treatment in endemic areas.

Central nervous system infection with Acanthamoeba in a malnourished child.

A 3-year-old male child presented with moderate-to-high grade fever and non-projectile vomiting, generalised seizures and altered sensorium for 1 month. CT scan revealed a communicating hydrocephalus with no basal exudates. The microbiological tests were negative for Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitides, brucellosis, cryptococcosis, HIV and Mycobacterium tuberculosis. Intracranial pressure was relieved by ventriculo-peritoneal shunt, and the child was empirically started on ceftriaxone, and antitubercular therapy with isoniazid, rifampicin, ethambutol and streptomycin, along with steroids and supportive treatment for seizures. The symptoms persisted. On further investigation the cerebrospinal fluid showed growth of Acanthamoeba spp., following which the initial treatment was stopped and a combination antiamoebic regimen of cotrimoxazole, rifampicin and ketoconazole was started, after which he showed clinical improvement. The treatment was continued for 6 months and on follow-up at 1, 3 and 6 months, there was a remarkable clinical improvement with no residual symptoms.

Next generation of non-mammalian blood-brain barrier models to study parasitic infections of the central nervous system.

Transmigration of neuropathogens across the blood-brain barrier is a key step in the development of central nervous system infections, making it a prime target for drug development. The ability of neuropathogens to traverse the blood-brain barrier continues to inspire researchers to understand the specific strategies and molecular mechanisms that allow them to enter the brain. The availability of models of the blood-brain barrier that closely mimic the situation in vivo offers unprecedented opportunities for the development of novel therapeutics.

Henneguya torpedo sp. nov. (Myxozoa), a parasite from the nervous system of the Amazonian teleost Brachyhypopomus pinnicaudatus (Hypopomidae).

A new species of Myxosporea, Henneguya torpedo sp. nov., is described from the brain and spinal cord of the Amazonian teleostean fish Brachyhypopomus pinnicaudatus collected from the Peixe Boi River, State of Park, Brazil. The spores were surrounded by a thick hyaline sheath that is homogeneous and electron translucent and consists of 2 layers of different densities. The total spore length is 48.62 +/- 0.51 microm (mean +/- SE), the ellipsoidal spore body length is 28.53 +/- 0.36 microm, the body width is 7.25 +/- 0.31 microm and the body thickness is 3.06 +/- 0.26 microm. Each of the 2 equal-sized valves presented a tapering tail (19.64 +/- 0.44 microm in length). The 2 equal-sized thin and smooth valves surrounded 2 equal-sized and elongated ellipsoidal polar capsules (6.41 +/- 0.26 x 1.84 +/- 0.19 microm) that contained 5 to 6 (rarely 7) polar filament coils. The binucleated sporoplasm contained numerous spherical sporoplasmosomes (-260 x -280 nm) with a laterally eccentric-dense structure containing a half-crescent section. The sporoplasmosomes are surrounded by a hyaline homogenous sheath. Based on the data obtained by light and electron microscopy and on the host specificity, the spores differed from the previously described Henneguya spp., mainly in the presence of a sheath surrounding the spores, the spore shape and size and the number and arrangement of the polar filament coils. Therefore, from this description we propose the establishment of a new species, which we have named Henneguya torpedo sp. nov.