Neglected Parasitic Infections: What Family Physicians Need to Know-A CDC Update.

Chagas disease, cysticercosis, and toxoplasmosis affect millions of people in the United States and are considered neglected parasitic diseases. Few resources are devoted to their surveillance, prevention, and treatment. Chagas disease, transmitted by kissing bugs, primarily affects people who have lived in Mexico, Central America, and South America, and it can cause heart disease and death if not treated. Chagas disease is diagnosed by detecting the parasite in blood or by serology, depending on the phase of disease. Antiparasitic treatment is indicated for most patients with acute disease. Treatment for chronic disease is recommended for people younger than 18 years and generally recommended for adults younger than 50 years. Treatment decisions should be individualized for all other patients. Cysticercosis can manifest in muscles, the eyes, and most critically in the brain (neurocysticercosis). Neurocysticercosis accounts for 2.1% of all emergency department visits for seizures in the United States. Diagnosing neurocysticercosis involves serology and neuroimaging. Treatment includes symptom control and antiparasitic therapy. Toxoplasmosis is estimated to affect 11% of people older than six years in the United States. It can be acquired by ingesting food or water that has been contaminated by cat feces; it can also be acquired by eating undercooked, contaminated meat. Toxoplasma infection is usually asymptomatic; however, people who are immunosuppressed can develop more severe neurologic symptoms. Congenital infection can result in miscarriage or adverse fetal effects. Diagnosis is made with serologic testing, polymerase chain reaction testing, or parasite detection in tissue or fluid specimens. Treatment is recommended for people who are immunosuppressed, pregnant patients with recently acquired infection, and people who are immunocompetent with visceral disease or severe symptoms.

Transcriptome profiling of Cysticercus Pisiformis provides insight into responses to host bile acids.

Bile acids in host intestine activate larvae of tapeworms and facilitate its invasion. However, the mechanism underlying this process is poorly understood. In order to better understand responses of tapeworms to host biles, we used RNA-Seq profiling method to study the transcriptomes of Cysticercus Pisiformis (larvae of Taenia Pisiformis) after host bile acid treatment. A total of 338.32 million high-quality clean reads were obtained by Illumina Hiseq platform. Totally, 62,009 unigenes were assembled, 38,382 of which were successfully annotated to known databases. A total of 9324 unigenes were identified as differentially expressed genes (DEGs), of which 5380 and 3944 genes were up- and down-regulated in the group treated with bile acids, respectively. Gene Ontology analysis revealed that biosynthesis and energy metabolism potential were significantly strengthened after host bile treatment in C. pisiformis. Similarly, KEGG pathway analysis revealed an enrichment of pathways related to lipid metabolism and carbohydrate metabolism. Among them, 'AMPK signaling pathway' which is critical in balancing cellular energy, was significantly enriched after bile acids activation. In addition, pathways of 'Fatty acid biosynthesis', 'Fatty acid elongation', 'Starch and sucrose metabolism', and 'glycolysis gluconeogenesis' were also significantly changed after bile acid treatment. qRT-PCR analysis confirmed the differential abundances of some key genes in these pathways. Our data suggest that host bile acids remarkably promote the pathways of energy metabolism of this parasite and regulate the genes involved in balancing lipid metabolism and carbohydrate metabolism. These findings provide new insights on the lifecycle of Taenia parasites.

Influence of the interaction between cysticercosis and obesity on rabbit behavior and productive parameters.

Parasites induce behavioral changes in the host and obesity is a health problem affecting different animal species. Cysticercosis caused by Taenia pisiformis affects some behavior of rabbits and reproductive behavior of does. Rabbits do not escape from metabolic disorders, being long-live animals useful in breeding, research and companion animals. Here, we addressed the interaction between parasitosis and obesity, and studied how these conditions or the comorbidity affect behavioral and productive parameters in bucks infected with 3000 T. pisiformis eggs. We found that the chronic infection reduced locomotor activity by 28.5% in obese, 18.5% in infected and 47% in obese-infected group (comorbid). The exploratory activity reduced by 42% in obese, 48% in infected and 68% in comorbid rabbits (P ≤ 0.001). Chinning was not affected by obesity, while infection decreased it by 25%. Behavioral reproductive parameters like response time, the mount latency and number of ejaculates were affected by infection and obesity. Furthermore, obesity seems to increase the parasite load promoting the formation of liver granulomas (16% granulomas compared with normal weight), with a higher number of cysticerci in obese animals (86% more than normal weight). Infection decreases body weight, body mass index and the zoometric index BW/LV in obese and normal weight rabbits. In conclusion, infection with T. pisiformis altered behavioral and productive parameters, and obesity magnifies the impact caused by the infection. Also, obesity leads to major susceptibility to infection with T. pisiformis.

Historical perspective: The British contribution to the understanding of neurocysticercosis.

Neurocysticercosis, or brain infestation with the larval stage of Taenia solium, is the most common risk factor for epilepsy in many endemic regions of the world. Hardly any cases are seen in Western developed countries, including Britain. However, a sizeable number (n = 450) was seen among British soldiers returning from deputation to India, then a British colony, first reported by Col. MacArthur at the Queen Alexandria Military Hospital in 1931. Here, we review the influence of the perceptive observations of British Army medics on the understanding of the parasitic disorder. The majority of these people presented with epilepsy. Among the contributions of the army medics were establishing the diagnosis, initially by histological examination of subcutaneous and muscular infestation, and later by radiography, clarifying the prognosis and the role of medical and surgical treatments and uncovering the close relationship between the larval (cysticercosis) and adult (intestinal tapeworm) stages of T. solium.

Mathematical model of the life cycle of taenia-cysticercosis: transmission dynamics and chemotherapy (Part 1).

BACKGROUND: Taenia solium is the aetiological agent of human taeniasis, pig cysticercosis and human neurocysticercosis, which are serious public health problems, especially in developing countries. METHODS: A mathematical model of the transmission dynamics of taeniasis-cysticercosis is formulated. The model consists of a coupled system of differential equations, which are density-dependent equations for describing the flow of the parasite through the life cycle. The model is hybrid since it comprises deterministic equations with stochastic elements which describe changes in the mean parasite burden and incorporates the overall pattern of the parasites' distribution. RESULTS: Sensitivity and bifurcation analyses were carried out to determine the range of values of the model. The model can reproduce the observed epidemiological patterns of human taeniasis, pig and human cysticercosis. For example, for a wide range of parameter values, the mean intensity of adult worms tends to rapidly stabilize in one parasite per individual host. From this model, we also derived a Susceptible-Infected model to describe the prevalence of infection in humans and pigs. Chemotherapeutic interventions against pig cysticercosis or human taeniasis may reduce rapidly and effectively the mean intensity of human taeniasis, pig cysticercosis and human cysticercosis. This effect can be achieved even if the protective efficacy of the drug is of the order of 90% and the coverage rate is 90%. This means that health in humans infected either with adult worms or cysticerci may be achieved by the application of anthelmintic drugs against pig cysticercosis. However, treatment against human cysticercosis alone, does not influence neither human teniasis nor pig cysticercosis. This is because human cysticercosis infection does not influence the value of the basic reproductive number (Ro). CONCLUSIONS: Even coverage of 100% in the administration of anthelmintics did not eliminate the infection. Then elimination of the infection in all hosts does not seem a feasible goal to achieve by administering only chemotherapeutic interventions. Throughout the manuscript a discussion of our model in the context of other models of taeniasis-cysticercosis is presented.

Elucidating the influence of praziquantel nanosuspensions on the in vivo metabolism of Taenia crassiceps cysticerci.

The aim of this work was to develop nanosuspensions of praziquantel (PZQ) and to evaluate their influence on the energetic metabolism of cysticerci inoculated in BALB/c mice. We analyzed metabolic alterations of glycolytic pathways and the tricarboxylic acid cycle in the parasite. The nanosuspensions were prepared by precipitation and polyvinyl alcohol (PVA), poloxamer 188 (P188) and poloxamer 407 (P407) were used as stabilizers. Nanosuspension prepared with PVA had a particle size of 100nm, while P188- and P407-based nanosuspensions had particle sizes of 74nm and 285nm, respectively. The zeta potential was -8.1, -8.6, and -13.2 for the formulations stabilized with PVA, P188 and P407, respectively. Treatments of T. crassiceps cysticerci-infected mice resulted in an increase in glycolysis organic acids, and enhanced the partial reversion of the tricarboxylic acid cycle, the urea cycle and the production of ketonic bodies in the parasites when compared to the groups treated with conventional PZQ. These data suggest that PZQ nanosuspensions greatly modified the energetic metabolism of cysticerci in vivo. Moreover, the remarkable metabolic alterations produced by the stabilizers indicate that further studies on nanoformulations are required to find potentially suitable nanomedicines.

Somatostatin negatively regulates parasite burden and granulomatous responses in cysticercosis.

Cysticercosis is an infection of tissues with the larval cysts of the cestode, Taenia solium. While live parasites elicit little or no inflammation, dying parasites initiate a granulomatous reaction presenting as painful muscle nodules or seizures when cysts are located in the brain. We previously showed in the T. crassiceps murine model of cysticercosis that substance P (SP), a neuropeptide, was detected in early granulomas and was responsible for promoting granuloma formation, while somatostatin (SOM), another neuropeptide and immunomodulatory hormone, was detected in late granulomas; SOM's contribution to granuloma formation was not examined. In the current studies, we used somatostatin knockout (SOM(-/-)) mice to examine the hypothesis that SOM downmodulates granulomatous inflammation in cysticercosis, thereby promoting parasite growth. Our results demonstrated that parasite burden was reduced 5.9-fold in SOM(-/-) mice compared to WT mice (P < 0.05). This reduction in parasite burden in SOM(-/-) mice was accompanied by a 95% increase in size of their granulomas (P < 0.05), which contained a 1.5-fold increase in levels of IFN-γ and a 26-fold decrease in levels of IL-1ß (P < 0.05 for both) compared to granulomas from WT mice. Thus, SOM regulates both parasite burden and granulomatous inflammation perhaps through modulating granuloma production of IFN-γ and IL-1ß.

Helminth infection alters mood and short-term memory as well as levels of neurotransmitters and cytokines in the mouse hippocampus.

UNLABELLED: Helminthic infections are important causes of morbidity and mortality in many developing countries, where children bear the greatest health burden. The ability of parasites to cause behavioral changes in the host has been observed in a variety of host-parasite systems, including the Taenia crassiceps-mouse model. In murine cysticercosis, mice exhibit a disruption in the sexual, aggressive and avoidance predator behaviors. OBJECTIVE: The present study was conducted to characterize short-term memory and depression-like behavior, as well as levels of neurotransmitters and cytokines in the hippocampus of cysticercotic male and female mice. METHODS: Cytokines were detected by RT-PCR and neurotransmitters were quantified by HPLC. RESULTS: Chronic cysticercosis infection induced a decrease in short-term memory in both male and female mice, having a more pronounced effect in females. Infected females showed a significant increase in forced swimming tests with a decrease in immobility. In contrast, male mice showed an increment in total activity and ambulation tests. Serotonin levels decreased by 30% in the hippocampus of infected females whereas noradrenaline levels significantly increased in infected males. The hippocampal expression of IL-4 increased in infected female mice, but decreased in infected male mice. CONCLUSION: Our study suggests that intraperitoneal chronic infection with cysticerci in mice leads to persistent deficits in tasks dependent on the animal's hippocampal function. Our findings are a first approach to elucidating the role of the neuroimmune network in controlling short-term memory and mood in T. crassiceps-infected mice.

Toxocariasis/cysticercosis seroprevalence in a long-term rural settlement, São Paulo, Brazil.

Seroprevalence of Toxocara and Taenia solium and risk factors for infection with these parasites were explored in a long-term rural settlement in São Paulo state, Brazil. An ELISA for the detection of anti-Toxocara IgG and IgE and anti-T. solium cysticerci was standardized using Toxocara excretory-secretory antigens (TES) obtained from the cultured second-stage larvae of T. canis and by vesicular fluid antigen from Taenia crassiceps cysticerci (VF). For cysticercosis, the reactive ELISA samples were assayed by Western blot using 18 kDa and 14 kDa proteins purified from VF. Out of 182 subjects, 25 (13.7%) presented anti-Toxocara IgG and a positive correlation between total IgE and the reactive index of specific anti-TES IgE (P=0.0265) was found amongst the subjects found seropositive for anti-Toxocara IgG. In these individuals 38.0% showed ocular manifestations. The frequency of anti-T. solium cysticerci confirmed by Western blot was 0.6%. Seropositivity for Toxocara was correlated with low educational levels and the owning of dogs. Embryonated eggs of Toxocara spp. were found in 43.3% of the analysed areas.

Neonatal exposure to estradiol induces resistance to helminth infection and changes in the expression of sex steroid hormone receptors in the brain and spleen in adult mice of both sexes.

A single injection of 17beta-estradiol administered to 4-day-old male and female mice increased the cellular immune response, and induced resistance to Taenia crassiceps cysticercosis as well as changes in the expression pattern of progesterone (PR) and estrogen receptor (ER) isoforms in the brain and splenocytes. Regardless of gender, when treated mice reached adulthood, they were highly resistant to infection. Female mice presented early vaginal opening and altered estrous cycles. In male and female mice, the expression of the PR and ER isoforms in the brain was differentially regulated after neonatal exposure to estradiol. Moreover, an increase in the expression of IL-4 and IFN-gamma was found in the serum of experimentally infected neonatally estrogenized animals, which correlated with the observed protection against T. crassiceps infection. In conclusion, early exposure to estradiol permanently modifies immune system activity and sex steroid hormone receptors in the brain, and causes profound changes in sex-associated susceptibility, leading to resistance to helminth parasite infection.

Extraocular muscle cysticercosis: clinical features and management outcome.

BACKGROUND: Extraocular muscle cysticercosis is rare and can be classified based on the stage of evolution as viable, degenerating, and inactive. A tailored approach to therapy using a combination of albendazole and steroids has been proposed. In this study, we have evaluated the clinical features and response of "viable" extraocular muscle cysticercosis to a tailored therapy with oral albendazole and steroids. METHODS: A retrospective review of 32 patients with viable extraocular muscle cysticercosis was performed over a 3-year period. Ultrasound examination was performed at 3 weeks and 6 weeks for resolution of the cyst and clinical signs following treatment with oral albendazole and prednisolone. The clinical presentation, ocular alignment, motility restriction, and ultrasound examination details were recorded on serial visits. RESULTS: The mean age was 19.5 years. The most common presenting signs included limitation of ocular motility in 75%, conjunctival mass in 37.5%, diplopia in 28.1%, and proptosis in 28.1% of the patients, respectively. Ocular alignment evaluation revealed esotropia in 3.1%, exotropia in 12.5%, and hypertropia in 6.25%. Restriction of abduction and abduction in elevation was present in two patients each. The average time for complete resolution was 65.9 days. All the patients had resolution, except four, who had residual motility limitation but were asymptomatic. CONCLUSIONS: Combination therapy with oral albendazole and steroids is effective in the management of viable extraocular muscle cysticercosis. However, residual motility restriction may persist despite treatment.

Spontaneous extrusion of subconjunctival cysticercosis.

We report on a case of subconjunctival cysticercosis in a patient who presented with redness on the medial side, fever, and pain and swelling on the inside of the right eye. There was no diplopia, restriction of ocular movements in any gaze or diminution of vision. Cyst excision was scheduled and oral albendazole was administered. However, the cyst extruded spontaneously prior to surgery.

Cysticercosis of temporalis muscle: an unusual cause of temporal headaches. A case report.

Cysticercosis is a common parasitic infection caused by encysted larvae of the helminth Taenia solium (pork tapeworm). The central nervous system (CNS) is the most important primary site of infection and the disease can present with solitary or multiple space occupying lesions. Less common presentations in the CNS include the racemose variety with macroscopic groups of cysticerci in the subarachnoid space giving the appearance of a cluster of grapes and basal or ventricular cysticercosis causing obstructive hydrocephalus. Involvement of other organs: skeletal muscle, eyes, myocardium and the lungs has also been reported. Cases of cysticercosis presenting as isolated muscle mass (pseudotumours) without involvement of the CNS have also been recently described in the literature. We present a case of a 43-year-old woman who complained of subacute onset of left temporal pain and headache. Magnetic resonance imaging (MRI) showed characteristic imaging findings suggestive of cysticercosis of the temporalis muscle.

Cefalea crónica como manifestación de Cisticercosis / Chronic headaches as a manifestation of C ysticercosis

La cisticercosis es una enfermedad parasitaria que ocurre como consecuencia de la infección por el estado invasivo de la taenia solium, que se produce cuando el hombre se convierte, de forma accidental, en el huésped intermediario al ingerir huevos en la carne de cerdo contaminado. Presentamos un caso de neurocisticercosis con clínica de cefalea crónica (AU)

Cysticercosis is a parasitic disease that occurs as a consequence of infection by the invasive stage of taenia solium, which occurs when man accidentally becomes an intermediate host after ingesting the eggs in pork from contaminated pigs. We present a case of neurocysticercosis with chronic clinical headache (AU)

Impact of naturally acquired Taenia solium cysticercosis on the hormonal levels of free ranging boars.

In chronically infected BALBc/AnN male mice, Taenia crassiceps cysticercosis induces changes in the host's sex steroids hormone that lead to their estrogenization and deandrogenization, with possible repercussions on their susceptibility to infections. Here reported are the serum steroid levels in free range cysticercotic male boars. Therefore, the possible effects of Taenia solium cysticerci over the pig steroid levels were evaluated. Herein are described the sex steroids and cortisol levels of non-cysticercotic (n=25) and cysticercotic (n=22) adult boars, as diagnosed by tongue inspection, all free-ranging in a typical village of an endemic rural area in Mexico. A significant reduction of testosterone (P=0.022) and a likely one of 17beta-estradiol (P=0.08) levels were found in the cysticercotic boars in comparison with those non-cysticercotic, whilst no significant differences in the cortisol and DHEA levels were detected. Serum levels of specific antibodies did not correlate with infection nor with the levels of any of the hormones measured. Results suggest that T. solium cysticercosis significantly affects the hormonal status of its porcine host independently of their antibody response.