Drug discovery for primary amebic meningoencephalitis: from screen to identification of leads.

Introduction: Naegleria fowleri is responsible for primary amebic meningoencephalitis (PAM) which has a fatality rate of >97%. Because of the rarity of the disease, pharmaceutical companies do not pursue new drug discovery for PAM. Yet, it is possible that the infection is underreported and finding a better drug would have an impact on people suffering from this deadly infection.Areas covered: This paper reports the efforts undertaken by different academic groups over the last 20 years to test different compounds against N. fowleri. The drug discovery research encompassed synthesis of new compounds, development and use of high-throughput screening methods and attempts to repurpose clinically developed or FDA-approved compounds for the treatment of PAM.Expert opinion: In absence of economic investment to develop new drugs for PAM, repurposing the FDA-approved drugs has been the best strategy so far to identify new leads against N. fowleri. Increasing use of high-throughput phenotypic screening has the potential to accelerate the identification of new leads, either in monotherapy or in combination treatment. Since phase II clinical trial is not possible for PAM, it is critical to demonstrate in vivo efficacy of a clinically safe compound to translate the discovery from lab to the clinic.

Aberrant and accidental trichomonad flagellate infections: rare or underdiagnosed?

The clinical significance and frequency of human infections with trichomonad flagellates in aberrant locations (locations other than the predilection sites) and accidental infections (infections with non-human trichomonads) are unclear. The total number of case reports in the literature is low, with the identification of the infection largely the outcome of investigations for the cause of clinical signs. At least seven species have been identified in either aberrant or accidental infections, with these infections occurring worldwide. Results of prospective and retrospective surveys of adults with respiratory disease suggest that aberrant and accidental trichomonad infections are less rare than the number of case reports suggest, with Trichomonas tenax being the most frequent. Surveys of neonates and infants suggest that aberrant Trichomonas vaginalis infections can be higher and more serious than suggested by the few case reports. The density and location of infection might be as important, if not more so, than species in determining pathogenicity. Molecular diagnostic methods including DNA sequencing can be used to better diagnose infections and enable identification to assist in determining the clinical significance of different species. Raising awareness of these infections among clinicians and adding them to their differential lists are strongly suggested.

Human lagochilascariasis-A rare helminthic disease.

Lagochilascariasis is a parasitic disease caused by a helminth of the order Ascaroidea, genus Lagochilascaris that comprises 6 species, among which only Lagochilascaris minor Leiper, 1909, is implicated in the human form of the disease. It is remarkable that the majority of cases of human lagochilascariasis in the Americas have been reported in Brazil. The natural definitive hosts of this parasite seem to be wild felines and canines. Lagochilascariasis is mostly a chronic human disease that can persist for several years, in which the parasite burrows into the subcutaneous tissues of the neck, paranasal sinuses, and mastoid. L. minor exhibits remarkable ability to migrate through the tissues of its hosts, destroying even bone tissue. Fatal cases have been described in which the parasite was found in the lungs or central nervous system. Treatment is often palliative, with recurrence of lesions. This paper summarizes the main features of the disease and its etiologic agent, including prevalence, life cycle, clinical course, and treatment.

Intracranial hydatid cyst: imaging findings of a rare disease.

Hydatid disease (echinococcosis) is a worldwide zoonosis produced by the larval stage of the Echinococcus tapeworm. The disease is endemic in many parts of the world, particularly in the Middle East, Australia, New Zealand, South America and central and south Europe. Intracranial hydatid disease is considered a rare disease and may be sometimes very difficult to diagnose based on the clinical and laboratory findings. Therefore, it is important to be aware of the condition and the imaging findings even in the non-endemic parts of the world. We report the case of a 12-year-old boy who presented with headache and vomiting for a few months. The mass was totally excised, with no postoperative complications. We present MR spectroscopy (MRS) findings in this operatively proven case of hydatid cyst of the brain. We discuss imaging findings, in particular the findings on MRS, which is rarely reported in the literature.

Thelazia callipaeda--first human case of thelaziosis in Croatia.

A case of the first ocular thelaziosis in a human male patient in Croatia is presented. Thelaziosis is a zoonosis caused by the nematodes of the genus Thelazia. In all, two types of the genus have been described as causes of infection in humans, Thelazia callipaeda and Thelazia californiensis. This zoonosis, called "oriental eye worm" is very rare in humans in European countries, with high incidence in Asian countries, especially in China, Thailand, and Japan.

Primary retroperitoneal hydatid cyst: a rare case report.

Hydatid disease is a parasitic tapeworm infestation that usually involves liver and lungs. Primary retroperitoneal hydatid without liver and lung involvement is very rare. Surgery is the principle method of treatment for large retroperitoneal hydatid, whenever feasible. We report a case of primary retroperitoneal hydatid cyst in 29-year-old male patient.

Leishmania (Viannia) naiffi: rare enough to be neglected?

In the Brazilian Amazon, American tegumentary leishmaniasis (ATL) is endemic and presents a wide spectrum of clinical manifestations due, in part, to the circulation of at least seven Leishmania species. Few reports of Leishmania (Viannia) naiffi infection suggest that its occurrence is uncommon and the reported cases present a benign clinical course and a good response to treatment. This study aimed to strengthen the clinical and epidemiological importance of L. (V.) naiffi in the Amazon Region (Manaus, state of Amazonas) and to report therapeutic failure in patients infected with this species. Thirty Leishmania spp samples isolated from cutaneous lesions were characterised by multilocus enzyme electrophoresis. As expected, the most common species was Leishmania (V.) guyanensis (20 cases). However, a relevant number of L. (V.) naiffi patients (8 cases) was observed, thus demonstrating that this species is not uncommon in the region. No patient infected with L. (V.) naiffi evolved to spontaneous cure until the start of treatment, which indicated that this species may not have a self-limiting nature. In addition, two of the patients experienced a poor response to antimonial or pentamidine therapy. Thus, either ATL cases due to L. (V.) naiffi cannot be as uncommon as previously thought or this species is currently expanding in this region.

Prenatal education for congenital toxoplasmosis.

BACKGROUND: Congenital toxoplasmosis is considered a rare but potentially severe infection. Prenatal education about congenital toxoplasmosis could be the most efficient and least harmful intervention, yet its effectiveness is uncertain. OBJECTIVES: To assess the effects of prenatal education for preventing congenital toxoplasmosis. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015), and reference lists of relevant papers, reviews and websites. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials of all types of prenatal education on toxoplasmosis infection during pregnancy. Cluster-randomized trials were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: Two cluster-randomized controlled trials (RCTs) (involving a total of 5455 women) met the inclusion criteria. The two included trials measured the effectiveness of the intervention in different ways, which meant that meta-analysis of the results was not possible. The overall quality of the two studies, as assessed using the GRADE approach, was low, with high risk of detection and attrition bias in both included trials.One trial (432 women enrolled) conducted in Canada was judged of low methodological quality. This trial did not report on any of the review's pre-specified primary outcomes and the secondary outcomes reported results only as P values. Moreover, losses to follow-up were high (34%, 147 out of 432 women initially enrolled). The authors concluded that prenatal education can effectively change pregnant women's behavior as it increased pet, personal and food hygiene. The second trial conducted in France was also judged of low methodological quality. Losses to follow-up were also high (44.5%, 2233 out of 5023 women initially enrolled) and differential (40% in the intervention group and 52% in the control group). The authors concluded that prenatal education for congenital toxoplasmoses has a significant effect on improving women's knowledge, whereas it has no effect on changing women's behavior. In this trial 17/3949 pregnant women seroconverted for toxoplasmosis: 13/2591 (0.5%) in the intervention group and 4/1358 (0.3%) in the control group. The rate of seroconversion detected during the study did not differ between groups (risk ratio (RR) 1.70, 95% confidence interval (CI) 0.56 to 5.21; participants = 3949; studies = one, low quality evidence). The number of events was too small to reach conclusions about the effect of prenatal education on seroconversion rate during pregnancy.No other randomized trials on the effect of prenatal education on congenital toxoplasmosis rate, or toxoplasmosis seroconversion rate during pregnancy were detected. AUTHORS' CONCLUSIONS: Even though primary prevention of congenital toxoplasmosis is considered a desirable intervention, given the lack of related risks compared to secondary and tertiary prevention, its effectiveness has not been adequately evaluated. There is very little evidence from RCTs that prenatal education is effective in reducing congenital toxoplasmosis even though evidence from observational studies suggests it is. Given the lack of good evidence supporting prenatal education for congenital toxoplasmosis prevention, further RCTs are needed to confirm any potential benefits and to further quantify the impact of different sets of educational intervention.

[A rare case of Hymenolepis diminuta infection in a small child]. / Nadir bir olgu olarak küçük bir çocukta Hymenolepis diminuta enfeksiyonu.

Unlike Hymenolepis nana that transmits directly from person to person, the transmission of Hymenolepis diminuta to human is via accidentally ingesting of arthropods carrying cysticercoid larvae as intermediate host. In places with poor hygienic conditions, this cestod may cause seldom infections especially in children. Studies carried out on various populations have reported the prevalence rate of H.diminuta between 0.001% and 5.5%. Although the reported cases are mostly children, the disease can be seen in every age group. In this report, a pediatric case of H.diminuta infection is presented. A twenty one-month-old male patient with the symptoms of vomiting 3-4 times a day along with mud-like diarrhea continuing for a week was admitted to the pediatric outpatient clinic. According to the history, it was learned that the house where he lived was above a barn and there was a history of insect swallowing. Laboratory findings revealed iron-deficiency anemia. The macroscopic appearance of the stool was in a pale clay-like form, and by direct microscopic examination with lugol solution, 70-75 µm in diameter, thick-shelled and six central hookleted eggs that are characteristic for H.diminuta were identified. A six-day course of oral niclosamide was administered to the patient beginning with 500 mg on the first day and 250 mg on the following five days, together with the treatment for the iron deficiency anemia. After fifteen days, the oral niclosamide treatment was repeated. No H.diminuta eggs were detected in the parasitological examination performed one month after completion of the second round of treatment. This case has been presented to call attention to the importance of patient anamnesis and microscopic examination in the diagnosis of H.diminuta infection which is a rarely seen parasitosis.

Prenatal education for congenital toxoplasmosis.

BACKGROUND: Congenital toxoplasmosis is considered a rare but potentially severe infection. Prenatal education about congenital toxoplasmosis could be the most efficient and least harmful intervention, yet its effectiveness is uncertain. OBJECTIVES: To assess the effects of prenatal education for preventing congenital toxoplasmosis. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (15 January 2012), PubMed (1966 to 15 January 2012), EMBASE (1980 to 15 January 2012), CINAHL (1982 to 15 January 2012), LILACS (1982 to 15 January 2012), IMEMR (1984 to 15 January 2012), and reference lists of relevant papers, reviews and websites. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials (RCTs) of all types of prenatal education on toxoplasmosis infection during pregnancy. Cluster-randomized trials were included. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and study quality. Two review authors extracted data. Data were checked for accuracy. MAIN RESULTS: Two cluster-randomized controlled trials (involving a total of 5455 women) met the inclusion criteria. The two included trials measured the effectiveness of the intervention in different ways which meant that meta-analysis of the results was not possible One trial (432 women enrolled) conducted in Canada was judged of low methodological quality. The authors did not report measure of association but only provided P values (P less than 0.05) for all outcomes. Moreover, losses to follow-up were high (34%, 147 out of 432 women initially enrolled). The authors concluded that prenatal education can effectively change pregnant women's behavior as it increased pet, personal and food hygiene. The second trial conducted in France was also judged of low methodological quality. Losses to follow-up were high (44.5%, 2233 out of 5023 women initially enrolled) and differential (40% in the intervention group and 52% in the control group). The authors concluded that prenatal education for congenital toxoplasmoses has a significant effect on improving women's knowledge whereas it has no effect on changing women's behavior. In this trial 17/3949 pregnant women seroconverted for toxoplasmosis: 13/2591 (0.5%) in the intervention group and 4/1358 (0.3%) in the control group. The number of events was too small to reach conclusions about the effect of prenatal education on seroconversion rate during pregnancy.No other randomized trials on the effect of prenatal education on congenital toxoplasmosis rate, or toxoplasmosis seroconversion rate during pregnancy were detected. AUTHORS' CONCLUSIONS: Even though primary prevention of congenital toxoplasmosis is considered a desirable intervention, given the lack of related risks compared to secondary and tertiary prevention, its effectiveness has not been adequately evaluated. There is very little evidence from RCTs that prenatal education is effective in reducing congenital toxoplasmosis even though evidence from observational studies suggests it is. Given the lack of good evidence supporting prenatal education for congenital toxoplasmosis prevention, further RCTs are needed to confirm any potential benefits and to further quantify the impact of different sets of educational intervention.

Cerebral coenurosis in a cat caused by Taenia serialis: neurological, magnetic resonance imaging and pathological features.

CLINICAL SUMMARY: A 4-year-old Birman cat was presented with marked obtundation and non-ambulatory tetraparesis. Two well-demarcated, intra-axial T2-hyperintense, T1-hypointense structures, which did not contrast enhance, were evident on magnetic resonance imaging (MRI). Histopathology of the structures revealed metacestodes that were morphologically indicative of larval stages of Taenia species. Polymerase chain reaction amplification of a fragment within the 12S rRNA gene confirmed the subspecies as Taenia serialis. PRACTICAL SIGNIFICANCE: This is the first report of MRI findings of cerebral coenurosis caused by T serialis in a cat. Early MRI should be considered an important part of the diagnostic work-up for this rare clinical disease, as it will help guide subsequent treatment and may improve the prognosis.

Isolated leishmanial lymphadenopathy - a rare type of leishmaniasis in India: a case report.

A patient presented with isolated, soft to firm, inguinal swelling since childhood clinically thought to be a benign lipomatous lesion. Fine-needle aspiration of the swelling revealed amastigote form of Leishmania donovani in a background of reactive lymphoid hyperplasia. Excision of the swelling resulted in reversal of positive Aldehyde test. Isolated leishmanial lymphadenopathy in an immunocompetent person, is a rare manifestation of leishmaniasis in India. The possible role of transplacental transmission is discussed.

[Observation of dirofilariosis in the practical work of the otorhinolaryngologist].

A case of dirofilariosis is reported. The disease is believed to be caused by the contact with the cat that the patient brought in from Uzbekistan. The authors emphasize the importance of analysis of the medical history of the patients presenting with the pathology being considered, their medical examination, and correct interpretation of X-ray images of the paranasal sinuses taking into account the possibility of distribution of rare helminth species beyond their usual ranges.

[Baylisascariasis--a new dangerous zoonosis]. / Baylisaskarioza--nowa niebezpieczna zoonoza.

Baylisascaris procyonis is a large nematode of the order Ascaridida, specific for raccoon (Procyon lotor). In North America, raccoons are extremely common in rural, suburban, and urban settings, where they have become well adapted to living alongside people. In the 1930s raccoons were introduced into Europe (i. a. Poland) and Asia for the commercial fur trade and into Japan as pets. The prevalence of B. procyonis infection in raccoons is often high, and infected animals can disseminate in their feces enormous numbers of parasite eggs. Raccoons defecate in preferred communal sites, termed latrines which play a vital role in the transmission dynamics of B. procyonis. Intestinal infections of non-raccoon species have been documented in dogs, rabbits in Japan and experimentally in opossums. Over 100 species mammals and birds can be paratenic host for B. procyonis. This parasite has emerged in recent years as one of the most serious causes of zoonotic visceral, ocular, and neural larva migrans and, in particular, of devastating encephalitis in young children. Several probable or confirmed cases of severe or fatal human B. procyonis infection have been documented. Diagnosis of Baylisascaris encephalitis is based on clinical central nervous system disease, peripheral and cerebrospinal fluid eosinophilia, deep white matter lesions visible by magnetic resonance imaging, and positive results of serologic tests. Treatment efficacy in clinical cases is poor, but albendazole prevents disease if given promptly after infection. While human baylisascariasis appears to be rare, the devastating neurologic disease that is caused by this infection and the lack of effective treatment make it a disease of public health importance. Certain characteristics of B. procyonis make it a feasible bioterrorist agent, because eggs can survive in the environment for extended periods of time, and the infectious dose of B. procyonis is relatively low. Moreover, the organism causes a severe, frequently fatal infection in humans, and no effective therapy or vaccine exists.

Left ventricular hydatid cyst presenting with acute ischemic stroke: case report.

Cardiac hydatid cysts are rarely seen. The presentation of an acute stroke secondary to embolization from a cardiac hydatid cyst is also rare. We report a young boy with left ventricular hydatid cyst who presented with acute ischemic stroke.

[Sonographic evaluation of periportal fibrosis in children living in a Schistosoma mansoni endemic region]. / Fibrose périportale chez les enfants en zone d'endémie à Schistosoma mansoni: évaluation échographique.

PURPOSE: To assess with ultrasound periportal fibrosis due to chronic Schistosoma mansoni infection in children living in an endemic region. Materials and methods. A total of 441 children underwent two stool examinations and abdominal sonography. Liver echotexture was assessed by two observers and compared to pre-defined image patterns and a fibrosis score was assigned ranging from 0 to 8. Ultrasound features were correlated to age, sex, and parasitologic findings. RESULTS: Prevalence of Schistosoma mansoni infestation was 63%. Two cases of advanced fibrosis (E pattern or fibrosis score of 6) were observed. Fibrosis correlated with age. No correlation existed between fibrosis and intensity of egg-output. A correlation between the two examinors was noted in 84% of examinations with a kappa coefficient of 0.7. CONCLUSION: Although severe periportal fibrosis is a rare finding in this endemic region, follow-up sonography must be performed because it is the only non invasive and reliable tool for detection of periportal fibrosis.