Knowledge of female genital schistosomiasis and urinary schistosomiasis among final-year midwifery students in the Volta Region of Ghana.

BACKGROUND: Female genital schistosomiasis (FGS) is a gynaecological complication of urinary schistosomiasis (US) with an estimated burden of 20-120 million cases in endemic areas. A neglected sexual and reproductive health disease in sub-Saharan Africa, FGS increases susceptibility to sexually transmitted infections including cervical cancer and infertility among other morbidities. However, there appears to be limited FGS knowledge among practicing and pre-service health providers with implications for control. We assessed FGS awareness among final-year midwifery students who would soon be delivering primary maternal and reproductive health care. METHODS: A cross-sectional study was conducted among 193 randomly selected final-year students from all three midwifery training institutions in the Volta region of Ghana in August/September, 2022. Data on participants' demographics and knowledge of the transmission, signs and symptoms, complications, treatment and prevention of both FGS and US were collected using structured questionnaires. Summary statistics were presented as frequencies, proportions and percentages. RESULTS: Only 23.3% (44/189) of participants had heard about FGS compared to 64% (123/192) for US. Of the former, 42 (95%), 40 (91%) and 36 (81.8%) respectively identified genital itching/burning sensation, bloody vaginal discharge and pelvic pain/pain during intercourse as part of the symptoms of FGS. Less than a third (13/44) and about half (25/44) of those who indicated hearing about FGS knew it can be a risk for ectopic pregnancies and infertility respectively. Majority of these participants, 40 (91%), wrongly selected antibiotics as treatment for FGS while 9 indicated it is prevented by sleeping in insecticide-treated nets. CONCLUSION: Awareness of FGS was limited among the study participants. The high prevalence of knowledge of some FGS symptoms related to the genitalia needs cautious interpretation. Health care training institutions must make deliberate efforts to highlight FGS in the training of midwives as the condition has diagnostic and management implications for some sexual and reproductive health conditions.

Multiple-bead assay for the differential serodiagnosis of neglected human cestodiases: Neurocysticercosis and cystic echinococcosis.

BACKGROUND: Neurocysticercosis (NCC), and cystic echinococcosis (CE) are two neglected diseases caused by cestodes, co-endemic in many areas of the world. Imaging studies and serological tests are used in the diagnosis of both parasitic diseases, but cross-reactions may confound the results of the latter. The novel multiplex bead-based assay with recombinant antigens has been reported to increases the diagnostic accuracy of serological techniques. METHODOLOGY: We set-up an immunoassay based on the multiplex bead-based platform (MBA), using the rT24H (against Cysticercus cellulosae, causing cysticercosis) and r2B2t (against Echinococcus granulosus sensu lato, causing CE) recombinant antigens, for simultaneous and differential diagnosis of these infections. The antigens were tested on 356 sera from 151 patients with CE, 126 patients with NCC, and 79 individuals negative for both diseases. Specificity was calculated including sera from healthy donors, other neurological diseases and the respective NCC or CE sera counterpart. The diagnostic accuracy of this assay was compared with two commercial ELISA tests, Novalisa and Ridascreen, widely used in the routine diagnosis of cysticercosis and CE, respectively. MAIN FINDINGS: For the diagnosis of NCC, sensitivity ranged from 57.94-63.49% for the rT24H-MBA, and 40.48-46.03% for Novalisa ELISA depending on exclusion or inclusion of sera having equivocal results on ELISA from the analysis; specificities ranged from 90.87-91.30% and 70.43-76.96%, respectively. AUC values of the ROC curve were 0.783 (rT24H) and 0.619 (Novalisa) (p-value < 0.001). For the diagnosis of CE, the sensitivity of the r2B2t-MBA ranged from 68.87-69.77% and of Ridascreen ELISA from 50.00-57.62%; specificities from 92.47-92.68% and from 74.15-80.98%, respectively. AUC values were 0.717 and 0.760, respectively. CONCLUSIONS/SIGNIFICANCE: Overall, the recombinant antigens tested with the bead-based technology showed better diagnostic accuracy than the commercial assays, particularly for the diagnosis of NCC. The possibility of testing the same serum sample simultaneously for the presence of antibodies against both antigens is an added value particularly in seroprevalence studies for cysticercosis linked to control programs in endemic areas where these two parasites coexist.

Eosinophils participate in modulation of liver immune response and tissue damage induced by Schistosoma mansoni infection in mice.

The severity of chronic schistosomiasis has been mainly associated with the intensity and extension of the inflammatory response induced by egg-secreted antigens in the host tissue, especially in the liver and intestine. During acute schistosomiasis, eosinophils account for approximately 50% of the cells that compose the liver granulomas; however, the role of this cell-type in the pathology of schistosomiasis remains controversial. In the current study, we compared the parasite burden and liver immunopathological changes during experimental schistosomiasis in wild-type (WT) BALB/c mice and BALB/c mice selectively deficient for the differentiation of eosinophils (ΔdblGATA). Our data demonstrated that the absence of eosinophil differentiation did not alter the S. mansoni load or the liver retention of parasite eggs; however, there were significant changes in the liver immune response profile and tissue damage. S. mansoni infection in ΔdblGATA mice resulted in significantly lower liver concentrations of IL-5, IL-13, IL-33, IL-17, IL-10, and TGF-ß and higher concentrations of IFN-γ and TNF-α, as compared to WT mice. The changes in liver immune response observed in infected ΔdblGATA mice were accompanied by lower collagen deposition, but higher liver damage and larger granulomas. Moreover, the absence of eosinophils resulted in a higher mortality rate in mice infected with a high parasite load. Therefore, the data indicated that eosinophils participate in the establishment and/or amplification of liver Th-2 and regulatory response induced by S. mansoni, which is necessary for the balance between liver damage and fibrosis, which in turn is essential for modulating disease severity.

Sodium butyrate ameliorates Schistosoma japonicum-induced liver fibrosis by inhibiting HMGB1 expression.

Schistosomiasis is a prevalent zoonotic parasitic disease caused by schistosomes. Its main threat to human health is hepatic granuloma and fibrosis due to worm eggs. Praziquantel remains the first choice for the treatment of schistosomiasis but has limited benefit in treating liver fibrosis. Therefore, the need to develop effective drugs for treating schistosomiasis-induced hepatic fibrosis is urgent. High-mobility group box 1 protein (HMGB1) is a potential immune mediator that is highly associated with the development of some fibrotic diseases and may be involved in the liver pathology of schistosomiasis. We speculated that HMGB1 inhibitors could have an anti-fibrotic effect. Sodium butyrate (SB), a potent inhibitor of HMGB1, has shown anti-inflammatory activity in some animal disease models. In this study, we evaluated the effects of SB on a murine schistosomiasis model. Mice were percutaneously infected with 20 ± 2 cercariae of Schistosoma japonicum. SB (500 mg/kg/day) was administered every 3 days for the entire experiment period. The activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), liver histopathology, HMGB1 expression, and the levels of interferon gamma (IFN-γ), transforming growth factor-ß1 (TGF-ß1), and interleukin-6 (IL-6) in serum were analyzed. SB reduced hepatic granuloma and fibrosis of schistosomiasis, reflected by the decreased levels of ALT and AST in serum and the reduced expression of pro-inflammatory and fibrogenic cytokines (IFN-γ, TGF-ß1, and IL-6). The protective effect could be attributable to the inhibition of the expression of HMGB1 and release by SB.

Furan derivatives impair proliferation and affect ultrastructural organization of Trypanosoma cruzi and Leishmania amazonensis.

Chagas disease and leishmaniasis are neglected diseases caused by parasites of the Trypanosomatidae family and together they affect millions of people in the five continents. The treatment of Chagas disease is based on benznidazole, whereas for leishmaniasis few drugs are available, such as amphotericin B and miltefosine. In both cases, the current treatment is not entirely efficient due to toxicity or side effects. Encouraged by the need to discover valid targets and new treatment options, we evaluated 8 furan compounds against Trypanosoma cruzi and Leishmania amazonensis, considering their effects against proliferation, infection, and ultrastructure. Many of them were able to impair T. cruzi and L. amazonensis proliferation, as well as cause ultrastructural alterations, such as Golgi apparatus disorganization, autophagosome formation, and mitochondrial swelling. Taken together, the results obtained so far make these compounds eligible for further steps of chemotherapy study.

Cerebral Coenurosis of a Long-Tailed Goral, Naemorhedus caudatus, in Korea.

We intended to describe a case of cerebral coenurosis in a long-tailed goral, Naemorhedus caudatus, from Hwacheon-gun, Gangwon-do (Province), in the Korea. The goral, a 10-year-old male, was suffering from neurological symptoms, such as turning the circle to one side without lifting the head straight, and died at 30 days after admission to the wildlife medical rescue center in Chuncheon-si, Gangwon-do. A fluid-filled cyst was detected in the left cerebral hemisphere by computed tomography and magnetic resonance imaging. The cyst removed from the deceased goral was transparent, about 3×3 cm in size, contained a clear fluid and approximately 320 protoscolices invaginating from the internal germinal layer. The protoscolex had 4 suckers and a rostellum with 28 hooklets arranged in 2 rows. By the present study, a case of cerebral coenurosis was first confirmed in a long-tailed goral, N. caudatus, from Gangwon-do, in Korea. The residents frequently exposed in the sylvatic environment should be careful the accidental infections of zoonotic metacestode of Taenia multiceps, Coenurus cerebralis, in Korea.

Polymorphism in the catalytic subunit of the PI3Kγ gene is associated with Trypanosoma cruzi-induced chronic chagasic cardiomyopathy.

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. During the chronic phase of disease, while most infected people do not present symptoms, characterizing the asymptomatic form, some patients develop the cardiac form or chronic chagasic cardiomyopathy, which is considered the most severe manifestation of this disease. Considering that the activation of the PI3Kγ signaling pathway is essential for an efficient immune response against T. cruzi infection, we evaluated the PIK3CG C > T (rs1129293) polymorphism in exon 3 of this gene, which encodes the catalytic subunit of PI3Kγ. The PIK3CG CT and TT genotypes were found to be associated with an increased risk of developing the cardiac form of the disease rather than the asymptomatic or digestive forms. In conclusion, the presence of the T allele at single or double doses may differentiate the cardiac from other clinical manifestations of Chagas disease. This finding should help in further studies to evaluate the mechanisms underlying the differential association of PIK3CG in Chagas disease.

Molecular Context of ADP-ribosylation in Schistosomes for Drug Discovery and Vaccine Development.

Schistosome infection is regarded as one of the most important and neglected tropical diseases associated with poor sanitation. Like other living organisms, schistosomes employ multiple biological processes, of which some are regulated by a post-translational modification called Adenosine Diphosphate-ribosylation (ADP-ribosylation), catalyzed by ADP-ribosyltransferases. ADP-ribosylation is the addition of ADP-ribose moieties from Nicotinamide Adenine Dinucleotide (NAD+) to various targets, which include proteins and nucleotides. It is crucial in biological processes such as DNA repair, apoptosis, carbohydrate metabolism and catabolism. In the absence of a vaccine against schistosomiasis, this becomes a promising pathway in the identification of drug targets against various forms of this infection. The tegument of the worm is an encouraging immunogenic target for anti-schistosomal vaccine development. Vaccinology, molecular modeling and target-based drug discovery strategies have been used for years in drug discovery and for vaccine development. In this paper, we outline ADP-ribosylation and other different approaches to drug discovery and vaccine development against schistosomiasis.

Describing nearly two decades of Chagas disease in Germany and the lessons learned: a retrospective study on screening, detection, diagnosis, and treatment of Trypanosoma cruzi infection from 2000 - 2018.

BACKGROUND: The highly complex and largely neglected Chagas disease (CD) has become a global health problem due to population movements between Latin America and non-endemic countries, as well as non-vectorial transmission routes. Data on CD testing and treatment from routine patient care in Germany of almost two decades was collected and analysed. METHODS: German laboratories offering diagnostics for chronic Trypanosoma cruzi (T. cruzi) infection in routine patient care were identified. All retrievable data on tests performed during the years of 2000-2018 were analysed. Additional clinical information regarding patients diagnosed with CD was collected through questionnaires. RESULTS: Five German laboratories with diagnostics for T. cruzi infection in routine patient care were identified. Centres in Hamburg and Munich offered two independent serological tests to confirm the CD diagnosis, as recommended by WHO during the entire time period 2000-2018. Overall, a total of n = 10,728 independent tests involving n = 5991 individuals were identified with a progressive increase in testing rates over time, only n = 130 (16.0%) of the tested individuals with known nationality came from CD endemic countries. Of all test units conducted at the included institutes, a total of n = 347/10,728 (3.2%) tests on CD were positive, of which n = 200/347 (57.6%) were ELISA, n = 133/347 (38.3%) IFT, n = 10/347 (2.9%) PCR, and n = 4/347 (1.2%) RDT. Of the n = 5991 individuals only n = 81 (1.4%) with chronic infection were identified, n = 52 females and n = 28 males. Additional clinical information could only be collected from n = 47. CONCLUSION: The results of this study give insight into the deployment of screening, detection, diagnosis, and treatment of T. cruzi over the last two decades in Germany and existing deficits therein; the creation of guidelines for Germany could be a step forward to improve the existing gaps.

Progress on the national echinococcosis control programme in China: analysis of humans and dogs population intervention during 2004-2014.

BACKGROUND: A national control program for echinococcosis has been in effect since 2005 in China. This program has applied a comprehensive strategy, and good control results have been achieved. Human echinococcosis prevalence rate decrease from 1.08% in 2004 to 0.24% in 2012. The objective of this study is focusing on assessment of the programme with two indices, including patient treatment and registered dogs deworming, in endemic areas of echincoccosis control over the period of 10 years (2004-2014) in China. METHODS: We established the database including demography at county and township levels with coverage for ten provinces and autonomous regions of China in this study. We using methods of epidemiological descriptive, instead the expectation-maximization for missing value filling for grouping available patients into those subjected to surgery and those receiving drug treatment after population screening and the dogs population after registered by deworming. We performed Microsoft Excel software and SPSS software on the results as percentages with the corresponding 95% confidence intervals (95% CIs). We also statistically analyzed the economics data on patient treatment and dogs deworming after the corresponding discount with annual bank interest rates (USD 1 = CNY 6.5, bank discount average changes of 2.3-3.3%). RESULTS: During 2004-2014, the grant total average rate of surgical patient (after surgical operation) treatment had increased with 32.4% and with 81.3% for medical treatment with albendazole. Meanwhile, it increased by 58.6% for the deworming of registered dog since 2007. The accumulated costs amounted to USD 27.03 million after discount for patients and registered dog treatment, which is 1/4 of the total accumulated financial inputs (USD 110.67 million from the Chinese Government). Since the implementation of the national program, it has increased 57 times with respect to the annual financial inputs (costs) and 368 times with respect to all accumulated financial inputs (costs). CONCLUSIONS: This study showed that in endemic areas, patient diagnosis and management, dog management and treatment over this period helped reduce the parasite load to control the disease. More attention should be paid to controlling wild canines during the ongoing program period and sustainable follow-up evaluations are crucial for success and continued implementation of the national program.

Loop-Mediated Isothermal Amplification as Point-of-Care Diagnosis for Neglected Parasitic Infections.

The World Health Organisation (WHO) has placed twenty diseases into a group known as neglected tropical diseases (NTDs), twelve of them being parasitic diseases: Chagas' disease, cysticercosis/taeniasis, echinococcosis, food-borne trematodiasis, human African trypanosomiasis (sleeping sickness), leishmaniasis, lymphatic filariasis, onchocerciasis (river blindness), schistosomiasis, soil-transmitted helminthiasis (ascariasis, hookworm, trichuriasis), guinea-worm and scabies. Such diseases affect millions of people in developing countries where one of the main problems concerning the control of these diseases is diagnosis-based due to the most affected areas usually being far from laboratories having suitable infrastructure and/or being equipped with sophisticated equipment. Advances have been made during the last two decades regarding standardising and introducing techniques enabling diagnoses to be made in remote places, i.e., the loop-mediated isothermal amplification (LAMP) technique. This technique's advantages include being able to perform it using simple equipment, diagnosis made directly in the field, low cost of each test and the technique's high specificity. Using this technique could thus contribute toward neglected parasite infection (NPI) control and eradication programmes. This review describes the advances made to date regarding LAMP tests, as it has been found that even though several studies have been conducted concerning most NPI, information is scarce for others.

The associations of hub gene polymorphisms in PI3K/AKT/mTOR pathway and Schistosomiasis Japonica infection and hepatic fibrosis.

INTRODUCTION: Increasing evidence shows that the PI3K/AKT/mTOR pathway can be activated by a variety of stimulus in immune cells. Schistosomiasis Japonica is a serious threat to human health in some lakes of China. METHODS: We analyzed the potential associations between the hub gene (PTEN, mTOR, AKT1 and AKT2) polymorphisms of PI3K/AKT/mTOR pathway and S. japonica risk, including infection risk, as well as immunological hepatic fibrosis risk. An immune database named Database of Immune Cell Expression, Expression quantitative trait loci and Epigenomics (DICE) was used to analyze the expression profiles of the hub genes in 15 types of immune cells. RESULTS: Of them, two SNPs rs2295080 (mTOR) and rs7254617 (AKT2) were found associated with the risk of infection and fibrosis. We also performed a multivariant Cox regression analysis and found that HBV infection may increase hepatic fibrosis in chronic schistosomiasis patients, instead of genetic polymorphisms on PI3K/AKT/mTOR pathway or any other factors. We also found the expressions of mTOR (RICTOR) and AKT2 in T cells were higher than those in monocyte cells. And, the expressions of PTEN, mTOR (RICTOR) and AKT1 reduced both in activated CD4 T cells and activated CD8 T cells. CONCLUSIONS: We concluded that rs2295080 may be an important marker in the diagnosis of susceptibility to schistosomiasis infection. But HBV infection not rs2295080 could promote immunological liver damage with fibrosis in patients with chronic schistosomiasis infection.

Cystic echinococcosis in the Eastern Mediterranean region: Neglected and prevailing!

Cystic echinococcosis (CE) is distributed worldwide, extending from China to the Middle East and from Mediterranean countries to the sub-Saharan Africa and South America. According to WHO, one million people around the world are suffering from CE with an estimated burden of 183,573 DALYs. The annual monetary burden of the disease due to treatment costs and CE-related livestock losses has been estimated at US$ 3 billion. CE is endemic in all countries within the WHO Eastern Mediterranean Regional Office (EMRO). The region, which includes most of the Middle East and North Africa, is one of the most ancient foci of the domestic cycle of CE and is recognized as one of the major hotspots of CE. There are 22 countries in the EMRO, where about 688 million people are living at risk of CE. In many EMRO countries, little is known about CE epidemiology and transmission. WHO included echinococcosis in a list of 17 neglected tropical diseases (NTDs) and 12 neglected zoonotic diseases (NZDs). Accordingly, different regional offices of WHO organized several initiatives for CE control and prevention. WHO's Western Pacific regional office considered echinococcosis as one of the region's major health topics, and several preventive measures have been implemented in the American region with the support of Pan American Health Organization (PAHO) in Argentina, Peru, Uruguay, and Chile. Although CE is endemic in all 22 EMRO countries, surprisingly, CE is absent from the health topics list of diseases and conditions in this region. Therefore, CE clearly requires further attention in the WHO EMRO agenda, and the need for elaboration of specific measures for CE control is becoming apparent in EMRO countries, where substantial collaborations among the member states and WHO EMRO is of paramount importance. Major topics of collaborative activities include training programs and health communication on different aspects of CE control, analysis of CE burden, national and international surveillance and disease registry systems, technical support to promote epidemiological studies for collecting baseline data, cost-benefit analysis of control interventions, and intersectoral cooperation among the agriculture, veterinary, medical, and health sectors.

Screening Marine Natural Products for New Drug Leads against Trypanosomatids and Malaria.

Neglected Tropical Diseases (NTD) represent a serious threat to humans, especially for those living in poor or developing countries. Almost one-sixth of the world population is at risk of suffering from these diseases and many thousands die because of NTDs, to which we should add the sanitary, labor and social issues that hinder the economic development of these countries. Protozoan-borne diseases are responsible for more than one million deaths every year. Visceral leishmaniasis, Chagas disease or sleeping sickness are among the most lethal NTDs. Despite not being considered an NTD by the World Health Organization (WHO), malaria must be added to this sinister group. Malaria, caused by the apicomplexan parasite Plasmodium falciparum, is responsible for thousands of deaths each year. The treatment of this disease has been losing effectiveness year after year. Many of the medicines currently in use are obsolete due to their gradual loss of efficacy, their intrinsic toxicity and the emergence of drug resistance or a lack of adherence to treatment. Therefore, there is an urgent and global need for new drugs. Despite this, the scant interest shown by most of the stakeholders involved in the pharmaceutical industry makes our present therapeutic arsenal scarce, and until recently, the search for new drugs has not been seriously addressed. The sources of new drugs for these and other pathologies include natural products, synthetic molecules or repurposing drugs. The most frequent sources of natural products are microorganisms, e.g., bacteria, fungi, yeasts, algae and plants, which are able to synthesize many drugs that are currently in use (e.g. antimicrobials, antitumor, immunosuppressants, etc.). The marine environment is another well-established source of bioactive natural products, with recent applications against parasites, bacteria and other pathogens which affect humans and animals. Drug discovery techniques have rapidly advanced since the beginning of the millennium. The combination of novel techniques that include the genetic modification of pathogens, bioimaging and robotics has given rise to the standardization of High-Performance Screening platforms in the discovery of drugs. These advancements have accelerated the discovery of new chemical entities with antiparasitic effects. This review presents critical updates regarding the use of High-Throughput Screening (HTS) in the discovery of drugs for NTDs transmitted by protozoa, including malaria, and its application in the discovery of new drugs of marine origin.

Epidemiological characteristics of hepatic echinococcosis, concurrent cerebral echinococcosis, and pulmonary echinococcosis in Ganzi County, Sichuan Province, China.

Human echinococcosis has become a major public health problem in most parts of the world. The objective of this article was to study the demographics of patients with hepatic echinococcosis in Ganzi County to elucidate the main risk factors, as well as to report the concurrent prevalence of cerebral echinococcosis and pulmonary echinococcosis.We recruited 195 patients with hepatic echinococcosis from the Datongma area of Ganzi County from January 2018 to November 2018. The patients' demographics, living environments, supported medical resources, knowledge of echinococcosis prevention and control, and hygienic practices were investigated and analyzed. The prevalence of cerebral echinococcosis and pulmonary echinococcosis were also investigated.The data were analyzed to identify risk factors for human echinococcosis. Our analysis showed that the herding Tibetan population within the 20 to 60 age group, and females, in particular, were at the highest risk of human echinococcosis infection. Having stray dogs around habitations and intimate activities with dogs and livestock were also behavioral risk factors. People with poor health literacy and low educational qualifications had possible risks of infection. In terms of hygiene, not using tap water as the drinking water source and lack of medical staff were significantly correlated with echinococcosis prevalence. Four patients were diagnosed with cerebral echinococcosis. Among them, 1 patient had both cerebral echinococcosis and pulmonary echinococcosis.Possible high-risk factors for echinococcosis were being female, herding population, in the 20 to 60 age group, having stray dogs around habitations, having activities with dogs and livestock, having poor health literacy, having low educational qualifications, and not using tap water as a drinking water source. The detection rate for brain echinococcosis in patients with hepatic echinococcosis was high (2.05%). Effective preventive strategies should be implemented in epidemic areas. Head CT scans should be applied for early detection of cerebral echinococcosis to carry out the treatment.

Efficacy and safety of dimeticones in the treatment of epidermal parasitic skin diseases with special emphasis on tungiasis: an evidence-based critical review

ABSTRACT Epidermal parasitic skin diseases encompass scabies, pediculosis, cutaneous larva migrans, myiasis, and tungiasis. Tungiasis is probably the most neglected of all Neglected Tropical Diseases (NTD). It occurs in South America, the Caribbean and Sub-Saharan Africa and affects marginalized populations where people live in extreme poverty. In endemic communities the prevalence can be up to 30% in general population and 85% in children. Over time, chronic pathology develops characterized by hyperkeratosis, edema around the nail rim, fissures, ulcers, deformation and loss of nails. This leads to a pattern of disabilities, eventually resulting in impairment of mobility.Dimeticones are a family of silicon oils with a potential to kill parasites located on top or inside the epidermis by a physical mode of action. They are considered the treatment of choice for pediculosis capitis and pediculosis pubis. With regard to tungiasis, the so called rear abdominal cone of the parasites has been identified as a target for treatment with dimeticones. NYDA®, a mixture of two dimeticones with different viscosity, is the only dimeticone product for which data on the mode of action, efficacy and safety with regard to tungiasis exists. The product has been shown highly effective against embedded sand fleas, even in very intense infection with more than 500 parasites situated on top of each other. A randomized controlled trial showed that seven days after a targeted application of NYDA® 97% (95% CI 94-99%) of the embedded sand fleas had lost all signs of viability.Comprehensive toxicological investigations on the dimeticones contained in NYDA® showed that there is practically no risk of embryotoxicity, fetotoxicity, teratogenicity, and other toxicity. The safety of dimeticones was also demonstrated in clinical trials with a total of 106 participants with tungiasis, in which not a single adverse event was observed.

Leishmanicidal activity of Piper marginatum Jacq. from Santarém-PA against Leishmania amazonensis.

Leishmaniasis is an infectious disease that has high endemicity and is among the six parasitic diseases of higher occurrence in the world. The current treatments are limited due to their toxicity, treatment resistance and high cost which have increased the search for new substances of natural origin for its therapy. Based on this, an in vitro biological and chemical investigation was carried out to evaluate the potential of Piper marginatum against Leishmania amazonesis. P. marginatum leaves were collected to obtain the essential oil (EO) and the ethanolic extract (CE). The chemical profile of the CE and fractions was obtained by 1H NMR. The analysis of the EO chemical composition was performed by GC-MS. EO, CE and fractions were submitted to antileishmanial and cytotoxicity assays against macrophages. The chromatographic profiles of EO, CE and fractions showed the presence of phenolic compounds and terpenoids, having 3,4-Methylenedioxypropiophenone as a major compound. All P. marginatum samples showed low toxicity to macrophages. The CE and the methanolic, hexane and ethyl acetate fractions had low cytotoxicity when compared to Pentamidine. All tested samples inhibited growth of L. amazonensis promastigotes. The antileishmanial activity of EO, CE and fractions were evaluated in macrophages infected with L. (L.) amazonensis and treated with the concentrations 1, 10 and 100 µg/mL for 48 h. All samples were active, but EO and CE showed superior activity against amastigote forms when compared to the promastigote forms of L. amazonensis. This work describes for the first time the antileishmanial activity of the species P. marginatum and its cytotoxicity against macrophages, suggesting that it can be an alternative source of natural products in the phytotherapeutic treatment of leishmaniasis.

Thinking in paracoccidioidomycosis: a delayed diagnosis of a neglected tropical disease, case report and review of clinical reports and eco-epidemiologic data from Colombia since the 2000.

BACKGROUND: Paracoccidioidomycosis is a neglected tropical disease, endemic in several countries of South America including Colombia. We report a case of a patient with Chronic Multifocal Paracoccidioidomycosis with long-standing symptoms and a delayed diagnosis caused by several barriers to achieve it. We did a review of the papers published in Colombia about this disease, focusing in clinical data and eco-epidemiology with the finding of a lack of new information on this topic since the 2000 in our region. CASE PRESENTATION: We present a 54-year-old man, farmer in his youth, with a chronic ulcerated lesion in the lower lip similar to a lip carcinoma, a deforming lesion in the nose, and respiratory symptoms with emphysematous lung. Lip biopsy with silver methenamine stain revealed small and large budding yeasts that resembles a "mariner's wheel" confirming Chronic Multifocal Paracoccidioidomycosis. He was treated successfully but subsequently lost to follow up. CONCLUSIONS: It is very important to focus attention, reinforce the search and create networks for the study of neglected tropical diseases. The presented case illustrates a usual clinical presentation, but with a delayed diagnosis due to the difficulties that still occur in some regions like ours for the early recognition of a case of chronic multifocal paracoccidioidomycosis.

Comparative study of different forms of Jellein antimicrobial peptide on Leishmania parasite.

Typically, antimicrobial peptides (AMPs) are short positive charged peptides serving a key role in innate immunity as well as antimicrobial activity. Discovering novel therapeutic agents is considered as an undeniable demand due to increasing microbial species with antibiotic resistance. In this direction, the unique ability of AMPs to modulate immune responses highlighted them as novel drug candidates in the field of microbiology. Patients affected by leishmaniasis; a neglected tropical disease, confront serious problems for their treatment including resistance to common drugs as well as toxicity and high cost of therapy. So, there is a need for development of new drug candidates to control the diseases. Jellein, a peptide derived from royal jelly of honeybee has been shown to have promising effect against several bacterial and fungal species. In current study, anti-leishmanial effect of Jellein and its lauric acid conjugated form was investigated against two forms of Leishmania major (L. major) parasite. Moreover, cytotoxic effect of these peptides was studied in THP1 cell line and human Red Blood Cells (RBCs). Furthermore, the mechanism of action of peptides on L. major promastigotes was assessed through different methods. The results demonstrated that, conjugation of lauric acid to Jellein not only had no effect on the elevation of antimicrobial activity but also halted it completely. Moreover, Jellein caused a limitation in the number of L. major promastigotes by pore formation as well as changing the membrane potential rather than induction of apoptosis or activation of caspases.