Intestinal parasitic infection: prevalence,knowledge, attitude,and practices among schoolchildren in an urban area of Taiz city,Yemen

BackgroundIntestinal parasitic infections (IPIs) are regarded as one of the main public health problems and socio-economic issues adversely affecting the health of millions of people worldwide. Our study aimed to describe the knowledge, attitude, and practices of local urban schoolchildren in Taiz City towards intestinal parasitic infections.Methods and materialThis is a cross-sectional study conducted in Taiz, Yemen from March to May 2019. A total of 385 schoolchildren were selected using a random sampling technique from 7 primary schools. Wet-mount microscopic examination, formol-ether concentration techniques, and Lugols'' iodine were employed in parasite detection and cyst identification.ResultsOf the 385 schoolchildren examined for IPIs, 107 (27.8%) were positive for the presence of enteric parasites, some having multiple infections. The prevalence was slightly higher in males 46 (28.6%) than in females 61 (27.2%) but have no statistical difference (P = 0.77). Entamoeba histolytica/dispar was the most common infection with 16.4% of cases. A substantial percentage (40.5%) of the respondents displayed poor knowledge. The respondents also revealed inappropriate attitudes and practices that contribute to the prevalence of IPIs in the study.ConclusionsThe study revealed the prevalence of intestinal parasites among the schoolchildren in Taiz, Yemen, suggesting that IPIs remain a major public health problem. Entamoeba histolytica/dispar was the most prevalent intestinal parasites identified among the schoolchildren. Age, poor knowledge of the mode of transmission, prevention, and acquisition of IPIs, and poor habitual hygiene practices increase the risk of acquiring intestinal infections.     

吉林市人体肠道寄生虫感染调查

目的：调查吉林市肠道寄生虫感染情况。方法：对1389人进行粪便普查和流行病学调查。结果：共检出肠道寄生虫9种,总感染率为71.13％,感染率从高到低依次为蛔虫(64.07％)、肝吸虫(2.23％)、贾第鞭毛虫(1.94％)、结肠阿米巴(1.51％)、鞭虫(0.79％)、嗜碘阿米巴(0.28％)、肠人毛滴虫(0.14％)、痢疾阿米巴及钩虫(均为0.07％)。结论：吉林市人体肠道寄生虫感染率较高,应注意建立一套完整的防治措施。,Objective:To investigate the human intestine parasitization in Jilin City.Methods: Mass survey of feces and epidemiological survey were carried out in 1389 persons.Results:Nine kinds of intestinal parasites had been detected and the total infection rate was71.13%. From high to low, the infection rates were respectively(64.07％)for ascaris lumbri-coides(2.23％) for clonorchis sinensis, (1.94％) for giardia lamblia(1.51％) for entamoe-ba coli (0.74％) for trichuris trichiura(0.28％) for iodamoeba bvetschlii (0.14％) fortrichomonas hominis(0.07％) for entamoeba histolytica and ancylostoma duodenale. Conclusion :The intestinal parasitization rate is higher in Jilin City, and this result suggests that we setup a series of prophylectico-therapeutic measures.     

Induction of immunogenicity by live attenuated Leishmania donovani centrin deleted parasites in dogs

Zoonotic visceral leishmaniasis, caused by the intracellular protozoan parasite Leishmania infantum, is a neglected tropical disease that is often fatal when untreated. Dogs are considered the main reservoir of L. infantum in zoonotic VL as the presence of infected dogs may increase the risk for human infection. Canine visceral leishmaniasis (CVL) is a major veterinary and public health problem in Southern Europe, Middle East and South America. Control of animal reservoirs relies on elimination of seropositive dogs in endemic areas. However, treatment of infected dogs is not considered a favorable approach as this can lead to emergence of drug resistance since the same drugs are used to treat human infections. Therefore, vaccination against CVL remains the best alternative in control of the animal reservoirs. In this study, we present data on the immunogenicity profile of a live attenuated parasite LdCen^−/− in a canine infection model and compared it to that of Leishmune^®, a commercially available recombinant vaccine. The immunogenicity of the LdCen^−/− parasites was evaluated by antibody secretion, production of intracytoplasmic and secreted cytokines, activation and proliferation of T cells. Vaccination with LdCen^−/− resulted in high immunogenicity as revealed by the higher IgGTotal, IgG1, and IgG2 production and higher lymphoproliferative response. Further, LdCen^−/− vaccinated dogs showed higher frequencies of activated CD4+ and CD8+ T cells, IFN-γ production by CD8+ T cells, increased secretion of TNF-α and IL-12/IL-23p40 and decreased secretion of IL-4. These results contribute to the understanding of immunogenicity elicited by live attenuated L. donovani parasites and, consequently, to the development of effective vaccines against visceral leishmaniasis.     

First-in-human evaluation of genetically attenuated Plasmodium falciparum sporozoites administered by bite of Anopheles mosquitoes to adult volunteers

Background

Immunization with genetically engineered, attenuated malaria parasites (GAP) that arrest during liver infection confers sterile protection in mouse malaria models. A first generation Plasmodium falciparum GAP (Pf p52⁻/p36⁻ GAP) was previously generated by deletion of two pre-erythrocytic stage-expressed genes (P52 and P36) in the NF54 strain.

Methods

A first-in-human, proof-of-concept, safety and immunogenicity clinical trial in six human volunteers was conducted. Exposure consisted of delivery of Pf p52⁻/p36⁻ GAP sporozoites via infected Anopheles mosquito bite with a five-bite/volunteer exposure followed by an approximately 200-bite exposure/volunteer one month later.

Results

The exposures were well tolerated with mild to moderate local and systemic reactions. All volunteers remained blood stage negative after low dose exposure. Five volunteers remained blood stage negative after high dose exposure. One volunteer developed peripheral parasitemia twelve days after high dose exposure. Together the findings indicate that Pf p52⁻/p36⁻ GAP was severely but not completely attenuated. All six volunteers developed antibodies to CSP. Furthermore, IFN-γ responses to whole sporozoites and multiple antigens were elicited in 5 of 6 volunteers, with both CD4 and CD8 cell cytokine production detected.

Conclusion

Severe attenuation and favorable immune responses following administration of a first generation Pf p52⁻/p36⁻ GAP suggests that further development of live-attenuated strains using genetic engineering should be pursued.     

Dual-Stage Picolinic Acid-Derived Inhibitors of Toxoplasma gondii

Toxoplasma gondii causes a prevalent human infection for which only the acute stage has an FDA-approved therapy. To find inhibitors of both the acute stage parasites and the persistent cyst stage that causes a chronic infection, we repurposed a compound library containing known inhibitors of parasitic hexokinase, the first step in the glycolysis pathway, along with a larger collection of new structural derivatives. The focused screen of 22 compounds showed a 77% hit rate (>50% multistage inhibition) and revealed a series of aminobenzamide-linked picolinic acids with submicromolar potency against both T. gondii parasite forms. Picolinic acid 23, designed from an antiparasitic benzamidobenzoic acid class with challenging ADME properties, showed 60-fold-enhanced solubility, a moderate LogD_7.4, and a 30% improvement in microsomal stability. Furthermore, isotopically labeled glucose tracing revealed that picolinic acid 23 does not function by hexokinase inhibition. Thus, we report a new probe scaffold to interrogate dual-stage inhibition of T. gondii.     

长链非编码RNA在医学寄生虫学研究中的进展

长链非编码RNA（long non-coding RNA,lncRNA）是一类长度大于200 nt且基本不编码蛋白质的转录本,以RNA形式在表观遗传水平、转录及转录后水平影响基因的表达,广泛参与机体的病理生理过程。本文围绕lncRNA分子在寄生虫学领域中的研究进展做一综述,旨在为防治寄生虫疾病寻找新的靶点。     

Few colonies of the host Bombus terrestris disproportionately affect the genetic diversity of its parasite,Crithidia bombi

Sex and recombination have long been considered as necessary means for hosts to keep up with and resist to their faster reproducing parasites. On the other hand, comparatively little attention has been paid to potential benefits of recombination for the parasites. Using as model organisms the bumblebee Bombus terrestris and its genetically highly variable trypanosomatid parasite Crithidia bombi we analysed the infection dynamics as well as the relative frequency of parasite recombinants over time, in colonies that were either immune-challenged with heat-killed bacteria or sham-inoculated. In addition, we used infective cells from a given colony to infect workers from other, untreated colonies, to investigate whether recombinant parasite strains may have a competitive advantage over the parental strains to infect the surrounding host population. We show that in our experimental setup the host immune status does not influence the proportion of recombinant parasite cells in the infection. Neither do recombinant parasite strains have an advantage over the parental ones at infecting workers unrelated to the host colony the infection originally came from. However, we found that the prevalence of recombinants was highly variable among colonies, with one particular colony producing significantly more recombinant strains than others. As the successful infection of daughter queens – the only individuals surviving the winter to the next year – is proportional to the number of circulating parasite strains in the colony, we suggest that such “super-producing” colonies may be responsible for most of the infections happening in the next year.     

Recent initiatives and strategies to developing new drugs for tropical parasitic diseases

Background: Despite the toll of tropical parasitic diseases on human life in the developing world, present therapies still rely on drugs developed decades ago. In many cases, the clinical usefulness of these compounds is limited due to poor efficacy, toxicity and the constant attrition of drug resistance. The absence of a profit incentive regarding diseases afflicting the very poor has resulted in a lack of investment by the pharmaceutical industry in new chemotherapies. Objective: Given this background, this review addresses what alternative economic and scientific strategies have been implemented to procure novel drugs. Methods: The latest chemical, genetic and screening technologies to discover and develop drugs for tropical parasitic diseases are reviewed. In many cases these strategies are being implemented within the framework of public-private partnerships established to sustain dynamic drug development portfolios. Examples of public-private partnerships and their portfolios are discussed. Further, the contribution of dedicated academic screening centres to target discovery and preclinical prosecution of new small molecules is also highlighted. In every case, the latest scientific literature is cited, but also relevant press releases and website information to indicate the present vitality in the field. Conclusion: The tools, institutions and consortia are now in place and evolving to deliver new pharmaceuticals. Short-term results have already been realised in the clinic, mainly through the provision of new formulations of existing drugs. Long-term and consistent investment will be required, however, to identify, develop and clinically validate new chemical entities.     

川楝子的化学成分、药理作用及其毒性研究进展

川楝子作为传统中药,广泛应用于驱虫,是天然的杀虫剂。川楝子化学成分丰富,主要含有柠檬苦素型三萜、木脂素、黄酮、甾体、有机酸等成分,其具有抗肿瘤、抗氧化、抗菌、消炎镇痛、抗病毒、驱虫等广泛的药理作用,但由于川楝子有肝毒性、妊娠毒性等使其应用受到一定的限制。对川楝子的化学成分、药理作用和毒性研究进展进行综述,为其进一步的开发研究和临床应用提供科学依据。     

Novel molecular targets for antimalarial drug development

Malaria with one million deaths and about 500 million new cases reported annually is a challenge to drug therapy and discovery. As current antimalarial therapeutics become increasingly ineffective because of parasitic resistance, there exists an urgent need to develop and pursue new therapeutic strategies. Antimalarial drug development can follow several strategies, ranging from minor modifications of existing agents to the design of novel agents that act against new targets. Recent advances in our knowledge of parasite biology as well as the availability of the genome sequence provide a wide range of novel targets for drug design. Several promising targets for drug intervention have been revealed in recent years. This review discusses novel molecular targets of the malaria parasite available to the drug discovery scientist.