Designing efficient multi-epitope peptide-based vaccine by targeting the antioxidant thioredoxin of bancroftian filarial parasite.

Thioredoxin is a low molecular weight redox-active protein of filarial parasite that plays a crucial role in downregulating the host immune response to prolong the survival of the parasite within the host body. It has the ability to cope up with the oxidative challenges posed by the host. Hence, the antioxidant protein of the filarial parasite has been suggested to be a useful target for immunotherapeutic intervention of human filariasis. In this study, we have designed a multi-epitope peptide-based vaccine using thioredoxin of Wuchereria bancrofti. Different MHC-I and MHC-II epitopes were predicted using various web servers to construct the vaccine model as MHC-I and MHC-II epitopes are crucial for the development of both humoral and cellular immune responses. Moreover, TLRs specific adjuvants were also incorporated into the vaccine candidates as TLRs are the key immunomodulator to execute innate immunity. Protein-protein molecular docking and simulation analysis between the vaccine and human TLR was performed. TLR5 is the most potent receptor to convey the vaccine-mediated inductive signal for eliciting an innate immune response. A satisfactory immunogenic report from an in-silico immune simulation experiment directed us to propose our vaccine model for experimental and clinical validation. The reverse translated vaccine sequence was also cloned in pET28a(+) to apply the concept in a wet lab experiment in near future. Taken together, this in-silico study on the design of a vaccine construct to target W. bancrofti thioredoxin is predicted to be a future hope in saving human-being from the threat of filariasis.

Contributions to the lymphatic filariasis elimination programme and post-elimination surveillance in China by NIPD-CTDR.

China was once one of the most heavily endemic for lymphatic filariasis (LF), with a heavy disease burden. Due to decades of sustained efforts, LF was eliminated from China in 2007. The historical tales in the control and elimination of LF in China and current post-elimination surveillance are reviewed and concluded. In the course of LF control and elimination, National Technical Steering Group for Filariasis Control and Research, and Collaborating Research Group on the Transmission Threshold of Filariasis, led by the National Institute of Parasitic Diseases, carried out researches, developed control measures, and applied in practical control and surveillance. The main of the results include: in theoretical study, (1) formulating the microfilaria rate below 1% as the transmission threshold of filariasis, (2) developing anti-filarial drugs and establishing animal model for drug screening, (3) studying the vectorial capacity of mosquitoes transmitted filariasis; in clinical diagnostic and therapy, (1) developing antigens for serological diagnostics, (2) studying different administration regimes for alleviating the side-response of diethylcarbamazine (DEC), (3) studying on the recurrence of acute adenolymphangitis and lymphadenitis of malayan filariasis, (4) observing lymphoedema of the lower extremity using lymphangiography; in practical control and surveillance, (1) establishing the control strategy taking elimination of infection source as the major focus, (2) formulating safe, feasible and effective DEC-mass drug administration, (3) revealing the transmission pattern of filariasis at the post-control phase, (4) establishing comprehensive active surveillance system, (5) formulating the criteria of basic elimination and elimination of filariasis. In the post-elimination surveillance phase, special monitoring and investigation in key areas were conducted for clearing way potential residual infection sources. Two schemes on LF surveillance in the post-elimination phase and caring for chronic filariasis patients were issued to maintain the diagnosis and treatment skills of filariasis all levels of disease control and prevention workers in future. Also, the Notifiable Diseases Reporting System, which included LF in 2004, plays an important role in LF post-elimination surveillance to prevent LF resurgence in China. The strategies and measures of LF control, elimination and post-elimination surveillance in China provide valuable practical experience and promote the progress of Global Programme of Elimination of Lymphatic Filariasis in worldwide.

The Genetic Polymorphisms of 24 Base Pair Duplication and Point G102S of Human Chitotriosidase to Bancroftian Filariasis at the Thai⁻Myanmar Border.

Lymphatic filariasis, caused by lymphatic filarial parasites, Wuchereria bancrofti, and Brugia malayi, causes significant morbidity and disability to 120 million people in the tropics and subtropics. Chitin has an important role for embryogenesis in adult worms and is a component of microfilaria sheath. Human chitotriosidase (CHIT1) is a chitin-degrading enzyme which provides a protective role against chitin-containing pathogens. Here, we determined the association of CHIT1 polymorphisms with susceptibility to bancroftian filariasis (BF) in 88 individuals at the Thai⁻Myanmar border. Two common polymorphisms of CHIT1, contributing inactive CHIT protein, including 24 base pair (24 bp) duplication in exon 10, and p. G102S in exon 4 were genotyped by allele-specific Polymerase Chain Reaction (PCR) and PCR sequencing, respectively. Unexpectedly, genotype frequencies of 24 bp duplication insertion homozygous (INS/INS) were significantly higher in endemic normal (EN) (40.0%) than BF patients (31.4%). In contrast, genotype frequencies of p. G102S homozygous (A/A) in BF patients (21.6%) was higher than in EN (19.0%) without statistical difference. Mutant allele frequencies of 24 bp duplication were 0.6125 (98/160) and p. G102S were 0.392 (69/176). Genotype and allele frequencies of CHIT1, 24 bp duplication, and p. G102S, showed no association with BF patients.

Evaluation of sevafilachek immunoassays and rapid ICT-filariasis test for detection of bancroftian filariasis.

A comparative analysis was made on the utility of SEVAFILACHEK-stick based immunoassays and commercially available ICT-filariasis test to detect active infection in different groups of bancroftian filariasis. The SEVAFILACHEK immunoassays were found to be useful to detect filarial infection in microfilaraemia and in a significant number of clinical filarial cases with acute, chronic and occult clinical manifestations. In the clinical cases, microfilariae are not usually detected in peripheral circulation. Employing SEVAFILACHEK assays 6 and 5 of the 7 samples of patients with chronic filarial disease, and 6 and 5 of 6 microfilaraemic cases gave positivity for filarial IgG antibodies and antigen respectively. Four of the 6 occult filarial samples were positive for antibodies and antigen. Filarial antigen was detected by ICT-filariasis test in blood samples of all the 6 microfilariaemic cases, 1 chronic filarial and 2 occult filarial samples. The main advantage of ICT assay is its rapid format and convenience for field use.

Diethylcarbamazine and non-diethylcarbamazine related bancroftian granuloma: an immunohistochemical study of eosinophil toxic proteins.

It has been suggested, mostly using in vitro experiments, that defenses against parasites involve mainly activated eosinophils and their toxic proteins, such as major basic protein (MBP), eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO). Eosinophil degranulation has been described around degenerating onchocercal microfilariae in patients treated with diethylcarbamazine (DEC). In bancroftian filariasis, traditional histopathologic studies have shown remarkable numbers of eosinophils in granulomatous lesions associated with both DEC-induced and spontaneous death of adult Wuchereria bancrofti parasites. No immunohistochemical study targeting eosinophil degranulation has been previously performed in these granulomas, which are found mainly within intrascrotal lymphatic vessels. This investigation was undertaken in 22 (12 DEC-treated and 10 untreated) male patients in order to determine the immunohistochemical expressions of MBP, EPO and ECP in bancofitian granulomas, using the indirect method. Stained intact esosinophils, as well as granular, extra-cellular material positive for all three proteins, were found in all granulomas. The immunohistochemical patterns were similar in both DEC-treated and untreated cases, irrespective of microfilaremia, blood eosinophilia, and granuloma age. Positive intact cells were observed mostly at the periphery of the granulomas, whereas granular material predominated in central areas around dead or degenerating parasites. These results indicate that eosinophils accumulate in the granulomas and degranulate preferentially in close proximity to degenerating or dead adult parasites. In bancroftian granulomas, influx and degranulation of eosinophils are considered a consequence of parasite death, rather than its cause.

Survey of Bancroftian filariasis infection in humans and Culex mosquitoes in the western Brazilian Amazon region: implications for transmission and control

Introduction The aim of this work was to identify possible lymphatic filariasis foci in the western Brazilian Amazonian that could be established from the reports of Rachou in the 1950s. The study was conducted in three cities of the western Brazilian Amazon region - Porto Velho and Guajará-Mirim (State of Rondônia) and Humaitá (State of Amazonas). Methods For human infection evaluation thick blood smear stained with Giemsa was used to analyze samples collected from 10pm to 1am. Polymerase chain reaction (PCR) was used to examine mosquito vectors for the presence of Wuchereria bancrofti DNA. Humans were randomly sampled from night schools students and from inhabitants in neighborhoods lacking sanitation. Mosquitoes were collected from residences only. Results A total 2,709 night students enrolled in the Program for Education of Young Adults (EJA), and 935 people registered in the residences near the schools were examined, being 641 from Porto Velho, 214 from Guajará-Mirim and 80 from Humaitá. No individual examined was positive for the presence of microfilariae in the blood stream. A total of 7,860 female Culex quinquefasciatus specimens examined were negative by PCR. Conclusions This survey including human and mosquito examinations indicates that the western Amazon region of Brazil is not a focus of Bancroftian filariasis infection or transmission. Therefore, there is no need to be included in the Brazilian lymphatic filariasis control program. .

Mudanças de paradigmas na filariose bancroftiana / Paradigm shift in bancroftian filariasis

Ao longo do tempo, a maneira como se entende um determinado assunto passa por modificações através da pesquisa científica. Na maioria das vezes, essas mudanças causam pequenas diferenças na estrutura total do tópico em questão. Outras vezes, entretanto, ocorrem mudanças revolucionárias que não só alteram a compreensão do assunto em si, mas promovem a abertura de diferentes perspectivas que podem desencadear o início de novas etapas de interpretações e de novos caminhos de conhecimento. Exemplo disso foram os estudos de Gregor Johann Mendel que levaram à descoberta de leis da hereditariedade que, por sua vez, revolucionaram a biologia e traçaram as bases da genética. Em algumas situações, as mudanças não só modificam a forma de pensar, mas também têm implicações práticas ao melhorar a qualidade de vida de muitos seres humanos. No seu livro A Estrutura de Revoluções Científicas, Thomas Kuhn se refere às ruturas nessa evolução científica como "mudanças de paradigma", um termo que hoje é usado de uma forma genérica para descrever uma modificação profunda em nossos pontos de referência. O paradigma de que o estágio adulto da Wuchereria bancrofti causava a obstrução do vaso linfático e desencadeava uma reação imunológica inevitável em indivíduos predispostos, provocando a elefantíase, foi substituído pela esperança de que ser infectado não mais significa, necessariamente, ser um potencial portador da forma mais deformante da disfunção linfática. A infecção bacteriana secundária de repetição (semelhante clinicamente à erisipela) é hoje reconhecida como o fator mais importante para a instalação e a progressão do linfedema crônico, nos indivíduos que vivem em áreas endêmicas de filariose linfática. Evitar ou minimizar os episódios agudos bacterianos é um processo factível para a maioria dos habitantes das comunidades endêmicas, através do uso regular de água e sabão: a forma mais simples de higiene já conhecida pelo ser humano.

The way a particular subject is understood changes over time as a result of scientific research. In most cases, these changes are minor, with limited effect on the overall knowledge on the subject. Sometimes, however, revolutionary changes occur and not only modify the understanding of the subject but open perspectives that can trigger new interpretations and new ways for expansion of scientific knowledge. The studies of Gregor Johann Mendel were a good example. They led to discovery of the laws of inheritance which, in turn, have revolutionized biology and provided the foundation for genetics. In certain situations, changes not only alter ways of thinking, but have practical implications, also improving the quality of life for many people. In his book The Structure of Scientific Revolutions, Thomas Kuhn refers to discontinuities in scientific development as a "change of paradigm", a term now used in a generic manner to describe a profound changes in our reference points. For lymphatic filariasis the old paradigm stated that Wuchereria bancrofti at the adult stage causes lymphatic vessel obstruction, triggering an inevitable immune response in predisposed individuals and leading to elephantiasis. This has been replaced by a new paradigm, which offers hope that W. bancrofti infection does not necessarily predispose to the disfiguring outward manifestation of lymphatic dysfunction. Repeated secondary bacterial infections (erysipela-like) are now recognized as the most important factor for initiation and progression of chronic lymphedema in individuals living in filariasis-endemic areas. Most inhabitants of endemic communities can prevent and minimize the acute bacterial episodes by regular use of soap and water, the simplest form of hygiene already well known to human beings.

Aspectos da realidade social de crianças e adolescentes atendidos em serviço de referência para filariose bancroftiana, Recife, estado de Pernambuco / Aspects of the social realities of children and adolescents seen at a reference service for bancroftian filariasis in Recife, state of Pernambuco

Os autores abordam aspectos da realidade social de crianças e adolescentes residentes em Jaboatão dos Guararapes/PE, diagnosticados como portadores de infecção filarial bancroftiana e tratados no Núcleo de Ensino, Pesquisa e Assistência em Filariose da Universidade Federal de Pernambuco (Centro de Ciências da Saúde), um serviço terciário de referência para filariose. Quantificam e classificam as condições de moradia como subumanas, estando em relação direta com a manutenção da transmissão da bancroftose, e alertam para a necessidade de decisão política quanto à implementação de obras de saneamento básico.

The authors report on aspects of the social realities of children and adolescents living in Jaboatão dos Guararapes, State of Pernambuco, who were diagnosed with Bancroftian filariasis infection and were treated at the Filariasis Teaching, Research and Care Center of the Federal University of Pernambuco (Health Sciences Center), which is a tertiary-level reference service for filariasis. The patients’ housing conditions were quantified and classified as subhuman, with a direct relationship with the maintenance of Bancroftian filariasis transmission, and the authors highlight the need for political decisions regarding the implementation of basic sanitation projects.

A complexidade do custo socioeconômico da filariose linfática / The complexity of the socioeconomic costs of lymphatic filariasis

A falta de conhecimento do impacto socioeconômico das diversas doenças é, geralmente, um dos maiores obstáculos para a obtenção de verbas para investimentos em pesquisa aplicada, assim como para iniciar a implementação de programas de controle necessários aos países em desenvolvimento. Os autores analisam e ressaltam aspectos relevantes da complexidade de quantificação do impacto socioeconômico da filariose linfática e enfatizam as lacunas existentes em algumas áreas do conhecimento, que ainda não foram devidamente exploradas para os portadores da doença. Aos dados de literatura aliam os ecos do aprendizado adquirido através do atendimento de pacientes portadores de infecção e doença bancroftiana em serviço terciário de referência do Núcleo de Ensino Pesquisa e Assistência em Filariose (NEPAF), Recife, Brasil. O impacto social, no seu sentido mais abrangente, mostra indícios fortes de perdas na qualidade de vida dos pacientes, infelizmente ainda pouco documentadas e, até certo ponto, de muito difícil contabilização, pelo tão peculiar abandono social das comunidades endêmicas.

Lack of knowledge of the socioeconomic impact of various diseases is generally one of the biggest obstacles to obtaining funds for investment in applied research and for starting to implement control programs that are needed in developing countries. The authors analyze and emphasize important aspects of the complexity of quantifying the socioeconomic impact of lymphatic filariasis. They highlight the gaps that exist within some fields of knowledge and that these gaps have still not been properly explored with regard to individuals with this disease. They bring together the data in the literature and echoes from their own experience gained through caring for patients with Bancroftian infection and disease at a tertiary referral service (NEPAF - Filariasis Care, Research and Teaching Center, Recife, Brazil). The social impact, in its broadest sense, consists of strong indications of losses of quality of life among patients. Unfortunately, this is still poorly documented and, up to a certain point, very difficult to quantify because of the very particular social abandonment of the endemic communities.