22 research outputs found
The Colposcopic Atlas of Schistosomiasis in the Lower Female Genital Tract Based on Studies in Malawi, Zimbabwe, Madagascar and South Africa
Background Schistosoma (S.) haematobium is a neglected tropical disease which may affect any part of the genital tract in women. Female genital schistosomiasis (FGS) may cause abnormal vaginal discharge, contact bleeding, genital tumours, ectopic pregnancies and increased susceptibility to HIV. Symptoms may mimic those typical of sexually transmitted infections (STIs) and women with genital schistosomiasis may be incorrectly diagnosed. An expert consensus meeting suggested that the following findings by visual inspection should serve as proxy indicators for the diagnosis of schistosomiasis of the lower genital tract in women from S. haematobium endemic areas: sandy patches appearing as (1) single or clustered grains or (2) sandy patches appearing as homogenous, yellow areas, or (3) rubbery papules. In this atlas we aim to provide an overview of the genital mucosal manifestations of schistosomiasis in women. Methodology/Principal findings Photocolposcopic images were captured from women, between 1994 and 2012 in four different study sites endemic for S. haematobium in Malawi, Zimbabwe, South Africa and Madagascar. Images and specimens were sampled from sexually active women between 15 and 49 years of age. Colposcopic images of other diseases are included for differential diagnostic purposes. Significance This is the first atlas to present the clinical manifestations of schistosomiasis in the lower female genital tract. It will be freely available for online use, downloadable as a presentation and for print. It could be used for training purposes, further research, and in clinical practice
Downregulation of MIP-1α/CCL3 with praziquantel treatment in Schistosoma haematobium and HIV-1 co-infected individuals in a rural community in Zimbabwe
The results of our study show that the MIP-1alpha/CCL3 levels were positively associated with S. haematobium egg counts at baseline but not with HIV-1 infection status. MIP-1alpha/CCL3 levels were significantly reduced at three months post treatment with praziquantel. We therefore conclude that MIP-1alpha/CCL3 is produced during infection with S haematobium. S. haematobium infection is associated with increased MIP-1alpha/CCL3 levels in an egg intensity-dependent manner and treatment of S. haematobium is associated with a reduction in MIP-1alpha/CCL3
Genetic Manipulation of Schistosoma haematobium, the Neglected Schistosome
More people are infected with Schistosoma haematobium than other major human schistosomes yet it has been less studied because of difficulty in maintaining the life cycle in the laboratory. S. haematobium might be considered the ‘neglected schistosome’ since minimal information on the genome and proteome of S. haematobium is available, in marked contrast to the other major schistosomes. In this report we describe tools and protocols to investigate the genome and genetics of this neglected schistosome. We cultured developmental stages of S. haematobium, and investigated the utility of introducing gene probes into the parasites to silence two model genes. One of these, firefly luciferase, was a reporter gene whereas the second was a schistosome gene encoding a surface protein, termed Sh-tsp-2. We observed that both genes could be silenced – a phenomenon known as experimental RNA interference (RNAi). These findings indicated that the genome of S. haematobium will be amenable to genetic manipulation investigations designed to determine the function and importance of genes of this schistosome and to investigate for novel anti-parasite treatments
Restricted Genetic Diversity of HIV-1 Subtype C Envelope Glycoprotein from Perinatally Infected Zambian Infants
Background: Mother-to-child transmission of HIV-1 remains a significant problem in the resource-constrained settings where anti-retroviral therapy is still not widely available. Understanding the earliest events during HIV-1 transmission and characterizing the newly transmitted or founder virus is central to intervention efforts. In this study, we analyzed the viral env quasispecies of six mother-infant transmission pairs (MIPs) and characterized the genetic features of envelope glycoprotein that could influence HIV-1 subtype C perinatal transmission.
Methodology and Findings: The V1-V5 region of env was amplified from 6 MIPs baseline samples and 334 DNA sequences in total were analyzed. A comparison of the viral population derived from the mother and infant revealed a severe genetic bottleneck occurring during perinatal transmission, which was characterized by low sequence diversity in the infant. Phylogenetic analysis indicates that most likely in all our infant subjects a single founder virus was responsible for establishing infection. Furthermore, the newly transmitted viruses from the infant had significantly fewer potential N-linked glycosylation sites in Env V1-V5 region and showed a propensity to encode shorter variable loops compared to the nontransmitted viruses. In addition, a similar intensity of selection was seen between mothers and infants with a higher rate of synonymous (dS) compared to nonsynonymous (dN) substitutions evident (dN/dS\u3c1).
Conclusions: Our results indicate that a strong genetic bottleneck occurs during perinatal transmission of HIV-1 subtype C. This is evident through population diversity and phylogenetic patterns where a single viral variant appears to be responsible for infection in the infants. As a result the newly transmitted viruses are less diverse and harbored significantly less glycosylated envelope. This suggests that viruses with the restricted glycosylation in envelope glycoprotein appeared to be preferentially transmitted during HIV-1 subtype C perinatal transmission. In addition, our findings also indicated that purifying selection appears to predominate in shaping the early intrahost evolution of HIV-1 subtype C envelope sequences
GM-CSF Increases Mucosal and Systemic Immunogenicity of an H1N1 Influenza DNA Vaccine Administered into the Epidermis of Non-Human Primates
Background: The recent H5N1 avian and H1N1 swine-origin influenza virus outbreaks reaffirm that the threat of a worldwide influenza pandemic is both real and ever-present. Vaccination is still considered the best strategy for protection against influenza virus infection but a significant challenge is to identify new vaccine approaches that offer accelerated production, broader protection against drifted and shifted strains, and the capacity to elicit anti-viral immune responses in the respiratory tract at the site of viral entry. As a safe alternative to live attenuated vaccines, the mucosal and systemic immunogenicity of an H1N1 influenza (A/New Caledonia/20/99) HA DNA vaccine administered by particle-mediated epidermal delivery (PMED or gene gun) was analyzed in rhesus macaques. Methodology/Principal Findings: Macaques were immunized at weeks 0, 8, and 16 using a disposable single-shot particlemediated delivery device designed for clinical use that delivers plasmid DNA directly into cells of the epidermis. Significant levels of hemagglutination inhibiting (HI) antibodies and cytokine-secreting HA-specific T cells were observed in the periphery of macaques following 1-3 doses of the PMED HA DNA vaccine. In addition, HA DNA vaccination induced detectable levels of HA-specific mucosal antibodies and T cells in the lung and gut-associated lymphoid tissues of vaccinated macaques. Importantly, co-delivery of a DNA encoding the rhesus macaque GM-CSF gene was found to significantly enhance both the systemic and mucosal immunogenicity of the HA DNA vaccine. Conclusions/Significance: These results provide strong support for the development of a particle-mediated epidermal DNA vaccine for protection against respiratory pathogens such as influenza and demonstrate, for the first time, the ability of skindelivered GM-CSF to serve as an effective mucosal adjuvant for vaccine induction of immune responses in the gut and respiratory tract. © 2010 Loudon et al
Putting the treatment of paediatric schistosomiasis into context
Abstract Despite increased international efforts to control schistosomiasis using preventive chemotherapy, several challenges still exist in reaching the target populations. Until recently, preschool-aged children had been excluded from the recommended target population for mass drug administration, i.e. primary school children aged 6–15 years. Our studies and those of others provided the evidence base for the need to treat preschool-aged children that led to recommendations by the World Health Organization to include preschool-aged children in treatment programmes in 2010. The major challenge now lies in the unavailability of a child-size formulation of the appropriate anthelmintic drug, praziquantel. The currently available formulation of praziquantel presents several problems. First, it is a large tablet, making it difficult for young children and infants to swallow it and thus requires its breaking/crushing to allow for safe uptake. Second, it is bitter so it is often mixed with a sweetener to make it palatable for young children. Third, the current formulation of 600 mg does not allow for flexible dose adjustments for this age group. Thus, there is a need to formulate a child-appropriate praziquantel tablet. This paper discusses the target product profile for paediatric praziquantel, as well as knowledge gaps pertinent to the successful control of schistosome infection and disease in preschool-aged children
The impact of repeated treatment with praziquantel of schistosomiasis in children under six years of age living in an endemic area for Schistosoma haematobium infection
Praziquantel was given every eight weeks for two years to children aged under six years of age, living in a Schistosoma haematobium endemic area. Infection with S. haematobium and haematuria were examined in urine and antibody profiles (IgA, IgE, IgM, IgG1, IgG2, IgG3, and IgG4) against S. haematobium adult worm and egg antigens were determined from sera collected before each treatment. Chemotherapy reduced infection prevalence and mean intensity from 51.8% and 110 eggs per 10 ml urine, respectively, before starting re-treatment programme to very low levels thereafter. Praziquantel is not accumulated after periodic administration in children. Immunoglobulin levels change during the course of treatment with a shift towards 'protective' mechanisms. The significant changes noted in some individuals were the drop in 'blocking' IgG2 and IgG4 whereas the 'protecting' IgA and IgG1 levels increased. The antibody profiles in the rest of the children remained generally unchanged throughout the study and no haematuria was observed after the second treatment. The removal of worms before production of large number of eggs, prevented the children from developing morbidity