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1.
J Helminthol ; 90(1): 39-47, 2016 Jan.
Article in English | MEDLINE | ID: mdl-25315797

ABSTRACT

Here we report findings to optimize and standardize conditions to attenuate metacercariae of Opisthorchis viverrini by ionizing radiation to elicit protective immune responses to challenge infection. Metacercariae were gamma-irradiated and the ability of irradiated metacercariae to prevent patent infection of challenge metacercariae in hamsters was determined, as well as their ability to induce a host antibody response. Metacercariae irradiated in a dose-dependent manner, with 3, 5, 10, 12, 20, 25 and 50 Gray, were used to infect Syrian golden hamsters by stomach gavage to ascertain the effect of irradiation on ability of the worms to establish infection. In addition, other hamsters were infected with metacercariae irradiated with 20-50 Gray, followed by challenge with intact/wild-type (non-irradiated) metacercariae to determine the protective effect as established by the numbers of adult flukes, eggs of O. viverrini in hamster faeces and anti-O. viverrini antibody titres. Significantly fewer worms were recovered from hamsters immunized with metacercariae irradiated at 20, 25 and 50 Gray than from control hamsters infected with intact metacercariae or 0 Gray, and the worms showed damaged reproductive organs. Faecal egg numbers were decreased significantly in hamsters immunized with 25 and 50 Gray metacercariae of O. viverrini. Moreover, hamsters administered metacercariae that were protected elicited a robust, specific anti-fluke immunoglobulin G response compared to control hamsters, suggesting a role for antibody in protection elicited by radiation-attenuated metacercariae.


Subject(s)
Metacercariae/radiation effects , Opisthorchiasis/parasitology , Opisthorchis/immunology , Animals , Antibodies, Helminth/immunology , Cricetinae , Feces/parasitology , Female , Gamma Rays , Humans , Immunization , Liver/parasitology , Male , Mesocricetus , Metacercariae/growth & development , Metacercariae/immunology , Metacercariae/physiology , Opisthorchiasis/microbiology , Opisthorchis/growth & development , Opisthorchis/physiology , Opisthorchis/radiation effects , Reproduction/radiation effects
2.
Parasite Immunol ; 36(8): 358-66, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25337625

ABSTRACT

Human hookworm infection is one amongst the most prevalent of the neglected tropical diseases. An informative experimental animal model, that is, one that parallels a human infection, is not available for the study of human hookworm infection. Much of our current understanding of the human immune response during hookworm infection relies on the studies from experimental infection of hookworm-naïve individuals or the natural infections from individuals residing in hookworm-endemic areas. The experimental human infections tend to be acute, dose-controlled infections, often with a low larval inoculum so that they are well tolerated by human volunteers. Natural hookworm infections usually occur in areas where hookworm transmission is constant and infection is chronic. In cases where there has been drug administration in an endemic area, re-infection often occurs quickly even amongst those who were treated. Hence, although many of the characteristics of experimental and natural hookworm infection differ, both models have elements in common: mainly an intense Th2 response with the production of total and specific IgE as well as elevated levels of eosinophilia, IL-5, IL-10 and TNF. While hookworm infection affects millions of individuals worldwide, much of the human immunology of this infection still needs to be studied and understood.


Subject(s)
Hookworm Infections/immunology , Ancylostomatoidea/immunology , Ancylostomatoidea/physiology , Animals , Cytokines/genetics , Cytokines/metabolism , Gene Expression Regulation/immunology , Humans
3.
Infect Immun ; 80(4): 1606-14, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22311924

ABSTRACT

Vaccines have been at the forefront of global research efforts to combat malaria, yet despite several vaccine candidates, this goal has yet to be realized. A potentially effective approach to disrupting the spread of malaria is the use of transmission-blocking vaccines (TBV), which prevent the development of malarial parasites within their mosquito vector, thereby abrogating the cascade of secondary infections in humans. Since malaria is transmitted to human hosts by the bite of an obligate insect vector, mosquito species in the genus Anopheles, targeting mosquito midgut antigens that serve as ligands for Plasmodium parasites represents a promising approach to breaking the transmission cycle. The midgut-specific anopheline alanyl aminopeptidase N (AnAPN1) is highly conserved across Anopheles vectors and is a putative ligand for Plasmodium ookinete invasion. We have developed a scalable, high-yield Escherichia coli expression and purification platform for the recombinant AnAPN1 TBV antigen and report on its marked vaccine potency and immunogenicity, its capacity for eliciting transmission-blocking antibodies, and its apparent lack of immunization-associated histopathologies in a small-animal model.


Subject(s)
Antibodies/immunology , CD13 Antigens/immunology , Insect Vectors/enzymology , Malaria Vaccines/immunology , Plasmodium vivax/immunology , Animals , Anopheles/enzymology , Anopheles/immunology , Anopheles/parasitology , Female , Humans , Insect Vectors/immunology , Insect Vectors/parasitology , Malaria/immunology , Malaria/prevention & control , Malaria/transmission , Mice , Mice, Inbred BALB C , Plasmodium berghei/immunology , Vaccines, Synthetic/immunology
4.
Clin Exp Dermatol ; 34(8): e709-11, 2009 Dec.
Article in English | MEDLINE | ID: mdl-20055840

ABSTRACT

Acute generalized exanthematous pustulosis (AGEP) is an uncommon disease, which presents as a nonfollicular erythematous sterile pustular eruption. More than 90% of the cases are induced by adverse drug reactions, often triggered by anti-infectious systemic drugs. We report a case of itraconazole-induced AGEP in a 22-year-old man, with an assessment of his cytokine/chemokine production and drug-specific cell reactivity. We found that AGEP, like other T cell-mediated drug eruptions, alters the immunological status of the patient, probably favouring T-cell activation, recruitment and regulation. Few cases of itraconazole-induced AGEP have been described in the literature, and to our knowledge, this is the first report in which the cellular immunological features are assessed.


Subject(s)
Acute Generalized Exanthematous Pustulosis/immunology , Antifungal Agents/adverse effects , Drug Eruptions/immunology , Itraconazole/adverse effects , Lymphocyte Activation/immunology , Acute Generalized Exanthematous Pustulosis/chemically induced , Humans , Male , T-Lymphocytes/physiology , Young Adult
5.
Parasite Immunol ; 29(7): 347-58, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17576364

ABSTRACT

We describe how hookworms interact with their human hosts by comparing lymphocyte phenotyping, proliferative responses, and cytokine and chemokine secretion patterns in adults who are either mono-infected with Necator americanus or egg-negative controls resident in an area of high transmission in Brazil. Cellular immune responses against crude hookworm antigen extracts from different developmental stages were evaluated simultaneously. Principal component analysis (PCA) was used to reduce the standardized immune responses. Random effects multivariate regression was then used to investigate whether principal components (PC) differ between the two groups once potential confounders and effect modifiers have been accounted for. Although hookworm patients had reduced percentages of T and B cells, they had higher levels of activated CD4(+) T and CD19(+) B cells. This state of 'immune activation' coincided with lower proliferative responses, especially to third-stage larval antigen. Cytokine levels in mono-infected adults were also lower and characterized by a mixed Th1/Th2-type profile. Excretory/secretory antigen from adult worms was a potent modulator of the immune response, resulting in diminished TNF-alpha and IL-10 secretion in peripheral blood mononuclear cells (PBMC) from hookworm infected patients. We propose that the longevity of hookworms in their human hosts results from a stage-specific, down-modulation of the immune response.


Subject(s)
Life Cycle Stages , Lymphocyte Activation/immunology , Lymphocyte Subsets/immunology , Necator americanus/growth & development , Necator americanus/immunology , Necatoriasis/immunology , Adolescent , Adult , Aged , Animals , Antigens, Helminth/immunology , Brazil , Cytokines/biosynthesis , Female , Host-Parasite Interactions , Humans , Male , Middle Aged , Necator americanus/pathogenicity , Necatoriasis/parasitology , Principal Component Analysis
6.
Ann Trop Med Parasitol ; 100(7): 551-70, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16989681

ABSTRACT

In the tropics, helminths are among the most common chronic infections of humans and Plasmodium infections the most deadly. As these two groups of parasites have similar geographical distributions, co-infection is commonplace. It has increasingly been speculated that helminth infections may alter susceptibility to clinical malaria, and there is now increasing interest in investigating the consequences of co-infection, with studies yielding contrasting results. The immunological interactions between helminths and malarial parasites are unclear, although several hypotheses have been proposed. This review provides an epidemiological overview of the possible interactions between helminths and malarial parasites, in relation to geographical distributions and disease patterns, and provides a critical discussion of the results of the epidemiological studies that have so far been conducted to investigate the possible associations. Future studies that might be considered, in order to address the gaps in knowledge, are also considered.


Subject(s)
Helminthiasis/epidemiology , Malaria/epidemiology , Africa South of the Sahara/epidemiology , Age Distribution , Antimalarials/therapeutic use , Child, Preschool , Climate , Comorbidity , Disease Susceptibility/epidemiology , Female , Helminthiasis/immunology , Humans , Incidence , Infant , Malaria/immunology , Malaria/prevention & control , Pregnancy , Prevalence , Research Design , Risk Factors , Socioeconomic Factors
7.
Parasitology ; 133 Suppl: S63-79, 2006.
Article in English | MEDLINE | ID: mdl-17274849

ABSTRACT

This paper summarises the progress towards vaccine development against the major blood-feeding nematodes of man and livestock, the hookworms and Haemonchus contortus, respectively. The impact of the diseases and the drivers for vaccine development are summarized as well as the anticipated impact of the host immune response on vaccine design. The performance requirements are discussed and progress towards these objectives using defined larval and adult antigens, many of these being shared between species. Specific examples include the Ancylostoma secreted proteins and homologues in Haemonchus as well as proteases used for digestion of the blood meal. This discussion shows that many of the major vaccine candidates are shared between these blood-feeding species, not only those from the blood-feeding stages but also those expressed by infective L3s in the early stages of infection. Challenges for the future include: exploiting the expanding genome information for antigen discovery, use of different recombinant protein expression systems, formulation with new adjuvants, and novel methods of field testing vaccine efficacy.


Subject(s)
Ancylostomatoidea/immunology , Haemonchiasis/prevention & control , Haemonchus/immunology , Hookworm Infections/prevention & control , Vaccination , Ancylostomatoidea/enzymology , Animals , Antigens, Helminth/immunology , Global Health , Haemonchiasis/veterinary , Haemonchus/enzymology , Hookworm Infections/veterinary , Humans , Peptide Hydrolases/metabolism
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