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Biomedical subjects

Paul Hagan

Publications and source records attributed to Paul Hagan.

10 recordsLinked to original sources

Role of the employment status and education of mothers in the prevalence of intestinal parasitic infections in Mexican rural schoolchildren.

BACKGROUND: Intestinal parasitic infections are a public health problem in developing countries such as Mexico. As a result, two governmental programmes have been implemented: a) "National Deworming Campaign" and b) "Opportunities" aimed at maternal care. However, both programmes are developed separately and their impact is still unknown. We independently investigated whether a variety of socio-economic factors, including maternal education and employment levels, were associated with intestinal parasite infection in rural school children. METHODS: This cross-sectional study was conducted in 12 rural communities in two Mexican states. The study sites and populations were selected on the basis of the following traits: a) presence of activities by the national administration of albendazole, b) high rates of intestinal parasitism, c) little access to medical examination, and d) a population having less than 2,500 inhabitants. A total of 507 schoolchildren (mean age 8.2 years) were recruited and 1,521 stool samples collected (3 per child). Socio-economic information was obtained by an oral questionnaire. Regression modelling was used to determine the association of socio-economic indicators and intestinal parasitism. RESULTS: More than half of the schoolchildren showed poliparasitism (52%) and protozoan infections (65%). The prevalence of helminth infections was higher in children from Oaxaca (53%) than in those from Sinaloa (33%) (p < 0.0001). Giardia duodenalis and Hymenolepis nana showed a high prevalence in both states. Ascaris lumbricoides, Trichuris trichiura and Entamoeba hystolitica/dispar showed low prevalence. Children from lower-income families and with unemployed and less educated mothers showed higher risk of intestinal parasitism (odds ratio (OR) 6.0, 95% confidence interval (CI) 1.6-22.6; OR 4.5, 95% CI 2.5-8.2; OR 3.3, 95% CI 1.5-7.4 respectively). Defecation in open areas was also a high risk factor for infection (OR 2.4, 95% CI 2.0-3.0). CONCLUSION: Intestinal parasitism remains an important public health problem in Sinaloa (north-western Mexico) and Oaxaca (south-eastern Mexico). Lower income, defecation in open areas, employment status and a lower education level of mothers were the significant factors related to these infections. We conclude that mothers should be involved in health initiatives to control intestinal parasitism in Mexico.

Analysis of Variance↗

Schistosomiasis control: keep taking the tablets.

Despite the limited reports of praziquantel resistance, the relative success of chemotherapy-based control programmes for schistosomiasis has prompted overdue efforts to expand the use of cheap, generic, praziquantel in sub-Saharan Africa. The likely impact of such programmes on the development and spread of praziquantel resistance is uncertain, but this possibility reinforces the need for monitoring the spectrum of praziquantel sensitivity of schistosome populations and for an improved knowledge of the precise targets for the action of the drug. The search for alternatives to praziquantel and other tools for control of schistosomiasis must continue.

Administration, Oral↗

Leishmania mexicana and Leishmania major: attenuation of wild-type parasites and vaccination with the attenuated lines.

A method for attenuation of Leishmania species by culturing in vitro under gentamicin pressure has been used successfully with Leishmania mexicana, L. major, L. infantum, and L. donovani. The attenuated lines invaded but were unable to survive within bone marrow-derived macrophages in vitro, whereas wild-type parasites survived and multiplied. The attenuated lines of L. mexicana and L. major both failed to induce cutaneous lesions in the majority of BALB/c mice over a minimum 12-week observation period after subcutaneous injection of stationary phase parasites. The attenuated line of L. mexicana retained its properties in gentamicin-free medium over 40 subcultures. The attenuated lines of L. mexicana and L. major both induced significant protection in mice against challenge with wild-type parasites.

Animals↗

Chemotherapy-induced, age-related changes in antischistosome antibody responses.

Humoral responses directed against Schistosoma mansoni soluble egg antigen were studied in Zimbabwean children before and after treatment with either praziquantel (PZQ) or oxamniquine (OXAM). Treated children showed a significant increase in the proportion producing IgE and IgG3 and in mean levels of IgE, IgM, IgG3 six weeks post-treatment. At 18 weeks post-treatment, the proportion of treated children producing IgA, IgE, and IgG3 increased while the proportion producing IgG1 and IgG4 decreased. Mean levels of IgA, IgE, and IgG3 were higher than pre-treatment levels while levels of IgG1, IgG4 and IgM were lower. Statistical analyses showed that the magnitude of change in levels of IgE, IgM and IgG3 at 6 weeks post-treatment and of IgE, IgG3 and IgG4 at 18 weeks post-treatment was significantly greater in treated compared to untreated children, and there were no significant differences in immune responses between children treated with praziquantel and those treated with oxamniquine. The magnitude of change in IgE at 6 and 18 weeks, IgM at 6 weeks and IgG3 at 18 weeks post-treatment were significantly associated with age in treated but not in untreated children, with the change being greater in younger children. This suggests that treatment induced a change in the age-antibody relationship for these isotypes, and that the age-antibody relationship is not robust to chemotherapy. Pre-treatment infection levels were significantly associated (positive correlation) with the magnitude of change for IgE and IgG3 at 18 weeks post-treatment. Taken together, these results indicate that the age-antibody relationship observed in these children is due, at least in part, to cumulative host experience of parasite antigens and not host age alone.

Adolescent↗

Schistosomiasis vaccines.

While there are many challenges in vaccine development, none is greater than that of developing vaccines against large metazoan parasites such as schistosomes, the parasitic worms that are responsible for schistosomiasis. Initial optimism stemming from the identification of the first vaccine candidate antigens that gave protection in animals has been dashed by the failure, as yet, of any of the vaccine candidate antigens to enter Phase III clinical trials. Now, despite an improved understanding of the biology of the parasites and of the immune responses they stimulate in naturally exposed populations, the vaccine effort is stalled. The control effort has switched heavily in favour of the wider use of conventional chemotherapy with praziquantel, which is now affordable by all but the poorest countries. Disagreements among researchers in the schistosome field as to whether or not a vaccine is needed have not helped convince funding agencies that schistosomiasis vaccines, rather than drugs, should be a priority. With the schistosome genome projects at an advanced stage plus the power of the proteomics, perhaps it is still too early to call time on schistosome vaccine development.

Animals↗

A novel and sensitive method to monitor helminth infections by faecal sampling.

The Kato-Katz technique is the method routinely used for diagnosing human schistosomiasis mansoni by estimating faecal egg burdens. To improve the sensitivity of faecal diagnosis, we established and validated a novel separation technique based upon the greater density of viable schistosome eggs relative to faecal material. Subsequently, it was used for faecal examination of 27 schistosomiasis patients in El-Sharkia, Egypt, with Kato-Katz smears as criterion standard. Low intensity infections (<100 eggs/g) were only detected by our technique. Moreover, triple Kato-Katz analysis on consecutive samples still missed 7.4% of all human patients, whereas the new method diagnosed 100% of samples correctly on second analysis. We conclude that in endemic areas many patients are being systematically missed by routine diagnosis. Moreover, the sensitivity of our method allows its use in proposed pre-clinical and clinical vaccine trials in non-human primates and humans, where reliable estimates of faecal egg counts are essential.

Animals↗

The importance of models of infection in the study of disease resistance.

Models currently occupy the crucial first step in the research flow for the development of new drugs and vaccines. Some animal models are better at reflecting the host-pathogen interaction in humans than others; this depends on the pathogen and its host specificity. Data gathered from what are often poorly adapted models provide a mosaic of sometimes contradictory information, yet there is little incentive to better delineate the relevance of models or to exploit recent advances to develop improved ones. This review reports on three particularly intractable human pathogens - Mycobacterium, Plasmodium and Schistosoma - and reflects that the extent to which these model systems mimic infection and protection processes in humans might not be sufficiently well defined.

Animals↗

P38 mitogen-activated protein kinase influence on the production of IL-10 in human schistosomiasis mansoni.

Schistosomiasis mansoni remains a significant public health problem in many parts of the tropics and subtropics. Clinical manifestations range from the asymptomatic intestinal form through to the hepatosplenic form of the disease, a potentially lethal clinical condition in a subsection of the exposed population. In this study, we investigated the mechanisms by which interleukin (IL)-10 production could be differentially controlled in patients with the intestinal and hepatosplenic forms of the disease, as IL-10 may play a fundamental role in the development of the hepatosplenic disease state. It is reported that p38 mitogen-activated protein (MAP) kinase signalling, and in particular p38 MAPK activation, is central to IL-10 production of cells from patients with schistosomiasis. Furthermore, the difference in the levels of activated p38 MAPK and the activation transcription factor (ATF-2), may explain the difference in the amount of IL-10 produced by cells from intestinal and hepatosplenic patients. We suggest that the type of immune response triggered in patients with hepatosplenomegaly could be influenced by the levels of phosphorylated p38 MAPK.

Adult↗

Leishmania mexicana H-line attenuated under pressure of gentamicin, potentiates a Th1 response and control of cutaneous leishmaniasis in BALB/c mice.

An attenuated line of Leishmania mexicana (the L. mexicana H-line) has been established by culturing in vitro under gentamicin pressure. BALB/c mice infected with the L. mexicana H-line developed a CD4(+)Th1-like response, indicated by the cytokine profile of their splenocytes stimulated by L. mexicana wild-type (WT) promastigotes. This profile is sustained after these mice are challenged with L. mexicana WT. Control mice infected with L. mexicana WT alone developed a CD4(+)Th2-like cytokine profile. In mice immunized with L. mexicana H-line and then challenged with WT-line, were eliminated when immunizing H-line parasites persisted in the skin and draining popliteal lymph nodes (PLNs). In experiments in which mice were inoculated with attenuated and WT parasites at the same time, either at the same site or on separate sides of the mouse, growth of the WT parasites was significantly contained and controlled, indicating a possible therapeutic role for the attenuated parasites.

Animals↗