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Biomedical subjects

E Michael

Publications and source records attributed to E Michael.

At least 19 recordsLinked to original sources

A review of the present status of lymphatic filariasis in Vietnam.

Establishing the current status of an infectious disease forms the starting point of any attempt at parasite control. Although data on the prevalence and distribution of lymphatic filariasis exist for Vietnam from the early 1900s, the present situation regarding the disease is less well-known. Here, we review the results of recent surveys conducted by the Institute of Malariology, Parasitology and Entomology, Hanoi, to update the existing information on filariasis epidemiology and distribution for this country. The present results are from surveys carried out on some 135,000 individuals in 24 provinces of Vietnam. The highest prevalences of microfilaraemia (primarily Brugia malayi ) are observed in lowland areas of the Red River Delta and in Quang-binh Province where the survey results show microfilaraemia (mf) prevalences in the range of 0.9-5.5%. The most common type of chronic clinical manifestation is shown to be leg elephantiasis. A significant finding is that an overall decrease in mf prevalence was observed to occur in five communities which were surveyed twice over an 11-21-year period, even though no interventions were carried out between the two surveys. The changes are probably caused by environmental changes, such as increased standards of housing and drainage. Studies on the effect of selective chemotherapy and mass chemotherapy using diethylcarbamazine showed reductions in community mf prevalences of 69 and 72-88%, respectively. Furthermore, cats do not appear to represent significant reservoirs of infection. These findings of geographical restriction of infection, effective and well-tolerated drug therapy, low significance of animal reservoirs, together with the existence of an effective national health network, suggest a good prognosis for the control of filariasis in this country.

Animals

Herd immunity to filarial infection is a function of vector biting rate.

Despite the existence of an impressive body of work on human immune responses against filarial infections, the occurrence of a protective response to infection remains unclear. Here, we use a combined modelling and comparative data analysis framework to address this issue for human infections with the filarial parasite, Wuchereria bancrofti. By analogy with previous work, the analysis involves the comparison of observed field patterns of infection with epidemiological patterns predicted by a mathematical model of parasite immunity. Unlike most other human helminths, which are transmitted by ingestion or dermal penetration, exposure to infection with lymphatic filariasis can be measured explicitly in terms of vector mosquito biting rates, thereby also allowing, probably for the first time, examination of the suggested role of exposure in generating herd immunity to macroparasites. Observed field patterns in this study were derived from 19 different published studies, which gave parallel estimates of community exposure rates and the corresponding age--prevalence patterns of infection, while predictions of the epidemiological impact of herd immunity were obtained using a catalytic model framework. The results provide the first conclusive evidence to date that variations in the observed age--prevalence patterns of infection in filariasis can be effectively explained by the occurrence of an exposure-driven acquisition of herd immunity. We discuss this result in terms of implications for the new World Health Organization-led initiative for the global control of this parasitic disease.

Animals

Modelling variability in lymphatic filariasis: macrofilarial dynamics in the Brugia pahangi--cat model.

A striking feature of lymphatic filariasis is the considerable heterogeneity in infection burden observed between hosts, which greatly complicates the analysis of the population dynamics of the disease. Here, we describe the first application of the moment closure equation approach to model the sources and the impact of this heterogeneity for macrofilarial population dynamics. The analysis is based on the closest laboratory equivalent of the life cycle and immunology of infection in humans--cats chronically infected with the filarial nematode Brugia pahangi. Two sets of long-term experiments are analysed: hosts given either single primary infections or given repeat infections. We begin by quantifying changes in the mean and aggregation of adult parasites (inversely measured by the negative binomial parameter, kappa in cohorts of hosts using generalized linear models. We then apply simple stochastic models to interpret observed patterns. The models and empirical data indicate that parasite aggregation tracks the decline in the mean burden with host age in primary infections. Conversely, in repeat infections, aggregation increases as the worm burden declines with experience of infection. The results show that the primary infection variability is consistent with heterogeneities in parasite survival between hosts. By contrast, the models indicate that the reduction in parasite variability with time in repeat infections is most likely due to the 'filtering' effect of a strong, acquired immune response, which gradually acts to remove the initial variability generated by heterogeneities in larval mortality. We discuss this result in terms of the homogenizing effect of host immunity-driven density-dependence on macrofilarial burden in older hosts.

Animals

Epidemiology of soil-transmitted nematode infections in Ha Nam Province, Vietnam.

Baseline epidemiological data are presented from a parasitological survey conducted in Thuy Loi commune, Ha Nam province, Vietnam; a farming community where night soil is routinely used as fertilizer for crops. 177 households were visited and 543 individuals (aged 1-88 years) recruited to the study. Helminth infection intensity was assessed by Kato-Katz to determine the density of parasite eggs per gram of stool (epg). Ascaris lumbricoides, Trichuris trichiura and hookworm infections were the only species detected. 83% of individuals were infected with A. lumbricoides (mean epg = 11,971), 94% with T. trichiura (mean epg = 793) and 59% with hookworm (mean epg = 302). Age-dependent patterns of infection prevalence and intensity were similar for A. lumbricoides and T. trichiura, but markedly different for hookworm infection. Similarly, age-dependency in the k-values for the three infections was due to covariance with the respective mean intensities with age rather than to independent age effects, with similar patterns for A. lumbricoides and T. trichiura, and a different pattern for hookworm. Three major conclusions can be drawn from the multiple-species analyses: There is positive interaction between A. lumbricoides and T. trichiura infections; high-intensity A. lumbricoides infections are significantly associated with high-intensity T. trichiura infections; and there is positive interaction between these two species such that infection intensity of A. lumbricoides is higher in individuals with concurrent T. trichiura infection than in individuals without and vice versa.

Adolescent

Epifil: a dynamic model of infection and disease in lymphatic filariasis.

The lack of a quantitative framework that describes the dynamic relationships between infection and morbidity has constrained efforts aimed at the community-level control of lymphatic filariasis. In this paper, we describe the development and validation of EPIFIL, a dynamic model of filariasis infection intensity and chronic disease. Infection dynamics are modeled using the well established immigration-death formulation, incorporating the acquisition of immunity to infective larvae over time. The dynamics of disease (lymphodema and hydrocele) are modeled as a catalytic function of a variety of factors, including worm load and the impact of immunopathological responses. The model was parameterized using age-stratified data collected from a Bancroftian filariasis endemic area in Pondicherry in southern India. The fitted parameters suggest that a relatively simple model including only acquired immunity to infection and irreversible progression to disease can satisfactorily explain the observed infection and disease patterns. Disease progression is assumed to be a consequence of worm induced damage and to occur at a high rate for hydrocele and a low rate for lymphodema. This suggests that immunopathology involvement may not be a necessary component of observed age-disease profiles. These findings support a central role for worm burden in the initiation and progression of chronic filarial disease.

Adolescent

Re-assessing the global prevalence and distribution of lymphatic filariasis.

This paper estimates the global burden of lymphatic filariasis based on a review of the published literature on infection and disease surveys. A method for aggregating and projecting prevalence data from individual studies to national, regional and global levels, which also facilitates the estimation of gender and age-specific burdens, is presented. The method weights in favour of the larger, and hence presumbably more reliable, studies and relies on estimated empirical relationships between gender, age, infection and disease in order to correct studies with incomplete data. The results presented here suggest that although the overall prevalence of filariasis cases is 2.0% globally (approximately totalling 119 million cases), the disease continues to be of considerable local importance, particularly in India and Sub-Saharan Africa. Estimates by age and gender clearly show that, unlike other helminth infections, filariasis is mainly a disease of the adult and older age-classes and appears to be more prevalent in males. This work suggests that the derivation of more accurate estimates of the burden of filariasis will require a better understanding of both the epidemiology and the spatial aspects of infection and disease. It also suggests that filariasis is preventable based on a geographically targeted strategy for control.

Age Factors

Past exposure and the dynamics of lymphatic filariasis infection in young children.

This study utilizes parallel, longitudinal entomological and parasitological data collected during a 5-year vector control programme in Pondicherry, South India, to quantify Wuchereria bancrofti transmission from the vector to the human population. A simple mathematical model, derived from the standard catalytic model, is used to examine the hypothesis that current infection prevalence in young children is a dynamical function of their cumulative past exposure to infective bites. Maximum likelihood fits of the model to the observed data indicate a constant child infection rate with age, above a threshold representing the pre-patent period, or equivalently, the cumulative biting intensity required to produce patent infections. Extrapolation of the model allows the crude estimation of the equilibrium microfilaria age-prevalence curve due to control. The results suggest that vector control alone may have little impact on the overall age-prevalence of infection even when sustained for long periods. These observations are discussed in terms of the likely impact of density dependent mechanisms, such as acquired immunity, on model predictions.

Age Factors

Cost and cost effectiveness of mass diethylcarbamazine chemotherapy for the control of bancroftian filariasis: comparison of four strategies in Tanzania.

This study examines the costs and cost effectiveness of four different mass diethylcarbamazine (DEC) chemotherapy regimens-standard dose, semi-annual single dose, low monthly dose and DEC-medicated salt-in reducing microfilarial (mf) prevalence at the community level. Costs were estimated for each intervention in relation to both ingredient and activity, by the derivation and use of detailed itemized cost menus. The most expensive and most effective strategy in reducing community mf prevalence over 2 years was DEC salt intervention, followed in order of costs by the standard, low monthly and semi-annual DEC strategies. The most cost effective strategy was the low monthly DEC treatment. Cost and sensitivity analyses, however, suggest that the optimal choice of mass DEC strategy for reducing mf is very sensitive to programme design parameters. In particular, the results demonstrate that if the salt delivery structure is simplified, DEC salt has the potential to be the dominant intervention for filariasis control. The results suggest that economies of scale considerations might militate against the adoption of this intervention for large-scale applications, unless perhaps offset by its potential for cost recovery by direct patient purchase. Further analyses require a more realistic evaluation of filariasis intervention effectiveness by addressing changes in infection intensity and by accounting for the population dynamics of parasite transmission and control.

Adolescent

Congenital toxoplasmosis transmitted from an immunologically competent mother infected before conception.

Congenital transmission of Toxoplasma gondii from a mother who was apparently immunologically competent and who had toxoplasmic lymphadenitis 2 months before conception is described. Since no T. gondii-specific serological data were available for this mother from the time her lymph node biopsy specimen was obtained, the specimen was studied by polymerase chain reaction (PCR) to determine whether the T. gondii B1 gene was present. The predictive diagnostic value of histologic findings previously considered to be classic signs of T. gondii lymphadenitis also was studied. This was done by correlation of serological tests diagnostic of acute acquired T. gondii infection and presence of characteristic findings in biopsy specimens from persons without known immunocompromise. Both PCR and review of the characteristic features of her lymph node biopsy specimen confirmed the diagnosis of preconceptual infection in the mother. We also discuss two other cases in which apparently immunologically competent mothers with preconceptually acquired infection transmitted this parasite to their fetuses.

Animals

Frequency distribution of Wuchereria bancrofti infection in the vector host in relation to human host: evidence for density dependence.

This paper uses detailed entomological data from Pondicherry to compare the microfilaria distribution in vector with that of human and also to examine the evidence for the operation of density dependence on parasite transmission. Analysis showed that the distribution in vector is similar to that in human. The expected distribution derived from the fit of a zero-truncated negative binomial to the human data, closely reflected the observed microfilaria distribution in the vector. This implies that a relatively large proportion of observed microfilaria negatives in the vector population may be true zeros, as observed in human, arising from the biting on true negatives (as yet uninfected, with unmated female worms or immune) in humans, rather than attributable to the blood sampling process. Further it was found that both the prevalence of infection and the degree of parasite aggregation in the vector population falls significantly with parasite stage, implying the operation of density dependence, perhaps via parasite-induced vector mortality.

Animals

Prevalence of antibodies to hepatitis C virus and other markers in Jamaica.

Three population groups, 1500 blood donors, 513 antenatal women representing a normal population group and 250 sicklers representing a multiply transfused group were studied to determine the prevalence of hepatitis C viral (HCV) infection in Jamaica. The relationship to liver enzyme levels, hepatitis B infection, syphilis and HIV infection was also investigated. Sera were screened by enzyme-linked immunoassay (EIA) for anti-HCV C100-3 and subsequently tested by a supplementary second generation recombinant immunoblot assay (RIBA). In the blood donors, the prevalence of anti-HCV was low, 0.3%-0.4%, the same level as that reported by several European countries. In the multiply transfused sicklers, the prevalence was more than seven times higher. No HCV infection was detected in the antenatal group. There was little correlation between HCV infection and surrogate markers alanine aminotransferase (ALT) and antibody to hepatitis B core antigen (anti-HBc) and no correlation with sexually transmitted diseases.

Adult

The association between microfilaraemia and disease in lymphatic filariasis.

A standard tenet in the epidemiology of lymphatic filariasis is that patent infection is negatively related to chronic disease. We examine the empirical evidence for this relation by using published data from field studies carried out in a variety of bancroftian filariasis endemic areas. Meta-analysis of the individual study results for each disease category of hydrocele in males only, lymphoedema only, and both conditions combined (total chronic disease) indicate, contrary to expectation, no evidence for a negative association between infection and disease. Indeed, the trend of the empirical evidence is towards the opposite direction, with the majority of studies showing equal propensity of disease in microfilaraemics (mf+ves) and amicrofilaraemics (mf-ves), and more studies indicating a positive rather than a negative relation. There was also a trend for more positive studies for hydrocele compared to lymphoedema. Theoretical analysis suggests that between-study differences in blood sample volumes are unlikely to confound this finding. Analysis of between-study heterogeneity suggests that variations in the local incidence or prevalence of infection rather than unique geographical, including vector, differences might underlie the observed between-study variability in the microfilaraemia-disease association. These results are discussed in terms of dynamic explanations for infection-disease relations in lymphatic filariasis.

Animals

Protein content of CBA/Ca mouse diet: relationship with host antibody responses and the population dynamics of Trichuris muris (Nematoda) in repeated infection.

The influence of host dietary protein on acquired immunity and intestinal helminth population dynamics during repeated infection was studied using the mouse-Trichuris muris experimental model. CBA/Ca mice fed a 2% (by mass) protein diet ad libitum maintained body weight during the experiment, but when fed diets containing either 4% or 16% (by mass) protein gained weight steadily. Infection with T. muris did not affect the growth of the latter mice but significantly reduced the growth of animals fed on the 2% protein diet. When repeatedly infected with either 5 or 50 eggs every 10 days, the mice fed the 2% or 4% protein diet accumulated adults in proportion to infection dose. The results show that this is due to both the establishment of larvae at each repeated infection and the survival of established adults. In contrast, very few worms were recovered from animals fed the 16% protein diet, principally as a result of the development of strong acquired immunity to reinfection. T. muris egg output/mouse increased with infection dose in animals fed the low protein diets, but no parasite eggs were detected in the faeces of hosts fed the 16% protein diet. Mouse antibody responses to adult worm excretory/secretory antigen were time- and infection dose-dependent in all 3 dietary groups. The major finding was that the specific antibody response was more intense, both quantitatively (serum OD levels) and qualitatively (antigen recognition by IgG1), in mice fed the low protein diets, even though they remained susceptible to infection. This study shows that host dietary protein deficiency, even at levels irrelevant to normal growth, can markedly potentiate the transmission of T. muris via alterations in host resistance. The high levels of antibody in susceptible animals suggest that this defect in resistance is unlikely to be due to nutrient deficiency-associated defects in humoral immunity.

Analysis of Variance

Nutrition, immunity and helminth infection: effect of dietary protein on the dynamics of the primary antibody response to Trichuris muris (Nematoda) in CBA/Ca mice.

The effect of dietary protein on the specific antibody responses (total immunoglobulins, IgG1 and IgA) to the intestinal nematode Trichuris muris was studied in CBA/Ca mice fed isocaloric diets containing 16% or 4% protein. Mice fed the 16% diet and given a high infection dose of 650 eggs expelled almost their entire primary infection by day 21 post infection. In similarly infected animals fed the 4% protein diet, there was prolonged survival of adult worms. At a low infection dose of 10 eggs, there was no evidence of an expulsion response in either dietary group. The primary antibody response to parasite excretory/secretory (E/S) antigen was time-dependent, regardless of dietary protein or infection dose, and was predominantly an IgG1 response. Within each dietary group, antibody production and antigen recognition occurred earlier and the antibody responses were more intense in mice given the higher infection dose. The principal finding was that the specific antibody response was more vigorous, both quantitatively (serum titres) and qualitatively (antigen recognition by IgG1), in mice on a low protein diet, even though worm expulsion did not occur in these hosts. This result suggests that serum antibody level or antigen recognition is not related simply to protective immunity against T. muris in CBA/Ca mice.

Animals

The effect of the protein content of CBA/Ca mouse diet on the population dynamics of Trichuris muris (Nematoda) in primary infection.

The relationship between host dietary protein and intestinal helminth population biology during primary infection was studied using a mouse-T. muris experimental model. Uninfected CBA/Ca mice fed either a 4% (by mass) or 16% protein diet grew at a similar rate, but both suffered significant growth retardation when infected with T. muris. T. muris initial establishment and fecundity were unaffected by dietary protein content, but were significantly influenced by infection dose, declining at the higher level of infection. Dietary protein deficiency increased parasite survival at high infection levels. Heavily infected hosts fed the 16% protein diet were found to expel almost the whole of their infections around day 21 p.i. By contrast, this response appeared defective in hosts fed the lower 4% protein diet, resulting in the establishment and survival of large, chronic and patent infections. Mean faecal egg output per mouse increased with infection dose in animals fed a low protein diet, but was low and unrelated to infection exposure in hosts fed the 16% protein diet. It is concluded that low protein levels in diet, via alterations in host resistance, may have an important influence on the transmission of T. muris.

Analysis of Variance

Surgery of the parotid region: a new approach.

Many disorders of the parotid gland require treatment by subtotal or total parotidectomy. In such situations functional and esthetic complications may arise due to the location of the incisions or from permanent or temporary injuries to the facial nerve. This report describes a modified revision that gives good esthetic and functional results. A review of a similar series of cases treated surgically by the same surgeons using Yoel and Bilesio's technique showed no differences in morbility associated with parotidectomy performed using the proposed incision.

Adolescent

Density dependence in establishment, growth and worm fecundity in intestinal helminthiasis: the population biology of Trichuris muris (Nematoda) infection in CBA/Ca mice.

The results are presented of an experimental study of the population biology of chronic Trichuris muris (Nematoda) infection in cortisone-treated CBA/Ca mice. Attention is focused upon both the validity of the common use of faecal egg counts to demonstrate density dependence in helminth fecundity, and the identification of other possible density-dependent mechanisms that may regulate worm numbers in chronic trichuriasis. The results show that faecal egg counts, although demonstrating high daily variation, are not an artefact of host faecal output but a significant density-dependent function of worm burden. This finding contrasts with the observations on Heligmosomoides polygyrus infection in outbred MFI mice, but accords with similar studies in a wide variety of host - helminth systems. Worm establishment in the murine host is found to be a density related function of infection dose. This is attributed to the probable existence of a physical gut-carrying capacity in the murine host for T. muris. Worm distribution in the gut is also shown to the density dependent, with worms being displaced from the caecum to the colon at increasing intensities of infection. The sex ratio of the adult parasites, however, is found to be both unitary and independent of worm burden. Evidence for a significant density-dependent decline in female T. muris growth or size is presented. The results also show a significant positive association between female T. muris weight and per capita fecundity. These findings indicate that the stunted growth of individual worms at high parasite densities may be a potential mechanism underlying density dependence in helminth fecundity.

Animals