Generalized linear modelling for parasitologists

We estimate the parameters of a stochastic process model for a macroparasite population within a host using approximate Bayesian computation (ABC). The immunity of the host is an unobserved model variable and only mature macroparasites at sacrifice of the host are counted. With very limited data, process rates are inferred reasonably precisely. Modeling involves a three variable Markov process for which the observed data likelihood is computationally intractable. ABC methods are particularly useful when the likelihood is analytically or computationally intractable. The ABC algorithm we present is based on sequential Monte Carlo, is adaptive in nature, and overcomes some drawbacks of previous approaches to ABC. The algorithm is validated on a test example involving simulated data from an autologistic model before being used to infer parameters of the Markov process model for experimental data. The fitted model explains the observed extra-binomial variation in terms of a zero-one immunity variable, which has a short-lived presence in the host.

Estimation of parameters for macroparasite population evolution using approximate bayesian computation.

Immunological tolerance: The key feature in human filariasis?

The basic tenet of the immunological perspective of fuiarial disease is that differential immune responsiveness among individuals exposed to infection results in the different clinical manifestations that develop. The mechanisms involved in this differential responsiveness appear to reflect different T-cell cytokine response patterns. Asymptomatic patients with the clinically silent presentation of ‘asymptomatic microfilaraemia’, who have been previously described as being ‘immunosuppressed’ with respect to their generating pro-inflammatory (Th1-type) immune responses to parasite antigen, are now recognized to be fully responsive to parasite antigen but to produce cytokines and mediators that have primarily anti-inflammatory (Th2-like) effects. Studies with immunodeficient mice have indicated the existence of two alternative pathways to the development of lymphatic pathology: one dependent on the induction of inflammatory reactions by the host immune response, the other entirely independent of the immune system and reflecting the direct actions of the parasite or its products on the lymphatics. As histopathology of affected human lymphatics is consistent with this hypothesis, it may be that the lymphatic pathology seen normally in the amicrofilaraemic, highly immunoresponsive infected patients derives from inflammation induced by immune responses to parasite antigen, whereas the lymphatic pathology sometimes seen coexisting with the ‘immunosuppressed’ state of asymptomatic microfilaraemia actually reflects lymphatic damage that is not immunologically mediated. Though little information exists about the ‘natural history’ of lymphatic filariasis, there is no evidence for an inevitable progression from one clinical form to another. Instead, there appears to be a definite plasticity in the response that depends on prior (? pre-natal) and current exposure to the parasite as well as on the immunomodulatory effects it induces. This plasticity does not appear to be complete, however, as there is no evidence that a chronically infected host who has developed strong pro-inflammatory immune responses can subsequently become sufficiently ‘down-regulated’ to support an asymptomatic microfilaraemia type of infection. Another possible constraint to the plasticity of the clinical and immunological responses may be the genetic determination of certain unusual syndromes, such as tropical pulmonary eosinophilia or TPE, though this hypothesis remains to be proven.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0031182000075259

The Wellcome Trust Lecture. Infection and disease in lymphatic filariasis: an immunological perspective.

Lymphatic filariasis: new insights into an old disease

A glass chamber method of counting living microfilariae in 20–100 c.mm. samples of freshly haemolyzed blood proved to be substantially more sensitive than, and as reliable as, the use of standard wet or stained dry films. The method has the further advantages of simplicity and brevity. The results showed that with the “normal” thick smear technique between 30 and 40% of microfilariae are lost during processing of the slide. It is suggested that the chamber counting method has practical field and laboratory utility.

Comparison of a counting chamber and thick smear methods of counting microfilariae

Using the indirect fluorescent antibody technique, the antibody response of cats to Brugia pahangi infections was studied using whole microfilariae and sectioned adult worms of B. pahangi as antigens. Microfilarial antigen was ineffective in detecting antibody response in cats during the microfilaraemic phase of the infection, although it was possible to detect circulating antibody in cats which became microfilaria negative after repeated and prolonged reinfection and in one cat which after infection failed to show microfilariae in its blood

Studies with Brugia pahangi 4. Antibodies against adult and microfilarial stages

Studies with Brugia pahangi. I. Parasitological observations on primary infections of cats (Felis catus).

Cats infected with Brugia pahangi by single or repeated inoculation of infective larvae for different periods of time, were autopsied and the affected lymph nodes examined histologically, stained with methyl green and pyronin Y, haematoxylin and eosin, Lendrum's eosinophil stain, Mallory's trichrome stain or the May-Grunwald Giemsa technique. In single infections, there was initially a cell-mediated type immunological response which was characterized by proliferation of mononuclear thymus-dependent cells in the paracortical region of the lymph node. The antibody-type response became more evident as the infections progressed. This response was characterized by proliferation of lymphocytes in rapidly enlarging germinal centres and the production of large numbers of plasma cells in the cortico-medullary junction and medullary cords of the nodes. In long term infections, the affected afferent lymphatic vessel and popliteal node were almost obliterated by fibrous tissue, but an inguinal lymph node complex usually developed to replace lymphatic filtration in the limb. Repeated infections produced more complicated changes. Both types of response occurred to varying degrees throughout the infection. No significant increase in mast cells or eosinophil cells was seen. Fibrous tissue increased in the lymph nodes only after long periods of infection; such nodes often became non-functional, and by-passed by new lymphatic vessels.

T. Ponnudurai

Papers

Comparison of a counting chamber and thick smear methods of counting microfilariae

Studies with Brugia pahangi 4. Antibodies against adult and microfilarial stages

Studies with Brugia pahangi. I. Parasitological observations on primary infections of cats (Felis catus).

Studies with Brugia pahangi. III: Histological changes in the affected lymph nodes of infected cats.

Studies with Brugia pahangi. II. The effect of repeated infection on parasite levels in cats.