Reducing global health inequalities. Part 1.

This paper summarizes four UK reviews of socially stratified health inequalities that were undertaken during the past five decades. It describes the background of misplaced optimism and false hopes which characterized the UK's own record of health inequalities; the broken promises on debt cancellations which was the experience of developing countries. It describes why the UK's past leadership record in international health provides grounds for optimism for the future and for benefits for both developed and developing countries through the adoption of more collaborative approaches to global health than have characterized international relationships in the past. It recalls the enthusiasm generated in the UK, and internationally, by the establishment of the Global Commission on the Social Determinants of Health. It promotes the perception of health both as a global public good and as a developmental issue and why a focus on poverty is essential to the address of global health issues. It sees the designing of appropriate strategies and partnerships towards the achievement of the Millennium Development Goals as an important first step for achieving successful address to global public health issues.

History of the World Association for the Advancement of Veterinary Parasitology (WAAVP).

Forty years ago the first meeting of the World Association for the Advancement of Veterinary Parasitiology (WAAVP) was held in Hannover, Germany. We now have a thriving, internationally recognized organization; the meetings attract hundreds of scientists, attendance is increasing with almost every meeting. It is a useful time to review our beginnings, our development and our future. Our history has been one of innovation and activity and contributed to by its members in important areas of veterinary parasitology.

Antibiotic resistance--an evolving problem.

In 1998, an influential report on antimicrobial resistance from the House of Lords Select Committee on Science and Technology highlighted the threat posed to public health by resistance, and called for products to be used more prudently in both human and veterinary medicine. Here, Lord Soulsby, who chaired the Lords' committee on antimicrobials, and Richard Wise, who advised the committee and is now chairman of the Government's Specialist Advisory Committee on Antimicrobial Resistance, consider what has been achieved since then, along with the challenges that remain.

Intestinal changes in puppies infected with Toxocara canis.

Small intestinal histopathology and absorption were examined in Beagle puppies infected with either a moderate or a low burden of Toxocara canis. Infection with T. canis significantly reduced absorption of xylose, but only slightly delayed absorption of para-aminobenzoic acid. Fat assimilation was reduced and faecal proteolytic activity was increased. A significant reduction in villous height occurred and was inversely related to the extent of the infection. Villous goblet cell numbers, particularly those in the luminal third of the villus, were lowest and crypt goblet cell numbers were highest in the most heavily infected of the puppies. Villous goblet cell numbers increased rapidly after treatment of the puppies with piperazine or after the spontaneous elimination of the T. canis infection while crypt goblet cell numbers were less affected by elimination of the parasites. Intra-epithelial lymphocyte numbers were lowest in 33- to 37-day-old puppies infected with greater than 127 T. canis and highest in 44- to 46-day-old puppies losing their infection. Infection with T. canis had no apparent effect on mast cell numbers or pyroninophilic cell numbers in the lamina propria.

Use of sentinel lambs for early monitoring of the South Powys Hydatidosis Control Scheme: prevalence of Echinococcus granulosus and some other helminths.

Sentinel lambs were used to identify young Echinococcus granulosus infections in sheep, to provide an early indication of the progress of the South Powys Hydatidosis Control Scheme. Four sentinel lambs were purchased on each of 60 farms, from inside and outside the control area; they were examined when approximately six, 10 and 15 months of age. Gross examination, thin slicing of organs and histological examination of the lesions in the viscera revealed no E granulosus hydatid cysts in lambs born within the control area, whereas 25 per cent of the 15-month-old lambs from outside the area harboured E granulosus cysts (less than 1 to 2 mm in diameter). Lambs from E granulosus infected farms had significantly higher anti-E granulosus ELISA antibody titres than lambs from uninfected farms. It was concluded that within one year of beginning to treat dogs with praziquantel every six weeks the transmission of E granulosus to sheep had ceased. In contrast, this treatment did not prevent infections with Taenia hydatigena or T ovis; an examination of the 240 lambs revealed T hydatigena in 33.3 per cent of them, Tovis in 4.2 per cent, Dictyocaulus filaria in 12.1 per cent and Meullerius capillaris in 49.2 per cent.

The evasion of the immune response and immunological unresponsiveness: parasitic helminth infections.

A selective review is given of the mechanisms associated with the evasion of the immune response by parasitic helminths and immunological unresponsiveness as it applies to helminth infections. Immunosuppression caused by parasites leading to reduced responsiveness of lymphocytes to mitogens is discussed, and mechanisms that inhibit effector mechanisms at the parasite surface and polyclonal activation of lymphocyte populations are dealt with. Physiological immunosuppression associated with parturition and lactation and the immunological unresponsiveness of young ruminants are dealt with in detail.

Reaginic and homocytotropic IgG antibody response of Mastomys natalensis in experimental infections of filarial parasites (Litomosoides carinii, Dipetalonema viteae, Brugia malayi, B. pahangi).

Reaginic and homocytotropic IgG antibodies in sera using passive cutaneous anaphylaxis (PCA) test and antigen from Litomosoides carinii were followed in Mastomys natalensis, infected with L. carinii, Dipetalonema viteae, Brugia malayi or B. pahangi. Groups of animals with infections of various ages so as to cover a total infection period of up to 300 to 420 days post-infection (p.i.), depending on the species of parasites, were bled at 1- to 3-week intervals over periods of 50-112 days. In addition, intradermal tests were performed on animals infected with L. carinii to detect immediate type hypersensitivity. Reaginic antibodies were usually first detected in the 3rd week after infection. Thereafter, a marked increase of PCA titres was observed in the 4th week p.i. leading to maximum titres 4 weeks after infection with D. viteae and B. pahangi and 6 weeks after B. malayi infection. Mean maximum titres were between 1:40 and 1:160. Following the peak response, titres decreased markedly until the beginning of patency in infections with D. viteae, B. malayi and B. pahangi whereas a constant course was observed at this time in animals infected with L. carinii. A further rise in PCA titres occurred in all infections around the beginning of patency, resulting in maximum reagin levels in L. carinii infections (mean titre 1:80) and moderate titres in the other infections. During early patency there was an inverse relationship between microfilaraemia density and levels of reaginic antibodies. However, in the phase of decreasing parasitaemia in L. carinii infected animals, microfilariae counts and PCA titres were directly correlated. Homocytotropic IgG antibodies showed relatively constant PCA titres of about 1:20 in L. carinii infected Mastomys throughout the observation period. In D. viteae infections they were demonstrated at 30 days p.i., reaching titres of about 1:40. B. malayi infected animals showed a maximum titre of 1:40 40 days p.i.. Thereafter, titres decreased continuously and homocytotropic IgG antibodies were absent at 110 days p.i.. High titres were observed at day 150 but thereafter sera were negative. B. pahangi infected animals showed moderate titres (1:5) 35 days p.i.. Thereafter, antibodies were found at low titres until 115 days p.i.. Intradermal reactions in L. carinii infected animals generally increased in size from 30-60 but decreased when microfilariae appeared in the blood.(ABSTRACT TRUNCATED AT 400 WORDS)

Advances in immunoparasitology.

A selective review of the advances in immunoparasitology is presented. It is selective simply because it is not feasible to embrace the whole field of parasitology within the compass of a single review paper, for if it were attempted, it would suffer undue abbreviation. Emphasis is placed on the advances in helminthology and especially the gastro-intestinal parasites of ruminants, an obvious selection because of the interests of the author. Reviews are always somewhat retrospective in outlook; to write a review at the present time is especially foolhardy since developments in biology are such that totally new concepts can arise almost overnight, as it were. This is a particularly healthy state, and the discipline of parasitology is caught up in the application and interpretation of molecular biological considerations. "Parasitism" is a field of increasing importance and challenge.

Onchocerciasis: experimental models of ocular disease.

Onchocerciasis is a leading cause of blindness in equatorial Africa and in endemic regions in Central America. Understanding of the pathologic processes involved in onchocercal eye disease and of the role of immunopathologic mechanisms in its development has been substantially limited by the shortage of eyes for histologic study and by the lack of a naturally occurring animal model. The inoculation of microfilariae of Onchocerca species into the eyes of laboratory animals may reproduce selected aspects of onchocercal eye disease, such as punctate keratitis. Studies in these models support the hypothesis that immunopathologic mechanisms mediated by IgE antibody are involved in the development of ocular lesions. In some laboratory animal models, diethylcarbamazine citrate, a microfilaricidal drug that causes severe inflammatory reactions to microfilariae in humans, increases the severity of ocular lesions, and stimulates IgE antibody responses. Laboratory animal studies are potentially highly useful for understanding the immunopathogenesis of ocular onchocerciasis.

Antibody levels in adoptively immunized mice after infection with Babesia microti or injection with antigen fractions.

Specific IgG anti-Babesia antibodies could be detected by an ELISA test in the serum of adoptively immunized mice which subsequently were infected with Babesia microti. Initially, higher IgG antibody levels were present in the recipients of either untreated immune spleen cells or mitomycin C-treated immune spleen cells compared with the values in control mice which received the infection alone. Subsequently, a marked anamnestic response occurred only in mice which received untreated immune spleen cells and not in the recipients of mitomycin C-treated cells, demonstrating a requirement for proliferation of B memory cells in the anamnestic response. When mice were injected with either T or B enriched spleen cell subpopulations and infected with B. microti, the anamnestic antibody response in each animal correlated well with protection against infection. The stimulation of the adoptively transferred immune spleen cells in recipient mice by injection of B. microti antigen fractions prepared by DEAE cellulose chromatography increased the level of antibody production and protection against infection in these mice. A highly significant correlation between these two parameters could be demonstrated for certain antigen fractions.

Babesia microti in mice. Adoptive transfer of immunity with serum and cells.

Protection against infection with Babesia microti in mice was passively transferred with either serum or cells. Immune spleen cells were more effective than were immune mesenteric lymph node (MLN) cells in reducing parasitaemias in recipient mice, and the level of protection correlated with the donor to recipient ratio rather than with the number of cells transferred. Protection against primary infection in recipient mice was adoptively transferred by nylon wool adherent, B cell enriched subpopulations of spleen cells. In contrast, higher peak parasitaemias were apparent in mice which received nylon wool non-adherent, T enriched spleen cells in comparison with the control mice. However, if the recipient mice were reinfected, control of this second infection was greatest in the recipients of the T enriched cell subpopulation. Treatment of the protective nylon wool adherent, B cell subpopulation with anti-theta serum and complement abolished both the protective effect and the anamnestic antibody response in the recipient mice. This suggested that primed T cells controlled the expression of the protective antibody response by primed B cells.

Babesia microti in mice. Subpopulations of cells involved in the adoptive transfer of immunity with immune spleen cells.

Protection against a primary Babesia microti infection in mice, induced by the adoptive transfer of immune spleen cells, was abolished when the immune spleen cells were treated with mitomycin C prior to transfer. Since mitomycin C treatment prevents the replication of lymphocytes without affecting other cell functions, these results would suggest that the transferred cells required proliferation in the recipient mice before they could exert their protective effect, and this excludes the already differentiated antibody-forming cells (AFC's), macrophages and sensitised helper T cells. This was partly supported by the finding that Sephadex G-10 non-adherent immune cells, depleted of macrophages and AFC's, still conferred a strong protection after transfer. However, the Sephadex G-10 adherent cells, on a cell to cell basis, initially conferred a better protection against B. microti than did the non-adherent cells or unfractionated immune spleen cells. The possibility of the retention of an intermediate B memory cell type on the Sephadex G-10 columns and the suppression of antibody production are discussed in view of these results.

Haematological and biochemical values in horses naturally infected with Strongylus vulgaris.

The concentrations of serum proteins (beta 1, beta 2, gamma, alpha 1, alpha 2 globulins and albumin) and absolute numbers of eosinophils, neutrophils and lymphocytes were examined in 64 naturally infected horses and ponies in which the number of larvae of Strongylus vulgaris in the cranial mesenteric artery and the severity of the lesion of verminous arteritis could be determined. The horses were grouped according to the number of larvae found and the severity of the arteritis. The results demonstrated that, although some significant deviation from a random distribution occurred in certain of the values (chi 2 test), there was considerable individual variation in the values obtained for individual animals within groups and overlap of the range of values between groups. Also the number of larvae present in the artery did not necessarily accurately reflect the severity of the arterial lesion. Thus, the parameters examined could not be used reliably to estimate the intensity of infection with S vulgaris in an individual animal.

Ocular immunopathologic findings of experimental onchocerciasis.

Ocular immunopathologic responses of inbred guinea pigs infected with Onchocerca microfilariae from domesticated animals were studied as a laboratory model of human ocular onchocerciasis. A single intracorneal infection of normal guinea pigs with microfilariae produced only minimal ocular lesions. In contrast, intracorneal infection of guinea pigs previously immunized by systemic infection with microfilariae produced intense corneal and uveal inflammation. Transfer of splenic lymphocytes from immunized donors to syngeneic normal recipients substituted effectively for the active immunization. Cell recipients produced marked corneal inflammatory reactions when challenged by a single intracorneal infection. Fresh and cryopreserved microfilariae produced identical reactions. The corneal inflammatory infiltrates were composed primarily of eosinophils, neutrophils, and plasma cells and resembled human onchocercal keratitis. Diethylcarbamazine citrate administration after a challenge intracorneal infection increased the severity of the corneal inflammatory response in immunized animals.