F. E. G. Cox

Concomitant infections, parasites and immune responses

Concomitant infections are common in nature and often involve parasites. A number of examples of the interactions between protozoa and viruses, protozoa and bacteria, protozoa and other protozoa, protozoa and helminths, helminths and viruses, helminths and bacteria, and helminths and other helminths are described. In mixed infections the burden of one or both the infectious agents may be increased, one or both may be suppressed or one may be increased and the other suppressed. It is now possible to explain many of these interactions in terms of the effects parasites have on the immune system, particularly parasite-induced immunodepression, and the effects of cytokines controlling polarization to the Th1 or Th2 arms of the immune response. In addition, parasites may be affected, directly or indirectly, by cytokines and other immune effector molecules and parasites may themselves produce factors that affect the cells of the immune system. Parasites are, therefore, affected when they themselves, or other organisms, interact with the immune response and, in particular, the cytokine network. The importance of such interactions is discussed in relation to clinical disease and the development and use of vaccines.

History of Human Parasitology

SUMMARY Humans are hosts to nearly 300 species of parasitic worms and over 70 species of protozoa, some derived from our primate ancestors and some acquired from the animals we have domesticated or come in contact with during our relatively short history on Earth. Our knowledge of parasitic infections extends into antiquity, and descriptions of parasites and parasitic infections are found in the earliest writings and have been confirmed by the finding of parasites in archaeological material. The systematic study of parasites began with the rejection of the theory of spontaneous generation and the promulgation of the germ theory. Thereafter, the history of human parasitology proceeded along two lines, the discovery of a parasite and its subsequent association with disease and the recognition of a disease and the subsequent discovery that it was caused by a parasite. This review is concerned with the major helminth and protozoan infections of humans: ascariasis, trichinosis, strongyloidiasis, dracunculiasis, lymphatic filariasis, loasis, onchocerciasis, schistosomiasis, cestodiasis, paragonimiasis, clonorchiasis, opisthorchiasis, amoebiasis, giardiasis, African trypanosomiasis, South American trypanosomiasis, leishmaniasis, malaria, toxoplasmosis, cryptosporidiosis, cyclosporiasis, and microsporidiosis.

History of the discovery of the malaria parasites and their vectors.

Malaria is caused by infection with protozoan parasites belonging to the genus Plasmodium transmitted by female Anopheles species mosquitoes. Our understanding of the malaria parasites begins in 1880 with the discovery of the parasites in the blood of malaria patients by Alphonse Laveran. The sexual stages in the blood were discovered by William MacCallum in birds infected with a related haematozoan, Haemoproteus columbae, in 1897 and the whole of the transmission cycle in culicine mosquitoes and birds infected with Plasmodium relictum was elucidated by Ronald Ross in 1897. In 1898 the Italian malariologists, Giovanni Battista Grassi, Amico Bignami, Giuseppe Bastianelli, Angelo Celli, Camillo Golgi and Ettore Marchiafava demonstrated conclusively that human malaria was also transmitted by mosquitoes, in this case anophelines. The discovery that malaria parasites developed in the liver before entering the blood stream was made by Henry Shortt and Cyril Garnham in 1948 and the final stage in the life cycle, the presence of dormant stages in the liver, was conclusively demonstrated in 1982 by Wojciech Krotoski. This article traces the main events and stresses the importance of comparative studies in that, apart from the initial discovery of parasites in the blood, every subsequent discovery has been based on studies on non-human malaria parasites and related organisms.

Acquired immunity to Babesia microti and Babesia rodhaini in mice.

Mice infected with Babesia rodhaini can be cured with a single injection of Diampron and are immune to challenge with the same species. Mice infected with B. microti recover naturally from their infections and are also immune to challenge. The immunity extends to the heterologous species in both infections. In some cases parasites persist at a low level after recovery but in others the immunity is of a true sterile type. Immunity once established is unaffected by splenectomy in mice which have recovered from B. rodhaini and challenged with either B. rodhaini or B. microti. We wish to express our thanks to May and Baker Ltd. who kindly provided us with the Diampron used in these experiments.

Heterologous immunity between piroplasms and malaria parasites: the simultaneous elimination of Plasmodium vinckei and Babesia microti from the blood of doubly infected mice.

Mice which have recovered from infections with the avirulent piroplasm Babesia microti are also resistant to challenge with the virulent malaria parasite Plasmodium vinckei. In mice infected with P. vinckei before the peak of the B. microti infection the numbers of malaria parasites in the blood increase until that peak and are then eliminated at the same time as the piroplasms. In mice infected with P. vinckei at or after the peak there is no apparent multiplication and the malaria parasites begin to disappear from the blood immediately. The malaria parasites in doubly infected mice show signs of degeneration similar to those seen in mice pre-treated with Corynebacterium parvum and it is suggested that a common mechanism exists in homologous and heterologous immunity and in immunity following pre-treatment with C. parvum or BCG.

Immunity to malaria and piroplasmosis in mice following low level infections with Anthemosoma garnhami (Piroplasmea: Dactylosomidae)

Mice which have recovered from infections with A. garnhami do not succumb to; challenge with the piroplasms B. rodhaini or B. microti and over half such animals are protected against the malaria parasites P. v. vinckei and P. v. chabaudi . This protection does not extend to the malaria parasites P. b. berghei or P. b. yoelii . Mice which have recovered from infections with the piroplasms are protected against A. garnhami , as are those which have recovered from infections with P. v. vinckei or P. v. chabaudi . About half the mice which have recovered from infections with P. b. berghei or P. b. yoelii are also protected against A. garnhami . This interaction between intra-erythrocytic protozoa may influence the incidence of these parasites in the wild. A. garnhami is unlikely to be of any use in the immunization of humans against malaria but could be of use in the protection of cattle against piroplasmosis.

Absence of immunity between Trypanosoma musculi and intra-erythrocytic protozoa in mice

Mice which have recovered from, infections with Trypanosoma musculi exhibit no immunity to challenge with the malaria parasites, Plasmodium v. vinckei, P. v. chabaudi, P. b. berghei, P. b. yoelii or P. atheruri , the piroplasms Babesia rodhaini or B. microti or the dactylosomid Anihemosoma garnhami . Recovery from infections with any one of these parasites confers no immunity against T. musculi . These results indicate that heterologous immunity between intra-erythrocytic protozoa does not extend to trypanosomes.

The Golden Age of parasitology-1875-1925: the Scottish contributions.

The period 1875-1925 was remarkable in the history of parasitology partly because of the number of significant discoveries made, especially the elucidation of important life cycles, and partly because of the achievements of the clinicians and scientists who made these discoveries. What is remarkable is that so many of these individuals were Scots. Preeminent in this pantheon was Patrick Manson, who not only discovered the mosquito transmission of filarial worms but was instrumental in directly encouraging others to make significant discoveries in the fields of malaria, Guinea worm disease (dracunculiasis), onchocerciasis, loiasis and schistosomiasis and, indirectly, sleeping sickness and leishmaniasis. This chapter describes and discusses the contributions made by Douglas Argyll-Robertson, Donald Blacklock, David Bruce, David Cunningham, Robert Leiper, William Leishman, George Low, Patrick Manson, Muriel Robertson and Ronald Ross together with short biographical notes.

George Henry Falkiner Nuttall and the origins of parasitology and Parasitology

By the beginning of the twentieth century, most of the major discoveries concerning the nature and life cycles of parasites had been made and tropical medicine was beginning to establish itself as a discipline but parasitology still lacked any real cohesion or focus. This focus arrived in 1908 when George Nuttall founded a new journal, Parasitology, as a Supplement to the Journal of Hygiene in order to cater for increasing numbers of papers on protozoological, helminthological and entomological topics that were being submitted for publication to that journal; thus bringing these three subjects together under one heading and, in doing so, established the discipline of parasitology. The events leading up to and the subsequent development of the discipline are discussed.

Robert Leiper and the London School of (Hygiene and) Tropical Medicine.

Robert Leiper is best known for his discoveries in the fields of Guinea worm and schistosomiasis, but he also made major contributions to parasitology during his career as helminthologist and later Professor of Helminthology at the London School of (Hygiene and) Tropical Medicine. He was particularly involved in establishing the London Schools Winches Farm Field Station and stimulating the research carried out there, work that has made a number of important contributions to our understanding of parasites. Leiper founded the Commonwealth Bureau of Agricultural Parasitology and was also instrumental in initiating, and editing, the Journal of Helminthology, Helminthological Abstracts and establishing, indirectly, Protozoological Abstracts.