A large focus of naturally acquired Plasmodium knowlesi infections in human beings

In this chapter, we discuss the diseases and related pathologic alterations that may be encountered in the gastrointestinal tract and associated organs of various species of laboratory animals, birds, fish, reptiles, and amphibians. Diseases of various segments of the gastrointestinal tract, the salivary glands, liver, and pancreas are discussed and categorized as inflammatory, parasitic, neoplastic, or miscellaneous. The latter category includes developmental anomalies and metabolic lesions. Due to space limitations, this presentation is not an all-inclusive review, but it does provide a rather extensive review of these lesions. We have also included a rather comprehensive literature review, with a list of references for those readers who want more detailed information with respect to specific diseases.

The Digestive System

Quinoline Antimalarials: Mechanisms of Action and Resistance and Prospects for New Agents

Antifolate antimalarial drugs interfere with folate metabolism, a pathway essential to malaria parasite survival. This class of drugs includes effective causal prophylactic and therapeutic agents, some of which act synergistically when used in combination. Unfortunately, the antifolates have proven susceptible to resistance in the malaria parasite. Resistance is caused by point mutations in dihydrofolate reductase and dihydropteroate synthase, the two key enzymes in the folate biosynthetic pathway that are targeted by the antifolates. Resistance to these drugs arises relatively rapidly in response to drug pressure and is now common worldwide. Nevertheless, antifolate drugs remain first-line agents in several sub-Saharan African countries where chloroquine resistance is widespread, at least partially because they remain the only affordable, effective alternative. New antifolate combinations that are more effective against resistant parasites are being developed and in one case, recently introduced into use. Combining these antifolates with drugs that act on different targets in the parasite should greatly enhance their effectiveness as well as deter the development of resistance. Molecular epidemiological techniques for monitoring parasite drug resistance may contribute to development of strategies for prolonging the useful therapeutic life of this important class of drugs.

Mechanisms of Resistance of Malaria Parasites to Antifolates

Microsporidia are long-known parasitic organisms of almost every animal group, including invertebrates and vertebrates. Microsporidia emerged as important opportunistic pathogens in humans when AIDS became pandemic and, more recently, have also increasingly been detected in otherwise immunocompromised patients, including organ transplant recipients, and in immunocompetent persons with corneal infection or diarrhea. Two species causing rare infections in humans, Encephalitozoon cuniculi and Brachiola vesicularum, had previously been described from animal hosts (vertebrates and insects, respectively). However, several new microsporidial species, including Enterocytozoon bieneusi, the most prevalent human microsporidian causing human immunodeficiency virus-associated diarrhea, have been discovered in humans, raising the question of their natural origin. Vertebrate hosts are now identified for all four major microsporidial species infecting humans (E. bieneusi and the three Encephalitozoon spp.), implying a zoonotic nature of these parasites. Molecular studies have identified phenotypic and/or genetic variability within these species, indicating that they are not uniform, and have allowed the question of their zoonotic potential to be addressed. The focus of this review is the zoonotic potential of the various microsporidia and a brief update on other microsporidia which have no known host or an invertebrate host and which cause rare infections in humans.

http://lib.ajaums.ac.ir/booklist/clinical microbiology reviews-july.pdf

Zoonotic Potential of the Microsporidia

Summary
Three cases of chloroquine-resistant malaria were studied in persons who contracted Plasmodium falciparum while exposed to infection by mosquito bite for a limited time in the Paillin District of Western Cambodia. The basis for the conclusion that the malaria did not respond normally to chloroquine was that 1) attacks occurred following chloroquine prophylaxis, and 2) relapses occurred following normal therapeutic regimens with the same drug. In one case, relapse occurred twice in the presence of plasma levels generally considered to be therapeutic.
One of the cases appeared to be resistant to pyrimethamine also. This point was not studied in the other two cases because pyrimethamine was not used.

Plasmodium falciparum resistant to chloroquine in cambodia.

Prior to 1960, no natural vectors were known for any species of simian malaria. In the course of investigations in Southeast Asia during the last 3 years, natural vectors for five of these malarias have been found; four have been transmitted in the laboratory. Natural vectors for the African and New World species are still unknown. In a series of tables, in the appendix, the authors summarize the literature on the potential experimental vectors. The ecology of simian malaria in Malaya is reviewed with particular reference to members of the Anopheles leucosphyrus group of mosquitoes in which three natural vectors of simian malaria have been identified. Because they are also vectors of human malaria, it is with this group of mosquitoes that the greatest possibility of a liaison between human and simian malaria exists in Southeast Asia. Interest in the vectors of simian malaria has been stimulated by the transmission of the Malayan monkey parasite Plasmodium cynomolgi bastianellii from man to monkeys by the bite of infected mosquitoes. The original infections in man were acquired accidentally in three different laboratories in the United States from experimentally infected Anopheles freeborni mosquitoes (Eyles et al., 1960; Schmidt et al., 1961). Subsequently other strains of Plasmodium cynomolgi, which is closely related to the human parasite P. vivax, were transmitted to man (Coatney et al., 1961) and it has been shown that man-to-man transmission of the parasite can occur under laboratory conditions. It is also known that the Central American monkey parasite, P. brasilianum, is transmissible to man (Contacos et al., 1963). These findings have led to efforts to determine the vectors of simian malaria in nature and to see whether there are ecological barriers Received for publication 8 October 1963. * Presented at the XVI International Congress of Zoology, Washington, D. C., on 21 August 1963 and sponsored by the American Society of Parasitologists and the British Society of Parasitology. t Present address: Division of Entomology, Commonwealth Scientific and Industrial Organization, Brisbane, Australia. which would prevent the transmission of monkey malaria to man under natural conditions in the field. These investigations have been centered mainly in Southeast Asia, particularly in Malaya, but it is pertinent at this stage to review briefly what is known about the vectors of simian malaria the world over. VECTORS OF SIMIAN MALARIA IN AFRICA Four members of the genus Plasmodium have been isolated from subhuman primates in Africa (Table I). Three species come from the great apes, Plasmodium reichenowi; a falciparum parasite of gorillas and chimpanzees; Plasmodium schwetzi, a vivax parasite of gorillas and chimpanzees; and Plasmodium malariae, a quartan parasite, similar to the human quartan parasite, of chimpanzees. The natural vectors of simian malaria are unknown in Africa, and information on the development of parasites under experimental conditions is scanty. Bray (1957) reported gut infections with Plasmodium reichenowi in experimentally fed Anopheles gambiae but mosquitoes dissected for gland infections were all negative. A similar observation was made by Rodhain and Lassman (1940) when they noted that A. atroparvus fed on chimpanzees infected with P. schwetzi developed gut infections, but no

https://www.jstor.org/stable/info/3275715

The vectors of simian malaria: identity, biology, and geographical distribution.

The Chesson strain of Plasmodium vivax was studied in Aotus trivirgatus monkeys. Parasitemia in intact and splenectomized animals was similar to that reported for this strain in man. Comparative infectivity studies with mosquitoes fed on infected monkeys indicated that the most susceptible was Anopheles freeborni, followed by An. balabacensis, An. culicifacies, An. maculatus, An. atroparvus, An. stephensi, An. quadrimaculatus, and An. albimanus. Transmissions via sporozoites from An. maculatus was demonstrated on two occasions; prepatent periods were 30 and 32 days.

The Chesson strain of Plasmodium vivax in Aotus monkeys and anopheline mosquitoes.

The Santa Lucia strain of Plasmodium falciparum was isolated from El Salvador, Central America, and established in Aotus trivirgatus monkeys. Transmission from monkey to monkey via the bites of infected Anopheles freeborni, A. maculatus, and A, albimanus mosquitoes was obtained in 20 of 27 attempts. Prepatent periods in the monkeys ranged from 17 to 46 days with a mean of 24.3 days. Parasitemias and mortality were higher following sporozoite inoculation into animals which had been previously infected with P. vivax than in those with no previous malaria experience. Monkeys previously infected with P. vivax and P. cynomolgi had lower maximum parasitemias than those previously infected with P. vivax only.

Studies on the Santa Lucia (El Salvador) strain of Plasmodium falciparum in Aotus trivirgatus monkeys.

Anopheles freeborni mosquitoes were much more heavily infected with the Santa Lucia strain of Plasmodium falciparum from coastal El Salvador than were any of the other species tested. Of 5 strains of A. albimanus examined, the most heavily infected was the CA-109A and the least was the Melara, both of which come from coastal El Salvador. Of the exotic anophelines, the A. maculatus was infected at a slightly higher level than was the A. balabacensis. The incidence of highly infected individual mosquitoes was greatest in the Panama-Escobal strain of A. albimanus from the Republic of Panama; the incidence was lowest in the Melara strain from El Salvador. All strains of A. albimanus developed infected salivary glands, but the A. freeborni and A. maculatus mosquitoes appeared to develop infected glands more effeciently. Infection rates in A. freeborni mosquitoes were highest if mosquitoes were fed on Aotus trivirgatus monkeys between the 19th and 25th days of patent gametocytemia.

McWilson Warren

Papers

Plasmodium falciparum resistant to chloroquine in cambodia.

The vectors of simian malaria: identity, biology, and geographical distribution.

The Chesson strain of Plasmodium vivax in Aotus monkeys and anopheline mosquitoes.

Studies on the Santa Lucia (El Salvador) strain of Plasmodium falciparum in Aotus trivirgatus monkeys.

Infectivity of the Santa Lucia (El Salvador) strain of Plasmodium falciparum to different anophelines.