troglodytes). caution has been raised about the adequacy of the description of these new species. a report of a new species that clusters with p. falciparum and p. reichenowi in chimpanzees has been published, although to date the species has been identified only from the sequence of its mitochondrion. further work will be needed to describe this new species, however, it appears to have diverged from the p. falciparum- p. reichenowi clade about 21 million years ago. a second report has confirmed the existence of this species in chimpanzees. this report has also shown that p. falciparum is not a uniquely human parasite as had been previously believed. a third report on the epidemiology of p. falciparum has been published. this study investigated two mitochondrial genes (cytb and cox1), one plastid gene (tufa), and one nuclear gene (ldh) in 12 chimpanzees and two gorillas from cameroon and one lemur from madagascar. plasmodium falciparum was found in one gorilla and two chimpanzee samples. two chimpanzee samples tested positive for plasmodium ovale and one for plasmodium malariae. additionally one chimpanzee sample showed the presence of p. reichenowi and another p. gaboni. a new species - plasmodium malagasi - was provisionally identified in the lemur. this species seems likely to belong to the vinckeia subgenus but further work is required. a study of ~3000 wild ape specimens collected from central africa has shown that plasmodium infection is common and is usually with multiple species. the ape species included in the study were western gorillas (gorilla gorilla), eastern gorillas (gorilla beringei), bonobos (pan paniscus) and chimpanzees (pan troglodytes). 99% of the strains fell into six species within the subgenus laverina. p. falciparum formed a monophyletic lineage within the gorilla parasite radiation suggesting an origin in gorillas rather than chimpanzees. it has been shown that p. falciparum forms a clade with the species p. reichenowi. this clade may have originated between 3 million years ago and 10000 years ago. it is proposed that the origin of p. falciparum may have occurred when its precursors developed the ability to bind to sialic acid neu5ac possibly via erythrocyte binding protein 175. humans lost the ability to make the sialic acid neu5gc from its precursor neu5ac several million years ago and this may have protected them against infection with p. reichenowi. another paper has suggested that the p. falciparum isolates found in apes are derived from humans and that p. falciparum and p. reichenowi diverged when humans and chimpanzees/gorillas did (between 5 million years ago and 7 million years ago). it is considered that p. falciparum in humans originated from a single transmission event and that the great apes do not represent a potential reservoir for on going transmission. the origin of p. falciparum in humans seems likely to have been from bonobos rather than gorillas or chimpanzees. another estimate of the most recent common ancestor of the extant strains that has been published is 452,000 years ago. a review of this subgenus has been published based on the analysis of the cytochrome b gene the relationships in this subgenus appear to as follows: p. falciparum and p. reichenowi are sister species. their closest relation is p. billcollinsi. p. gaboni and p. billbrayi are sister species whose closest relation is p. gora. p. gorb is more closely related to the p. falciparum/reichenowi/billcollinsi clade than the p. gaboni/billbrayi/gora clade. this putative taxonomy will need confirmation from other dna studies. a second study seems to confirm this proposed grouping. another estimate puts the divergence between falciparum and reichenowi at ~200,000 years before present. the dates of the evolution of the species within the subgenus laverania have been estimated as follows: laverania: 12 million years ago (mya) (95% estimated range: 6 million years ago - 19 million years ago) p. falciparum in humans: 0.2 million years ago (range: 0.078 million years ago - 0.33 million years ago) p. falciparum in pan paniscus: 0.77 million years ago (range: 0.43 million years ago - 1.6 million years ago) p. falciparum in humans and pan paniscus: 0.85 million years ago (0.46 million years ago - 1.3 million years ago) p. reichenowi - p. falciparum in pan paniscus: 2.2 million years ago (range: 0.41 million years ago - 3.1 million years ago) p. reichenowi - 1.8 million years ago (range: 0.6 million years ago - 3.2 million years ago) p. billbrayi - p. falciparum 1.1 million years ago (range: 0.52 million years ago - 1.7 million years ago) p. billcollinsi - 0.97 million years ago (range: 0.38 million years ago - 1.7 million years ago) p. praefalciparum - p. falciparum in gorilas 40,000-60,000 years ago another estimate using the mutation rate (1.2 x 10−8 subsititutions/site/year) of the cytochrome b gene placed the spread of p. falciparum to humans at 365,000 years ago (95% credible interval: 112,000 to 1,036,000 years). revised names have been proposed for the p. gora and p. gorb species - plasmodium blacklocki and plasmodium adleri respectively. these names were chosen to honour the malariologists saul adler (1895–1966) and donald blacklock (1879–1953). it has also been proposed that the p. falciparum strains infecting gorillas should be renamed plasmodium praefalciparum. this proposal appears to have been accepted. the species p. billbrayi seems to be synonymous with earlier named p. gaboni. host-parasite relations: p. falciparum has been isolated from chimpanzees, gorillas and humans. the non human strains may be reclassified as p. praefalciparum. p. reichenowi has been isolated from chimpanzees. p. billcollinsi has been isolated from chimpanzees. p. billbrayi has been isolated from chimpanzees. p. gaboni has been isolated from chimpanzees. p. adleri has been isolated from gorillas. p. blacklocki has been isolated from gorillas. p. lomamiensis has been isolated from bonobos. p. praefalciparum has been isolated from gorillas. another analysis has proposed the following arrangement of species: p. billcollinsi, p. gaboni and p. reichenowi only infect chimpanzees while p. adleri, p. blacklocki and p. praefalciparum only infect gorillas. p. praefalciparum appears to be the closest relation to p. falciparum. a review of the genomes of all the known species in this subgenus found that the divergence between p. falciparum and p. praefalciparum occurred between 40,000 and 60,000 years ago. the expansion of p. falciparum encountered a bottle neck between 4,000 and 6,000 years ago. it appears that p. falciparum has been introduced into south america on several occasions. the extant strains fall into two clades - one northern and one southern. the most probable origin of these strains is africa and it seems that they were introduced with the slave trade. analysis of 45 single copy nuclear genes from eight species (p. berghei, p. chabaudi, p. falciparum, p. gallinaceum, p. knowlesi, p. reichenowi, p. vivax, p. yoelii) using several different phylogenetic methods suggest a divergence data between 294 and 314 between theileria and plasmodium. estimates of the mutation rates suggest a date of divergence between p. falciparum and p. reichenowi between 5 million years ago and 7 million years ago. analysis of polymorphisms in the mitochondrial genes suggests a sub saharan origin for p. falciparum with separate colonisations of southeast asia and oceania. given the distributions of the other members of laverinia it seems likely all the known members of this subgenus originated in africa. another species - plasmodium lomamiensis - has been described from bonobos. the name is derived from the lomami national park where the parasite was first identified. the relationship of this species to others in the subgenus has yet to be clarified. another study has shown that the ancestor of p. falciparum was the gorilla parasite p. praefalciparum. this species first infected humans between 40,000-60,000 years ago and then underwent a population bottleneck 4,000-6,000 years ago. the common ancestor of this subgenus existed between 0.7 million years ago and 1.2 million years ago. at this time a division occurred into clade a (p. adleri and p. gaboni) and clade b - the other species in the subgenus. within clade b, p. blacklocki diverged about 960,000 years ago and p. billcollinsi about 500,000 years ago. within clade a, p. adleri and p. gaboni diverged about 140–230 thousand years ago. p. reichenowi and the ancestor of p. praefalciparum/p. falciparum also diverged about the same time. the p. falciparum population reached a nadir about 5,000 years ago (ne ~3000). plasmodium colobine and macaque monkeys migrated from africa into the eurasian continent 10 and 6 millions of years ago respectively and became the ancestors of the extant asian old world monkey species. asian old world monkey malaria parasite species infect both colobine and macaque monkeys. the existing divergence between the asian and african clade of this subgenus seems likely to have been caused by intercontinental allopatric speciation along with that of their hosts. malaria parasites of the lemurs are not traditionally grouped with the subgenus plasmodium being placed rather within subgenus vinckeia. this classification may not be correct. based on an analysis of the mitochondria, these parasites seem to group with the others infecting primates. the origin of the primate infecting species (excluding those in the laverina subgenus) may date back to the eocene - a time when the primate radiation began. this analysis also suggests that the species infecting gorillas and humans may have originated in chimps. plasmodium: asian clade at least nine species belong to the 'asian' clade of plasmodium. these species include plasmodium coatneyi, plasmodium cynomolgi, plasmodium fieldi, plasmodium fragile, plasmodium inui, plasmodium hylobati, plasmodium simiovale, plasmodium simium and plasmodium vivax. as a rule (with the noticeable exception of p. knowesli), the asian species have a 72-hour intra erythroctytic life cycle. analysis of the merozoite surface protein in ten species of the asian clade suggest that this group diversified between 3 and 6.3 million years ago - a period that coincided with the radiation of the macques within south east asia. the inferred branching order differs from that found from the analysis of other genes suggesting that this phylogenetic tree may be difficult to resolve. positive selection on this gene was also found. in an analysis of the ssu rrna gene it was found that all asian simian plasmodium species have a single s-type-like gene and several a-type-like genes. a 50 residue insertion in the v7 variable region near the stem 43 is shared exclusively by the s-type like sequences of the asian simian plasmodium species and the s- and o-type sequences of p. vivax. this is consistent with their shared ancestry. plasmodium vivax may have originated in asia and the related species plasmodium simium appears to be derived through a transfer from the human p. vivax to new world monkey species in south america. this was proposed in a study of howler monkeys near são paulo, brasil. another paper has suggested an african origin for p. vivax. another paper reported the presence of p. vivax in gorillas and chimpanzees. the dna sequences analysed fell into two clades. one clade included all the human strains: the second clade seems likely to be an undescribed species. the gorilla and chimpanzee strains did not group by species suggesting that p. vivax transmission occurs between these species. the authors suggested an africa origin for p. vivax. a paper has suggested that p. vivax has an african origin and underwent a severe bottleneck and then expanded rapidly once it left africa. an african origin for p. vivax would explain the presence of p. gonderi - an africa species - within this clade. plasmodium species have been isolated from orangutans. these isolates appear to belong to the asian clade and share an ancestor with plasmodium inui and plasmodium hylobati. a paper has suggested that p. vivax is basal to the asian clade branching after p. gonderi. this is consistent with an african origin of the asian clade. a study of worldwide isolates of p. vivax found the maximum diversity to lie within south east asia, suggesting this as the origin of this species. the same paper found that isolates in the americas fell into two groups suggesting that there were at least 2 separate introductions of this parasite into the americas. time to most recent common ancestor p. vivax appears to have evolved between 45,000 and 82,000 years ago from a species that infects south east asian macques. this is consistent with the other evidence of a south eastern origin of this species. a