Non-human primates (NHPs) often serve as reservoir of pathogens of human diseases. The yellow fever virus (Ellis and Barrett, 2008), Chikungunya virus (McCrae et al., 1971; Labadie et al., 2010), and the protozoa Giardia lamblia that cause diarrhea (Kowalewski et al., 2011), are all examples of pathogens that originate from NHPs and are infectious to humans. Malaria is caused by parasites of the genus Plasmodium that can infect a wide range of vertebrate hosts from reptiles, birds to mammals. Only five Plasmodium species are known to cause malaria in humans: Plasmodium falciparum, P. knowlesi, P. malariae, P. ovale, and P. vivax. Of these five species, P. falciparum is most common and most lethal (WHO, 2011).

Plasmodium parasites are, however, also found in other primates than humans. Plasmodium reichenowi was the first Plasmodium species identified in NHPs, isolated from an infected chimpanzee (Coatney et al., 1971; Rayner et al., 2011). Other NHP Plasmodium species have been identified (Coatney et al., 1971; Rayner et al., 2011) and their identity can be studied in more detail since the development of molecular tools. A recent study in which mitochondrial, apicoplast, and nuclear gene sequences from 2700 fecal samples from wild-living African apes have been analyzed, showed that Plasmodium species are widely distributed in NHPs and with high prevalence (Liu et al., 2010). The detected parasites could be classified into six discrete major clades, all belonging to the subgenus, termed Laverania, which discriminates them from more divergent Plasmodium species (Liu et al., 2010; Rayner et al., 2011). Interestingly, some of these Laverania clades were only associated with chimpanzee (Pan troglodytes) samples and others only with samples from western lowland gorilla’s (Gorilla gorilla).

Although infections with Plasmodium parasites appear to be host-specific, chimpanzees, and gorillas were nevertheless found to be infected with mitochondrial DNA similar to that of human P. vivax (Liu et al., 2010). Chimpanzees were also found to be infected with P. ovale and P. malariae, which may have contributed to the perseverance of these human malaria parasites in Africa (Duval et al., 2009, 2010; Hayakawa et al., 2009; Krief et al., 2010; Duval and Ariey, 2012). Several studies performed between 1940 and 1956 showed that these species can be transmitted from apes to humans (Rodhain and Dellaert, 1955a,b; Garnham et al., 1956; Rayner et al., 2011). P. falciparum has not been found in wild NHPs but has been detected in captive chimpanzees and bonobos (Liu et al., 2010; Rayner et al., 2011). Interestingly, mitochondrial sequence analysis has revealed that western lowland gorillas probably served as the source of human P. falciparum (Liu et al., 2010) and P. falciparum diverged between 112,000 and 1,036,000 years ago (Baron et al., 2011).

Little is known about the ability of NHP malaria parasites to infect humans, except for the fifth human Plasmodium parasite, P. knowlesi, which was long known only as a parasite of monkeys. The parasite was extensively studied for basic immunological, chemotherapeutic, and biological relationships between malaria parasites and their primate hosts (Collins, 2012). A study in 2004 in Malaysian Borneo revealed that 58% of blood samples from people that had been diagnosed with P. malariae, were actually infected with P. knowlesi after detection by PCR (Singh et al., 2004). These findings have led people to consider P. knowlesi to be the fifth human malaria parasite (White, 2008; Collins, 2012). This example indicates that care should be taken when screening for Plasmodium by standard blood smears or rapid diagnostic tests, which will not reveal if a person is infected with ape Plasmodium.

In recent years the diversity and origin of malaria parasites has been studied in detail using advanced molecular techniques (Krief et al., 2010; Liu et al., 2010; Baron et al., 2011; Prugnolle et al., 2011). In several reviews on this topic the potential risk of a parasite exchange between NHPs and humans has been identified (Kevin, 2009; Rayner et al., 2011; Duval and Ariey, 2012). The authors of these studies suggest that: (a) Humans living near wild-ape communities should be tested for zoonotic infections using molecular approaches capable of differentiating between human and zoonotic parasites, (b) Wild NHPs should be screened for P. vivax, P. malariae, and P. ovale, because the evidence for cross-transmission is the strongest for these Plasmodium species, and (c). Mosquito species should be identified that could transmit Plasmodium parasites between NHPs and humans. Techniques for screening for Plasmodium parasites in humans and NHPs have advanced in recent years and have been applied in some of the studies on NHP Plasmodium mentioned above. The identification of mosquito species that are likely to transmit Plasmodium parasites between NHPs and humans has received little attention and will be discussed below.

Mosquitoes play a key role in the transmission of Plasmodium parasites between humans. Mosquito species characteristics will therefore influence the Plasmodium transmission between humans and NHPs. Transmission studies with malaria vectors have mainly focused on those mosquito species that transmit Plasmodium between humans. Mosquito species that are likely to facilitate a cross-species exchange of Plasmodium have occasionally been studied for their capability of transmitting P. knowlesi in Asia (Collins, 2012). Such studies have not been done in Africa, and consequently knowledge about the role of African mosquitoes as Plasmodium bridge vectors is lacking (Figure 1).

In 2007 the Bill and Melinda Gates Foundation, followed by the World Health Organization (WHO) and the Roll Back Malaria (RBM) Partnership declared that the paradigm of malaria control and elimination has been extended to encompass an ultimate goal of malaria eradication (Roberts and Enserink, 2007; Roll Back Malaria Partnership, 2008; Alonso et al., 2011). Since that declaration the discussion on the probability of malaria eradication has intensified (Roberts and Enserink, 2007; Greenwood, 2008; Ferguson et al., 2010; Kappe et al., 2010; Alonso et al., 2011; The malERA Consultative Group on Vector Control, 2011). However, in 2010 there were still an estimated 216 million human cases of malaria and 655,000 deaths and the consequences of malaria may decrease gross domestic product by as much as 1.3% (WHO, 2011).

The possibility that NHPs act as a reservoir for human Plasmodium or are a source of NHP Plasmodium that may affect human health should be investigated before malaria eradication is considered. Current vector control efforts are focused on human habitats, mainly because the most important vector of human malaria A. gambiae s.s. is highly anthropophilic and found only around human settlements (Costantini et al., 1998; Takken and Knols, 1999; Pates et al., 2001). In the process of malaria elimination in any country, emphasis is often laid on monitoring parasite prevalence in humans. The case of P. knowlesi has shown that conventional methods of screening for Plasmodium parasites will not reveal human infections with NHP Plasmodia and therefore humans living near wild-ape communities will need more detailed testing to detect these parasites (Kevin, 2009; Rayner et al., 2011).

The significance of NHPs as a potential source for human infection will largely depend on the vector species that transmit Plasmodium between apes, and whether their behavior facilitates transmission to humans. By understanding how mosquito species are attracted to NHPs, and using this knowledge to identify the vectors that may transmit Plasmodium between apes and humans, we can understand the zoonotic potential of NHP Plasmodium parasites. Identification of the bacterial volatiles that specifically attract mosquitoes that may form a bridge between humans and NHPs may lead to the development of selective odor-baited mosquito traps (Mukabana et al., 2012). These traps can be used for monitoring or mass trapping of mosquito species that facilitate such a cross-species exchange of Plasmodium parasites (Figure 3). Detailed screening for Plasmodium parasites and trapping of vectors in areas where humans and NHPs coexist will help to focus on critical areas that should receive additional interventions when attempting to eliminate or eradicate malaria.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.