Landscape drives zoonotic malaria prevalence in non-human primates

Abstract

Land conversion is understood to increase the risk of emergent zoonotic diseases. In simians and humans, infection risk has been linked to fragmented habitats. However, the role of fragmentation on disease dynamics in wildlife hosts is rarely quantified at macroecological scales due to the lack of systematic surveys. In Southeast Asia, non-human primates (NHPs) host Plasmodium knowlesi, a prominent zoonotic malaria. We examine reported primate P. knowlesi to investigate how landscape impacts parasite prevalence. Firstly, we conducted a meta-analysis of NHP P. knowlesi prevalence. Overall prevalence was 9.6% (CI95% 6.3-13.4), with considerable regional heterogeneity (I2=96.6%; CI95% 95.7-97.3) and high estimates in Borneo (52.4%, CI95% 22.8-81.3). Higher prevalence in NHPs shows clear spatial overlap with human infection foci. Secondly, environmental covariates were assembled from remote sensing data and statistical models were fitted to prevalence at multiple spatial scales. We demonstrate a strong relationship between forest fragmentation (20km, p<0.0001) and P. knowlesi in NHPs, suggesting that zoonotic malaria prevalence is maximised at intermediate levels of habitat complexity. Findings indicate a previously hypothesised trade-off between epidemiological and ecological mechanisms determining P. knowlesi infection in wildlife reservoirs, and that parasite prevalence in NHPs may be a key driver of human spillover risk.

The threat of increased transmission of non-knowlesi zoonotic malaria in humans: a systematic review

“…Infected mosquitoes must bite humans for zoonotic Plasmodium species to infect them. This necessitates being close to an infectious vector, which is often linked to shifts in land use, occupation and housing design (Ramasamy, 2014 ; Johnson et al ., 2022 ). Additionally, humans and vectors that readily prey on humans and reservoir animals must be in proximity to the reservoir hosts or wildlife that harbours parasites.…”

No evidence of sustained nonzoonotic Plasmodium knowlesi transmission: estimating species-specific spatiotemporally varying reproduction numbers for malaria in Malaysia

“…Other potential sources include asymptomatic or unreported infections. However, given the high coverage of the Malaysian surveillance system, infrequency and low parasite density of asymptomatic human P. knowlesi infections [34,35] and widespread distribution of infected simian reservoirs [14], unobserved infections would appear to be mostly from zoonotic sources. As higher rates of low density, asymptomatic P. knowlesi infections have been reported in people residing near clinical cases, further studies are needed to identify whether peri-domestic, or localised nonzoonotic P. knowlesi transmission is occurring but not detected by clinical surveillance systems [34].…”

“…Evidence suggests P. knowlesi infections are typically chronic with low-level parasitemias in long-tailed macaques (Macaca fascicularis), the main reservoir [13]. The spatial distribution of human cases mirrors P. knowlesi infection rates in macaques, with the highest infection rates in humans and macaques reported in Malaysian Borneo [14]. The feasibility of human-mosquitohuman transmission of P. knowlesi has been demonstrated once experimentally in a laboratory study [15] but has not been formally described in natural settings.…”

Primate malaria of human importance

“…In addition to this, a significant relationship between deforestation (20 km, P < 0.0001) and P. knowlesi in monkeys has been demonstrated which suggest that monkey malaria prevalence is high at areas which have increased contact with humans. [ 74 ] Another school of thought is that there is a presence of some amount of cross-reactive immunity between P. vivax , P. knowlesi , and P. cynomolgi , and with reduced incidence of human malaria due to the malaria elimination program, the cross-reactive immunity may also have declined, thereby causing an increased incidence of zoonotic malaria. If this hypothesis holds true, then a vaccine against P. vivax malaria could provide cross-reactive immunity to other zoonotic malaria infections in future.…”