TY - JOUR

T1 - No evidence of sustained nonzoonotic Plasmodium knowlesi transmission in Malaysia from modelling malaria case data

AU - Fornace, Kimberly M.

AU - Topazian, Hillary M.

AU - Routledge, Isobel

AU - Asyraf, Syafie

AU - Jelip, Jenarun

AU - Lindblade, Kim A.

AU - Jeffree, Mohammad Saffree

AU - Ruiz Cuenca, Pablo

AU - Bhatt, Samir

AU - Ahmed, Kamruddin

AU - Ghani, Azra C.

AU - Drakeley, Chris

N1 - Funding Information: This work was funded by the World Health Organisation (WHO). KMF is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant No. 221963/Z/20/Z). S.B., A.G. and H.M.T. acknowledge support from the MRC Centre for Global Infectious Disease Analysis (MR/R015600/1), jointly funded by the UK Medical Research Council (MRC) and the UK Foreign, Commonwealth & Development Office (FCDO), under the MRC/ FCDO Concordat agreement, and also part of the EDCTP2 programme supported by the European Union. HMT and AG are supported by the Wellcome Trust (Grant No. 220900/Z/20/Z). S.B. acknowledges support from the Novo Nordisk Foundation via The Novo Nordisk Young Investigator Award (NNF20OC0059309) and the Danish National Research Foundation via a chair position. S.B. acknowledges support from The Eric and Wendy Schmidt Fund for Strategic Innovation via the Schmidt Polymath Award (G-22-63345). S.B. acknowledges support from the National Institute for Health Research (NIHR) via the Health Protection Research Unit in Modelling and Health Economics. The authors would like to thank the Director General of the Ministry of Health in Malaysia for giving permission to publish this paper. For the purpose of open access, the author has applied a “Creative Commons Attribution (CC BY) licence (where permitted by UKRI, “Open Government Licence” or “Creative Commons Attribution No-derivatives (CC-BY-ND) licence may be stated instead) to any Author Accepted Manuscript version arising. Funding Information: This work was funded by the World Health Organisation (WHO). KMF is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant No. 221963/Z/20/Z). S.B., A.G. and H.M.T. acknowledge support from the MRC Centre for Global Infectious Disease Analysis (MR/R015600/1), jointly funded by the UK Medical Research Council (MRC) and the UK Foreign, Commonwealth & Development Office (FCDO), under the MRC/ FCDO Concordat agreement, and also part of the EDCTP2 programme supported by the European Union. HMT and AG are supported by the Wellcome Trust (Grant No. 220900/Z/20/Z). S.B. acknowledges support from the Novo Nordisk Foundation via The Novo Nordisk Young Investigator Award (NNF20OC0059309) and the Danish National Research Foundation via a chair position. S.B. acknowledges support from The Eric and Wendy Schmidt Fund for Strategic Innovation via the Schmidt Polymath Award (G-22-63345). S.B. acknowledges support from the National Institute for Health Research (NIHR) via the Health Protection Research Unit in Modelling and Health Economics. The authors would like to thank the Director General of the Ministry of Health in Malaysia for giving permission to publish this paper. For the purpose of open access, the author has applied a “Creative Commons Attribution (CC BY) licence (where permitted by UKRI, “Open Government Licence” or “Creative Commons Attribution No-derivatives (CC-BY-ND) licence may be stated instead) to any Author Accepted Manuscript version arising. Publisher Copyright: © 2023, The Author(s).

PY - 2023

Y1 - 2023

N2 - Reported incidence of the zoonotic malaria Plasmodium knowlesi has markedly increased across Southeast Asia and threatens malaria elimination. Nonzoonotic transmission of P. knowlesi has been experimentally demonstrated, but it remains unknown whether nonzoonotic transmission is contributing to increases in P. knowlesi cases. Here, we adapt model-based inference methods to estimate RC, individual case reproductive numbers, for P. knowlesi, P. falciparum and P. vivax human cases in Malaysia from 2012–2020 (n = 32,635). Best fitting models for P. knowlesi showed subcritical transmission (RC < 1) consistent with a large reservoir of unobserved infection sources, indicating P. knowlesi remains a primarily zoonotic infection. In contrast, sustained transmission (RC > 1) was estimated historically for P. falciparum and P. vivax, with declines in RC estimates observed over time consistent with local elimination. Together, this suggests sustained nonzoonotic P. knowlesi transmission is highly unlikely and that new approaches are urgently needed to control spillover risks.

AB - Reported incidence of the zoonotic malaria Plasmodium knowlesi has markedly increased across Southeast Asia and threatens malaria elimination. Nonzoonotic transmission of P. knowlesi has been experimentally demonstrated, but it remains unknown whether nonzoonotic transmission is contributing to increases in P. knowlesi cases. Here, we adapt model-based inference methods to estimate RC, individual case reproductive numbers, for P. knowlesi, P. falciparum and P. vivax human cases in Malaysia from 2012–2020 (n = 32,635). Best fitting models for P. knowlesi showed subcritical transmission (RC < 1) consistent with a large reservoir of unobserved infection sources, indicating P. knowlesi remains a primarily zoonotic infection. In contrast, sustained transmission (RC > 1) was estimated historically for P. falciparum and P. vivax, with declines in RC estimates observed over time consistent with local elimination. Together, this suggests sustained nonzoonotic P. knowlesi transmission is highly unlikely and that new approaches are urgently needed to control spillover risks.

U2 - 10.1038/s41467-023-38476-8

DO - 10.1038/s41467-023-38476-8

M3 - Journal article

C2 - 37263994

AN - SCOPUS:85160942420

VL - 14

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 2945

ER -