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Increasing Incidence of Plasmodium Knowlesi Malaria Following Control of P Increasing incidence of Plasmodium knowlesi malaria following control of P. falciparum malaria in Sabah, Malaysia Bridget Barber1,2, Timothy William1,3, Jenarun Jelip3, Hasan Rahman3, Yusof Ibrahim3, Jayaram Menon1,3, Matthew Grigg1,2, Tsin Yeo2, Nicholas Anstey2 1. Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia, 2. Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia, 3. Department of Health, Kota Kinabalu, Sabah, Malaysia Background • The increase in P. malariae/P. knowlesi notifications occurred state-wide, appearing to have begun initially in the Interior Division, in the southwest of the state adjacent to • Malaysia aims to eliminate malaria by 2020 [1]. However, the simian parasite Sarawak, and progressed north-easterly to the Kudat Division. Plasmodium knowlesi is now a common cause of human malaria in the eastern states of Sarawak and Sabah [2-4], and threatens the prospect of malaria elimination. Figure 2. Map showing districts and divisions of • Little is known about the emergence of P. knowlesi over time, particularly in Sabah, Sabah, with bar graphs showing annual P. mainly because of misreporting of P. knowlesi as P. malariae due to their microscopic malariae/P. knowlesi notifications, by division, near-identity from 2001-2011 • We therefore reviewed the Sabah Department of Health malaria notification records to investigate the trend of each malaria species over time, and in particular to determine if P. knowlesi represents an emerging infection in humans. Methods • Reporting of microscopy-diagnosed malaria cases in Sabah is mandatory • We reviewed all available Department of Health malaria notification records, including (i) annual notifications by species and by district from 1992-2011, and (ii) epidemiological characteristics of patients from 2007-2011 • Notifications of P. malariae and P. knowlesi were considered as a single group Results • P. falciparum notifications peaked at 33,153 in 1994 and decreased 55-fold to 605 in 2011 • P. vivax peaked at 15,857 in 1995 and decreased 25-fold to 628 in 2011 • P. malariae/P. knowlesi notifications peaked at 614 in 1994, then decreased to ≈100/year in the late 1990s/early 2000s • P. malariae/P. knowlesi notifications increased >10-fold between 2004 (n=59) and 2011 Males (N=1686) Females (N=495) (n=703), while P. falciparum continued to decrease • Patients with P. malariae/P. knowlesi were older 8 • The incidence of P. malariae/P. knowlesi increased from ≈0.2-0.4/1000 people/year than those with P. falciparum or P. vivax (median during 2000-2006 to 0.21/1000 people in 2011 ages 31, 23 and 23 years respectively, p=0.001). 6 • In 1992 P. falciparum, P. vivax and P. malariae/P. knowlesi monoinfections accounted for • Males with P. malariae/P. knowlesi demonstrated 4 70%, 24% and 1% respectively of total malaria notifications, compared to 30%, 31% and an approximately normal age distribution (mean 2 35% in 2011 and median 33 and 30 years respectively) • Females with P. malariae/P. knowlesi 0 0 10 20 30 40 50 60 70 80 90 100 0 10 20 30 40 50 60 70 80 90 100 Percent of P.malariae/P. knowlesi ofnotifications Percent Figure 1. demonstrated a bimodal age distribution (local Age (years) maxima 9-12 and 50 years). Figure 3. Age distribution of patients with P. malariae/P. knowlesi, 2007-2011 Discussion • Recent studies have demonstrated very low rates of P. malariae in Sabah when PCR methods are used [2,4], hence the large majority of these microscopy-diagnosed P. malariae/P. knowlesi cases are likely to be P. knowlesi. • Our results therefore demonstrate a significant recent increase in incidence of P. knowlesi, following dramatic reduction of the other human malaria species. • This increase is likely due partly to environmental change, particularly deforestation, which has led to increased interaction between humans, monkeys and mosquito vectors, as well as a possible change in vector behaviour or a vector shift. • However the very recent increase in incidence of P.knowlesi, long after the extensive deforestation of the 1970s/1980s, indicates that decreasing rates of P. vivax and P. falciparum are likely to have contributed directly to this trend, possibly as a result of loss of cross- protective immunity. • The finding that P. knowlesi incidence has increased following control of the other malaria species has implications for other countries throughout Southeast Asia where P. knowlesi is known to occur [5]. Furthermore, human-to-human transmission, if not already occurring, may become more likely in Sabah as prevalence increases. • Further research is required to determine risk factors for knowlesi malaria in order that malaria control programs can address the increasing incidence of this species. References 1. Rundi C: Malaria Elimination in Malaysia. Third annual meeting of the Asia Pacific Malaria Elimination Network (APMEN); Kota Kinabalu, Sabah, Malaysia; 2011: Available: http://apmen.org/apmen-iii-meeting-proceedings/. 2. Barber B, William T, Jikal M et al (2011) Plasmodium knowlesi malaria in children. Emerg Infect Dis 17(5): 814- 820. 3. Cox-Singh J, Davis TM, Lee KS et al (2008) Plasmodium knowlesi malaria in humans is widely distributed and potentially life threatening. Clin Infect Dis 46(2): 165-171 4. Joveen-Neoh WF, Chong KL, Wong C et al (2011) Incidence of malaria in the Interior Division of Sabah, Malaysian Borneo, based on nested PCR. J Parasitol Res 2011: DOI: 10.1155/2011/104284. Contact: Bridget Barber, email: [email protected] 5. Kantele A, Sakari Jokiranta, T (2011) Review of cases with the emerging fifth human malaria parasite, Plasmodium knowlesi. Clin Infect Dis 52(11): 1356-1362 .
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