Figure 1 - available via license: Creative Commons Attribution 4.0 International
Content may be subject to copyright.
Peninsular Malaysia map showing states (divided into administrative levels of district) and federal territories.
Source publication
The life-threatening zoonotic malaria cases caused by Plasmodium knowlesi in Malaysia has recently been reported to be the highest among all malaria cases; however, previous studies have mainly focused on the transmission of P. knowlesi in Malaysian Borneo (East Malaysia). This study aimed to describe the transmission patterns of P. knowlesi infect...
Contexts in source publication
Context 1
... study area primarily focused on Peninsular Malaysia which spreads from latitude 1 • 15 50.0 N to 6 • 43 36 N and from longitude 99 • 35 E to 104 • 36 E. Peninsular Malaysia covers a land area of 13.21 million hectares (Figure 1) [18]. Forested areas account for approximately 5.76 million hectares, which is equivalent to 43.6% of the land area of Peninsular Malaysia [18]. ...
Context 2
... mean daily temperature ranges from 25 to 28 °C. Peninsular Malaysia is divided into 11 states (Perlis, Kedah, Pulau Pinang, Perak, Selangor, Negeri Sembilan, Melaka, Johor, Kelantan, Terengganu, and Pahang) and 2 federal territories (Kuala Lumpur and Putrajaya) (Figure 1). Approximately 24.7% of the population of Peninsular Malaysia reside in sub-urban and rural areas. ...
Context 3
... indigenous malaria case is a case contracted locally with no evidence of importation and no direct link to transmission from an imported case, whereas an imported malaria is a case in which the infection was acquired outside the area in which it was diagnosed [22]. The case Peninsular Malaysia is divided into 11 states (Perlis, Kedah, Pulau Pinang, Perak, Selangor, Negeri Sembilan, Melaka, Johor, Kelantan, Terengganu, and Pahang) and 2 federal territories (Kuala Lumpur and Putrajaya) (Figure 1). Approximately 24.7% of the population of Peninsular Malaysia reside in sub-urban and rural areas. ...
Context 4
... number of indigenous P. knowlesi cases was apparently higher than other indigenous human malaria cases (P. malariae, P. falciparum, and P. vivax) in most years except 2011 and 2016 ( Figure A1). Although fewer females were infected with P. knowlesi as compared to males, female patients (median 39 years, interquartile range 23-52 years) were generally older than the males (median 34 years, interquartile range 25.5-45 years). ...
Citations
... This highlights the complexity of zoonotic transmission to humans as different species may vary in transmissibility, exposure and susceptibility to humans. Spatial analysis of P. knowlesi human cases in Peninsular Malaysia from 2011-2018 revealed that P. knowlesi cases tended to cluster around the Kelantan-Pahang border, particularly in the Gua Musang (Kelantan) and Kuala Lipis (Pahang) districts [25]. Here we report a P. knowlesi macaque prevalence of 19.4% and 61.6% for Kelantan and Pahang, respectively. ...
The parasite Plasmodium knowlesi has been the sole cause of malaria in Malaysia from 2018–2022. Due to the high burden of P. knowlesi in Malaysia, this has hampered Malaysia from achieving the malaria-free status awarded by the World Health Organisation (WHO). Due to the zoonotic nature of P. knowlesi infections, it is important to study the prevalence of the parasite in the macaque host, the long-tailed macaque ( Macaca fascicularis ). Apart from P. knowlesi , the long-tailed macaque is also able to harbour Plasmodium cynomolgi, Plasmodium inui, Plasmodium caotneyi and Plasmodium fieldi. Here we report the prevalence of the 5 simian malaria parasites in the wild long-tailed macaque population in 12 out of the 13 states in Peninsular Malaysia using a nested PCR approach targeting the 18s ribosomal RNA (18s rRNA) gene. It was found that all five Plasmodium species were widely distributed throughout Peninsular Malaysia except for states with major cities such as Kuala Lumpur and Putrajaya. Of note, Pahang reported a malaria prevalence of 100% in the long-tailed macaque population, identifying it as a potential hotspot for zoonotic transmission. Overall, this study shows the distribution of the 5 simian malaria parasite species throughout Peninsular Malaysia, the data of which could be used to guide future malaria control interventions to target zoonotic malaria.
... Furthermore, the influx of migrant workers from malaria-endemic countries and challenges of drug resistance have exacerbated the risk of re-emergence of the disease. Due to the large-scale clearing of forest areas for logging and agricultural purposes, Malaysia faces the problem of increasing cases of simian malaria driven by the migration of macaques to human settlements, particularly in the remote areas where the aboriginal populations live [3,5,8,10]. Although Malaysia has been recognized as one of the countries free from indigenous human malaria since 2018 [1], it is essential to acknowledge the prevalence of non-human malaria and strengthen the effectiveness of the national elimination program. ...
Malaria remains a public health problem in many parts of the world, including Malaysia. Although Malaysia has been recognized as one of the countries free from indigenous human malaria since 2018, the rising trend of zoonotic malaria, particularly Plasmodium knowlesi cases, poses a threat to public health and is of great concern to the country’s healthcare system. We reviewed previously scattered information on zoonotic malaria infections in both Peninsular Malaysia and Malaysian Borneo to determine the epidemiology and distribution of emerging zoonotic malaria infections. Given the high prevalence of zoonotic malaria in Malaysia, efforts should be made to detect zoonotic malaria in humans, mosquito vectors, and natural hosts to ensure the success of the National Malaria Elimination Strategic Plan.
... From 2011 to 2019, 36.6% (189) of all malaria cases reported in Johor were caused by P. knowlesi. As the human malaria cases reduced over the years, the cases of P. knowlesi malaria have increased in Peninsular Malaysia [31]. Thus, the distribution and bionomics of simian malaria vectors are significant aspects required for zoonotic malaria prevention. ...
... This kind of landscape provides clean and suitable water bodies for the breeding of the Anopheles mosquitoes. Based on previous studies [31,41,42], the current results concur that people working in the jungle like police or army and people involved in the agricultural sector were more likely to be exposed to the infection than other occupations. The number of males infected with knowlesi malaria was higher than the female because of their type of profession. ...
Background
Plasmodium knowlesi, a simian malaria parasite infection, increases as Plasmodium falciparum and Plasmodium vivax infections decrease in Johor, Malaysia. Therefore, this study aimed to identify the distribution of vectors involved in knowlesi malaria transmission in Johor. This finding is vital in estimating hotspot areas for targeted control strategies.
Methods
Anopheles mosquitoes were collected from the location where P. knowlesi cases were reported. Cases of knowlesi malaria from 2011 to 2019 in Johor were analyzed. Internal transcribed spacers 2 ( ITS2 ) and cytochrome c oxidase subunit I ( COI ) genes were used to identify the Leucosphyrus Group of Anopheles mosquitoes. In addition, spatial analysis was carried out on the knowlesi cases and vectors in Johor.
Results
One hundred and eighty-nine cases of P. knowlesi were reported in Johor over 10 years. Young adults between the ages of 20–39 years comprised 65% of the cases. Most infected individuals were involved in agriculture and army-related occupations (22% and 32%, respectively). Four hundred and eighteen Leucosphyrus Group Anopheles mosquitoes were captured during the study. Anopheles introlatus was the predominant species, followed by Anopheles latens . Spatial analysis by Kriging interpolation found that hotspot regions of P. knowlesi overlapped or were close to the areas where An. introlatus and An. latens were found. A significantly high number of vectors and P. knowlesi cases were found near the road within 0–5 km.
Conclusions
This study describes the distribution of P. knowlesi cases and Anopheles species in malaria-endemic transmission areas in Johor. Geospatial analysis is a valuable tool for studying the relationship between vectors and P. knowlesi cases. This study further supports that the Leucosphyrus Group of mosquitoes might be involved in transmitting knowlesi malaria cases in Johor. These findings may provide initial evidence to prioritize diseases and vector surveillance.
Background:
The elimination of malaria in Southeast Asia has become more challenging as a result of rising knowlesi malaria cases. In addition, naturally occurring human infections with other zoonotic simian malaria caused by Plasmodium cynomolgi and Plasmodium inui adds another level of complexity in malaria elimination in this region. Unfortunately, data on vectors which are responsible for transmitting this zoonotic disease is very limited.
Methodology/principal findings:
We conducted longitudinal studies to investigate the entomological parameters of the simian malaria vectors and to examine the genetic diversity and evolutionary pattern of their simian Plasmodium. All the captured Anopheles mosquitoes were dissected to examine for the presence of oocysts, sporozoites and to determine the parous rate. Our study revealed that the Anopheles Leucosphyrus Group mosquitoes are highly potential competent vectors, as evidenced by their high rate of parity, survival and sporozoite infections in these mosquitoes. Thus, these mosquitoes represent a risk of human infection with zoonotic simian malaria in this region. Haplotype analysis on P. cynomolgi and P. inui, found in high prevalence in the Anopheles mosquitoes from this study, had shown close relationship between simian Plasmodium from the Anopheles mosquitoes with its vertebrate hosts. This directly signifies the ongoing transmission between the vector, macaques, and humans. Furthermore, population genetic analysis showed significant negative values which suggest that both Plasmodium species are undergoing population expansion.
Conclusions/significance:
With constant microevolutionary processes, there are potential for both P. inui and P. cynomolgi to emerge and spread as a major public health problem, following the similar trend of P. knowlesi. Therefore, concerted vector studies in other parts of Southeast Asia are warranted to better comprehend the transmission dynamics of this zoonotic simian malaria which eventually would aid in the implementation of effective control measures in a rapidly changing environment.
The emergence of potentially life-threatening zoonotic malaria caused by Plasmodium knowlesi nearly two decades ago has continued to challenge Malaysia healthcare. With a total of 376 P. knowlesi infections notified in 2008, the number increased to 2,609 cases in 2020 nationwide. Numerous studies have been conducted in Malaysian Borneo to determine the association between environmental factors and knowlesi malaria transmission. However, there is still a lack of understanding of the environmental influence on knowlesi malaria transmission in Peninsular Malaysia. Therefore, our study aimed to investigate the ecological distribution of human P. knowlesi malaria in relation to environmental factors in Peninsular Malaysia. A total of 2,873 records of human P. knowlesi infections in Peninsular Malaysia from 1st January 2011 to 31st December 2019 were collated from the Ministry of Health Malaysia and geolocated. Three machine learning-based models, maximum entropy (MaxEnt), extreme gradient boosting (XGBoost), and ensemble modeling approach, were applied to predict the spatial variation of P. knowlesi disease risk. Multiple environmental parameters including climate factors, landscape characteristics, and anthropogenic factors were included as predictors in both predictive models. Subsequently, an ensemble model was developed based on the output of both MaxEnt and XGBoost. Comparison between models indicated that the XGBoost has higher performance as compared to MaxEnt and ensemble model, with AUCROC values of 0.933 ± 0.002 and 0.854 ± 0.007 for train and test datasets, respectively. Key environmental covariates affecting human P. knowlesi occurrence were distance to the coastline, elevation, tree cover, annual precipitation, tree loss, and distance to the forest. Our models indicated that the disease risk areas were mainly distributed in low elevation (75–345 m above mean sea level) areas along the Titiwangsa mountain range and inland central-northern region of Peninsular Malaysia. The high-resolution risk map of human knowlesi malaria constructed in this study can be further utilized for multi-pronged interventions targeting community at-risk, macaque populations, and mosquito vectors.
Plasmodium knowlesi infections in Malaysia are a new threat to public health and to the national efforts on malaria elimination. In the Kapit division of Sarawak, Malaysian Borneo, two divergent P. knowlesi subpopulations (termed Cluster 1 and Cluster 2) infect humans and are associated with long-tailed macaque and pig-tailed macaque hosts, respectively. It has been suggested that forest-associated activities and environmental modifications trigger the increasing number of knowlesi malaria cases. Since there is a steady increase of P. knowlesi infections over the past decades in Sarawak, particularly in the Kapit division, we aimed to identify hotspots of knowlesi malaria cases and their association with forest activities at a geographical scale using the Geographic Information System (GIS) tool. A total of 1064 P. knowlesi infections from 2014 to 2019 in the Kapit and Song districts of the Kapit division were studied. Overall demographic data showed that males and those aged between 18 and 64 years old were the most frequently infected (64%), and 35% of infections involved farming activities. Thirty-nine percent of Cluster 1 infections were mainly related to farming surrounding residential areas while 40% of Cluster 2 infections were associated with activities in the deep forest. Average Nearest Neighbour (ANN) analysis showed that humans infected with both P. knowlesi subpopulations exhibited a clustering distribution pattern of infection. The Kernel Density Analysis (KDA) indicated that the hotspot of infections surrounding Kapit and Song towns were classified as high-risk areas for zoonotic malaria transmission. This study provides useful information for staff of the Sarawak State Vector-Borne Disease Control Programme in their efforts to control and prevent zoonotic malaria.
Background
The aim of Malaysia to eliminate malaria nationwide by 2020 seems need to be prolonged. Whilst Malaysia has successfully eliminated human malaria transmission, simian malaria parasites such as Plasmodium knowlesi , P . cynomolgi , P . inui and P . cynomolgi are the emerging cause of malaria in humans. The epidemiological study of simian malaria in primates provides useful information in identifying the risk of human-macaques Plasmodium infection.
Methodology/Principal findings
This study was performed to gather all available data in terms of simian malaria epidemiology study among macaques in Malaysia over the last two decades. This systematic review was conducted according to the PRISMA guidelines to select appropriate articles as references. Data searches were performed through international databases such as Google Scholar, PubMed, CrossRef, Scopus, Web of Science and Science Direct for original articles published from 2000 until 2021. The review identified seven simian malaria epidemiology studies in Malaysia over the 20-year study period. Most studies were conducted in Peninsular Malaysia (5/7; 71%) followed by East Malaysia (2/7; 29%). All studies showed positive detection of Plasmodium parasites in macaques. The most prevalent Plasmodium species in macaques was P . inui (49.27%) and the least prevalent was P . fieldi (4.76%). The prevalence of simian malaria was higher in East Malaysia compared to Peninsular Malaysia. The mono, dual and triple infection types were the most common among macaques.
Conclusion/Significance
The non-human primates like macaques are the reservoir of simian plasmodium in Malaysia. Hence, the study of host epidemiology is an important insight to public health management as there is a high occurrence of simian malaria in Malaysia. The right measurement can be taken as well to prevent the transmission of simian malaria from macaques to humans.
Objectives:
To characterise the state-wide epidemiology of indigenous knowlesi malaria in Sarawak from 2011 to 2019.
Methods:
Longitudinal retrospective study was conducted based on Sarawak knowlesi malaria surveillance data recorded from 2011-2019. Only indigenous cases were included and information extracted for analysis comprised age, sex, occupation, ethnicity, case severity, hospital admission and parasite density.
Results:
Over the 9 years, 8473 indigenous knowlesi malaria cases were recorded. Age group 40-49 years, males, plantation workers and Iban communities recorded the highest percentage of cases in each demographic variable. Most of the cases were uncomplicated (n = 7292; 86.1%) and 89.6% (n = 7589) of the total cases were reported with ≤20 000 parasites/μl of blood. Age group and ethnic group are associated with the severity of knowlesi malaria in Sarawak. Multivariable logistic regression indicated that the age group 60+ years had the highest odds of developing severe knowlesi malaria compared with other age groups (AOR 2.48; 95% CI 1.22, 5.02; p = 0.012). Bidayuh patients were more likely to develop severe knowlesi malaria than Ibans, the largest ethnic group among knowlesi malaria patients (AOR 1.97; 95% CI 1.31, 2.97; p = 0.001).
Conclusions:
Identification of risk groups is important for the implementation of prevention programs and treatments targeting at specific group to combat knowlesi malaria effectively.
Plasmodium knowlesi is a zoonotic malaria parasite that has gained increasing medical interest over the past two decades. This zoonotic parasitic infection is prevalent in Southeast Asia and causes many cases with fulminant pathology. Despite several biogeographical restrictions that limit its distribution, knowlesi malaria cases have been reported in different parts of the world due to travelling and tourism activities. Here, breakthroughs and key information generated from recent (over the past five years, but not limited to) studies conducted on P. knowlesi were reviewed, and the knowledge gap in various research aspects that need to be filled was discussed. Besides, challenges and strategies required to control and eradicate human malaria with this emerging and potentially fatal zoonosis were described.
