Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes fatal encephalitis in humans. The initial outbreak of NiV infection occurred in Malaysia and Singapore in 1998-1999; relatively small, sporadic outbreaks among humans have occurred in Bangladesh since 2001. We characterized the complete genomic sequences of identical NiV isolates from 2 patients in 2008 and partial genomic sequences of throat swab samples from 3 patients in 2010, all from Bangladesh. All sequences from patients in Bangladesh comprised a distinct genetic group. However, the detection of 3 genetically distinct sequences from patients in the districts of Faridpur and Gopalganj indicated multiple co-circulating lineages in a localized region over a short time (January-March 2010). Sequence comparisons between the open reading frames of all available NiV genes led us to propose a standardized protocol for genotyping NiV; this protcol provides a simple and accurate way to classify current and future NiV sequences.
Deaths from Plasmodium knowlesi malaria have been linked to delayed parenteral treatment. In Malaysia, early intravenous artesunate is now recommended for all severe malaria cases. We describe P. knowlesi fatalities in Sabah, Malaysia, during 2012-2014 and report species-specific fatality rates based on 2010-2014 case notifications. Sixteen malaria-associated deaths (caused by PCR-confirmed P. knowlesi [7], P. falciparum [7], and P. vivax [1] and microscopy-diagnosed "P. malariae" [1]) were reported during 2012-2014. Six patients with severe P. knowlesi malaria received intravenous artesunate at hospital admission. For persons ≥15 years of age, overall fatality rates during 2010-2014 were 3.4, 4.2, and 1.0 deaths/1,000 P. knowlesi, P. falciparum, and P. vivax notifications, respectively; P. knowlesi-associated fatality rates fell from 9.2 to 1.6 deaths/1,000 notifications. No P. knowlesi-associated deaths occurred among children, despite 373 notified cases. Although P. knowlesi malaria incidence is rising, the notification-fatality rate has decreased, likely due to improved use of intravenous artesunate.
Macacine herpesvirus 1 (MaHV1; B virus) naturally infects macaques (Macaca spp.) and can cause fatal encephalitis in humans. In Peninsular Malaysia, wild macaques are abundant, and translocation is used to mitigate human-macaque conflict. Most adult macaques are infected with MaHV1, although the risk for transmission to persons who handle them during capture and translocation is unknown. We investigated MaHV1 shedding among 392 long-tailed macaques (M. fascicularis) after capture and translocation by the Department of Wildlife and National Parks in Peninsular Malaysia, during 2009-2011. For detection of MaHV1 DNA, PCR was performed on urogenital and oropharyngeal swab samples. Overall, 39% of macaques were shedding MaHV1 DNA; rates of DNA detection did not differ between sample types. This study demonstrates that MaHV1 was shed by a substantial proportion of macaques after capture and transport and suggests that persons handling macaques under these circumstances might be at risk for exposure to MaHV1.
During November 2012-July 2013, a marked increase of adenovirus type 7 (Ad7) infections associated with severe disease was documented among pediatric patients in Singapore. Phylogenetic analysis revealed close genetic links with severe Ad7 outbreaks in China, Taiwan, and other parts of Asia.
Most malaria in Malaysia is caused by Plasmodium knowlesi parasites through zoonotic infection from macaque reservoir hosts. We obtained genome sequences from 28 clinical infections in Peninsular Malaysia to clarify the emerging parasite population structure and test for evidence of recent adaptation. The parasites all belonged to a major genetic population of P. knowlesi (cluster 3) with high genomewide divergence from populations occurring in Borneo (clusters 1 and 2). We also observed unexpected local genetic subdivision; most parasites belonged to 2 subpopulations sharing a high level of diversity except at particular genomic regions, the largest being a region of chromosome 12, which showed evidence of recent directional selection. Surprisingly, we observed a third subpopulation comprising P. knowlesi infections that were almost identical to each other throughout much of the genome, indicating separately maintained transmission and recent genetic isolation. Each subpopulation could evolve and present a broader health challenge in Asia.
We report the transmission dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across different settings in Brunei. An initial cluster of SARS-CoV-2 cases arose from 19 persons who had attended the Tablighi Jama'at gathering in Malaysia, resulting in 52 locally transmitted cases. The highest nonprimary attack rates (14.8%) were observed from a subsequent religious gathering in Brunei and in households of attendees (10.6%). Household attack rates from symptomatic case-patients were higher (14.4%) than from asymptomatic (4.4%) or presymptomatic (6.1%) case-patients. Workplace and social settings had attack rates of <1%. Our analyses highlight that transmission of SARS-CoV-2 varies depending on environmental, behavioral, and host factors. We identify red flags for potential superspreading events, specifically densely populated gatherings with prolonged exposure in enclosed settings, persons with recent travel history to areas with active SARS-CoV-2 infections, and group behaviors. We propose differentiated testing strategies to account for differing transmission risk.
We detected the simian malaria parasites Plasmodium knowlesi, P. cynomolgi, P. inui, P. coatneyi, P. inui-like, and P. simiovale among forest fringe-living indigenous communities from various locations in Malaysia. Our findings underscore the importance of using molecular tools to identify newly emergent malaria parasites in humans.
We detected 2 natural, asymptomatic Plasmodium inui monoinfections in humans in Malaysia by using nested PCR on concentrated high-volume blood samples. We found a P. inui-positive Anopheles cracens mosquito in the same site as the human infections. Investigators should use ultrasensitive detection methods to identify simian malaria parasite transmission in humans.
We report human infection with simian Plasmodium cynomolgi in a tourist from Denmark who had visited forested areas in peninsular Malaysia and Thailand in August and September 2018. Because P. cynomolgi may go unnoticed by standard malaria diagnostics, this malaria species may be more common in humans than was previously thought.
We conducted an in-depth characterization of the Nipah virus (NiV) isolate previously obtained from a Pteropus lylei bat in Cambodia in 2003 (CSUR381). We performed full-genome sequencing and phylogenetic analyses and confirmed CSUR381 is part of the NiV-Malaysia genotype. In vitro studies revealed similar cell permissiveness and replication of CSUR381 (compared with 2 other NiV isolates) in both bat and human cell lines. Sequence alignments indicated conservation of the ephrin-B2 and ephrin-B3 receptor binding sites, the glycosylation site on the G attachment protein, as well as the editing site in phosphoprotein, suggesting production of nonstructural proteins V and W, known to counteract the host innate immunity. In the hamster animal model, CSUR381 induced lethal infections. Altogether, these data suggest that the Cambodia bat-derived NiV isolate has high pathogenic potential and, thus, provide insight for further studies and better risk assessment for future NiV outbreaks in Southeast Asia.
Multilocus microsatellite genotyping of Plasmodium knowlesi isolates previously indicated 2 divergent parasite subpopulations in humans on the island of Borneo, each associated with a different macaque reservoir host species. Geographic divergence was also apparent, and independent sequence data have indicated particularly deep divergence between parasites from mainland Southeast Asia and Borneo. To resolve the overall population structure, multilocus microsatellite genotyping was conducted on a new sample of 182 P. knowlesi infections (obtained from 134 humans and 48 wild macaques) from diverse areas of Malaysia, first analyzed separately and then in combination with previous data. All analyses confirmed 2 divergent clusters of human cases in Malaysian Borneo, associated with long-tailed macaques and pig-tailed macaques, and a third cluster in humans and most macaques in peninsular Malaysia. High levels of pairwise divergence between each of these sympatric and allopatric subpopulations have implications for the epidemiology and control of this zoonotic species.
During 2005, 764 children were brought to a large children's hospital in Ho Chi Minh City, Vietnam, with a diagnosis of hand, foot, and mouth disease. All enrolled children had specimens (vesicle fluid, stool, throat swab) collected for enterovirus isolation by cell culture. An enterovirus was isolated from 411 (53.8%) of the specimens: 173 (42.1%) isolates were identified as human enterovirus 71 (HEV71) and 214 (52.1%) as coxsackievirus A16. Of the identified HEV71 infections, 51 (29.5%) were complicated by acute neurologic disease and 3 (1.7%) were fatal. HEV71 was isolated throughout the year, with a period of higher prevalence in October-November. Phylogenetic analysis of 23 HEV71 isolates showed that during the first half of 2005, viruses belonging to 3 subgenogroups, C1, C4, and a previously undescribed subgenogroup, C5, cocirculated in southern Vietnam. In the second half of the year, viruses belonging to subgenogroup C5 predominated during a period of higher HEV71 activity.
Population genetic analysis revealed that Plasmodium knowlesi infections in Malaysian Borneo are caused by 2 divergent parasites associated with long-tailed (cluster 1) and pig-tailed (cluster 2) macaques. Because the transmission ecology is likely to differ for each macaque species, we developed a simple genotyping PCR to efficiently distinguish between and survey the 2 parasite subpopulations. This assay confirmed differences in the relative proportions in areas of Kapit division of Sarawak state, consistent with multilocus microsatellite analyses. Analyses of 1,204 human infections at Kapit Hospital showed that cluster 1 caused approximately two thirds of cases with no significant temporal changes from 2000 to 2018. We observed an apparent increase in overall numbers in the most recent 2 years studied, driven mainly by increased cluster 1 parasite infections. Continued monitoring of the frequency of different parasite subpopulations and correlation with environmental alterations are necessary to determine whether the epidemiology will change substantially.
To monitor the incidence of Plasmodium knowlesi infections and determine whether other simian malaria parasites are being transmitted to humans, we examined 1,047 blood samples from patients with malaria at Kapit Hospital in Kapit, Malaysia, during June 24, 2013-December 31, 2017. Using nested PCR assays, we found 845 (80.6%) patients had either P. knowlesi monoinfection (n = 815) or co-infection with other Plasmodium species (n = 30). We noted the annual number of these zoonotic infections increased greatly in 2017 (n = 284). We identified 6 patients, 17-65 years of age, with P. cynomolgi and P. knowlesi co-infections, confirmed by phylogenetic analyses of the Plasmodium cytochrome c oxidase subunit 1 gene sequences. P. knowlesi continues to be a public health concern in the Kapit Division of Sarawak, Malaysian Borneo. In addition, another simian malaria parasite, P. cynomolgi, also is an emerging cause of malaria in humans.
We tested a sample of 234 wild long-tailed macaques (Macaca fascicularis) trapped in Peninsular Malaysia in 2009, 2010, and 2016 for Zika virus RNA and antibodies. None were positive for RNA, and only 1.3% were seropositive for neutralizing antibodies. Long-tailed macaques are unlikely to be reservoirs for Zika virus in Malaysia.
A strategic multilateral dialogue related to biosecurity risks in Southeast Asia, established in 2014, now includes participants from Singapore, Malaysia, Indonesia, Thailand, Philippines, and the United States. This dialogue is conducted at the nonministerial level, enabling participants to engage without the constraints of operating in their official capacities. Participants reflect on mechanisms to detect, mitigate, and respond to biosecurity risks and highlight biosecurity issues for national leadership. Participants have also identified factors to improve regional and global biosecurity, including improved engagement and collaboration across relevant ministries and agencies, sustainable funding for biosecurity programs, enhanced information sharing for communicable diseases, and increased engagement in international biosecurity forums.
After orangutans in Indonesia were reported as infected with Plasmodium cynomolgi and P. vivax, we conducted phylogenetic analyses of small subunit ribosomal RNA gene sequences of Plasmodium spp. We found that these orangutans are not hosts of P. cynomolgi and P. vivax. Analysis of >or=1 genes is needed to identify Plasmodium spp. infecting orangutans.