Enterovirus 71 (EV71) (genus Enterovirus, family Picornaviridae), a common cause of hand, foot, and mouth disease (HFMD), may also cause severe neurological diseases, such as encephalitis and poliomyelitis-like paralysis. To examine the genetic diversity and rate of evolution of EV71, we have determined and analyzed complete VP1 sequences (891 nucleotides) for 113 EV71 strains isolated in the United States and five other countries from 1970 to 1998. Nucleotide sequence comparisons demonstrated three distinct EV71 genotypes, designated A, B, and C. The genetic variation within genotypes (12% or fewer nucleotide differences) was less than the variation between genotypes (16.5 to 19.7%). Strains of all three genotypes were at least 94% identical to one another in deduced amino acid sequence. The EV71 prototype strain, BrCr-CA-70, isolated in California in 1970, is the sole member of genotype A. Strains isolated in the United States and Australia during the period from 1972 to 1988, a 1994 Colombian isolate, and isolates from a large HFMD outbreak in Malaysia in 1997 are all members of genotype B. Although strains of genotype B continue to circulate in other parts of the world, none have been isolated in the United States since 1988. Genotype C contains strains isolated in 1985 or later in the United States, Canada, Australia, and the Republic of China. The annual rate of evolution within both the B and C genotypes was estimated to be approximately 1.35 x 10(-2) substitutions per nucleotide and is similar to the rate observed for poliovirus. The results indicate that EV71 is a genetically diverse, rapidly evolving virus. Its worldwide circulation and potential to cause severe disease underscore the need for additional surveillance and improved methods to identify EV71 in human disease.
Seven members of a 15-man U.S. military team that had operated in rural Malaysia developed an acute illness consisting of fever, myalgias, bronchospasm, fleeting pruritic rashes, transient lymphadenopathy, and subcutaneous nodules associated with eosinophilia, elevated erythrocyte sedimentation rate, and elevated levels of muscle creatinine kinase. Sarcocysts of an unidentified Sarcocystis species were found in skeletal muscle biopsies of the index case. Albendazole ameliorated symptoms in the index case; however, his symptoms persisted for more than 5 years. Symptoms in 5 other men were mild to moderate and self-limited, and 1 team member with laboratory abnormalities was asymptomatic. Of 8 team members tested for antibody to Sarcocystis, 6 were positive; of 4 with the eosinophilic myositis syndrome who were tested, all were positive. We attribute this outbreak of eosinophilic myositis to accidental tissue parasitism by Sarcocystis.
Nine Newcastle disease virus (NDV) isolates from Newcastle disease (ND) outbreaks in different regions of Iran were characterized at molecular level. Sequence analysis revealed that the isolates shared two pairs of arginine and a phenylalanine at the N-terminus of the fusion (F) protein cleavage site similarly to other velogenic isolates of NDV characterized earlier. Eight of the nine isolates had the same amino acid sequence as VOL95, a Russian NDV isolate from 1995. However, one isolate, MK13 showed 5 amino acid substitutions, of which 3 have been reported for other velogenic NDV isolates. These results suggest that the origin of the outbreaks of ND in different parts of Iran in 1995-1998 is VOL95.
Traceback systems in most countries of Asia are not well developed, as indicated by responses to a questionnaire by veterinary officials in thirteen countries. Marking of animals for traceback is practised only in a limited number of countries in specific areas or zones and for specific purposes only. In Malaysia, traceback has been undertaken by marking farm code tattoos on pigs. This enables the identification of the farm of origin of pigs found to be infected by Nipah virus in sero-surveillance programmes. The origin of the foot and mouth disease (FMD) virus that surfaced in the Republic of Korea in March 2000 was investigated through several epidemiological studies of suspected sources of contamination such as imported hay, yellow sand, milk collection trucks and feed delivery trucks. None of these studies gave results that indicated the origin of the FMD virus. The origin of the FMD virus that was recorded in Japan in March 2000 was also investigated in epidemiological studies; in this case, imported wheat straw was incriminated as the most likely source of infection. Comparative studies of the pathogenicities of FMD (type O) viruses isolated in Taipei China, the Republic of Korea and Japan, suggest that these viruses might have originated as vaccine strains used in a third country.
To characterize the dengue epidemic that recently occurred in Malaysia, we sequenced cDNAs from nine 1993-1994 dengue virus type-3 (DEN-3) isolates in Malaysia (DEN-3 was the most common type in Malaysia during this period). Nucleic acid sequences (720 nucleotides in length) from the nine isolates, encompassing the precursor of membrane protein (preM) and membrane (M) protein genes and part of the envelope (E) protein gene were aligned with various reference DEN-3 sequences to generate a neighbor-joining phylogenetic tree. According to the constructed tree, the nine Malaysian isolates were grouped into subtype II, which comprises Thai isolates from 1962 to 1987. Five earlier DEN-3 virus Malaysian isolates from 1974 to 1981 belonged to subtype I. The present data indicate that the recent dengue epidemic in Malaysia was due to the introduction of DEN-3 viruses previously endemic to Thailand.
The principal etiologic agent of human eosinophilic meningitis, Angiostrongylus cantonensis, was first detected in rats in Canton, China in 1933. The first human case was detected on Taiwan in 1944. Epidemic outbreaks were noted on Ponape (E. Caroline Is.) from 1944 to 1948. The disease may present as transient meningitis or a more severe disease involving the brain, spinal cord and nerve roots, with a characteristic eosinophilia of the peripheral blood and CSF. Since 1961 it has been known that human infections are usually acquired by purposeful or accidental ingestion of infective larvae in terrestrial mollusks, planaria and fresh-water crustacea. There is no effective specific treatment. The African land snail, Achatina fulica played an important role in the panpacific dispersal of the organism: it will be important in Africa in the future as well. Rats were, and will continue to be the principal agents of expansion of the parasite beyond the Indopacific area. During and just after WWII the parasite was introduced, and/or spread passively from South and Southeast Asia into the Western Pacific islands and eastward and southward through Micronesia, Melanesia, Australia and into Polynesia, sequestered in shipments of war material and facilitated by post-war commerce. In the 1950s numerous cases were identified for the first time on Sumatra, the Philippines, Taiwan, Saipan, New Caledonia, and as far east as Rarotonga and Tahiti. Then cases were detected in Vietnam, Thailand, Cambodia, Java, Sarawak, the New Hebrides, Guam and Hawaii during the 1960s. Subsequently in the Pacific Basin the disease has appeared on Okinawa, other Ryukyu islands, Honshu, Kyushu, New Britain, American Samoa and Western Samoa, Australia, Hong Kong, Bombay, India, Fiji and most recently in mainland China. The parasite in rats now occurs throughout the Indopacific Basin and littoral. Beyond the Indopacific region, the worm has been found in rodents in Madagascar (ca 1963), Cuba (1973), Egypt (1977), Puerto Rico (1984), New Orleans, Louisiana (1985) and Port Harcourt, Nigeria (1989). Human infections have now been detected in Cuba (1973), Réunion Island (1974) and Côte d'Ivoire (1979) and should be anticipated wherever infected rats of mollusks have been introduced. Caged primates became infected in zoos in Hong Kong (1978) and New Orleans and Nassau, Bahamas (1987). The use of mollusks and crustacea as famine foods, favored delicacies and medicines has resulted in numerous outbreaks and isolated infections. Economic and political instability, illicit trade, unsanitary peridomestic conditions and lack of health education promote the local occurrence and insidious global expansion of parasitic eosinophilic meningitis.(ABSTRACT TRUNCATED AT 400 WORDS)
Matched MeSH terms: Disease Outbreaks/statistics & numerical data
Since its first emergence in 1998 in Malaysia, Nipah virus (NiV) has become a great threat to domestic animals and humans. Sporadic outbreaks associated with human-to-human transmission caused hundreds of human fatalities. Here, we collected all available NiV sequences and combined phylogenetics, molecular selection, structural biology and receptor analysis to study the emergence and adaptive evolution of NiV. NiV can be divided into two main lineages including the Bangladesh and Malaysia lineages. We formly confirmed a significant association with geography which is probably the result of long-term evolution of NiV in local bat population. The two NiV lineages differ in many amino acids; one change in the fusion protein might be involved in its activation via binding to the G protein. We also identified adaptive and positively selected sites in many viral proteins. In the receptor-binding G protein, we found that sites 384, 386 and especially 498 of G protein might modulate receptor-binding affinity and thus contribute to the host jump from bats to humans via the adaption to bind the human ephrin-B2 receptor. We also found that site 1645 in the connector domain of L was positive selected and involved in adaptive evolution; this site might add methyl groups to the cap structure present at the 5'-end of the RNA and thus modulate its activity. This study provides insight to assist the design of early detection methods for NiV to assess its epidemic potential in humans.
Here, we investigated an outbreak of leptospirosis among reserve military recruits that occurred following a survival exercise in the Hulu Perdik forest within the Hulu Langat district, Kuala Lumpur, Malaysia. Blood samples from the 12 patients that presented symptoms for febrile illness on clinical examination were subjected to laboratory investigation, comprising Lepto IgM rapid test, IgM ELISA, and microscopic agglutination test (MAT). All these patients were interviewed for possible risk factors for leptospirosis. Rodent trapping and environmental sampling for possible isolation of leptospires in the outbreak site was performed. The isolated leptospires were genetically characterized and investigated for the potential epidemiological link with human leptospirosis. Among the 12 patients, two (2/12; 16.6%) were confirmed positive for leptospirosis by microscopic agglutination test (MAT with titers 400-800; serovar autumnalis and hardjobovis). Two Leptospira species from rodents (L. interrogans and L. borgpetersenii) and two from the environment (L. kmetyi and L. wolffii) were identified. The possible epidemiological link between human serovars and animal Leptospira species indicates rodents as the potential reservoir while the environment (soil and water) serves as a transmission route. This investigation highlights the robust presence of pathogenic leptospires on Malaysian environment and rodents which may present the risk of infection, especially among high-risk individuals. Hence, occupational risk individuals are cautioned to observe appropriate preventive measures including prophylaxis and seek immediate medical attention for any illness following similar activities.
Equine influenza is a major cause of respiratory infections in horses and can spread rapidly despite the availability of commercial vaccines. In this study, we carried out molecular characterization of Equine Influenza Virus (EIV) isolated from the Malaysian outbreak in 2015 by sequencing of the HA and NA gene segments using Sanger sequencing. The nucleotide and amino acid sequences of HA and NA were compared with representative Florida clade 1 and clade 2 strains using phylogenetic analysis. The Florida clade 1 viruses identified in this outbreak revealed numerous amino acid substitutions in the HA protein as compared to the current OIE vaccine strain recommendations and representative strains of circulating Florida sub-lineage clade 1 and clade 2. Differences in HA included amino acids located within antigenic sites which could lead to reduced immune recognition of the outbreak strain and alter the effectiveness of vaccination against the outbreak strain. Detailed surveillance and genetic information sharing could allow genetic drift of equine influenza viruses to be monitored more effectively on a global basis and aid in refinement of vaccine strain selection for EIV.
Carbapenem-resistant Enterobacteriaceae (CRE) represent an urgent threat to human health. Here we report the application of several complementary whole-genome sequencing (WGS) technologies to characterise a hospital outbreak of blaIMP-4 carbapenemase-producing E. hormaechei. Using Illumina sequencing, we determined that all outbreak strains were sequence type 90 (ST90) and near-identical. Comparison to publicly available data linked all outbreak isolates to a 2013 isolate from the same ward, suggesting an environmental source in the hospital. Using Pacific Biosciences sequencing, we resolved the complete context of the blaIMP-4 gene on a large IncHI2 plasmid carried by all IMP-4-producing strains across different hospitals. Shotgun metagenomic sequencing of environmental samples also found evidence of ST90 E. hormaechei and the IncHI2 plasmid within the hospital plumbing. Finally, Oxford Nanopore sequencing rapidly resolved the true relationship of subsequent isolates to the initial outbreak. Overall, our strategic application of three WGS technologies provided an in-depth analysis of the outbreak.
Challenges arising from epidemic infectious disease outbreaks can be more effectively met if traditional public health is enhanced by sociology. The focus is normally on biomedical aspects, the surveillance and sentinel systems for infectious diseases, and what needs to be done to bring outbreaks under control quickly. Social factors associated with infectious disease outbreaks are often neglected and the aftermath is ignored. These factors can affect outbreak severity, its rate and extent of spread, influencing the welfare of victims, their families, and their communities. We propose an agenda for research to meet the challenges of infectious disease outbreaks. What social factors led to the outbreak? What social factors affected its severity and rate and extent of spread? How did individuals, social groups, and the state react to it? What are the short- and long-term effects on individuals, social groups, and the larger society? What programs can be put in place to help victims, their families, and affected communities to cope with the consequences--impaired mental and physical health, economic losses, and disrupted communities? Although current research on infectious disease outbreaks pays attention to social factors related to causation, severity, rate and extent of spread, those dealing with the "social chaos" arising from outbreaks are usually neglected. Inclusion, by combining traditional public health with sociological analysis, will enrich public health theory and understanding of infectious disease outbreaks. Our approach will help develop better programs to combat outbreaks and equally important, to help survivors, their families, and their communities cope better with the aftermath.
Numerous lessons have been learned so far in controlling H5N1 avian influenza in Asia. Early detection of incursions of virus prevented establishment of the disease in several countries, notably Japan, South Korea, and Malaysia. In countries where detection of early cases was delayed, infection is endemic and has been for three or more years. Control measures implemented in these countries need to reflect this finding. Vaccination will continue to be one of the key measures used in these endemically infected countries. Used alone, vaccination will not result in elimination of H5N1 viruses from a country, but, if used correctly, it will markedly reduce the prevalence of and susceptibility to infection. Vaccination has already played a valuable role in reducing the adverse effects of H5N1 viruses. Mass culling also reduces the level of infection in infected areas. However, the long-term benefits are limited in endemically infected countries owing to the high probability of reinfection on restocking unless other measures are used in parallel. Full epidemiological studies have not been conducted in many infected countries. Nevertheless, it is recognized that the number of clinical cases does not truly reflect the levels of infection. Domestic ducks and large live poultry markets have played a key role in the persistence of infection, because they can be infected silently. In tackling this disease, countries should adopt integrated control programs using the combination of measures best suited to the local environment. All surveillance data should be shared, both positive and negative, and should include information on cases of infection and disease. Socioeconomic and ecological implications of all control measures should be assessed before implementation, especially the impact on the rural poor.
Rotavirus B (RVB) infection in cattle is poorly understood. The objective of this study was to describe the epidemiological features of repeated outbreaks of epidemic diarrhea due to RVB infection in adult cattle on a large dairy farm complex in Japan. In October 2002, approximately 550 adult cows and approximately 450 in February 2005 had acute watery diarrhea at several farms on the complex. Four months before the first outbreak, RVB antibody-positive rates at subsequently affected farms were significantly lower than at non-affected farms (30% to 32% versus 61% to 67%). During the acute phase of both outbreaks, RVB antibody-positive rates in diarrheal cows tested were as low as 15% to 26%. Most of the farms affected in the second outbreak were also involved in the first outbreak. Some adult cows with RVB diarrhea in the first outbreak showed not only RVB seroresponse, but also RVB shedding in the second outbreak, although none of these cows developed diarrhea. Nucleotide sequences of the VP7 and VP4 genes revealed a close relationship between RVB strains in both outbreaks. Taken together, these results indicate that outbreaks of epidemic RVB diarrhea in adult cows might be influenced by herd immunity and could occur repeatedly at the same farms over several years. To our knowledge, this is the first report on repeated RVB infections in the same cattle.
The resistance status of Selangor Aedes aegypti (Linnaeus) larvae against four major groups of insecticides (i.e., organochlorines, carbamates, organophosphates and pyrethroids) was investigated. Aedes aegypti were susceptible against temephos (organophosphate), although resistance (RR50 = 0.21-2.64) may be developing. The insecticides susceptibility status of Ae. aegypti larvae were found heterogeneous among the different study sites. Results showed that Ae. aegypti larvae from Klang, Sabak Bernam and Sepang were susceptible against all insecticides tested. However, other study sites exhibited low to high resistance against all pyrethroids (RR50 = 1.19-32.16). Overall, the application of synergists ethacrynic acid, S.S.S.- tributylphosphorotrithioate and piperonyl butoxide increased the toxicity of insecticides investigated. However, the application failed to increase the mortality to susceptible level (>97%) for certain populations, therefore there are chances of alteration of target site resistance involved. Biochemical assays revealed that α-esterase, (Gombak, Kuala Langat, Kuala Selangor and Sabak Bernam strains) β-esterase (Klang and Sabak Bernam strains), acetylcholinesterase (Kuala Selangor and Sabak Bernam strains), glutathione-S-transferase (Kuala Selangor and Sabak Bernam strains) and mono-oxygenases (Gombak, Hulu Langat, Hulu Selangor and Kuala Langat strains) were elevated. Spearman rank-order correlation indicated a significant correlation between resistance ratios of: DDT and deltamethrin (r = 0.683, P = 0.042), cyfluthrin and deltamethrin (r = 0.867, P =0.002), cyflyuthrin and lambdacyhalothrin (r = 0.800, P =0.010), cyfluthrin and permethrin (r = 0.770, P =0.015) deltamethrin and permethrin (r = 0.803, P =0.088), propoxur and malathion (r = 0.867, P = 0.002), malathion and temephos (r = 0.800, P = 0.010), etofenprox and MFO enzyme (r = 0.667, P =0.050). The current study provides baseline information for vector control programs conducted by local authorities. The susceptibility status of Ae. aegypti should be monitored sporadically to ensure the effectiveness of current vector control strategy in Selangor.
The H7N9 subtype of avian influenza is an enzootic and airborne virus which caused an influenza outbreak in China. Infected individuals mostly worked with poultry, suggesting H7N9 virus-infected poultry as the primary source of human infection. Significantly increased levels of proinflammatory mediators (chemokines, cytokines) during virus infection could hamper the immune system and aggravate the infection. Severe cases are marked by fulminant pneumonia, acute respiratory distress syndrome (ARDS) and encephalopathy. Left untreated, the condition may rapidly progress to multi-organ failure and death. Reverse transcription polymerase chain reaction (rRT-PCR) is the gold standard diagnostic test for H7N9 avian influenza. Use of neurominidase inhibitor antivirals remain the main treatment. New antivirals are developed to counteract neurominidase inhibitor resistance H7N9 viral strains. Corticosteroid use in viral pneumonia may provoke mortality and longer viral shedding time. Subjects at high risk of contracting avian influenza H7N9 infection are recommended to receive annual seasonal influenza vaccination.
Although Plasmodium vivax parasites are the predominant cause of malaria outside of sub-Saharan Africa, they not always prioritised by elimination programmes. P. vivax is resilient and poses challenges through its ability to re-emerge from dormancy in the human liver. With observed growing drug-resistance and the increasing reports of life-threatening infections, new tools to inform elimination efforts are needed. In order to halt transmission, we need to better understand the dynamics of transmission, the movement of parasites, and the reservoirs of infection in order to design targeted interventions. The use of molecular genetics and epidemiology for tracking and studying malaria parasite populations has been applied successfully in P. falciparum species and here we sought to develop a molecular genetic tool for P. vivax. By assembling the largest set of P. vivax whole genome sequences (n = 433) spanning 17 countries, and applying a machine learning approach, we created a 71 SNP barcode with high predictive ability to identify geographic origin (91.4%). Further, due to the inclusion of markers for within population variability, the barcode may also distinguish local transmission networks. By using P. vivax data from a low-transmission setting in Malaysia, we demonstrate the potential ability to infer outbreak events. By characterising the barcoding SNP genotypes in P. vivax DNA sourced from UK travellers (n = 132) to ten malaria endemic countries predominantly not used in the barcode construction, we correctly predicted the geographic region of infection origin. Overall, the 71 SNP barcode outperforms previously published genotyping methods and when rolled-out within new portable platforms, is likely to be an invaluable tool for informing targeted interventions towards elimination of this resilient human malaria.
As of 4 November, 2012, 100 patients with an acute muscular Sarcocystis-like illness associated with travel to Tioman Island, Malaysia, have been identified. Thirty-five travelled there mostly during July and August 2011 and 65 mostly during July and August 2012, suggesting an ongoing outbreak. Epidemiological investigations are ongoing. Public health agencies and practicing clinicians should be aware of this rarely-reported disease in humans and consider it as differential diagnosis in travellers returning from Tioman Island.
It is widely accepted that Newcastle disease is endemic in most African countries, but little attention has been afforded to establishing the sources and frequency of the introductions of exotic strains. Newcastle disease outbreaks have a high cost in Africa, particularly on rural livelihoods. Genotype VIIh emerged in South-East Asia and has since caused serious outbreaks in poultry in Malaysia, Indonesia, southern China, Vietnam and Cambodia. Genotype VIIh reached the African continent in 2011, with the first outbreaks reported in Mozambique. Here, we used a combination of phylogenetic evidence, molecular dating and epidemiological reports to trace the origins and spread of subgenotype VIIh Newcastle disease in southern Africa. We determined that the infection spread northwards through Mozambique, and then into the poultry of the north-eastern provinces of Zimbabwe. From Mozambique, it also reached neighbouring Malawi and Zambia. In Zimbabwe, the disease spread southward towards South Africa and Botswana, causing outbreaks in backyard chickens in early-to-mid 2013. In August 2013, the disease entered South Africa's large commercial industry, and the entire country was infected within a year, likely through fomites and the movements of cull chickens. Illegal poultry trading or infected waste from ships and not wild migratory birds was the likely source of the introduction to Mozambique in 2011.
Nipah virus is an emerging zoonotic paramyxovirus that causes severe and often fatal respiratory and neurological disease in humans. The virus was first discovered after an outbreak of encephalitis in pig farmers in Malaysia and Singapore with subsequent outbreaks in Bangladesh or India occurring almost annually. Due to the highly pathogenic nature of NiV, its pandemic potential, and the lack of licensed vaccines or therapeutics, there is a requirement for research and development into highly sensitive and specific diagnostic tools as well as antivirals and vaccines to help prevent and control future outbreak situations.
Matched MeSH terms: Disease Outbreaks/prevention & control