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Esbjornsson J.,Lund University | Mansson F.,Lund University | Kvist A.,Skåne University Hospital | Isberg P.-E.,Lund University | And 8 more authors.
New England Journal of Medicine | Year: 2012

Background: Progressive immune dysfunction and the acquired immunodeficiency syndrome (AIDS) develop in most persons with untreated infection with human immunodeficiency virus type 1 (HIV-1) but in only approximately 20 to 30% of persons infected with HIV type 2 (HIV-2); among persons infected with both types, the natural history of disease progression is poorly understood. Methods: We analyzed data from 223 participants who were infected with HIV-1 after enrollment (with either HIV-1 infection alone or HIV-1 and HIV-2 infection) in a cohort with a long follow-up duration (approximately 20 years), according to whether HIV-2 infection occurred first, the time to the development of AIDS (time to AIDS), CD4+ and CD8+ T-cell counts, and measures of viral evolution. Results: The median time to AIDS was 104 months (95% confidence interval [CI], 75 to 133) in participants with dual infection and 68 months (95% CI, 60 to 76) in participants infected with HIV-1 only (P = 0.003). CD4+ T-cell levels were higher and CD8+ T-cell levels increased at a lower rate among participants with dual infection, reflecting slower disease progression. Participants with dual infection with HIV-2 infection preceding HIV-1 infection had the longest time to AIDS and highest levels of CD4+ T-cell counts. HIV-1 genetic diversity was significantly lower in participants with dual infections than in those with HIV-1 infection alone at similar time points after infection. Conclusions: Our results suggest that HIV-1 disease progression is inhibited by concomitant HIV-2 infection and that dual infection is associated with slower disease progression. The slower rate of disease progression was most evident in participants with dual infection in whom HIV-2 infection preceded HIV-1 infection. These findings could have implications for the development of HIV-1 vaccines and therapeutics. (Funded by the Swedish International Development Cooperation Agency-Swedish Agency for Research Cooperation with Developing Countries and others.) Copyright © 2012 Massachusetts Medical Society.


Chua K.B.,National Public Health Laboratory | Chua K.B.,International Medical University | Voon K.,International Medical University | Yu M.,Commonwealth Science and Industry Research Organisation Livestock Industries | And 3 more authors.
PLoS ONE | Year: 2011

Bats are increasingly being recognized as important reservoir hosts for a large number of viruses, some of them can be highly virulent when they infect human and livestock animals. Among the new bat zoonotic viruses discovered in recent years, several reoviruses (respiratory enteric orphan viruses) were found to be able to cause acute respiratory infections in humans, which included Melaka and Kampar viruses discovered in Malaysia, all of them belong to the genus Orthoreovirus, family Reoviridae. In this report, we describe the isolation of a highly related virus from an adult patient who suffered acute respiratory illness in Malaysia. Although there was no direct evidence of bat origin, epidemiological study indicated the potential exposure of the patient to bats before the onset of disease. The current study further demonstrates that spillover events of different strains of related orthoreoviruses from bats to humans are occurring on a regular basis, which calls for more intensive and systematic surveillances to fully assess the true public health impact of these newly discovered bat-borne zoonotic reoviruses. © 2011 Chua et al.


Shakya G.,National Public Health Laboratory
Journal of Nepal Health Research Council | Year: 2012

Different diagnostic test kits are used for rapid diagnosis of malaria. Most are based on antigen detection (pLDH, Pan Aldolase, HRP-2). In context of Nepal the diagnostic reliability and sensitivity of these tests is unknown. Hexagon Malaria Combi™ is one of the most commonly used test kit in Nepal for rapid diagnosis of malaria. The aim of the present study is to evaluate the sensitivity of the Hexagon malaria Combi test in comparison with parasitic density by microscopy technique. A Cross sectional prospective study was conducted in three districts of Nepal from September to November 2009. Blood samples were collected from the suspected cases of malaria. Thick and thin smear were prepared from all the samples and Giemsa stain was done. Simultaneously RDT (hexagon) for malaria was done. When RDT was found to be positive, blood was serially diluted in 6 tubes as 1:2, 1:4, 1:8, 1:16, 1:32 and 1:64. RDT was done on diluted blood till RDT test gave negative result. Parasitic density was calculated for undiluted and diluted blood samples and sensitivity of RDT in various parasitic densities was calculated. Hexagon malaria combi test is sensitive (86%) when malarial parasitic density is >500/μl. Sensitivity was found to be directly related to parasitic density. Its sensitivity is very low (2.9%) when parasitic density is less than 500/ μl. The sensitivity of rapid diagnostic test (hexagon Combi test detecting malarial pLDH antigen) is high only if the parasitic density is more than 500/μl.


Omar N.,National Public Health Laboratory | Bakar J.,University Putra Malaysia | Muhammad K.,University Putra Malaysia
Food Control | Year: 2013

Pacific white shrimp (Litopenaeus vannamei) collected during dry and rainy seasons from three different states in Malaysia were analyzed for nine organochlorine pesticides (OCPs) (α-HCH, β-HCH, γ-HCH, δ-HCH, trans-chlordane, cis-chlordane, p,p'-DDE, p,p'-DDD and p,p'-DDT) using QuEChERS sample preparation method and GC-MS SIM with split/splitless injection mode. The efficiency of combination of primary and secondary amine (PSA) and octadecyl (C18) at 25mg of PSA and 25mg of C18 per mL of shrimp extract as the clean-up sorbent to remove matrix interferences was evaluated. By combining PSA and C18, matrix interferences such as gamma-tocopherol and cholesterol were not able to be eliminated. Good separation and high recoveries which ranged from 90 to 105% with associated RSD<15% were obtained for all OCPs at 3-75ng/g. No significant difference in recoveries due to seasonal variation for studied OCPs, except for α-HCH, β-HCH, δ-HCH and p,p'-DDT were obtained. The limits of detection and quantification ranged from 0.3 to 4.5ng/g and 3 to 15ng/g, respectively. The linearity for matrix matched standard calibrations was >0.99. © 2013 Elsevier Ltd.


Kansakar P.,National Public Health Laboratory | Baral P.,Tribhuvan University | Malla S.,National Public Health Laboratory | Ghimire G.R.,National Public Health Laboratory
Journal of Infection in Developing Countries | Year: 2011

Introduction: The prevalence and antimicrobial susceptibility patterns of the bacterial enteropathogens Vibrio cholerae, Salmonella species and Shigella species were investigated. Methodology: A total of 877 stool samples were received for culture at the National Public Health Laboratory (NPHL), Kathmandu, Nepal, during January 2002 to December 2004, from diarrhoea patients attending Shukraraj Tropical Infectious Hospital and referral outpatients. All samples collected were processed for isolation and antibiotic susceptibility testing of Vibrio cholerae, Salmonella spp. and Shigella spp. Results: Of the 877 stool samples, 148 (16.8%) were culture positive for one of the three bacterial enteropathogens investigated. Among them, Vibrio cholerae, Shigella spp. and Salmonella spp. accounted for 98/877 (11.1%), 41/877 (4.6%), 9/877 (1.02%) of the isolates respectively. A year-to-year variation was seen in the type of predominant organism, with Shigella spp. being the most prevalent in 2002 and 2003 and Vibrio spp. in 2004. In all three years, Vibrio cholerae were encountered only during the months of April to June while Salmonella spp. and Shigella spp. were isolated throughout the whole year. All Vibrio cholerae and Salmonella isolates were susceptible to ciprofloxacin. All Shigella isolates were susceptible to ceftriaxone. Ciprofloxacin resistance was observed among isolates of Shigella dysenteriae type-1 isolated after 2003. Conclusion: Vibrio cholerae, Salmonella and Shigella infections are prevalent in Kathmandu, Nepal. A gradual increase in resistance to commonly used antimicrobials was seen among bacterial enteropathogens. Antimicrobial resistance surveillance is necessary to guide empirical treatment. © 2011 Kansakar et al.


Tate M.D.,Monash Institute of Medical Research | Job E.R.,University of Melbourne | Deng Y.-M.,Peter Doherty Institute for Infection and Immunity | Gunalan V.,Agency for Science, Technology and Research Singapore | And 5 more authors.
Viruses | Year: 2014

Seasonal influenza A viruses (IAV) originate from pandemic IAV and have undergone changes in antigenic structure, including addition of glycans to the hemagglutinin (HA) glycoprotein. The viral HA is the major target recognized by neutralizing antibodies and glycans have been proposed to shield antigenic sites on HA, thereby promoting virus survival in the face of widespread vaccination and/or infection. However, addition of glycans can also interfere with the receptor binding properties of HA and this must be compensated for by additional mutations, creating a fitness barrier to accumulation of glycosylation sites. In addition, glycans on HA are also recognized by phylogenetically ancient lectins of the innate immune system and the benefit provided by evasion of humoral immunity is balanced by attenuation of infection. Therefore, a fine balance must exist regarding the optimal pattern of HA glycosylation to offset competing pressures associated with recognition by innate defenses, evasion of humoral immunity and maintenance of virus fitness. In this review, we examine HA glycosylation patterns of IAV associated with pandemic and seasonal influenza and discuss recent advancements in our understanding of interactions between IAV glycans and components of innate and adaptive immunity. © 2014 by the authors; licensee MDPI, Basel, Switzerland.


Chua K.B.,National Public Health Laboratory | Kasri A.R.,National Public Health Laboratory
Virologica Sinica | Year: 2011

Hand foot and mouth disease is a febrile sickness complex characterized by cutaneous eruption(exanthem) on the palms and soles with simultaneous occurrence of muco-cutanous vesiculo-ulcerative lesions(enanthem) affecting the mouth. The illness is caused by a number of enteroviruses with coxsackievirus A16 andenterovirus 71 as the main causative agents. Human enterovirus 71 (EV71) belongs to the species Humanenterovirus A under the genus Enterovirus within the family Picornaviridae. EV71 has been associated with anarray of clinical diseases including hand foot and mouth disease (HFMD), aseptic meningitis, encephalitis andpoliomyelitis-like acute flaccid paralysis.A large outbreak of HFMD due to highly neurovirulent EV71 emerged in Malaysia in 1997, and caused 41deaths amongst young children. In late 2000, a recurrence of an outbreak of HFMD occurred in Malaysia with 8fatalities in peninsular Malaysia. Outbreak of HFMD due to EV71 recurred in 2003 with an unknown number ofcases and mortalities. A similar outbreak of HFMD with 2 recorded deaths in young children occurred inpeninsular Malaysia in late 2005 and this was followed by a larger outbreak in Sarawak (Malaysian Borneo) with6 reported fatalities in the early part of 2006. The current on-going outbreak of HFMD started in peninsularMalaysia in epidemiological week 12 of 2010. As with other HFMD outbreaks in Malaysia, both EV71 and CA16were the main aetiological viruses isolated. In similarity with the HFMD outbreak in 2005, the isolation of CA16preceded the appearance of EV71. Based on the VP1 gene nucleotide sequences, 4 sub-genogroups of EV71 (C1,C2, B3 and B4) co-circulated and caused the outbreak of hand, foot and mouth disease in peninsular Malaysia in1997. Two sub-genogroups (C1 and B4) were noted to cause the outbreak in 2000 in both peninsular Malaysia andSarawak. EV71 of sub-genogroup B5 with smaller contribution from sub-genogroup C1 caused the outbreak in2003. In the 2005 outbreak, besides the EV71 strains of sub-genogroup C1, EV71 strains belonging tosub-genogroup B5 were isolated but formed a cluster which was distinct from the EV71 strains from thesub-genogroup B5 isolated in 2003. The four EV71 strains isolated from clinical specimens of patients with hand,foot and mouth disease in the Sarawak outbreak in early 2006 also belonged to sub-genogroup B5. Phylogeneticanalysis of the VP1 gene suggests that the EV71 strains causing the outbreak in Sarawak could have originated frompeninsular Malaysia. Epidemiological and molecular data since 1997 show the recurrence of HFMD due to EV71 inMalaysia every 2 to 4 years. In each of the past outbreaks, more than one sub-genogroup of the virus co-circulate. © Wuhan Institute of Virology, CAS and Springer-Verlag Berlin Heidelberg 2011.


Elduma A.H.,National Public Health Laboratory
Pan African Medical Journal | Year: 2012

Background: This study was conducted to evaluate the biosafety precautions that applied by diagnostic laboratories in Khartoum state, 2009. Methods: A total number of 190 laboratories were surveyed about their compliance with standard biosafety precautions. These laboratories included 51 (27%) laboratories from government, 75 (39%) from private sectors and 64 (34%) laboratories belong to organization providing health care services. Results: The study found that 32 (16.8%) of laboratories appointed biosafety officers. Only, ten (5.2%) participated in training about response to fire emergency, and 28 (14.7%) reported the laboratory accident occurred during work. 45 (23.7%) laboratories had a written standard operation procedures (SOPs), and 35 (18.4%) had written procedures for the lean-up of spills. Moreover, biosafety cabinet was found in 11 (5.8%) laboratories, autoclave in 28 (14.7%) and incinerator in only two (1.1%) laboratories. Sharp disposable containers were found in 84 (44.2%). Fire alarm system was found in 2 (1.1%) laboratories, fire extinguisher in 39 (20.5%) laboratories, and fire emergency exit found in 14 (7.4%) laboratories. Furthermore, 19 (10%) laboratories had a hepatitis B virus vaccination programme, 5 (6.2%) applied BCG vaccine, and 2 (1.1%0) vaccinated the staff against influenza. Conclusion: The study concluded that the standards biosafety precautions adopted by the diagnostic laboratories in Khartoum state was very low. Further, the laboratory personnel awareness towards biosafety principles implementation was very low too. © Adel Hussein Elduma et al.


Karki R.,Tribhuvan University | Bhatta D.R.,Tribhuvan University | Malla S.,National Public Health Laboratory | Dumre S.P.,National Public Health Laboratory
Japanese Journal of Infectious Diseases | Year: 2010

The major objective of this study was to deliver vital statistics related to cholera to health authorities so as to aid in their attempt to prioritize communicable diseases in Nepal. A laboratory-based surveillance was conducted from mid-June 2008 to mid-January 2009 at the National Public Health Laboratory, Nepal. Diarrheal samples alone were processed for Vibrio cholerae. Isolation and identification of the organisms were carried out as per standard protocol. Antimicrobial susceptibility tests were done according to the guidelines of the Clinical and Laboratory Standards Institute. The incidence of cholera was found to be 27.1%. Only V. cholerae Ol Ogawa biotype El Tor was found during the study. No variation was observed in the percentage of cases between genders (P < 0.05). The 15-30 year age group was found to be more susceptible to cholera (P < 0.05). The period from mid-June to mid-July had the highest incidence of cholera (P < 0.05). Ampicillin, tetracycline, ciprofloxacin, and erythromycin were highly effective, while 100% resistance was observed for furazolidone, nalidixic acid, and cotrimoxazole.


Moi M.L.,Japan National Institute of Infectious Diseases | Lim C.-K.,Japan National Institute of Infectious Diseases | Chua K.B.,National Public Health Laboratory | Takasaki T.,Japan National Institute of Infectious Diseases | Kurane I.,Japan National Institute of Infectious Diseases
PLoS Neglected Tropical Diseases | Year: 2012

Background: Progress in dengue vaccine development has been hampered by limited understanding of protective immunity against dengue virus infection. Conventional neutralizing antibody titration assays that use FcγR-negative cells do not consider possible infection-enhancement activity. We reasoned that as FcγR-expressing cells are the major target cells of dengue virus, neutralizing antibody titration assays using FcγR-expressing cells that determine the sum of neutralizing and infection-enhancing activity, may better reflect the biological properties of antibodies in vivo. Methods and Findings: We evaluated serum samples from 80 residents of a dengue endemic country, Malaysia, for neutralizing activity, and infection-enhancing activity at 1:10 serum dilution by using FcγR-negative BHK cells and FcγR-expressing BHK cells. The serum samples consisted of a panel of patients with acute DENV infection (31%, 25/80) and a panel of donors without acute DENV infection (69%, 55/80). A high proportion of the tested serum samples (75%, 60/80) demonstrated DENV neutralizing activity (PRNT 50≥10) and infection-enhancing activity. Eleven of 18 serum samples from patients with acute secondary DENV infection demonstrated neutralizing activity to the infecting serotype determined by using FcγR-negative BHK cells (PRNT 50≥10), but not when determined by using FcγR-expressing cells. Conclusion: Human serum samples with low neutralizing activity determined by using FcγR-negative cells showed DENV infection-enhancing activity using FcγR-expressing cells, whereas those with high neutralizing activity determined by using FcγR-negative cells demonstrate low or no infection-enhancing activity using FcγR-expressing cells. The results suggest an inverse relationship between neutralizing antibody titer and infection-enhancing activity, and that neutralizing activity determined by using FcγR-expressing cells, and not the activity determined by using FcγR-negative cells, may better reflect protection to DENV infection in vivo. © 2012 Moi et al.

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