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  Kết quả Nghiên cứu khoa học của một số đề tài
Danh sách các bài báo quốc tế năm 2010

 

DANH SÁCH CÁC BÀI BÁO QUỐC TẾ NĂM 2010

1. Choi SY, Lee JH, Jeon YS, Lee HR, Kim EJ, Ansaruzzaman M, Bhuiyan NA, Endtz HP, Niyogi SK, Sarkar BL, Nair GB, Nguyễn Bình Minh, Nguyễn Trần Hiển, Czerkinsky C, Clemens JD, Chun J, Kim DW. Multilocus variable-number tandem repeat analysis of Vibrio cholerae O1 El Tor strains harbouring classical toxin B.J Med Microbiol. 2010 Jul;59(Pt 7):763-9. Epub 2010 Mar 18.

Multilocus variable-number tandem repeat analysis of Vibrio cholerae O1 El Tor strains harbouring classical toxin B.

Choi SY, Lee JH, Jeon YS, Lee HR, Kim EJ, Ansaruzzaman M, Bhuiyan NA, Endtz HP, Niyogi SK, Sarkar BL, Nair GB, Nguyen BM, Hien NT, Czerkinsky C, Clemens JD, Chun J, Kim DW.

Abstract

Atypical Vibrio cholerae O1 strains - hybrid strains (strains that cannot be classified either as El Tor or classical biotype) and altered strains (El Tor biotype strains that produce classical cholera toxin) - are currently prevalent in Asia and Africa. A total of 74 hybrid and altered strains that harboured classical cholera toxin were investigated by multilocus variable-number tandem repeat analysis (MLVA). The results showed that the hybrid/altered strains could be categorized into three groups and that they were distant from the El Tor strain responsible for the seventh cholera pandemic. Hybrid/altered strains with a tandem repeat of the classical CTX prophage on the small chromosome were divided into two MLVA groups (group I: Mozambique/Bangladesh group; group III: Vietnam group), and altered strains with the RS1-CTX prophage containing the El Tor type rstR and classical ctxB on the large chromosome were placed in two MLVA groups (group II: India/Bangladesh group; group III: India/Vietnam group).   

2. Nguyễn Thu Yến, Duffy MR, Nguyễn Minh Hồng, Nguyễn Trần Hiển, Fischer M, Hills SL. Surveillance for Japanese encephalitis in Vietnam, 1998-2007.Am J Trop Med Hyg. 2010 Oct;83(4):816-9.

Surveillance for Japanese encephalitis in Vietnam, 1998-2007.

Yen NT, Duffy MR, Hong NM, Hien NT, Fischer M, Hills SL.

Abstract

Japanese encephalitis (JE) is recognized as an important public health problem in Vietnam. A JE immunization program was introduced in 1997 in high-risk districts and expanded to additional districts over subsequent years. We reviewed national acute encephalitis syndrome (AES) surveillance data for 1998-2007 and analyzed more detailed data regarding JE from five northern provinces in 2004 and 2005. The annual reported incidence of AES in Vietnam ranged from 3.0 to 1.4 cases per 100,000 population with a decreasing trend over the 10-year period. The mean annual incidence of AES was highest in the northern region of the country. Of 421 AES cases from five northern provinces with laboratory results reported, 217 (52%) had laboratory evidence of recent JEV infection. As Vietnam moves closer to control of JE through immunization, accurate JE surveillance data will be important to evaluate and guide the program.

3. Nghi NQ, Lamontagne DS, Bingham A, Rafiq M, Lê Thị Phương Mai, Nguyễn Thị Liên, Nguyễn Công Khanh, Dương Thị Hồng, Đỗ Thanh Huyền, Nguyễn Thi Thơ, Nguyễn Trần Hiển. Human papillomavirus vaccine introduction in Vietnam: formative research findings.Sex Health. 2010 Sep;7(3):262-70.

Human papillomavirus vaccine introduction in Vietnam: formative research findings.

Nghi NQ, Lamontagne DS, Bingham A, Rafiq M, Mai le TP, Lien NT, Khanh NC, Hong DT, Huyen DT, Tho NT, Hien NT.

Abstract

Background: Formative research is a useful tool for designing new health interventions. This paper presents key findings from formative research conducted in Vietnam to guide human papillomavirus (HPV) vaccine introduction. Methods: We explored the sociocultural environment, health system capacity and the policy-making process using a combined quantitative and qualitative methodology. Data collection was done through literature review, in-depth interviews, focus group discussions, observation checklists and a structured questionnaire on knowledge, attitudes and practices. Populations of interest included 11- to 14-year-old girls, their parents, community leaders, teachers, health workers, health and education officials, and policy-makers at all levels. Results:Although HPV vaccines are new, we found high potential acceptance among parents and girls. HPV vaccine introduction was also favourably supported by health professionals if assurances for system preparedness, e.g. cold chain and human resources, were made. There were no significant barriers from the policy perspective that would prevent the introduction of a new vaccine. However, several concerns related to this new vaccine would need to be adequately addressed before implementation. Conclusion: Our findings provide options for potential vaccine delivery strategies, appropriate communication strategies and targeted advocacy strategies to introduce HPV vaccines in the Vietnamese context.

4. Phạm Hồng Thắng, Ruffin N, Brodin D, Rethi B, Phùng Đắc Cam, Nguyễn Trần Hiển, Lopalco L, Vivar N, Chiodi F. The role of IL-1beta in reduced IL-7 production by stromal and epithelial cells: a model for impaired T-cell numbers in the gut during HIV-1 infection. J Intern Med. 2010 Aug;268(2):181-93. Epub 2010 Apr 20.

The role of IL-1beta in reduced IL-7 production by stromal and epithelial cells: a model for impaired T-cell numbers in the gut during HIV-1 infection.

Thang PH, Ruffin N, Brodin D, Rethi B, Cam PD, Hien NT, Lopalco L, Vivar N, Chiodi F.

Abstract

Objectives: Interleukin (IL)-7 is a key cytokine in T-cell homeostasis. Stromal cells, intestinal epithelial cells and keratinocytes are known to produce this cytokine. The mechanisms and cellular factors regulating IL-7 production are still unclear. We assessed whether IL-1beta and interferon (IFN)-gamma, cytokines produced during inflammatory conditions, may impact on IL-7 production.

Design: We used human intestinal epithelial cells (DLD-1 cell line) and bone marrow stromal cells (HS27 cell line), known to produce IL-7; IL-7 production was evaluated at the mRNA and protein levels. To assess whether treatment of HS27 cells with IL-1beta and/or IFN-gamma leads to changes in the gene expression of cytokines, Toll-like receptors (TLRs) and chemokines, we analysed gene expression profiles using the whole-genome microarray Human Gene 1.0 ST.

Results: We found that IFN-gamma enhanced the expression of IL-7 mRNA (P < 0.001) in both cell lines. IL-1beta treatment led to a significant down-regulation (P < 0.001) of IL-7 mRNA expression in both cell lines. The IL-7 concentration in supernatants collected from treated DLD-1 and HS27 cell cultures reflected the trend of IL-7 mRNA levels. The gene profiles revealed dramatic changes in expression of cytokines and their receptors (IL-7/IL-7R alpha; IL-1alpha,IL-1beta/IL-1R1; IFN-gamma/IFN-gammaR1), of IFN regulatory factors (IRF-1 and 2), of TLRs and of important chemo-attractants for T cells. The microarray results were verified by additional methods.

Conclusions: Our results are discussed in the setting of inflammation and T-cell survival in the gut compartment during HIV-1 infection where stromal and epithelial cells may produce factors that contribute to impaired IL-7 homeostasis and homing of T cells.

5. Horby P, Sudoyo H, Viprakasit V, Fox A, Phạm Quang Thái, Yu H, Davila S, Hibberd M, Dunstan SJ, Monteerarat Y, Farrar JJ, Marzuki S, Nguyễn Trần Hiển. What is the evidence of a role for host genetics in susceptibility to influenza A/H5N1? Epidemiol Infect. 2010 Nov;138(11):1550-8.

What is the evidence of a role for host genetics in susceptibility to influenza A/H5N1?

Horby P, Sudoyo H, Viprakasit V, Fox A, Thai PQ, Yu H, Davila S, Hibberd M, Dunstan SJ, Monteerarat Y, Farrar JJ, Marzuki S, Hien NT.

Abstract

The apparent family clustering of avian influenza A/H5N1 has led several groups to postulate the existence of a host genetic influence on susceptibility to A/H5N1, yet the role of host factors on the risk of A/H5N1 disease has received remarkably little attention compared to the efforts focused on viral factors. We examined the epidemiological patterns of human A/H5N1 cases, their possible explanations, and the plausibility of a host genetic effect on susceptibility to A/H5N1 infection. The preponderance of familial clustering of cases and the relative lack of non-familial clusters, the occurrence of related cases separated by time and place, and the paucity of cases in some highly exposed groups such as poultry cullers, are consistent with a host genetic effect. Animal models support the biological plausibility of genetic susceptibility to A/H5N1. Although the evidence is circumstantial, host genetic factors are a parsimonious explanation for the unusual epidemiology of human A/H5N1 cases and warrant further investigation.  

6. Suzuki M, Vũ Đình Thiểm, Yoshida LM, Đặng Đức Anh, Kilgore PE, Ariyoshi K. Who is exposed to smoke at home? A population-based cross-sectional survey in central Vietnam.Tob Control. 2010 Aug;19(4):344-5. Epub 2010 Jun 27. No abstract available

Who is exposed to smoke at home? A population-based cross-sectional survey in central Vietnam.

Suzuki M, Thiem VD, Yoshida LM, Anh DD, Kilgore PE, Ariyoshi K.

7. Tsuzuki A, Vũ Đình Thiểm, Suzuki M, Yanai H, Matsubayashi T, Yoshida LM, Tho le H, Minh TT, Đặng Đức Anh, Kilgore PE, Takagi M, Ariyoshi K. Can daytime use of bed nets not treated with insecticide reduce the risk of dengue hemorrhagic fever among children in Vietnam?Am J Trop Med Hyg. 2010 Jun;82(6):1157-9. 

Can daytime use of bed nets not treated with insecticide reduce the risk of dengue hemorrhagic fever among children in Vietnam?

Tsuzuki A, Thiem VD, Suzuki M, Yanai H, Matsubayashi T, Yoshida LM, Tho le H, Minh TT, Anh DD, Kilgore PE, Takagi M, Ariyoshi K.

Abstract

The purpose of this study was to investigate the prevalence of bed net use and elucidate the effect of daytime bed net use on preventing dengue hemorrhagic fever (DHF) among children in Vietnam. We conducted a population-based cross-sectional survey and a matched case-control study in Khanh Hoa Province where not only some pre-schoolchildren but also some school children, who take a nap during lunch break prior to returning to school, used bed nets during the day. Among 36,901 children 2-10 years of age, most used untreated bed nets during the night (98.3%) compared with 8.4% during the day. The results of the case-control study, which defined 151 cases who were hospitalized with DHF in the provincial hospitals and 604 age-matched neighborhood controls, did not support our hypothesis that children using untreated bed nets during the day are less likely to be hospitalized with DHF (adjusted odds ratio = 0.56, 95% confidence interval = 0.23-1.39).

8. Minh HV
, Phan Thị Ngà. Tobacco use among women: gendered perspective to be included in global tobacco control policies. Indian J Med Res. 2010 May;131:600-2. No abstract available

Tobacco use among women: gendered perspective to be included in global tobacco control policies.

Minh HV, Nga PT.

9. Okamoto K, Endo Y, Inoue S, Nabeshima T, Phan Thị Ngà, Guillermo PH, Yu F, Đỗ Phương Loan, Bùi Minh Trang, Natividad FF, Hasebe F, Morita K. Development of a rapid and comprehensive proteomics-based arboviruses detection system.J Virol Methods. 2010 Jul;167(1):31-36. Epub 2010 Mar 19. 

Development of a rapid and comprehensive proteomics-based arboviruses detection system.

Okamoto K, Endo Y, Inoue S, Nabeshima T, Nga PT, Guillermo PH, Yu F, Loan do P, Trang BM, Natividad FF, Hasebe F, Morita K.

Abstract

A rapid and comprehensive protocol, which combines simple purification and liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI/MS/MS), was developed for identification of arboviruses in infected culture fluid. Using this protocol, various arboviruses were detected including uncommon viruses that were described previously as Banna virus and Yunnan orbivirus. This approach is useful for the rapid screening of viral samples that cannot be identified by conventional gene amplification or immunological methods. 

10. Varma JK, McCarthy KD, Tasaneeyapan T, Monkongdee P, Kimerling ME, Buntheoun E, Sculier D, Keo C, Phanuphak P, Teeratakulpisarn N, Udomsantisuk N, Dung NH, Lan NT, Nguyễn Thu Yến, Cain KP. Bloodstream infections among HIV-infected outpatients, Southeast Asia.Emerg Infect Dis. 2010 Oct;16(10):1569-75.  

Bloodstream infections among HIV-infected outpatients, Southeast Asia.

Varma JK, McCarthy KD, Tasaneeyapan T, Monkongdee P, Kimerling ME, Buntheoun E, Sculier D, Keo C, Phanuphak P, Teeratakulpisarn N, Udomsantisuk N, Dung NH, Lan NT, Yen NT, Cain KP.

Abstract

Bloodstream infections (BSIs) are a major cause of illness in HIV-infected persons. To evaluate prevalence of and risk factors for BSIs in 2,009 HIV-infected outpatients in Cambodia, Thailand, and Vietnam, we performed a single Myco/F Lytic blood culture. Fifty-eight (2.9%) had a clinically significant BSI (i.e., a blood culture positive for an organism known to be a pathogen). Mycobacterium tuberculosis accounted for 31 (54%) of all BSIs, followed by fungi (13 [22%]) and bacteria (9 [16%]). Of patients for whom data were recorded about antiretroviral therapy, 0 of 119 who had received antiretroviral therapy for ≥14 days had a BSI, compared with 3% of 1,801 patients who had not. In multivariate analysis, factors consistently associated with BSI were fever, low CD4+ T-lymphocyte count, abnormalities on chest radiograph, and signs or symptoms of abdominal illness. For HIV-infected outpatients with these risk factors, clinicians should place their highest priority on diagnosing tuberculosis.

11. Kay BH, Tuyet Hanh TT, Nguyễn Hoàng Lê, Quy TM, Vũ Sinh Nam, Hang PV, Nguyễn Thị Yên, Hill PS, Vos T, Ryan PA. Sustainability and cost of a community-based strategy against Aedes aegypti in northern and central Vietnam.Am J Trop Med Hyg. 2010 May;82(5):822-30.  

Sustainability and cost of a community-based strategy against Aedes aegypti in northern and central Vietnam.

Kay BH, Tuyet Hanh TT, Le NH, Quy TM, Nam VS, Hang PV, Yen NT, Hill PS, Vos T, Ryan PA.

Abstract

We previously reported a new community-based mosquito control that resulted in the elimination of Aedes aegypti in 40 of 46 communes in northern and central Vietnam. During 2007 and 2008, we revisited Nam Dinh and Khanh Hoa provinces in northern and central Vietnam, respectively, to evaluate whether or not these programs were still being maintained 7 years and 4.5 years after formal project activities had ceased, respectively. Using a previously published sustainability framework, we compared 13 criteria from Tho Nghiep commune in Nam Dinh where the local community had adopted our community-based project model using Mesocyclops from 2001. These data were compared against a formal project commune, Xuan Phong, where our successful intervention activities had ceased in 2000 and four communes operating under the National Dengue Control Program with data available. In Khanh Hoa province, we compared 2008 data at Ninh Xuan commune with data at project completion in 2003 and benchmarked these, where possible, against an untreated control commune, Ninh Binh, where few control activities had been undertaken. The three communes where the above community-based strategy had been adopted were rated as well-sustained with annual recurrent total costs (direct and indirect) of $0.28-0.89 international dollars per person.

12. Higa Y, Nguyễn Thị Yên, Kawada H, Trần Hải Sơn, Nguyễn Thúy Hoa, Takagi M. Geographic distribution of Aedes aegypti and Aedes albopictus collected from used tires in Vietnam.J Am Mosq Control Assoc. 2010 Mar;26(1):1-9.

Geographic distribution of Aedes aegypti and Aedes albopictus collected from used tires in Vietnam.

Higa Y, Yen NT, Kawada H, Son TH, Hoa NT, Takagi M.

Abstract

The spatial distribution of Aedes aegypti and Aedes albopictus in environmental and geographical zones, e.g., urban-rural, coastal-mountainous, and north-south, was investigated throughout Vietnam. Immature stages were collected from used tires along roads. The effects of regions, seasons, and the degree of urbanization on the density and the frequency were statistically analyzed. Aedes aegypti predominated in the southern and central regions, while Ae. albopictus predominated in the northern region, which may be related to climatic conditions (temperature and rainfall). Larval collection from used tires may be suitable to assess rapidly the current distribution of dengue mosquitoes for estimating health risks and implementing vector control measures. 

13. Yen NT, Bogdanović X, Palm GJ, Kühl O, Hinrichs W. Structure of the Ni(II) complex of Escherichia coli peptide deformylase and suggestions on deformylase activities depending on different metal(II) centres.J Biol Inorg Chem. 2010 Feb;15(2):195-201. 

Structure of the Ni(II) complex of Escherichia coli peptide deformylase and suggestions on deformylase activities depending on different metal(II) centres.

Yen NT, Bogdanović X, Palm GJ, Kühl O, Hinrichs W.

Abstract

Crystal structures of polypeptide deformylase (PDF) of Escherichia coli with nickel(II) replacing the native iron(II) have been solved with chloride and formate as metal ligands. The chloro complex is a model for the correct protonation state of the hydrolytic hydroxo ligand and the protonated status of the Glu133 side chain as part of the hydrolytic mechanism. The ambiguity that recently some PDFs have been identified with Zn(2+) ion as the active-site centre whereas others are only active with Fe(2+) (or Co(2+), Ni(2+) is discussed with respect to Lewis acid criteria of the metal ion and substrate activation by the CD loop.

14. Nguyễn Thanh Thủy, Trần Quang Huy, Đỗ Thị Thoa, Nguyễn Minh Liên, Dung N.T., Irene, D., Benedetti, E.L., Izumi, S.I., Man, N.V., 2010. Ultrastructure features of H5N1 avian influenza virus in vero cell line. J. Electr.Microsc. Technol. Med. Biol. 24 (1), 14-18 (2010)

Ultrastructure features of H5N1 avian influenza virus in vero cell line.

Thuy, N.T., Huy, T.Q., Thoa, D.T., Lien, N.M., Dung N.T., Irene, D., Benedetti, E.L., Izumi, S.I., Man, N.V., 2010..

15. Phuong Dinh Tam, Mai Anh Tuan, Trần Quang Huy, Anh-Tuan Le, Nguyen Van Hieu, 2010. Facile preparation of a DNA sensor for rapid herpes virus detection. Mat. Sci. Eng.: C, Vol. 30, 1145 – 1150 (2010)

Facile preparation of a DNA sensor for rapid herpes virus detection 

Phuong Dinh Tam, Mai Anh Tuan, Tran Quang Huy, Anh-Tuan Le and Nguyen Van Hieu

Abstract

In this paper, a simple DNA sensor platform was developed for rapid herpes virus detection in real samples. The deoxyribonucleic acid (DNA) sequences of the herpes simplex virus (DNA probe) were directly immobilized on the surface of interdigitated electrodes by electrochemical polymerization along with pyrrole monomers. The potential was scanned from − 0.7 to + 0.6 V, and the scanning rate was 100 mV/s. Fourier transform infrared spectroscopy was employed to verify specific DNA sequence binding and the conducting polymer. The morphology of the conducting polymer doped with DNA strands was characterized using a field emission scanning electron microscope. As-obtained DNA sensor was used to detect the herpes virus DNA in the real samples. The results show that the current DNA sensors detected the lowest DNA concentration of 2 nM. This sensitivity appears to be better than that of the DNA sensors prepared by immobilization of the DNA probe on the 3-aminopropyl-triethoxy-silance (APTS) membrane. 

16. Anh-Tuan Le, Le Thi Tam, Phuong Dinh Tam, P.T Huy, Trần Quang Huy, Nguyen Van Hieu, A A Kudrinskiy, Yu A Krutyakov. Synthesis of oleic acid-stabilized silver nanoparticles and analysis of their antibacterial activity. Mat. Sci. Eng.: C, Vol. 30, (6), 910-916 (2010)

Synthesis of oleic acid-stabilized silver nanoparticles and analysis of their antibacterial activity 

Anh-Tuan Le, Le Thi Tam, Phuong Dinh Tam, P.T Huy, Tran Quang Huy, Nguyen Van Hieu, A A Kudrinskiy and Yu A Krutyakov 

Abstract 

The development of new and simple green chemical methods for synthesizing colloidal solutions of functional nanoparticles is desirable for environment-friendly applications. In the present work, we report a feasible method for synthesizing colloidal solutions of silver nanoparticles (Ag NPs) based on the modified Tollens technique. The Ag NPs were stabilized by using oleic acid as a surfactant and were produced for the first time by the reduction of silver ammonium complex [Ag(NH3)2]+(aq) by glucose with UV irradiation treatment. A stable and nearly monodisperse aqueous Ag NPs solution with average-sized particles (~ 9–10 nm) was obtained. The Ag NPs exhibited high antibacterial activity against both Gram-negative Escherichia Coli (E. coli) and Gram-positive Staphylococcus aureus bacteria. Electron microscopic images and analyses provided further insights into the interaction and bactericidal mechanism of the Ag NPs. The proposed method of synthesis is an effective way to produce highly bactericidal colloidal solutions for medical, microbiological, and industrial applications.

17. Anh-Tuan Le, P.T. Huy, Phuong Dinh Tam, Trần Quang Huy, Phùng Đắc Cam, A.A. Kudrinskiy, Yu A. Krutyakov. Green synthesis of finely-dispersed highly bactericidal silver nanoparticles via modified Tollens technique.  Current Applied Physics, Vol. 10, Iss. 3, 910-916 (2010).

Green synthesis of finely-dispersed highly bactericidal silver nanoparticles via modified Tollens technique 

Anh-Tuan Le, P.T Huy, Phuong Dinh Tam, Tran Quang Huy, Phung Dac Cam, A.A. Kudrinskiy and Yu A. Krutyakov

   Abstract 

In this article, we represent a versatile and effective technique which using non-toxic chemicals to prepare stable aqueous dispersions of silver nanoparticles (NPs) via modified Tollens process. It was shown that as-prepared silver colloids consisted of finely-dispersed NPs with average diameter about 10 nm and a relatively narrow size distribution. Moreover, they could be stored very stable after several months without observation of aggregates or sedimentation. In comparison with previous works where Tollens process was being used, we for the first time applied UV-irradiation simultaneously with glucose reduction of silver salt through NPs preparation. The colloidal solutions of silver NPs were found to exhibit a high antibacterial activity against gram-negative Escherichia coli. The concentration of silver leading to a complete inhibition of bacteria growth was revealed as low as at 1.0 μg ml−1 and found much lower compared to earlier reports. These advantages of aqueous dispersions of silver NPs make them ideal for green industrial, medicinal, microbiological and other applications.

18. Anh-Tuan Le, P.T. Huy, Trần Quang Huy, Phùng Đắc Cam, A.A. Kudrinskiy, A. Yu. Olenin, G. V. Lisichkin, Yu A. Krutyakov. Photochemical synthesis of highly bactericidal silver nanoparticles. Nanotechnologies in Rusia. Vol. 5, N. 7-8, 554-563 (2010).
 
Photochemical synthesis of highly bactericidal silver nanoparticles

Anh-Tuan Le
, P. T. Huy, Tran Quang Huy, Phung Dac Cam,A.A. Kudrinskiy, A.Yu. Olenin, G.V. Lisichkin, Yu.A. Krutyakov.

Abstract 

In this work we describe an experimental technique that makes it possible to obtain highly bactericidal silver nanoparticles (NPs). Synthesis was carried out using nontoxic reagents, and the technique consisted of reducing silver by glucose via UV irradiation in the presence of oleic or myristic acids as stabilizers. The size of the NPs fell in the range of 4–18 nm, and the average diameter was about 7 ± 1 nm (oleic acid) and 4 ± 1 nm (myristic acid). Unlike previous reports, where the Tollens reaction was used only with the assistance of thermal activation, we conducted the UV reduction of a silver nitrate solution, glucose, and the stabilizer at room temperature for the first time. The minimum inhibition concentration of nanosized silver against a gram-negative Escherichia coli was 1 μg/ml. Thus, the activity of the NPs appeared to be considerably higher than that of nanosilver samples that arecurrently known.

19. Barennes H, Keophithoun T, Nguyễn Hải Tuấn, Strobel M, Odermatt P. Survival and health status of DOTS tuberculosis patients in rural Lao PDR. BMC Infectious Disease, Volume 10: 265 – 271 (2010)

Survival and health status of DOTS tuberculosis patients in rural Lao PDR

Hubert Barennes, Thongdam Keophithoun, Tuan H Nguyen, Michel Strobeland Peter Odermatt

Abstract

Background

Contact tracing of tuberculosis (TB) patients is rarely performed in low-income countries. Our objective was to assess the outcome of and compliance with directly observed treatment (DOTS) of TB patients over a 3 year period in rural Lao PDR.

Methods

We performed a retrospective cohort study in which we enrolled TB patients who started DOTS treatment at Attapeu Provincial Hospital. We traced, through hospital records, all patients in their residential village. We conducted a standardized questionnaire with all TB patients and performed physical and anthropometric examinations as well as evaluations of compliance through counting of treatment pills at home and at the health facilities.

Results

Of 172 enrolled TB patients (sex ratio female/male: 0.52, mean age: 46.9 years ± 16.9), 26 (15.1%) died. These had a lower weight at the start (34.6 vs. 40.8 kg, p < 0.001) and were less compliant (91.6% vs. 19.2%, p < 0.001) than survivors. Low compliance was associated with poor accessibility to health care (p = 0.01) and symptomatic improvement (p = 0.02). Survivors had persistently poor health status. They were underweight (54.7%), and still had clinical symptoms (53.5%), including dyspnoea (28.8%) and haemoptysis (9.5%).

Conclusion

Our study suggests a lower rate of survival than expected from official statistics. Additionally, it showed that follow-up of TB patients is feasible although the patients lived in very remote area of Laos. Follow-up should be strengthened as it can improve patient compliance, and allow contact tracing, detection of new cases and collection of accurate treatment outcome information.

20. K Zaman, Đặng Đức Anh, John C Victor, Sunheang Shin, Md Yunus, Michael J Dallas, Goutam Podder, Vũ Đình Thiểm, Lê Thị Phương Mai,Stephen P Luby, Le Huu Tho, Michele L Coia, Kristen Lewis, Stephen B Rivers, David A Sack, Florian Schödel, A Duncan Steele, Kathleen M Neuzil, Max Ciarlet. Ecacy of pentavalent rotavirus vaccine against severerotavirus gastroenteritis in infants in developing countriesin Asia: a randomised, double-blind, placebo-controlled trial. The Lancet Vol 376 August 21, 2010.

Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in Asia: a randomised, double-blind, placebo-controlled triall

K Zaman, Dang Duc Anh, John C Victor, Sunheang Shin, Md Yunus, Michael J Dallas, Goutam Podder, Vu Dinh Thiem, Le Thi Phuong Mai, Stephen P Luby, Le Huu Tho, Michele L Coia, Kristen Lewis, Stephen B Rivers, David A Sack, Florian Schödel, A Duncan Steele, Kathleen M Neuzil, Max Ciarlet

Abstract

Background

Rotavirus vaccine has proved effective for prevention of severe rotavirus gastroenteritis in infants in developed countries, but no efficacy studies have been done in developing countries in Asia. We assessed the clinical efficacy of live oral pentavalent rotavirus vaccine for prevention of severe rotavirus gastroenteritis in infants in Bangladesh and Vietnam.

Methods

In this multicentre, double-blind, placebo-controlled trial, undertaken in rural Matlab, Bangladesh, and urban and periurban Nha Trang, Vietnam, infants aged 4—12 weeks without symptoms of gastrointestinal disorders were randomly assigned (1:1) to receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks, 10 weeks, and 14 weeks of age, in conjunction with routine infant vaccines including oral poliovirus vaccine. Randomisation was done by computer-generated randomisation sequence in blocks of six. Episodes of gastroenteritis in infants who presented to study medical facilities were reported by clinical staff and from parent recollection. The primary endpoint was severe rotavirus gastroenteritis (Vesikari score ≥11) arising 14 days or more after the third dose of placebo or vaccine to end of study (March 31, 2009; around 21 months of age). Analysis was per protocol; infants who received scheduled doses of vaccine or placebo without intervening laboratory-confirmed naturally occurring rotavirus disease earlier than 14 days after the third dose and had complete clinical and laboratory results were included in the analysis.

Findings

2036 infants were randomly assigned to receive pentavalent rotavirus vaccine (n=1018) or placebo (n=1018). 991 infants assigned to pentavalent rotavirus vaccine and 978 assigned to placebo were included in the per-protocol analysis. Median follow up from 14 days after the third dose of placebo or vaccine until final disposition was 498 days (IQR 480—575). 38 cases of severe rotavirus gastroenteritis (Vesikari score ≥11) were reported during more than 1197 person-years of follow up in the vaccine group, compared with 71 cases in more than 1156 person years in the placebo group, resulting in a vaccine efficacy of 48·3% (95% CI 22·3—66·1) against severe disease (p=0·0005 for efficacy >0%) during nearly 2 years of follow-up. 25 (2·5%) of 1017 infants assigned to receive vaccine and 20 (2·0%) of 1018 assigned to receive placebo had a serious adverse event within 14 days of any dose. The most frequent serious adverse event was pneumonia (vaccine 12 [1·2%]; placebo 15 [1·5%]).

Interpretation

In infants in developing countries in Asia, pentavalent rotavirus vaccine is safe and efficacious against severe rotavirus gastroenteritis, and our results support expanded WHO recommendations to promote its global use.

21. Lê Quỳnh Mai, Heiman F.L. Wertheim, Trần Như Dương, Rogier van Doorn, Juliet Bryant, Jeremy Farrar, Nguyen Van Kinh, Nguyễn Trần Hiển, Peter Horby. Limited community transmission of oseltamivir resistant pandemic influenza (H1N1) 2009. New England Journal of Medicine, 2010.

A Community Cluster of Oseltamivir-Resistant Cases of 2009 H1N1 Influenza

Le Quynh Mai, Heiman F.L. Wertheim, Tran Nhu Duong, H. Rogier van Doorn, Nguyen Tran Hien, Peter Horby

Abstract

Oseltamivir-resistant infection with the 2009 pandemic influenza A (H1N1) virus has so far been described only rarely and is conferred by the H275Y substitution in the neuraminidase enzyme.1 Only 3 of the 32 patients with oseltamivir-resistant infection reported on as of this writing were not receiving oseltamivir when the resistant viruses were detected, and ongoing community transmission has not yet been shown.1 However, the emergence of oseltamivir-resistant 2009 H1N1 influenza remains a grave concern, since widespread oseltamivir resistance has been observed in seasonal H1N1. This resistance was unrelated to selective drug pressure, and the H275Y substitution did not appear to reduce transmissibility or severity.2,3 We report on a cluster of seven cases of oseltamivir-resistant 2009 H1N1 infection in Vietnam.

22. T. Kubo, M. Agoh, Lê Quỳnh Mai, H. Nishimura, A. Yamaguchi, M. Hirano, A. Yoshikawa, F. Hasebe, K. Morita. Development of reverse transcription-loop-mediated isothermal amplification assay for swine-origin influenza A (H1N1) virus as a novel molecular based testing for pandemic influenza even in resource limited settings. Journal of Clinical Microbiology,2010 (p.728-735; Vol 48, No 3).

Development of a Reverse Transcription-Loop-Mediated Isothermal Amplification Assay for Detection of Pandemic (H1N1) 2009 Virus as a Novel Molecular Method for Diagnosis of Pandemic Influenza in Resource-Limited Settings

Toru Kubo, Masanobu Agoh, Le Q. Mai, Kiyoyasu Fukushima, Hidekazu Nishimura,Akinori Yamaguchi, Manabu Hirano, Akira Yoshikawa, Futoshi Hasebe, Shigeru Kohno and Kouichi Morita

Abstract

This paper reports on the development of a one-step, real-time reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay targeting the hemagglutinin (HA) gene for the rapid molecular-based detection of pandemic (H1N1) 2009 virus. The detection limit of the pandemic (H1N1) 2009 virus HA-specific RT-LAMP assay was same as that of the currently used real-time reverse transcription-PCR method. The assay detected the pandemic (H1N1) 2009 virus HA gene in 136 RNA samples extracted from nasopharyngeal swab specimens from Japanese and Vietnamese patients. No cross-reactive amplification with the RNA of other seasonal influenza viruses was observed, and the detection of specific viral genome targets in clinical specimens was achieved in less than 40 min. The sensitivity and specificity of the pandemic (H1N1) 2009 virus HA-specific RT-LAMP assay obtained in this study were 97.8% and 100%, respectively. Use of the (H1N1) 2009 virus HA-specific RT-LAMP assay will enable the faster and easier diagnosis of pandemic (H1N1) 2009 virus infection, especially in resource-limited situations in developing countries.

23. M. Kiso, K, Takahashi, Y. Tagawa, K.Shinya, S.Sakabe, Lê Quỳnh Mai, M.Ozawa, Y.Furuta and Y.Kawaoka. T-705 (favipiravir) activity against lethal H5N1 influenza A Viruses. Pnas, 2010 (Vol 107, No.2).

T-705 (favipiravir) activity against lethal H5N1 influenza A viruses

Maki Kiso, Kazumi Takahashi, Yuko Sakai-Tagawa, Kyoko Shinya, Saori Sakabe, Quynh Mai Le, Makoto Ozawa, Yousuke Furuta, and Yoshihiro Kawaoka

Abstract

The neuraminidase inhibitors oseltamivir and zanamivi are used to treat H5N1 influenza. However, oseltamivir-resistant H5N1 viruses have been isolated from oseltamivir-treated patients. Moreover, reassortment between H5N1 viruses and oseltamvir-resistant human H1N1 viruses currently circulating could create oseltamivir-resistant H5N1 viruses, rendering the oseltamivir stockpile obsolete. Therefore, there is a need for unique and effective antivirals to combat H5N1 influenza viruses. The investigational drug T-705 (favipiravir; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has antiviral activity against seasonal influenza viruses and a mouse-adapted H5N1 influenza virus derived from a benign duck virus. However, its efficacy against highly pathogenic H5N1 viruses, which are substantially more virulent, remains unclear. Here, we demonstrate that T-705 effectively protects mice from lethal infection with oseltamivir-sensitive or -resistant highly pathogenic H5N1 viruses. Furthermore, our biochemical analysis suggests that T-705 ribofuranosyl triphosphate, an active form of T-705, acts like purines or purine nucleosides in human cells and does not inhibit human DNA synthesis. We conclude that T-705 shows promise as a therapeutic agent for the treatment of highly pathogenic H5N1 influenza patients.

24. M. Kiso, S.Kubo, M.Ozawa, Lê Quỳnh Mai, Chairul A. Nidom, M Yamshita ,Y.Kawaoka. Efficacy of the New Neuraminidase Inhibitor CS-8958 against H5N1 influenza viruses. PLoS pathogens, 2010 (vol 6, issue 2).

Efficacy of the New Neuraminidase Inhibitor CS-8958 against H5N1 Influenza Viruses

Maki Kiso, Shuku Kubo, Makoto Ozawa, Quynh Mai Le, Chairul A. Nidom, Makoto Yamashita, and Yoshihiro Kawaoka

Abstract

Currently, two neuraminidase (NA) inhibitors, oseltamivir and zanamivir, which must be administrated twice daily for 5 days for maximum therapeutic effect, are licensed for the treatment of influenza. However, oseltamivir-resistant mutants of seasonal H1N1 and highly pathogenic H5N1 avian influenza A viruses have emerged. Therefore, alternative antiviral agents are needed. Recently, a new neuraminidase inhibitor, R-125489, and its prodrug, CS-8958, have been developed. CS-8958 functions as a long-acting NA inhibitor in vivo (mice) and is efficacious against seasonal influenza strains following a single intranasal dose. Here, we tested the efficacy of this compound against H5N1 influenza viruses, which have spread across several continents and caused epidemics with high morbidity and mortality. We demonstrated that R-125489 interferes with the NA activity of H5N1 viruses, including oseltamivir-resistant and different clade strains. A single dose of CS-8958 (1,500 µg/kg) given to mice 2 h post-infection with H5N1 influenza viruses produced a higher survival rate than did continuous five-day administration of oseltamivir (50 mg/kg twice daily). Virus titers in lungs and brain were substantially lower in infected mice treated with a single dose of CS-8958 than in those treated with the five-day course of oseltamivir. CS-8958 was also highly efficacious against highly pathogenic H5N1 influenza virus and oseltamivir-resistant variants. A single dose of CS-8958 given seven days prior to virus infection also protected mice against H5N1 virus lethal infection. To evaluate the improved efficacy of CS-8958 over oseltamivir, the binding stability of R-125489 to various subtypes of influenza virus was assessed and compared with that of other NA inhibitors. We found that R-125489 bound to NA more tightly than did any other NA inhibitor tested. Our results indicate that CS-8958 is highly effective for the treatment and prophylaxis of infection with H5N1 influenza viruses, including oseltamivir-resistant mutants.

25. Yuko Sakai- Tagawa, M.Ozawa ,Daisuke Tamura, Lê Thị Quỳnh Mai, Chairul A.Nidom, Norio Sugaya and Yoshihiro Kawaoka. Sensitivity of Influenza Rapid Diagnostic test to H5N1 and 2009 pandemic H1N1 viruses. Journal of Clinical Microbiology, 2010 (p.2872-2877; Vol 48, No 8).

Sensitivity of influenza rapid diagnostic tests to H5N1 and 2009 pandemic H1N1 viruses 

Yuko Sakai-Tagawa, Makoto Ozawa, Daisuke Tamura, Quynh Mai Le, Chairul A. Nidom, Norio Sugaya, and Yoshihiro Kawaoka

Abstract 

Simple and rapid diagnosis of influenza is useful to treatmentdecision-making in the clinical setting. Although many influenzarapid diagnostic tests (IRDTs) are available for the detectionof seasonal influenza virus infections, their sensitivity forother viruses, such as H5N1 viruses and the recently emergedswine-origin pandemic (H1N1) 2009 virus, remains largely unknown.Here, we examined the sensitivity of 20 IRDTs to various influenzavirus strains, including H5N1 and 2009 pandemic H1N1 viruses.Our results indicate that the detection sensitivity to swine-originH1N1 viruses varies widely among IRDTs, with some tests lackingsufficient sensitivity to detect the early stages of infectionwhen the virus load is low.

26. Lê Quỳnh Mai, Mutsumi Ito, Yukiko Muramoto, Vũ Hoàng Mai Phương,Vương Đức Cường, Yoko Sakai-Tagawa, Maki Kiso, Makoto Ozawa, Ryo Takano, Yoshihiro Kawaoka. Pathogenicity of highly pathogenic avian H5N1 influenza A viruses isolated from human between 2003-2008 in northern Vietnam. Journal of General virology; 2010; vol 91 no 10,p.2485-2490.

Pathogenicity of highly pathogenic avian H5N1 influenza A viruses isolated from humans from 2003 to 2008 in Northern Vietnam

Quynh Mai Le, Mutsumi Ito, Yukiko Muramoto, Phuong Vu Mai Hoang, Cuong Duc Vuong, Yuko Sakai-Tagawa, Maki Kiso, Makoto Ozawa, Ryo Takano and Yoshihiro Kawaoka

Abstract

Vietnam is one of the countries most affected by highly pathogenicH5N1 influenza A viruses. To evaluate the potential pathogenicityin mammals of H5N1 viruses isolated from humans in Vietnam,we determined the sequences of all eight genes of twenty-twohuman isolates collected between 2003 and 2008 and comparedtheir virulence in mice. The isolates were classified into clade1 and clade 2.3.4 and differed in pathogenicity for mice. Whilelysine at position 627 (PB2-627K) is a critical virulence determinantfor the clade 2.3.4 viruses, asparagine at position 701 of PB2and other unknown virulence determinants appear to be involvedin the high pathogenicity of clade 1 viruses, warranting furtherstudies to determine the factors responsible for the high virulenceof H5N1 viruses in mammals.

27. H .Takakuwa, T. Yamashiro, Lê Quỳnh Mai, Lien S.Phuong, H.Ozaki, R. Tsuneuki, T.Usui, H.Ito, T.Yamaguchi, T.Ito,T.Murase, E.Ono and K.Otsuki.Possible circulation of H5N1 avian influenza viruses in healthy duck on farms in northen Vietnam. Microbiol Immunol, 2010, Vol 54; p:58-62.

Possible circulation of H5N1 avian influenza viruses in healthy ducks on farms in northern Vietnam

Takakuwa H, Yamashiro T, Le MQ, Phuong LS, Ozaki H, Tsunekuni R, Usui T, Ito H, Yamaguchi T, Ito T, Murase T, Ono E, Otsuki K.

Abstract

To estimate the prevalence of influenza A subtype H5N1 viruses among domestic ducks in the period between October and November 2006 when H5N1 outbreaks had been absent, 1106 healthy ducks raised in northern Vietnam were collected. Inoculation of all throat and cloacae samples into embryonated eggs resulted in the isolation of subtype H3N8 in 13 ducks, but not H5N1 viruses. Serological analyses demonstrated that five ducks (0.45%) solely developed H5N1 subtype-specific hemagglutinin-inhibiting and neuraminidase-inhibiting antibodies together with anti-non-structural protein 1 antibodies. The results suggested that the ducks were naturally infected with H5N1 viruses when obvious H5N1 outbreaks were absent.

28. Maki Kiso, Kyoko Shinya, Masayuki Shimojima, Ryo Takano, Kei Takahashi, Hiroaki Katsura, Satoshi Kakugawa, Lê Thị Quỳnh Mai, Makoto Yamashita, Yousuke Furuta, Makoto Ozawa, and Yoshihiro Kawaoka. Characterization of Oseltamivir-Resistant 2009 H1N1 Pandemic Influenza A Viruses. Plos Pathogen. Vol 6 (8), Aug, 2010.

Characterization of Oseltamivir-Resistant 2009 H1N1 Pandemic Influenza A Viruses

Maki Kiso, Kyoko Shinya, Masayuki Shimojima, Ryo Takano, Kei Takahashi, Hiroaki Katsura, Satoshi Kakugawa, Mai thi Quynh Le, Makoto Yamashita, Yousuke Furuta, Makoto Ozawa, and Yoshihiro Kawaoka

Abstract

Influenza viruses resistant to antiviral drugs emerge frequently. Not surprisingly, the widespread treatment in many countries of patients infected with 2009 pandemic influenza A (H1N1) viruses with the neuraminidase (NA) inhibitors oseltamivir and zanamivir has led to the emergence of pandemic strains resistant to these drugs. Sporadic cases of pandemic influenza have been associated with mutant viruses possessing a histidine-to-tyrosine substitution at position 274 (H274Y) in the NA, a mutation known to be responsible for oseltamivir resistance. Here, we characterized in vitro and in vivo properties of two pairs of oseltaimivir-sensitive and -resistant (possessing the NA H274Y substitution) 2009 H1N1 pandemic viruses isolated in different parts of the world. An in vitro NA inhibition assay confirmed that the NA H274Y substitution confers oseltamivir resistance to 2009 H1N1 pandemic viruses. In mouse lungs, we found no significant difference in replication between oseltamivir-sensitive and -resistant viruses. In the lungs of mice treated with oseltamivir or even zanamivir, 2009 H1N1 pandemic viruses with the NA H274Y substitution replicated efficiently. Pathological analysis revealed that the pathogenicities of the oseltamivir-resistant viruses were comparable to those of their oseltamivir-sensitive counterparts in ferrets. Further, the oseltamivir-resistant viruses transmitted between ferrets as efficiently as their oseltamivir-sensitive counterparts. Collectively, these data indicate that oseltamivir-resistant 2009 H1N1 pandemic viruses with the NA H274Y substitution were comparable to their oseltamivir-sensitive counterparts in their pathogenicity and transmissibility in animal models. Our findings highlight the possibility that NA H274Y-possessing oseltamivir-resistant 2009 H1N1 pandemic viruses could supersede oseltamivir-sensitive viruses, as occurred with seasonal H1N1 viruses.

29. Hirotaka Imai, Kyoko Shinya, Ryo Takano, Maki Kiso, Yukiko Muramoto, Saori Sakabe, ShinMurakami, Mutsumi Ito, Shinya Yamada, Lê Thị Quỳnh Mai, Chairul A. Nidom, Yuko Sakai-Tagawa,Kei Takahashi, Yasuyuki Omori, Takeshi Noda, Masayuki Shimojima, Satoshi Kakugawa,Hideo Goto, Kiyoko Iwatsuki-Horimoto, Taisuke Horimoto, Yoshihiro Kawaoka. The HA and NS genes of human H5N1 influenza A virus contribute to high virulence in ferrets. Plos Pathogen . Vol 6(9), Sept, 2010.

The HA and NS Genes of Human H5N1 Influenza A Virus Contribute to High Virulence in Ferrets

Hirotaka Imai, Kyoko Shinya, Ryo Takano, Maki Kiso, Yukiko Muramoto, Saori Sakabe, Shin Murakami, Mutsumi Ito, Shinya Yamada, Mai thi Quynh Le, Chairul A. Nidom, Yuko Sakai-Tagawa, Kei Takahashi, Yasuyuki Omori, Takeshi Noda, Masayuki Shimojima, Satoshi Kakugawa, Hideo Goto, Kiyoko Iwatsuki-Horimoto, Taisuke Horimoto, and Yoshihiro Kawaoka

Abstract

Highly pathogenic H5N1 influenza A viruses have spread across Asia, Europe, and Africa. More than 500 cases of H5N1 virus infection in humans, with a high lethality rate, have been reported. To understand the molecular basis for the high virulence of H5N1 viruses in mammals, we tested the virulence in ferrets of several H5N1 viruses isolated from humans and found A/Vietnam/UT3062/04 (UT3062) to be the most virulent and A/Vietnam/UT3028/03 (UT3028) to be avirulent in this animal model. We then generated a series of reassortant viruses between the two viruses and assessed their virulence in ferrets. All of the viruses that possessed both the UT3062 hemagglutinin (HA) and nonstructural protein (NS) genes were highly virulent. By contrast, all those possessing the UT3028 HA or NS genes were attenuated in ferrets. These results demonstrate that the HA and NS genes are responsible for the difference in virulence in ferrets between the two viruses. Amino acid differences were identified at position 134 of HA, at positions 200 and 205 of NS1, and at positions 47 and 51 of NS2. We found that the residue at position 134 of HA alters the receptor-binding property of the virus, as measured by viral elution from erythrocytes. Further, both of the residues at positions 200 and 205 of NS1 contributed to enhanced type I interferon (IFN) antagonistic activity. These findings further our understanding of the determinants of pathogenicity of H5N1 viruses in mammals.

30. Sakabe S, Iwatsuki-Horimoto K, Horimoto T, Nidom CA, Lê Thị Quỳnh Mai,Takano R, Kubota-Koketsu R, Okuno Y, Ozawa M, Kawaoka Y. A cross-reactive neutralizing monoclonal antibody protects mice from H5N1 and pandemic (H1N1) 2009 virus infection.Antiviral Res. 2010 Dec 16. [Epub ahead of print]

A cross-reactive neutralizing monoclonal antibody protects mice from H5N1 and pandemic (H1N1) 2009 virus infection

Sakabe S, Iwatsuki-Horimoto K, Horimoto T, Nidom CA, Le MQ, Takano R, Kubota-Koketsu R, Okuno Y, Ozawa M, Kawaoka Y.

Abstract

A novel influenza (H1N1) virus caused an influenza pandemic in 2009, while highly pathogenic H5N1 avian influenza viruses have continued to infect humans since 1997. Influenza, therefore, remains a serious health threat. Currently, neuraminidase (NA) inhibitors are the mainstay for influenza therapy; however, drug-resistant mutants of seasonal H1N1 and H5N1 viruses have emerged highlighting the need for alternative therapeutic approaches. One such approach is antibody immunotherapy. Here, we show that the monoclonal antibody C179, which recognizes a neutralizing epitope common among H1, H2, H5, and H6 hemagglutinins (HAs), protected mice from a lethal challenge with various H5N1 and pandemic (H1N1) 2009 viruses when administered either intraperitoneally or intranasally. The protective efficacy of intranasally inoculated C179 was comparable to that of intraperitoneal administration. Our results suggest that direct administration of this anti-influenza antibody to viral replication sites is an effective strategy for prophylaxis and therapy.

31. Monteerarat Y, Sakabe S, Ngamurulert S, Srichatraphimuk S, Jiamtom W, Chaichuen K, Thitithanyanont A, Permpikul P, Songserm T, Puthavathana P, Nidom CA, Lê Quỳnh Mai, Iwatsuki-Horimoto K, Kawaoka Y, Auewarakul P. Induction of TNF-alpha in human macrophages by avian and human influenza viruses. Arch Virol. 2010 Aug;155(8):1273-9.

Induction of TNF-α in human macrophages by avian and human influenza viruses

Yuwarat Monteerarat, Saori Sakabe, Somying Ngamurulert, Sirawat Srichatraphimuk, Wasana Jiamtom, Kridsada Chaichuen, Arunee Thitithanyanont, Parichart Permpikul, Taweesak Songserm, Pilaipan Puthavathana, Chairul A. Nidom, Le Quynh Mai, Kiyoko Iwatsuki-Horimoto, Yoshihiro Kawaoka, Prasert Auewarakul

Abstract

The highly pathogenic avian influenza virus H5N1 is known to induce high level of tumor necrosis factor α (TNF-α) from primary macrophages. However, it is still unclear whether current H5N1 strains also induce high TNF-α production, as most of the data were derived from extinct clade 0 H5N1 strain. Here, we show that current clade 1 and 2 H5N1 strains induce variable levels of TNF-α that are not necessarily higher than those induced by seasonal influenza viruses. The result suggests that hyper-induction of TNF-α in human macrophages is not always associated with a highly pathogenic phenotype. We further tested the contribution of the NS gene segment from H5N1 isolates to TNF-α induction by using reverse genetics. While NS conferred some variation in TNF-α induction when incorporated into an H1N1 virus genetic background, it did not affect TNF-α induction in an H5N1 virus genetic background, suggesting that other viral genes are involved.

32. Đặng Đức Anh; Riewpaiboon Arthorn; Le Tho Huu; Kim Soon Ae; Nyambat Batmunkh; Kilgore Paul. Treatment costs of pneumonia, meningitis, sepsis, and other diseases among hospitalized children in Viet Nam. Journal of health, population, and nutrition 2010;28(5):436-42.

Treatment costs of pneumonia, meningitis, sepsis, and other diseases among hospitalized children in Viet Nam.

Anh Dang Duc; Riewpaiboon Arthorn; Tho Le Huu; Kim Soon Ae; Nyambat Batmunkh; Kilgore Paul

Abstract

The aim of this study was to estimate the costs of treatment of children who present with the signs and symptoms of invasive bacterial diseases in Khanh Hoa province, Viet Nam. The study was an incidence-based cost-of-illness analysis from the health system perspective. The hospital costs included labour, materials and capital costs, both direct and indirect. Costs were determined for 980 children, with an average age of 12.67 months (standard deviation +/- 11.38), who were enrolled in a prospective surveillance at the Khanh Hoa General Hospital during 2005-2006. Of them, 57% were male. By disease-category, 80% were suspected of having pneumonia, 8% meningitis, 3% very severe disease consistent with pneumococcal sepsis, and 9% other diseases. Treatment costs for suspected pneumonia, meningitis, very severe disease, and other diseases were US$ 31, US$ 57, US$ 73, and US$ 24 respectively. Costs ranged from US$ 24 to US$ 164 across different case-categories. Both type of disease and age of patient had statistically significant effects on treatment costs. The results showed that treatment costs for bacterial diseases in children were considerable and might differ by as much as seven times among invasive pneumococcal diseases. Changes in costs were sensitive to both age of patient and case-category. These cost-of-illness data will be an important component in the overall evidence base to guide the development of vaccine policy in Viet Nam.

33. Trần Quang Bình,Vu Thi Thu Hien,Nguyen Cong Khan, Nguyen Thi Lam,Le Bach Mai, Masayo Nakamori, Shigeru Yamamoto. Relationship between vitamin D receptor gene polymorphisms and anaemiain postmenopausal Vietnamese women. Asian Biomed; 2010, Dec; 4(6): 869-75.

Relationship between vitamin D receptor gene polymorphisms and anaemiain postmenopausal Vietnamese women

Tran Quang Binh,Vu Thi Thu Hien,Nguyen Cong Khan, Nguyen Thi Lam,Le Bach Mai, Masayo Nakamori, Shigeru Yamamoto.

Abstract

Background:Both in vitro and in vivo studies have shown that calcitriol, the active form of vitamin D, is involved in hematopoiesis. Vitamin D receptor (VDR) gene has been suggested as one of the candidate genes for anaemia.

Objective:Investigate relationship between anaemia and the commonly studied polymorphisms of VDR gene (FokI, BsmI, ApaI and TaqI) in terms of genotype and haplotype in Vietnamese cohort.

Methods: A case-control study including 132 postmenopausal women without chronic kidney diseases was designed to investigate the relationship between VDR polymorphism and anaemia.Four single nucleotide polymorphisms (SNPs)FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) were typed by polymerase chain reaction and restriction fragment length polymorphism method.

Results: Genotype distributions of four SNPs were in Hardy–Weinberg equilibrium in both anaemia and controlgroups. The SNPs at the 3’end of the VDR gene (BsmI, ApaI and TaqI) exhibited a strong linkage disequilibrium. There was no significant association between anaemia and VDR polymorphism in terms of allele, genotype and haplotype in the analyses unadjusted or adjusted for the covariates (age, body mass index, educational level, serum ferritin, iron and albumin).

Conclusion:VDR gene did not influence anaemia in postmenopausal women without chronic kidneydisease. For further study on the association between VDR gene and anaemia, use of larger sample size, prospective study design, and additional markers would enhance the findings.

34. Azevedo MS, Gonzalez AM, Yuan L, Jeong KI, Iosef C, Nguyễn Vân Trang, Lovgren-Bengtsson K, Morein B, Saif LJ. An oral versus intranasal prime/boost regimen using attenuated human rotavirus or VP2 and VP6 virus-like particles with immunostimulating complexes influences protection and antibody-secreting cell responses to rotavirus in a neonatal gnotobiotic pig model. Clin Vaccine Immunol. 2010 Mar;17(3):420-8.

An oral versus intranasal prime/boost regimen using attenuated human rotavirus or VP2 and VP6 virus-like particles with immunostimulating complexes influences protection and antibody-secreting cell responses to rotavirus in a neonatal gnotobiotic pig model.

Azevedo MS, Gonzalez AM, Yuan L, Jeong KI, Iosef C, Van Nguyen T, Lovgren-Bengtsson K, Morein B, Saif LJ.

Abstract

We determined the impact of mucosal prime/boost regimens and vaccine type (attenuated Wa human rotavirus [AttHRV] or nonreplicating Wa 2/6 rotavirus-like particles [VLP]) on protection and antibody-secreting cell (ASC) responses to HRV in a neonatal gnotobiotic pig disease model. Comparisons of delivery routes for AttHRV and evaluation of nonreplicating VLP vaccines are important as alternative vaccine approaches to overcome risks associated with live oral vaccines. Groups of neonatal gnotobiotic pigs were vaccinated using combinations of oral (PO) and intranasal (IN) inoculation routes as follows: (i) 3 oral doses of AttHRV (AttHRV3xPO); (ii) AttHRV3xIN; (iii) AttHRVPO, then 2/6VLP2xIN; (iv) AttHRVIN, then 2/6VLP2xIN; and (v) mock-inoculated controls. Subsets of pigs from each group were challenged with virulent Wa HRV [P1A(8) G1] (4 weeks post-primary inoculation) to assess protection. The AttHRVPO+2/6VLP2xIN pigs had the highest protection rates against virus shedding and diarrhea (71% each); however, these rates did not differ statistically among the vaccine groups, except for the AttHRVIN+2/6VLPIN group, which had a significantly lower protection rate (17%) against diarrhea. The isotype, magnitude, and tissue distribution of ASCs were analyzed by enzyme-linked immunospot assay. The highest mean numbers of virus-specific IgG and IgA ASCs were observed pre- and postchallenge in both intestinal and systemic lymphoid tissues of the AttHRVPO+2/6VLPIN group. Thus, the AttHRVPO+2/6VLPIN vaccine regimen using immunostimulating complexes (ISCOM) and multiple mucosal inductive sites, followed by AttHRV3xPO or IN regimens, were the most effective vaccine regimens, suggesting that either AttHRVPO+2/6VLPIN or AttHRV3xIN may be an alternative approach to AttHRV3xPO for inducing protective immunity against rotavirus diarrhea.

35. Moon SS, Wang Y, Shane AL, Nguyễn Vân Trang, Ray P, Dennehy P, Baek LJ, Parashar U, Glass RI, Jiang B. Inhibitory effect of breast milk on infectivity of live oral rotavirus vaccines. Pediatr Infect Dis J. 2010 Oct;29(10):919-23.

Inhibitory effect of breast milk on infectivity of live oral rotavirus vaccines.        

Moon SS, Wang Y, Shane AL, Nguyen T, Ray P, Dennehy P, Baek LJ, Parashar U, Glass RI, Jiang B.

Abstract

Background:Live oral rotavirus vaccines have been less immunogenic and efficacious among children in poor developing countries compared with middle income and industrialized countries for reasons that are not yet completely understood. We assessed whether the neutralizing activity of breast milk could lower the titer of vaccine virus and explain this difference in vitro.

Methods:Breast milk samples were collected from mothers who were breast-feeding infants 4 to 29 weeks of age (ie, vaccine eligible age) in India (N = 40), Vietnam (N = 77), South Korea (N = 34), and the United States (N = 51). We examined breast milk for rotavirus-specific IgA and neutralizing activity against 3 rotavirus vaccine strains-RV1, RV5 G1, and 116E using enzyme immunoassays. The inhibitory effect of breast milk on RV1 was further examined by a plaque reduction assay.

Findings:Breast milk from Indian women had the highest IgA and neutralizing titers against all 3 vaccine strains, while lower but comparable median IgA and neutralizing titers were detected in breast milk from Korean and Vietnamese women, and the lowest titers were seen in American women. Neutralizing activity was greatest against the 2 vaccine strains of human origin, RV1 and 116E. This neutralizing activity in one half of the breast milk specimens from Indian women could reduce the effective titer of RV1 by 2 logs, of 116E by 1.5 logs, and RV5 G1 strain by 1 log more than that of breast milk from American women.

Interpretation:The lower immunogenicity and efficacy of rotavirus vaccines in poor developing countries could be explained, in part, by higher titers of IgA and neutralizing activity in breast milk consumed by their infants at the time of immunization that could effectively reduce the potency of the vaccine. Strategies to overcome this negative effect, such as delaying breast-feeding at the time of immunization, should be evaluated.

 
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