wdb Da7m*gv lemrsm;. a7m*gt a-ct ae/ ydk;r$m;t a-ct ae u dk, fchpgrf;t m;whk -yefr+esi fhu dk, fwgi f;aq ;0g;ju rrmav hv m-ci f;

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1 Vol. 25, No. 11 Published Since 1986 July, 2013 CONTENTS Highlights of Useful Research Findings Applicable to Health 1 Tuberculosis News about Medicine & Health 2 Frequently asked questions about pneumococcal vaccine Promising new method for nextgeneration live-attenuated viral vaccines against Chikungunya virus NIH investigators discover new gene that affects clearance of hepatitis C virus p53 mutations in liver cancer Multidrug-resistant plasmodium vivax associated with severe and fatal malaria: a prospective study in Papua, Indonesia Many false-positive HIV test results for those in AIDS vaccine trials The objective of this Bulletin is to disseminate international news about health and medicine, developments, activities in medical and health research in DMR (LM). The Bulletin is published monthly and delivered to township hospitals. The Editorial Committee, therefore, invites contributions concerning information about research activities and findings in the field of medicine and health. Please address all your correspondence to: Publication Division Department of Medical Research (Lower Myanmar) Ministry of Health No. 5, Ziwaka Road Dagon Township, Yangon, publicationdmr@gmail.com , , Ext: 123 Published by the Editorial Committee Department of Medical Research (LM) Restricted for Internal Use Only Highlights of Useful Research Findings Applicable to Health Evaluation of Clinical, Bacteriological, Pharmacological Factors and Immunological Responses of Pulmonary Tuberculosis Patients Tuberculosis is one of the five major diseases in Myanmar and treatment failure is one of the unwanted outcomes in tuberculosis management. An analytical study was carried out from January 2011 to December 2011 at Mingalardone and MingalarTaungNyunt TB center, Yangon to evaluate the clinical, bacteriological, immunological responses and pharmacokinetics of Rifampicin and Isoniazid. Out of 1290 TB patients, 50 newly diagnosed sputum positive patients, 50 Category I cured and 50 Category I treatment failure patients were randomly selected for socio-economic, clinical and immunological study, among which 30 patients were reselected for the pharmacokinetic evaluation. Methodology involved the use of proforma for details on knowledge, economic and other factors influencing their treatment responses, ELISA test for immunological study, culture and drug sensitivity testing for bacteriological study and chromatographic analysis for pharmacokinetic study. Serum Interferon γ level for immunological responses showed significantly higher in treatment failure cases than new cases and blood concentration of rifampicin was significantly lower in Cat I regime failure patients than cured patients. In bacteriological study of 15 Cat I treatment failure patients, MDR TB was found in 4 (26.6%) isolate, 3 (20%) isolates were resistant to isoniazid and ethambutol and 8 (53.3%) isolate were sensitive to all 4 drugs. In this group, 8 (53.3%) patients were still sputum positive after completion of the Cat II regime. It was concluded that pharmacological factors (reduced bioavailability) and bacteriological factors (drug resistant strain) are major risk factors of treatment failure and the development of MDR-TB. wdb Da7m*gv lemrsm;. a7m*gt a-ct ae/ ydk;r$m;t a-ct ae u dk, fchpgrf;t m;whk -yefr+esi fhu dk, fwgi f;aq ;0g;ju rrmav hv m-ci f; wdb Da7m*go n f _refrm_yn f7dst "du a7m*gju D;(5)rsdK;wGi f wpfckt ygt 0i f-zpf-yd; u ko r+rat mi f-ri f-ci f;o n f wdb Da7m*gu dkx def;cskyfr+-yk7mwgi f t cu ft cj-zpfap ygo n f? wdb Dv lemrsm;. aq ;u ko aysmu fu i f;r+7v ' ft a-ct aet m; a7m*g ydk;r$m;t a-ct ae/ u dk, fchpgrf;t m;whk -yefr+t a-ct ae/ wdb Daq ;rsm;. ceqmu dk, f wgi f;aq ;0g;a7mu f7sdr+wdk. o u fa7mu fv $rf;rdk;edki fr+u dkr*fv m' Hk_rdKŒe, f/ r*fv m awmi f! Gef _rdkœe, f wdb Du kxmewdk wgi fu ko r+ch, laeju ao mv lemr sm;t m;2011ckespf

2 Zefe0g7Dv rs' DZi fb mv t x d av hv mx m;ygo n f? t q dkyg v lem150t m; o v dyfydk;awg 7Sdv lemt o pft kyfpk/ wdb Da7m*g u ko r+ t q i fh=1-zi fh aysmu fu i f;ao m v lemt kyfpk/ wdb D a7m*gu ko r+ t q i fh=1-zi fh raysmu fu i f;ao m v lemt kyfpk [ li wpft kyfpkv #i f 50u spd-zi fhcgj-cm;x m;ygo n f? t x u fyg v lemr sm;rsv lem(30)t m; x yfr Ha7G;cs, fi wdb D aq ;rsm;. ce<mu dk, fwgi f; aq ;0g;a7mu f7sdr+t a-ct aeu dk av hv mygo n f? x dko dk av hv m7mwgi f v lemrsm;. pd;ygm;a7; t a-ct ae/ a7m*gesi fhywfo u fao ma[ ko kwpo -zi fht ao ; pdwft csu ft v u frsm;u dkar;cgef;v $myhkph-zi fh7, lygo n f? u dk, fchpgrf;t m;pepf. whk -yefr+u dk t Dv dki fzm en f;yn m-zi fh wdki f;wmygo n f? a7m*gydk;r$m;t a-ct aeesi fhywfo u fi a7m*g ydk;u dkarg;-rli aq ;, Ofyg;r+t a-ct aeu dk av hv mygo n f? ce<mu dk, fwgi f wdb Daq ;a7mu f7sdr+t a-ct aeu dkc7kdrwdk*7yf en f;yn mu dkt o Hk;-yKI wdki f;wmygo n f? u kd, fchpgrf;t m;whk -yef r+u dkav hv m7mwgi f ao G;t wgi f;7sdt i fwmz7gef*grmyrm%t m; wdki f;wmju n fh7m t x u fygt kyfpk(3)ckv Hk;wGi fo do mx i f&sm;pgm u GJ-ym;-ci f;r7sdaju mi f;awgœ7sd7ygo n f? 7dki fzefypi fwdb Daq ;. ao G;t wgi f;a7mu f7sdr+yrm%rsm a7m*gysmu fu i f;ao mv lrsm; wgi f ydkrdkr sm;-ym;i a7m*graysmu fao mo lr sm;wgi fr l ydkr dk en f;yg;aju mi f; awg 7Sd7ygo n f? wdb Da7m*gu ko r+t q i fh=1 -zi fh raysmu fu i f;ao m v lem (15) a, mu frswdb Daq ; (4)rsdK; Rifampicin, Isoniazid, Streptomycin ESi fh Ethambutolwdk t m; aq ;, Ofyg;r+ t a-ct aeu dk av hv m ju n fhygo n f? x dko dk av hv mju n hf7m v lem(3)od;wgi f aq ;ESpfrsdK;t m;, Ofyg; aju mi f;awg 7_yD;/ (4)OD;wGi faq ;av ;rsdk;v Hk;t m;, Ofyg;aju mi f; awg 7ygo n f? u sef(8)od;wgi f aq ;, Ofyg;r+r7Sdaju mi f; awg 7Sd 7ygo n f? o dk -zpfygi v lemrsm;. ceqmu dk, fwgi f; wdb Daq ;0g;ju rrmesi fh a7m*gydk;r$m;r sm;. aq ;, Ofyg;r +t a-ct aewdk o n f wdb D a7m*gu ko r+ t q i fh=1-zi fh u ko ao mv lemrsm;. a7m*g aysmu fu i f;r+/ raysmu fu i f;r+esi fhaq ;, Ofyg;wDb Dt -zpfa-ymi f; v JEdki fr+wdk t ay:wgi f o u fa7mu fv $rf;rdk;edki faju mi f; av hv m awg 7Sd7ygo n f? Reference: Khin Chit, Khin Saw Aye, Thandar Lwin, Tin Mi Mi Khaing, et al. 41 st Myanmar Health Research Congress Programme & Abstracts; 77. (Third Prize for Best Basic Research Paper) News about Medicine & Health Frequently Asked Questions about Pneumococcal Vaccine What Pneumococcal vaccines are available? There are two types of pneumococcal vaccine. Pneumococcal Polysaccharide Vaccine The 23-valent pneumococcal polysaccharide vaccine (PPV) is currently recommended for all adults over 65 years of age and those at-risk over 2 years of age. The vaccine provides protection against 23 types (or serotypes) of pneumococcal bacteria. At-risk children should be offered the PPV when they reach the age of 2 years. Pneumococcal Conjugate Vaccine The pneumococcal conjugate vaccine (PCV) contains the 7 most common serotypes of pneumococcal bacteria. PCV should be given to children at 2 months, 4 months and 13 months. The vaccine is also recommended for children from two months to under 5 years of age falling into one of the recommended risk groups. All at-risk children should be offered PCV in the schedule for the routine immunisation programme. In addition, all at-risk children should be offered a single dose of PPV when they are two years of age. Who needs pneumococcal vaccine? The objective of the pneumococcal immunisation programme is to protect all those for whom 2 pneumococcal infection is likely to be more common or more serious. This includes two groups: 1. All those aged 65 and over (PPV) 2. All those aged 2 months to under 2 year 3. Those under 65 with an at-risk condition (listed below) Children and adults falling into a clinical risk group Since 1992, PPV has been recommended for people who fall into a group at higher risk of invasive pneumococcal disease. Currently, this includes all person aged from two to 65 years of age with; Asplenia or dysfunction of the spleen Chronic respiratory disease Chronic heart disease Chronic renal disease Chronic liver disease Diabetes Immunosuppression Individuals with cochlear implants How often should adults receive the PPV vaccine? It is currently recommended that most adults will need only one dose of PPV in their lifetime. Revaccination every five years is only recommended

3 for those groups whose antibody levels are likely to decline. This includes those with splenic dysfunction or chronic renal disease. Is it safe to have the Pneumococcal vaccine at the same time as the annual influenza jab? Yes. In fact co-administration of the 2 vaccines is advocated. Are there any adverse reactions? PPV - Mild soreness can occur at the site of injection lasting one to three days and less commonly a lowgrade fever may occur. More severe systemic reactions are rare. PCV - swelling and redness at the injection site and low-grade fever are the most commonly reported adverse reactions. Is it possible to get the disease from the vaccine? The pneumococcal polysaccharide vaccine (PPV) and the pneumococcal conjugate vaccine (PCV) are inactivated and do not contain any live organisms. They cannot cause the disease against which they protect. Is there anyone who should not be vaccinated? There are very few persons who cannot receive the pneumococcal vaccines. The vaccines should not be given to anyone who has had: A confirmed anaphylactic reaction to a previous dose of the vaccine. A confirmed anaphylactic reaction to any component of the vaccine. Source: Contributed by Bacteriology Research Division Promising New Method for Next-Generation Live-Attenuated Viral Vaccines Against Chikungunya Virus Researchers have successfully applied a novel method of vaccine creation for Chikungunya virus (CHIKV) using a technique called large scale random codon reencoding. Using this approach, a group from the UMR_D 190, Emerging viruses Department in Marseille, France in collaboration with the University of Sydney, Australia, demonstrated that the engineered viruses exhibit a stable phenotype with a significantly decreased viral fitness (i.e., replication capacity), making it a new vaccine candidate for this emerging viral disease. There is an immense need for the development of vaccines targeting many emerging viral pathogens. CHIKV has been responsible for several million human cases over the last decade and represents a striking example of a re-emerging, arthropod-borne, human pathogen for which no licensed vaccine exists. Worryingly, one of the vectors of CHIKV, the mosquito Aedes albopictus, has dispersed into new regions (including temperate areas) resulting in outbreaks of this disease where they had never been previously observed, for example in Italy. Using the large-scale codon re-encoding method, Antoine Nougairede and colleagues were able to synthetically modify the nucleic acid composition of the virus without modifying the encoded viral proteins. When this method was applied to poliovirus and Influenza A virus, it resulted in a live but attenuated virus that had significant reduction of viral fitness. In contrast with previous studies, which employed a targeted approach of codon re-encoding, this new study demonstrates that a random approach reduced the replicative fitness of CHIKV in both primate and arthropod cells. The employed strategy also prevented the reversion of the attenuated phenotype by mutation or recombination, thus reducing the possibility that the newly created virus strain could evolve back to the pathogenic version. The findings by Nougairede et al. suggest that largescale codon re-encoding can provide a strong basis for the rapid design of next-generation viral vaccines against emerging viral pathogens, as soon as their genome sequence has been determined. It represents an exciting route to vaccine development because it intrinsically alleviates the likelihood of novel pathogenic properties of the designed live vaccine, and allows modulation of the amount of reduced fitness by altering the terms and degree of the genetic re-encoding. Thus, this strategy potentially allows for the generic development of live attenuated vaccines against many new viral pathogens, with reduced costs and the potential single dose induction of long-term immunity. Source: sciencedaily.com/ Contributed by Virology Research Division NIH Investigators Discover New Gene that Affects Clearance of Hepatitis C Virus Scientists have discovered a gene that interferes with the clearance of hepatitis C virus infection. They also identified an inherited variant within this gene, Interferon Lambda 4 (IFNL4), that predicts how people respond to treatment for hepatitis C infection. The results of this study, by investigators at the National Cancer Institute (NCI), part of the NIH, and their collaborators at NIH and other institutions, were published online in Nature Genetics on Jan 6, Chronic infection with hepatitis C virus is a cause of 3

4 liver cirrhosis and liver cancer. Up to 80 percent of people who are acutely infected with hepatitis C fail to clear the virus and develop chronic hepatitis C infection, and of these, approximately 5 percent develop liver cancer. Individuals of African ancestry do not respond as well to current treatments of hepatitis C infection compared to patients of European or Asian ancestry. Previously, results from genome-wide association studies (GWAS) identified common inherited genetic markers that were associated with response to hepatitis C virus treatment and spontaneous clearance of the infection. Those markers are located on chromosome 19 near a known interferon gene, IFNL3. However, molecular investigations into IFNL3 did not explain the GWAS association with spontaneous virus clearance or treatment response. To find the new gene, the investigators used a technology involving RNA sequencing on human liver cells treated to mimic hepatitis C virus infection. "By using RNA sequencing we looked outside the box to search for something beyond what was already known in this region. We hit the jackpot with the discovery of a new gene. It is possible that other important genes may be discovered using this approach," said co-lead investigator Ludmila Prokunina-Olsson, Ph.D., of the Laboratory of Translational Genomics in NCI's Division of Cancer Epidemiology and Genetics (DCEG). The researchers found that the IFNL4 region harbors a variant that is found in two alternative forms. One form, called deltag, results in a deletion in one of the four bases that comprise DNA. The change creates an alteration known as a frameshift, which produces the IFNL4 protein, while the form without the deletion does not produce IFNL4. By analyzing data from hepatitis C-infected African-Americans and European- Americans participating in clinical studies, the authors found that the presence of the IFNL4 protein is associated with poorer clearance and response to treatment than the form that does not produce IFNL4. The deletion variant is more common in people of African ancestry, which helps partially explain why African-Americans have a lower response to current hepatitis C treatments than patients of Asian and European ancestry. "Our work fulfills several promises of the genomic era," said NCI's Thomas R. O'Brien, M.D., Infections and Immunoepidemiology Branch, DCEG. "One, a better understanding of biology; two, personalized medicine; and three, new potential treatments. We deliver immediately on the first two. We've identified a new gene that may help us better understand response to viral infection and the new genetic marker may transition to clinical practice because it predicts treatment outcome for African-American patients better than the current genetic test. For the third, the INFL4 protein may be used as a novel therapeutic target for hepatitis C virus infection, and possibly other diseases." The new gene belongs to what is now a family of four interferon-lambda protein-encoding genes, three of which were discovered more than ten years ago (IFNL1, IFNL2 and IFNL3). The mechanism by which the IFNL 4 protein impairs hepatitis C virus clearance remains unknown. Further studies will explore molecular function of this novel protein in normal and disease conditions. This study was conducted collaboratively with the National Institute of Diabetes and Digestive and Kidney Diseases at NIH, as well as the U.S. Food and Drug Administration, and a number of universities and research institutions. Funding was provided by NCI grant Z01 CP The National Cancer Institute (NCI) leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. Source: utm-source=twitter... Contributed by Experimental Medicine Research Division p53 Mutations in Liver Cancer A number of epidemiological studies have established a strong association between infection with hepatitis B virus and hepatocellular carcinoma. Aflatoxin Bl has been considered to be a significant etiological factor for liver cancer in southern Africa and Asia. Aflatoxins are compounds produced by fungal strains (such as Aspergilus flavus for aflatoxins Bl) that are known food contaminants in these countries. Aflatoxins are highly carcinogenic in experimental 4 animals, producing liver tumours in newborn mice, rats, fish, ducks and monkeys, although clear evidence for a causal association with human cancer has been difficult to obtain. In 1991, two reports showed that of all the mutations in the p53 gene in hepatocellular carcinoma, there was a predominance of the G:C to T:A transversions at the third base of codon 249 (Arg to Ser) in patients from Mozambique and China. Worldwide epidemiological studies showed that the mutation in codon 249 was

5 strictly specific to countries in which food was contaminated by aflatoxin B1. In Mozambique, for example, more than 50% of the mutations were found in codon 249 and aflatoxin Bl is a common contaminant. In Transkei, which borders on Mozambique and has a similar rate of chronic HBV infection, but less aflatoxin B1 contaminantion, the mutation rate at codon 249 was less than l0%. A similar situation has been observed in various parts of China which differ in their levels of aflatoxin exposure. In countries which do not consume contaminated food (including Europe and the USA), the rate of p53 muta- tions in hepatocellular carcinoma is low and the mutations are scattered along the central part of p53, as for the other types of cancer. It has been demonstrated in vitro and in vivo, in human cells, that this phenomenon is due to the very high sensitivity of the p53 codon 249 to the action of aflatoxin B1. This observation, along with the fact that this 249 mutation is deleterious for p53 function, explains the existence of this mutational hot-spot. Source: Database/p53-cancer/p53-Liver. html. Contributed by Pathology Research Division Multidrug-Resistant Plasmodium Vivax Associated with Severe and Fatal Malaria: A Prospective Study in Papua, Indonesia Multidrug-resistant Plasmodium vivax (Pv) is widespread in Eastern Indonesia, and emerging elsewhere in Asia-Pacific and South America, but is generally regarded as a benign disease. The aim of the study was to review the spectrum of disease associated with malaria due to Pv and P. falciparum (Pf) in patients presenting to a hospital in Timika, Southern Papua, Indonesia. In this region, malaria accounted for l6% of the all hospital outpatient consultations 32% of admissions, a quarter of which were attributable to Pv. Severe disease was present in 22% of hospitalised patients, with a greater risk among patients infected with Pv than in those with Pf (OR=l.l9). Inpatient case fatality rates of 1.6% of patients with Pv did not differ significantly from the 2.2% mortality among patients with pure Pf infection. Importantly, whereas mixed infections have been associated previously with a lower risk of severe disease and anaemia, in our study they were at significantly greater risk than either species alone. Our prospective study supports these findings, adding further weight to the body of evidence highlighting Pv as a major cause of severe malaria, particularly in settings with established or emerging chloroquine resistance. The global emergence of chloroquine resistance in Pf has been associated with a rise in falciparum-related malaria morbidity and mortality. It is likely that chloroquine resistance makes a similar contribution to the high burden of uncomplicated and severe vivax malaria in Papua and other regions where resistance is now emerging. Recurrent infections due to treatment failure and relapse from the liver stages result in up to 80% of patients having recurrent malaria within 4 weeks, and provide a plausible explanation for our observations that almost 20% of patients hospitalised with Pv in Papua have severe anaemia. In conclusion our study demonstrates a major burden of vivax malaria in Southern Papua, similar to that observed in a recent retrospective hospital study in Northern Papua and a prospective community-based study in Papua New Guinea. The clinical spectrum of disease associated with Pv in this region is greater than that reported elsewhere, with infants and those with mixed infections at greatest risk. Further studies are needed to confirm the underlying pathogenesis of severe disease, and the degree to which this is related to the emergence of multidrug resistant stains of Pv. The spread of drug resistant Pv to other parts of Indonesia, Southeast Asia, and South America highlights an urgent need to re-examine the spectrum and burden of vivax malaria and for appropriately resourced control measures to be implemented against this emerging but neglected disease. Source: PLOS medicine: June 17, Contributed by Parasitology Research Division Many False-Positive HIV Test Results for those in AIDS Vaccine Trials Almost half of HIV-negative people who participate in clinical trials for HIV vaccines end up testing positive on routine HIV tests--even though they're not actually infected, a new study shows. They underwent what experts call "vaccine-induced seropositivity/ reactivity" (VISP), meaning that they possess immune system antibodies to the virus but not the virus itself. That's an important distinction, since routine HIV screening looks for virus antibodies only. Experts pointed out that the results are not new or surprising, but simply underline the delicacies of conducting trials into HIV/AIDS. The participants need to make sure to use other forms of testing for HIV, for example, viral load or p24 antigen, not just HIV antibodies. They also need to know their antibody status by the end of the trial. In a study of almost 2,200 people -- all participants in HIV vaccine trials percent underwent VISP and tested positive for 5

6 HIV antibodies. And those rates differed depending on the type of vaccine administered, ranging from 6.3 percent to 86.7 percent. A second study, also being presented at the conference and published in JAMA, found that a screening program used in emergency departments where patients can "opt out" did not turn up very many new cases of HIV. These types of screening programs routinely test people entering the emergency room, regardless of their suspected level of risk or the presence or absence of symptoms. A third paper in the journal recommended that all cancer patients be screened for HIV. This might sway cancer treatment decisions, for instance, helping doctors and patients avoid drugs that suppress the immune system, the authors noted. Source: Journal of the American Medical Association July 21, Contributed by Virology Research Division RECENT ARRIVALS AT CENTRAL BIOMEDICAL LIBRARY, DMR (LM) 1. ACP Annals of Coloproctolog 29(2): April, Circulation Journal 77(6): June, Hiroshima Journal of Medical Sciences 62(1): March, International Journal of Hematology 93(4): April, International Journal of Hematology 95(2): Feb, International Journal of Hematology 95(3): March, Japanese Journal of Ophthalmology 52(6): Journal of Clinic Biochemistry and Nutrition 47(2), Journal of Clinic Biochemistry and Nutrition 48(1): January, The Korean Journal of Parasitology 51(2): April, WHO Drug Information 27(1): WHO Technical Report Series No. (981), ဆသတသနဦစဌန (အကမနမပည) ကကယဆင ရဂရဖရဆခန တင အသညရင အသဝဘ ကကယဆထပခင လအပသစစဆမမင ဓတခစမသပမမပလပပခင အသညရငအသဝဘပ/စပ သယဆငသလနမအ ဆ အကပ လမန ကသပခငမက န စ (ဖငရက) နနက ၁၀နရမ ညန ၃နရအတင ဆငရကပနပသည ဆသတသနဦစဌန (အကမနမပည)မ သတသနပညရငမင ကနမရဦစဌန ဗဟအမ သမဆကမ သဖမယပအထကဆရဝနကမ ပပငဆငရကသ သအမခငကငဆ စမသပဖထတသညဆခန က ဆသတသနဦစဌန (အကမနမပည)တင ဖငလစ စမသပ စစဆလသအမသမမက အဂန ငသကန နနက၁၀နရမ ၁၂နရအတင အခမ စစဆပ လကရပသည ဆအဆပအတကဖစခင(Poisoning)င ပတသကသည သတငအခကအလကမသရလပလင ဆသတ သနဦစဌန(အကမနမပည)ရအမသအဆပထနခပရဌန(ဖန-၃၇၉၄၈၀)သ ဆက သယဆငပသည ဆသတသနဦစဌန (အကမနမပည) မပကနမရအမအဖ သသန တယလဖနလင (၀၉-၇၃၂၅၀၄၉၉) က ဖငလစထရထပသဖင မညသမဆမပကနမရငပတသက သလသညမ မမနလပက ဖငရကမတင နနက၁၀နရမ ညန၃နရအတင မမနငပသည သ က န မ ရ ဝန က ဌ နမ ဝန ထမ မ အ ဖ န ဝ ပ ပ ရန မတ ရပ ခ အပ ပ သည