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Scientific Annual Report for 2015

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Scientific Annual Report for 2015 SCIENTIFIC ANNUAL REPORT FOR 2015 LAO-OXFORD-MAHOSOT HOSPITAL-WELLCOME TRUST RESEARCH UNIT (LOMWRU) MICROBIOLOGY LABORATORY MAHOSOT HOSPITAL VIENTIANE, LAO PDR TO MINISTRY OF HEALTH GOVERNMENT OF THE LAO PDR Antibiotic susceptibility test on Escherichia coli cultured from a foot infection in a 50 year old Lao woman with diabetes. The organism is resistant to all antibiotics tested apart from amikacin, a potentially toxic agent, and meropenem, which is not yet easily available in Laos. The bottom plate shows that this resistance is due in part to the production of an extended spectrum beta lactamase (ESBL) enzyme. Such infections are seen increasingly in Laos and reflect a growing global threat LAO-OXFORD-MAHOSOT HOSPITAL-WELLCOME TRUST RESEARCH UNIT ANNUAL REPORT 2015 CONTENTS 1. SUMMARY 6 2. INTRODUCTION 9 3. STAFF AND HUMAN CAPACITY BUILDING 11 4. RESULTS AND THEIR PUBLIC HEALTH IMPLICATIONS 12 5. ENGAGEMENT 24 6. OTHER ACTIVITIES 26 7. KEY COLLABORATIONS 27 8. TITLES AND ABSTRACTS OF PAPERS PUBLISHED OR IN PRESS 2015 30 Meeting in Nong District, Savanakhet Province to discuss targeted malaria elimination with the community 1 ANNUAL REPORT 2015 LAO-OXFORD-MAHOSOT HOSPITAL-WELLCOME TRUST RESEARCH UNIT ບົດສັງລວມ꺍㛉 2 LAO-OXFORD-MAHOSOT HOSPITAL-WELLCOME TRUST RESEARCH UNIT ANNUAL REPORT 2015 3 ANNUAL REPORT 2015 LAO-OXFORD-MAHOSOT HOSPITAL-WELLCOME TRUST RESEARCH UNIT 4 LAO-OXFORD-MAHOSOT HOSPITAL-WELLCOME TRUST RESEARCH UNIT ANNUAL REPORT 2015 Preparations for Womens’ Day at Mahosot Hospital 5 ANNUAL REPORT 2015 LAO-OXFORD-MAHOSOT HOSPITAL-WELLCOME TRUST RESEARCH UNIT SUMMARY CryptoDex trial investigators meeting in Ho Chi Minh City A. The Lao-Oxford-Mahosot Hospital-Wellcome Trust performs clinical research and builds diagnostic and research Research Unit (LOMWRU) is a clinical research unit human capacity through training and active participation. embedded within the Microbiology Laboratory of LOMWRU also works with the Centre for Malariology, Mahosot Hospital. It was founded in 2000. It is funded Parasitology and Entomology on malaria projects in Sekong predominantly by the Wellcome Trust of Great Britain, with and Savannakhet Provinces and with the Food and Drug significant additional support from the US Naval Medical Department (FDD) on the quality of medicines. Research Centre, US Centres for Disease Control (CDC), the Bill & Melinda Gates Foundation, The European D. The main focus of the research work is on the causes Union, Fondation Total/Institute Pasteur, the World of fever and their epidemiology, their optimal diagnosis Health Organisation (WHO), the French Government and optimum treatment, the diagnosis, epidemiology Ministry of Foreign and International Affairs and the Joint and prevention of infantile beriberi, and the quality of Inter-Agency Task Force of the Global Fund. Considerable medicines globally. assistance in kind is given by the Institut de Recherche pour le Développement/Aix-Marseille University and the E. We supported 23 visits by Lao staff to five international Rickettsial Diseases Research Program, Naval Medical meetings and supported two Lao staff to read for PhD/MSc Research Center, USA. degrees in 2015. B. The Microbiology Laboratory is composed of 31 Lao F. In 2015 we published or have in press 47 peer-reviewed Government staff and 45 project-funded staff; 91% are papers, three book chapters, and one WHO report. Lao and 61% are female. The Microbiology Laboratory LOMWRU authors are the most cited in the Lao public has clinical microbiology, molecular, serology and BSL3 health literature since 2000, with 255 papers published or laboratories. It follows University of Oxford biosafety in press, including 16 book chapters. policies and guidelines. G. Previous LOMWRU research translated into policy C. LOMWRU supports the infectious disease diagnostic in Laos includes the implementation of vaccination service of Mahosot Hospital, assists provincial hospitals in against the pneumococcus and the Japanese encephalitis Luang Nam Tha, Salavan and Xieng Khouang Provinces, virus (JEV) and the change in national antimalarial and 6 LAO-OXFORD-MAHOSOT HOSPITAL-WELLCOME TRUST RESEARCH UNIT ANNUAL REPORT 2015 typhoid treatment policies. It also demonstrated the (CRP) assays are potentially useful markers of the need presence of numerous important pathogens for the first for antibiotic therapy amongst those presenting with time in Laos, and highlighted the global importance of fever. In addition, evidence from rural Laos suggests scrub typhus, leptospirosis, typhoid, melioidosis and JEV, that CRP rapid diagnostic tests are accurate and may providing evidence on their epidemiology and prompting offer a mechanism for determining whether antibiotics interventions. are needed in settings without formal laboratory diagnostic microbiology tests. H. The main findings, in brief, from work published, in • The esultsr of a clinical trial of steroids in HIV-associated press or in preparation in 2015 of immediate relevance to cryptococcal meningitis suggests that steroids are Laos (please see caveats in text!), are: associated with a high incidence of adverse effects and should not be used in conjunction with amphotericin. • Antimicrobial resistance (AMR) is, as elsewhere in the • Melioidosis is an important and under-recognised world, increasingly becoming a cause of significant cause of sepsis in Laos, as well as other tropical regions. concern for Lao public health. Extended spectrum beta- We have diagnosed over 940 culture-positive patients lactamase producing Enterobacteriaceae are not only since 1999. increasingly important causes of infection in Mahosot • We have now documented five patients with sennetsu Hospital but are also common in stools of healthy (Neorickettsia sennetsu) infection in Laos and have kindergarten children in Vientiane City and Province established direct diagnostic methods for Neorickettsia and in the stools of healthy people in a remote village sennetsu. We have found fewer patients than we were of Xieng Khouang Province. We have also assisted expecting. with a large outbreak of hospital-acquired sepsis due • The agent of Whipple’s disease, Tropheryma whipplei, to multidrug resistant ESBL producing Klebsiella occurs in the stools of healthy children in Vientiane. pneumoniae at the Children’s Hospital, Vientiane. This bacterium can cause diarrhoea, malabsorption, Furthermore, knowledge about antibiotic resistance CNS problems and, rarely, endocarditis – its importance patterns and appropriate prescribing amongst doctors in causing disease in Laos is uncertain. was relatively low – interventions targeting these gaps • At least one brand of dengue RDT (Standard are urgently needed. The spread of drug resistance Diagnostics, NS1/IgM/IgG) retains diagnostic in Laos will have many deleterious consequences for accuracy when exposed to Lao hot season temperatures patients, the community and the economy and greater long term. There are issues with malaria RDT stability emphasis on infection control, antibiotic stewardship in hot climates so these data are reassuring for the use and regulation is urgently needed. of dengue RTDs in rural Laos, but we only evaluated • The majority of cerebrospinal fluid examinations have one brand. abnormal CSF cell counts, suggesting that lumbar • There are concerns that the conventional CSF anti-JEV punctures in inpatients with suspected central nervous IgM ELISA for diagnosing Japanese virus encephalitis system (CNS) infections should be facilitated to ensure has lower than appreciated specificity and that new that patients with these infections are not missed. diagnostic tests are urgently needed. • Typhoid bacteria can be accurately, quickly and • Dengue ‘serotype’ can be determined by PCR assays of relatively inexpensively identified in blood culture fluid the pad in NS1 dengue positive rapid diagnostic tests, using typhoid antigen detecting rapid diagnostic tests potentially facilitating surveillance of dengue serotypes (RDTs). Furthermore, PCR assays of the pad of positive in the large areas of Asia without such surveillance. RDTs can quickly determine whether the bacteria are • There emainr serious concerns about the spread likely to be susceptible to fluoroquinolones. These of artemisinin resistance P. falciparum parasites in techniques may enable provincial hospital laboratories southern Laos and discussions are needed as to what to diagnose this important disease with a centralised therapy will be recommended if double-therapy ACTs system of PCR testing for markers of fluoroquinolone fail. resistance and facilitate investigation of typhoid • There emainr severe, at least focal, problems with the outbreaks. quality of diverse medicines globally. • Scrub typhus, murine typhus and leptospirosis are • In Laos, there is evidence that the quality of antimalarials important causes of central nervous system infections has improved over the last decade but that it is vital in Vientiane and probably elsewhere in Asia. These data that surveillance of antimalarial quality is continued. suggest a low threshold for inclusion of doxycycline in • Thereis limited awareness in Vientiane residents of patients with meningitis/encephalitis along with third the risks of medicines and more engagement with generation cephalosporins as the conventional empirical the public would make a valuable contribution to the therapy as the later alone will not treat typhus. appropriate use of medicines • Data from fever studies in Laos, Cambodia and the • We argue that the CONSORT guidelines
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