Significant achievements LOMWRU

• We have found Japanese encephalitis virus (JEV) RNA in human throat samples, apparently for the first time, suggesting that testing patients’ throat swabs for JEV RNA could be performed on a larger scale to investigate the epidemiology of JEV.
• Dengue ‘serotype’ can be determined by PCR assays of the pad in NS1 dengue positive rapid diagnostic tests (RDTs), potentially facilitating surveillance of dengue serotypes in the large areas of Asia currently without such surveillance. This has been expanded to test utility of PCR of dengue RDTs for Zika and Chikungunya virus surveillance.
• We have completed a prospective study in 2015-2018 of the diagnostic accuracy of 5 different scrub typhus RDTs to determine which one(s) are the optimal for the diagnosis of this important disease in rural Asia.

• The Expanded Fever Surveillance (EFS) project is investigating the aetiology of fever in inpatients attending Xieng Khouang, Salavan and Luang Nam Tha Provincial Hospitals. These data will be useful for informing treatment algorithms. We have recently started the FIEBRE multicountry fever study in Vientiane Province.
• 1,354 patients have been diagnosed with culture-positive melioidosis since 1999 (120 in 2018) and we are concerned that there is substantial unrecognised but potentially treatable mortality due to Burkholderia pseudomallei elsewhere, especially in southern Laos. Analysis of the association between climatic factors and the occurrence of melioidosis in patients from Laos and Cambodia, suggested that humidity, low visibility and maximum wind speed were important in Laos, and humidity, rainy days and maximum wind speed in Cambodia.
• Through innovative collaboration with soil scientists and hydrologists from the Institut de recherche pour le développement and the International Water Management Institute, LOMWRU is expanding our understanding of the ecology of B. pseudomallei and the reasons for its distribution in different soil and water habitats.
• After PCV13 introduction in Laos there was a 23% relative reduction in PCV13-type carriage in children aged 12-23 months, and no significant change in non-PCV13 serotype carriage, suggesting that the reductions in PCV13 serotype carriage in vaccine-eligible children are likely to result in reductions in pneumococcal transmission and disease in Laos. We are working with Professor Fiona Russell and the  Murdoch Children's Research Institute to monitor the longer term impact of PCV13 introduction in Laos, including prevalence of drug-resistant serotypes.
• We concluded that there are currently no anti-Leptospira spp. antibody detecting RDTs with good sensitivity and specificity for use in Laos. However, data suggest that PCR of urine and serum is a useful technique. We found no evidence of Leptospira spp. resistance to azithromycin, ceftriaxone, ciprofloxacin, doxycycline, gentamicin and penicillin G.
• We found evidence that Streptococcus agalactiae (Group B Streptococcus - GBS) in Laos is potentially a fish-borne pathogen; fish may represent an under-recognised source of GBS infection regionally.
• A novel mathematical model, incorporating a time-varying discovery rate, estimated that some further 10-11 species of human pathogens are currently waiting to be discovered in Laos.
• A study of the antibiotic susceptibility of Orientia tsutsugamushi (the agent of scrub typhus) did not support the current existence of doxycycline- and chloramphenicol-resistant scrub typhus in northern Thailand and Laos.
• With evidence of low herd immunity in Vientiane, Zika virus represents a risk for future largescale outbreaks in Laos
• The first whole genome sequencing was performed in Laos, at Mahosot Hospital in 2018, using the portable MinION next generation sequencing platform, for the whole genome of Rickettsia typhi, the agent of murine typhus.

The causes of central nervous system infection from the first 1,065 lumbar punctures at Mahosot Hospital, 2003-2011, have been analysed. The mortality was high at 26.3%. Patients with bacterial infection were more likely to have a history of diabetes than those without. Factors that showed strong association with death were higher CSF lactate and lower GCS. The Lao data suggest that particular attention should be paid to patients presenting with decreased GCS and the provision of supportive care for unconscious patients, such as high-dependency units (HDU), along with appropriate urgent antimicrobial therapy may be key factors in improving outcome.

• Intensive epidemiological studies and a trial of mass drug administration (MDA) have been completed in rural southern Lao villages, with the Centre for Malariology, Parasitology and Entomology (CMPE) and coordinated by MORU-Bangkok. This included confirmation of the presence of foci of high levels of asymptomatic Plasmodium falciparum and P. vivax parasitaemia, a study of ACT + primaquine MDA as a tool for elimination, and social science studies of the acceptability of this approach. The preliminary results suggest that MDA with dihydroartemisinin-piperaquine plus a single low dose of primaquine is feasible, acceptable and safe but its impact on malaria transmission needs to be further investigated.
• Continued surveillance of antimalarial drug resistance, through both phenotypic studies and molecular markers has shown that piperaquine resistance has spread into southern Laos from neighbouring countries, even though the drug has never been used as treatment. Thus there are serious concerns as to what therapy will be recommended if artemether-lumefantrine (the first-line treatment) fails. We have participated in the multicentre TRAC ll study, with CMPE and coordinated by MORU-Bangkok, at Sekong Provincial Hospital.
• We conducted surveys of the prevalence of phenotypic and genotypic markers of G6PD deficiency in Laos to inform safer use of 8-aminoquinolines (e.g. primaquine) in vivax malaria. Estimated G6PD deficient or mutated hemizygous male prevalence was 8.1% in Laos and we also evaluated promising spot and rapid diagnostic tests for G6PD deficiency detection in Laos to decide on primaquine treatment.

• Paul Newton, Céline Caillet and their Vientiane based team continue to play a global leadership role in medicine quality research
• We are tabulating the accessible data on the quality of maternal health medicines, antibiotics, antidiabetics, anti-retrovirals, antituberculous drugs, and are mapping these before expanding to other classes of essential medicines
• With funding from the Asian Development Bank, we are completing the first evaluation of multiple innovative medicine quality screening devices that has led to increased global understanding of the pluses and minuses of these devices. The study raised concerns that those using these devices may develop false confidence in the devices and reduce the vital visual inspection of medicines. With the current evidence, it is unlikely that any one device would be able to effectively monitor the quality of all medicines.
• A stratified random survey, using mystery shoppers, of the availability and quality of antibiotics sold to patients in the private sector in five southern Lao provinces found that all contained the stated active pharmaceutical ingredient (API) without evidence for falsification. However, substandard antibiotics were found that will have reduced therapeutic efficacy and are likely to engender AMR.
• We continue to provide evidence to the Member State Mechanism of WHO on medicine quality issues
• We organised the 4th course on Medicine Quality and Public Health and 1st International Conference on Medicine Quality and Public Health in Oxford, in 2018

• With the University of Health Sciences, we organise Science Cafés in Laos, which have become a regular feature of the Vientiane scientific ‘scene’. The topics discussed included road crashes, diabetes and post-partum food avoidance behaviour and dengue
• We are engaging with diverse departments in Ministry of Health and with WHO on innovative dashboards for the accessible and straightforward representation of data about the epidemiology of dengue, antimicrobial resistance and antimicrobial use in Laos.

LOMWRU has an active, successful postgraduate student programme for Lao and international students. If you’re interested in doing a postgraduate degree with us, have a look at MORU’s Students page. Then, contact one of our principal investigators for a potential supervisor or Prof Stuart Blacksell, Post-Graduate Student Coordinator.

• We assist with the publication of the Lao Medical Journal, the first Lao language medical journal.
• We continue to build extensive microbiology, molecular biology and serology diagnostic, clinical and research capacity in Mahosot Hospital – an essential pre-requisite for addressing the causes of infectious disease burden.
• We built and support the University of Health Sciences e-library, where all our papers are lodged
• We assist provincial hospitals in Luang Nam Tha, Salavan, Xieng Khouang & Vientiane Provinces and perform clinical research and build diagnostic and research human capacity through training and active participation.
• We are implementing partners in the Fleming Fund Lao Country Grant to strengthen AMR surveillance at three hospitals in the country and are working with a Thai University to develop an intensive training programme for Lao medical technologists.