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Dance D.,Lao Oxford Mahosot Hospital Wellcome Trust Research Unit LOMWRU | Dance D.,University of Oxford
International Journal of Antimicrobial Agents | Year: 2014

Melioidosis, infection with Burkholderia pseudomallei, is being recognised with increasing frequency and is probably more common than currently appreciated. Treatment recommendations are based on a series of clinical trials conducted in Thailand over the past 25 years. Treatment is usually divided into two phases: in the first, or acute phase, parenteral drugs are given for =10 days with the aim of preventing death from overwhelming sepsis; in the second, or eradication phase, oral drugs are given, usually to complete a total of 20 weeks, with the aim of preventing relapse. Specific treatment for individual patients needs to be tailored according to clinical manifestations and response, and there remain many unanswered questions. Some patients with very mild infections can probably be cured by oral agents alone. Ceftazidime is the mainstay of acute-phase treatment, with carbapenems reserved for severe infections or treatment failures and amoxicillin/clavulanic acid (co-amoxiclav) as second-line therapy. Trimethoprim/sulfamethoxazole (co-trimoxazole) is preferred for the eradication phase, with the alternative of co-amoxiclav. In addition, the best available supportive care is needed, along with drainage of abscesses whenever possible. Treatment for melioidosis is unaffordable for many in endemic areas of the developing world, but the relative costs have reduced over the past decade. Unfortunately there is no likelihood of any new or cheaper options becoming available in the immediate future. Recommendations for prophylaxis following exposure to B. pseudomallei have been made, but the evidence suggests that they would probably only delay rather than prevent the development of infection. © 2014 The Author. Source


Mayxay M.,Health Science University | Mayxay M.,Lao Oxford Mahosot Hospital Wellcome Trust Research Unit LOMWRU | Mayxay M.,University of Oxford | Cui W.,University of Melbourne | And 6 more authors.
BMC Public Health | Year: 2013

Background: Dengue remains an important cause of morbidity in Laos. Good knowledge, attitudes and practices (KAP) among the public regarding dengue prevention are required for the success of disease control. Very little is known about dengue KAP among the Lao general population. Methods. This was a KAP household survey on dengue conducted in a peri-urban Pak-Ngum district of Vientiane capital, Laos. A two-stage cluster sampling method was used to select a sample of participants to represent the general community. Participants from 231 households were surveyed using an interviewer-administered questionnaire. Results: Although 97% of the participants heard of dengue, there was a lack of depth of knowledge on dengue: 33% of them did not know that malaria and dengue were different diseases, 32% incorrectly believed that Aedes mosquito transmits malaria, 36% could not correctly report that Aedes mosquitoes bite most frequently at sunrise and sunset; and < 10% of them recognized that indoor water containers could be Aedes mosquito breeding sites. Attitude levels were moderately good with a high proportion (96%) of participants recognizing that dengue was a severe yet preventable disease. Self reported prevention methods were quite high yet observation of the participants' yards showed use of prevention methods to be only moderate. The majority (93%) of the interviewees did not believe that they had enough information on dengue. There was an association between good knowledge and better practices, but good knowledge was associated with worse attitudes. Conclusions: There is a lack of depth of knowledge regarding dengue in Pak-Ngum community and observation methods revealed that more needs to be done by community members themselves to prevent the spread of Aedes mosquitoes. © 2013 Mayxay et al.; licensee BioMed Central Ltd. Source


Tabernero P.,University of Oxford | Tabernero P.,Lao Oxford Mahosot Hospital Wellcome Trust Research Unit LOMWRU | Fernandez F.M.,Georgia Institute of Technology | Green M.,U.S. Center for Disease Control and Prevention | And 4 more authors.
Malaria Journal | Year: 2014

Background: Poor quality medicines threaten the lives of millions of patients and are alarmingly common in many parts of the world. Nevertheless, the global extent of the problem remains unknown. Accurate estimates of the epidemiology of poor quality medicines are sparse and are influenced by sampling methodology and diverse chemical analysis techniques. In order to understand the existing data, the Antimalarial Quality Scientific Group at WWARN built a comprehensive, open-access, global database and linked Antimalarial Quality Surveyor, an online visualization tool. Analysis of the database is described here, the limitations of the studies and data reported, and their public health implications discussed. Methods. The database collates customized summaries of 251 published anti-malarial quality reports in English, French and Spanish by time and location since 1946. It also includes information on assays to determine quality, sampling and medicine regulation. Results: No publicly available reports for 60.6% (63) of the 104 malaria-endemic countries were found. Out of 9,348 anti-malarials sampled, 30.1% (2,813) failed chemical/packaging quality tests with 39.3% classified as falsified, 2.3% as substandard and 58.3% as poor quality without evidence available to categorize them as either substandard or falsified. Only 32.3% of the reports explicitly described their definitions of medicine quality and just 9.1% (855) of the samples collected in 4.6% (six) surveys were conducted using random sampling techniques. Packaging analysis was only described in 21.5% of publications and up to twenty wrong active ingredients were found in falsified anti-malarials. Conclusions: There are severe neglected problems with anti-malarial quality but there are important caveats to accurately estimate the prevalence and distribution of poor quality anti-malarials. The lack of reports in many malaria-endemic areas, inadequate sampling techniques and inadequate chemical analytical methods and instrumental procedures emphasizes the need to interpret medicine quality results with caution. The available evidence demonstrates the need for more investment to improve both sampling and analytical methodology and to achieve consensus in defining different types of poor quality medicines. © 2014 Tabernero et al.; licensee BioMed Central Ltd. Source


Dittrich S.,Lao Oxford Mahosot Hospital Wellcome Trust Research Unit LOMWRU | Dittrich S.,University of Oxford | Rattanavong S.,Lao Oxford Mahosot Hospital Wellcome Trust Research Unit LOMWRU | Lee S.J.,University of Oxford | And 19 more authors.
The Lancet Global Health | Year: 2015

Background: Scrub typhus (caused by Orientia tsutsugamushi), murine typhus (caused by Rickettsia typhi), and leptospirosis are common causes of febrile illness in Asia; meningitis and meningoencephalitis are severe complications. However, scarce data exist for the burden of these pathogens in patients with CNS disease in endemic countries. Laos is representative of vast economically poor rural areas in Asia with little medical information to guide public health policy. We assessed whether these pathogens are important causes of CNS infections in Laos. Methods: Between Jan 10, 2003, and Nov 25, 2011, we enrolled 1112 consecutive patients of all ages admitted with CNS symptoms or signs requiring a lumbar puncture at Mahosot Hospital, Vientiane, Laos. Microbiological examinations (culture, PCR, and serology) targeted so-called conventional bacterial infections (Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, S suis) and O tsutsugamushi, Rickettsia typhi/Rickettsia spp, and Leptospira spp infections in blood or cerebrospinal fluid (CSF). We analysed and compared causes and clinical and CSF characteristics between patient groups. Findings: 1051 (95%) of 1112 patients who presented had CSF available for analysis, of whom 254 (24%) had a CNS infection attributable to a bacterial or fungal pathogen. 90 (35%) of these 254 infections were caused by O tsutsugamushi, R typhi/Rickettsia spp, or Leptospira spp. These pathogens were significantly more frequent than conventional bacterial infections (90/1051 [9%] vs 42/1051 [4%]; p<0· 0001) by use of conservative diagnostic definitions. CNS infections had a high mortality (236/876 [27%]), with 18% (13/71) for R typhi/Rickettsia spp, O tsutsugamushi, and Leptospira spp combined, and 33% (13/39) for conventional bacterial infections (p=0· 076). Interpretation: Our data suggest that R typhi/Rickettsia spp, O tsutsugamushi, and Leptospira spp infections are important causes of CNS infections in Laos. Antibiotics, such as tetracyclines, needed for the treatment of murine typhus and scrub typhus, are not routinely advised for empirical treatment of CNS infections. These severely neglected infections represent a potentially large proportion of treatable CNS disease burden across vast endemic areas and need more attention. Funding: Wellcome Trust UK. © 2015 Dittrich et al. Open Access article published under the terms of CC BY. Source


Mayxay M.,Lao Oxford Mahosot Hospital Wellcome Trust Research Unit LOMWRU | Mayxay M.,Health Science University | Mayxay M.,University of Oxford | Castonguay-Vanier J.,Lao Oxford Mahosot Hospital Wellcome Trust Research Unit LOMWRU | And 38 more authors.
The Lancet Global Health | Year: 2013

Background: Because of reductions in the incidence of Plasmodium falciparum malaria in Laos, identification of the causes of fever in people without malaria, and discussion of the best empirical treatment options, are urgently needed. We aimed to identify the causes of non-malarial acute fever in patients in rural Laos. Methods: For this prospective study, we recruited 1938 febrile patients, between May, 2008, and December, 2010, at Luang Namtha provincial hospital in northwest Laos (n=1390), and between September, 2008, and December, 2010, at Salavan provincial hospital in southern Laos (n=548). Eligible participants were aged 5-49 years with fever (≥38°C) lasting 8 days or less and were eligible for malaria testing by national guidelines. Findings: With conservative definitions of cause, we assigned 799 (41%) patients a diagnosis. With exclusion of influenza, the top five diagnoses when only one aetiological agent per patient was identified were dengue (156 [8%] of 1927 patients), scrub typhus (122 [7%] of 1871), Japanese encephalitis virus (112 [6%] of 1924), leptospirosis (109 [6%] of 1934), and bacteraemia (43 [2%] of 1938). 115 (32%) of 358 patients at Luang Namtha hospital tested influenza PCR-positive between June and December, 2010, of which influenza B was the most frequently detected strain (n=121 [87%]). Disease frequency differed significantly between the two sites: Japanese encephalitis virus infection (p=0·04), typhoid (p=0·006), and leptospirosis (p=0·001) were more common at Luang Namtha, whereas dengue and malaria were more common at Salavan (all p<0·0001). With use of evidence from southeast Asia when possible, we estimated that azithromycin, doxycycline, ceftriaxone, and ofloxacin would have had significant efficacy for 258 (13%), 240 (12%), 154 (8%), and 41 (2%) of patients, respectively. Interpretation: Our findings suggest that a wide range of treatable or preventable pathogens are implicated in non-malarial febrile illness in Laos. Empirical treatment with doxycycline for patients with undifferentiated fever and negative rapid diagnostic tests for malaria and dengue could be an appropriate strategy for rural health workers in Laos. Funding: Wellcome Trust, WHO-Western Pacific Region, Foundation for Innovative New Diagnostics, US Centers for Disease Control and Prevention. © 2013 Mayxay et al. Source

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