ObjectivesTo review the scientific evidence base on antimicrobial use (AMU) and antimicrobial resistance (AMR) in human and animal sectors in the Lao PDR (Laos).MethodsWe reviewed all publications ...from July 1994 (the first article describing AMR in Laos) to December 2020. Electronic searches were conducted using Google Scholar and PubMed with specific terms relating to AMR and AMU in Lao, French and English languages.FindingsWe screened 1,357 peer-reviewed and grey reports by title and abstract and then full articles/reports. Of 80 included, 66 (83%) related to human health, nine (11%) to animal health, four (5%) to both animal and human health and one (1%) to the environment. Sixty-two (78%) were on AMR and 18 (22%) on AMU. Extended spectrum beta lactamase-producing Escherichia coli was the greatest concern identified; the proportion of isolates increased fivefold from 2004 to 2016 (2/28 (7%) to 27/78 (35%)) from blood cultures submitted to the Microbiology Laboratory, Mahosot Hospital, Vientiane. Carbapenem resistant Escherichia coli was first identified in 2015. Methicillin-resistant Staphylococcus aureus (MRSA) was uncommon, with 15 cases of MRSA from blood cultures between its first identification in 2017 and December 2020. AMR patterns of global antimicrobial resistance surveillance system (GLASS) target pathogens from livestock were less well documented. There were few data on AMU in human health and none on AMU in livestock. The first hospital AMU survey in Laos showed that 70% (1,386/1,981) of in-patients in five hospitals from 2017 to 2018 received antimicrobial(s). Antibiotic self-medication was common.ConclusionAMR in Laos is occurring at relatively low proportions for some GLASS pathogens, giving the country a window of opportunity to act quickly to implement strategies to protect the population from a worsening situation. Urgent interventions to roll out new guidelines with enhanced one-health antibiotic stewardship, reduce antibiotic use without prescriptions, enhance surveillance and improve understanding of AMU and AMR are needed.
Laos has the highest maternal mortality ratio in mainland Southeast Asia but there has been little research conducted with pregnant women. We aim to discuss ethical challenges in enrolling pregnant ...women in research as a part of large pregnancy cohort study in Laos. From 2013 to 2015, a prospective cohort study was conducted with 1000 pregnant women in a rural area of Vientiane, Laos, to determine whether fevers were associated with maternal morbidity and small for gestational age. Incidence of fever was 10% and incidence of small for gestational age was 12%. Level of education, cultural norms about family decision-making, and misconceptions about healthcare during pregnancy were three common issues encountered in enrolling pregnant women to this study. Only 47% of recruited women had completed primary school with no further education, which could affect the decisions women make to participate and remain in the study. Family decision-making is common in Laos; in some cases, we could not recruit pregnant women without agreement from their families. In Laos, many pregnant women and their families had strong beliefs in travelling during late pregnancy or losing small amount of blood (giving ~5 ml blood sample) could negatively impact their pregnancies. These misconceptions affected not only the quality of the study but also the women's opportunities to access healthcare. Good engagement between the research team and study participants, and the provision of more health information to the community, were essential to reducing issues experienced in enrolling pregnant women in this study.
Summary
Objective To examine the accuracy of the admission tourniquet test in the diagnosis of dengue infection among Lao adults.
Methods Prospective assessment of the predictive diagnostic value ...of the tourniquet test for the diagnosis of dengue infection, as defined by IgM, IgG and NS1 ELISAs (Panbio Ltd, Australia), among Lao adult inpatients with clinically suspected dengue infection.
Results Of 234 patients with clinically suspected dengue infection on admission, 73% were serologically confirmed to have dengue, while 64 patients with negative dengue serology were diagnosed as having scrub typhus (39%), murine typhus (11%), undetermined typhus (12%), Japanese encephalitis virus (5%), undetermined flavivirus (5%) and typhoid fever (3%); 25% had no identifiable aetiology. The tourniquet test was positive in 29.1% (95% CI = 23.2–34.9%) of all patients and in 34.1% (95% CI = 27.0–41.2%) of dengue‐seropositive patients, in 32.7% (95% CI = 23.5–41.8) of those with dengue fever and in 36.4% (95% CI = 24.7–48.0) of those with dengue haemorrhagic fever. Interobserver agreement for the tourniquet test was 90.2% (95% CI = 86.4–94.0) (Kappa = 0.76). Using ELISAs as the diagnostic gold standard, the sensitivity of the tourniquet test was 33.5–34%; its specificity was 84–91%. The positive and negative predictive values were 85–90% and 32.5–34%, respectively.
Conclusions The admission tourniquet test has low sensitivity and adds relatively little value to the diagnosis of dengue among Lao adult inpatients with suspected dengue. Although a positive tourniquet test suggests dengue and that treatment of alternative diagnoses may not be needed, a negative test result does not exclude dengue.
Objectif: Examiner l’exactitude du test du tourniquet à l’admission dans le diagnostic de l’infection dengue chez les adultes au Laos.
Méthodes: Analyse prospective de la valeur prédictive du test du tourniquet pour le diagnostic de l’infection dengue, telle que définie par les IgM, IgG et l’ELISA NS1 (Panbio Ltd, Australie), chez les adultes du Laos hospitalisés avec une suspicion clinique d’infection dengue.
Résultats: Sur 234 patients suspectés d’infection clinique dengue à l’admission, 73% ont été confirmés sérologiquement pour avoir la dengue, tandis que ceux ayant une sérologie négative pour la dengue ont été diagnostiqués comme ayant le typhus des broussailles (11%), le typhus murin (3%), le typhus indéterminé (3%), le virus de l’encéphalite japonaise (1%), un flavivirus indéterminé (1%) et la fièvre typhoïde (1%). 7% d’entre eux n’avaient pas d’étiologie identifiable. Le test du tourniquet a été positif chez 29,1% (IC95%: 23,2–34,9) et 34,1% (IC95%: 27,0–41,2) des patients séropositifs pour la dengue, chez 32,7% (IC95%: 23,5 à 41,8) de ceux avec de la fièvre dengue et chez 36,4% (IC95%: 24,7–48,0) de ceux avec une fièvre dengue hémorragique. La concordance inter‐observateur pour le test du tourniquet était de 90,2% (IC95%: 86,4–94,0) (Kappa = 0,76). En utilisant l’ELISA comme référence, la sensibilité du test était de 33,5 à 34%, sa spécificitéétait de 84 à 91%. Les valeurs prédictives positives et négatives étaient de 85 à 90% et de 32,5 à 34%, respectivement.
Conclusions: Le test du tourniquet à l’’admission est peu sensible et ajoute peu de valeur pour le diagnostic de la dengue chez les patients adultes hospitalisés du Laos avec suspicion de dengue. Même si un test du tourniquet positif suggère la dengue et si le traitement de diagnostics alternatifs peut ne pas être nécessaire, un résultat négatif du test n’exclut pas la dengue.
Objetivo: Examinar la precisión de la prueba de torniquete realizada al momento de la admisión, en el diagnóstico de la infección por dengue en adultos, en Laos.
Métodos: Evaluación prospectiva del valor predictivo de la prueba del torniquete para el diagnóstico de la infección por dengue, definido por IgM, IgG y ELISAs NS1 (Panbio Ltd, Australia), en adultos de Laos ingresados con sospecha clínica de dengue.
Resultados: De 234 pacientes con sospecha clínica de dengue al momento de la admisión, a un 73% se le confirmó el dengue mediante serología, mientras que aquellos con una serología negativa para dengue fueron diagnosticados con tifus exantemático (11%), tifus murino (3%), tifus de origen indeterminado (3%), virus de encefalitis Japonesa (1%), flavivirus indeterminado (1%), y fiebre tifoidea (1%); 7% tenían una etiología no identificable. La prueba de torniquete era positiva en 29.1% (95% IC = 23.2–34.9%) y en 34.1% (95% IC = 27.0–41.2%) de los pacientes seropositivos, en 32.7% (95% IC = 23.5–41.8) de aquellos con fiebre del dengue y en 36.4% (95% IC = 24.7–48.0) de los que tenían una fiebre hemorrágica por dengue. La concordancia inter‐observador para la prueba del torniquete era del 90.2% (95% IC = 86.4–94.0) (Kappa = 0.76). Utilizando los ELISAs como referencia, la sensibilidad de la prueba del torniquete era del 33.5‐34%; y su especificidad del 84–91%. Los valores predictivos positivos y negativos eran 85–90% y 32.5–34%, respectivamente.
Conclusiones: En el momento de la admisión, la prueba del torniquete tenía una baja sensibilidad y añadía relativamente poco valor al diagnóstico del dengue entre los pacientes ingresados en Laos con sospecha de dengue. Aunque una prueba positiva del torniquete sugiere dengue, y el tratamiento de diagnósticos alternativos puede no ser requerido, una prueba con resultado negativo no excluye la presencia de la enfermedad.
Case-based surveillance of antimicrobial resistance (AMR) provides more actionable data than isolate- or sample-based surveillance. We developed A Clinically Oriented antimicrobial Resistance ...surveillance Network (ACORN) as a lightweight but comprehensive platform, in which we combine clinical data collection with diagnostic stewardship, microbiological data collection and visualisation of the linked clinical-microbiology dataset. Data are compatible with WHO GLASS surveillance and can be stratified by syndrome and other metadata. Summary metrics can be visualised and fed back directly for clinical decision-making and to inform local treatment guidelines and national policy.
An ACORN pilot was implemented in three hospitals in Southeast Asia (1 paediatric, 2 general) to collect clinical and microbiological data from patients with community- or hospital-acquired pneumonia, sepsis, or meningitis. The implementation package included tools to capture site and laboratory capacity information, guidelines on diagnostic stewardship, and a web-based data visualisation and analysis platform.
Between December 2019 and October 2020, 2294 patients were enrolled with 2464 discrete infection episodes (1786 community-acquired, 518 healthcare-associated and 160 hospital-acquired). Overall, 28-day mortality was 8.7%. Third generation cephalosporin resistance was identified in 54.2% (39/72) of
and 38.7% (12/31) of
isolates
Almost a quarter of
isolates were methicillin resistant (23.0%, 14/61). 290/2464 episodes could be linked to a pathogen, highlighting the level of enrolment required to achieve an acceptable volume of isolate data. However, the combination with clinical metadata allowed for more nuanced interpretation and immediate feedback of results.
ACORN was technically feasible to implement and acceptable at site level. With minor changes from lessons learned during the pilot ACORN is now being scaled up and implemented in 15 hospitals in 9 low- and middle-income countries to generate sufficient case-based data to determine incidence, outcomes, and susceptibility of target pathogens among patients with infectious syndromes.
Although Japanese encephalitis virus (JEV) infection is an important cause of acute febrile illness in Lao PDR (Laos), patient outcome has not been evaluated. We prospectively followed up 123 ...JEV-infected patients (70 children < 15 years and 53 adults ≥ 15 years) admitted at Mahosot Hospital, Vientiane, from 2003 to 2013. Japanese encephalitis virus infection was diagnosed by the detection of anti-JEV IgM in cerebrospinal fluid and/or IgM seroconversion. Neurological sequelae were assessed using the Liverpool Outcome Score (LOS), total (maximum score = 75), and final (maximum score = 5). The median (interquartile range IQR) age of the patients was 12.0 (7.5-18.8) years, and 57% were male. The median (IQR) duration of patients' follow-up was 4.5 (3.2-7.3) years. Of all patients, 10/123 (8.1%) died during hospitalization, and 13/123 (10.6%) died at home after discharge, giving a mortality of 18.7% (23/123) (33 26.8% patients were lost to follow-up). The frequency of neurological sequelae at the last follow-up was 61.2% (48.4% in adults and 69.4% in children, P = 0.135). The proportion of patients with severe and moderate functional impairment at the last follow-up was significantly higher in children (25%) than in adults (6.5%), P = 0.042. Half of the patients who were still alive at the last follow-up (67) and for whom LOS data were available (22) had improvements in their total and final LOS between discharge and the last follow-up. The total and final LOS at discharge were not significantly different between children and adults, but total LOS at the last follow-up was significantly higher in adults than in children (median IQR: 74.5 73-75 versus 73.0 73-75, P = 0.019).
In the Lao People's Democratic Republic (Laos), rickettsial infections, including scrub and murine typhus, account for a significant burden of fevers. The Mahosot Hospital Microbiology Laboratory in ...Vientiane, Laos, routinely performs rickettsial isolation from hospitalized patients with suspected rickettsioses using mammalian cell culture systems. We review the clinical and laboratory factors associated with successful
and
isolations from this laboratory over a period of 6 years between 2008 and 2014. The overall isolation success was 7.9% for all samples submitted and 17.3% for samples for which the patient had a positive
or
rapid diagnostic test (RDT), serology, or PCR. The frequency of successful isolation was highest for samples submitted in November, at the end of the wet season (28.3%). A longer median duration of reported illness, a positive result for a concurrent
or
spp. quantitative PCR, and the use of antibiotics by the patient in the week before admission were significantly associated with isolation success (
< 0.05). Buffy coat inoculation and a shorter interval between sample collection and inoculation in the laboratory were associated with a higher frequency of isolation (both
< 0.05). This frequency was highest if cell culture inoculation occurred on the same day as blood sample collection. Factors related to the initial rickettsial bacterial concentration are likely the main contributors to isolation success. However, modifiable factors do contribute to the rickettsial isolation success, especially delays in inoculating patient samples into culture.
Abstract
Background
Murine typhus, or infection with Rickettsia typhi, is a global but neglected disease without randomized clinical trials to guide antibiotic therapy.
Methods
A prospective, open, ...randomized trial was conducted in nonpregnant, consenting inpatient adults with rapid diagnostic test evidence of uncomplicated murine typhus at 2 hospitals in Vientiane, Laos. Patients were randomized to 7 days (D7) or 3 days (D3) of oral doxycycline or 3 days of oral azithromycin (A3). Primary outcome measures were fever clearance time and frequencies of treatment failure and relapse.
Results
Between 2004 and 2009, the study enrolled 216 patients (72 per arm); 158 (73.2%) had serology/polymerase chain reaction (PCR)–confirmed murine typhus, and 52 (24.1%) were R. typhi PCR positive. The risk of treatment failure was greater for regimen A3 (22.5%; 16 of 71 patients) than for D3 (4.2%; 3 of 71) or D7 (1.4%; 1 of 71) (P < .001). Among R. typhi PCR–positive patients, the area under the time-temperature curve and the fever clearance time were significantly higher for A3 than for D3 (1.8- and 1.9-fold higher, respectively; P = .005) and D7 (1.5- and 1.6-fold higher; P = .02). No patients returned with PCR-confirmed R. typhi relapse.
Conclusion
In Lao adults, azithromycin is inferior to doxycycline as oral therapy for uncomplicated murine typhus. For doxycycline, 3- and 7-day regimens have similar efficacy. Azithromycin use in murine typhus should be reconsidered. Investigation of genomic and phenotypic markers of R. typhi azithromycin resistance is needed.
Clinical Trial Registration
ISRCTN47812566.
A clinical trial of murine typhus, or infection with Rickettsia typhi, in Lao adults suggests that azithromycin is inferior to doxycycline for the oral therapy of uncomplicated murine typhus. Three and 7 days of doxycycline have similar efficacy.
Abstract
Nitrofurantoin, a broad-spectrum antibiotic available since 1953, is used widely for the treatment of urinary tract infections as it often retains activity against drug-resistant ...uropathogens. It is contraindicated in pregnant women at term, and in neonates. Like trimethoprim/sulfamethoxazole, nitrofurantoin carries a warning for patients with known sensitivity to oxidant drugs, notably glucose-6-phosphate dehydrogenase (G6PD) deficiency, in whom it may cause haemolytic anaemia. This is a barrier to uptake in tropical regions where there is a high burden of antimicrobial resistance and where G6PD deficiency is common. Early studies of erythrocyte survival following nitrofurantoin suggest it is less likely to cause oxidant haemolysis in individuals with G6PD deficiency than primaquine. Here we review reports of haemolysis associated with nitrofurantoin from the published literature and from USA (FDA Adverse Event Reporting System; FAERS) and European (VigiBase) pharmacovigilance databases. In total, 318 episodes of haemolytic anaemia were reported and 10 deaths, with 42 (13%) in individuals with confirmed or highly probable G6PD deficiency, out of at least 245 million exposures. A causal link between death and exposure was not reported and a precise risk estimation in G6PD-deficient individuals was not possible as there are few reports from regions where this enzymopathy is most prevalent. The evidence suggests a total daily dose of 200 mg nitrofurantoin may be used for short (3–5 day) course urinary tract infection treatment without G6PD screening when accompanied by appropriate advice. Pharmacovigilance in countries with high prevalence of G6PD-deficiency is recommended to monitor for serious adverse events.
Abstract
Background
The importance of autoimmune encephalitis and its overlap with infectious encephalitides are not well investigated in South-East Asia.
Methods
We report autoantibody testing, ...using antigen-specific live cell-based assays, in a series of 134 patients (cerebrospinal fluid and sera) and 55 blood donor controls (sera), undergoing lumbar puncture for suspected meningoencephalitis admitted in Vientiane, Lao People's Democratic Republic (PDR).
Results
Eight of 134 (6%) patients showed detectable serum neuronal autoantibodies, against the N-methyl-D-aspartate and gamma-aminobutyric acid A receptors (NMDAR and GABAAR), and contactin-associated protein-like 2 (CASPR2). Three of eight patients had accompanying autoantibodies in cerebrospinal fluid (two with NMDAR and one with GABAAR antibodies), and in two of these the clinical syndromes were typical of autoimmune encephalitis. Three of the other five patients had proven central nervous system infections, highlighting a complex overlap between diverse infectious and autoimmune causes of encephalitis. No patients in this cohort were treated with immunotherapy, and the outcomes were poor, with improvement observed in a single patient.
Conclusions
In Lao PDR, autoimmune encephalitis is underdiagnosed and has a poor prognosis. Empiric immunotherapy should be considered after treatable infectious aetiologies are considered unlikely. Awareness and diagnostic testing resources for autoimmune encephalitis should be enhanced in South-East Asia.
PDF
