Antimicrobial use and resistance data in human and animal sectors in the Lao PDR: evidence to inform policy.

OBJECTIVES: To review the scientific evidence base on antimicrobial use (AMU) and antimicrobial resistance (AMR) in human and animal sectors in the Lao PDR (Laos). METHODS: We 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. FINDINGS: We 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. CONCLUSION: AMR 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.

Epidemiology of food-borne trematodes and other parasite infections in a fishing community on the Nam Ngum reservoir, Lao PDR.

Food-borne trematodes (FBT) are important causes of parasitic infections in many Asian countries. Parasitological surveys in Xai Udom, a small fishing community on the Nam Ngum reservoir, Lao People's Democratic Republic, revealed an overall parasitic infection rate in May 1999 of 68.8% (n = 173) and in December 1999 of 65.9% (n = 261). The liver fluke, Opisthorchis viverrini accounted for most of the infections (prevalences of 53.8% and 42.1%, during the first and second surveys, respectively). The prevalence and intensity showed increasing trends with age. Minute intestinal flukes were also present but with relatively low infection rates (3.8-10.9%). The second common group of parasites comprised soil-transmitted nematodes, Trichuris trichiura, Ascaris lumbricoides, hookworm and Strongyloides stercoralis, with prevalences of 22.4 and 17.6%, 20.8 and 8.0%, 16.8 and 13.4%, and 4.0 and 15.3% (first and second surveys, respectively). Most people had no or only light infections, with a few people having heavy infections. Coexisting intestinal protozoa were Giardia lamblia (5.2 and 4.9%) and Entamoeba coli (6.9 and 6.5%). Concurrent tapeworm infections were Taenia (1.7 and 1.1%) and Hymenolepis nana (0.7 and 0.6%) (first and second surveys, respectively). Despite the availability of effective anthelmintic drugs, the results of our study reaf-firm that FBT are still a major health threat in this fishing area of Lao PDR, similar to a decade ago.

A molecular epidemiologic study of point mutations for pyrimethamine-sulfadoxine resistance of Plasmodium falciparum isolates from Lao PDR.

To understand the current condition of pyrimethamine-sulfadoxine (PS) resistant falciparum malaria in Lao PDR, the frequency of point mutations in dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes of Plasmodium falciparum were examined in 50 blood samples collected from the patients with P. falciparum infection in Southern Lao PDR. Point mutations in 5 codons of the DHFR gene, which is known to be related to pyrimethamine resistance, were detected in 15 out of the 50 samples (30%). Among the 15 samples, 10 samples showed a double mutation of codons 59 and 108 (Cys59Arg with Ser108Asn). In the remaining 5 samples, an additional mutation was observed in codon 51 (Asn51 lle), providing a triple mutation of codons 51, 59 and 108. On the other hand, point mutations in the 4 codons of DHPS gene related to sulfadoxine resistance were observed only in 2 samples (4.0%), namely in codon 437 (Ala437Gly). Only one sample showed mutations in both DHFR and DHPS genes. From the results, it should be considered that the frequency of PS resistant malaria is still low in Lao PDR. Continuous monitoring for the PS resistant malaria, however, is necessary because of the increasing use of PS in this country.

A randomized comparison of oral chloroquine and sulfadoxine-pyrimethamine for the treatment of uncomplicated Plasmodium falciparum malaria in Laos.

Between June and October 2000 we conducted the first randomized trial in Laos comparing chloroquine (CQ) with sulfadoxine-pyrimethamine (SP) in the treatment of uncomplicated Plasmodium falciparum malaria (n = 29, 42-d follow-up, age > 5 years). The proportion of patients with treatment failure was high (CQ = 78%, RIII 46%; SP = 36%, RIII 15%). The treatment policy for uncomplicated P. falciparum malaria in Laos needs to be reviewed urgently.

Field application and evaluation of a rapid immunochromatographic test for detection of Plasmodium falciparum infection among the inhabitants of Lao PDR.

Field application and evaluation of a rapid immunochromatographic test (ICT) for detection of Plasmodium falciparum infection were performed in 13 villages in a southern province of Lao PDR in 1999. More than 2,000 inhabitants, accounting for 61.8% of the total estimated population, were examined. Malaria infection was confirmed in all villages surveyed by ICT and microscopic diagnosis. The positive rates of P. falciparum malaria by microscopy ranged from 9.7% to 59.2% (mean 27.2%), whereas by ICT they were from 11.6% to 64.5% (mean 29.8%). The positive rates by ICT were generally higher in 8 out of 13 villages. However, a significant difference between the positive rates by microscopy and ICT was not observed in all villages. Plasmodium falciparum infection was actually confirmed by microscopy in 84.1% of specimens that tested positive by ICT. The results by ICT were consistent with those of the microscopic diagnosis, the discrepancy of the results was less than 10% (141/2,066). The ICT was falsely-positive in 4.7% and falsely-negative in 2.1% of the test cases. These results showed the efficacy of ICT not only in the diagnosis of the respective cases, but also in the mass-examination in the field.

Epidemiology of food-borne trematodes and other parasite infections in a fishing community on the Nam Ngum reservoir, Lao PDR.

Food-borne trematodes (FBT) are important causes of parasitic infections in many Asian countries. Parasitological surveys in Xai Udom, a small fishing community on the Nam Ngum reservoir, Lao People's Democratic Republic, revealed an overall parasitic infection rate in May 1999 of 68.8% (n = 173) and in December 1999 of 65.9% (n = 261). The liver fluke, Opisthorchis viverrini accounted for most of the infections (prevalences of 53.8% and 42.1%, during the first and second surveys, respectively). The prevalence and intensity showed increasing trends with age. Minute intestinal flukes were also present but with relatively low infection rates (3.8-10.9%). The second common group of parasites comprised soil-transmitted nematodes, Trichuris trichiura, Ascaris lumbricoides, hookworm and Strongyloides stercoralis, with prevalences of 22.4 and 17.6%, 20.8 and 8.0%, 16.8 and 13.4%, and 4.0 and 15.3% (first and second surveys, respectively). Most people had no or only light infections, with a few people having heavy infections. Coexisting intestinal protozoa were Giardia lamblia (5.2 and 4.9%) and Entamoeba coli (6.9 and 6.5%). Concurrent tapeworm infections were Taenia (1.7 and 1.1%) and Hymenolepis nana (0.7 and 0.6%) (first and second surveys, respectively). Despite the availability of effective anthelmintic drugs, the results of our study reaf-firm that FBT are still a major health threat in this fishing area of Lao PDR, similar to a decade ago.

A molecular epidemiologic study of point mutations for pyrimethamine-sulfadoxine resistance of Plasmodium falciparum isolates from Lao PDR.

To understand the current condition of pyrimethamine-sulfadoxine (PS) resistant falciparum malaria in Lao PDR, the frequency of point mutations in dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes of Plasmodium falciparum were examined in 50 blood samples collected from the patients with P. falciparum infection in Southern Lao PDR. Point mutations in 5 codons of the DHFR gene, which is known to be related to pyrimethamine resistance, were detected in 15 out of the 50 samples (30%). Among the 15 samples, 10 samples showed a double mutation of codons 59 and 108 (Cys59Arg with Ser108Asn). In the remaining 5 samples, an additional mutation was observed in codon 51 (Asn51 lle), providing a triple mutation of codons 51, 59 and 108. On the other hand, point mutations in the 4 codons of DHPS gene related to sulfadoxine resistance were observed only in 2 samples (4.0%), namely in codon 437 (Ala437Gly). Only one sample showed mutations in both DHFR and DHPS genes. From the results, it should be considered that the frequency of PS resistant malaria is still low in Lao PDR. Continuous monitoring for the PS resistant malaria, however, is necessary because of the increasing use of PS in this country.

Field application and evaluation of a rapid immunochromatographic test for detection of Plasmodium falciparum infection among the inhabitants of Lao PDR.

Field application and evaluation of a rapid immunochromatographic test (ICT) for detection of Plasmodium falciparum infection were performed in 13 villages in a southern province of Lao PDR in 1999. More than 2,000 inhabitants, accounting for 61.8% of the total estimated population, were examined. Malaria infection was confirmed in all villages surveyed by ICT and microscopic diagnosis. The positive rates of P. falciparum malaria by microscopy ranged from 9.7% to 59.2% (mean 27.2%), whereas by ICT they were from 11.6% to 64.5% (mean 29.8%). The positive rates by ICT were generally higher in 8 out of 13 villages. However, a significant difference between the positive rates by microscopy and ICT was not observed in all villages. Plasmodium falciparum infection was actually confirmed by microscopy in 84.1% of specimens that tested positive by ICT. The results by ICT were consistent with those of the microscopic diagnosis, the discrepancy of the results was less than 10% (141/2,066). The ICT was falsely-positive in 4.7% and falsely-negative in 2.1% of the test cases. These results showed the efficacy of ICT not only in the diagnosis of the respective cases, but also in the mass-examination in the field.