To contain multidrug-resistant Plasmodium falciparum, malaria elimination in the Greater Mekong subregion needs to be accelerated while current antimalarials remain effective. We evaluated the ...safety, effectiveness, and potential resistance selection of dihydroartemisinin–piperaquine mass drug administration (MDA) in a region with artemisinin resistance in Myanmar.
We did a cluster-randomised controlled trial in rural community clusters in Kayin (Karen) state in southeast Myanmar. Malaria prevalence was assessed using ultrasensitive quantitative PCR (uPCR) in villages that were operationally suitable for MDA (villages with community willingness, no other malaria control campaigns, and a population of 50–1200). Villages were eligible to participate if the prevalence of malaria (all species) in adults was greater than 30% or P falciparum prevalence was greater than 10% (or both). Contiguous villages were combined into clusters. Eligible clusters were paired based on P falciparum prevalence (estimates within 10%) and proximity. Community health workers provided routine malaria case management and distributed long-lasting insecticidal bed-nets (LLINs) in all clusters. Randomisation of clusters (1:1) to the MDA intervention group or control group was by public coin-flip. Group allocations were not concealed. Three MDA rounds (3 days of supervised dihydroartemisinin–piperaquine target total dose 7 mg/kg dihydroartemisinin and 55 mg/kg piperaquine and single low-dose primaquine target dose 0·25 mg base per kg) were delivered to intervention clusters. Parasitaemia prevalence was assessed at 3, 5, 10, 15, 21, 27, and 33 months. The primary outcomes were P falciparum prevalence at months 3 and 10. All clusters were included in the primary analysis. Adverse events were monitored from the first MDA dose until 1 month after the final dose, or until resolution of any adverse event occurring during follow-up. This trial is registered with ClinicalTrials.gov, NCT01872702.
Baseline uPCR malaria surveys were done in January, 2015, in 43 villages that were operationally suitable for MDA (2671 individuals). 18 villages met the eligibility criteria. Three villages in close proximity were combined into one cluster because a border between them could not be defined. This gave a total of 16 clusters in eight pairs. In the intervention clusters, MDA was delivered from March 4 to March 17, from March 30 to April 10, and from April 27 to May 10, 2015. The weighted mean absolute difference in P falciparum prevalence in the MDA group relative to the control group was −10·6% (95% CI −15·1 to −6·1; p=0·0008) at month 3 and −4·5% (−10·9 to 1·9; p=0·14) at month 10. At month 3, the weighted P falciparum prevalence was 1·4% (0·6 to 3·6; 12 of 747) in the MDA group and 10·6% (7·0 to 15·6; 56 of 485) in the control group. Corresponding prevalences at month 10 were 3·2% (1·5 to 6·8; 34 of 1013) and 5·8% (2·5 to 12·9; 33 of 515). Adverse events were reported for 151 (3·6%) of 4173 treated individuals. The most common adverse events were dizziness (n=109) and rash or itching (n=20). No treatment-related deaths occurred.
In this low-transmission setting, the substantial reduction in P falciparum prevalence resulting from support of community case management was accelerated by MDA. In addition to supporting community health worker case management and LLIN distribution, malaria elimination programmes should consider using MDA to reduce P falciparum prevalence rapidly in foci of higher transmission.
The Global Fund to Fight AIDS, Tuberculosis and Malaria.
Neglected tropical diseases (NTDs) affect most impoverished communities in developing countries, like Myanmar in Southeast Asia. NTDs have been understudied and underreported in Myanmar.
A systematic ...review of published and grey literature (1900-2023) on neglected tropical diseases (NTDs) in Myanmar was conducted. The literature search included five international databases: PubMed, EMBASE, Ovid Global Health, and Web of Science Core Collection and one national database: the Myanmar Central Biomedical Library (locally published papers and grey literature). The selection criteria included articles with all types of study designs of current or previous infections conducted in humans, that reported NTDs, recognised by WHO, US CDC, and listed in PLoS NTDs. We included melioidosis and rickettsioses which we consider also meet the definition of an NTD.
A total of 5941 records were retrieved and screened, of which, 672 (11%) met the selection criteria and were included in this review. Of the included articles, 449 (65%) were published after 2000 and 369 (55%) were from two regions (Yangon and Mandalay) of Myanmar. Of the included articles, 238 (35%) reported bacterial NTDs, 212 (32%) viral NTDs, 153 (23%) helminth NTDs, 25 (4%) protozoal NTDs and 39 (6%) reported more than one aetiology. Based on reported frequency in descending order, the bacterial NTDs were leprosy, Escherichia coli enteritis, salmonellosis, cholera, shigellosis, melioidosis, leptospirosis and rickettsioses; the viral NTDs were dengue, chikungunya and Japanese encephalitis virus (JEV) infection; the protozoal NTDs were amoebiasis, giardiasis and leishmaniasis, and the helminth NTDs were ascariasis, trichuriasis, hookworm disease, filariasis and strongyloidiasis.
This review summarises NTDs reported in Myanmar over the past 100 years. The findings suggest that most NTDs are likely to be under reported, especially from the majority of the country which is far from academic centres. Research capacity building together with strengthening of laboratory systems would lead to better understanding of the true burden of NTDs in Myanmar.
PROSPERO registration ID: CRD42018092627.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The risk of emergence and spread of antibiotic resistance is high in Southeast Asian countries and various strategies are being used to raise awareness about appropriate antibiotic use and antibiotic ...resistance within communities. Public engagement in science has not been widely practised in Myanmar. We describe the use of a forum theatre to engage with the community about antibiotic use. The engagement activities took place in a peri-urban township in Yangon, Myanmar. Five preliminary story gathering workshops with the community were carried out to develop scripts and songs for the forum theatre. After that, we organised forum theatre plays between September and October 2018. Following each play we provided four simple key messages based on WHO's world antibiotic awareness week advocacy materials; 1) Antibiotics are medicines used to treat bacterial infections 2) Antibiotics are not useful for coughs and colds 3) Never use leftover antibiotics or share antibiotics with others 4) Prevent infections by regularly washing hands, preparing food hygienically, avoiding close contact with sick people, and keeping vaccinations up to date. We evaluated the engagement activities by conducting focus group discussions (FGD) with audience members. Ten forum theatre plays were performed on two topics; "Fever and antibiotics" and "Mixed medicines", reaching 1175 community members. Four themes emerged from our thematic analysis: 1) Knowledge dissemination, 2) Enjoyment and fun, 3) Willingness to support and recommendations for future engagement activities and 4) Preference over traditional methods of health education. We found improvement of antibiotic related knowledge and enjoyment among audience who were also willing to support future engagement activities and preferred forum theatre approach over formal health talks. We conclude that forum theatre is an effective innovative approach to engage and disseminate knowledge on appropriate use of antibiotics with the community in a participatory way.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Melioidosis was first identified in Myanmar in 1911 but for the last century it has remained largely unreported there. Burkholderia pseudomallei was first isolated from the environment of Myanmar in ...2016, confirming continuing endemicity. Recent genomic studies showed that B. pseudomallei originated in Australia and spread to Asia, with phylogenetic evidence of repeated reintroduction of B. pseudomallei across countries bordered by the Mekong River and the Malay Peninsula. We present the first whole-genome sequences of B. pseudomallei isolates from Myanmar: nine clinical and seven environmental isolates. We used large-scale comparative genomics to assess the genetic diversity, phylogeography and potential origins of B. pseudomallei in Myanmar. Global phylogenetics demonstrated that Myanmar isolates group in two distantly related clades that reside in a more ancestral Asian clade with high amounts of genetic diversity. The diversity of B. pseudomallei from Myanmar and divergence within our global phylogeny suggest that the original introduction of B. pseudomallei to Myanmar was not a recent event. Our study provides new insights into global patterns of B. pseudomallei dissemination, most notably the dynamic nature of movement of B. pseudomallei within densely populated Southeast Asia. The role of anthropogenic influences in both ancient and more recent dissemination of B. pseudomallei to Myanmar and elsewhere in Southeast Asia and globally requires further study.
Burkholderia pseudomallei is a Gram-negative bacterium found in soil and water in many tropical countries. It causes melioidosis, a potentially fatal infection first described in 1911 in Myanmar. ...Melioidosis is a common cause of sepsis and death in South and South-east Asia, but it is rarely diagnosed in Myanmar. We conducted a nationwide soil study to identify areas where B. pseudomallei is present.
We collected soil samples from 387 locations in all 15 states and regions of Myanmar between September 2017 and June 2019. At each site, three samples were taken at each of three different depths (30, 60 and 90 cm) and were cultured for B. pseudomallei separately, along with a pooled sample from each site (i.e. 10 cultures per site). We used a negative binomial regression model to assess associations between isolation of B. pseudomallei and environmental factors (season, soil depth, soil type, land use and climate zones). B. pseudomallei was isolated in 7 of 15 states and regions. Of the 387 sites, 31 (8%) had one or more positive samples and of the 3,870 samples cultured, 103 (2.7%) tested positive for B. pseudomallei. B. pseudomallei was isolated more frequently during the monsoon season RR-2.28 (95% CI: 0.70-7.38) and less in the hot dry season RR-0.70 (95% CI: 0.19-2.56) compared to the cool dry season, and in the tropical monsoon climate zone RR-2.26; 95% CI (0.21-6.21) compared to the tropical dry winter climate zone. However, these associations were not statistically significant. B. pseudomallei was detected at all three depths and from various soil types (clay, silt and sand). Isolation was higher in agricultural land (2.2%), pasture land (8.5%) and disused land (5.8%) than in residential land (0.4%), but these differences were also not significant.
This study confirms a widespread distribution of B. pseudomallei in Myanmar. Clinical studies should follow to obtain a better picture of the burden of melioidosis in Myanmar.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Neglected tropical diseases (NTDs) affect most impoverished communities in developing countries, like Myanmar in Southeast Asia. NTDs have been understudied and underreported in Myanmar. ...Methods A systematic review of published and grey literature (1900-2023) on neglected tropical diseases (NTDs) in Myanmar was conducted. The literature search included five international databases: PubMed, EMBASE, Ovid Global Health, and Web of Science Core Collection and one national database: the Myanmar Central Biomedical Library (locally published papers and grey literature). The selection criteria included articles with all types of study designs of current or previous infections conducted in humans, that reported NTDs, recognised by WHO, US CDC, and listed in PLoS NTDs. We included melioidosis and rickettsioses which we consider also meet the definition of an NTD. Results A total of 5941 records were retrieved and screened, of which, 672 (11%) met the selection criteria and were included in this review. Of the included articles, 449 (65%) were published after 2000 and 369 (55%) were from two regions (Yangon and Mandalay) of Myanmar. Of the included articles, 238 (35%) reported bacterial NTDs, 212 (32%) viral NTDs, 153 (23%) helminth NTDs, 25 (4%) protozoal NTDs and 39 (6%) reported more than one aetiology. Based on reported frequency in descending order, the bacterial NTDs were leprosy, Escherichia coli enteritis, salmonellosis, cholera, shigellosis, melioidosis, leptospirosis and rickettsioses; the viral NTDs were dengue, chikungunya and Japanese encephalitis virus (JEV) infection; the protozoal NTDs were amoebiasis, giardiasis and leishmaniasis, and the helminth NTDs were ascariasis, trichuriasis, hookworm disease, filariasis and strongyloidiasis. Conclusion This review summarises NTDs reported in Myanmar over the past 100 years. The findings suggest that most NTDs are likely to be under reported, especially from the majority of the country which is far from academic centres. Research capacity building together with strengthening of laboratory systems would lead to better understanding of the true burden of NTDs in Myanmar. Trial registration PROSPERO registration ID: CRD42018092627.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In southeast Asia, antibiotic prescription in febrile patients attending primary care is common, and a probable contributor to the high burden of antimicrobial resistance. The objective of this trial ...was to explore whether C-reactive protein (CRP) testing at point of care could rationalise antibiotic prescription in primary care, comparing two proposed thresholds to classify CRP concentrations as low or high to guide antibiotic treatment.
We did a multicentre, open-label, randomised, controlled trial in participants aged at least 1 year with a documented fever or a chief complaint of fever (regardless of previous antibiotic intake and comorbidities other than malignancies) recruited from six public primary care units in Thailand and three primary care clinics and one outpatient department in Myanmar. Individuals were randomly assigned using a computer-based randomisation system at a ratio of 1:1:1 to either the control group or one of two CRP testing groups, which used thresholds of 20 mg/L (group A) or 40 mg/L CRP (group B) to guide antibiotic prescription. Health-care providers were masked to allocation between the two intervention groups but not to the control group. The primary outcome was the prescription of any antibiotic from day 0 to day 5 and the proportion of patients who were prescribed an antibiotic when CRP concentrations were above and below the 20 mg/L or 40 mg/L thresholds. The primary outcome was analysed in the intention-to-treat and per-protocol populations. The trial is registered with ClinicalTrials.gov, number NCT02758821, and is now completed.
Between June 8, 2016, and Aug 25, 2017, we recruited 2410 patients, of whom 803 patients were randomly assigned to CRP group A, 800 to CRP group B, and 807 to the control group. 598 patients in CRP group A, 593 in CRP group B, and 767 in the control group had follow-up data for both day 5 and day 14 and had been prescribed antibiotics (or not) in accordance with test results (per-protocol population). During the trial, 318 (39%) of 807 patients in the control group were prescribed an antibiotic by day 5, compared with 290 (36%) of 803 patients in CRP group A and 275 (34%) of 800 in CRP group B. The adjusted odds ratio (aOR) of 0·80 (95% CI 0·65–0·98) and risk difference of −5·0 percentage points (95% CI −9·7 to −0·3) between group B and the control group were significant, although lower than anticipated, whereas the reduction in prescribing in group A compared with the control group was not significant (aOR 0·86 0·70–1·06; risk difference −3·3 percentage points –8·0 to 1·4). Patients with high CRP concentrations in both intervention groups were more likely to be prescribed an antibiotic than in the control group (CRP ≥20 mg/L: group A vs control group, p<0·0001; CRP ≥40 mg/L: group B vs control group, p<0·0001), and those with low CRP concentrations were more likely to have an antibiotic withheld (CRP <20 mg/L: group A vs control group, p<0·0001; CRP <40 mg/L: group B vs control group, p<0·0001). 24 serious adverse events were recorded, consisting of 23 hospital admissions and one death, which occurred in CRP group A. Only one serious adverse event was thought to be possibly related to the study (a hospital admission in CRP group A).
In febrile patients attending primary care, testing for CRP at point of care with a threshold of 40 mg/L resulted in a modest but significant reduction in antibiotic prescribing, with patients with high CRP being more likely to be prescribed an antibiotic, and no evidence of a difference in clinical outcomes. This study extends the evidence base from lower-income settings supporting the use of CRP tests to rationalise antibiotic use in primary care patients with an acute febrile illness. A key limitation of this study is the individual rather than cluster randomised study design which might have resulted in contamination between the study groups, reducing the effect size of the intervention.
Wellcome Trust Institutional Strategic Support Fund grant (105605/Z/14/Z) and Foundation for Innovative New Diagnostics (FIND) funding from the Australian Government.
•Evidence on causes of fever is limited in Southeast Asia, especially in primary care.•Point-of-care diagnostic tools could guide health workers’ antibiotic prescription.•C-reactive protein was ...significantly increased in cases of bacterial infections.•Most primary care patients recovered regardless of antibiotic prescription.•Antibiotic prescription should be an exception in the primary levels of care.
This study investigated causes of fever in the primary levels of care in Southeast Asia, and evaluated whether C-reactive protein (CRP) could distinguish bacterial from viral pathogens.
Blood and nasopharyngeal swab specimens were taken from children and adults with fever (>37.5 °C) or history of fever (<14 days) in Thailand and Myanmar.
Of 773 patients with at least one blood or nasopharyngeal swab specimen collected, 227 (29.4%) had a target organism detected. Influenza virus type A was detected in 85/227 cases (37.5%), followed by dengue virus (30 cases, 13.2%), respiratory syncytial virus (24 cases, 10.6%) and Leptospira spp. (nine cases, 4.0%). Clinical outcomes were similar between patients with a bacterial or a viral organism, regardless of antibiotic prescription. CRP was higher among patients with a bacterial organism compared with those with a viral organism (median 18 mg/L, interquartile range 10–49 versus 10 mg/L ≤8–22, p = 0.003), with an area under the curve of 0.65 (95% CI 0.55–0.75).
Serious bacterial infections requiring antibiotics are an exception rather than the rule in the first line of care. CRP testing could assist in ruling out such cases in settings where diagnostic uncertainty is high and routine antibiotic prescription is common.
The original CRP randomised controlled trial was registered with ClinicalTrials.gov, number NCT02758821.
•Diagnosis of rickettsial infections is difficult in low-resource settings; this leads to delays in receiving appropriate treatment.•Before this study, the distribution of rickettsioses in Myanmar ...was not known.•This serosurvey shows that rickettsioses are widespread in Myanmar.•Particularly high prevalence of scrub typhus was found in central and northern regions.
Little research has been published on the prevalence of rickettsial infections in Myanmar. This study determined the seroprevalence of immunoglobulin G (IgG) antibodies to rickettsial species in different regions of Myanmar.
Seven hundred leftover blood samples from patients of all ages in primary care clinics and hospitals in seven regions of Myanmar were collected. Samples were screened for scrub typhus group (STG), typhus group (TG) and spotted fever group (SFG) IgG antibodies using enzyme-linked immunosorbent assays (ELISA). Immunofluorescence assays were performed for the same rickettsial groups to confirm seropositivity if ELISA optical density ≥0.5.
Overall IgG seroprevalence was 19% 95% confidence interval (CI) 16–22% for STG, 5% (95% CI 3–7%) for TG and 3% (95% CI: 2–5%) for SFG. The seroprevalence of STG was particularly high in northern and central Myanmar (59% and 19–33%, respectively). Increasing age was associated with higher odds of STG and TG seropositivity per 10-year increase, adjusted odds ratio estimate 1.68 (p < 0.01) and 1.24 (p = 0.03), respectively.
Rickettsial infections are widespread in Myanmar, with particularly high seroprevalence of STG IgG antibodies in central and northern regions. Healthcare workers should consider rickettsial infections as common causes of fever in Myanmar.