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Neonatal meningitis is a devastating disease associated with high mortality and neurological sequelae. Escherichia coli is the second most common cause of neonatal meningitis in full-term infants (herein NMEC) and the most common cause of meningitis in preterm neonates. Here, we investigated the genomic relatedness of a collection of 58 NMEC isolates spanning 1974–2020 and isolated from seven different geographic regions. We show NMEC are comprised of diverse sequence types (STs), with ST95 (34.5%) and ST1193 (15.5%) the most common. No single virulence gene profile was conserved in all isolates; however, genes encoding fimbrial adhesins, iron acquisition systems, the K1 capsule, and O antigen types O18, O75, and O2 were most prevalent. Antibiotic resistance genes occurred infrequently in our collection. We also monitored the infection dynamics in three patients that suffered recrudescent invasive infection caused by the original infecting isolate despite appropriate antibiotic treatment based on antibiogram profile and resistance genotype. These patients exhibited severe gut dysbiosis. In one patient, the causative NMEC isolate was also detected in the fecal flora at the time of the second infection episode and after treatment. Thus, although antibiotics are the standard of care for NMEC treatment, our data suggest that failure to eliminate the causative NMEC that resides intestinally can lead to the existence of a refractory reservoir that may seed recrudescent infection.

Abstract Mycobacterium tuberculosis (Mtb) has different features depending on different geographic areas. We collected Mtb strains from patients with smear-positive pulmonary tuberculosis in Da Nang, central Vietnam. Using a whole genome sequencing platform, including genome assembly complemented by long-read-sequencing data, genomic characteristics were studied. Of 181 Mtb isolates, predominant Vietnamese EAI4_VNM and EAI4-like spoligotypes (31.5%), ZERO strains (5.0%), and part of EAI5 (11.1%) were included in a lineage-1 (L1) sublineage, i.e., L1.1.1.1. These strains were found less often in younger people, and they genetically clustered less frequently than other modern strains. Patients infected with ZERO strains demonstrated less lung infiltration. A region in RD2bcg spanning six loci, i.e., PE_PGRS35, cfp21, Rv1985c, Rv1986, Rv1987, and erm(37), was deleted in EAI4_VNM, EAI4-like, and ZERO strains, whereas another 118 bp deletion in furA was specific only to ZERO strains. L1.1.1.1-sublineage-specific deletions in PE_PGRS4 and PE_PGRS22 were also identified. RD900, seen in ancestral lineages, was present in majority of the L1 members. All strains without IS6110 (5.0%) had the ZERO spoligo-pattern. Distinctive features of the ancestral L1 strains provide a basis for investigation of the modern versus ancestral Mtb lineages and allow consideration of countermeasures against this heterogeneous pathogen.

Background: Tetanus remains common in many low- and middle-income countries (LMICs) yet the evidence base guiding management of this disease is extremely limited, particularly with respect to contemporary management options. Sharing knowledge about practice may facilitate improvement in outcomes elsewhere. Methods: We describe clinical interventions and outcomes of 180 adult patients ≥16 years-old with tetanus enrolled in prospective observational studies at a specialist infectious diseases hospital in Southern Vietnam. Patients were treated according to a holistic management protocol encompassing wound-care, antitoxin, antibiotics, symptom control, airway management, nutrition and de-escalation criteria. Results: Mortality rate in our cohort was 2.8%, with 90 (50%) patients requiring mechanical ventilation for a median 16 [IQR 12-24] days. Median [IQR] duration of ICU stay was 15 [8-23] days. Autonomic nervous system dysfunction occurred in 45 (25%) patients. Hospital acquired infections occurred in 77 (43%) of patients. Conclusion: We report favourable outcomes for patients with tetanus in a single centre LMIC ICU, treated according to a holistic protocol. Nevertheless, many patients required prolonged intensive care support and hospital acquired infections were common.

Background: Tetanus remains common in many low- and middle-income countries (LMICs) yet the evidence base guiding management of this disease is extremely limited, particularly with respect to contemporary management options. Sharing knowledge about practice may facilitate improvement in outcomes elsewhere. Methods: We describe clinical interventions and outcomes of 180 adult patients ≥16 years-old with tetanus enrolled in prospective observational studies at a specialist infectious diseases hospital in Southern Vietnam. Patients were treated according to a holistic management protocol encompassing wound-care, antitoxin, antibiotics, symptom control, airway management, nutrition and de-escalation criteria. Results: Mortality rate in our cohort was 2.8%, with 90 (50%) patients requiring mechanical ventilation for a median 16 [IQR 12-24] days. Median [IQR] duration of ICU stay was 15 [8-23] days. Autonomic nervous system dysfunction occurred in 45 (25%) patients. Hospital acquired infections occurred in 77 (43%) of patients. Conclusion: We report favourable outcomes for patients with tetanus in a single centre LMIC ICU, treated according to a holistic protocol. Nevertheless, many patients required prolonged intensive care support and hospital acquired infections were common.

Increasing numbers of people are surviving critical illness throughout the world, but survivorship is associated with long-term disability. In high-income settings physical rehabilitation is commonly employed to counter this and improve outcomes. These utilize highly-trained multidisciplinary teams and are unavailable and unaffordable in most low and middle income countries (LMICs). We aimed to design a sustainable intensive care unit (ICU) rehabilitation program and to evaluate its feasibility in a LMIC setting. In this project patients, care-givers and experts co-designed an innovative rehabilitation programme that can be delivered by non-expert ICU staff and family care-givers in a LMIC. We implemented this programme in adult patient with patients with tetanus at the Hospital for Tropical Diseases, Ho Chi Minh City over a 5-month period, evaluating the programme's acceptability, enablers and barriers. A 6-phase programme was designed, supported by written and video material. The programme was piloted in total of 30 patients. Rehabilitation was commenced a median 14 (inter quartile range (IQR) 10-18) days after admission. Each patient received a median of 25.5 (IQR 22.8-34.8) rehabilitation sessions out of a median 27 (22.8-35) intended (prescribed) sessions. There were no associated adverse events. Patients and staff found rehabilitation to be beneficial, enhanced relationships between carers, patients and staff and was deemed to be a positive step towards recovery and return to work. The main barrier was staff time. The programme was feasible for patients with tetanus and viewed positively by staff and participants. Staff time was identified as the major barrier to ongoing implementation.

BackgroundThe emergence and spread of multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion (GMS) threatens global malaria elimination efforts. Mass drug administration (MDA), the presumptive antimalarial treatment of an entire population to clear the subclinical parasite reservoir, is a strategy to accelerate malaria elimination. We report a cluster randomised trial to assess the effectiveness of dihydroartemisinin-piperaquine (DP) MDA in reducing falciparum malaria incidence and prevalence in 16 remote village populations in Myanmar, Vietnam, Cambodia, and the Lao People's Democratic Republic, where artemisinin resistance is prevalent.Methods and findingsAfter establishing vector control and community-based case management and following intensive community engagement, we used restricted randomisation within village pairs to select 8 villages to receive early DP MDA and 8 villages as controls for 12 months, after which the control villages received deferred DP MDA. The MDA comprised 3 monthly rounds of 3 daily doses of DP and, except in Cambodia, a single low dose of primaquine. We conducted exhaustive cross-sectional surveys of the entire population of each village at quarterly intervals using ultrasensitive quantitative PCR to detect Plasmodium infections. The study was conducted between May 2013 and July 2017. The investigators randomised 16 villages that had a total of 8,445 residents at the start of the study. Of these 8,445 residents, 4,135 (49%) residents living in 8 villages, plus an additional 288 newcomers to the villages, were randomised to receive early MDA; 3,790 out of the 4,423 (86%) participated in at least 1 MDA round, and 2,520 out of the 4,423 (57%) participated in all 3 rounds. The primary outcome, P. falciparum prevalence by month 3 (M3), fell by 92% (from 5.1% [171/3,340] to 0.4% [12/2,828]) in early MDA villages and by 29% (from 7.2% [246/3,405] to 5.1% [155/3,057]) in control villages. Over the following 9 months, the P. falciparum prevalence increased to 3.3% (96/2,881) in early MDA villages and to 6.1% (128/2,101) in control villages (adjusted incidence rate ratio 0.41 [95% CI 0.20 to 0.84]; p = 0.015). Individual protection was proportional to the number of completed MDA rounds. Of 221 participants with subclinical P. falciparum infections who participated in MDA and could be followed up, 207 (94%) cleared their infections, including 9 of 10 with artemisinin- and piperaquine-resistant infections. The DP MDAs were well tolerated; 6 severe adverse events were detected during the follow-up period, but none was attributable to the intervention.ConclusionsAdded to community-based basic malaria control measures, 3 monthly rounds of DP MDA reduced the incidence and prevalence of falciparum malaria over a 1-year period in areas affected by artemisinin resistance. P. falciparum infections returned during the follow-up period as the remaining infections spread and malaria was reintroduced from surrounding areas. Limitations of this study include a relatively small sample of villages, heterogeneity between villages, and mobility of villagers that may have limited the impact of the intervention. These results suggest that, if used as part of a comprehensive, well-organised, and well-resourced elimination programme, DP MDA can be a useful additional tool to accelerate malaria elimination.Trial registrationClinicalTrials.gov NCT01872702.

Sponge-associated prokaryotic diversity has been studied from a wide range of marine environments across the globe. However, for certain regions, e.g., Vietnam, Thailand, Cambodia, and Singapore, an overview of the sponge-associated prokaryotic communities is still pending. In this study we characterized the prokaryotic communities from 27 specimens, comprising 18 marine sponge species, sampled from the central coastal region of Vietnam. Illumina MiSeq sequencing of 16S ribosomal RNA (rRNA) gene fragments was used to investigate sponge-associated bacterial and archaeal diversity. Overall, 14 bacterial phyla and one archaeal phylum were identified among all 27 samples. The phylum Proteobacteria was present in all sponges and the most prevalent phylum in 15 out of 18 sponge species, albeit with pronounced differences at the class level. In contrast, Chloroflexi was the most abundant phylum in Halichondria sp., whereas Spirastrella sp. and Dactylospongia sp. were dominated by Actinobacteria. Several bacterial phyla such as Acidobacteria, Actinobacteria, Bacteroidetes, Chloroflexi, Deferribacteres, Gemmatimonadetes, and Nitrospirae were found in two-thirds of the sponge species. Moreover, the phylum Thaumarchaeota (Archaea), which is known to comprise nitrifying archaea, was highly abundant among the majority of the 18 investigated sponge species. Altogether, this study demonstrates that the diversity of prokaryotic communities associated with Vietnamese sponges is comparable to sponge-prokaryotic assemblages from well-documented regions. Furthermore, the phylogenetically divergent sponges hosted species-specific prokaryotic communities, thus demonstrating the influence of host identity on the composition and diversity of the associated communities. Therefore, this high-throughput 16S rRNA gene amplicon analysis of Vietnamese sponge-prokaryotic communities provides a foundation for future studies on sponge symbiont function and sponge-derived bioactive compounds from this region.

In many low- and middle-income countries (LMICs), a poor link between antibiotic policies and practices exists. Numerous contextual factors may influence the degree of antibiotic access, appropriateness of antibiotic provision, and actual use in communities. Therefore, improving appropriateness of antibiotic use in different communities in LMICs probably requires interventions tailored to the setting of interest, accounting for cultural context. Here we present the ABACUS study (AntiBiotic ACcess and USe), which employs a unique approach and infrastructure, enabling quantitative validation, contextualization of determinants, and cross-continent comparisons of antibiotic access and use. The community infrastructure for this study is the INDEPTH-Network (International Network for the Demographic Evaluation of Populations and Their Health in Developing Countries), which facilitates health and population research through an established health and demographic surveillance system. After an initial round of formative qualitative research with community members and antibiotic suppliers in three African and three Asian countries, household surveys will assess the appropriateness of antibiotic access, provision and use. Results from this sample will be validated against a systematically conducted inventory of suppliers. All potential antibiotic suppliers will be mapped and characterized. Subsequently, their supply of antibiotics to the community will be measured through customer exit interviews, which tend to be more reliable than bulk purchase or sales data. Discrepancies identified between reported and observed antibiotic practices will be investigated in further qualitative interviews. Amartya Sen’s Capability Approach will be employed to identify the conversion factors that determine whether or not, and the extent to which appropriate provision of antibiotics may lead to appropriate access and use of antibiotics. Currently, the study is ongoing and expected to conclude by 2019. ABACUS will provide important new insights into antibiotic practices in LMICs to inform social interventions aimed at promoting optimal antibiotic use, thereby preserving antibiotic effectiveness.

Introduction: Antiviral resistance has been reported in seasonal influenza A viruses and avian influenza A(H5N1) viruses in Viet Nam, raising concerns about the efficacy of treatment. Methods: We analysed specimens from two sources during the period 2009–2012: influenza-positive samples from influenza-like illness patients at sentinel clinics in northern Viet Nam and isolates from patients with confirmed A(H5N1) infections. Pyrosequencing was used to detect mutations: H275Y [for A(H1N1) and A(H5N1)], E119V [for A(H3N2)] and I117V [for A(H5N1)]. A neuraminidase inhibition assay was used to determine the Inhibitory Concentration 50 (IC50) values for all influenza A and B isolates. Results: There were 341 influenza A positive samples identified; influenza A(H1N1)pdm09 was identified most frequently (n = 215). In 2009, oseltamivir resistance was observed in 100% (19 of 19) of seasonal A(H1N1) isolates and 1.4% (3/215) of A(H1N1)pdm09 isolates. This H275Y mutation was not found in influenza subtypes A(H5N1) or A(H3N2) isolates. Discussion: In Viet Nam, seasonal and A(H5N1) influenza vaccines are not currently available; thus, effective treatment is required. The presence of oseltamivir-resistant viruses is therefore a concern. Active surveillance for oseltamivir resistance among influenza viruses circulating in Viet Nam should be continued.

This paper contributes evidence documenting the continued decline in all-cause mortality and changes in the cause of death distribution over time in four developing country populations in Africa and Asia. We present levels and trends in age-specific mortality (all-cause and cause-specific) from four demographic surveillance sites: Agincourt (South Africa), Navrongo (Ghana) in Africa; Filabavi (Vietnam), Matlab (Bangladesh) in Asia. We model mortality using discrete time event history analysis. This study illustrates how data from INDEPTH Network centers can provide a comparative, longitudinal examination of mortality patterns and the epidemiological transition. Health care systems need to be reconfigured to deal simultaneously with continuing challenges of communicable disease and increasing incidence of non-communicable diseases that require long-term care. In populations with endemic HIV, long-term care of HIV patients on ART will add to the chronic care needs of the community.

During 2005, 764 children were brought to a large children’s hospital in Ho Chi Minh City, Vietnam, with a diagnosis of hand, foot, and mouth disease. All enrolled children had specimens (vesicle fluid, stool, throat swab) collected for enterovirus isolation by cell culture. An enterovirus was isolated from 411 (53.8%) of the specimens: 173 (42.1%) isolates were identified as human enterovirus 71 (HEV71) and 214 (52.1%) as coxsackievirus A16. Of the identified HEV71 infections, 51 (29.5%) were complicated by acute neurologic disease and 3 (1.7%) were fatal. HEV71 was isolated throughout the year, with a period of higher prevalence in October–November. Phylogenetic analysis of 23 HEV71 isolates showed that during the first half of 2005, viruses belonging to 3 subgenogroups, C1, C4, and a previously undescribed subgenogroup, C5, cocirculated in southern Vietnam. In the second half of the year, viruses belonging to subgenogroup C5 predominated during a period of higher HEV71 activity.

To evaluate risk factors for human infection with influenza A subtype H5N1, we performed a matched case-control study in Vietnam. We enrolled 28 case-patients who had laboratory-confirmed H5N1 infection during 2004 and 106 age-, sex-, and location-matched control-respondents. Data were analyzed by matched-pair analysis and multivariate conditional logistic regression. Factors that were independently associated with H5N1 infection were preparing sick or dead poultry for consumption

A widespread epidemic of dengue hemorrhagic fever (DHF) occurred in southern Vietnam in 1998, with 438.98 cases/100,000 population and 342 deaths. The number of DHF cases and deaths per 100,000 population increased 152.4% and 151.8% over a 1997 epidemic. Dengue viruses were isolated from 143 patient blood samples; DEN-3 virus was identified as the predominant serotype, although a resurgence of DEN-4 was noted.