Markers of prolonged hospitalisation in severe dengue.

BACKGROUND: Dengue is one of the most common diseases in the tropics and subtropics. Whilst mortality is a rare event when adequate supportive care can be provided, a large number of patients get hospitalised with dengue every year that places a heavy burden on local health systems. A better understanding of the support required at the time of hospitalisation is therefore of critical importance for healthcare planning, especially when resources are limited during major outbreaks. METHODS: Here we performed a retrospective analysis of clinical data from over 1500 individuals hospitalised with dengue in Vietnam between 2017 and 2019. Using a broad panel of potential biomarkers, we sought to evaluate robust predictors of prolonged hospitalisation periods. RESULTS: Our analyses revealed a lead-time bias, whereby early admission to hospital correlates with longer hospital stays - irrespective of disease severity. Importantly, taking into account the symptom duration prior to hospitalisation significantly affects observed associations between hospitalisation length and previously reported risk markers of prolonged stays, which themselves showed marked inter-annual variations. Once corrected for symptom duration, age, temperature at admission and elevated neutrophil-to-lymphocyte ratio were found predictive of longer hospitalisation periods. CONCLUSION: This study demonstrates that the time since dengue symptom onset is one of the most significant predictors for the length of hospital stays, independent of the assigned severity score. Pre-hospital symptom durations need to be accounted for to evaluate clinically relevant biomarkers of dengue hospitalisation trajectories.

A simple method for detection of a novel coronavirus (SARS-CoV-2) using one-step RT-PCR followed by restriction fragment length polymorphism.

A novel coronavirus associated with acute respiratory disease (named SARS-CoV-2) is recently identified in Wuhan city, China, spread rapidly worldwide. Early identification of this novel coronavirus by molecular tools is critical for surveillance and control of the epidemic outbreak. We aimed to establish a simple method for the detection of SARS-CoV-2 in differentiating with SARS-CoV. Primers of our in-house reverse transcription polymerase chain reaction (RT-PCR) assays were designed to target conserved regions of the RdRP gene and E gene, selected restriction enzymes EcoRI, Tsp45I, and AluI to distinguish between SARS-CoV-2 and SARS-CoV. In this report, a 396-bp fragment of the RdRp gene and 345-bp fragment of the E gene were amplified by one-step RT-PCR. Enzyme Tsp45I cuts the RdRP-amplified product of SARS-CoV-2 generating three fragments of 45, 154, and 197 bp, but it did not cut the amplicon of SARS-CoV. In contrast, the amplified product of SARS-CoV was digested with EcoRI producing two fragments of 76 and 320 bp, whereas the amplicon of SARS-CoV-2 was undigested by Tsp45I help to distinguish clearly SARS-CoV-2 from SARS-CoV on gel electrophoresis. In addition, AluI cut the amplicon of the E gene of SARS-CoV-2 generating two fragments of 248 and 97 bp without cutting to SARS-CoV. The accuracy of the assay was confirmed by sequencing and phylogenetic analysis. When evaluated on clinical samples showed a high sensitivity of 95%, specificity of our assay was 100% and clinical performance for detection of SARS-CoV-2 in comparison with other reference assays. In conclusion, in the present study, we successfully developed a simple method for molecular detection of SARS-CoV-2 in differentiating with SARS-CoV.

Association of FCN2 polymorphisms and Ficolin-2 levels with dengue fever in Vietnamese patients.

BACKGROUND AND OBJECTIVE: The human ficolin-2, encoded by FCN2, recognizes pathogen-associated acetylated residues on their cell surfaces and activates the lectin complement cascade. This study aimed to investigate the contribution of human ficolin-2 and the functional FCN2 genetic variants in dengue virus (DENV) infection and in clinical progression. METHODS: FCN2 genetic polymorphisms in the promoter, intron 7 and exon 8 were genotyped in 279 patients with dengue fever and in 200 healthy controls by direct Sanger sequencing. The ficolin-2 levels were measured in serum samples by ELISA and correlated with clinical data. RESULTS: The frequencies of +6031GG, +6220GG and +6424TT genotypes were significantly higher in dengue patients compared to healthy controls indicating an increased risk of dengue fever. The SNPs rs11103563 (+6031A/G), rs7872508 (+6220 T/G), and rs7851696 (+6424G/T) significantly regulated ficolin-2 levels in dengue patients (P < 0.0001). Ficolin-2 levels were increased in patients with dengue and Dengue with Warning Signs (DWS) compared to healthy controls (P < 0.0001 and P = 0.038, respectively). Ficolin-2 levels were significantly increased after 10-14 days of admission in both dengue and DWS patients and then slightly decreased after three weeks of discharge, indicating that ficolin-2 levels were modulated during the progression of dengue fever. In addition, ficolin-2 levels were negatively correlated with AST levels and positively correlated with platelet counts. CONCLUSIONS: FCN2 polymorphisms are associated with dengue fever in the Vietnamese population. Ficolin-2 levels are modulated during the progression of dengue fever and correlated with clinical parameters and thus may play a possible role in the pathogenesis of DENV infection.

Identification of Trombiculid Chigger Mites Collected on Rodents from Southern Vietnam and Molecular Detection of Rickettsiaceae Pathogen

Trombiculid “chigger” mites (Acari) are ectoparasites that feed blood on rodents and another animals. A crosssectional survey was conducted in 7 ecosystems of southern Vietnam from 2015 to 2016. Chigger mites were identified with morphological characteristics and assayed by polymerase chain reaction for detection of rickettsiaceae. Overall chigger infestation among rodents was 23.38%. The chigger index among infested rodents was 19.37 and a mean abundance of 4.61. A total of 2,770 chigger mites were identified belonging to 6 species, 3 genera, and 1 family, and pooled into 141 pools (10-20 chiggers per pool). Two pools (1.4%) of the chiggers were positive for Orientia tsutsugamushi. Ricketsia spp. was not detected in any pools of chiggers. Further studies are needed including a larger number and diverse hosts, and environmental factors to assess scrub typhus.

Antiretroviral drug resistance mutations among patients failing first-line treatment in Hanoi, Vietnam.

Objectives: To study the prevalence of drug resistance and genotype testing for HIV drug resistance on HIV/AIDS patients with first-line antiretroviral treatment failure at Dong Da Hospital, Hanoi, Vietnam. Patients and methods: Forty-seven patients in Dong Da Hospital, Hanoi, with confirmation of first-line antiretroviral therapy (ART) failure were enrolled in this study from June 2006 to December 2016. Both the protease and reverse transcriptase genes were amplified and sequenced using Trugene® HIV-1 Genotyping Kit and OpenGene® DNA system at the biomolecular laboratory of the National Institute of Hygiene and Epidemiology, Vietnam. The Stanford HIV database algorithm was used for interpretation of resistance data and genotyping. Results: Drug resistance mutations were 90.7% in patients with first-line treatment failure. Amongst patients with drug resistance mutation, 97.7% resisted to non-nucleoside reverse transcriptase inhibitors (NNRTIs), followed by nucleoside reverse transcriptase inhibitors (NRTIs, 95.3%) and protease inhibitors (PIs, 11.6%). Amongst the genetic mutations resistant to NNRTIs, G190S mutation was the highest (51.2%), K101HQ mutation was 39.5% and Y181I mutation was 34.9%. In genetic mutations to NRTIs, M184V mutation was 88.4%. In thymidine analogue mutations, K70R mutation was the most common (37.2%), followed by D67N, T215F and T69N mutations (27.9%, 27.9% and 25.6%, respectively). In genetic mutations in PIs, M36I and K20R mutations made up 9.3%. In NNRTIs, the prevalence of nevirapine resistance was 55.8%, and that of efavirenz resistance was 4.7%. In NRTIs, the ratio of lamivudine resistance was 93.0%, and that of zidovudine resistance was 9.3%. No lopinavir/ritonavir resistance was recorded. Conclusions: Drug resistance mutations in patients with first-line ART failure had a high prevalence of NNRTI and NRTI resistance but still susceptible to PIs.

Antibiotic Resistance Profile and Diversity of Subtypes Genes in Escherichia coli Causing Bloodstream Infection in Northern Vietnam.

BACKGROUND: Evaluating the antibiotic susceptibility and resistance genes is essential in the clinical management of bloodstream infections (BSIs). But there are still limited studies in Northern Vietnam. AIM: The aim of the study was to determine the antibiotic resistance profile and characteristics of subtypes genes in Escherichia coli causing BSIs in Northern Vietnam. METHODS: The cross-sectional study was done in the period from December 2012 to June 2014 in two tertiary hospitals in Northern Vietnam. Tests were performed at the lab of the hospital. RESULTS: In 56 E. coli strains isolating 39.29 % produced ESBL. 100% of the isolates harbored blaTEM gene, but none of them had the blaPER gene. The prevalence of ESBL producers and ESBL non-producers in blaCTX-M gene was 81.82%, and 73.53%, in blaSHV gene was 18.18% and 35.29%. Sequencing results showed three blaTEM subtypes (blaTEM 1, 79, 82), four blaCTX-M subtypes (blaCTX-M-15, 73, 98, 161), and eight blaSHV subtypes (blaSHV 5, 7, 12, 15, 24, 33, 57, 77). Antibiotic resistance was higher in ampicillin (85.71%), trimethoprim/sulfamethoxazole (64.29%) and cephazolin (50%). Antibiotics were still highly susceptible including doripenem (96.43%), ertapenem (94.64%), amikacin (96.43%), and cefepime (89.29%). CONCLUSION: In Escherichia coli causing BSIs, antibiotic resistance was higher in ampicillin, trimethoprim/sulfamethoxazole and cephazolin. Antibiotics was highly susceptible including doripenem, ertapenem, amikacin, and cefepime.

Antibiotic Resistance Profile and Methicillin-Resistant Encoding Genes of Staphylococcus aureus Strains Isolated from Bloodstream Infection Patients in Northern Vietnam.

BACKGROUND: Evaluating the antibiotic susceptibility and resistance genes is essential in the clinical management of bloodstream infections (BSIs). Nevertheless, there are still limited studies in Northern Vietnam. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). AIM: This study aimed to determine the antibiotic resistance profile and methicillin-resistant encoding genes of Staphylococcus aureus (S. aureus) causing BSIs in Northern Vietnam. METHODS: The cross-sectional study was done from December 2012 to June 2014 in two tertiary hospitals in Northern Vietnam. Tests performed at the lab of the hospital. RESULTS: In 43 S. aureus strains isolating, 53.5 % were MRSA. Distribution of gene for overall, MRSA, and MSSA strains were following mecA gene (58.1 %; 95.7%, and 15%), femA gene (48.8%, 47.8%, and 50%), femB gene (88.4%, 82.6%, and 95%). Antibiotic resistance was highest in penicillin (100%), followed by erythromycin (65.1%) and clindamycin (60.5%). Several antibiotics were susceptible (100%), including vancomycin, tigecycline, linezolid, quinupristin/dalfopristin. Quinolone group was highly sensitive, include ciprofloxacin (83.7%), levofloxacin (86%) and moxifloxacin (86%). CONCLUSION: In S. aureus causing BSIs, antibiotic resistance was higher in penicillin, erythromycin, and clindamycin. All strains were utterly susceptible to vancomycin, tigecycline, linezolid, quinupristin/dalfopristin.

Risks for HIV, HBV, and HCV infections among male injection drug users in northern Vietnam: a case-control study.

Injection drug use (IDU) and HIV infection are important public health problems in Vietnam. The IDU population increased 70% from 2000 to 2004 and is disproportionately affected by HIV and AIDS -- the country's second leading cause of death. Hepatitis B virus (HBV) and hepatitis C virus (HCV) share transmission routes with HIV and cause serious medical consequences. This study aimed to determine risk factors for acquisition of HIV, HBV, and HCV infections among IDUs in a northern province. We conducted a matched case-control study among active IDUs aged 18-45 who participated in a community-based survey (30-minute interview and serologic testing). Each HIV-infected IDU (case) was matched with one HIV-uninfected IDU (control) by age, sex (males only), and study site (128 pairs). Similar procedures were used for HBV infection (50 pairs) and HCV infection (65 pairs). Conditional logistic regression models were fit to identify risk factors for each infection. Among 309 surveyed IDUs, the HIV, HBV, and HCV prevalence was 42.4%, 80.9%, and 74.1%, respectively. Only 11.0% reported having been vaccinated against hepatitis B. While 13.3% of the IDUs reported sharing needles (past six months), 63.8% engaged in indirect sharing practices (past six months), including sharing drug solutions, containers, rinse water, and frontloading drugs. In multivariable models, sharing drugs through frontloading was significantly associated with HIV infection (odds ratio [OR]=2.8), HBV infection (OR=3.8), and HCV infection (OR=4.6). We report an unrecognized association between sharing drugs through frontloading and higher rates of HIV, HBV and HCV infections among male IDUs in Vietnam. This finding may have important implications for bloodborne viral prevention for IDUs in Vietnam.

Social injecting and other correlates of high-risk sexual activity among injecting drug users in northern Vietnam.

BACKGROUND: Sexual risk and STDs are relatively high among injecting drug users (IDUs) in Vietnam. We sought to determine characteristics of sexually active IDUs and correlates of high-risk sexual practices among IDUs in Bac Ninh province in northern Vietnam. METHODS: We used data collected for a community-based cross-sectional pilot study to identify correlates of recent high-risk sex (>1 sex partner and inconsistent/no condom use in the past year). Factors associated with high-risk sex were identified using logistic regression. RESULTS: Among 216 sexually active male IDUs, one third (n=72) had engaged in high-risk sex within the last year. IDUs who reported injecting with others more frequently, having someone else inject their drugs at last injection, sharing needles or sharing any injection equipment were more likely to have reported recent high-risk sex. Factors independently associated with high-risk sexual activity were not injecting oneself [AOR: 2.22; 95% CI (1.09-4.51)], and sharing needles in the past 12 months [AOR: 2.57; 95% CI (1.10-5.99)]. CONCLUSIONS: IDUs who inject socially and IDUs who share needles are likely to engage in high-risk sexual behaviours and may serve as an important bridge group for epidemic HIV transmission in Vietnam. In addition to messages regarding the dangers of sharing needles and other injection equipment, preventive interventions among newly initiated IDUs should also focus on reducing sexual risk.

High HIV sexual risk behaviors and sexually transmitted disease prevalence among injection drug users in Northern Vietnam: implications for a generalized HIV epidemic.

BACKGROUND: HIV prevalence in Vietnam is currently concentrated among injection drug users (IDUs). The extent to which this core risk group represents a potential for broader HIV transmission to the general population is currently unknown. METHODS: A community-based cross-sectional study among IDUs in Vietnam assessed sexually transmitted disease (STD) prevalence and behavioral risk factors. Qualitative interview data enhanced quantitative findings. RESULTS: The prevalence of any STDs among 272 IDUs was 30% (chlamydia, 9%; herpes simplex virus type 2 [HSV-2], 22%; gonorrhea, 0%; and syphilis, 1%). Part-time work or unemployment (odds ratio [OR] = 2.74, 95% confidence interval [CI]: 1.1 to 6.9), sex with > or =2 sex workers in the past year (OR = 4.9, 95% CI: 1.91 to 12.6), having ever smoked heroin (OR = 4.5, 95% CI: 1.1 to 18.3), and injecting less frequently than daily (OR = 3.9, 95% CI: 1.43 to 10.6) were independently associated with chlamydial infection. Urban residency (OR = 4.0, 95% CI: 1.4 to 11.0) and daily injecting (OR = 2.2, 95% CI: 1.1 to 4.4) were independently associated with HSV-2. Odds of HSV-2 among older (> or =28 years of age) IDUs who had sex with <2 sex workers in the past year was higher than among younger IDUs who had sex with more sex workers (OR = 6.4, 95% CI: 2.1 to 18.4). CONCLUSIONS: High STD prevalence and high-risk sexual and parenteral behaviors among IDUs indicate the potential for HIV/STD transmission to the general Vietnamese population.

Intra-couple communication dynamics of HIV risk behavior among injecting drug users and their sexual partners in Northern Vietnam.

This paper elucidates the social context of HIV risk behavior and intra-couple risk communication among injecting drug users (IDUs) and their main sex partner. Data on shared injection equipment, unprotected sex with multiple partners, unprotected sex with a main partner and couples' dynamics and risk communication were gathered through separate in-depth interviews with 11 active male IDUs and 11 of their primary female sex partners in Northern Vietnam. The majority of IDUs' sex partners does not inject drugs and is monogamous. In contrast, most IDUs reported a wide range of risky practices including needle sharing and unprotected sex with multiple, often concurrent, sex partners. Men rarely used condoms with primary partners. Many IDUs worried about their HIV-status, but none disclosed their injecting or sexual practices to their sex partners, leaving their partners unaware of their HIV risk. Among women who worried about HIV/AIDS, the vast majority was unable to influence their partner's needle sharing or extramarital affairs and most would not initiate condom use because they feared their partner's reaction. Couple-based interventions to facilitate risk communication combined with programs to promote condom use among male IDUs, may help to reduce HIV transmission from IDUs to their primary partners.