Mattias Larsson

Antibiotic use and resistance in emerging economies: a situation analysis for Viet Nam

BackgroundAntimicrobial resistance is a major contemporary public health threat. Strategies to contain antimicrobial resistance have been comprehensively set forth, however in developing countries where the need for effective antimicrobials is greatest implementation has proved problematic. A better understanding of patterns and determinants of antibiotic use and resistance in emerging economies may permit more appropriately targeted interventions.Viet Nam, with a large population, high burden of infectious disease and relatively unrestricted access to medication, is an excellent case study of the difficulties faced by emerging economies in controlling antimicrobial resistance.MethodsOur working group conducted a situation analysis of the current patterns and determinants of antibiotic use and resistance in Viet Nam. International publications and local reports published between 1-1-1990 and 31-8-2012 were reviewed. All stakeholders analyzed the findings at a policy workshop and feasible recommendations were suggested to improve antibiotic use in Viet Nam.Here we report the results of our situation analysis focusing on: the healthcare system, drug regulation and supply; antibiotic resistance and infection control; and agricultural antibiotic use.ResultsMarket reforms have improved healthcare access in Viet Nam and contributed to better health outcomes. However, increased accessibility has been accompanied by injudicious antibiotic use in hospitals and the community, with predictable escalation in bacterial resistance. Prescribing practices are poor and self-medication is common – often being the most affordable way to access healthcare. Many policies exist to regulate antibiotic use but enforcement is insufficient or lacking.Pneumococcal penicillin-resistance rates are the highest in Asia and carbapenem-resistant bacteria (notably NDM-1) have recently emerged. Hospital acquired infections, predominantly with multi-drug resistant Gram-negative organisms, place additional strain on limited resources. Widespread agricultural antibiotic use further propagates antimicrobial resistance.ConclusionsFuture legislation regarding antibiotic access must alter incentives for purchasers and providers and ensure effective enforcement. The Ministry of Health recently initiated a national action plan and approved a multicenter health improvement project to strengthen national capacity for antimicrobial stewardship in Viet Nam. This analysis provided important input to these initiatives. Our methodologies and findings may be of use to others across the world tackling the growing threat of antibiotic resistance.

Peer support and improved quality of life among persons living with HIV on antiretroviral treatment: A randomised controlled trial from north-eastern Vietnam

BackgroundAmong people living with HIV (PLHIV) on antiretroviral therapy (ART), it is important to determine how quality of life (QOL) may be improved and HIV-related stigma can be lessened over time. This study assessed the effect of peer support on QOL and internal stigma during the first year after initiating ART among a cohort of PLHIV in north-eastern Vietnam.MethodsA sub-sample study of a randomised controlled trial was implemented between October 2008 and November 2010 in Quang Ninh, Vietnam. In the intervention group, participants (nu2009=u2009119) received adherence support from trained peer supporters who visited participants’ houses biweekly during the first two months, thereafter weekly. In the control group, participants (nu2009=u2009109) were treated according to standard guidelines, including adherence counselling, monthly health check and drug refills. Basic demographics were measured at baseline. QOL and internal stigma were measured using a Vietnamese version of the WHOQOL-HIVBREF and Internal AIDS-related Stigma Scale instruments at baseline and 12u2009months. T-tests were used to detect the differences between mean values, multilevel linear regressions to determine factors influencing QOL.ResultsOverall, QOL improved significantly in the intervention group compared to the control group. Among participants initiating ART at clinical stages 3 and 4, education at high school level or above and having experiences of a family member dying from HIV were also associated with higher reported QOL. Among participants at clinical stage 1 and 2, there was no significant effect of peer support, whereas having children was associated with an increased QOL. Viral hepatitis was associated with a decreased QOL in both groups. Lower perceived stigma correlated significantly but weakly with improved QOL, however, there was no significant relation to peer support.ConclusionThe peer support intervention improved QOL after 12u2009months among ART patients presenting at clinical stages 3 and 4 at baseline, but it had no impact on QOL among ART patients enrolled at clinical stages 1 and 2. The intervention did not have an effect on Internal AIDS-related stigma. To improve QOL for PLHIV on ART, measures to support adherence should be contextualized in accordance with individual clinical and social needs.

Providing Impetus, Tools, and Guidance to Strengthen National Capacity for Antimicrobial Stewardship in Viet Nam

Heiman Wertheim and colleagues describe the launch and impact of VINARES, an initiative to strengthen antimicrobial stewardship in Vietnam.

High prevalence of antibiotic resistance in commensal Escherichia coli among children in rural Vietnam

BackgroundCommensal bacteria represent an important reservoir of antibiotic resistance genes. Few community-based studies of antibiotic resistance in commensal bacteria have been conducted in Southeast Asia. We investigated the prevalence of resistance in commensal Escherichia coli in preschool children in rural Vietnam, and factors associated with carriage of resistant bacteria.MethodsWe tested isolates of E. coli from faecal samples of 818 children aged 6-60 months living in FilaBavi, a demographic surveillance site near Hanoi. Daily antibiotic use data was collected for participating children for three weeks prior to sampling and analysed with socioeconomic and demographic characteristics extracted from FilaBavis re-census survey 2007. Descriptive statistics were generated, and a logistic regression model was used to identify contributions of the examined factors.ResultsHigh prevalences of resistance were found to tetracycline (74%), co-trimoxazole (68%), ampicillin (65%), chloramphenicol (40%), and nalidixic acid (27%). Two isolates were resistant to ciprofloxacin. Sixty percent of isolates were resistant to three or more antibiotics. Recent sulphonamide use was associated with co-trimoxazole resistance [OR 3.2, 95% CI 1.8-5.7], and beta-lactam use with ampicillin resistance [OR 1.8, 95% CI 1.3-2.4]. Isolates from children aged 6-23 months were more likely to be resistant to ampicillin [OR 1.8, 95% CI 1.3-2.4] and co-trimoxazole [OR 1.5, 95% CI 1.1-2.0]. Associations were identified between geographical areas and tetracycline and ampicillin resistance.ConclusionsWe present high prevalence of carriage of commensal E. coli resistant to commonly used antibiotics. The identified associations with recent antibiotic use, age, and geographical location might contribute to our understanding of carriage of antibiotic resistant commensal bacteria.

Clinical characteristics and outcome of Penicillium marneffei infection among HIV-infected patients in northern Vietnam

ObjectiveThis study reports the clinical characteristics and outcome of HIV-associated Penicilliummarneffei infection in northern Vietnam.MethodsWe conducted a retrospective chart review of all patients with laboratory confirmed Penicilliummarneffei infection admitted to the National Hospital for Tropical Diseases in Hanoi, Vietnam, between July 2006 and September 2009.Results127 patients with P. marneffei infection were identified. All were HIV-infected; median CD4+ T-cell count was 24 cells/μl (IQR:12-48); 76% were men. Common clinical features were fever (92.9%), skin lesions (82.6%), hepatomegaly (61.4%), lymphadenopathy (40.2%), weight loss (59.1%) and cough (49.6%). Concurrent opportunistic infections were present in 22.0%; half of those had tuberculosis. Initial treatment regimens were: itraconazole or ketoconazole capsule (77.2%), amphotericin B (20.5%), and fluconazole (1.6%). In-hospital mortality was 12.6% and showed no significant difference in patients treated with itraconazole (or ketoconazole) and amphotericin B (pu2009=u20090.43). Dyspnea, ascites, and increased LDH level were independent predictors of mortality. No seasonality was observed.ConclusionThe clinical features, treatments and outcomes of HIV-associated P. marneffei infection in northern Vietnam are similar to those reported in other endemic regions. Dyspnea was an important predictor of mortality. More patients were treated with itraconazole than amphotericin B and no significant difference in treatment outcome was observed. It would be of clinical value to compare the efficacy of oral itraconazole and amphotericin B in a clinical trial.

Transmitted drug resistance and phylogenetic analysis of HIV CRF01_AE in Northern Vietnam

The HIV epidemic in Vietnam began in injecting drug users (IDUs), but increasingly affects the general population. It is therefore important to monitor the spread of infection and, since antiretroviral therapy (ART) is now used more frequently, the prevalence of transmitted drug resistance. Sixty-three 1000 bp pol-gene sequences were generated from treatment-naive HIV-1 CRF01_AE infected patients from four clinics in Northern Vietnam. Four drug resistance mutations; Y181C, L210W, L74I and V75M, were found in four different patients, giving a prevalence of 6.3% (4/63). Earlier studies have shown a lower prevalence and the transmission rate should be regularly monitored prospectively in Vietnam. Additional CRF01_AE (N=190) and outgroup subtype B sequences (N=4) were retrieved from databases and included for phylogenetic analysis and calculations of the time of the most recent common ancestor (tMRCA). The 63 samples from our study clustered into two distinct groups; one small clade (N=3) that had a tMRCA in year 1997.5 and a larger group with an estimated tMRCA in 1989.8. The Vietnamese samples in the large group were distinct from CRF01_AE sequences from Thailand, but closely related to previously sequenced isolates from Vietnam, southern China and the Czech Republic, while the samples in the smaller clade appeared to represent a more recent introduction from Southern Vietnam. Our results showed that sequences from IDUs were intermingled with sequences from sexually infected patients, indicating frequent exchange of virus between the transmission risk groups in Northern Vietnam.

Prophylactic Platelets in Dengue: Survey Responses Highlight Lack of an Evidence Base

Dengue is the most important arboviral infection of humans. Thrombocytopenia is frequently observed in the course of infection and haemorrhage may occur in severe disease. The degree of thrombocytopenia correlates with the severity of infection, and may contribute to the risk of haemorrhage. As a result of this prophylactic platelet transfusions are sometimes advocated for the prevention of haemorrhage. There is currently no evidence to support this practice, and platelet transfusions are costly and sometimes harmful. We conducted a global survey to assess the different approaches to the use of platelets in dengue. Respondents were all physicians involved with the treatment of patients with dengue. Respondents were asked that their answers reflected what they would do if they were the treating physician. We received responses from 306 physicians from 20 different countries. The heterogeneity of the responses highlights the variation in clinical practice and lack of an evidence base in this area and underscores the importance of prospective clinical trials to address this key question in the clinical management of patients with dengue.

Stigma, an important source of dissatisfaction of health workers in HIV response in Vietnam: a qualitative study

BackgroundLike in many other low- and middle-income countries, the recent development of an HIV epidemic in Vietnam has led to a growing need for prevention, treatment, care, and support services for people living with HIV (PLHIV). This puts greater demands on the national HIV services, primarily on health workers, which increases the importance of their job satisfaction and working conditions. This study describes health worker perceptions and explores the factors that influence job satisfaction and dissatisfaction of health personnel working on the HIV response in Vietnam. Spector’s job satisfaction model was used as the theoretical framework for the study design and analysis.MethodsThe study employed a qualitative design with 7 focus group discussions and 15 semi-structured interviews with health workers, purposively selected from national and provincial organizations responsible for HIV services in 5 cities and provinces in Vietnam. Data were analyzed using a hybrid approach of theory-driven and data-driven coding and theme development using qualitative analysis software.ResultsHIV services are perceived by Vietnamese health workers as having both positive and negative aspects. Factors related to job satisfaction included training opportunities, social recognition, and meaningful tasks. Factors related to job dissatisfaction included unsatisfactory compensation, lack of positive feedback and support from supervisors, work-related stress from a heavy workload, fear of infection, and HIV-related stigma because of association with PLHIV. An adjusted Spector’s model of job satisfaction for HIV service health workers was developed from these results.ConclusionThis study confirmed the relationship between stigmatization of PLHIV and stigma experienced by staff because of association with PLHIV from families, colleagues, and society. The experiencing stigma results in additional work-related stress, low self-esteem, poor views of their profession, and lower income. The study shows the importance of actions to improve staff job satisfaction such as pay raises, supportive supervision, stress management, stigma reduction and workplace safety. Immediate actions could be the provision of more information; education and communication in mass media to improve the public image of HIV services, as well as improvement of workplace safety, therefore making health workers feel that their work is valued and safe.

Impact of peer support on virologic failure in HIV-infected patients on antiretroviral therapy - a cluster randomized controlled trial in Vietnam.

BackgroundThe effect of peer support on virologic and immunologic treatment outcomes among HIVinfected patients receiving antiretroviral therapy (ART) was assessed in a cluster randomized controlled trial in Vietnam.MethodsSeventy-one clusters (communes) were randomized in intervention or control, and a total of 640 patients initiating ART were enrolled. The intervention group received peer support with weekly home-visits. Both groups received first-line ART regimens according to the National Treatment Guidelines. Viral load (VL) (ExaVir™ Load) and CD4 counts were analyzed every 6xa0months. The primary endpoint was virologic failure (VL >1000 copies/ml). Patients were followed up for 24xa0months. Intention-to-treat analysis was used. Cluster longitudinal and survival analyses were used to study time to virologic failure and CD4 trends.ResultsOf 640 patients, 71% were males, mean age 32xa0years, 83% started with stavudine/lamivudine/nevirapine regimen. After a mean of 20.8xa0months, 78% completed the study, and the median CD4 increase was 286 cells/μl. Cumulative virologic failure risk was 7.2%. There was no significant difference between intervention and control groups in risk for and time to virologic failure and in CD4 trends. Risk factors for virologic failure were ART-non-naïve status [aHR 6.9;(95% CI 3.2–14.6); pu2009<u20090.01]; baseline VL ≥100,000 copies/ml [aHR 2.3;(95% CI 1.2–4.3); pu2009<u20090.05] and incomplete adherence (self-reported missing more than one dose during 24xa0months) [aHR 3.1;(95% CI 1.1–8.9); pu2009<u20090.05]. Risk factors associated with slower increase of CD4 counts were: baseline VL ≥100,000 copies/ml [adj.sq.Coeff (95% CI): −0.9 (−1.5;−0.3); pu2009<u20090.01] and baseline CD4 count <100 cells/μl [adj.sq.Coeff (95% CI): −5.7 (−6.3;−5.4); pu2009<u20090.01]. Having an HIV-infected family member was also significantly associated with gain in CD4 counts [adj.sq.Coeff (95% CI): 1.3 (0.8;1.9); pu2009<u20090.01].ConclusionThere was a low virologic failure risk during the first 2xa0years of ART follow-up in a rural low-income setting in Vietnam. Peer support did not show any impact on virologic and immunologic outcomes after 2 years of follow up.Trial registrationNCT01433601.

HIV sero-discordance among married HIV patients initiating anti-retroviral therapy in northern Vietnam

AbstractBackgroundIn many countries in Asia, the HIV epidemic is in a concentrated phase, with high prevalence in certain risk groups, such as men who inject drugs. There is also a rapid increase of HIV among women. The latter might be due to high levels of sero-discordant couples and increasing transmission from male to female partners over time.MethodsAll adult married patients initiating antiretroviral treatment at four out-patient clinics in Quang Ninh province in north-eastern Vietnam between 2007 and 2009 were asked to participate in the study. Clinical information was extracted from patients’ records, and a structured questionnaire was used to collect social, demographic and economic data.ResultsTwo hundred eighty-eight married patients for whom information on the HIV status of their spouse was available were included in the study. Overall, the sero-discordance rate was 58%. The sero-discordance rate was significantly higher among married males, 71% had spouses not infected, than married females, of whom 18% had spouses not infected. Other factors associated with a high rate of sero-discordance were injection drug use (IDU) history, tuberculosis (TB) history and the availability of voluntary counselling and testing (VCT) in residential locations. High sero-concordance was associated with college/university education.ConclusionThe sero-discordance was significantly higher among married males than married females. Other factors also related to high sero-discordance were history of IDU, history of TB and the availability of VCT in residential locations. In contrast, college/university education and female sex were significantly related to low sero-discordance. To contain the increasing HIV prevalence among women, measures should be taken to prevent transmission among sero-discordant couples.n Trial registration NCT01433601