Risk Assessment After a Severe Hospital-Acquired Infection Associated With Carbapenemase-Producing Pseudomonas aeruginosa.

Importance: Resistance of gram-negative bacilli to carbapenems is rapidly emerging worldwide. In 2016, the World Health Organization defined the hospital-built environment as a core component of infection prevention and control programs. The hospital-built environment has recently been reported as a source for outbreaks and sporadic transmission events of carbapenemase-producing gram-negative bacilli from the environment to patients. Objective: To assess risk after the identification of an unexpected, severe, and lethal hospital-acquired infection caused by carbapenemase-producing Pseudomonas aeruginosa in a carbapenemase-low endemic setting. Design, Settings, and Participants: A case series study in which a risk assessment was performed on all 11 patients admitted to the combined cardiothoracic surgery and pulmonary diseases ward and the hospital-built environment in the Radboud University Medical Center, the Netherlands, in February 2018. Exposures: Water and aerosols containing carbapenemase-producing (Verona integron-mediated metallo-ß-lactamase [VIM]) P aeruginosa. Main Outcomes and Measures: Colonization and/or infection of patients and/or contamination of the environment after the detection of 1 patient infected with carbapenemase-producing (VIM) P aeruginosa. Results: A total of 5 men (age range, 60-84 years) and 6 women (age range, 55-74 years) were admitted to the combined cardiothoracic surgery and pulmonary diseases ward. The risk assessment was performed after carbapenemase-producing (VIM) P aeruginosa was unexpectedly detected in a man in his early 60s, who had undergone a left-sided pneumonectomy and adjuvant radiotherapy. No additional cases (colonization or infection) of carbapenemase-producing (VIM) P aeruginosa were detected. Plausible transmission of carbapenemase-producing P aeruginosa from the hospital environment to the patient via the air was confirmed by whole-genome sequencing, which proved the relation of Pseudomonas strains from the patient, the shower drains in 8 patient rooms, 1 sink, and an air sample. Conclusions and Relevance: This study suggests that rethinking the hospital-built environment, including shower drains and the sewage system, will be crucial for the prevention of severe and potential lethal hospital-acquired infections.

Disease characteristics and treatment of patients with diabetes mellitus attending government health services in Indonesia, Peru, Romania and South Africa.

OBJECTIVE: To describe the characteristics and management of Diabetes mellitus (DM) patients from low- and middle-income countries (LMIC). METHODS: We systematically characterised consecutive DM patients attending public health services in urban settings in Indonesia, Peru, Romania and South Africa, collecting data on DM treatment history, complications, drug treatment, obesity, HbA1c and cardiovascular risk profile; and assessing treatment gaps against relevant national guidelines. RESULTS: Patients (median 59 years, 62.9% female) mostly had type 2 diabetes (96%), half for >5 years (48.6%). Obesity (45.5%) and central obesity (females 84.8%; males 62.7%) were common. The median HbA1c was 8.7% (72 mmol/mol), ranging from 7.7% (61 mmol/mol; Peru) to 10.4% (90 mmol/mol; South Africa). Antidiabetes treatment included metformin (62.6%), insulin (37.8%), and other oral glucose-lowering drugs (34.8%). Disease complications included eyesight problems (50.4%), EGFR <60 ml/min (18.9%), heart disease (16.5%) and proteinuria (14.7%). Many had an elevated cardiovascular risk with elevated blood pressure (36%), LDL (71.0%) and smoking (13%), but few were taking antihypertensive drugs (47.1%), statins (28.5%) and aspirin (30.0%) when indicated. Few patients on insulin (8.0%), statins (8.4%) and antihypertensives (39.5%) reached treatment targets according to national guidelines. There were large differences between countries in terms of disease profile and medication use. CONCLUSION: DM patients in government clinics in four LMIC with considerable growth of DM have insufficient glycaemic control, frequent macrovascular and other complications, and insufficient preventive measures for cardiovascular disease. These findings underline the need to identify treatment barriers and secure optimal DM care in such settings.

Defining a Research Agenda to Address the Converging Epidemics of Tuberculosis and Diabetes: Part 1: Epidemiology and Clinical Management.

There is growing interest in the interaction between type 2 diabetes mellitus (DM) and TB, but many research questions remain unanswered. Epidemiologists, basic scientists, and clinical experts recently convened and identified priorities. This is the first of two reviews on this topic, summarizing priority areas of research regarding epidemiology, clinical management, and public health. First, from an epidemiologic point of view, more study is needed to determine the importance of transient hyperglycemia in patients with TB and on the importance of DM for the global epidemic of multidrug resistant (MDR)-TB. Second, regarding the screening and clinical management of combined TB and DM (TB-DM), clinical trials and large cohort studies should examine the benefits of improved DM care as well as prolonged or intensified TB treatment on the outcome of TB-DM and investigate the cost-effectiveness of screening methods for DM among patients newly diagnosed with TB. Third, from a public health and health systems point of view, the population health impact and cost-effectiveness of different interventions to prevent or treat DM and TB in high-burden populations should be examined, and health-system interventions should be developed for routine TB-DM screening, management of DM after completion of TB treatment, and better access to DM services worldwide. Studies are needed across different ethnicities and settings given the heterogeneity of metabolic perturbations, inflammatory responses, medications, and access to health care. Finally, studies should address interactions between TB, DM, and HIV because of the convergence of epidemics in sub-Saharan Africa and some other parts of the world.

Routine or targeted HIV screening of Indonesian prisoners.

PURPOSE: Routine HIV screening of prisoners is generally recommended, but rarely implemented in low-resource settings. Targeted screening can be used as an alternative. Both strategies may provide an opportunity to start HIV treatment but no formal comparisons have been done of these two strategies. The paper aims to discuss these issues. DESIGN/METHODOLOGY/APPROACH: The authors compared yield and costs of routine and targeted screening in a narcotic prison in Indonesia. Routine HIV screening was done for all incoming prisoners from August 2007-February 2009, after it was switched for budgetary reasons to targeted ("opt-out") HIV screening of inmates classified as people who inject drugs (PWIDs), and "opt-in" HIV testing for all non-PWIDs. FINDINGS: During routine screening 662 inmates were included. All 115 PWIDs and 93.2 percent of non-PWIDs agreed to be tested, 37.4 percent and 0.4 percent respectively were HIV-positive. During targeted screening (March 2009-October 2010), of 888 inmates who entered prison, 107 reported injecting drug use and were offered HIV testing, of whom 31 (29 percent) chose not to be tested and 25.0 percent of those tested were HIV-positive. Of 781 non-PWIDs, 187 (24 percent) came for testing (opt-in), and 2.1 percent were infected. During targeted screening fewer people admitted drug use (12.0 vs 17.4 percent). Routine screening yielded twice as many HIV-infected subjects (45 vs 23). The estimated cost per detected HIV infection was 338 USD for routine and 263 USD for targeted screening. ORIGINALITY/VALUE: In a resource limited setting like Indonesia, routine HIV screening in prison is feasible and more effective than targeted screening, which may be stigmatizing. HIV infections that remain unrecognized can fuel ongoing transmission in prison and lead to unnecessary disease progression and deaths.

Costs of HIV/AIDS treatment in Indonesia by time of treatment and stage of disease.

BACKGROUND: We report an economic analysis of Human Immunodeficiency Virus (HIV) care and treatment in Indonesia to assess the options and limitations of costs reduction, improving access, and scaling up services. METHODS: We calculated the cost of providing HIV care and treatment in a main referral hospital in West Java, Indonesia from 2008 to 2010, differentiated by initiation of treatment at different CD4 cell count levels (0-50, 50-100, 100-150, 150-200, and >200 cells/mm(3)); time of treatment; HIV care and opportunistic infections cost components; and the costs of patients for seeking and undergoing care. DISCUSSION: Before antiretroviral treatment (ART) initiation, costs were dominated by laboratory tests (>65 %), and after initiation, by antiretroviral drugs (≥60 %). Average treatment costs per patient decreased with time on treatment (e.g. from US$580 per patient in the first 6 month to US$473 per patient in months 19-24 for those with CD4 cell counts under 50 cells/mm(3)). Higher CD4 cell counts at initiation resulted in lower laboratory and opportunistic infection treatment costs. Transportation cost dominated the costs of patients for seeking and undergoing care (>40 %). CONCLUSIONS: Costs of providing ART are highest during the early phase of treatment. Costs reductions can potentially be realized by early treatment initiation and applying alternative laboratory tests with caution. Scaling up ART at the community level in certain high prevalence settings may improve early uptake, adherence, and reduce transportation costs.

Management of children exposed to Mycobacterium tuberculosis: a public health evaluation in West Java, Indonesia.

OBJECTIVE: To investigate qualitatively and quantitatively the performance of a programme for managing the child contacts of adult tuberculosis patients in Indonesia. METHODS: A public health evaluation framework was used to assess gaps in a child contact management programme at a lung clinic. Targets for programme performance indicators were derived from established programme indicator targets, the scientific literature and expert opinion. Compliance with tuberculosis screening, the initiation of isoniazid preventive therapy in children younger than 5 years, the accuracy of tuberculosis diagnosis and adherence to preventive therapy were assessed in 755 child contacts in two cohorts. In addition, 22 primary caregivers and 34 clinic staff were interviewed to evaluate knowledge and acceptance of child contact management. The cost to caregivers was recorded. Gaps between observed and target indicator values were quantified. FINDINGS: THE GAPS BETWEEN OBSERVED AND TARGET PERFORMANCE INDICATORS WERE: 82% for screening compliance; 64 to 100% for diagnostic accuracy, 50% for the initiation of preventive therapy, 54% for adherence to therapy and 50% for costs. Many staff did not have adequate knowledge of, or an appropriate attitude towards, child contact management, especially regarding isoniazid preventive therapy. Caregivers had good knowledge of screening but not of preventive therapy and had difficulty travelling to the clinic and paying costs. CONCLUSION: The study identified widespread gaps in the performance of a child contact management system in Indonesia, all of which appear amenable to intervention. The public health evaluation framework used could be applied in other settings where child contact management is failing.

Implementation of LED fluorescence microscopy for diagnosis of pulmonary and HIV-associated tuberculosis in a hospital setting in Indonesia.

BACKGROUND: Fluorescence microscopy (FM) has not been implemented widely in TB endemic settings and little evaluation has been done in HIV-infected patients. We evaluated diagnostic performance, time and costs of FM with light-emitting diodes technology (LED-FM), compared with conventional (Zieh-Neelsen) microscopy in a hospital in Indonesia which acts as referral centre for HIV-infected patients. METHOD: We included pulmonary tuberculosis suspects from the outpatient and HIV clinic. Direct and concentrated sputum smears were examined using LED-FM and ZN microscopy by two technicians who were blinded for the HIV-status and the result of the comparative test. Mean reading time per slide was recorded and cost of each slide was calculated. Mycobacteria culture served as the reference standard. RESULTS: Among 404 tuberculosis suspects from the outpatient clinic and 256 from the HIV clinic, mycobacteria culture was positive in 12.6% and 27%, respectively. The optimal sensitivity of LED-FM was achieved by using a threshold of ≥2 AFB/length. LED-FM had a higher sensitivity (75.5% vs. 54.9%, P<0.01) but lower specificity (90.0% vs 96.6%, P<0.01) compared to ZN microscopy. HIV was associated with a lower sensitivity but similar specificity. The average reading time using LED-FM was significantly shorter (2.23±0.78 vs 5.82±1.60 minutes, P<0.01), while costs per slide were similar. CONCLUSION: High sensitivity of LED-FM combined with shorter reading time of sputum smear slides make this method a potential alternative to ZN microscopy. Additional data on specificity are needed for effective implementation of this technique in high burden TB laboratories.

Cost-effectiveness of scaling up voluntary counselling and testing in West-Java, Indonesia.

AIM: to evaluate the costs-effectiveness of scaling up community-based VCT in West-Java. METHODS: the Asian epidemic model (AEM) and resource needs model (RNM) were used to calculate incremental costs per HIV infection averted and per disability-adjusted life years saved (DALYs). Locally monitored demographic, epidemiological behavior and cost data were used as model input. RESULTS: scaling up community-based VCT in West-Java will reduce the overall population prevalence by 36% in 2030 and costs US$248 per HIV infection averted and US$9.17 per DALY saved. Cost-effectiveness estimation were most sensitive to the impact of VCT on condom use and to the population size of clients of female sex workers (FSWs), but were overall robust. The total costs for scaling up community-based VCT range between US$1.3 and 3.8 million per year and require the number of VCT integrated clinics at public community health centers to increase from 73 in 2010 to 594 in 2030. CONCLUSION: scaling up community-based VCT seems both an effective and cost-effective intervention. However, in order to prioritize VCT in HIV/AIDS control in West-Java, issues of budget availability and organizational capacity should be addressed.

Cost-effectiveness of methadone maintenance therapy as HIV prevention in an Indonesian high-prevalence setting: a mathematical modeling study.

BACKGROUND: Indonesia faces an HIV epidemic that is in rapid transition. Injecting drug users (IDUs) are among the most heavily affected risk populations, with estimated prevalence of HIV reaching 50% or more in most parts of the country. Although Indonesia started opening methadone clinics in 2003, coverage remains low. METHODS: We used the Asian Epidemic Model and Resource Needs Model to evaluate the long-term population-level preventive impact of expanding Methadone Maintenance Therapy (MMT) in West Java (43 million people). We compared intervention costs and the number of incident HIV cases in the intervention scenario with current practice to establish the cost per infection averted by expanding MMT. An extensive sensitivity analysis was performed on costs and epidemiological input, as well as on the cost-effectiveness calculation itself. RESULTS: Our analysis shows that expanding MMT from 5% coverage now to 40% coverage in 2019 would avert approximately 2400 HIV infections, at a cost of approximately US$7000 per HIV infection averted. Sensitivity analyses demonstrate that the use of alternative assumptions does not change the study conclusions. CONCLUSION: Our analyses suggest that expanding MMT is cost-effective, and support government policies to make MMT widely available as an integrated component of HIV/AIDS control in West Java.

Low cost HIV-1 quantitative RT-PCR assay in resource-limited settings: improvement and implementation.

Monitoring of HIV viral load in low and middle income settings is limited by high cost of the commercial assays. Therefore, we developed a novel RT-PCR quantitative assay was developed. This assay targets the HIV-1 pol integrase gene (INT). Subsequently, the performance of the INT assay, described previously as a Long Terminal Repeat (LTR) assay and a combined INT/LTR dual target RT-PCR assay was compared. The LTR-assay was found to be sensitive and cost-effective (50-70% cheaper than commercial assays) with the lowest coefficient of variation (%CV). Introduction of an internal standard further improved assay reliability. Therefore, this LTR assay was implemented in West Java, Indonesia. Linearity and precision of the LTR assay were good: %CV ranged from 1.0% to 10.4%. The limit of quantitation was 616 copies/ml. Performance was comparable with the commercial assay (Abbott assay) (r(2)=0.01), although on average the viral loads were 0.39 log(10)copies/ml lower. In clinical practice, it had excellent capability for monitoring treatment failure, the positive predictive value was 99% and the negative predictive value was 93%. In conclusion, the implementation of the improved HIV-1 viral load LTR-assay for routine diagnosis in resource poor settings can be a good alternative when commercial assays are unaffordable.

Total lymphocyte count is a good marker for HIV-related mortality and can be used as a tool for starting HIV treatment in a resource-limited setting.

OBJECTIVES: Total lymphocyte counts (TLC) may be used as an alternative for CD4 cell counts to monitor HIV infection in resource-limited settings, where CD4 cell counts are too expensive or not available. METHODS: We used prospectively collected patient data from an urban HIV clinic in Indonesia. Predictors of mortality were identified via Cox regression, and the relation between TLC and CD4 cell counts was calculated by linear regression. Receiver operating characteristics (ROC) curves were used to choose the cut-off values of TLC corresponding with CD4 cell counts <200 and ≤350 cells/µl. Based on these analyses, we designed TLC-based treatment algorithms. RESULTS: Of 889 antiretroviral treatment (ART)-naïve subjects included, 66% had CD4 cell counts <200 and 81% had 350 ≤ cells/µl at baseline. TLC and CD4 cell count were equally strong predictors of mortality in our population, where ART was started based on CD4 cell count criteria. The correlation coefficient (R) between TLC and √CD4 was 0.70. Optimal cut-off values for TLC to identify patients with CD4 cell counts <200 and ≤350 cells/µl were 1500 and 1700 cells/µl, respectively. Treatment algorithms based on a combination of TLC, gender, oral thrush, anaemia and body mass index performed better in terms of predictive value than WHO staging or TLC alone. In our cohort, such an algorithm would on average have saved $14.05 per patient. CONCLUSION: Total lymphocyte counts is a good marker for HIV-associated mortality. Simple algorithms including TLC can prioritize patients for HIV treatment in a resource-limited setting, until affordable CD4 cell counts will be universally available.

Costs and outcomes of VCT delivery models in the context of scaling up services in Indonesia.

OBJECTIVE: To evaluate costs and outcomes of voluntary counselling and testing (VCT) service delivery models in urban Indonesia. METHODS: We collected primary data on utilization, costs and outcomes of VCT services in a hospital clinic (568 clients), HIV community clinic (28 clients), sexually transmitted infection (STI) community clinic (784 clients) and prison clinic (574 clients) in Bandung, Indonesia, in the period January 2008-April 2009. RESULTS: The hospital clinic diagnosed the highest proportion and absolute number of HIV infections, but with the lowest average CD4 cell count and with the highest associated travelling and waiting time. The prison clinic detected fewer cases, but at an earlier stage, and all enrolled in HIV care. The community clinics detected the smallest number of cases, and only 0-8% enrolled in HIV care. The unit cost per VCT was highest in the hospital clinic (US$74), followed by the STI community clinic (US$65), the HIV community clinic (US$39) and the prison (US$23). CONCLUSION: We propose a reorientation of the delivery models for VCT and related HIV/AIDS treatment in this setting. We call for the scaling up of community clinics for VCT to improve access, promote earlier detection and to perform (early) treatment activities. This would reduce the burden of the hospital clinic to orient itself towards the treatment of AIDS patients. This is one of very few studies addressing this issue in Asia and the first of its kind in Indonesia, which has a rapidly growing HIV epidemic. The conceptual framework and overall conclusions may be relevant to other low-income settings.

Costs of hospital-based methadone maintenance treatment in HIV/AIDS control among injecting drug users in Indonesia.

OBJECTIVE: To assess the cost of hospital-based methadone maintenance treatment (MMT) for injecting drug users (IDUs) in Bandung, Indonesia; to address concerns of financial sustainability at the hospital level and financial accessibility and economic attractiveness at the health care policy level. METHODS: In a 1 year observation period in 2006-2007, MMT service delivery costs were estimated on the basis of a micro-costing approach. Patient costs were estimated on the basis of a survey among 48 methadone clients. RESULTS: A total number of 129 clients attended the MMT clinic, resulting in a total of 16,335 client visits. Total annual societal costs of running the MMT clinic equalled Rp 1130 mln (US$123,672), or Rp 69,206 (US$7.57) per client visit. Of total costs, patient costs established the largest share (65%), followed by that of central government (20%), and the hospital (15%). Present consultation tariffs already cover hospital costs and the patient costs of accessing MMT services constitute almost 70% of their income. CONCLUSION: Under current circumstances, MMT services are financially sustainable to the hospital. MMT services are subsidized by the central government, and this is warranted considering the important role of the program in HIV/AIDS among IDUs. Still, the present user fee seems a barrier to utilization, and a higher level of subsidy might be justified to reduce the cost to the patient.