Assessment and Simplification of Treatment Eligibility Among Patients With Chronic Hepatitis B Infection in Vietnam

Background Treatment eligibility and the accuracy of its simplified criteria have been poorly documented in patients with chronic hepatitis B virus (HBV) infection worldwide, especially in low- and middle-income countries. Methods From a cohort of HBV-infected patients in Vietnam, we assessed the proportion of patients eligible for treatment using the national guidelines based on reference tests (HBV DNA quantification and FibroScan); and the accuracy of simplified treatment criteria free from HBV DNA and FibroScan (Treatment Eligibility in Africa for the Hepatitis B Virus [TREAT-B] score and simplified World Health Organization [WHO] criteria) to select patients for antiviral therapy using the national guidelines as a reference. Results We analyzed 400 consecutive treatment-naïve HBV-monoinfected patients: 49% males, median age 38 years (range, 18–86), 32% hepatitis B e antigen-positive, median HBV DNA 4.8 log10 IU/mL (undetectable −8.4), median FibroScan 5.3 kPa (3.0–67.8), and 25% having significant liver fibrosis including 12% with cirrhosis. Of these, 167 (42%) fulfilled treatment criteria according to national guidelines. Using the national criteria as a reference, the performance of TREAT-B to select patients for treatment was high (area under the receiver operating characteristic [AUROC], 0.89 [95% confidence interval 0.87-0.92]) with a sensitivity of 74.3% and a specificity of 88.4%. In a subset of patients with 2 alanine aminotransferase measurements over a 6-month period (n = 89), the AUROC of TREAT-B was significantly higher than that of the simplified WHO criteria (P < .001). Conclusions Our study suggests that a large proportion of patients with chronic HBV infection require antiviral therapy in Vietnam. Compared with the simplified WHO criteria free from HBV DNA quantification, TREAT-B is a better alternative to easily indicate treatment eligibility and might help scale up treatment intervention in Vietnam

A Look Back at an Ongoing Problem: Shigella dysenteriae Type 1 Epidemics in Refugee Settings in Central Africa (1993–1995)

BACKGROUND: Shigella dysenteriae type 1 (Sd1) is a cause of major dysentery outbreaks, particularly among children and displaced populations in tropical countries. Although outbreaks continue, the characteristics of such outbreaks have rarely been documented. Here, we describe the Sd1 outbreaks occurring between 1993 and 1995 in 11 refugee settlements in Rwanda, Tanzania and Democratic Republic of the Congo (DRC). We also explored the links between the different types of the camps and the magnitude of the outbreaks. METHODOLOGY/PRINCIPAL FINDINGS: Number of cases of bloody diarrhea and deaths were collected on a weekly basis in 11 refugee camps, and analyzed retrospectively. Between November 1993 and February 1995, 181,921 cases of bloody diarrhea were reported. Attack rates ranged from 6.3% to 39.1% and case fatality ratios (CFRs) from 1.5% to 9.0% (available for 5 camps). The CFRs were higher in children under age 5. In Tanzania where the response was rapidly deployed, the mean attack rate was lower than in camps in the region of Goma without an immediate response (13.3% versus 32.1% respectively). CONCLUSIONS/SIGNIFICANCE: This description, and the areas where data is missing, highlight both the importance of collecting data in future epidemics, difficulties in documenting outbreaks occurring in complex emergencies and most importantly, the need to assure that minimal requirements are met

Randomised pharmacokinetic trial of rifabutin with lopinavir/ritonavir-antiretroviral therapy in patients with HIV-associated tuberculosis in Vietnam.

BACKGROUND: Rifampicin and protease inhibitors are difficult to use concomitantly in patients with HIV-associated tuberculosis because of drug-drug interactions. Rifabutin has been proposed as an alternative rifamycin, but there is concern that the current recommended dose is suboptimal. The principal aim of this study was to compare bioavailability of two doses of rifabutin (150 mg three times per week and 150 mg daily) in patients with HIV-associated tuberculosis who initiated lopinavir/ritonavir-based antiretroviral therapy in Vietnam. Concentrations of lopinavir/ritonavir were also measured. METHODS: This was a randomized, open-label, multi-dose, two-arm, cross-over trial, conducted in Vietnamese adults with HIV-associated tuberculosis in Ho Chi Minh City (Clinical trial registry number NCT00651066). Rifabutin pharmacokinetics were evaluated before and after the introduction of lopinavir/ritonavir -based antiretroviral therapy using patient randomization lists. Serial rifabutin and 25-O-desacetyl rifabutin concentrations were measured during a dose interval after 2 weeks of rifabutin 300 mg daily, after 3 weeks of rifabutin 150 mg daily with lopinavir/ritonavir and after 3 weeks of rifabutin 150 mg three times per week with lopinavir/ritonavir. RESULTS: Sixteen and seventeen patients were respectively randomized to the two arms, and pharmacokinetic analysis carried out in 12 and 13 respectively. Rifabutin 150 mg daily with lopinavir/ritonavir was associated with a 32% mean increase in rifabutin average steady state concentration compared with rifabutin 300 mg alone. In contrast, the rifabutin average steady state concentration decreased by 44% when rifabutin was given at 150 mg three times per week with lopinavir/ritonavir. With both dosing regimens, 2 - 5 fold increases of the 25-O-desacetyl- rifabutin metabolite were observed when rifabutin was given with lopinavir/ritonavir compared with rifabutin alone. The different doses of rifabutin had no significant effect on lopinavir/ritonavir plasma concentrations. CONCLUSIONS: Based on these findings, rifabutin 150 mg daily may be preferred when co-administered with lopinavir/ritonavir in patients with HIV-associated tuberculosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00651066

Using European travellers as an early alert to detect emerging pathogens in countries with limited laboratory resources

BACKGROUND: The volume, extent and speed of travel have dramatically increased in the past decades, providing the potential for an infectious disease to spread through the transportation network. By collecting information on the suspected place of infection, existing surveillance systems in industrialized countries may provide timely information for areas of the world without adequate surveillance currently in place. We present the results of a case study using reported cases of Shigella dysenteriae serotype 1 (Sd1) in European travellers to detect "events" of Sd1, related to either epidemic cases or endemic cases in developing countries. METHODS: We identified papers from a Medline search for reported events of Sd1 from 1940 to 2002. We requested data on shigella infections reported to the responsible surveillance entities in 17 European countries. Reports of Sd1 from the published literature were then compared with Sd1 notified cases among European travellers from 1990 to 2002. RESULTS: Prior to a large epidemic in 1999–2000, no cases of Sd1 had been identified in West Africa. However, if travellers had been used as an early warning, Sd1 could have been identified in this region as earlier as 1992. CONCLUSION: This project demonstrates that tracking diseases in European travellers could be used to detect emerging disease in developing countries. This approach should be further tested with a view to the continuous improvement of national health surveillance systems and existing European networks, and may play a significant role in aiding the international public health community to improve infectious disease control

Zooplankton nutrition, storage and fecal lipid composition in different water masses associated with the Agulhas and Subtropical Fronts

Fecal pellets of zooplankton can be important carriers of organic matter from surface to deep waters of the oceans, The summer cruise ANTARES 4 gave us the opportunity to collect zooplankton from the frontal subantarctic zone (station 7 or s-ant) and adjacent subtropical waters (station 8 or s-trop). Triglyceride fatty acid profiles were used to assess the trophic position of two copepods (Metridia lucens and Pleuromamma spp.), three euphausiids (Euphausia spinifera, Nematoscelis megalops, and Thysanoessa sp) and a decapod Acanthephyra sp. The euphausiid E. spinifera was studied at the two sites and its reaction to contrasting trophic environments and hydrology was highlighted by variations in its lipid composition. Most species showed various degree of omnivory: E. spinifera from subantarctic showed the highest degree of herbivory on phytoplankton (high proportion of 16:4(n-1), 18:5(n-3), 16:1(n-7)), while the same species at the subtropical station, as well as Thysanoessa sp and M lucens from the subantarctic station displayed more omnivorous feeding characteristics, partly linked to the abundance of microzooplankton cells. Acanthephirasp, N. megalops and Pleuromammasp from station 8 (s-trop) appear to be essentially carnivorous (high 18:1 n-9/18:1n-7 ratio, high levels of 20: 1 (n-9) or 22: 1 (n-11)). The trophic position influenced the composition of feces, with higher PUFA percentages in fecal pellets from carnivorous species. Hence, the surface faunal assemblage and the season controlled not only the quantity but also the quality of the food supply as PUFA exported towards the benthic domain. (c) 2007 Elsevier B.V. All rights reserved

Prevalence, determinants of positivity, and clinical utility of cryptococcal antigenemia in Cambodian HIV-infected patients.

OBJECTIVES: To determine the prevalence, determinants ofpositivity, and clinical utility of serum cryptococcal polysaccharide (CPS) antigen testing among HIV-infected patients in 2004 in Cambodia, an area highly endemic for cryptococcosis. METHODS: All HIV-infected patients with a CD4+ count &lt;200 cells/mm3 attending 1 of 2 Phnom Penh hospitals for the first time were systematically screened for serum CPS. Patients with positive test results were further investigated to identify those with cryptococcal meningitis (CM), pulmonary cryptococcosis, or isolated positive cryptococcal antigenemia (IPCA). RESULTS: The median (interquartile range [IQR]) CD4+ count of 327 enrolled patients was 24 (IQR: 8 to 65) cells/mm3. The prevalence of cryptococcal infection was 59 (18.0%) of 327 cases, of which 41 were CM and 10 were IPCA. In the absence of serum CPS detection, 17 (28.8%) of 59 cryptococcal infections would have been missed on the day of consultation. In patients with no specific symptoms of meningoencephalitis, the prevalence of positive serum CPS detection was 32 (10.8%) of 295 cases. Countryside residence (adjusted odds ratio [AOR] = 3.6), headache (AOR = 3.2), body mass index &lt;15.4 kg/m2 (AOR = 3.4), CD4+ count &lt;50 cells/mm3 (AOR = 4.0), and male gender (marginally, AOR = 2.1) were all independently associated with a positive test results. CONCLUSION: Serum CPS screening among AIDS patients with a CD4+ count &lt;100 cells/mm3 is useful in areas highly endemic for cryptococcosis, allowing early diagnosis and treatment of this opportunistic infection

Confirmation of HCV viremia using HCV RNA and core antigen testing on dried blood spot in HIV infected peoples who inject drugs in Vietnam

Background Nucleic acid tests performed on blood samples collected on Dried Blood Spot (DBS) and detection of HCV core antigen (HCVcAg) are two approaches that may facilitate access to HCV diagnosis in low and middle incomes countries. In this study we evaluate HCV RNA and HCV antigen testing on DBS in HIV/HCV co-infected peoples who inject drugs in Vietnam. Method One hundred and four HIV/HCV seropositive patients managed in outpatient care at the Haiphong Viet Tiep hospital were included in this study from February to March, 2014 (ANRS 12262 study). Results Eighty-six subjects were tested positive for HCV RNA in serum, median (IQR): 6.9 log10 IU/ml (5.6–7.4 log10 IU/ml). Genotypes consisted of 57 G1 (69%), 3 G3 (4%), and 22 G6 (27%). HCV RNA was detected on DBS specimens in 79 out 86 subjects with chronic hepatitis C (sensitivity 92.5%; 95% CI: 85.1–96.9%). HCV RNA level on DBS and serum was moderately correlated (r = 0.24; p = 0.05) suggesting a degradation of HCV RNA due to transportation and storage conditions. HCVcAg was detected in 75/86 dB specimens (sensitivity: 87.2%; 95% CI: 78.3–93.4%), with a strong positive relationship between DBS HCVcAg and serum HCV RNA levels (r = 0.80; P < 0.0001). Conclusions Quantification of HCVcAg on DBS appears to benefit from substantial stability under prolonged storage conditions but with a lower analytical sensitivity compared to DBS HCV RNA testing. Detection of HCV RNA on DBS is an interesting approach for confirming viral replication in HCV seropositive persons but the impact of pre-analytical conditions on the integrity of HCV RNA needs to be controlled

N Engl J Med

Background In regions with high burdens of tuberculosis and human immunodeficiency virus (HIV), many HIV-infected adults begin antiretroviral therapy (ART) when they are already severely immunocompromised. Mortality after ART initiation is high in these patients, and tuberculosis and invasive bacterial diseases are common causes of death. Methods We conducted a 48-week trial of empirical treatment for tuberculosis as compared with treatment guided by testing in HIV-infected adults who had not previously received ART and had CD4+ T-cell counts below 100 cells per cubic millimeter. Patients recruited in Ivory Coast, Uganda, Cambodia, and Vietnam were randomly assigned in a 1:1 ratio to undergo screening (Xpert MTB/RIF test, urinary lipoarabinomannan test, and chest radiography) to determine whether treatment for tuberculosis should be started or to receive systematic empirical treatment with rifampin, isoniazid, ethambutol, and pyrazinamide daily for 2 months, followed by rifampin and isoniazid daily for 4 months. The primary end point was a composite of death from any cause or invasive bacterial disease within 24 weeks (primary analysis) or within 48 weeks after randomization. Results A total of 522 patients in the systematic-treatment group and 525 in the guided-treatment group were included in the analyses. At week 24, the rate of death from any cause or invasive bacterial disease (calculated as the number of first events per 100 patient-years) was 19.4 with systematic treatment and 20.3 with guided treatment (adjusted hazard ratio, 0.95; 95% confidence interval [CI], 0.63 to 1.44). At week 48, the corresponding rates were 12.8 and 13.3 (adjusted hazard ratio, 0.97 [95% CI, 0.67 to 1.40]). At week 24, the probability of tuberculosis was lower with systematic treatment than with guided treatment (3.0% vs. 17.9%; adjusted hazard ratio, 0.15; 95% CI, 0.09 to 0.26), but the probability of grade 3 or 4 drug-related adverse events was higher with systematic treatment (17.4% vs. 7.2%; adjusted hazard ratio 2.57; 95% CI, 1.75 to 3.78). Serious adverse events were more common with systematic treatment. Conclusions Among severely immunosuppressed adults with HIV infection who had not previously received ART, systematic treatment for tuberculosis was not superior to test-guided treatment in reducing the rate of death or invasive bacterial disease over 24 or 48 weeks and was associated with more grade 3 or 4 adverse events