Present and future use of antimicrobials in pigs in developing countries and case studies from Uganda and Vietnam

Demand for pork is growing rapidly in developing countries, and will be mostly met by intensive production. Although this can produce large quantities of affordable meat, it can have environmental, social and human health externalities. We report on recent studies conducted by ILRI and partners on antimicrobial use in pork production in developing countries and antimicrobial resistance (AMR) in pork

Combination Antifungal Therapy for Cryptococcal Meningitis

Background Combination antifungal therapy (amphotericin B deoxycholate and flucytosine) is the recommended treatment for cryptococcal meningitis but has not been shown to reduce mortality, as compared with amphotericin B alone. We performed a randomized, controlled trial to determine whether combining flucytosine or high-dose fluconazole with high-dose amphotericin B improved survival at 14 and 70 days. Methods We conducted a randomized, three-group, open-label trial of induction therapy for cryptococcal meningitis in patients with human immunodeficiency virus infection. All patients received amphotericin B at a dose of 1 mg per kilogram of body weight per day; patients in group 1 were treated for 4 weeks, and those in groups 2 and 3 for 2 weeks. Patients in group 2 concurrently received flucytosine at a dose of 100 mg per kilogram per day for 2 weeks, and those in group 3 concurrently received fluconazole at a dose of 400 mg twice daily for 2 weeks. Results A total of 299 patients were enrolled. Fewer deaths occurred by days 14 and 70 among patients receiving amphotericin B and flucytosine than among those receiving amphotericin B alone (15 vs. 25 deaths by day 14; hazard ratio, 0.57; 95% confidence interval [CI], 0.30 to 1.08; unadjusted P=0.08; and 30 vs. 44 deaths by day 70; hazard ratio, 0.61; 95% CI, 0.39 to 0.97; unadjusted P=0.04). Combination therapy with fluconazole had no significant effect on survival, as compared with monotherapy (hazard ratio for death by 14 days, 0.78; 95% CI, 0.44 to 1.41; P=0.42; hazard ratio for death by 70 days, 0.71; 95% CI, 0.45 to 1.11; P=0.13). Amphotericin B plus flucytosine was associated with significantly increased rates of yeast clearance from cerebrospinal fluid (−0.42 log10 colony-forming units [CFU] per milliliter per day vs. −0.31 and −0.32 log10 CFU per milliliter per day in groups 1 and 3, respectively; P<0.001 for both comparisons). Rates of adverse events were similar in all groups, although neutropenia was more frequent in patients receiving a combination therapy. Conclusions Amphotericin B plus flucytosine, as compared with amphotericin B alone, is associated with improved survival among patients with cryptococcal meningitis. A survival benefit of amphotericin B plus fluconazole was not found

A prospective descriptive study of cryptococcal meningitis in HIV uninfected patients in Vietnam - high prevalence of Cryptococcus neoformans var grubii in the absence of underlying disease

<p>Abstract</p> <p>Background</p> <p>Most cases of cryptococcal meningitis occur in patients with HIV infection: the course and outcome of disease in the apparently immunocompetent is much more poorly understood. We describe a cohort of HIV uninfected Vietnamese patients with cryptococcal meningitis in whom underlying disease is uncommon, and relate presenting features of patients and the characteristics of the infecting species to outcome.</p> <p>Methods</p> <p>A prospective descriptive study of HIV negative patients with cryptococcal meningitis based at the Hospital for Tropical Diseases, Ho Chi Minh City. All patients had comprehensive clinical assessment at baseline, were cared for by a dedicated study team, and were followed up for 2 years. Clinical presentation was compared by infecting isolate and outcome.</p> <p>Results</p> <p>57 patients were studied. <it>Cryptococcus neoformans var grubii </it>molecular type VN1 caused 70% of infections; <it>C. gattii </it>accounted for the rest. Most patients did not have underlying disease (81%), and the rate of underlying disease did not differ by infecting species. 11 patients died while in-patients (19.3%). Independent predictors of death were age ≥ 60 years and a history of convulsions (odds ratios and 95% confidence intervals 8.7 (1 - 76), and 16.1 (1.6 - 161) respectively). Residual visual impairment was common, affecting 25 of 46 survivors (54.3%). Infecting species did not influence clinical phenotype or outcome. The minimum inhibitory concentrations of flucytosine and amphotericin B were significantly higher for <it>C. neoformans var grubii </it>compared with <it>C. gattii </it>(p < 0.001 and p = 0.01 respectively).</p> <p>Conclusion</p> <p>In HIV uninfected individuals in Vietnam, cryptococcal meningitis occurs predominantly in people with no clear predisposing factor and is most commonly due to <it>C. neoformans var grubii</it>. The rates of mortality and visual loss are high and independent of infecting species. There are detectable differences in susceptibility to commonly used antifungal drugs between species, but the clinical significance of this is not clear.</p

Unraveling a 146 Years Old Taxonomic Puzzle: Validation of Malabar Snakehead, Species-Status and Its Relevance for Channid Systematics and Evolution

The current distribution of C. diplogramma and C. micropeltes is best explained by vicariance. The significant variation in the key taxonomic characters and the results of the molecular marker analysis points towards an allopatric speciation event or vicariant divergence from a common ancestor, which molecular data suggests to have occurred as early as 21.76 million years ago. The resurrection of C. diplogramma from the synonymy of C. micropeltes has hence been confirmed 146 years after its initial description and 134 years after it was synonymised, establishing it is an endemic species of peninsular India and prioritizing its conservation value

Quantifying salmonella contamination in pig slautherhouses in Hung Yen, Vietnam

The risk of Salmonella contamination along the pork production is a worldwide concern. Not only the biological contamination, but also personal perception and individual behavior play a role for risk assessment along a chain. This study is to identify the prevalence and number of Salmonella in 3 pig slaughterhouses in relation to several risk factors. During January to April 2013, a total of 87 samples (carcasses, workers' hands, cutting board and belly skin material) were collected from 4 visits to each slaughterhouse. A 3-tube Most Probable Number (MPN) was applied to quantify the number of Salmonella from carcass, workers' hands, cutting board and belly skin samples (35 samples). The result showed that Salmonella prevalence was 36.9% (26.7-47.8%), mostly found on worker's hands (50%) and the lowest from cutting board (33.3%). The highest number of Salmonella on carcass and cutting boards was less than 0.075 MPN/cm2 and 1.2 MPN/cm2, respectively. Potential riskfactors were tested however they were not statistical significant. This study underlines the necessity of good hygiene practices and management in slaughterhouses. In terms of food safety, further risk assessment of Salmonella in pork production chains is needed

Comparative Pharmacokinetics of Intramuscular Artesunate and Artemether in Patients with Severe Falciparum Malaria

A new technique is proposed for upper bounding the error probability of fixed length block codes with feedback. Error analysis is inspired by Gallager's error analysis for block codes without feedback. Zigangirov-D'yachkov (Z-D ) encoding scheme is analyzed with the technique on binary input channels and k-ary symmetric channels. A strict improvement is obtained for k-ary symmetric channels

Comparative Pharmacokinetics of Intramuscular Artesunate and Artemether in Patients with Severe Falciparum Malaria

The first-dose pharmacokinetic properties of intramuscular (i.m.) artesunate (ARTS; 2.4 mg/kg immediately [stat], followed by 1.2 mg/kg i.m. daily) and artemether (ARM; 3.2 mg/kg i.m. stat, followed by 1.6 mg/kg i.m. daily) were compared in Vietnamese adults with severe falciparum malaria. A total of 19 patients were studied; 9 received ARTS, and 10 received ARM. ARTS was absorbed very rapidly; concentrations in plasma peaked between 1,362 and 8,388 nmol/liter (median, 5,710 nmol/liter) within 20 min of injection and then declined with a median (range) half-life (t(1/2)) of 30 (3 to 67) min. ARTS was hydrolyzed rapidly and completely to the biologically active metabolite dihydroartemisinin (DHA). Peak DHA concentrations in plasma ranged between 1,718 and 7,080 nmol/liter (median, 3,060 nmol/liter) and declined with a t(1/2) of 52 (26 to 69) min. In contrast, ARM was slowly and erratically absorbed. The absorption profile appeared biphasic. Maximum ARM concentrations in plasma ranged between 67 nmol/liter (a value close to the 50% inhibitory concentration for some Plasmodium falciparum isolates) and 1,631 nmol/liter (median, 574 nmol/liter) and occurred at a median (range) of 10 (1.5 to 24) h. There was relatively little conversion to DHA. After i.m. injection in cases of severe malaria, absorption of the water-soluble ARTS is rapid and extensive, whereas the oil-based ARM is slowly and erratically absorbed, with relatively little conversion to the more active DHA. On the basis of this pharmacological study, parenteral ARTS is preferable to ARM as an initial antimalarial therapy, particularly in the most seriously ill patients. These findings should be formally assessed by a randomized clinical trial