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1.
Trials ; 17(1): 279, 2016 06 06.
Article in English | MEDLINE | ID: mdl-27266697

ABSTRACT

BACKGROUND: Anthelmintics are one of the more commonly available classes of drugs to treat infections by parasitic helminths (especially nematodes) in the human intestinal tract. As a result of their cost-effectiveness, mass school-based deworming programs are becoming routine practice in developing countries. However, experimental and clinical evidence suggests that anthelmintic treatments may increase susceptibility to other gastrointestinal infections caused by bacteria, viruses, or protozoa. Hypothesizing that anthelmintics may increase diarrheal infections in treated children, we aim to evaluate the impact of anthelmintics on the incidence of diarrheal disease caused by viral and bacterial pathogens in school children in southern Vietnam. METHODS/DESIGN: This is a randomized, double-blinded, placebo-controlled trial to investigate the effects of albendazole treatment versus placebo on the incidence of viral- and bacterial-induced diarrhea in 350 helminth-infected and 350 helminth-uninfected Vietnamese school children aged 6-15 years. Four hundred milligrams of albendazole, or placebo treatment will be administered once every 3 months for 12 months. At the end of 12 months, all participants will receive albendazole treatment. The primary endpoint of this study is the incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance. Secondary endpoints include the prevalence and intensities of helminth, viral, and bacterial infections, alterations in host immunity and the gut microbiota with helminth and pathogen clearance, changes in mean z scores of body weight indices over time, and the number and severity of adverse events. DISCUSSION: In order to reduce helminth burdens, anthelmintics are being routinely administered to children in developing countries. However, the effects of anthelmintic treatment on susceptibility to other diseases, including diarrheal pathogens, remain unknown. It is important to monitor for unintended consequences of drug treatments in co-infected populations. In this trial, we will examine how anthelmintic treatment impacts host susceptibility to diarrheal infections, with the aim of informing deworming programs of any indirect effects of mass anthelmintic administrations on co-infecting enteric pathogens. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02597556 . Registered on 3 November 2015.


Subject(s)
Albendazole/adverse effects , Anthelmintics/adverse effects , Diarrhea/epidemiology , Helminthiasis/prevention & control , Opportunistic Infections/epidemiology , Adolescent , Age Factors , Albendazole/administration & dosage , Anthelmintics/administration & dosage , Child , Clinical Protocols , Diarrhea/diagnosis , Diarrhea/microbiology , Diarrhea/virology , Double-Blind Method , Drug Administration Schedule , Female , Helminthiasis/diagnosis , Helminthiasis/epidemiology , Helminthiasis/parasitology , Humans , Incidence , Male , Opportunistic Infections/diagnosis , Opportunistic Infections/microbiology , Opportunistic Infections/virology , Prevalence , Research Design , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Vietnam/epidemiology
2.
J Med Microbiol ; 64(10): 1162-1169, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26297024

ABSTRACT

Acinetobacter baumannii has become one of the major infection threats in intensive care units (ICUs) globally. Since 2008, A. baumannii has been the leading cause of ventilator-associated pneumonia (VAP) in our ICU at an infectious disease hospital in southern Vietnam. The emergence of this pathogen in our setting is consistent with the persistence of a specific clone exhibiting resistance to carbapenems. Antimicrobial combinations may be a strategy to treat infections caused by these carbapenem-resistant A. baumannii. Therefore, we assessed potential antimicrobial combinations against local carbapenem-resistant A. baumannii by measuring in vitro interactions of colistin with four antimicrobials that are locally certified for treating VAP. We first performed antimicrobial susceptibility testing and multilocus variable number tandem repeat analysis (MLVA) genotyping on 74 A. baumannii isolated from quantitative tracheal aspirates from patients with VAP over an 18-month period. These 74 isolates could be subdivided into 21 main clusters by MLVA and >80 % were resistant to carbapenems. We selected 56 representative isolates for in vitro combination synergy testing. Synergy was observed in four (7 %), seven (13 %), 20 (36 %) and 38 (68 %) isolates with combinations of colistin with ceftazidime, ceftriaxone, imipenem and meropenem, respectively. Notably, more carbapenem-resistant A. baumannii isolates (36/43; 84 %) exhibited synergistic activity with a combination of colistin and meropenem than carbapenem-susceptible A. baumannii isolates (2/13; 15 %) (P = 0.023; Fisher's exact test). Our findings suggest that combinations of colistin and meropenem should be considered when treating carbapenem-resistant A. baumannii infections in Vietnam, and we advocate clinical trials investigating combination therapy for VAP.


Subject(s)
Acinetobacter baumannii/drug effects , Anti-Bacterial Agents/pharmacology , Carbapenems/pharmacology , Colistin/pharmacology , Drug Synergism , Pneumonia, Ventilator-Associated/microbiology , Acinetobacter baumannii/classification , Acinetobacter baumannii/genetics , Acinetobacter baumannii/isolation & purification , Cluster Analysis , Genotype , Hospitals , Humans , Microbial Sensitivity Tests , Multilocus Sequence Typing , Pneumonia, Ventilator-Associated/epidemiology , Vietnam/epidemiology , beta-Lactam Resistance
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