Marks M.E.,The Hospital for Tropical Diseases |
Armstrong M.,The Hospital for Tropical Diseases |
Suvari M.M.,Hospital for Tropical Diseases |
Batson S.,University College London |
And 4 more authors.
BMC Infectious Diseases | Year: 2013
Background: Malaria is the commonest imported infection in the UK. Malaria requiring ICU admission has a reported mortality of up to 25%. The relationship between ethnicity, immunity, and risk of malaria is complex. The Malaria Score for Adults (MSA) and Coma Acidosis Malaria (CAM) score have recently been proposed to risk stratify patients with malaria. Methods: Retrospective study of patients with WHO severe falciparum malaria admitted to ICU at the Hospital for Tropical Diseases, London, UK. The relationship between clinical variables and risk of death or a prolonged ICU stay were examined with logistic regression. The predictive value of the MSA and CAM score were calculated. Results: 124 patients were included. Cerebral malaria and acute kidney injury occurred earlier (median day 1) than acute respiratory distress syndrome (median day 3). Six patients had community acquired bacterial co-infection. Eight patients were co-infected with HIV, five of whom were newly diagnosed. The positive predictive value of a CAM score ≥2 or an MSA ≥5 for death were 12% and 22% respectively. Five patients died. No variable was significantly associated with risk of death. There were no significant differences between individuals raised in endemic countries compared to non-endemic countries. Conclusions: Mortality in patients managed in a specialist centre was low. Patients who died succumbed to complications associated with a prolonged stay on ICU rather than malaria per se. The clinical usefulness of the MSA and CAM score was limited. Co-infection with HIV was relatively common but compared to studies in children, bacteraemia was uncommon. The relationship between ethnicity and immunity to severe disease is complex. © 2013 Marks et al; licensee BioMed Central Ltd.
PubMed | Hung Vuong Hospital, Childrens Hospital No 1, Dong Thap Hospital, University of Melbourne and 5 more.
Type: | Journal: International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases | Year: 2015
Previous studies indicate a high burden of diarrhoeal disease in Vietnamese children, however longitudinal community-based data on burden and aetiology are limited. The findings from a large, prospective cohort study of diarrhoeal disease in infants in southern Vietnam are presented herein.Infants were enrolled at birth in urban Ho Chi Minh City and a semi-rural district in southern Vietnam, and followed for 12 months (n=6706). Diarrhoeal illness episodes were identified through clinic-based passive surveillance, hospital admissions, and self-reports.The minimum incidence of diarrhoeal illness in the first year of life was 271/1000 infant-years of observation for the whole cohort. Rotavirus was the most commonly detected pathogen (50% of positive samples), followed by norovirus (24%), Campylobacter (20%), Salmonella (18%), and Shigella (16%). Repeat infections were identified in 9% of infants infected with rotavirus, norovirus, Shigella, or Campylobacter, and 13% of those with Salmonella infections.The minimum incidence of diarrhoeal disease in infants in both urban and semi-rural settings in southern Vietnam was quantified prospectively. A large proportion of laboratory-diagnosed disease was caused by rotavirus and norovirus. These data highlight the unmet need for a rotavirus vaccine in Vietnam and provide evidence of the previously unrecognized burden of norovirus in infants.
PubMed | Pham Ngoc Thach University of Medicine, Cu Chi Preventive Medicine Center, The Hospital for Tropical Diseases, The Royal Veterinary College and 2 more.
Type: Journal Article | Journal: Trials | Year: 2016
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.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 ofalbendazole, or placebo treatment will be administered once every 3months for 12months. At the end of 12months, all participants will receive albendazole treatment. The primary endpoint of this study is the incidence of diarrheal disease assessed by 12months 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.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.ClinicalTrials.gov: NCT02597556 . Registered on 3 November 2015.
PubMed | University of Amsterdam, University of Edinburgh, Global Viral, Hanoi Medical University and 4 more.
Type: Journal Article | Journal: EcoHealth | Year: 2016
The effect of newly emerging or re-emerging infectious diseases of zoonotic origin in human populations can be potentially catastrophic, and large-scale investigations of such diseases are highly challenging. The monitoring of emergence events is subject to ascertainment bias, whether at the level of species discovery, emerging disease events, or disease outbreaks in human populations. Disease surveillance is generally performed post hoc, driven by a response to recent events and by the availability of detection and identification technologies. Additionally, the inventory of pathogens that exist in mammalian and other reservoirs is incomplete, and identifying those with the potential to cause disease in humans is rarely possible in advance. A major step in understanding the burden and diversity of zoonotic infections, the local behavioral and demographic risks of infection, and the risk of emergence of these pathogens in human populations is to establish surveillance networks in populations that maintain regular contact with diverse animal populations, and to simultaneously characterize pathogen diversity in human and animal populations. Vietnam has been an epicenter of disease emergence over the last decade, and practices at the human/animal interface may facilitate the likelihood of spillover of zoonotic pathogens into humans. To tackle the scientific issues surrounding the origins and emergence of zoonotic infections in Vietnam, we have established The Vietnam Initiative on Zoonotic Infections (VIZIONS). This countrywide project, in which several international institutions collaborate with Vietnamese organizations, is combining clinical data, epidemiology, high-throughput sequencing, and social sciences to address relevant one-health questions. Here, we describe the primary aims of the project, the infrastructure established to address our scientific questions, and the current status of the project. Our principal objective is to develop an integrated approach to the surveillance of pathogens circulating in both human and animal populations and assess how frequently they are exchanged. This infrastructure will facilitate systematic investigations of pathogen ecology and evolution, enhance understanding of viral cross-species transmission events, and identify relevant risk factors and drivers of zoonotic disease emergence.
Campbell J.I.,University of Oxford |
Lan N.P.H.,The Hospital for Tropical Diseases |
Qui P.T.,The Hospital for Tropical Diseases |
Dung L.T.,The Hospital for Tropical Diseases |
And 2 more authors.
BMC Infectious Diseases | Year: 2013
Background: Chromobacterium violaceum is a proteobacterium found in soil and water in tropical regions. The organism rarely causes infection in humans, yet can cause a severe systemic infection by entering the bloodstream via an open wound.Case presentation: We recently identified a case of severe bacteremia caused by Chromobacterium violaceum at the Hospital for Tropical Diseases (HTD) in Ho Chi Minh City, Vietnam. Here, we describe how rapid microbiological identification and a combination of antimicrobials was used to successfully treat this life threatening infection in a four-year-old child.Conclusions: This case shows the need for rapid diagnosis when there is the suspicion of a puncture wound contaminated with water and soil in tropical regions. We suggest that the aggressive antimicrobial combination used here is considered when this infection is suspected. © 2013 Campbell et al.; licensee BioMed Central Ltd.
PubMed | University of Oxford, London School of Hygiene and Tropical Medicine and The Hospital for Tropical Diseases
Type: | Journal: Scientific reports | Year: 2016
Acinetobacter baumannii is a significant cause of opportunistic hospital acquired infection and has been identified as an important emerging infection due to its high levels of antimicrobial resistance. Multidrug resistant A. baumannii has risen rapidly in Vietnam, where colistin is becoming the drug of last resort for many infections. In this study we generated spontaneous colistin resistant progeny (up to >256g/l) from four colistin susceptible Vietnamese isolates and one susceptible reference strain (MIC <1.5g/l). Whole genome sequencing was used to identify single nucleotide mutations that could be attributed to the reduced colistin susceptibility. We identified six lpxACD and three pmrB mutations, the majority of which were novel. In addition, we identified further mutations in six A. baumannii genes (vacJ, pldA, ttg2C, pheS and conserved hypothetical protein) that we hypothesise have a role in reduced colistin susceptibility. This study has identified additional mutations that may be associated with colistin resistance through novel resistance mechanisms. Our work further demonstrates how rapidly A. baumannii can generate resistance to a last resort antimicrobial and highlights the need for improved surveillance to identified A. baumannii with an extensive drug resistance profile.
News Article | November 30, 2016
Significant numbers of patients whose HIV strains developed resistance to older generation drugs are also resistant to modern drugs, finds a new study led by UCL and funded by Wellcome. The research, co-authored by researchers at the London School of Hygiene and Tropical Medicine and published in The Lancet Infectious Diseases, studied 712 HIV patients across the world whose HIV was not controlled by antiretrovirals. The study found that 16% of people who stopped responding to modern first-line treatments had HIV mutations associated with resistance to an older generation of drugs called thymidine analogues. Among patients with a thymidine analogue mutation, 80% were also resistant to tenofovir, the main drug in most modern HIV treatment and prevention strategies. "We were very surprised to see that so many people were resistant to both drugs, as we didn't think this was possible," explains lead author Professor Ravi Gupta (UCL Infection & Immunity), who is also an Honorary Consultant in Infectious Diseases at The Hospital for Tropical Diseases, UCLH NHS Foundation Trust. "Mutations for thymidine analogue resistance were previously thought to be incompatible with mutations for tenofovir resistance, but we now see that HIV can be resistant to both at once. This emphasises the need to check the genetic profile of patient's virus before prescribing first-line treatments, as they may have already developed resistance to other treatments that they did not mention having taken." Resistance to a drug typically occurs when a patient doesn't take their medication regularly enough, and for first-line treatments to work patients generally need to take their medication 85-90% of the time. When treatment is not taken as advised the virus can develop a resistance to the drugs, and the latest study shows that HIV can be resistant to many different drugs simultaneously. "To prevent these multi-resistant strains from developing, we need cheap, reliable systems to assess people before treatment," says Professor Gupta. "Ideally, we need simple resistance testing kits to help screen for drug resistance before giving treatment. This would also help us to monitor HIV drug resistance globally more effectively. However, until such kits are widely available, we could test the amount of virus in the bloodstream before and after giving treatment. Although not as precise as resistance testing, this could help us to detect treatment failure earlier and switch patients to second line drugs." If a patient's virus becomes resistant to first-line drugs, the next stage is expensive second-line treatment with greater side effects. Many rural patients do not have access to such drugs, so it is important to try to preserve the effectiveness of first-line treatments.
Parry C.M.,University of Oxford |
Parry C.M.,Mahidol University |
Vinh H.,The Hospital for Tropical Diseases |
Chinh N.T.,The Hospital for Tropical Diseases |
And 5 more authors.
PLoS Neglected Tropical Diseases | Year: 2011
Background: Infection with Salmonella enterica serovar Typhi (S. Typhi) with reduced susceptibility to fluoroquinolones has been associated with fluoroquinolone treatment failure. We studied the relationship between ofloxacin treatment response and the ofloxacin minimum inhibitory concentration (MIC) of the infecting isolate. Individual patient data from seven randomised controlled trials of antimicrobial treatment in enteric fever conducted in Vietnam in which ofloxacin was used in at least one of the treatment arms was studied. Data from 540 patients randomised to ofloxacin treatment was analysed to identify an MIC of the infecting organism associated with treatment failure. Principal Findings: The proportion of patients failing ofloxacin treatment was significantly higher in patients infected with S. Typhi isolates with an MIC≥0.25 μg/mL compared with those infections with an MIC of ≤0.125 μg/mL (p<0.001). Treatment success was 96% when the ofloxacin MIC was ≤0.125 μg/mL, 73% when the MIC was between 0.25 and 0.50 μg/mL and 53% when the MIC was 1.00 μg/mL. This was despite a longer duration of treatment at a higher dosage in patients infected with isolates with an MIC≥0.25 μg/mL compared with those infections with an MIC of ≤0.125 μg/mL. Significance: There is a clear relationship between ofloxacin susceptibility and clinical outcome in ofloxacin treated patients with enteric fever. An ofloxacin MIC of ≥0.25 μg/mL, or the presence of nalidixic acid resistance, can be used to define S. Typhi infections in which the response to ofloxacin may be impaired. © 2011 Parry et al.
PubMed | Korean International Vaccine Institute, University of Oxford, University of Cambridge and The Hospital for Tropical Diseases
Type: Journal Article | Journal: PLoS neglected tropical diseases | Year: 2016
Invasive non-typhoidal Salmonella (iNTS) infections are now a well-described cause of morbidity and mortality in children and HIV-infected adults in sub-Saharan Africa. In contrast, the epidemiology and clinical manifestations of iNTS disease in Asia are not well documented. We retrospectively identified >100 cases of iNTS infections in an infectious disease hospital in Southern Vietnam between 2008 and 2013. Clinical records were accessed to evaluate demographic and clinical factors associated with iNTS infection and to identify risk factors associated with death. Multi-locus sequence typing and antimicrobial susceptibility testing was performed on all organisms. Of 102 iNTS patients, 71% were HIV-infected, >90% were adults, 71% were male and 33% reported intravenous drug use. Twenty-six/92 (28%) patients with a known outcome died; HIV infection was significantly associated with death (p = 0.039). S. Enteritidis (Sequence Types (ST)11) (48%, 43/89) and S. Typhimurium (ST19, 34 and 1544) (26%, 23/89) were the most commonly identified serovars; S. Typhimurium was significantly more common in HIV-infected individuals (p = 0.003). Isolates from HIV-infected patients were more likely to exhibit reduced susceptibility against trimethoprim-sulfamethoxazole than HIV-negative patients (p = 0.037). We conclude that iNTS disease is a severe infection in Vietnam with a high mortality rate. As in sub-Saharan Africa, HIV infection was a risk factor for death, with the majority of the burden in this population found in HIV-infected adult men.