Active clinical trials for "Typhoid Fever"

Typhoid and paratyphoid (enteric) fever affects more than 11 million children and adults globally each year including 7 million in South Asia. Up to 1% of patients who get typhoid may die of the disease and, in those that survive, a prolonged period of ill health and catastrophic financial cost to the family may follow. In the last 20 years, treatment of typhoid fever with a 7-day course of a single oral antimicrobial, such as ciprofloxacin, cefixime or azithromycin, given in an out-patient setting has led to patient recovery in 4 to 6 days without the need for expensive hospitalization. Increasing antimicrobial resistance in Asia and sub-Saharan Africa, threatens the effectiveness of these treatments and increases the risk of prolonged illness and severe disease. The recent emergence of a particularly resistant typhoid strain in Pakistan, and subsequent international spread, adds urgency to this problem and Salmonella is now listed as a high (Priority 2) pathogen by world health organisation. Treatment with combinations of antimicrobials may be more effective for treating typhoid fever and mitigate the problems of resistance. This suggestion is based on expert opinion but not backed up by good quality evidence. The ACT-South Asia study aims to compare a combination of azithromycin and cefixime with azithromycin alone in the outpatient treatment of clinically suspected and confirmed uncomplicated typhoid fever. The total recruitment will be 1500 patients across sites in Bangladesh, India, Nepal and Pakistan. A placebo (sugar pill) will be used instead of cefixime in the single drug arm so that neither the patient nor the study team know which patient is receiving which treatment.Investigators will assess whether treatment outcomes are better with the combination after one week of treatment and at one and three month follow-up. Both antimicrobials are widely used and have excellent safety profiles. If the combination treatment is better than the single antibiotic treatment, this will be an important result for patients across South Asia and other typhoid endemic areas. This study will additionally investigate the financial implications for families and health system.

This is a double blinded, randomized-controlled, non-inferiority trial of a typhoid conjugate vaccine, Typhocon (Vi- polysaccharide conjugated to diphtheria toxoid, Vi-DT), manufactured by a local company, Incepta Vaccine Limited. The vaccine will be tested among individuals from 6 months to 60 years of age residing in Mirpur area of Dhaka city. The Typbar-TCV (Vi-polysaccharide conjugated to tetanus toxoid, Vi-TT), manufactured by Bharat Biotech International Limited will be used as a reference vaccine in this study. In Phase I the Typhocon vaccine will be tested in 30 adults. Safety and immunogenicity data of the vaccine for 30 adults will be submitted to the Data Safety Monitoring Board (DSMB), IRB and Directorate General of Drug Administration (DGDA). Upon receiving approval letter, the investigators will initiate the Phase II study including 600 individuals. The Phase II study will be conducted in age de-escalation manner (6-23 months, 2-5 years, 6-17 years and 18-60 years). Equal number of participants of all age groups will be enrolled for vaccination. Blood specimens will also be collected for carrying out the clinical chemistry (complete blood count with differential for white blood count, hemoglobin, absolute neutrophil count, platelet count, serum alanine transaminase, serum creatinine) on day -7 to day -2 for screening of participants before vaccination and on day 28, postvaccination. Based on blood reports of clinical chemistry, 600 participants will be randomized in a 1:1 ratio to allocate Typhocon or Typbar-TCV vaccine. Memory aid will be used to collect solicited adverse events following vaccination (AEFI) data up to day 7. Data on unsolicited AEFI and serious adverse events (SAEs) will be collected up to 28 days after vaccination. All study update including adverse events and serious adverse events will be reported to the DSMB. Blood specimen will be obtained on day 0 before vaccination, and day 28 for carrying out Enzyme-linked Immunosorbent Assay (ELISA) to determine anti-Vi-IgG antibody.

This cluster randomised trial will examine the impact of introducing TyphiBEV, a typhoid conjugate vaccine licensed in India, on the incidence of typhoid fever in a high burden urban setting in South India.

A bivalent Typhoid and Paratyphoid A conjugate investigational vaccine aimed to prevent both typhoid and paratyphoid enteric fever in infants and older age groups has been developed by GlaxoSmithKline (GSK). The purpose of this first-time-in-human study is to evaluate the safety and immunogenicity profile of a low and a full dose of the investigational vaccine, formulated with or without adjuvant, administered in 2 doses, 24 weeks apart, in healthy adults 18 to 50 years of age in Europe.

This is a prospective cohort evaluation of vaccine effectiveness of a single dose of Typbar-TCV® against symptomatic blood culture-confirmed typhoid fever when administered through a mass vaccination campaign to children 9 months to <16 years of age in Kisantu, DRC.

The purpose of this study is to assess the safety, reactogenicity, and immune response induced by the GlaxoSmithKline Biologicals SA (GSK) Vaccines Institute for Global Health (GVGH) invasive nontyphoidal Salmonella-typhoid conjugate (iNTS-TCV) candidate vaccine to be administered for the first time in humans. The study intervention will be evaluated in European adults in Stage 1 (a 2-step staggered design) followed by African adults in Stage 2.

The purpose of this study is to determine if adding dietary fiber, such as inulin, to a diet that does not have enough fiber would raise the levels of potentially beneficial bacteria, such as Bifidobacterium, in the gut. There is evidence to suggest that these microbes can affect gut health and immune response, including to vaccines. The investigators will examine how inulin in the diet (compared to the maltodextrin control) (1) causes changes in the composition and function of the gut microbes, (2) reduces gut inflammation and gut leakiness caused by the vaccine, (3) increases immune response to vaccination, and (4) changes the expression of important adhesion molecules on the surface of white blood cells. Intestinal and whole-body responses will be measured in all participants.

A cluster-randomised controlled Phase IV trial (cRCT) assessing the impact of a Vi-Polysaccharide conjugate vaccine in preventing typhoid infection in Asante Akim, Ghana (TyVEGHA) with a primary endpoint of determining the total protection conferred by single-dose vaccination with Vi-TT against blood culture-confirmed symptomatic S. Typhi infection in the intervention vaccine clusters, compared with the control vaccine clusters.

This is an open-label, non-randomized study. The purpose of this study is to better understand how vaccines against typhoid fever and cholera affect the normal immune system and bacteria in the intestine. Patients having standard-of-care endoscopies (colonoscopy and/or esophagogastroduodenoscopy (EGD)) will be divided into 3 groups: Group 1: Vivotif typhoid vaccination and/or Vaxchora cholera vaccination then endoscopy Group 2: Endoscopy, then Vivotif typhoid vaccination and/or Vaxchora cholera vaccination, then follow-up endoscopy Group 3: Endoscopy without vaccination. Both vaccines used in this study are licensed by the Food and Drug Administration (FDA) for travelers to developing countries. Volunteers will be asked to donate tissue, blood, saliva and stool samples for studying how the body responds to the typhoid and/or cholera vaccine.

This study will evaluate the efficacy of a Typhoid conjugate vaccine (Vi-TCV) in Malawi, Africa among children age 9 months through 12 years. Participants will be randomized in a 1:1 ration to receive the study vaccine or the control vaccine (meningococcal group A conjugate vaccine - MCV-A).