Assessing the Impact of a Vi-polysaccharide Conjugate Vaccine in Preventing Typhoid Infection Among Bangladeshi Children: A Protocol for a Phase IIIb Trial.

BACKGROUND: Typhoid fever illnesses are responsible for more than 100 000 deaths worldwide each year. In Bangladesh, typhoid fever is endemic, with incidence rates between 292-395 per 100 000 people annually. While considerable effort has been made to improve access to clean water and sanitation services in the country, there is still a significant annual typhoid burden, which particularly affects children. A typhoid conjugate vaccine (Vi-TCV) was recently prequalified by the World Health Organization and recommended for use, and offers the potential to greatly reduce the typhoid burden in Bangladesh. METHODS: This study is a double-blind, cluster-randomized, controlled trial of Vi-TCV in a geographically defined area in Dhaka, Bangladesh. At least 32 500 children from 9 months to <16 years of age will be vaccinated and followed for 2 years to assess the effectiveness and safety of Vi-TCV in a real-world setting. All cluster residents will also be followed to measure the indirect effect of Vi-TCV in this community. ETHICS AND DISSEMINATION: This protocol has been approved by the International Centre for Diarrhoeal Disease Research, Bangladesh; a University of Oxford research review; and both ethical review committees. Informed written consent and assent will be obtained before enrollment. Vi-TCV has been shown to be safe and effective in previous, smaller-scale studies. The results of this study will be shared through a series of peer-reviewed journal articles. The findings will also be disseminated to the local government, stakeholders within the community, and the population within which the study was conducted. CONCLUSIONS: This trial is the largest and only cluster-randomized control trial of Vi-TCV ever conducted, and will describe the effectiveness of Vi-TCV in an endemic population. The results of this trial may provide important evidence to support the introduction of TCVs in countries with a high burden of typhoid. CLINICAL TRIALS REGISTRATION: ISRCTN11643110.

[Spatial and temporal clustering characteristics of typhoid and paratyphoid fever and its change pattern in 3 provinces in southwestern China, 2001-2012].

Objective: To analyze the spatial and temporal clustering characteristics of typhoid and paratyphoid fever and its change pattern in Yunnan, Guizhou and Guangxi provinces in southwestern China in recent years. Methods: The incidence data of typhoid and paratyphoid fever cases at county level in 3 provinces during 2001-2012 were collected from China Information System for Diseases Control and Prevention and analyzed by the methods of descriptive epidemiology and geographic informatics. And the map showing the spatial and temporal clustering characters of typhoid and paratyphoid fever cases in three provinces was drawn. SaTScan statistics was used to identify the typhoid and paratyphoid fever clustering areas of three provinces in each year from 2001 to 2012. Results: During the study period, the reported cases of typhoid and paratyphoid fever declined with year. The reported incidence decreased from 30.15 per 100 000 in 2001 to 10.83 per 100 000 in 2006(annual incidence 21.12 per 100 000); while during 2007-2012, the incidence became stable, ranging from 4.75 per 100 000 to 6.83 per 100 000 (annual incidence 5.73 per 100 000). The seasonal variation of the incidence was consistent in three provinces, with majority of cases occurred in summer and autumn. The spatial and temporal clustering of typhoid and paratyphoid fever was demonstrated by the incidence map. Most high-incidence counties were located in a zonal area extending from Yuxi of Yunnan to Guiyang of Guizhou, but were concentrated in Guilin in Guangxi. Temporal and spatial scan statistics identified the positional shifting of class Ⅰ clustering area from Guizhou to Yunnan. Class Ⅰ clustering area was located around the central and western areas (Zunyi and Anshun) of Guizhou during 2001-2003, and moved to the central area of Yunnan during 2004-2012. Conclusion: Spatial and temporal clustering of typhoid and paratyphoid fever existed in the endemic areas of southwestern China, and the clustering area covered a zone connecting the central areas of Guizhou and Yunnan. From 2004 to 2012, the most important clustering area shifted from Guizhou to Yunnan. Findings from this study provided evidence for the identifying key areas for typhoid and paratyphoid fever control and prevention and allocate health resources.

[Surveillance data on typhoid fever and paratyphoid fever in 2015, China].

Objective: Through analyzing the surveillance data on typhoid fever and paratyphoid fever in 2015 to understand the related epidemiological features and most possible clustering areas of high incidence. Methods: Individual data was collected from the passive surveillance program and analyzed by descriptive statistic method. Characteristics on seasonal, regional and distribution of the diseases were described. Spatial-temporal clustering characteristics were estimated, under the retrospective space-time method. Results: A total of 8 850 typhoid fever cases were reported from the surveillance system, with incidence rate as 0.65/100 000. The number of paratyphoid fever cases was 2 794, with incidence rate as 0.21/100 000. Both cases of typhoid fever and paratyphoid fever occurred all year round, with high epidemic season from May to October. Most cases involved farmers (39.68%), children (15.89%) and students (12.01%). Children under 5 years showed the highest incidence rate. Retrospective space-time analysis for provinces with high incidence rates would include Yunnan, Guangxi, Guizhou, Hunan and Guangdong, indicating the first and second class clusters were mainly distributed near the bordering adjacent districts and counties among the provinces. Conclusion: In 2015, the prevalence rates of typhoid fever and paratyphoid fever were low, however with regional high prevalence areas. Cross regional transmission existed among provinces with high incidence rates which might be responsible for the clusters to appear in these areas.

Typhoid vaccination for international travelers from Greece visiting developing countries.

BACKGROUND: Typhoid fever is one of the most common diagnoses in returned international travelers. Our aim was to study the typhoid vaccine prescription practices for travelers from Greece visiting developing countries. METHODS: A prospective questionnaire-based study was conducted during 2009-2012 in 57 Public Health Departments, which are the only sources of typhoid vaccine in Greece. RESULTS: A total of 3,680 travelers were studied (median age: 38.1 years). Typhoid vaccine was delivered to 1,108 (30.1%) of them. Of those who traveled to sub-Saharan Africa, South America, the Middle East, the Indian subcontinent, Southeast Asia, South Africa, East Asia, North Africa, and Central America, 31.6, 17.1, 35, 44.2, 36.9, 31, 17.7, 31.6, and 36.8% received typhoid vaccine, respectively. Of travelers who stayed <1 month, 1 to <3 months, 3 to <6 months, and ≥6 months, 21.4, 63.1, 32.3, and 34.9% were vaccinated, respectively. According to the purpose of travel, typhoid vaccine was administered to 32.7% of those who traveled for leisure, to 28.8% of those who traveled for business, and to 24.1% of those visiting friends and relatives (VFRs). Of travelers who stayed in urban areas, rural areas, and urban and rural areas, 36.3, 30.1, and 26.8% were vaccinated, respectively. The majority of travelers who received the typhoid vaccine stayed in camps (62.9%) or at local residences (41%). Typhoid vaccine administration was statistically significantly associated with destination, duration of travel, purpose of travel, area of stay, and type of accommodation. DISCUSSION: There is a need to increase awareness of travelers and public health professionals for typhoid vaccination and particularly for high-risk groups of travelers, such as travelers to the Indian subcontinent and VFRs. Strategies for continuing professional education should be developed for travel health professionals.

Typhoid fever, complicated by myocarditis, in a traveller returning to the UK.

A 25-year-old male returning traveller presented with sudden onset chest pain. An ECG showed infero-lateral ischaemic changes, with an elevated troponin and inflammatory markers. An echocardiogram showed a normal size left ventricle, dynamic systolic function, structurally normal valves and no regional wall motion abnormality. Angiography revealed normal coronary arteries. A diagnosis of myocarditis was made. Five days later, he developed a significant pyrexia and diarrhoea. Salmonella typhi was isolated from blood cultures. The fever and symptoms resolved after 2 weeks of an intravenous third generation cephalosporin and the patient was discharged.

Typhoid fever outbreak associated with frozen mamey pulp imported from Guatemala to the western United States, 2010.

BACKGROUND: Fifty-four outbreaks of domestically acquired typhoid fever were reported between 1960 and 1999. In 2010, the Southern Nevada Health District detected an outbreak of typhoid fever among persons who had not recently travelled abroad. METHODS: We conducted a case-control study to examine the relationship between illness and exposures. A case was defined as illness with the outbreak strain of Salmonella serotype Typhi, as determined by pulsed-field gel electrophoresis (PFGE), with onset during 2010. Controls were matched by neighborhood, age, and sex. Bivariate and multivariate statistical analyses were completed using logistic regression. Traceback investigation was completed. RESULTS: We identified 12 cases in 3 states with onset from 15 April 2010 to 4 September 2010. The median age of case patients was 18 years (range, 4-48 years), 8 (67%) were female, and 11 (92%) were Hispanic. Nine (82%) were hospitalized; none died. Consumption of frozen mamey pulp in a fruit shake was reported by 6 of 8 case patients (75%) and none of the 33 controls (matched odds ratio, 33.9; 95% confidence interval, 4.9). Traceback investigations implicated 2 brands of frozen mamey pulp from a single manufacturer in Guatemala, which was also implicated in a 1998-1999 outbreak of typhoid fever in Florida. CONCLUSIONS: Reporting of individual cases of typhoid fever and subtyping of isolates by PFGE resulted in rapid detection of an outbreak associated with a ready-to-eat frozen food imported from a typhoid-endemic region. Improvements in food manufacturing practices and monitoring will prevent additional outbreaks.

Cases of malaria, hepatitis A, and typhoid fever among VFRs, Quebec (Canada).

BACKGROUND: Visiting friends and relatives (VFRs), especially young VFRs, are increasingly recognized in the industrialized world as a high-risk group of travelers. METHODS: We performed a descriptive, cross-sectional design study of cases of malaria, hepatitis A, and typhoid reported to the Quebec registry of notifiable diseases between January 2004 and December 2007, occurring in VFRs and non-VFRs travelers. RESULTS: VFRs account for 52.9% of malaria cases, 56.9% of hepatitis A cases, and 94.4% of typhoid cases reported in Quebec travelers. Almost all (91.6%) of the malaria cases among VFRs were acquired in Africa, particularly in sub-Saharan Africa. An important proportion of malaria cases among VFRs (86.4%) were due to Plasmodium falciparum. The vast majority (76.6%) of typhoid fever cases among VFRs were reported by travelers who had visited the Indian subcontinent. Among VFRs, 40% of total cases were under 20 y of age, compared to less than 6% among non-VFRs. Those under 20 years of age also accounted for 16.9% of malaria cases, 50% of typhoid cases, and 65.2% of hepatitis A cases among VFRs. CONCLUSION: Our study clearly shows that VFR children should be a primary target group for pre-travel preventive measures.

From the CDC: new country-specific recommendations for pre-travel typhoid vaccination.

Typhoid fever continues to be an important concern for travelers visiting many parts of the world. This communication provides updated guidance for pre-travel typhoid vaccination from the US Centers for Disease Control and Prevention (CDC) and describes the methodology for assigning country-specific recommendations.

Epidemiology and clinical aspects of enteric fever in Israel.

Enteric fever decreased in Israel in the last 50 years, but its current epidemiology is unknown. In a nationwide study, we evaluated all cases of enteric fever from 1995 to 2003. On hundred thirty-six cases met the case definition. During the period studied, the incidence of enteric fever decreased from 0.42 to 0.23/100,000. A total of 57.4% of the cases were acquired abroad. The incidence of endemic enteric fever was 2.7 times higher in Arabs than in Jews. In Arabs, Salmonella Typhi was the causative agent in all cases, and almost all cases were endemic. In Jews, most cases were imported, with a decrease in imported S. typhi, cases and an increase in imported S. Paratyphi A cases. Salmonella Paratyphi B was endemic, and restricted to the Jewish population. The reasons for the difference in causative agents along ethnic lines need further evaluation. A more efficient vaccine for travelers that includes S. Paratyphi A is needed.

Emergency department presentations of typhoid fever.

Typhoid fever, a systemic infectious disease caused by Salmonella typhi, is classically characterized by fever, paradoxical bradycardia, abdominal pain, and a rose colored rash. This was a retrospective review of 21 confirmed cases over a 5-year period. Mean age was 32.6 years (range 2-60 years), and Mexico (7/21) and El Salvador (3/21) represented the most common countries of origin. Recent travel to an endemic area was noted in 14 patients. The most common complaints were fever (15/21), headache (10/21), abdominal pain (9/21), and diarrhea (6/21). Average duration of symptoms before presentation to the Emergency Department (ED) was 7.9 days. High fever associated with bradycardia was noted in 12 patients. Leukopenia was present in 7 patients. Blood culture was the most sensitive confirmatory test while the Widal test was positive in 7 out of 11 cases. Fever of unknown origin (12/21), followed by presumed typhoid fever (3/21) were the most common ED diagnoses. It is important to recognize that patients with typhoid fever may present to EDs in the US and this disease should be included in the differential diagnosis of febrile patients from Latin America or those with a history of recent travel to endemic countries.

Characteristics of typhoid fever in children and adolescents in a major metropolitan area in the United States.

To examine the epidemiology of typhoid fever in children in an area that was not endemic, we analyzed 55 cases of typhoid fever in children and adolescents who were < or = 18 years and whose cases were reported to the Chicago and suburban Cook County Health Departments over 7 years. Cases had positive blood and/or stool cultures for Salmonella typhi. The ethnic distribution of the patients was as follows: 25% Asian, 22% Hispanic, 15% African American, 9% Caucasian, 18% other, and 11% unknown. Of the 55 cases, 35% were aged 0-5 years, 25% were aged 6-10 years, 31% were aged 11-15 years, and 9% were aged 16-18 years. Twelve patients did not have a history of travel. All patients recovered; none became carriers. Symptoms in 41 patients whose charts were available for review included fever (100%), diarrhea (77%), vomiting (50%), and dehydration (30%). Bacteremia was documented in 27 (66%) of 41 cases. In 17 of 41 cases, the household contacts were food handlers or health care workers. Eight (31%) of 26 isolates were resistant to both ampicillin and trimethoprim-sulfamethoxazole. The findings in our study were as follows: typhoid fever occurred frequently in children aged 0-5 years (in contrast with reports from areas of endemicity), approximately 20% of patients did not have a history of travel, and multidrug-resistant strains were prevalent.

[The course of typhoid fever in levomycetin resistance of the causative agent of the disease]. / O techenii briushnogo tifa pri rezistentnosti vozbuditelia bolezni k levomitsetinu.

Kept under observation was a patient aged 21 years, who had come from India, from whose blood taken at day 45 typhoid fever a causative agent S. typhi resistant to chloramphenicol, ampicillin, polymyxin was isolated. The condition presented with fever of long duration (60 days), apparent intoxication, jaundice, development of appendicular symptoms and intestinal hemorrhage continueing for 10 days. Treatment with chloramphenicol, ampicillin, gentamicin, furazolidone appeared to be ineffective. Detoxicational and hemostatic therapies were tried. The patient resumed his health.

Immigration of Ethiopians with typhoid fever to Israel: apparent lack of influence on the local population.

The epidemiology of typhoid fever in Western countries may be affected by immigration from developing countries. We studied the immigration of Ethiopian Jews to Israel to find the effects of an influx of many individuals infected with typhoid into an area with a low incidence of the disease. Typhoid fever affected 204 Israelis and 121 (1.1%) of 10,654 Ethiopian immigrants during the period of 1984-1985. Of those Ethiopian cases, 107 occurred during a 3-month period. During the 5 months following that 3-month period, there was no increase in the number of cases of typhoid among Israelis. Although after that time there was a local waterborne outbreak of typhoid that affected 83 Israelis, no Ethiopians resided in the area where the outbreak occurred; therefore, we concluded that these 83 cases of typhoid fever were not related to the immigration of Ethiopians into Israel. In fact, if those 83 cases were excluded from the statistical analysis, there was no increase in the occurrence of typhoid during the 2-year period studied. Therefore, the immigration of many people with typhoid into an area of low incidence does not necessarily confer a risk of infection to the local population.

Enteric fever in Scotland 1975-1990.

In the 16-year period 1975-90, there were 267 cases of acute infection with typhoidal salmonellae reported in Scotland, in addition to which 32 chronic carriers were identified. The overall incidence of disease changed little over this period, but there was a fall in indigenously acquired paratyphoid B and typhoid, and a rise in imported paratyphoid A. The majority, 215 (81%), had a history of recent travel and were considered to have acquired infection overseas. Only six of the indigenously acquired infections were traced to acutely infected persons, illustrating the low risk of transmission associated with acute enteric fever in the UK. Only one death was definitely ascribed to enteric fever, and one person with S. paratyphi B became a chronic carrier. Significant illness was observed in five chronically infected individuals, including one with carcinoma of the gallbladder. UK residents of 'Asian' ethnicity returning from the Indian subcontinent accounted for 63 (46%) of the 137 cases of typhoid, and 34 (64%) of the 53 cases of paratyphoid A. People of 'Asian' ethnicity were more likely to have acquired infection overseas than 'non-Asians': 110 (89%) of 123 persons compared with 105 (73%) of 144 (odds ratio 3.1, 95% confidence interval 1.5-6.6, P = 0.001). Although there seems to be limited scope for preventing indigenously acquired infection, immunisation of travellers could contribute significantly to reducing the incidence of typhoid.