INTRODUCTIONEnteric fever is a multisystemic infection which largely affects children. This study aimed to analyse the epidemiology, clinical presentation, treatment and outcome of paediatric enteric fever in Singapore.

MATERIALS AND METHODSA retrospective review of children diagnosed with enteric fever in a tertiary paediatric hospital in Singapore was conducted from January 2006 to January 2012. Patients with positive blood cultures for Salmonella typhi or paratyphi were identified from the microbiology laboratory information system. Data was extracted from their case records.

RESULTSOf 50 enteric fever cases, 86% were due to Salmonella typhi, with 16.3% being multidrug resistant (MDR) strains. Sixty-two percent of S. typhi isolates were of decreased ciprofloxacin susceptibility (DCS). Five cases were both MDR and DCS. The remaining 14% were Salmonella paratyphi A. There were only 3 indigenous cases. Ninety-four percent had travelled to typhoid-endemic countries, 70.2% to the Indian subcontinent and the rest to Indonesia and Malaysia. All patients infected with MDR strains had travelled to the Indian subcontinent. Anaemia was a significant finding in children with typhoid, as compared to paratyphoid fever (P = 0.04). Although all children were previously well, 14% suffered severe complications including shock, pericardial effusion and enterocolitis. None had typhoid vaccination prior to their travel to developing countries.

CONCLUSIONEnteric fever is largely an imported disease in Singapore and has contributed to significant morbidity in children. The use of typhoid vaccine, as well as education on food and water hygiene to children travelling to developing countries, needs to be emphasised.

Adolescent ; Anemia ; epidemiology ; Anti-Bacterial Agents ; therapeutic use ; Child ; Child, Preschool ; Drinking Water ; Drug Resistance, Multiple, Bacterial ; physiology ; Enterocolitis ; epidemiology ; Female ; Food Contamination ; Health Education ; Hospitals, Pediatric ; Humans ; India ; Indonesia ; Infant ; Malaysia ; Male ; Paratyphoid Fever ; drug therapy ; epidemiology ; microbiology ; Pericardial Effusion ; epidemiology ; Retrospective Studies ; Salmonella paratyphi A ; physiology ; Salmonella typhi ; physiology ; Shock ; epidemiology ; Singapore ; epidemiology ; Tertiary Care Centers ; Travel ; Typhoid Fever ; drug therapy ; epidemiology ; microbiology ; prevention & control ; Typhoid-Paratyphoid Vaccines ; therapeutic use

BACKGROUND: Travel-related risks for infectious diseases vary depending on travel patterns such as purpose, destination, and duration. In this study, we describe the patterns of travel and prescription of vaccines as well as malaria prophylaxis medication (MPM) at a travel clinic in South Korea to identify the gaps to fill for the optimization of pre-travel consultation. MATERIALS AND METHODS: A cohort of travel clinic visitors in 2011 was constructed and early one-third of the visitors of each month were reviewed. During the study period, 10,009 visited the travel clinic and a retrospective chart review was performed for 3,332 cases for analysis of travel patterns and prescriptions. RESULTS: People receiving yellow fever vaccine (YFV) (n = 2,933) were traveling more frequently for business and tourism and less frequently for providing non-medical service or research/education compared to the 399 people who did not receive the YFV. Overall, most people were traveling to Eastern Africa, South America, and Western Africa, while South-Eastern Asia was the most common destination for the non-YFV group. Besides YFV, the typhoid vaccine was the most commonly prescribed (54.2%), while hepatitis A presented the highest coverage (74.7%) considering the natural immunity, prior and current vaccination history. Additionally, 402 (82.5%) individuals received a prescription for MPM among the 487 individuals travelling to areas with high-risk of malaria infection. Age over 55 was independently associated with receiving MPM prescription, while purpose of providing service and travel duration over 10 days were associated with no MPM prescription, despite travelling to high-risk areas. CONCLUSION: Eastern Africa and South America were common travel destinations among the visitors to a travel clinic for YFV, and most of them were travelling for tourism and business. For the individuals who are traveling to areas with high-risk for malaria, more proactive approach might be required in case of younger age travelers, longer duration, and travel purpose of providing service to minimize the risk of malaria infection.
Africa, Eastern ; Africa, Western ; Antibiotic Prophylaxis ; Asia ; Cohort Studies ; Commerce ; Communicable Diseases ; Hepatitis A ; Immunity, Innate ; Korea* ; Malaria ; Prescriptions* ; Retrospective Studies ; South America ; Travel Medicine ; Typhoid-Paratyphoid Vaccines ; Vaccination* ; Vaccines ; Yellow Fever Vaccine ; Yellow Fever*

Typhoid fever, a serious systemic infection caused by Salmonella enterica serovar Typhi, breaks out in developing countries. However, existing vaccines only induce relatively low protective effects with humoral responses and do not stimulate secondary immune response, especially to young people. The objective of this study is to evaluate the immunogenicity of the vaccine containing virulence capsular polysaccharide (Vi) conjugated with the optimal ratios of non-toxic variant of diphtheria toxin (CRM(197)) in mice. Six-week-old BALB/c female mice were injected intraperitoneally three times at intervals of 14 days and sera were collected on days 0, 14, 28, 42 and 56 post-injection. The efficacy of the vaccine was evaluated by comparing between negative control group injected with PBS and vaccine groups injected with Vi or Vi-CRM(197) conjugate of different ratio. Vi and CRM(197)-specific antibody responses were evaluated using enzyme-linked immunosorbent assay. The result showed that Vi-CRM(197)-1 group revealed the highest and significant Vi-specific IgG immune responses among the other groups and Vi group (p < 0.01). In conclusion, Vi-CRM(197)-1 conjugate vaccine induced the highest humoral immune response in mice and may be used as an effective vaccine to replace the existing typhoid vaccine for infants under 2 years old.
Animals ; Antibody Formation ; Child, Preschool ; Developing Countries ; Diphtheria Toxin ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunity, Humoral ; Immunoglobulin G ; Infant ; Mice* ; Salmonella enterica* ; Salmonella typhi* ; Salmonella* ; Typhoid Fever ; Typhoid-Paratyphoid Vaccines ; Vaccines ; Virulence

Diarrhea is one of the most common causes of morbidity and mortality in children worldwide. Rotavirus is the most common cause of infectious diarrhea both in developed and developing countries. However, bacterial causes such as Salmonella typhi and Vibrio cholerae still play an important role in developing countries. Newly developed vaccines for rotavirus, S. typhi, and V. choleae are highly immunogenic and safe in children.
Child ; Developing Countries ; Diarrhea ; Humans ; Rotavirus ; Salmonella typhi ; Typhoid-Paratyphoid Vaccines ; Vaccines ; Vibrio cholerae

OBJECTIVEIn order to evaluate the safety and immunogenicity of group A + C meningococcal polysaccharide vaccine, a controlled field trial was performed among children at 6-24 months and 5-13 years old in Longsheng county, Guangxi Zhuang Autonomous Region.

METHODSMore than 600 children were selected in this trial. 428 children, aged 6-24 month-old and 5-13 year-old were involved in two experimental groups and were inoculated 100 microg of group A + C meningococcal polysaccharide vaccine. 103 children in positive control group were inoculated 50 microg of group A meningococcal polysaccharide vaccine while 94 children in negative control group were inoculated 30 microg of Typhoid Vi polysaccharide vaccine. Both systemic and local reactions were observed in each group at 6 h,24 h,48 h and 72 h after inoculation. Blood samples were collected in all children before and at 1 month after inoculation. Additionally, at least 50 blood samples were taken in each experimental group at 6 and 12 months after inoculation. Serum bactericidal antibody was tested by micro bactericidal test.

RESULTSBoth systemic and local reactions were mild in two experimental groups with only 3 children (0.7%) had > or = 37. 6 degrees C fever, 4 children (0.9%) appeared mild areola but all adverse reaction disappeared within 48 hours. In 5-13 year-old experimental group, the rates for four-fold increase of bactericidal antibody were 96.59% and 92.15% to group A and group C meningococcus respectively at 1 month after inoculation, and remained 90.91% and 90.08% at 12 months after inoculation.

CONCLUSIONGroup A + C meningococal polysaccharide vaccine was safe and having good immunogenicity among Chinese children.

Adolescent ; Antibodies, Bacterial ; blood ; immunology ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Meningococcal Vaccines ; adverse effects ; immunology ; Polysaccharides, Bacterial ; adverse effects ; immunology ; Typhoid-Paratyphoid Vaccines ; adverse effects ; immunology

OBJECTIVETo study the regulating effects of a novel CpG oligodeoxynuleotide and the synergistic effect of chitosan-nanoparticles (CNP) with CpG on immune responses of mice, which were used to develop a novel immunoadjuvant to boost immune response to conventional vaccines.

METHODSA novel CpG ODN containing 11 CpG motifs was synthesized and its bioactivities to stimulate the proliferation of lymphocytes of pig in vitro were detected. Then it was entrapped with CNP prepared in our laboratory by the method of ionic cross linkage, and immunized Kunming mice were co-inoculated with paratyphoid vaccine. The peripheral blood was collected weekly from the tail vein of inoculated mice to detect the contents of IgG, IgA, IgM, and specific antibody against salmonella as well as the levels of interleukin-2 (IL2), IL-4, and IL-6 by SABC-ELISA assay. The numbers of leucocytes, monocytes, granuloytes, and lymphocytes were calculated separately using the routine method. The experimental mice were orally challenged with virulent salmonella 35 days after inoculation.

RESULTSThis CpG ODN could remarkably provoke the proliferation of lymphocytes of pig in vitro in contrast with the control (P < 0.05). Compared with those of the control, immunoglobulins, including IgG, IgA, IgM, and specific antibodies to paratyphoid vaccine, increased significantly in sera from the CpG or CpG-CNP-vaccinated mice (P < 0.05). IL-2, IL-4, and IL-6 increased remarkably in sera from immunized mice (P < 0.05). The leucocytes, monocytes, granuloytes, and lymphocytes of the mice immunized with CpG or CpG-CNP were also increased in number (P < 0.05). After the challenge, these immunity values were elevated in the mice vaccinated with CpG or CpG-CNP. The immunized mice all survived, while the control mice fell ill with evident lesions with diffuse hemorrhage in stomach, small intestine, and peritoneum.

CONCLUSIONSCpG ODN entrapped with CNP is a promising effective immunoadjuvant for vaccination, which promotes humoral and cellular immune responses, enhances immunity and resistance against salmonella by co-administration with paratyphoid vaccine.

Adjuvants, Immunologic ; administration & dosage ; pharmacology ; Animals ; Antibodies, Bacterial ; blood ; Cell Proliferation ; Chitosan ; chemistry ; Drug Therapy, Combination ; Enzyme-Linked Immunosorbent Assay ; Immunoglobulin Isotypes ; blood ; Interleukins ; blood ; Lymphocyte Activation ; drug effects ; Lymphocytes ; cytology ; Mice ; Nanoparticles ; chemistry ; Oligodeoxyribonucleotides ; administration & dosage ; pharmacology ; Paratyphoid Fever ; immunology ; prevention & control ; Salmonella ; physiology ; Salmonella Infections, Animal ; immunology ; prevention & control ; Swine ; immunology ; Typhoid-Paratyphoid Vaccines ; immunology

Vaccination against yellow fever is recommended for travelers to areas where yellow fever has been reported, and they should be vaccinated 10 days before the travel at an approved center for the vaccination. When traveling to areas where chloroquine-resistant P. falciparum has not been reported, once-a-week use of chloroquine alone is recommended, but when traveling to areas where chloroquineresistant P. falciparum has been reported, other agents such as mefloquine, doxycycline, atovaquone/proguanil and primaquine should be chosen. Other recommended immunizations are typhoid vaccine and hepatitis A/B vaccine. Traveler's diarrhea is one of the major health problems in terms of frequency, but antimicrobial prophylaxis is not routinely recommended.
Chloroquine ; Communicable Diseases* ; Diarrhea ; Doxycycline ; Hepatitis ; Immunization ; Malaria ; Mefloquine ; Primaquine ; Travel Medicine ; Typhoid-Paratyphoid Vaccines ; Vaccination ; Yellow Fever

Cationic PLG nanoparticles and liposome were prepared and used as package molecules to pack up pUC18-CpG. The effects of the packed pUC18-CpG on the cellular and humoral immune responses were detected in the mice that were inoculated with pig paratyphoid vaccine. The results showed that compared with the control, the amount of IgG and the titre of specific antibody were significantly increased in the sera of mice immunized with the CpG plasmid entrapped by cationic PLG nanoparticles; the proliferation and induced IL-2 bioactivity of lymphocytes were significantly enhanced in the spleen of the immunized mice; the stimulatory effect of cationic PLG nanoparticles was similar to or stronger than that of cationic liposome. These indicated that cationic PLG nanoparticle could be employed as an effective package molecule to promote the immunostimulatory effect of pUC18-CpG.
Adjuvants, Immunologic ; pharmacology ; Animals ; Immunoglobulin G ; blood ; Interleukin-2 ; blood ; Liposomes ; Male ; Mice ; Mice, Inbred BALB C ; Nanostructures ; Oligodeoxyribonucleotides ; pharmacology ; Swine ; Typhoid-Paratyphoid Vaccines ; immunology

OBJECTIVETo describe the design and application of cluster randomized controlled method on typhoid Vi vaccine trial, and to assess the effect of implementation.

METHODSSimple size calculation of cluster-randomized trial was used to determine the sample size of the two groups and a vaccination campaign was conducted. The study group was given typhoid Vi vaccine and the control group was given meningococcal A vaccine.

RESULTSAccording to sample size calculation, a total sample of 96,121 participants was required and the study areas were divided into 108 clusters. In practice, 53 study clusters with 44,054 participants and 54 control clusters with 48,422 participants were stratified and matched according to size, location (urban or rural), characteristics (school, department, factory, demography) were randomized respectively. Confounding factors of two groups including age, sex, resident area, income, level of education were compared. It was found that the ratio of all confounding factors between the two groups were comparable and balanced.

CONCLUSIONConfounding factors can be better controlled between study group and the control group by applying cluster-randomized method on vaccine trail which enabled the intervention to be more scientifically evaluated; The implementation of cluster randomization trial was simple and easy to be accepted.

Adolescent ; Adult ; Child ; Child, Preschool ; China ; Cluster Analysis ; Female ; Humans ; Male ; Mass Vaccination ; organization & administration ; Middle Aged ; Polysaccharides, Bacterial ; immunology ; Typhoid Fever ; prevention & control ; Typhoid-Paratyphoid Vaccines ; immunology ; Vaccination

Salmonella Typhi capsular polysaccharide vaccines were encapsulated in the Micro-particles made from polyethylene glycol-poly-DL-lactide (PELA). BALB/c mouse were divided into three groups with 20 mice in each. Mouse were immunized respectively with controlled release microencapsulated Salmonella Typhi capsular polysaccharide vaccines and Salmonella Typhi capsular polysaccharide vaccines by oral and subcutaneous administration. The mice blood and salvia were collected at the 2nd, 4th and 8th weeks respectively for the titrating of IgG and sIgA antibodies by RIA. At the 8th week, live typhoid bacteria were injected into the immunized mice for the calculation of the rate of immunization protection. The IgG titers of the controlled release microencapsulated Salmonella Typhi capsular polysaccharide vaccines group were higher than those of the other groups(P < 0.05). The IgA titers of the low groups of controlled release microencapsulated Salmonella Typhi capsular polysaccharide vaccines (oral and subcutaneous) were higher than those of the group of Salmonella Typhi capsular polysaccharide vaccines (P < 0.05). The immunization protection rates of the three groups were 40%, 100% and 60% respectively. The controlled release microencapsulated Salmonella Typhi capsular polysaccharide vaccines possess the advantages of releasing slowly in vivo and persisting long time immunogenicity.
Administration, Oral ; Animals ; Delayed-Action Preparations ; Female ; Immunoglobulin A, Secretory ; analysis ; Immunoglobulin G ; blood ; Injections, Subcutaneous ; Mice ; Mice, Inbred BALB C ; Microspheres ; Polysaccharides, Bacterial ; administration & dosage ; immunology ; Typhoid-Paratyphoid Vaccines ; administration & dosage ; immunology ; Vaccination