Bernard Ivanoff

Typhoid fever—important issues still remain

Abstract The Third Asia Pacific Symposium on Typhoid Fever and Other Salmonellosis was held in Bali, Indonesia on 8–10 December 1997.

The Epidemiology and Disease Burden of Rotavirus in Vietnam: Sentinel Surveillance at 6 Hospitals

The disease burden of rotavirus diarrhea in Vietnam was assessed by surveillance of children <5 years old who were hospitalized for diarrhea at 3 centers in the north and 3 centers in the south. Rotavirus was identified in 56% (range, 47%-60%) of the 5768 patients surveyed between July 1998 and June 2000. G-typing of the first 224 strains indicated that only 2% were non-typeable, 9% were in mixed infections, and the remainder were of the common serotypes G1, G2, G3, G4, and G9. In Vietnam, diarrhea accounts for 9880 deaths per year, which is approximately 15% of all deaths among children <5 years old, or 6.5 deaths per 1000 children. If even 50% of these diarrhea-related deaths in Vietnam were due to rotavirus, the number would represent 4%-8% of all deaths among children <5 years old, 2700-5400 rotavirus-related deaths per year, and 1 death per 280-560 children during the first 5 years of life. Thus, the disease burden of rotavirus in Vietnam is substantial, and programs to encourage the use of oral rehydration should be encouraged while efforts to develop vaccines continue.

Diversity of Rotavirus Strains among Children with Acute Diarrhea in China: 1998-2000 Surveillance Study

ABSTRACT As part of a national rotavirus surveillance activity, we collected fecal specimens from 3,177 children with acute diarrhea in 10 regions of China between April 1998 and April 2000 and screened them for rotavirus. Rotavirus was detected in 41% (n = 1,305) of specimens, and in these, G1 was the predominant serotype (72.6%), followed by G3 (14.2%), G2 (12.1%), G4 (2.5%), G9 (0.9%), and G untypeable (0.7%). Among 327 G-typed strains tested for P genotype, 14 different P-G combinations were identified, with the globally common strains P[8]G1, P[4]G2, P[8]G3, and P[8]G4 representing 75.6% of all typed rotavirus strains. Among the uncommon strains, 11 were P[6]G9, and others included P[6]G1, P[6]G3, and five novel P-G combinations (P[9]G1, P[4]G1, P[4]G3, P[4]G4, and P[8]G2). Our results indicate that while the common rotavirus strains remain predominant, the diversity of strains is much greater than was previously recognized.

Investigations into the safety and immunogenicity of a killed oral cholera vaccine developed in Viet Nam

OBJECTIVE To evaluate a killed oral cholera vaccine produced in Viet Nam, and to compare the Vietnamese vaccine with one that is licensed internationally. METHOD Two-dose regimens of a locally produced, bivalent, anti-O1, anti-O139 killed oral whole-cell cholera vaccine (biv-WC) and of a commercially available, monovalent (anti-O1) oral recombinant B subunit-killed whole-cell cholera vaccine (rBS-WC) were compared in two trials in Viet Nam. In the first trial, 144 adults were randomized to biv-WC with or without buffer, rBS-WC with buffer, or placebo without buffer. In the second, 103 children aged 1-12 years were randomized to biv-WC without buffer, rBS-WC with buffer, or placebo without buffer. FINDINGS No regimen was associated with significant side-effects. In adults, ca 60% of recipients of either vaccine exhibited at least fourfold serum anti-O1 vibriocidal antibody responses and ca 40% of recipients of biv-WC demonstrated anti-O139 vibriocidal responses. Both anti-O1 (ca 90% in each vaccine groupand anti-O139 (68% in the biv-WC group) vibriocidal responses occurred more frequently in children. The responses to biv-WC were unaffected by the receipt of buffer. CONCLUSION It was concluded that biv-WC was safe and immunogenic, that it could be administered without buffer, and that it could elicit robust immune responses even in children, for whom the risk of endemic cholera is highest.

Current issues in adolescent immunization.

Based on the December 2006 Fondation Mérieux International Scientific Symposium, the current state of adolescent immunization is reviewed with a focus on the policy and programmatic issues that impact the acceptability, initiation, and successful implementation. Key questions are identified with proposed strategies to help achieve successful adolescent immunization programs. The role of current vaccines targeted to adolescents, such as those directed against invasive meningitis, pertussis, and the human papillomavirus, is reviewed as well as their role in rejuvenating interest in adolescent immunization, and more importantly, adolescent health as a whole.

New Lessons for Rotavirus Vaccines

Rotavirus infects nearly all humans early in their lives and can sometimes prove dangerous or fatal. In his Perspective, Glass recounts the successes of first and second generation vaccines against rotaviruses. Nevertheless he believes that two papers in this weeks issue [Ball et al. (p. 101) and Burns et al. (p. 104)] illuminate aspects of the virulence of rotavirus and its susceptibility to immune attack that may guide the development of an even more effective third generation vaccine.

Epidemiological Profile and Burden of Rotavirus Diarrhea in Vietnam: 5 Years of Sentinel Hospital Surveillance, 1998–2003

For 5 years, we have conducted sentinel surveillance for rotavirus at 6 hospitals in 4 cities in Vietnam. Stool samples obtained from >10,000 children <5 years old who were admitted to the hospital with diarrhea have been screened for rotavirus. Overall, 55% of samples were positive, and there was little variability in rates of detection of rotavirus between sites (44%-62%). In Vietnam, the characteristics of rotavirus infection more closely resemble those seen in developed countries, rather than those seen in developing countries: children become infected at an older age, the percentage of stool samples in which rotavirus is detected is extremely high, and the rotavirus strains appear to be the common types, with fewer mixed infections occurring. It is estimated that 5300-6800 children <5 years old die of rotavirus infection each year in Vietnam, representing 8%-11% of all deaths in this age group (cumulative risk per child by age 5 years, 1 in 200 to 1 in 285). Additional studies are ongoing to document the economic cost of the disease and to assess the burden of both fatal cases and milder cases of disease. Study outcomes will provide information for future testing and potential use of a rotavirus vaccine.

A mass vaccination campaign targeting adults and children to prevent typhoid fever in Hechi; Expanding the use of Vi polysaccharide vaccine in Southeast China: A cluster-randomized trial

BackgroundOne of the goals of this study was to learn the coverage, safety and logistics of a mass vaccination campaign against typhoid fever in children and adults using locally produced typhoid Vi polysaccharide (PS) and group A meningococcal PS vaccines in southern China.MethodsThe vaccination campaign targeted 118,588 persons in Hechi, Guangxi Province, aged between 5 to 60 years, in 2003. The study area was divided into 107 geographic clusters, which were randomly allocated to receive one of the single-dose parenteral vaccines. All aspects regarding vaccination logistics, feasibility and safety were documented and systematically recorded. Results of the logistics, feasibility and safety are reported.ResultsThe campaign lasted 5 weeks and the overall vaccination coverage was 78%. On average, the 30 vaccine teams gave immunizations on 23 days. Vaccine rates were higher in those aged ≤ 15 years (90%) than in adolescents and young adults (70%). Planned mop-up activities increased the coverage by 17%. The overall vaccine wastage was 11%. The cold chain was maintained and documented. 66 individuals reported of adverse events out of all vaccinees, where fever (21%), malaise (19%) and local redness (19%) were the major symptoms; no life-threatening event occurred. Three needle-sharp events were reported.ConclusionThe mass immunization proved feasible and safe, and vaccine coverage was high. Emphasis should be placed on: injection safety measures, community involvement and incorporation of mop-up strategies into any vaccination campaign. School-based and all-age Vi mass immunizations programs are potentially important public health strategies for prevention of typhoid fever in high-risk populations in southern China.

A multi-country cluster randomized controlled effectiveness evaluation to accelerate the introduction of Vi polysaccharide typhoid vaccine in developing countries in Asia : rationale and design

Phase‐III vaccine efficacy trials typically employ individually randomized designs intended to ensure that measurements of vaccine protective efficacy reflect only direct vaccine effects. As a result, decisions about introducing newly licensed vaccines into public health programmes often fail to consider the substantially greater protection that may occur when a vaccine is deployed in public health programmes, due to the combination of direct plus indirect vaccine protective effects. Vaccine total protection can be better evaluated with cluster randomized trials. Such a design was considered to generate policy relevant data to accelerate the rationale introduction of the licensed typhoid fever Vi polysaccharide (PS) vaccine in Asia by the Diseases of the Most Impoverished (DOMI) typhoid fever programme. The DOMIs programme multi‐country study is one of the largest cluster randomized vaccine trials ever mounted in Asia, which includes approximately 200 000 individuals. Its main objective is to determine the effectiveness of a licensed Vi PS vaccine. The rationale and design of this study are discussed. Preliminary results are presented that determined the final planning of the trial before immunization. Important methodological and practical issues regarding vaccine cluster randomized designs are illustrated.

Typhoid fever: continuing challenges from a resilient bacterial foe

Diarrhoeal diseases are still responsible for 3 million deaths each year, of which an estimated 600,000 deaths are caused by typhoid fever. Prevention of enteric diseases comprises basic sanitary and hygiene measures including purifying water supplies, improving water delivery and sewage control, supplying handwashing facilities, latrines, boiling water and supervising foodhandlers. Most of the time, however, it is difficult to apply these recommendations properly, and the problems are compounded by the emergence of drug-resistant strains of Salmonella typhi . Efforts to develop effective treatments and vaccines against these diseases are discussed.