Hospital-based surveillance and analysis of genotype variation in Nicaragua after the introduction of the pentavalent rotavirus vaccine.

BACKGROUND: A live, attenuated, pentavalent rotavirus vaccine (RV5) was introduced in Nicaragua in 2006 through a 3-year partnership between Merck & Co, Inc., and the Nicaraguan Ministry of Health. Nicaragua was the first developing nation to include rotavirus vaccine in its national childhood vaccine program. To monitor the possibility of changing circulating rotavirus strains after the introduction of RV5, we determined the genotypes responsible for rotavirus gastroenteritis-related hospitalization during the first 3 postvaccine years. METHODS: Stool samples were collected from children with acute gastroenteritis who presented to any of 6 participating hospitals within 7-14 days of symptom onset. Samples positive for rotavirus antigen were analyzed for P and G genotypes using a reverse transcription polymerase chain reaction method. RESULTS: Overall, the predominant strains were G2P[4] (41.5%), G1P[8] (40.6%), G4P[8] (5.1%) and G3P[8] (4.7%). Strain predominance varied by season. During the 2007 season, G4P[8] (53.2%) and G2P[4] (40.5%) predominated. In the 2008 season, G2P[4] (77.9%) and G1P[8] (12.6%) were predominant, while in the 2009 season, G1P[8] (79.3%) and G3P[8] (7.8%) were predominant. CONCLUSION: No new or unexpected strains were predominant in the years immediately following the introduction of RV5 into Nicaragua. RV5 does not appear to have substantially altered the historical pattern of seasonal fluctuation in rotavirus genotypes.

Effectiveness of vaccination with the pentavalent rotavirus vaccine in Nicaragua as determined using the screening method.

The screening method is a surveillance tool to evaluate vaccine effectiveness (VE) using coverage data on cases and available administrative estimates of vaccine coverage in the population. The aim of this analysis was to evaluate the utility and limitations of using the screening methodology to estimate VE, particularly in a developing world country with a high coverage rate, and to compare it with the VE estimates from 2 case-control studies. Using data from 2008, the screening method employed in this study estimated that VE for 3 doses of RV5 among children<12 mo of age to prevent wild-type severe disease, resulting in hospitalization or emergency department visits, was 92% (95% confidence interval [CI]: 78-100%). Additional sensitivity analysis demonstrated that the point estimates of VE against severe disease ranged from 72% (95% CI: 62-83%) to 92% (95% CI: 78-100%); this range of VE estimates, although wide, is relatively consistent with results reported from 2 case-control studies in Nicaragua for the same time period. When the infrastructure is in place to collect reasonably robust case data, the use of the screening method to estimate VE is possible in the developing world setting. Cases of severe wild-type rotavirus gastroenteritis were obtained through an observational, hospital-based, prospective, surveillance program to assess rotavirus acute gastroenteritis. The proportion of cases vaccinated was estimated using the child's vaccination card or health record. The proportion of the population vaccinated was estimated using administrative population-based vaccination coverage estimates provided by the Nicaraguan Ministry of Health.

Adaptation of a previously validated vaccination report card for use in adult vaccine clinical trials to align with the 2007 FDA Toxicity Grading Scale Guidance.

The Adult/Adolescent Vaccination Report Card (VRC) was developed and validated by Merck in 1998 for use in vaccine clinical trials to collect information from trial subjects on complaints for both local and systemic events after vaccination. This short report describes the revision to the original validated VRC in order to align with the guidelines outlined in the 2007 FDA Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Since the VRC elicits trial subjects' self-reports of any adverse experiences (AE) occurring post vaccination, it was important that subsequent modifications of the VRC retained the original user-friendly characteristics while gathering the appropriate information to align with the FDA Guidance. A convenience sample of 15 participants (71% females, 87% white and mean (SD) age 45 (13) years was recruited to obtain feedback in order to revise the Adult/Adolescent VRC. Based on the feedback received, the following were slightly revised: ruler for the measurements of local systemic reactions, severity ratings, and general instructions. The revised VRC is currently being used in Merck vaccine clinical trials.

Evaluating the health impact of a public-private partnership: to reduce rotavirus disease in Nicaragua.

The purpose of this article is to describe the RotaTeq(®) Nicaragua Partnership and the evaluation of the public health impact of the vaccine conducted by the partners, including the creation of a rotavirus surveillance program and a vaccine effectiveness assessment. The three main objectives of the partnership were to demonstrate that a new rotavirus vaccine could (1) be introduced rapidly in a developing country, (2) be successfully integrated into the existing vaccine delivery infrastructure, and (3) have a significant and measurable public health impact at the end of the 3-y program. The vaccine impact assessment required collaboration among partners with different areas of expertise, including the Nicaraguan Ministry of Health, Merck, local hospitals, government health clinics, laboratories, and a Technical Advisory Group. Through the partnership, RotaTeq(®) became available in a GAVI-eligible developing country, Nicaragua, in the same year it was approved in the United States. Vaccine coverage rapidly reached over > 90% of eligible Nicaraguan children. The impact assessment evaluated over 10,000 subjects and leveraged and enhanced the existing diarrheal surveillance infrastructure, ultimately providing the scientific community with some of the first real-world rotavirus vaccine effectiveness data from a developing country. The successful public-private partnership (PPP) was internationally recognized as a model for the rapid adoption of a new vaccine in a developing world setting. The model could be adapted to benefit other PPPs interested in demonstrating the impact of their own programs.

Case-control study of the effectiveness of vaccination with pentavalent rotavirus vaccine in Nicaragua.

BACKGROUND: In 2006, Merck & Co., Inc., partnered with the Nicaraguan Ministry of Health to demonstrate the public health impact of routine universal vaccination by delivering more than 1.3 million doses of the oral, pentavalent rotavirus vaccine (RV5) in a 3-year period. METHODS: A matched case-control study evaluated the effectiveness of RV5 in reducing the risk for severe wild-type rotavirus gastroenteritis (RGE) resulting in hospitalizations and emergency department visits among children who completed the recommended 3-dose regimen as part of the routine national vaccine program. Cases were identified from 6 hospitals from February 2007 to October 2009 and were age-matched with hospital controls and community controls. Vaccine effectiveness was calculated using conditional logistic regression. RESULTS: Three hundred RGE cases eligible for analysis were matched to 792 hospital and 851 community controls. Vaccine coverage of RV5 in the community reached 92%. Vaccine effectiveness during 2 years of follow-up against severe disease in children receiving 3 doses of RV5 was 87% (95% confidence interval [CI], 74-93) for community controls, 64% (95% CI, 44-78) for hospital controls, and 76% (95% CI, 63-84) when the groups were combined. For the combined groups, vaccine effectiveness was 85% (95% CI, 66-93) among children <12 months old at the time of RGE onset. CONCLUSIONS: The Merck-Nicaragua Rotavirus Vaccine Partnership promoted rapid and widespread uptake of a novel vaccine in a developing country. Vaccine effectiveness was greatest for children younger than 12 months of age who were at the highest risk for severe rotavirus disease.

Burden of childhood rotavirus disease on health systems in the United States.

BACKGROUND: To determine the burden of rotavirus disease before the introduction of rotavirus vaccines. METHODS: From February 2005 to June 2006, prospective rotavirus surveillance was conducted in Cincinnati, Ohio, and Durham, North Carolina. Children < 5 years of age presenting at hospitals and outpatient clinics with acute gastroenteritis (AGE) of < 72 hours duration were enrolled. Stool samples were first tested for rotavirus by EIA and the VP7 type was determined by RT-polymerase chain reaction for rotavirus-positive samples. Medical costs were obtained from billing or accounting data. RESULTS: A total of 1998 children were enrolled, with a mean age of 16.9 months. Among 1601 (80%) patients with a stool specimen, 44% were rotavirus positive. The rotavirus detection rate was 38% for patients admitted to hospital, 60% for patients requiring a short-stay hospital visit (< 24 hour hospitalization), 49% for emergency department visits, and 37% for outpatient visits. During the rotavirus season, rotavirus accounted for 56% of all AGE cases. Only 11% of rotavirus-positive children were assigned the rotavirus-specific ICD-9-CM code and this proportion varied considerably by clinical setting. The VP7 genotypes identified were G1, 79%; G2, 14%; G3, 5%; G9, 1%; and G12, 1%. For children hospitalized with rotavirus, the estimated median direct cost was $4565, the average length of stay was 1.9 days, and parents lost 3.4 days of work. For short-stay, emergency department, and outpatient visits, the estimated median costs were $3160, $867, and $75, respectively. CONCLUSIONS: Before the widespread use of rotavirus vaccines in the United States, rotavirus was prevalent among children treated in hospital-based and outpatient settings and was associated with a substantial proportion of pediatric medical visits for AGE.