Recently in Epidemiology Category

Despite the return of measles to the United Kingdom, the United States, and Gibraltar, worldwide deaths from the highly contagious, viral disease have dropped dramatically, according to the World Health Organisation. The plunge in measles-related deaths, from 750,000 in the year 2000 to 197,000 last year, is due to a massive, coordinated vaccination effort, the Measles Initiative. In Africa and countries of the Eastern Mediterranean region* specifically, the effort has resulted in a fall in measles deaths by approximately 90% during the same time period. The goal of the Measles Initiative—which is led by the American Red Cross, the CDC, the UN Foundation, UNICEF, and WHO—is to reduce the number of measles deaths worldwide by at least 90% by the year 2010.

Area	2000	2007	Drop, %
World, measles deaths	750,000	197,000	74
World, measles cases	852,937	279,006	67
Africa, deaths	395,000	45,000	89
Eastern Mediterranean, deaths	96,000	10,000	90

Because the majority of measles-related deaths no longer occur in Africa, vaccination efforts are now being intensified in other regions—particularly India, where 8.5 million children do not receive their first dose of measles vaccine by 1 year of age. According to a spokesperson for the UN Foundation, the success of the campaign depends on urgently needed funds for the next 2 years.

* Includes Afghanistan, Pakistan, Somalia, and Sudan.

Photo of measles vaccination in Bangladesh by Daniel Cima/American Red Cross.

From August 2001 to July of this year, roughly 40% of hospitalizations for diarrhea in children* worldwide were caused by rotavirus, according to a report in this week's MMWR. Rotavirus infection is known to be the leading cause of severe, acute diarrhea in young children; however, previous literature reviews had implicated rotavirus in fewer pediatric hospitalizations for diarrhea, 20%-30%.

The latest data were derived from a WHO surveillance program in 35 countries in Africa, Central and South America, Eastern Europe, the Eastern Mediterranean, Southeast Asia, and the Western Pacific. Detection was based on an enzyme immunoassay for rotavirus antigen in stool samples, and strain genotypes were identified by RT-PCR. The most common strains, excepting those in the Eastern Mediterranean region and Africa, were G1P[8], G9P[8], and G2P[4]—which accounted for two thirds of the strains detected.

WHO Region (No. Countries)	Median Detection Rate, % (Range)
Africa (4)	41
Americas (11)	34
Europe (3)	40
Eastern Mediterranean (9)	40
Southeast Asia/Western Pacific (8)	45
Total (35)	40

In trials in the Americas and Europe, 2 live, oral rotavirus vaccines—an attenuated G1P[8] human rotavirus vaccine (Rotarix; GSK Biologicals) and a live, pentavalent, human-bovine (WC3 strain) reassortment vaccine containing serotypes G1, G2, G3, G4 and P[8] (RotaTeq; Merck)—conferred 85%-98% protection against rotavirus diarrhea. These vaccines have been incorporated into the routine immunization programs in 11 countries in these regions and in Australia. Trials of these vaccines in low-income Asian and African countries are ongoing. Notably these vaccines confer protection against rotavirus serotypes that have not been included in their respective formulations.

The CDC recommends 3 doses of an FDA-approved rotavirus vaccine** between the ages of 6 and 32 weeks. An interim report indicates that, for the 2007-2008 rotavirus season in America, viral activity started much later and was much less extensive than in previous years. These changes are believed to be due to the uptake of rotavirus vaccine.

According to the MMWR, more than half a million young children in the world die each year from rotavirus-induced diarrhea; 85% of these deaths occur in low-income African or Asian countries.

RT-PCR = reverse-transcription polymerase chain reaction.

* Younger than 5 years of age.

** The tetravalent rhesus-human reassortment rotavirus vaccine (RotaShield; Wyeth) was voluntarily withdrawn from the market in 1999 owing to a low, but increased, risk of intussusception.

Transmission electron photomicrograph of intact rotavirus particles from the CDC.

According to WHO.

CHD = coronary heart disease; COPD = chronic obstructive pulmonary disease; CV = cerebrovascular; TB = tuberculosis.

Epi Wonk outs himself in the Atlanta Journal-Constitution by recounting his childhood experience with measles, which included hospitalization and treatment with an oxygen tent. Like many of a certain age, I also acquired measles as a youngster (despite having been vaccinated) and missed 2 weeks (2 weeks!) of junior high. And I didn't stay home because of contagiousness; I stayed home because I felt absolutely terrible.

Epi Wonk is right to chastise Washington for not initiating a progressive public-service campaign (where is our acting Surgeon General anyway?) to urge morbidity-reducing and life-saving vaccination and to counter the spurious claims of an increasingly vocal and attention-hungry antivax crowd.

Photo of child with measles rash from the CDC.

In a public letter dated September 16, Oxford statistician Richard Peto wrote heated responses to questions from US Representatives John Dingell (D-MI) and Bart Stupak (D-MI) about the clinical investigation of Vytorin (ezetimibe/simvastatin; Merck/Schering-Plough). The congressmen's questions, many of which imply professional collusion between Peto and Merck/Schering-Plough, were originally submitted to the drugmakers in letters dated August 21 and September 2.

In his response, Peto seemed to be particularly vexed by the request that the companies "make Dr. Peto available for a staff interview as soon as possible." In reply, Peto advised that "the companies have no control over him." However, Peto did offer his assistance as an epidemiologist and statistician to help the congressmen and their subcommittee (of Oversight and Investigations) understand "statistically appropriate ways of interpreting the hypothesis-generating and hypothesis-testing data sets from trials."

Peto is referring specifically to his and others' recent analysis of cancer data from the ongoing Vytorin studies SHARP and IMPROVE-IT. The analysis was conducted in response to an observed association between the drug and cancer rates in the completed SEAS trial (background here). The conclusion of the analysis of Peto et al, which was recently published in the NEJM, is that there is "no credible evidence" that Vytorin (and in particular, ezetimibe) affects cancer rates.

The debate generated from the NEJM analysis rests on whether data from the 3 studies should have been combined to assess the potential cancer risk with Vytorin, as advocated by US cardiologist Steven Nissen, or whether it is inappropriate to lump data from the hypothesis-generating trial (SEAS) with data from the hypothesis-testing trials (SHARP and IMPROVE-IT), as urged by Peto and "any competent trial statistician."

In response to several questions regarding the NEJM analysis, Peto advised the congressmen, more or less, to read the article. Peto further declared that the analysis was undertaken independently of the drug companies and was coordinated by his Oxford colleague Rory Collins, in agreement with the various chairs of the Data Monitoring and Steering Committees of SHARP and IMPROVE-IT.

Other requests from the congressmen were answered with sharp rebukes, including a request for all correspondence between Peto's department, the Clinical Trial Service Unit (CTSU) at Oxford, and Merck or Schering-Plough. Peto replied that this request seems "to constitute inappropriate harassment," given that CTSU has conducted 4 major independent trials of Merck's cholesterol-modifying drugs for more than 10 years. Peto also denied the existence of a "secret" FDA report of his cancer analysis; nor did he send any advance drafts of the study results to Merck or Schering-Plough.

In a curious postscript, Peto requested that the subcommittee declare its own potential conflicts of interest, suggesting that Dingell, in particular, may hold a personal grudge against Peto and the CTSU. In 1997, Peto and others published an article in Controlled Clinical Trials, in which they described the procedures of the subcommittee in its investigation of the National Surgical Adjuvant Breast and Bowel Project (NSABP) as "inappropriate" and Dingell's statements as prosecutorial.

IMPROVE-IT = Improved Reduction of Outcomes: Vytorin Efficacy International Trial; SEAS = Simvastatin and Ezetimibe in Aortic Stenosis; SHARP = Study of Heart and Renal Protection.

Photograph of Richard Peto from CTSU website.

The percentage of childless American women aged 40-44 years doubled during the last 30 years—from 10% to 20%—according to 2006 survey data released yesterday by the US Census Bureau. The survey also revealed that women of this age group had an average of 1.9 children, which is below "replacement level," and 13.5% had never married.

Childless women were more likely to be 40-something non-Hispanic whites (22.5%), be native born (21.4%), and have a graduate or professional degree (27.4%).

Not sure what any of this has to do with the price of tea in China—other than 1) it might provide you're-not-alone solace to 40-something childless women and 2) it might signal the time to learn Mandarin or Spanish.