Anticipating rotavirus vaccines: epidemiology and surveillance of rotavirus in South Africa

Rotavirus infection is associated with acute infantile gastroenteritis in infants and young children globally. In South Africa, rotavirus infection has been shown to be associated with approximately one-quarter of all diarrhoeal admissions to hospital. Rotavirus infection predominantly occurs in infants less than 12 months of age (75%) and has a peak of shedding during the cooler, drier months of the year. A secondary peak during the spring has been observed. Multiple infections with rotavirus and at least one other microbial agent are common. The circulating VP7 serotypes and VP4 genotypes have been determined in various regions of South Africa and show a geographic specific distribution. A decade previously, P[8]G1 or G4 strains predominated, and P[4]G2 strains occurred in an epidemic pattern in one region. More recently, rotavirus strains with P[6] genotype have become common and novel VP7/VP4 genotype combinations are occurring across the country. G9 strains have been reported from Cape Town to Vendaland. The circulating rotavirus types observed in this study add to the knowledge of the natural history of rotavirus infection and provide the groundwork to consider future vaccine strategies.     

Rotavirus vaccines and vaccination in Latin America.

Worldwide, rotaviruses account for more than 125 million cases of infantile gastroenteritis and nearly 1 million deaths per year, mainly in developing countries. Rather than other control measures, vaccination is most likely to have a major impact on rotavirus disease incidence. The peak incidence of rotavirus diarrhea occurs between 6 and 24 months of age. In developing countries, however, cases are not uncommon among children younger than 6 months. G serotypes 1 to 4 are responsible for most disease, but there are indications that in Brazil that G type 5 is of emerging epidemiological importance. Both homotypic and heterotypic responses are elicited during natural rotavirus infection, and the immunological response at the intestinal mucosal surface is probably the more consistent predictor of clinical immunity. With the primary objective of protecting children against life-threatening dehydrating diarrhea, many approaches to rotavirus vaccine development have been attempted. One vaccine, the tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV), was given licensing approval in the United States of America, introduced to the market, and later withdrawn. A number of studies have found better efficacy of RRV-TV in developed countries than in developing ones. Field trials with a 4 x 10(4) plaque-forming units (PFU) preparation of RRV-TV have been carried out in two countries in Latin America, Brazil and Peru. Those trials yielded protective efficacy rates against all rotavirus diarrhea ranging from 18% to 35%. Data from a large catchment trial in Venezuela with a higher RRV-TV dose, of 4 x 10(5) PFU/dose, indicated an efficacy rate of 48% against all rotavirus diarrhea and 88% against severe rotavirus diarrhea. It appears that breast-feeding does not compromise the efficacy of RRV-TV if three doses of the vaccine are administered. Similarly, possible interference of oral poliovirus vaccine with the "take" of the rotavirus vaccine can be overcome by giving three doses of the rotavirus vaccine or by using a higher-titer formulation of it. Wild enteroviruses, however, may cause primary rotavirus vaccine failure in developing countries. Studies in Peru with RRV-TV have shown a trend towards higher vaccine efficacy rates against "pure" (rotavirus-only) diarrheal episodes. Economic analyses made in the United States indicate that a vaccine that costs less than US$ 9 per dose would lead to a net savings in medical costs. To date, however, cost-benefit studies have not been done in developing countries. In the future, it is possible that some Latin American countries might adapt their polio production facilities to the preparation of rotavirus vaccines for human use. A year after RRV-TV was licensed for vaccination of infants in the United States, the occurrence of intussusception as an adverse event led to the vaccine's withdrawal from the market. The implications of that action, particularly for Latin America, will be addressed in this article, including the need to explore alternative rotavirus candidate vaccines, particularly through the conduct of parallel clinical trials in both developed and developing countries.     

The pharmacoeconomics of pneumococcal conjugate vaccines in Latin America

Streptococcus pneumoniae continues to be the most important causative agent of invasive bacterial infections in children and is the most common cause of vaccine-preventable deaths in children less than 5 years of age. Due to some conditions in the Latin America region, economic assessments of pneumococcal conjugate vaccines (PCVs) have unique characteristics. First, distribution of S. pneumoniae serotypes, and thus coverage by vaccines that incorporate certain serotypes, varies within the region and compared with other parts of the world. Second, the mortality rate of pneumococcal infections in developing countries is significantly higher than in the US and Europe. Third, the economies of the Latin American region are very different from those of developed countries. For these reasons, the Pan American Health Organization (PAHO) is promoting the need for economic valuation studies of the impact of pneumococcal vaccines Latin America. Given the importance of pneumonia in the burden of pneumococcal disease in Latin America, the number of pneumonia cases prevented by the vaccine has a large impact on the economic valuation of PCVs, due to a strong correlation with numbers of deaths averted, quality-adjusted life-years (QALYs) gained or disability-adjusted life-years (DALYs) avoided. In terms of cost, analysis of impact on acute otitis media (short-term) and sequelae (long-term) show a significant and important expenditure avoided by vaccination. Cost-effectiveness is significantly modified by vaccine cost, mortality due to pneumonia, vaccine efficacy/effectiveness and herd immunity. Finally the validity of certain assumptions based on the uncertainty of the data should be considered in economic assessments of new PCVs. These include assumptions related to the impact on otitis media, estimates of efficacy/effectiveness based on measured antibody levels and the extrapolation to PCV10 and PCV13 of previous experience with PCV7.     

Hepatitis B epidemiology in Latin America

The available data on prevalence of hepatitis B virus (HBV) infection in Latin America are incomplete and largely based on analysis of blood banks, which are not stratified by age or social class. An epidemiological study was recently undertaken in six countries in Latin America to update the data. The highest seroprevalence of antibody to the HBV core antigen (anti-HBc) was found in the Dominican Republic (21.4%), followed by Brazil (7.9%), Venezuela (3.2%) and Argentina (2.1%). The lowest seroprevalence was found in Mexico (1.4%) and Chile (0.6%). The seroprevalence in different regions of Brazil varied from 21% in Manaus to 1.2% in Fortaleza. There were no differences in seroprevalence of anti-HBc between females and males except in Brazil (significantly higher in males) and in the Dominican Republic (significantly higher in females). In Brazil alone, higher seroprevalence was associated with lower socioeconomic class. In both the Dominican Republic and Brazil, seroprevalence was high in childhood, and in Brazil and Argentina, anti-HBc was detected in 3.0-6.6% of children up to 1 year old, suggesting vertical transmission. Other risk factors included dental and surgical procedures, sexual activity and tattooing. There was an increase in seroprevalence in all countries at or after adolescence, suggesting that sexual activity is a major route of transmission.     

Hepatitis A shifting epidemiology in Latin America

In the past, Latin America was considered to be an area of high endemicity for hepatitis A virus (HAV) infection, with most people infected in early childhood. A seroepidemiological study was recently undertaken in six countries to determine whether this pattern has changed. The highest seroprevalence of antibodies to HAV (anti-HAV) was found in Mexico and the Dominican Republic. Analysis of the different age groups showed that at age 6-10 years, 30% of children in Chile and 54-55% in Brazil, Venezuela and Argentina had been infected, compared with almost 70% in Mexico and 80% in the Dominican Republic. At age 11-15 years, nearly 90% in Mexico and 91% in the Dominican Republic had been infected, compared with 54% in Argentina, 62% in Venezuela, 60% in Brazil and 70% in Chile. By age 31-40 years, over 80% of the populations in all six countries had been exposed to HAV. In all of the countries except Brazil and Venezuela, the seroprevalence of anti-HAV was significantly higher in females than in males. In Mexico, Argentina and Brazil, anti-HAV seroprevalence was significantly higher in the low socioeconomic groups than in the middle/high socioeconomic groups. The results show that there has been a shift from high to medium endemicity of HAV infection throughout Latin America, which may result in more clinical cases in adolescents and adults and a greater potential for outbreaks. The vaccination strategy for hepatitis A should thus be reviewed.     

The globalization of epidemiology: critical thoughts from Latin America

BACKGROUND: Epidemiology in Latin America, as in the rest of the world, has been developed for the purpose of contributing towards understanding the causes and determinants of the phenomena of health and disease in specific contexts. However, in that continent it has specific characteristics. METHODS: The paper explores epidemiology in the Latin American continent, emphasizing on the one hand epidemiology as a knowledge-producing, scientific discipline, and on the other hand, epidemiology in praxis, with its firm commitment to contributing towards transforming the health of the population. RESULTS: It has been possible to identify at least eight idiosyncrasies that characterize epidemiology in Latin America. It is being forged with a strong connection to the evolution of the discipline in an international context; however, it has its feet firmly planted in reality, seeking to extract from that reality elements that may contribute towards diminishing the serious health problems in that society. CONCLUSIONS: This paper presents a picture of the development of epidemiology in Latin America. It is very clear that as well as a lively, intense, intellectual debate, there is a frantic search for alternatives that will increase Latin American populations' possibilities of survival. However, one important aspect is that these two elements-theory and praxis-present consistent dialectic relationships and feedback; this is the main wealth of Latin American epidemiology.     

Identifying early adopters of COVID-19 vaccines in Latin America

COVID-19 vaccine hesitancy is currently-one of the main obstacles to worldwide herd immunity and socioeconomic recovery. Because vaccine coverage can vary between and within countries, it is important to identify sources of variation so that policies can be tailored to different population groups. In this paper, we analyze the results from a survey designed and implemented in order to identify early adopters and laggers in six big cities located in Argentina, Colombia, Chile, Ecuador, Peru, and Dominican Republic. We find that trust in government and science, accurate knowledge about the value of vaccination and vaccine effects, and perceived risk of getting sick is associated with a higher probability to get vaccinated. We also identify potential laggers such as women and populations with high education but low knowledge about vaccines. We discuss specific strategies to promote vaccination among these populations groups as well as more general strategies designed to gain trust. These findings are specific to the context of Latin America insofar as the underlying factors associated with the choice to be vaccinated vary significantly by location and in relation to individual-level factors.     

Effect of rotavirus vaccine on childhood diarrhea mortality in five Latin American countries

BackgroundThe aim of this study was to estimate the association between rotavirus vaccine (RV) introduction and reduction of all-cause diarrhea death rates among children in five Latin American countries that introduced RV in 2006.MethodsDiarrhea mortality data was gathered from 2002 until 2009 from the Pan American Health Organization Mortality Database for five “vaccine adopter” countries (Brazil, El Salvador, Mexico, Nicaragua, and Panama) that introduced RV in 2006 and four “control” countries (Argentina, Chile, Costa Rica, and Paraguay) that did not introduce RV by 2009. Time trend analyses were carried out, and effects and 95% confidence intervals (CI) were estimated.ResultsEach of the five vaccine adopter countries, except Panama, showed a significant trend in declining mortality rates during the post-vaccine period from 2006 to 2009, whereas no decline was seen in control countries during these years. Furthermore, trends of reduction of all-cause diarrhea mortality in both children <1 year of age and <5 years of age were greater in the post-vaccination period compared with the pre-vaccine period in all vaccine adopter countries (except for Nicaragua), whereas in control countries, a reverse pattern was seen with greater reduction in the early years from 2002 to 2005 versus 2006–2009. An estimatedtotal of 1777 of annual under-5 deaths were avoided in Brazil, El Salvador, Mexico, and Nicaragua during the post-vaccination period.ConclusionAll vaccine adopter countries, except Panama, showed a significant decrease in all-cause diarrhea-related deaths after RV implementation, even after adjusting for declining trends over time in diarrhea mortality. These data strongly support continuous efforts to increase vaccination coverage of RV vaccines, particularly in countries with high levels of child mortality from diarrhea.     

婴幼儿轮状病毒性腹泻的临床特点及分子流行病学分析

目的:通过分子流行病学调查银川地区婴幼儿轮状病毒性腹泻的病原学特点和临床相关性分析。方法:采用酶联免疫吸附试验(ELISA)及逆转录-聚合酶链反应(RT-PCR)法对银川地区2009年7月～2010年6月收集的256例婴幼儿腹泻粪便标本进行轮状病毒(RV)检测。结果:在256例标本中应用ELISA法检测RV阳性率为60.2%(154/256),RT-PCR法阳性率为53.9%(138/256);其中G2型55份(39.9%)、G3型42份(30.4%)、未能分型26份(18.8%),不同G型混合感染8份(5.8%),G1型7份(5.1%),未发现G4和G9型。对标本进行P分型,P[4]基因型62份(44.9%),未能分型40份(29%),P[8]基因型36份(26.1%),无混合感染,未发现P[6]、P[9]、P[10]型。RV G型与P型的关系主要为P[4]G2、P[8]G3。结论:HRV是银川地区婴幼儿病毒性腹泻的最主要病原,临床症状重于非HRV腹泻。     

上海市部分地区儿童轮状病毒腹泻的分子流行病学调查

A组轮状病毒(RV)是婴幼儿重症腹泻的主要病原,在发展中国家和发达国家都是一个重要的公共卫生问题.我国研究表明,在全年开展RV腹泻监测的医院中,住院腹泻患儿RV检出率中位数是46%,门诊腹泻患儿RV检出率中位数为29%,而社区腹泻患儿RV检出率占10%~[1].     

Molecular epidemiology of human rotavirus.

The epidemiology of human rotavirus (HRV) in north-east Scotland was investigated between 1982 and 1984. During this period 708 HRV infections were recorded. The majority (83%) of the infections were in children less than 5 years of age although some were recorded in adults. The peak incidence occurred in the winter months although a high number of HRV infections was reported during the summer of 1983. A total of 840 faecal specimens containing rotavirus were screened for HRV genome RNA by polyacrylamide gel electrophoresis. Seven hundred (83%) specimens gave RNA profiles suitable for establishing the HRV electrophoretype. Twenty-five different electrophoretypes were identified, of which 21 had ''long'' RNA profiles and four had ''short'' RNA profiles. There was extensive co-circulation of distinct electrophoretypes although during any one epidemic period the majority of viruses belonged to a relatively small number of types. Comparison of viruses collected from hospitalized and non-hospitalized patients showed no differences in electrophoretype distribution. HRV was identified in faecal specimens from a wide age group and no correlation was demonstrated between age of patient and electrophoretype of the infecting virus.     

苏州儿童医院2001—2002年婴幼儿轮状病毒腹泻的分子流行病学研究

目的 了解苏州地区婴幼儿轮状病毒腹泻的分子流行病学特征。方法 采用酶联免疫吸附试验，巢式聚合酶链反应对该院2001－2002年收集的婴幼儿腹泻标本进行轮状病毒检测及血清型研究，同时填写统一制定的调查表，分析流行特征。结果 775份婴幼儿腹泻标本轮状病毒阳性率为35．35％，血清型分型发现G3型为流行优势株，占49．0％；其次为G1型占32．9％，再次为G2，G4；未定型占12．0％；G9型有3例，为1a以内患儿，G1和G3全年季节性分布与轮状病毒阳性的分布一致。结论 苏州地区2001－2002年婴幼儿轮状病毒腹泻的主要血清型为G3和G1，G3为优势毒株。