Invited commentary: vaccine failure or failure to vaccinate?

Despite the availability of safe and effective measles vaccines since 1963, measles still accounts for approximately 10% of global mortality from all causes among children aged less than 5 years, an estimated 36.5 million cases and 1 million deaths in 1996. Worldwide in 1996, routine coverage with 1 dose of measles vaccine was 81%, although the African Region of the World Health Organization reports the lowest coverage, at 56%, and the largest proportion of measles cases and deaths. There is an urgent need to strengthen measles control and explore the best ways to achieve that end, especially in areas such as West Africa. However, the data presented by Cisse et al. do not show that the 1995 outbreak of measles in Niakhar, Senegal, was due mainly to the waning of vaccine-induced immunity among school-aged children. Waning immunity therefore cannot be used to justify the introduction of a multidose vaccination schedule as a key strategy for improving measles control in developing countries. The authors explain the basis for their opinions. The immediate objective of any measles control program should be to provide a first dose of measles vaccine to unvaccinated children.     

Stability of heat stable,live attenuated Rotavirus vaccine (ROTASIIL®)

Vaccines currently available across the globe are stored and transported in a continuous cold-chain at 2–8 °C or below −20 °C. A temperature excursion outside this range affects the potency of the vaccines. Such vaccines need to be discarded leading wastage. The Rotavirus disease burden is predominantly reported in developing and low-income countries and therefore, has entered or poised to enter their national immunization programs. These countries already have several limitations for effective storage, maintenance and distribution of vaccines in a cold-chain and this introduction is expected to further stress this fragile ecosystem. To help mitigate the cold chain related issues, SIIPL has developed a thermostable rotavirus vaccine ROTASIIL® which can be stored at a temperature below 25 °C for 36 months, completely by-passing the standard 2–8 °C cold storages. In addition it has the capability to withstand temperatures of 37 °C and 40 °C for 18 months and short term exposure to 55 °C. It can also tolerate a temperature shock of being thawed from an extreme cold temperature of −20 °C to a high temperature of 42 °C. The vaccine contains serotypes G1, G2, G3, G4 and G9 (UK-Bovine reassortant strains procured from National Institute of Health-USA). The vaccine is recently licensed in India.     

Rotavirus vaccine and intussusception: how much risk will parents in the United States accept to obtain vaccine benefits?

Postlicensure surveillance of a newly licensed rotavirus vaccine suggested an increased risk of intussusception. Little was known about the amount of risk parents would tolerate to obtain the vaccine's benefits or the extent to which risk would reduce the price parents would pay for the vaccine. Parents of infants aged 12 months or younger were asked to accept or reject two hypothetical vaccines associated with varying degrees of risk. Parents chose from a list the amount they would pay for two additional hypothetical vaccines, with and without a risk of intussuception. The authors conducted face-to-face surveys in September 1999 among a convenience sample of parents in three US cities. Of 405 eligible parents, 260 (64%) participated. To achieve a 90% acceptance rate, the vaccine could be associated with no more than 1,794 (95% confidence interval: 1,551, 2,025) cases of intussusception in a fully vaccinated, national cohort of infants. The median willingness to pay for three vaccine doses, when vaccination was associated with 1,400 cases of intussusception, was $36 (95% confidence interval: $28, $46) compared with $110 (95% confidence interval: $96, $126) for the risk-free vaccine. The most important aspect of this study may be the methodology to assess how parents balance the benefits and risks of childhood vaccines.     

Dengue vaccine safety signal: Immune enhancement,waning immunity,or chance occurrence?

A new dengue vaccine was associated with increased risk of hospitalized virologically-confirmed disease during year 3 of follow-up among children age 2–5 years. Among hypotheses to explain this finding, we could not distinguish definitively between antibody dependent enhancement, waning immunity, or chance occurrence. However, any theory must account for the following: (a) the signal occurred mainly because of decreased dengue among controls rather than increased dengue among vaccinees; (b) among 48 data points, a statistically significant increase in hospitalization among vaccinated children occurred for only one age group, during one year, and in one region; (c) cumulative risk was similar for vaccinated vs. control children age 2–5 years at the end of year 5 and lower for vaccinated vs. control children among older age groups; (d) the protective effect of vaccine against hospitalization decreased from years 1–2 to years 3–5 of follow-up for all age groups and regions.     

HPV vaccine information-seeking behaviors among US physicians: government, media, or colleagues?

The multiple information sources available may pose a challenge to physicians in providing accurate human papillomavirus (HPV) vaccine information to patients. The purpose of this study was to describe physicians’ HPV vaccine information-seeking behaviors and assess if these behaviors differ by physician specialty and sociodemographic characteristics. In 2009, 1008 Family Physicians (FPs), Pediatricians (Peds), and Obstetricians/Gynecologists (OBGYNs) completed a survey to assess their HPV vaccine information-seeking behaviors and vaccination practices. The largest proportion obtained HPV vaccine information from professional organizations (50.0%), followed by the Advisory Council on Immunization Practices (ACIP) (36.0%), and medical conferences (33.1%). Peds and FPs were more likely to obtain vaccine information from the ACIP (p-values < 0.05). OBGYNs, non-White/Caucasian physicians, and those aged 40-49 were more likely to obtain vaccine information from internet websites (p-values < 0.05). There is a need for targeted HPV vaccine communication approaches based on sociodemographic and physician specialty characteristics.     

Who is at risk of 13-valent conjugated pneumococcal vaccine failure?

BackgroundDespite high vaccine coverage rates in children and efficacy of pneumococcal conjugate vaccines, invasive pneumococcal disease (IPD) episodes due to serotypes included in the vaccine following completion of the recommended course of immunisation (i.e. vaccine failure) have been reported.MethodsWe used data gathered from a population-based enhanced passive surveillance for IPD in children under 18 years of age in Massachusetts and an ensemble model composed of three machine-learning algorithms to predict probability of 13-valent pneumococcal conjugated vaccine (PCV13) failure and to evaluate potential associated features including age, underlying comorbidity, clinical presentation, and vaccine schedule. Vaccine failure was defined as diagnosis of IPD due to vaccine serotype (VST), in a child who received age recommended doses recommended by Advisory Committee of Immunization Practices.ResultsDuring the 7-year study period, between April 01, 2010 and March 31, 2017, we identified 296 IPD cases. There were 107 (36%) IPD cases caused by VST, mostly serotype 19A (49, 17%), 7F (21, 7%), and 3 (18, 6%). Thirty-seven (34%) were in children who were completely vaccinated representing 13% of all IPD cases. Vaccine failure was more likely among children older than 60 months (predicted probability 0.40, observed prevalence 0.37, model prediction accuracy 79%), children presenting with pneumonia (predicted probability 0.27, observed prevalence 0.31, model accuracy 77%), and children with underlying comorbidity (predicted probability 0.24, observed prevalence 0.23, model accuracy 96%). Vaccine failure probability for those >60 months of age and had an underlying risk factor was 45% (observed prevalence 0.33, model accuracy 82%). The likelihood of vaccine failure was lowest among children who had completed 3 primary doses plus one booster dose PCV13 (predicted probability 0.14, observed prevalence 0.14, model prediction accuracy 100%).ConclusionPCV13 vaccine failure is more frequent among older children with underlying comorbidity, and among those who present with pneumococcal pneumonia. Our study provides a preliminary framework to predict the patterns of vaccine failures and may contribute to decision-making processes to optimize PCV immunization schedules.     

Failure to vaccinate or failure of vaccine? Effectiveness of the 23-valent pneumococcal polysaccharide vaccine program in Indigenous adults in the Northern Territory of Australia

Over the last decade, there has been no discernible reduction in Invasive Pneumococcal Disease (IPD) amongst Indigenous adults in the Northern Territory (NT) of Australia, despite increasing vaccination coverage. We examined the utility of two common methods, the screening method and the indirect method, to determine the 23-valent pneumococcal polysaccharide vaccine effectiveness (VE) in prevention of IPD amongst Indigenous adults in this setting. VE was calculated for the period 2001–2005 across two distinct geographical areas where the disease burden was known to differ. VE against vaccine-type IPD was 3.4% (95% CI −43, 35) for the NT. However, population vaccination coverage varied widely according to geographical region and where this was within the range appropriate for the use of the screening method, VE was within the expected range (67.2%, 95% CI 47, 80). VE according to the indirect cohort appeared unreliable in this setting due to the analysis being based on a very limited number of non-vaccine-type IPD cases. Surveillance based estimates of VE such as these need to be considered with caution, but the results suggest failure to vaccinate is the most likely reason vaccine-type IPD has not reduced in this setting.     

Hospital readmission rates: Signal of failure or success?

Hospital readmission rates are increasingly used as signals of hospital performance and a basis for hospital reimbursement. However, their interpretation may be complicated by differential patient survival rates. If patient characteristics are not perfectly observable and hospitals differ in their mortality rates, then hospitals with low mortality rates are likely to have a larger share of un-observably sicker patients at risk of a readmission. Their performance on readmissions will then be underestimated. We examine hospitals’ performance relaxing the assumption of independence between mortality and readmissions implicitly adopted in many empirical applications. We use data from the Hospital Episode Statistics on emergency admissions for fractured hip in 290,000 patients aged 65 and over from 2003 to 2008 in England. We find evidence of sample selection bias that affects inference from traditional models. We use a bivariate sample selection model to allow for the selection process and the dichotomous nature of the outcome variables.     

A decade of Medicare's prospective payment system--success or failure?

The growth in Medicare spending for inpatient hospital services slowed following the implementation of the prospective payment system (PPS) due to a decline in admission rates and limits on payment increases. Hospital costs, however, have increased faster than payments. Rather than reducing costs further, hospitals responded by charging privately insured patients more than the costs of their care and developing new revenue sources. PPS also redistributed Medicare payments across hospitals and was associated with increased spending in other settings. The PPS experience leaves policymakers with some immediate challenges and provides insights for the development of health care reform initiatives.     

Tuberculosis treatment failure and drug resistance--same strain or reinfection?

Tuberculosis patients may have Mycobacterium tuberculosis in their sputum at the end of treatment, and may show new drug resistance, due to either inadequate treatment of the original episode or reinfection with a new strain during therapy. In a cohort study of mineworkers with tuberculosis in South Africa, 57 of 438 patients had positive sputum cultures 6 months after recruitment in 1995. Of the 31 patients who initially had fully sensitive strains, 3 developed multidrug resistance (MDR) and 3 single-drug resistance (SDR). Of the 6 who started with SDR, 3 became MDR. HIV infection was not associated with drug resistance at enrollment or 6 months later. We compared pairs of DNA fingerprints from isolates of M. tuberculosis at recruitment and 6 months later in the 48 patients for whom we had both available. In 45, the pairs were identical. In 1 patient, although both isolates were fully sensitive, the later fingerprint had 1 less band (transposition). In 2 pairs, the fingerprint patterns were completely different: one seemed to be the result of laboratory error and the other was a true reinfection with an MDR strain. Despite a high risk of infection, with a moderate proportion of background drug-resistant strains (11% SDR, 6% MDR), reinfection is not a common cause of treatment failure or drug resistance at 6 months.