K. Lisa Cairns

Too little but not too late: Results of a literature review to improve routine immunization programs in developing countries

BackgroundGlobally, immunization services have been the center of renewed interest with increased funding to improve services, acceleration of the introduction of new vaccines, and the development of a health systems approach to improve vaccine delivery. Much of the credit for the increased attention is due to the work of the GAVI Alliance and to new funding streams. If routine immunization programs are to take full advantage of the newly available resources, managers need to understand the range of proven strategies and approaches to deliver vaccines to reduce the incidence of diseases. In this paper, we present strategies that may be used at the sub-national level to improve routine immunization programs.MethodsWe conducted a systematic review of studies and projects reported in the published and gray literature. Each paper that met our inclusion criteria was rated based on methodological rigor and data were systematically abstracted. Routine-immunization – specific papers with a methodological rigor rating of greater than 60% and with conclusive results were reported.ResultsGreater than 11,000 papers were identified, of which 60 met our inclusion criteria and 25 papers were reported. Papers were grouped into four strategy approaches: bringing immunizations closer to communities (n = 11), using information dissemination to increase demand for vaccination (n = 3), changing practices in fixed sites (n = 4), and using innovative management practices (n = 7).ConclusionImmunization programs are at a historical crossroads in terms of developing new funding streams, introducing new vaccines, and responding to the global interest in the health systems approach to improving immunization delivery. However, to complement this, actual service delivery needs to be strengthened and program managers must be aware of proven strategies. Much was learned from the 25 papers, such as the use of non-health workers to provide numerous services at the community level. However it was startling to see how few papers were identified and in particular how few were of strong scientific quality. Further well-designed and well-conducted scientific research is warranted. Proposed areas of additional research include integration of additional services with immunization delivery, collaboration of immunization programs with new partners, best approaches to new vaccine introduction, and how to improve service delivery.

Progress Toward Measles Elimination in the People's Republic of China, 2000–2009

In 2006, China set a goal of measles elimination by 2012. To describe progress toward this goal, we reviewed relevant policies and strategies and analyzed national data for 2000-2009. In response to implementation of these strategies, including increased routine measles vaccination coverage and province-specific supplementary immunization activities (SIAs), reported measles incidence decreased to a historically low level of 39.5 cases per million in 2009. A synchronized nationwide SIA was scheduled in 2010 to further decrease susceptibility to measles. However, reaching and maintaining measles elimination will require strong political commitment and efforts for strengthening surveillance, increasing 2-dose vaccine coverage to >95%, stricter enforcement of the requirement to check immunization status at school entry, and careful attention to measles susceptibility in those aged ≥15 years.

Measles outbreak in South Africa, 2003-2005.

OBJECTIVES Measles was virtually eliminated in South Africa following control activities in 1996/7. However, from July 2003 to November 2005, 1676 laboratory-confirmed measles cases were reported in South Africa. We investigated the outbreaks cause and the role of HIV. DESIGN We traced laboratory-confirmed case-patients residing in the Johannesburg metropolitan (JBM) and O. R. Tambo districts. We interviewed laboratory--or epidemiologically confirmed case-patients or their caregivers to determine vaccination status and, in JBM, HIV status. We calculated vaccine effectiveness using the screening method. SETTING Household survey in JBM and O. R. Tambo districts. Outcome measures. Vaccine effectiveness, case-fatality rate, and hospitalisations. RESULTS In JBM, 109 case-patients were investigated. Of the 57 case-patients eligible for immunisation, 27 (47.4%) were vaccinated. Fourteen (12.8%) case-patients were HIV infected, 46 (42.2%) were HIV uninfected, and 49 (45.0%) had unknown HIV status. Among children aged 12-59 months, vaccine effectiveness was 85% (95% confidence interval (CI): 63, 94) for all children, 63% for HIV infected, 75% for HIV uninfected, and 96% for children with unknown HIV status. (Confidence intervals were not calculated for sub-groups owing to small sample size.) In O. R. Tambo district, 157 case-patients were investigated. Among the 138 case-patients eligible for immunisation, 41 (29.7%) were vaccinated. Vaccine effectiveness was 89% (95% CI 77, 95). CONCLUSIONS The outbreaks primary cause was failure to vaccinate enough of the population to prevent endemic measles transmission. Although vaccine effectiveness might have been lower in HIV-infected than in uninfected children, population vaccine effectiveness remained high.

Should Outbreak Response Immunization Be Recommended for Measles Outbreaks in Middle- and Low-Income Countries? An Update

BACKGROUND Measles caused mortality in >164,000 children in 2008, with most deaths occurring during outbreaks. Nonetheless, the impact and desirability of conducting measles outbreak response immunization (ORI) in middle- and low-income countries has been controversial. World Health Organization guidelines published in 1999 recommended against ORI in such settings, although recently these guidelines have been reversed for countries with measles mortality reduction goals. METHODS We searched literature published during 1995-2009 for papers reporting on measles outbreaks. Papers identified were reviewed by 2 reviewers to select those that mentioned ORI. World Bank classification of country income was used to identify reports of outbreaks in middle- and low-income countries. RESULTS We identified a total of 485 articles, of which 461 (95%) were available. Thirty-eight of these papers reported on a total of 38 outbreaks in which ORI was used. ORI had a clear impact in 16 (42%) of these outbreaks. In the remaining outbreaks, we were unable to independently assess the impact of ORI. CONCLUSIONS These findings generally support ORI in middle- and low-income countries. However, the decision to conduct ORI and the nature and extent of the vaccination response need to be made on a case-by-case basis.

Impact of measles outbreak response vaccination campaign in Dar es Salaam, Tanzania.

We assessed the impact of a measles outbreak response vaccination campaign (ORV) in Dar es Salaam, Tanzania. Age-specific incidence rates were calculated before and after the ORV. Incidence rate ratios for the two time periods were compared and used to estimate expected cases and deaths prevented by ORV. The ratio of measles incidence rates in the age groups targeted and not targeted by ORV decreased from 5.8 prior to ORV to 1.8 (p<0.0001) after; 506 measles cases and 18 measles deaths were likely averted. These results support the need for revised recommendations concerning ORV in general settings in Africa.

Etiologies of Rash and Fever Illnesses in Campinas, Brazil

BACKGROUND Few population-based studies of infectious etiologies of fever-rash illnesses have been conducted. This study reports on enhanced febrile-rash illness surveillance in Campinas, Brazil, a setting of low measles and rubella virus transmission. METHODS Cases of febrile-rash illnesses in individuals aged <40 years that occurred during the period 1 May 2003-30 May 2004 were reported. Blood samples were collected for laboratory diagnostic confirmation, which included testing for adenovirus, dengue virus, Epstein-Barr virus (EBV), enterovirus, human herpes virus 6 (HHV6), measles virus, parvovirus-B19, Rickettsia rickettsii, rubella virus, and group A streptococci (GAS) infections. Notification rates were compared with the prestudy period. RESULTS A total of 1248 cases were notified, of which 519 (42%) had laboratory diagnosis. Of these, HHV-6 (312 cases), EBV (66 cases), parvovirus (30 cases), rubella virus (30 cases), and GAS (30 cases) were the most frequent causes of infection. Only 10 rubella cases met the rubella clinical case definition currently in use. Notification rates were higher during the study than in the prestudy period (181 vs 52.3 cases per 100,000 population aged <40 years). CONCLUSIONS Stimulating a passive surveillance system enhanced its sensitivity and resulted in additional rubella cases detected. In settings with rubella elimination goals, rubella testing may be considered for all cases of febrile-rash illness, regardless of suspected clinical diagnosis.

Measles Incidence Before and After Mass Vaccination Campaigns in Burkina Faso

Burkina Faso conducted mass measles vaccination campaigns among children aged 9 months to 4 years during December 1998 and December 1999. The 1998 campaign was limited to six cities and towns, while the 1999 campaign was nationwide. The last year of explosive measles activity in Burkina Faso was 1996. Measles surveillance data suggest that the 1998 urban campaigns did not significantly impact measles incidence. After the 1999 national campaign, the total case count decreased during 2000 and 2001. However, 68% of measles cases occurred among children aged 5 years or older who were not included in the mass vaccination strategy. During 2000 and 2001, areas with high measles incidence were characterized by low population density and presence of mobile and poor populations. Measles control strategies in Sahelian Africa must balance incomplete impact on virus circulation with cost of more aggressive strategies that include older age groups.

Measles outbreak in Tanzania, 2006-2007

We conducted a measles outbreak investigation in Dar es Salaam, Tanzania. Surveillance data were analyzed; a susceptibility profile developed, and case-control study conducted. The age distribution of cases peaked among those <2, 5-7, and > or =18 years, corresponding to the age distribution of susceptibles. Risk factors included being unvaccinated (aOR=5.7, p<0.01) or having received one dose of vaccine compared to two (aOR=2.4, p=0.01), being younger, and having a less-educated caretaker. Vaccine effectiveness was 88% (one dose) and 96% (two doses). Results highlight the importance of receiving one dose of measles vaccine, and the added benefit of two doses.

Cross-sectional survey methods to assess retrospectively mortality in humanitarian emergencies

Since the rates and causes of mortality are critical indicators of the overall health of a population, it is important to evaluate mortality even where no complete vital statistics reporting exists. Such settings include humanitarian emergencies. Experience in cross-sectional survey methods to assess retrospectively crude, age-specific, and maternal mortality in stable settings has been gained over the past 40 years, and methods appropriate to humanitarian emergencies have been developed. In humanitarian emergencies, crude and age-specific mortality can be gauged using methods based on the enumeration of individuals resident in randomly selected households-frequently referred to as a household census. Under-five mortality can also be assessed through a modified prior birth history method in which a representative sample of reproductive-aged women are questioned about dates of child births and deaths. Maternal mortality can be appraised via the initial identification of maternal deaths in the study population and a subsequent investigation to determine the cause of each death.

Challenges in measuring measles case fatality ratios in settings without vital registration

Measles, a highly infectious vaccine-preventable viral disease, is potentially fatal. Historically, measles case-fatality ratios (CFRs) have been reported to vary from 0.1% in the developed world to as high as 30% in emergency settings. Estimates of the global burden of mortality from measles, critical to prioritizing measles vaccination among other health interventions, are highly sensitive to the CFR estimates used in modeling; however, due to the lack of reliable, up-to-date data, considerable debate exists as to what CFR estimates are appropriate to use. To determine current measles CFRs in high-burden settings without vital registration we have conducted six retrospective measles mortality studies in such settings. This paper examines the methodological challenges of this work and our solutions to these challenges, including the integration of lessons from retrospective all-cause mortality studies into CFR studies, approaches to laboratory confirmation of outbreaks, and means of obtaining a representative sample of case-patients. Our experiences are relevant to those conducting retrospective CFR studies for measles or other diseases, and to those interested in all-cause mortality studies.