A review of measles supplementary immunization activities and the implications for Pacific Island countries and territories.

INTRODUCTION: Standard measles control strategies include achieving high levels of measles vaccine coverage using routine delivery systems, supplemented by mass immunization campaigns as needed to close population immunity gaps. Areas covered: This review looks at how supplementary immunization activities (SIAs) have contributed to measles control globally, and asks whether such a strategy has a place in Pacific Islands today. Expert commentary: Very high coverage with two doses of measles vaccine seems to be the optimal strategy for controlling measles. By 2015, all but two Pacific Islands had introduced a second dose in the routine schedule; however, a number of countries have not yet reached high coverage with their second dose. The literature and the country reviews reported here suggest that a high coverage SIA combined with one dose of measles vaccine given in the routine system will also do the job. The arguments for and against the use of SIAs are complex, but it is clear that to be effective, SIAs need to be well designed to meet specific needs, must be carried out effectively and safely with very high coverage, and should, when possible, carry with them other public health interventions to make them even more cost-effective.

Control of viral hepatitis infection in Africa: are we dreaming?

BACKGROUND: At least five different types of viral hepatitis cause problems of significant public health importance in Africa, where together they constitute a huge burden of disease. But until now, efforts to control the infections have been largely piecemeal. Analysis of the strategies needed to control each virus, however, reveals major overlaps. PROPOSAL: We propose that the control of these infections in the WHO African Region should start with the common strategies rather than with each disease. But this approach presents potentially huge problems to overcome, such as the difficulty of integrating multiple health service elements - the track record for successful integration of such services is not good. This is despite encouraging rhetoric from donors and national leaders alike. And to succeed, disparate programmes must work closely together. But we believe that the time is right to create new opportunities for prevention and treatment of hepatitis, including increasing education, and promoting screening and treatment for more than 500 million people already infected with hepatitis B and C viruses. IMPACT: The impact of these efforts on decreasing mortality and morbidity will be significant because of the high burden of disease from these infections, and also because the effect will spill over to benefit the control of other communicable diseases and health systems strengthening. Such a project will inevitably involve multiple strategies that will vary somewhat according to the epidemiology of the diseases and the location.

Rubella control in Papua New Guinea: age-specific immunity informs strategies for introduction of rubella vaccine.

AIM: To determine the age specific immunity profile for rubella from three discrete study populations in Papua New Guinea, and to inform policy regarding the possible introduction of rubella vaccine. BACKGROUND: In 2005, the Western Pacific Region (WPR), of which Papua New Guinea (PNG) is a member state, declared the goal of regional measles elimination by 2012. Recently, WPR has incorporated an accelerated control goal for rubella and congenital rubella syndrome (CRS). PNG currently recommends two doses of measles vaccination at 6 and 9 months of age with a monovalent measles vaccine, which does not include rubella vaccine. METHODS: Convenience samples were collected from 1326 eligible participants in PNG and assessed for rubella immunity using the Dade Behring Enzygnost™ Anti-Rubella-Virus enzyme immunoassay. Nearly 34% were collected during an age stratified prospective survey of febrile patients in Madang Province; approximately 49% were collected from women of childbearing age in East Sepik and Milne Bay Provinces. Remaining specimens were collected from 6 to 7-month-old infants in Port Moresby prior to receiving the first dose of measles vaccine. FINDINGS: Of all samples tested, 65.2% (95% confidence interval (CI): 62.6-67.8) had evidence of immunity to rubella infection. Of women more than 15 years of age, 91.6% (95% CI: 89.4-93.5) were immune. The force of infection was highest between 5 and 19 years of age. CONCLUSIONS: Although a population-based sample was not used, our multi-centre study of the population immunity profile suggests that immunity against rubella is extremely high in most women of childbearing age, but women who become pregnant at an early age may be at high risk of rubella infection during pregnancy and potential delivery of an infant with CRS. Routine measles vaccine coverage, a proxy for measles-rubella vaccine coverage, as measured in recently published studies, is well below the WHO target of 80% coverage. Introduction of a child or infant dose of rubella vaccine requires caution and further study.

Researching routine immunization-do we know what we don't know?

BACKGROUND: The Expanded Programme on Immunization (EPI), launched in 1974, has developed and implemented a range of strategies and practices over the last three decades to ensure that children and adults receive the vaccines they need to help protect them against vaccine-preventable diseases. Many of these strategies have been implemented, resulting in immunization coverage exceeding 80% among children one year of age in many countries. Yet millions of infants remain under-immunized or unimmunized, particularly in poorer countries. In November 2009, a panel of external experts met at the United States Centers for Disease Control and Prevention (CDC) to review and identify areas of research required to strengthen routine service delivery in developing countries. METHODS: Research opportunities were identified utilizing presentations emphasizing existing research, gaps in knowledge and key questions. Panel members prioritized the topics, as did other meeting participants. FINDINGS: Several hundred research topics covering a wide range were identified by the panel members and participants. However there were relatively few topics for which there was a consensus that immediate investment in research is warranted. The panel identified 28 topics as priorities. 18 topics were identified as priorities by at least 50% of non-panel participants; of these, five were also identified as priorities by the panel. Research needs included identifying the best ways to increase coverage with existing vaccines and introduce new vaccines, integrate other services with immunizations, and finance immunization programmes. INTERPRETATION: There is an enormous range of research that could be undertaken to support routine immunization. However, implementation of strategic plans, rather than additional research will have the greatest impact on raising immunization coverage and preventing disease, disability, and death from vaccine-preventable diseases. The panel emphasized the importance of tying operational research to programmatic needs, with a focus on efforts to scale up proven best practices in each country, facilitating the full implementation of immunization strategies.

Implementing a birth dose of hepatitis B vaccine for home deliveries in Africa--too soon?

Despite the recommendation of the World Health Organization (WHO) to provide the first hepatitis B vaccine dose at birth (within 24h), there are epidemiological, economic and logistical reasons why this may not be the best approach for home births in Africa. The WHO policy presupposes that the epidemiology of hepatitis B infection in Africa is similar to the rest of the world and that the organizational, infrastructural and financial support is adequate. While babies born in health facilities may be relatively easy to immunize at birth, health systems and infrastructures in many resource-poor countries in Africa would be severely challenged, if required to reach home deliveries within 24h of birth.

Are hard-to-reach populations being reached with immunization services? Findings from the 2005 Papua New Guinea national immunization coverage survey.

OBJECTIVE: To measure immunization coverage among children aged 12-23 months in Papua New Guinea (PNG) and to assess if and why there are differences between hard-to-reach and more accessible communities. METHODS: WHO cluster sampling methodology was employed to measure immunization coverage in PNG's four regions. Survey data were re-analyzed according to a local assessment of geographical accessibility indicated by census unit type: urban, rural and hard-to-reach. Census units were designated as hard-to-reach if they were five or more km from a health centre. FINDINGS: Nationwide coverage for most antigens falls below the national target of 80% although there are regional differences with Islands performing the best. Late doses are a major concern: just 4% were fully immunized with valid ("on time") doses by 1 year of age. Coverage was lower in both rural and remote communities: at 6 months 48% of children from urban units had received three valid doses of DTP-3 but only 16% in rural areas and 13% in hard-to-reach communities. Reasons for failure to immunize varied: 21% of mothers said their child was not immunized because distance, travel conditions or cost of transportation prevented access to local health centres; 27% cited a lack of knowledge or misconceptions about immunization; while 29% believed it was because of an issue with the health system. CONCLUSIONS: Throughout PNG there is an urgent need to increase immunization coverage and to ensure that children are immunized on time according to the schedule. Both coverage and timeliness of doses are worse for children living in hard-to-reach and rural areas. Achieving national immunization targets requires improvements in health service delivery, including outreach, especially for remote and rural communities, as well as greater community education and social mobilisation in support of immunization services.

Global control of hepatitis B virus: does treatment-induced antigenic change affect immunization?

Since its widespread introduction, the hepatitis B vaccine has become an essential part of infant immunization programmes globally. The vaccine has been particularly important for countries where the incidence of hepatitis B virus-related hepatocellular carcinoma is high. Effective treatment options for individuals with chronic hepatitis B infection were limited until 1998 when lamivudine, the first nucleoside analogue drug, was introduced. As a single treatment agent, however, lamivudine has a significant drawback: it induces lamivudine-resistant hepatitis B virus strains that may pose a risk to the global hepatitis B immunization programme. Mutations associated with drug treatment can cause changes to the surface antigen protein, the precise part of the virus that the hepatitis B vaccine mimics. However, the emergence of antiviral drug-associated potential vaccine escape mutants (ADAP-VEMs) in treated patients does not necessarily pose a significant, imminent threat to the global hepatitis B immunization programme. Nonetheless, there is already evidence that current treatment regimens have resulted in the selection of stable ADAP-VEMs. Treatment is currently intended to prevent the long-term complications of hepatitis B virus infection, with little consideration given to potential adverse public health impacts. To address individual and public health concerns, trials are urgently needed to find the optimal combination of existing drugs that are effective but do not induce the emergence of ADAP-VEMs. This paper examines the mechanism of antiviral drug-selected changes in the portion of the viral genome that also affects the surface antigen, and explores their potential impact on current hepatitis B immunization programmes.

Measles in Papua New Guinea: an age-specific serological survey.

We aimed to determine the proportion of the population in Madang (Papua New Guinea) immune to measles infection by age groups, with respect to immunization status and study location, using dried blood sampling technology. We performed a prospective cross-sectional sero-survey. Population immunity against measles was sub-optimal (77%) and reported measles vaccine coverage in children <10 years of age was low (41%). The urban population was more susceptible to measles infection, compared with the rural population (66% vs 79% immune, aOR=0.6, p=0.05). Sero-conversion and long term protection rates appeared to be higher when at least one dose of vaccine was provided at or after 12 months of age (84% vs 59%, aOR=4.3, p=0.004). Such a dose is, however, not currently prescribed by the national immunization schedule.

Using immunization delivery strategies to accelerate progress in Africa towards achieving the Millennium Development Goals.

Integration of health services brings together common functions within and between organizations to solve common problems, developing a commitment to a shared vision and goals, and using common technologies and resources to achieve these goals. Integration has been the frustrated rally call of Primary Health Care for 30 years. This paper discusses the process of integrating child survival strategies and other heath services with immunization in Africa. Immunization is arguably the most successful health programme throughout the continent, making it the logical vehicle for add-on services. Strong health systems are the best way of delivering cost-effective child survival interventions in a most sustainable manner. But the reality in many African countries is that health systems have been weak for a number of reasons. Joining additional cost-effective child survival interventions on to immunization services may provide the needed boost. The unacceptably high childhood mortality in parts of Africa makes it the ideal location to undertake this exercise. The urgency to scale-up child survival interventions that have proven cost-effective is especially important if the Millennium Development Goals (MDGs) are to be met by 2015. Africa has more to loose than most in failing to scale up to meet these goals, bearing as it does the highest burden of childhood mortality in the world. But so far, prospects do not look good for achieving MDG-4 for the countries with the highest mortality rates. The timeliness of this initiative towards integration could not be better. In the last five years, countries in Africa have received massive injections of financial resources for polio eradication and measles control as well as additional funding for a range of immunization-strengthening activities and the introduction of new and under-utilized vaccines. While the data to support integration are limited, the information to hand suggests the effectiveness of the strategy. Where immunization performance is strong, immunization contacts may be excellent vehicles for additional interventions such as de-worming or Integrated Management of Childhood Illness (IMCI). But where an immunization service is struggling, adding another child survival intervention on to immunization might be the straw that breaks its back. Health managers have a wide range of options for adding on to immunization services, but the best choice will depend very much on local situations.

Implementing the birth dose of hepatitis B vaccine in rural Indonesia.

Reaching mothers and their newborn infants around the time of birth with adequate health services has long been a difficult problem in developing countries. In parallel, similar problems have arisen in attempting to deliver hepatitis B (HepB) vaccine to infants born at home in many countries where mother-to-infant transmission is common. It is logical, and supported by experience in Indonesia, to find a combined solution for both problems. The World Health Organization (WHO) recommends that a timely birth dose of HepB vaccine be given, particularly in areas of high vertical transmission of hepatitis B virus (HBV). This can be achieved relatively easily in situations where almost all births occur in health facilities. But where a significant proportion of births occur at home and without birth attendants able to give injections, this is much more difficult. Barriers to the timely administration of the birth dose of HepB vaccine include weakness in policy development and implementation, difficulties in reliably supplying potent vaccine to community level, limited transport, poor communication, limited cold chain capacity, lack of effective training, and lack of a clear delineation of responsibility between health care professionals. Demonstration projects, such as those in Indonesia, suggest that there are significant opportunities to improve the timely delivery of HepB vaccine birth dose in existing maternal and child health programmes where health workers are trained to provide home delivery care.

Supervision in primary health care--can it be carried out effectively in developing countries?

There is nothing new about supervision in primary health care service delivery. Supervision was even conducted by the Egyptian pyramid builders. Those supervising have often favoured ridicule and discipline to push individuals and communities to perform their duties. A traditional form of supervision, based on a top-down colonial model, was originally attempted as a tool to improve health service staff performance. This has recently been replaced by a more liberal "supportive supervision". While it is undoubtedly an improvement on the traditional model, we believe that even this version will not succeed to any great extent until there is a better understanding of the human interactions involved in supervision. Tremendous cultural differences exist over the globe regarding the acceptability of this form of management. While it is clear that health services in many countries have benefited from supervision of one sort or another, it is equally clear that in some countries, supervision is not carried out, or when carried out, is done inadequately. In some countries it may be culturally inappropriate, and may even be impossible to carry out supervision at all. We examine this issue with particular reference to immunization and other primary health care services in developing countries. Supported by field observations in Papua New Guinea, we conclude that supervision and its failure should be understood in a social and cultural context, being a far more complex activity than has so far been acknowledged. Social science-based research is needed to enable a third generation of culture-sensitive ideas to be developed that will improve staff performance in the field.

A vaccine cold chain freezing study in PNG highlights technology needs for hot climate countries.

Fourteen data loggers were packed with vaccine vials at the national vaccine store, Port Moresby, Papua New Guinea (PNG), and sent to peripheral locations in the health system. The temperatures that the data loggers recorded during their passage along the cold chain indicated that heat damage was unlikely, but that all vials were exposed to freezing temperatures at some time. The commonest place where freezing conditions existed was during transport. The freezing conditions were likely induced by packing the vials too close to the ice packs that were themselves too cold, and with insufficient insulation between them. This situation was rectified and a repeat dispatch of data loggers demonstrated that the system had indeed been rectified. Avoiding freeze damage becomes even more important as the price of freeze-sensitive vaccines increases with the introduction of more multiple-antigen vaccines. This low-cost high-tech method of evaluating the cold chain function is highly recommended for developing and industrialized nations and should be used on a regular basis to check the integrity of the vaccine cold chain. The study highlights the need for technological solutions to avoid vaccine freezing, particularly in hot climate countries.

When science is not enough - a risk/benefit profile of thiomersal-containing vaccines.

Without a preservative, such as thiomersal (known as thimerosal in the US), multi-dose liquid presentations of vaccine are vulnerable to bacteriological contamination that can result in death or serious illness of the recipient. Concerns about levels of mercury exposure from thiomersal-containing vaccines were first raised in the US during 1999 in the context of Hepatitis B vaccine for newborns. Since then, a large body of evidence from animal and epidemiological studies has accumulated on the safety of thiomersal. Ironically, these data have become largely irrelevant in wealthy countries, where mono-dose, thiomersal-free vaccines have been introduced as a precautionary measure in almost all childhood vaccines, in part related to residual public scepticism. In poor countries, multi-dose vials remain important for vaccine delivery. There is a real danger that this controversy may result in the loss to the world of thiomersal as a preservative, simply from popular pressure. In reality, it would be impossible to cease overnight using thiomersal and maintain the supply of vital vaccines. This paper reviews and summarises the data available from published studies on mercury toxicity, and thiomersal in vaccines in particular, that overwhelmingly indicate continued use of thiomersal is safe in those countries where it is most needed.

Progress in the control of hepatitis B infection in the Western Pacific Region.

Hepatitis B virus infection is a serious problem globally, and particularly in the Western Pacific Region where the population suffers disproportionately from the infection and its sequelae. By 2001, every immunization programme in the Region had included hepatitis B vaccine in their schedule. However, many challenges remain if every one of the 26 million children born in the 37 countries and areas of the Region each year is to be protected against hepatitis B infection. In 2003, the Regional Committee of the World Health Organization's Western Pacific Region resolved to improve hepatitis B control by making it one of two new pillars for strengthening the Expanded Programme on Immunization. The Committee endorsed the strategies of the Regional Plan to improve hepatitis B control through immunization, reducing chronic HBV infection (chronic carriage rate) to less than 1%, and aiming for coverage of at least 80% of the birth cohort in every district with three doses of hepatitis B vaccine by 2005. To help guide this process, an assessment was made of the progress to date, and is reported in this paper. Coverage data used in this evaluation were not independently verified, and could over-estimate progress made in some countries. Whilst there has indeed been great progress in the Region, a number of national programmes still lack the ability to reach all children with immunization services. Other major issues that need to be addressed are the challenges of delivering a timely birth dose, and for certain countries, the affordability of the vaccine over the short- and long-term.

A qualitative evaluation of the immunization program in Papua New Guinea.

OBJECTIVE: An in-depth evaluation of rural immunization services in Papua New Guinea was conducted to determine the reasons for poor immunization coverage, as well as to document the impact of recent efforts to strengthen the national immunization program. METHOD: A qualitative process was used to complement quantitative monitoring data. An interview process, based on open-ended questions, active listening and observation, was designed whereby a team of program supervisors collected information from rural health staff. The teams interviewed health staff in 30 health centres that were selected to provide examples of contrasting field situations. RESULTS: This qualitative review provided valuable detail about why immunization services were failing, encompassing locally specific weaknesses, such as logistic reasons for not conducting outreach, and generic systemic problems such as lack of access to funding. In addition, the information gathered provided details on local solutions developed by better-performing facilities. Both these aspects added significant value to quantitative measures of program performance (derived from national health information system data and analysis of supervision checklists). The review also captured a number of behavioural reasons that will need to be overcome before an improvement in the services can be expected. CONCLUSIONS AND IMPLICATIONS: This in-depth evaluation provided valuable information about problems in peripheral immunization clinics and identified local solutions. The high level of detail collected will be important for planning future strengthening of the health system. The study modelled a supportive form of supervision with the potential to improve outcomes from future supervisory visits. Some of the major barriers to improved immunization were locally specific organizational issues, as well as complex human problems. While some issues can be remedied through further strengthening of immunization systems, others lack easy, rapid solutions.