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Abstract and Introduction
Abstract
Protein conjugate bacterial vaccines for invasive pneumococcal diseases have revolutionized the epidemiology of invasive bacterial disease in young children in most of the developed world, but only a small proportion of children at greatest risk of dying from this disease are vaccinated in less developed countries. Pneumococcal disease kills more children than any other illness - more than AIDS, malaria and measles combined. While the noble effort of international agencies to promote the use of pneumococcal vaccines is commendable, studies from several developing countries have failed to recognize invasive pneumococcal disease as a major problem. Thus, even at considerably subsidized vaccine pricing, this failure to recognize the pneumococcal disease burden will deter the introduction of vaccine programs in areas where it is most needed. This lack of awareness creates an impassé for the acceptance of a 'solution'. Whether this absence of evidence is real or simply misleading deserves further urgent evaluation. Such an evaluation could propose the use of the vaccine as a 'probe' for defining the problem. In settings where disease burden is likely to be highest, disease surveillance is nonexistent, childhood immunization programs are fractured or nonexistent, and there is no system to ensure delivery, even if the vaccine is offered free of charge. Ongoing challenges with global polio eradication programs suggest that, critical to the success of any immunization program, is investment in setting up credible disease surveillance systems for vaccine preventable diseases to generate local or regional disease burden data. This will promote local ownership of any immunization programs and reveal myths about a 'hidden agenda' by foreign vaccine manufacturers.
Introduction
In the past decade, better measures of pneumococcal disease incidence in children have evolved than exist for most other bacterial infections of childhood. Estimates based on reasonable assumptions suggest that the pneumococcus causes between 1 and 4 million episodes of pneumonia in the developing countries of Africa and at least 800,000 deaths in other developing countries worldwide. Estimates from three studies in sub-Saharan Africa suggest that the incidence of invasive pneumococcal disease (IPD) in children under 5 years of age range from 111 to 436 out of 100,000 per year. However, IPD represents only a small fraction of all pneumococcal disease, most of which present as nonbacteremic pneumonia (Figure 1). In the efficacy trial in The Gambia, there were 15 cases of radiologically confirmed pneumonia prevented by the nine-valent pneumococcal conjugate vaccine (PCV-9) for every two cases of IPD prevented. Extrapolating to estimate the IPD burden predicts that there are approximately 1-4 million cases of radiologically confirmed pneumococcal pneumonia in children in the developing countries of Africa each year.
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Figure 1.
Pneumococcal clinical syndromes.
A trial of PCV-9 in The Gambia demonstrated 77% (95% CI: 51-90%) efficacy against IPD with a 16% (95% CI: 3-28%) improvement in overall child survival, a testament to the hitherto poorly appreciated role of this agent as a major killer. This and other efficacy trials of PCVs in the USA and South Africa provided the impetus for the recommendation by the WHO in 2007 for the use of PCVs in developing countries. Although the nine-valent vaccine was not licensed, the seven-valent vaccine Prevnar and, more recently, Synflorix (GlaxoSmithKline Biologicals, Rixensart, Belgium), the Haemophilus influenzae protein D-conjugated vaccine containing serotypes 1, 5 and 7F in addition to the serotypes included in Prevnar, were licensed in Europe, Canada and Australia. The time lag between the introduction of a vaccine in a developed country and a developing country has taken as long as 20-30 years, as happened with H. influenzae type b (Hib) conjugate and hepatitis B vaccines. Thus, the accelerated introduction of a new vaccine into populations with high disease incidence and mortality is commendable but the case with Prevnar, in settings with a different disease epidemiology, is complex and deserves a cautious evaluation. In most developing countries, lack of epidemiologic data on disease burden or poor perception of disease burden, and lack of adequate surveillance tools for disease, the potential for replacement disease by nonvaccine serotypes and the readiness of recipient countries for the introduction of this vaccine all pose a significant challenge to the successful implementation of this recommendation. In this review, the appropriateness of the WHO recommendation and the opportunities and challenges that may be associated with this recommendation are debated.
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