Immunization in the 21st century--the way forward.

Major changes will impact the way national immunization programmes and services are planned and implemented over the next decade and beyond. This paper presents the most significant health policy contexts, the relevant features of health systems development and new prospects for service delivery. It outlines ways of transforming a dedicated disease control programme, polio eradication, for a broader health agenda. Progress anticipated in research for new vaccines and technologies is described. Reaching the new targets being established will require strong partnerships and the recent creation of the Global Alliance for Vaccines and Immunizations is an important step in this direction.

Herceptest: HER2 expression and gene amplification in non-small cell lung cancer.

HER2 is an erbB/HER type 1 tyrosine kinase receptor that is frequently over-expressed in malignant epithelial tumours. Herceptin, a humanised mouse monoclonal antibody to HER2, is proven therapeutically in the management of metastatic breast cancer, significantly prolonging survival when combined with cytotoxic chemotherapeutic agents. Immunohistochemical studies suggest that non-small-cell lung cancer (NSCLC) tumours may over-express HER2. Our aim was to evaluate HER2 gene amplification and semi-quantitative immuno-expression in NSCLC. A total of 344 NSCLC cases were immunostained for HER2 expression in 2 centres using the HercepTest. Fluorescence in situ hybridisation (FISH) analysis for HER2 gene amplification was performed on most positive cases and a subset of negative cases. Fifteen cases (4.3%) demonstrated 2+ or 3+ membranous HER2 immuno-expression. There was no correlation between immuno-expression and tumour histology or grade. Tumours from higher-stage disease were more often HercepTest-positive (p < 0.001). All 4 HercepTest 3+ cases demonstrated gene amplification. One of the 5 2+ cases tested for gene amplification showed areas of borderline amplification and areas of polyploidy. None of the 19 HercepTest-negative cases demonstrated gene amplification or polyploidy (p < 0.001). Gene amplification was demonstrated in all HercepTest 3+ scoring NSCLC cases. Unlike breast cancer, gene amplification and HER2 protein over-expression assessed by the HercepTest appeared to be uncommon in NSCLC. Herceptin may therefore target only a small proportion of NSCLC tumours and be of limited clinical value in this disease, particularly in the adjuvant setting.

The legacies of polio eradication.

PIP: Over the years, it has been made clear that the eradication drive of polio virus is on the way to a successful conclusion even in countries driven by conflict or with only rudimentary health services. Worldwide, in the 11 years since the World Health Assembly passed a resolution to eradicate polio, estimated numbers of paralytic polio cases have fallen from over 400,000 to under 20,000 a year. However, although qualitative evaluations in countries have mainly positive findings, strong negative effects were found related to the targeting strategy, and to a lesser degree to the involvement of leaders. Nevertheless, it is noted that any negative effects are surpassed by the tremendous legacies that the polio eradication initiative will leave. These legacies include 1) removal of the suffering caused by the disease; 2) monetary savings on the treatment and prevention of polio; 3) a stronger infrastructure for routine immunization, disease surveillance, health management, and the delivery of other health interventions; 4) greater visibility of health services generally and immunization in particular; and 5) establishment of a platform for preventive health services.^ieng

Disease eradication as a public health strategy: a case study of poliomyelitis eradication.

Disease eradication as a public health strategy was discussed at international meetings in 1997 and 1998. In this article, the ongoing poliomyelitis eradication initiative is examined using the criteria for evaluating candidate diseases for eradication proposed at these meetings, which covered costs and benefits, biological determinants of eradicability (technical feasibility) and societal and political considerations (operational feasibility). The benefits of poliomyelitis eradication are shown to include a substantial investment in health services delivery, the elimination of a major cause of disability, and far-reaching intangible effects, such as establishment of a "culture of prevention". The costs are found to be financial and finite, despite some disturbances to the delivery of other health services. The "technical" feasibility of poliomyelitis eradication is seen in the absence of a non-human reservoir and the presence of both an effective intervention and delivery strategy (oral poliovirus vaccine and national immunization days) and a sensitive and specific diagnostic tool (viral culture of specimens from acute flaccid paralysis cases). The certification of poliomyelitis eradication in the Americas in 1994 and interruption of endemic transmission in the Western Pacific since March 1997 confirm the operational feasibility of this goal. When the humanitarian, economic and consequent benefits of this initiative are measured against the costs, a strong argument is made for eradication as a valuable disease control strategy.

Disease eradication and health systems development.

This article provides a framework for the design of future eradication programmes so that the greatest benefit accrues to health systems development from the implementation of such programmes. The framework focuses on weak and fragile health systems and assumes that eradication leads to the cessation of the intervention required to eradicate the disease. Five major components of health systems are identified and key elements which are of particular relevance to eradication initiatives are defined. The dearth of documentation which can provide "lessons learned" in this area is illustrated with a brief review of the literature. Opportunities and threats, which can be addressed during the design of eradication programmes, are described and a number of recommendations are outlined. It is emphasized that this framework pertains to eradication programmes but may be useful in attempts to coordinate vertical and horizontal disease control activities for maximum mutual benefits.

Progress toward global polio eradication.

Significant progress is being made towards the global eradication of poliomyelitis by the year 2000. The strategies recommended by the World Health Organization for polio eradication are as follows: maintaining high routine immunization coverage; conducting nationwide mass immunization campaigns; building effective, laboratory-based surveillance for acute flaccid paralysis; and conducting localized immunization campaigns directed at the final reservoirs of virus transmission. Sixty-three countries have conducted nationwide anti-polio immunization campaigns. Three hundred million children were immunized in these campaigns worldwide in 1995. The reported incidence of poliomyelitis has fallen by approximately 80% since the global target was set in 1988, and the geographic range of polio is being restricted. The major challenges for achieving eradication are establishing effective surveillance systems in all countries and mobilizing the resources needed to fully implement the recommended strategies in the 67 countries in which polio remains endemic.

Disease eradication as a public health strategy: is measles next?

Following the failure of disease eradication efforts in the first half of this century, the success of smallpox eradication and the ongoing initiatives against poliomyelitis and dracunculiasis are re-establishing eradication as a viable disease control strategy. The perpetual benefits of eradication, together with the positive impact that such initiatives can have on health services in general, are changing the world's perception of these endeavours. Among the most obvious examples of this changing trend is the recent enthusiasm in both industrialized and developing countries for re-exploring the eradicability of measles. Increasingly, it appears that measles, the single leading cause of vaccine-preventable childhood morbidity and mortality worldwide, may be the next major organism targeted for global eradication.

Regional cerebral blood flow in chronic alcoholics measured by single photon emission computerized tomography.

Regional cerebral blood flow (CBF) was measured by single photon emission computerized tomography of inhaled 133-Xe in 20 chronic alcoholic men. Mean CBF was 51 ml/(100 g x min) compared with 53 ml/(100 g x min) in 20 normals. Reduced cerebellar blood flow correlated both to structural abnormalities seen on CT scan and to cognitive dysfunction. Slight abnormalities of the regional CBF was observed in the alcoholics. They had a higher incidence of regional low flow areas than a control group. Low flow areas were found in frontal and posterior parts of the brain not only in patients with atrophia, but also in patients without CT abnormalities, suggesting neuronal dysfunction. The occurrence of regional low flow areas was associated with the severity of alcoholism, cerebral atrophy and intellectual impairment.

Hypothalamic-pituitary and thyroid function in chronic alcoholics with neurological complications.

Endocrinological tests were performed in 14 chronic alcoholic men with signs of intellectual impairment and/or peripheral neuropathy. All had been abstinent from alcohol for at least 1 month. Basal serum growth hormone (GH) was consistently increased in only one patient whereas the GH responses to insulin hypoglycemia stimulation was normal in all patients. Thyroid function values (T4, T3, rT3, TSH) were normal in all patients whereas baseline serum prolactin values were significantly increased in alcoholics as compared with a control group. In a combined TRH- and GnRH-stimulation tests, GH-responses were also normal whereas TSH and prolactin responses were blunted or absent in about half of the patients, the responses correlating significantly (p less than 0.01). It is concluded that disturbances in the hypothalamic-pituitary axis may occur in chronic alcoholics with nervous impairment independently of the physical deterioration, which often is associated with chronic alcoholism.

Branched chain enriched amino acid versus glucose treatment of hepatic encephalopathy. A double-blind study of 65 patients with cirrhosis.

We studied the effects of infusion of a branched chain enriched amino acid mixture versus glucose on acute hepatic encephalopathy in patients with cirrhosis. Sixty-five patients were randomly treated with 1 g/kg per day of an amino acid mixture with 40% branched chain contents (32 patients), or isocaloric glucose (33 patients) for a maximum of 16 days. The regimens further included glucose infusion to a total of 26.5 kcal/kg per day and lactulose. The patients took part in the study for 5-6 days. In each group 17 patients woke up. In the amino acid group eleven died and four developed renal failure. In the glucose group ten died, three developed renal and two respiratory failure, and one remained encephalopathic. The coma score worsened in three of the patients who died in the amino acid group, but in all patients who died in the glucose group. The negative nitrogen balance on entry reversed in the amino acid group, but not in the glucose group. Thus, the branched chain enriched amino acid supplement did not change the prognosis for wake-up, but had other effects on the cerebral state and on nitrogen homeostasis.