Modeling the Effect of Herd Immunity and Contagiousness in Mitigating a Smallpox Outbreak.

The smallpox antiviral tecovirimat has recently been purchased by the U.S. Strategic National Stockpile. Given significant uncertainty regarding both the contagiousness of smallpox in a contemporary outbreak and the efficiency of a mass vaccination campaign, vaccine prophylaxis alone may be unable to control a smallpox outbreak following a bioterror attack. Here, we present the results of a compartmental epidemiological model that identifies conditions under which tecovirimat is required to curtail the epidemic by exploring how the interaction between contagiousness and prophylaxis coverage of the affected population affects the ability of the public health response to control a large-scale smallpox outbreak. Each parameter value in the model is based on published empirical data. We describe contagiousness parametrically using a novel method of distributing an assumed R-value over the disease course based on the relative rates of daily viral shedding from human and animal studies of cognate orthopoxvirus infections. Our results suggest that vaccination prophylaxis is sufficient to control the outbreak when caused either by a minimally contagious virus or when a very high percentage of the population receives prophylaxis. As vaccination coverage of the affected population decreases below 70%, vaccine prophylaxis alone is progressively less capable of controlling outbreaks, even those caused by a less contagious virus (R0 less than 4). In these scenarios, tecovirimat treatment is required to control the outbreak (total number of cases under an order of magnitude more than the number of initial infections). The first study to determine the relative importance of smallpox prophylaxis and treatment under a range of highly uncertain epidemiological parameters, this work provides public health decision-makers with an evidence-based guide for responding to a large-scale smallpox outbreak.

Increasing access to care for chronic myeloid leukemia patients: assessment of a scaling-up program.

BACKGROUND: The Glivec International Patient Assistance Program (GIPAP) is designed to provide access to the cancer therapy Imatinib (Glivec⊠), which is indicated for the treatment of chronic myelogenous leukemia (CML) and gastrointestinal stromal tumors (GIST). OBJECTIVES: To identify factors those influence the quality of care and structural improvements. Design . Physicians (n=50), hospital administrators (n=10) and Ministry of Health officials (n=7) in 39 developing countries participated in qualitative interviews. The interviews focused on the impact of GIPAP on service delivery, patient tracking systems and cancer registries, health financing, and workforce. RESULTS: Service delivery, patient management, access to care, diagnostic capacity, and health workers' skills improved at participants' institutions following implementation of GIPAP. CONCLUSIONS: Positive institutional changes that improve care of CML/GIST patients arose from GIPAP. Some of these changes may strengthen institutions' capacity to treat other diseases as well. The GIPAP model could be deployed to improve access to care for patients with other chronic diseases.

Improving access to care in low and middle-income countries: institutional factors related to enrollment and patient outcome in a cancer drug access program.

BACKGROUND: Limited access to drugs is a crucial barrier to reducing the growing impact of cancer in low- and middle-income countries. Approaches based on drug donations or adaptive pricing strategies yield promising but varying results across countries or programs, The Glivec International Patient Assistance Program (GIPAP) is a program designed to provide imatinib free of charge to patients with chronic myeloid leukemia (CML) or gastrointestinal stromal tumors (GIST). The objective of this work was to identify institutional factors associated with enrollment and patient survival in GIPAP. METHODS: We analyzed follow-up data from 4,946 patients participating in 47 institutions within 44 countries between 2003 and 2010. Active status in the program was considered as a proxy for survival. RESULTS: Presence of ≥1 hematologist or oncologist at the institution was associated with increased patient enrollment. After adjusting for individual factors such as age (>55 years: Hazard Ratio [HR] = 1.42 [1.16; 1.73]; p = 0.001) and initial stage of disease (accelerated or blast crisis at diagnosis: HR = 4.16 [1.87; 9.25]; p < 10⁻4), increased survival was found in institutions with research capabilities (HR = 0.55 [0.35; 0.86]; p = 0.01) and those with enrollment of >5 patients/year into GIPAP (HR = 0.48 [0.35; 0.67]; p < 10⁻4), while a non-significant trend for decreased survival was found for treatment at a public institution (HR = 1.32 [0.95; 1.84]; p = 0.10). The negative impact of an accelerated form of CML was attenuated by the presence of ≥1 hematologist or oncologist at the institution (interaction term HR = 0.43 [0.18; 0.99]; p = 0.05). CONCLUSIONS: Application of these findings to the support and selection of institutions participating in GIPAP may help to optimize care and outcomes for CML and GIST patients in the developing world. These results may also be applicable to the treatment of patients with other forms of cancer, due to the overlap of infrastructure and staff resources used to treat a variety of cancer indications. A multi-sector approach is required to address these barriers.

Treating chronic myeloid leukemia: improving management through understanding of the patient experience.

The tremendous progress made in chronic myeloid leukemia (CML) treatment affords patients more options than ever. Five currently available BCR-ABL inhibitors form the mainstay of CML treatment, including first-generation imatinib and more potent second-generation BCR-ABL inhibitors dasatinib and nilotinib, with bosutinib and ponatinib having been recently approved for market inclusion. Studies show that dasatinib and nilotinib exhibit greater efficacy than imatinib in first-line chronic-phase CML (CML-CP), allowing more patients to achieve deeper, more rapid responses associated with improved outcomes. With alternatives to imatinib for first-line CML-CP and the wealth of information (and misinformation) on the Internet, a tremendous need exists for clear, accurate facts to assist patients in making treatment decisions. Patients appreciate the guidance of their oncology nurse in providing disease, treatment, and monitoring information tailored to meet their needs. Oncology nurses who are able to clearly explain emerging data, including the meaning and significance of faster, deeper responses, will be a valuable resource to their patients.

Tecovirimat, a p37 envelope protein inhibitor for the treatment of smallpox infection.

Since the eradication of naturally occurring smallpox in 1980, the fear that variola virus could be used as a biological weapon has become real. Over the last 10 years, emergency preparedness programs have been launched to protect populations against a smallpox outbreak or the possible emergence in humans of other orthopoxvirus infections, such as monkeypox. Vaccination against smallpox was responsible for its eradication, but was linked with high rates of adverse events and contraindications. In this context, intensive research in the poxvirus field has led to the development of safer vaccines and to an increase in the number of anti-poxvirus agents in the pipeline. SIGA Technologies Inc, under license from ViroPharma Inc, is developing tecovirimat (ST-246). Tecovirimat is a novel antiviral that inhibits the egress of orthopoxviruses by targeting viral p37 protein orthologs. The development of tecovirimat during the last 5 years for the treatment of smallpox and for its potential use as adjunct to smallpox vaccine is reviewed here.