Gavi Support for Typhoid Conjugate Vaccines: Moving From Global Investments to Country Introduction.

Nine years elapsed between Gavi's investment decision to support typhoid conjugate vaccines (TCVs) in 2008 and Gavi support becoming available for countries to introduce TCV. The protracted path toward Gavi support for TCV highlights the challenges of vaccine development for lower-income countries and the importance of Gavi engagement as early as possible in product development processes to support the alignment of manufacturing, global policy, and program implementation. Early engagement would provide inputs to inform strategic vaccine investment decisions that transition more efficiently toward country implementation. Several countries have been approved for Gavi support to introduce TCV in 2019-2020. The paucity of generalizable typhoid epidemiological data in early introducing countries has reinforced the need for continued evidence generation regarding typhoid epidemiology and TCV impact. This has led to the development of guidance and tools to support country decision making for TCV introduction based on enhanced understanding of local typhoid burden and risk.

Estimated impact of aggressive empirical antiviral treatment in containing an outbreak of pandemic influenza H1N1 in an isolated First Nations community.

BACKGROUND: The 2009 influenza A (H1N1) pandemic was mild by historical standards, but was more severe in isolated Canadian Indigenous communities. Oseltamivir was used aggressively for outbreak control in an isolated northern Ontario First Nations community. We used mathematical modeling to quantify the impact of antiviral therapy on the course of this outbreak. METHODS: We used both a Richards growth model and a compartmental model to evaluate the characteristics of the outbreak based on both respiratory visits and influenza-like illness counts. Estimates of best-fit model parameters, including basic reproductive number (R0 ) and antiviral efficacy, and simulations, were used to estimate the impact of antiviral drugs compared to social distancing interventions alone. RESULTS: Using both approaches, we found that a rapidly growing outbreak slowed markedly with aggressive antiviral therapy. Richards model turning points occurred within 24 hours of antiviral implementation. Compartmental models estimated antiviral efficacy at 70-95%. Plausible estimates of R from both modeling approaches ranged from 4·0 to 15·8, higher than published estimates for southern Canada; utilization of aggressive antiviral therapy in this community prevented 962-1757 cases of symptomatic influenza and as many as 114 medical evacuations in this community. CONCLUSION: Although not advocated in other settings in Canada, aggressive antiviral therapy markedly reduced the impact of a pandemic-related influenza A (H1N1) outbreak in an isolated Canadian First Nations community in northern Ontario, Canada. The differential risk experienced by such communities makes tailored interventions that consider risk and lack of access to medical services, appropriate.

Characterization of the emerging HIV type 1 and HCV epidemics among injecting drug users in Dushanbe, Tajikistan.

This study aimed to determine HIV, HCV, and syphilis prevalence and correlates, and to characterize the molecular epidemiology of HIV-1 among injecting drug users (IDUs) in Dushanbe, Tajikistan. A cross-sectional study assessing risk factors for HIV and HCV through an interview administered survey was conducted. A total of 491 active adult IDUs were recruited from May to November 2004 in Dushanbe, Tajikistan. HIV-1 antibody status was determined with rapid testing and confirmed with ELISA. HCV antibody testing was conducted using a BIOELISA HCV kit. HIV-1 subtyping was done on a subset with full-length sequencing. Correlates of HIV and HCV infection were assessed using logistic regression. Overall prevalence of HIV was 12.1%, HCV was 61.3%, and syphilis was 15.7%. In a multivariate logistic regression model controlling for gender and ethnicity, daily injection of narcotics [odds ratio (OR) OR 3.22] and Tajik nationality (OR 7.06) were significantly associated with HIV status. Tajik nationality (OR 1.91), history of arrest (OR 2.37), living/working outside Tajikistan in the past 10 years (OR 2.43), and daily injection of narcotics (OR 3.26) were significantly associated with HCV infection whereas being female (OR 0.53) and always using a sterile needle (OR 0.47) were inversely associated with HCV infection. Among 20 HIV-1-positive IDU with specimens available for typing, 10 were subtype A, 9 were CRF02_AG, and one was an A-CRF02_AG recombinant. Epidemics of HIV-1, HCV, and drug use are underway in Dushanbe. The molecular epidemiology is distinctive, with West African variants accounting for roughly 50% of prevalent infections. Targeted prevention programs offering both needle exchange programs and opiate substitution therapies are urgently called for to prevent the further spread of HIV and HCV in Tajikistan.