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In 1999 Project HOPE initiated the Child Survival Program in Uzbekistan. Working with the Ministry of Health, local organizations, and encouraging family support, HOPE focused on reducing mortality and morbidity in children under five and mothers of reproductive age and also increasing adolescent's knowledge of reproductive and sexual health. The program addressed issues such as breastfeeding, pneumonia, diarrhea, nutrition, family planning and maternal newborn care. A baby friendly hospital initiative was implemented along with adolescent friendly services at both the clinical and community level.

In 2002 Project HOPE lead a group of international NGOs implementing the Healthy Family Program, a large-scale maternal, child, and reproductive health initiative, across three of the largest and most populous countries in Central Asia, Project HOPE was able to broker a national and regional policy in support of the plan.

HOPE's mission later grew to include the region-wide tuberculosis program with the goal of improving the effectiveness of the health system in response to Tuberculosis (TB). Project HOPE initiated an anti-TB strategy in Uzbekistan by implementing Directly Observed Therapy-Short Course (DOTS) in 2004. HOPE began another program to improve TB control in 2009 in Samarkand Oblast by implementing a TB management system and infection control training.

Also in 2008, Project HOPE responded to the Pandemic and Avian Influenza by implementing a technical assistance and training program in Uzbekistan. Regional governments were trained on public communications strategies for the prevention, identification and control of the spread of the avian influenza virus.

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