System-Wide Investments Enhance HIV, TB and Malaria Control in Malawi and Deliver Greater Health Impact

Global health initiatives have expanded access to treatment for infectious diseases - especially HIV, tuberculosis, and malaria (HTM) - in low- and middle-income countries. However, these "vertically"-funded programs often operate within fragile health systems, where workforce shortages and supply chain failures constrain their effectiveness and sustainability 1,2. Meanwhile, evaluating the health impact and value-for- money of "horizontal" investments in systems, such as supply chain strengthening or boosting healthcare workforce, and their synergies with vertical programs (through "diagonal" investments combining both) - remains challenging because their benefits are mediated through improvements in many aspects of healthcare delivery and are therefore difficult to measure3. Using a dynamic microsimulation model of Malawis healthcare system, we show that a diagonal investment approach yields a four-fold greater health impact, measured in disability-adjusted life years (DALYs) averted, than the vertical approach. This approach not only improves health outcomes for non-HTM causes of DALYs but also amplifies the effect on DALYs caused by HTM. Additionally, diagonal investments offer greater value for money and a 24.94% higher return on investment (6.67 [5.81 - 6.85] compared with 5.34 [3.44 - 6.24]), even after accounting for their additional costs. Our findings demonstrate that HSS investments generate synergistic effects, amplifying the benefits of GHIs while also strengthening broader healthcare delivery. These results support a shift toward more integrated global health financing strategies.