Hemophilia is a rare X-linked hereditary bleeding disorder, caused by a mutation in the F8 or F9 gene. In the last 50 years, hemophilia treatment has changed tremendously and the impact of these... Show moreHemophilia is a rare X-linked hereditary bleeding disorder, caused by a mutation in the F8 or F9 gene. In the last 50 years, hemophilia treatment has changed tremendously and the impact of these changes on current clinical outcomes is unknown.Therefore, we comprehensively assessed the changes in health status over time of patients with hemophilia using observational study data. Our results show that clinical outcomes of these patients have improved tremendously over the past decades. The annual bleeding rate and the proportion of patients with joint impairment have decreased strongly. In addition, HCV has almost been eradicated among patients with hemophilia in the Netherlands. As a result, life expectancy has increased to where it is almost equal to that of the general population.Although clinical outcomes have improved in many ways, inhibitor development continues to be a significant problem in patients treated with clotting factor products. Therefore, using three different study approaches, we also evaluated several methods to better predict the risk of inhibitor development (which is still a significant complication of treatment with FVIII). The results of these studies are promising and could be used to improve current inhibitor prediction strategies and inform future research on this topic. Show less
An estimated 6 million individuals are co-infected with HIV and schistosomiasis. This thesis seeks to add to the comprehension of the epidemiology of HIV and schistosome co-infections in Tanzania,... Show moreAn estimated 6 million individuals are co-infected with HIV and schistosomiasis. This thesis seeks to add to the comprehension of the epidemiology of HIV and schistosome co-infections in Tanzania, by Lake Victoria. It first evaluates Tanzania’s progress regarding HIV care and defines the study population and the challenges it faces in the fight against co-infections. It then explores the impact of Schistosoma infection on HIV outcomes and transmission. One of the main findings is that people who were infected with Schistosoma when they also acquired HIV infection, on average survive longer and have slower decline in CD4 counts than those who were not infected with Schistosoma in the first place. This thesis also shows that individuals with HIV and Schistosoma spp. co-infections have lower viral loads than those with HIV alone, when accounting for time infected with HIV, and estimates the first hazard rate of HIV transmission from co-infected partners. Finally, this thesis explores the impact of HIV infection on the detection of Schistosoma in co-infected people and concludes that co-infected individuals and women are less likely to excrete parasite eggs. Both local and systemic interactions are discussed in light of those results. Show less
Schistosomiasis is a helminthic worm infection that affects 260 million people worldwide, 90% of whom live in sub-Saharan Africa. In Tanzania, where the research in this thesis was conducted, two... Show moreSchistosomiasis is a helminthic worm infection that affects 260 million people worldwide, 90% of whom live in sub-Saharan Africa. In Tanzania, where the research in this thesis was conducted, two species of schistosomes are highly endemic (Schistosoma haematobium and S. mansoni), with more than 50% of adults infected with one or both schistosome species in many regions. In and of itself, schistosomiasis causes significant morbidity and mortality, with an estimated 200,000 deaths annually and 3.31 million disability-adjusted life-years. The possibility that it additionally impacts HIV transmission and disease progression render treatment and control of this neglected tropical disease even more urgent. This thesis focuses on HIV prevention and disease management in sub-Saharan Africa. It will first describe population-based epidemiological work in Tanzania associating HIV with S. haematobium and with S. mansoni. Subsequent chapters focus on treatment of S. haematobium infection in women, where it causes genital tract disease, and on the effects of schistosome infection on immunological response to treatment in people living with HIV infection. The final chapter focuses on implementation science work with high potential to improve HIV prevention and early diagnosis in Tanzania. Show less
The immune response upon (influenza, pneumococcal and rabies) vaccination in immunocompromized patients (HIV, anti-TNF, HSCT patients) has been studied.
