diarrhoea and jaundice) with lymphadenopathy developing only rarely.Trypanosomal chancre
Systemic disease is sometimes presaged by a trypanosomal chancre developing at the site of the infectious fly bite within 2 days of infection. The chancre is most commonly observed in T. b. rhodesiense infection, and only rarely in T. b. gambiense (however, in T. b. gambiense infection, chancres are more common in persons from non-endemic areas). Hemolymphatic phase
Incubation period is 1–3 weeks for T. b. rhodesiense, and longer (but less precisely characterised) in T. b. gambiense infection. The first/initial stage, known as the hemolymphatic phase, is characterized by non-specific, generalised symptoms like: fever (intermittent), headaches (severe), joint pains, itching, weakness, malaise, fatigue, weight loss, lymphadenopathy, and hepatosplenomegaly.Diagnosis may be delayed due to the vagueness of initial symptoms. The disease may also be mistaken for malaria (which may in fact occur as a co-infection).Intermittent fever
Fever is intermittent, with attacks lasting from a day to a week, separated by intervals of a few days to a month or longer. Episodes of fever become less frequent over the course of the disease.Lymphadenopathy
Invasion of the circulatory and lymphatic systems by the parasite is associated with severe swelling of lymph nodes, often to tremendous sizes. Posterior cervical lymph nodes are most commonly affected, however, axillary, inguinal, and epitrochlear lymph node involvement may also occur. Winterbottoms sign, the tell-tale swollen lymph nodes along the back of the neck, may appear.
This downwards trend leaves a gap for other funders, such as philanthropic foundations and private pharmaceutical companies to fill.Much of the progress that has been made in African sleeping sickness and neglected disease research as a whole is a result of the other non-public funders. One of these major sources of funding has come from foundations, which have increasingly become more committed to neglected disease drug discovery in the 21st century. In 2012, philanthropic sources provided 15.9% of the total funding. The Bill and Melinda Gates Foundation has been a leader in providing funding for neglected disease drug development. They have provided $444.1 million US dollars towards neglected disease research in 2012. To date, they have donated over $1.02 billion US dollars towards the neglected disease discovery efforts.For kinetoplastid infections specifically, they have donated an average of $28.15 million US dollars annually between the years 2007 to 2011. They have labeled human African trypanosomiasis a high-opportunity target meaning it is a disease that presents the greatest opportunity for control, elimination, and eradication, through the development of new drugs, vaccines, public-health programs, and diagnostics. They are the second-highest funding source for neglected diseases, immediately behind the US National Institutes of Health. At a time where public funding is decreasing and government grants for scientific research are harder to obtain, the philanthropic world has stepped in to push the research forward. Another important component of increased interest and funding has come from industry.