**12. Clinical signs and symptoms**

YF is the original viral haemorrhagic fever (VHF), a pansystemic viral sepsis with viraemia, fever, prostration, hepatic, renal, and myocardial injury, haemorrhage, shock, and high le‐ thality. Patients with yellow fever suffer with a terrifying and untreatable a clinical disease as yellow fever is responsible for 1000-fold more illness and death than Ebola. Yellow fever stands apart from Ebola and other VHFs in its severity of hepatic injury and the universal appearance of jaundice [10]. It is difficult to distinguish YF' clinically from many other tropi‐ cal diseases and often impossible when the condition is mild or atypical. The clinical symp‐ toms associated with the early stages of YF infection are indistinguishable from those of malaria, and where the two diseases coexist, YF should not be ruled out even in the absence of jaundice or the finding of malaria parasites in a blood smear [64,65]. The clinical disease varies from non-specific abortive illness to fatal haemorrhagic fever [66]. Disease onset is typically abrupt, with fever, chills, malaise, headache, lower back pain, generalised myalgia, nausea, and dizziness. On physical examination the patient is febrile and appears acutely ill, with congestion of the conjunctivae and face and a relative bradycardia with respect to the height of fever (Faget's sign). The average fever is 39o C and lasts for 3.3 days.

the fever and vomiting, relieving the headache and abdominal pains, and correcting the de‐ hydration. During the hepatorenal phase, suitable therapy based on careful patient monitor‐ ing should be administered to control the bleeding and manifestations associated with hepatorenal damage. Appropriate treatment to control malaria and secondary bacterial in‐

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Because no antiviral treatment exists for the disease, prevention through use of personal protection measures and vaccination is crucial to lower disease risk and mortality [14]. A number of approaches have been taken to control YF. Historically, the development of live vaccines was used to control the disease in Africa, whereas mosquito vector control was used in the Americas. Following the demonstration that YFV is transmitted by *Ae. aegypti* came the realization that it should be possible to control the disease by controlling mosquito populations [26]. The re-emergence of yellow fever in Africa and South America during the past decade tempers previous optimism that this disease as a public health problem could be eliminated during the twentieth century [15]. Vaccination and eradication of *Ae. aegypti* are the only effective strategies to reduce YF morbidity and mortality in the affected areas.

Yellow fever vaccine is given for two reasons: to protect travellers visiting areas with the risk of yellow fever virus transmission and to prevent the international spread by minimiz‐ ing the risk of importation and translocation of the virus by viraemictravellers [14]. Follow‐ ing the successful isolation of YFV in 1927 by American (strain Asibi) and French (strain French viscerotropic virus) workers, researchers placed great effort on the development of vaccines. The development of two live vaccines in the 1930s represents a milestone in the control of the disease. Strain Asibi was passaged through chicken tissue to develop the 17D vaccine strain, whereas strain French viscerotropic virus was passaged through mouse brain to develop the French neurotropic vaccine (FNV). Both vaccines are highly efficacious and they dramatically reduced the number of YF cases in Africa. Unfortunately, the FNV caused cases of postvaccinal neurotropic disease in vaccinees and was discontinued in 1971, where‐

Although immunity from vaccination probably lasts for a lifetime [68,69], a 10 year interval between vaccinations is stipulated in the International Health Regulations (2005) for individ‐ uals travelling to countries with a yellow fever vaccination entry requirement. The Interna‐ tional Certificate of Vaccination or Prophylaxis is a traveler's official documentation and it becomes valid 10 days after vaccination and remains so for 10 years [36]. Re-immunization is required every 10 years to maintain a valid international vaccination certificate. The World Health Organization recommends vaccination of children at 9 months old, concomi‐ tant with measles vaccination, because of better cost/benefit analysis than campaign vaccina‐ tions to control outbreaks [70]. It is recommended that the yellow fever vaccine be

fections should be administered when necessary [64,65].

as 17D is still used today throughout the world [26].

**15. Prevention and control**

**15.1. Yellow fever vaccine**
