**15. Prevention and control**

**12. Clinical signs and symptoms**

220 Encephalitis

height of fever (Faget's sign). The average fever is 39o

risk for fatal hemorrhage at the biopsy site [67].

**13. Diagnosis of YF**

**14. Treatment**

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

Clinical diagnosis of yellow fever is possible when the pathognomonic features of biphasic/ triphasic acute illness and typical clinical features occur in unvaccinated individuals with a compatible exposure history. Unfortunately, these features are present only in a minority of patients [67]. Laboratory confirmation of YF is pivotal to diagnosis, but unfortunately re‐ quires highly trained laboratory staff with access to specialized equipment and materials.

Laboratory diagnosis of YF is made by detection of either virus or virus antigen or genome (by enzymelinkedimmunosorbent assay (ELISA), polymerase chain reaction (PCR), or inoc‐ ulation virus into suckling mice, mosquitoes, or cell cultures), or by serology (immunoglo‐ bulin M capture ELISA), though cross-reactions with other flaviviruses complicate serologic methods of diagnosis. Postmortem examination of the liver reveals pathognomonic features of YF, including mid-zonal necrosis, and definitive diagnosis can be made by immunohisto‐ chemical staining of tissues (liver, heart, kidneys) for yellow fever antigen. It is important to note that liver biopsy should never be used for diagnosis during YF illness because of the

In the absence of specific therapy, treatment of YF is chiefly supportive. Because most YF cases occur in areas lacking basic hospital facilities and where patients do not have access to modern intensive care. In the early stages of the disease, therapy should focus on controlling

C and lasts for 3.3 days.

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.

#### **15.1. Yellow fever vaccine**

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

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 administered at 12 months of age. In the case of outbreaks, it can be administered as early as 6 months of age [71]. Yellow fever vaccine is a live vaccine, so theoretically it should not be given to pregnant women or to immunosuppressed individuals. A single fatal adverse reac‐ tion (encephalitis) has been reported in an immunosuppressed individual with HIV/AIDS.

ceptionally helpful to the travelers, who visit for a short-span of time in the disease endemic areas. The main advantage is that the repellents are relatively cheap, highly effective and

Yellow Fever Encephalitis: An Emerging and Resurging Global Public Health Threat in a Changing Environment

http://dx.doi.org/10.5772/46041

223

A laboratory study was carried out to evaluate the relative efficacy of N-N-diethylm-tolua‐ mide (DEET) and N,N-diethyl-phenylacetamide (DEPA)-treated wristbands against three major vector mosquitoes. Overall, both DEET and DEPA have shown various degrees of re‐ pellency impact against all three vector mosquitoes. DEPA treated wristbands did not show any significant differences in terms of reduction in human landing rate and the mean com‐ plete protection time against *An. stephensi* and *Ae. aegypti* were between 1.5 and 2.0 mg/cm2 [77]. A study revealed the repellent efficacy of dimethyl-phthalate (DMP) treated wristband against *Ae. aegypti* under the laboratory conditions. It is estimated that 74.4 and 86.5% of re‐ duction of man landing rates were obtained against *Ae. aegypti* at concentrations of 1.5 and 2.0 mg/cm2 respectively [1]. These studies results suggest that repellent-treated fabric strips could serve as a means of potential personal protection expedient to avoid insect's annoy‐

However, generally synthetic repellents have several limitations, including reduced efficacy owing to sweating, unpleasant odor, relatively expensive and can cause allergic reactions [72]. Plants have been used since ancient times to repel/kill blood-sucking insects in the hu‐ man history and even now, in many parts of the world, people use plant substances to drive-away the mosquitoes and other blood-sucking insects [78]. Currently repellents of plant origin have been receiving massive attention due to their environmental and user

It is unlikely that vector control strategies alone will result in the elimination of yellow fe‐ ver; such strategies must be combined with effective vaccination programs. Besides, in YF endemic countries, people particularly travelers should take precautions to avoid mosqui‐ to bites to reduce the risk of yellow fever. Besides, using insect repellents, people must use permethrin-impregnated clothing, and bed nets and staying in the screened room

YF has played a central role in the history of infectious diseases. It was the first disease to be demonstrated to be transmitted by an arthropod, one of the first diseases to be shown to be caused by a virus, and one of the first infectious agents to be controlled by the development of a live vaccine [80]. Indeed, the challenges and dangers posed by yellow fever remain for‐ midable. It is mainly contributed by the global warming, land use changes, uncontrolled population growth, unchecked urbanization, rural - urban migration, international trade, conflict and civil disruption. Although the tools for diagnosis, vector control, vaccine and surveillance are available, their implementation is extremely poor or inadequate in many of the resource-constrained YF endemic countries. In addition, the global-warming concomi‐

can be applied as a short-term measure [76].

ance and to reduce vector-borne disease transmission.

friendly nature [79].

could be advisable.

**16. Conclusion**

#### **15.2. Vector control**

Vector control is defined as measures of any kind directed against a vector of disease and intended to limit its ability to transmit the disease [72]. In yellow fever control specifically in certain circumstances, mosquito control is vital until vaccination takes effect.

#### *15.2.1. Source reduction*

The risk of yellow fever transmission in urban areas can be reduced by eliminating potential mosquito breeding sites and applying insecticides to water where they develop in their im‐ mature stages [13]. Indeed, source reduction is one of the key components in the vector con‐ trol programme since the target is exceptionally specific unlike adult control [73]. Vectorcontrol strategies that were once successful for elimination of yellow fever from many regions have faltered, leading to reemergence of the disease[3]. Application of spray insecti‐ cides to kill adult mosquitoes during urban epidemics, combined with emergency vaccina‐ tion campaigns, can reduce or halt yellow fever transmission and the "buying time" for vaccinated populations to build immunity [13].

Historically, mosquito control campaigns successfully eliminated *Ae. aegypti*, the urban yel‐ low fever vector, from most mainland countries of central and South America. However, this mosquito species has re-colonized urban areas in the region and poses a renewed risk of urban yellow fever. Mosquito control programmes targeting wild mosquitoes in forested areas are not practical for preventing jungle (or sylvatic) yellow fever transmission [13]. The period between about 1950 and the 1970s was one of the complacency about the control of YF, probably arising from the feeling that YF vaccination had solved the problem. *Ae. aegypti* control was reduced and overall disease record keeping appears to have diminished. For the period 1960–2005, only 110 yellow fever points were recorded in Africa and 171 in South America. In both regions, these records more or less fall within the same areas of risk shown for the first half of the last century, although there is a noticeable lack of new records in Cen‐ tral America and proportionately more cases within the Amazon basin [33].

#### *15.2.2. Insect repellents*

*Ae. aegypti*, has adapted their peak biting activities in the early evening and early morning, when their potential hosts are less protected. Mosquito repellents have a unique role under these conditions. Easily accessible, safe and effective mosquito repellents provide a valuable supplement to IRS and ITN use, and in areas with day-biting, exophagic vectors, this may be the only option for reducing the level of disease transmission [74]. The core principle of re‐ pellents usage is that they are extremely useful and helpful whenever and wherever other personal protection measures are impossible or impracticable [75]. Insect repellents are ex‐ ceptionally helpful to the travelers, who visit for a short-span of time in the disease endemic areas. The main advantage is that the repellents are relatively cheap, highly effective and can be applied as a short-term measure [76].

A laboratory study was carried out to evaluate the relative efficacy of N-N-diethylm-tolua‐ mide (DEET) and N,N-diethyl-phenylacetamide (DEPA)-treated wristbands against three major vector mosquitoes. Overall, both DEET and DEPA have shown various degrees of re‐ pellency impact against all three vector mosquitoes. DEPA treated wristbands did not show any significant differences in terms of reduction in human landing rate and the mean com‐ plete protection time against *An. stephensi* and *Ae. aegypti* were between 1.5 and 2.0 mg/cm2 [77]. A study revealed the repellent efficacy of dimethyl-phthalate (DMP) treated wristband against *Ae. aegypti* under the laboratory conditions. It is estimated that 74.4 and 86.5% of re‐ duction of man landing rates were obtained against *Ae. aegypti* at concentrations of 1.5 and 2.0 mg/cm2 respectively [1]. These studies results suggest that repellent-treated fabric strips could serve as a means of potential personal protection expedient to avoid insect's annoy‐ ance and to reduce vector-borne disease transmission.

However, generally synthetic repellents have several limitations, including reduced efficacy owing to sweating, unpleasant odor, relatively expensive and can cause allergic reactions [72]. Plants have been used since ancient times to repel/kill blood-sucking insects in the hu‐ man history and even now, in many parts of the world, people use plant substances to drive-away the mosquitoes and other blood-sucking insects [78]. Currently repellents of plant origin have been receiving massive attention due to their environmental and user friendly nature [79].

It is unlikely that vector control strategies alone will result in the elimination of yellow fe‐ ver; such strategies must be combined with effective vaccination programs. Besides, in YF endemic countries, people particularly travelers should take precautions to avoid mosqui‐ to bites to reduce the risk of yellow fever. Besides, using insect repellents, people must use permethrin-impregnated clothing, and bed nets and staying in the screened room could be advisable.
