Yellow fever is a viral infection that usually lasts only a few days. Fever, chills, lack of appetite, nausea, muscular pains – notably in the back – and headaches are the most common symptoms. Symptoms usually go away after five days. In roughly 15% of patients, the fever returns the next day, stomach discomfort sets in, and liver damage sets in, resulting in yellow skin. If this happens, there’s a higher chance of bleeding and renal issues.
The yellow fever virus causes the sickness, which is conveyed by the bite of an infected mosquito. It exclusively infects humans, other primates, and some mosquito species. It is typically carried in cities by Aedes aegypti, a mosquito species widespread across the tropics and subtropics.
The virus is an RNA virus belonging to the Flavivirus genus. It might be difficult to distinguish the condition from other ailments, especially in its early stages. Blood-sample testing using polymerase chain reaction is necessary to confirm a probable cause.
Yellow fever may be prevented with a safe and efficient vaccine, and some countries require tourists to get vaccinated. Reducing the number of transmitting mosquitoes is another way to prevent illness. To avoid epidemics in places where yellow fever is widespread, it is critical to diagnose illnesses early and immunize large populations. Once a person has been infected, there are no particular actions that can be taken to combat the infection. Up to half of the individuals who develop a serious sickness die.
Signs and symptoms
After a three to the six-day incubation period, yellow fever strikes. Fever, headache, chills, back pain, exhaustion, lack of appetite, muscular discomfort, nausea, and vomiting are the most common symptoms. The infection only lasts three to six days in many circumstances.
However, 15% of patients develop a second, toxic phase of the condition, which is marked by recurrent fever, this time accompanied by jaundice from liver damage and stomach discomfort.
Vomit-containing blood is caused by bleeding in the mouth, nose, eyes, and gastrointestinal system, thus the Spanish term for yellow fever, is vómito negro (“black vomit”). Kidney failure, hiccups, and delirium are all possibilities.
The death rate among individuals who develop jaundice is 20 to 50 percent, while the total fatality rate is 3 to 7.5 percent. Severe cases may have a mortality rate of more than 50%. Surviving the infection confers lifetime immunity and, in most cases, does not result in irreversible organ damage.
Yellow fever is caused by the yellow fever virus, a 40–50 nm wide enveloped RNA virus that is the type species and namesake of the Flaviviridae family. It was discovered by American doctor Walter Reed in 1900 to be transmissible by filtered human serum and spread by mosquitoes. The single-stranded, positive-sense RNA is approximately 10,862 nucleotides long and has a single open reading frame that codes for a polyprotein.
This polyprotein is broken into three structural (C, prM, E) and seven nonstructural proteins by host proteases; the enumeration corresponds to the order of the protein-coding genes in the genome.
The viral genome is reproduced in the rough endoplasmic reticulum (ER) and vesicle packages once it enters the host cell. Inside the ER, an immature version of the viral particle is formed, whose M-protein has not yet been cleaved to its mature form and hence is referred to as precursor M (prM), which forms a complex with protein E. The host protein furin, which cleaves prM to M, processes the immature particles in the Golgi apparatus. This frees E from the complex, allowing it to enter the mature, infectious virion.
The yellow fever virus is mostly transmitted via the bite of the yellow fever mosquito, Aedes aegypti, but other Aedes mosquitoes, such as the tiger mosquito (Aedes albopictus), can also function as vectors. When a female mosquito ingests the blood of an infected human or another primate, it picks up the yellow fever virus, just like other arboviruses that are transmitted by mosquitoes. Viruses enter the mosquito’s stomach, where they can infect epithelial cells and multiply if the viral concentration is high enough. They then make their way to the hemocoel (mosquitoes’ blood system) and the salivary glands.
The virus is spread from mosquitoes to humans or other primates in three epidemiologically distinct infectious cycles. Only the yellow fever mosquito Aedes aegypti is engaged in the “urban cycle.” It has adapted effectively to urban environments and may also spread other illnesses such as Zika, dengue, and chikungunya. The largest epidemics of yellow fever that occur in Africa are caused by the urban cycle. This urban cycle no longer occurs in South America, except a 1999 epidemic in Bolivia.
A sylvatic cycle (forest or jungle cycle) exists in both Africa and South America, with Aedes Africanus (in Africa) or mosquitoes of the genera Haemagogus and Sabethes (in South America) serving as vectors. Mosquitoes mostly infect nonhuman primates in the forest, and the illness is largely asymptomatic in African monkeys. The sylvatic cycle is now the sole mechanism for people to become infected in South America, which explains the continent’s low prevalence of yellow fever infections. Infected people in the bush can spread the virus to urban areas, where Aedes aegypti serves as a vector. Yellow fever cannot be eradicated due to this sylvatic cycle unless the mosquitoes that act as carriers are removed.
The viruses proliferate in the lymph nodes after being transmitted by a mosquito and infect dendritic cells in particular. They then go to the liver, where they infect hepatocytes (perhaps indirectly via Kupffer cells), causing eosinophilic breakdown and the production of cytokines. Councilman bodies are apoptotic aggregates that form in the cytoplasm of hepatocytes.
When cytokine storm, shock, and multiple organ failure ensue, death is possible.
Yellow fever is usually diagnosed clinically, based on symptoms and travel history. Only virological testing can confirm mild occurrences of the illness. Because even minor instances of yellow fever can contribute considerably to regional epidemics, every suspected case of yellow fever (fever, discomfort, nausea, and vomiting 6–10 days after leaving the infected area) is taken carefully.
The virus cannot be verified until 6–10 days after the sickness if yellow fever is suspected. Reverse transcription-polymerase chain reaction, which amplifies the virus’s genome, can provide direct evidence. Another direct way is to isolate the virus and cultivate it in cell culture using blood plasma; this can take anywhere from 1 to 4 weeks.
An enzyme-linked immunosorbent test employing specific IgM against yellow fever or a rise in specific IgG titer (relative to an earlier sample) can confirm yellow fever serologically during the acute phase of the disease. The presence of IgM or a four-fold rise in IgG titer, when combined with clinical symptoms, is considered adequate evidence of yellow fever. These indirect approaches cannot clearly show yellow fever infection since these tests can cross-react with other flaviviruses, such as the dengue virus.
Hepatocyte necrosis and inflammation can be confirmed by a liver biopsy, and viral antigens can be detected. Because yellow fever patients are prone to bleeding, a biopsy is only recommended after death to determine the cause of death. Yellow fever infections must be recognized from other feverish disorders such as malaria in a differential diagnosis. Ebola virus, Lassa virus, Marburg virus, and Junin virus are among the viral hemorrhagic fevers that must be ruled out.
Personal yellow fever prevention includes vaccination and avoiding mosquito bites in areas where yellow fever is endemic. Vaccination programs and mosquito control measures are examples of institutional measures for yellow fever prevention. Malaria and yellow fever cases are reduced as a result of programs that distribute mosquito nets for use in the home. When going outside, use an EPA-registered bug repellent. Even a little period of exposure might result in a mosquito bite. Long-sleeved clothes, long pants, and socks can help avoid infection. Larvicides applied to water-storage containers can aid in the elimination of possible mosquito breeding grounds. Yellow fever transmission is reduced with an EPA-registered pesticide spray.
- On exposed skin, apply insect repellent containing DEET, picaridin, ethyl butyl acetylamino propionate (IR3535), or oil of lemon eucalyptus.
- Wear appropriate clothes to avoid mosquito bites. When the weather permits, dress in long sleeves, long pants, and socks. Mosquitoes may bite through thin clothing, so spraying repellent containing permethrin or similar EPA-registered repellent on clothing provides additional protection. Permethrin-treated clothing is commercially available. Permethrin-containing mosquito repellents are not permitted to be applied directly to the skin.
- Many mosquito species bite most frequently between dusk and sunrise. However, Aedes aegypti, a mosquito that transmits the yellow fever virus, feeds throughout the day. Staying in motels with screened or air-conditioned rooms, especially during peak biting seasons, decreases the risk of bites.