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The differential diagnosis in a case of suspected human rabies may initially include any cause of encephalitis, in particular infection with viruses such as herpesviruses, enteroviruses, and arboviruses such as West Nile virus. The most important viruses to rule out are herpes simplex virus type one, varicella zoster virus, and (less commonly) enteroviruses, including coxsackieviruses, echoviruses, polioviruses, and human enteroviruses 68 to 71.
New causes of viral encephalitis are also possible, as was evidenced by the 1999 outbreak in Malaysia of 300 cases of encephalitis with a mortality rate of 40% caused by Nipah virus, a newly recognized paramyxovirus. Likewise, well-known viruses may be introduced into new locales, as is illustrated by the outbreak of encephalitis due to West Nile virus in the eastern United States. Epidemiologic factors, such as season, geographic location, and the patient's age, travel history, and possible exposure to bites, rodents, and ticks, may help direct the diagnosis.
Rabies can be difficult to diagnose, because, in the early stages, it is easily confused with other diseases or with aggressiveness. The reference method for diagnosing rabies is the fluorescent antibody test (FAT), an immunohistochemistry procedure, which is recommended by the World Health Organization (WHO). The FAT relies on the ability of a detector molecule (usually fluorescein isothiocyanate) coupled with a rabies-specific antibody, forming a conjugate, to bind to and allow the visualisation of rabies antigen using fluorescent microscopy techniques. Microscopic analysis of samples is the only direct method that allows for the identification of rabies virus-specific antigen in a short time and at a reduced cost, irrespective of geographical origin and status of the host. It has to be regarded as the first step in diagnostic procedures for all laboratories. Autolysed samples can, however, reduce the sensitivity and specificity of the FAT. The RT PCR assays proved to be a sensitive and specific tool for routine diagnostic purposes, particularly in decomposed samples or archival specimens. The diagnosis can be reliably made from brain samples taken after death. The diagnosis can also be made from saliva, urine, and cerebrospinal fluid samples, but this is not as sensitive and reliable as brain samples. Cerebral inclusion bodies called Negri bodies are 100% diagnostic for rabies infection but are found in only about 80% of cases. If possible, the animal from which the bite was received should also be examined for rabies.
Some light microscopy techniques may also be used to diagnose rabies at a tenth of the cost of traditional fluorescence microscopy techniques, allowing identification of the disease in less-developed countries.
The CDC recommends screening some pregnant women even if they do not have symptoms of infection. Pregnant women who have traveled to affected areas should be tested between two and twelve weeks after their return from travel. Due to the difficulties with ordering and interpreting tests for Zika virus, the CDC also recommends that healthcare providers contact their local health department for assistance. For women living in affected areas, the CDC has recommended testing at the first prenatal visit with a doctor as well as in the mid-second trimester, though this may be adjusted based on local resources and the local burden of Zika virus. Additional testing should be done if there are any signs of Zika virus disease. Women with positive test results for Zika virus infection should have their fetus monitored by ultrasound every three to four weeks to monitor fetal anatomy and growth.
In Haiti, few cases of human rabies are reported to health authorities. In 2016, a report of a woman who had been exposed to rabies three months prior and was showing symptoms went to the hospital where no treatment was administered to her. Even after being reported to both the CDC and the national Department of Epidemiology and Laboratory Research (DELR), as required by Haiti's surveillance program, the woman ended up passing away. This goes to show the lack of communication and effectiveness in caring for human subjects in Haiti, and the continued focus is on eliminating dog-mediated rabies altogether.
Human diploid cell culture rabies vaccine (HDCV) and purified chick embryo cell culture rabies vaccine (PCEC) are used to treat post-exposure immunization against a human rabies infection. Recommendations for treatment are given by governmental health care organizations and in health literature. Health care providers are encouraged to administer a regimen of four 1-mL doses of HDCV or PCEC vaccines. According to the CDC, these injections should be administered intramuscularly to persons who have not yet been vaccinated for rabies.
For those who are unvaccinated, the first of four doses is administered immediately after exposure to the rabies virus. Additional doses are given three, seven, and fourteen days after the first vaccination. Exposure usually means a bite from a rabid animal.
At an individual patient level, post-exposure prophylaxis (PEP) consists of local treatment of the wound, vaccination, and administration of immunoglobulin, if necessary [3]. At the program level, several components are critical, including: adequate and prompt recognition of the need for PEP by the public, if exposed, and by health officials, prompt and sufficient availability of high-quality PEP, and adequate follow-up of PEP use. Health officials' awareness of the need for PEP after a dog bite can only be achieved if the exposure is attended to immediately and communicated effectively.
For infants with suspected congenital Zika virus disease, the CDC recommends testing with both serologic and molecular assays such as RT-PCR, IgM ELISA and plaque reduction neutralization test (PRNT). RT-PCR of the infants serum and urine should be performed in the first two days of life. Newborns with a mother who was potentially exposed and who have positive blood tests, microcephaly or intracranial calcifications should have further testing including a thorough physical investigation for neurologic abnormalities, dysmorphic features, splenomegaly, hepatomegaly, and rash or other skin lesions. Other recommended tests are cranial ultrasound, hearing evaluation, and eye examination. Testing should be done for any abnormalities encountered as well as for other congenital infections such as syphilis, toxoplasmosis, rubella, cytomegalovirus infection, lymphocytic choriomeningitis virus infection, and herpes simplex virus. Some tests should be repeated up to 6 months later as there can be delayed effects, particularly with hearing.
Dog vaccination is most effective for controlling dog-mediated rabies. This can be seen throughout the American region where medical authorities have achieved rabies control.
In Haiti, the CDC is mainly focusing on dog-mediated rabies. Specifically in collaboration with the NGO Christian Veterinary Mission, the CDC has trained, to date, more than 20 MARNDR laboratory personnel in rabies diagnostic methods (Direct Fluorescent Antibody [DFA] and Direct Rapid Immunohistochemistry Test [dRIT]). The organizations have also improved a diagnostic laboratory in Port-au-Prince by providing it with advanced equipment. The surveillance system is a bite-reporting model where the public and medical providers report bite events to rabies control officers. In addition, more than 30 field veterinary and health agents were trained in rabies surveillance, in support of this effort.
In 2011, the CDC along with MARNDR initiated a five-year rabies infrastructure improvement program that focused on surveillance, diagnostics, and education. The MSPP also helped out by improving public education on rabies. Because Haiti has a gross national income per capita of US $1,035, it is the only country in the American region that is part of the group of low-income countries. The World Bank has classified 33 other low-income countries in Africa and Asia, where dog-mediated rabies is a major problem and results in thousands of deaths annually. The persistence of dog rabies is connected to limited resources and weak governance.
In conducting a rabies assessment, rabies control officers try to locate the offending animal. Animals that have bitten a victim are either euthanized and tested or quarantined for 14 days while remaining in their owner's residence. In addition, animals who show signs of rabies are tested, regardless of human exposure. This surveillance program is restricted to two of the ten geographical departments of the country (West and Artibonite) for security reasons. The area includes approximately 50 percent of the Haitian population. The CDC and the NGO Christian Veterinary Mission support the mission by maintaining four Haitian staff in the West Department and three in the Artibonite Department, respectively. Results of this mission showed the level of under-reporting of canine rabies. Specifically, six cases of rabid dogs in early December, 2012, were reported for the country.
During the first nine months of the surveillance mission, 42 rabid dogs were identified in just three communities in Port-au-Prince during the first nine months in 2012. That being said, no laboratory-based surveillance exists for the human population that is exposed to rabies and all diagnoses are based on clinical history. This is because of the lack of laboratory facilities, making it difficult to identify evidence for the virus in humans and shed light on the disease as a whole for them, in Haiti. There are insufficient numbers of pathologists to collect samples for human rabies, as well. There do exist other methods for viral antigen detection that may merit study.
In 2013, the CDC and its partners began an animal rabies surveillance program in several regions of Haiti and saw an 18-fold rise in detection of rabid animals. In 2015, the CDC evaluated Haiti’s canine rabies vaccination program and found that only 45 percent of dogs were vaccinated, far short of the 70 percent needed to stop the spread of rabies in the dog population. In addition, the researchers found that Haiti had nearly 1,000,000 dogs, twice as many as previously thought.
The CDC and its partners had already begun a dog vaccination trial in evaluating the best vaccination methods for dogs in Haiti. As a part of this effort, they vaccinated 3,000 dogs in just four days during the summer of 2016 and planned to vaccinate a total of 8,000 dogs as part of this campaign.
The MAYV infection is characterized by fever, headache, myalgia, rash, prominent pain in the large joints, and association with rheumatic disease, but these signs and symptoms are unspecific to distinguish from other Arbovirus. The MAYV infection can be confirmed by laboratory testing such us virus isolation, RT-PCR and serology. The virus isolation in cell culture is effective during viremia. RT-PCR helps to identify virus. Serology tests detect antibodies like IgM and the most common assay is IgM-capture enzyme-linked immunosorbant assays (ELISA). This test usually requires a consecutive retest to confirm increasing titers. While the IgG detection is applied for epidemiology studies.
In the 2010 recommendations of the international Vaccination Guidelines Group (VGG), they emphasized the importance of administering "non-adjuvanted" vaccines whenever possible.
The VGG also prefers serological testing over unnecessary re-vaccination or boosters of core vaccines after the initial 12-month booster that follows the puppy/kitten series of modified live virus [MLV] vaccines. This is because core vaccines show an excellent correlation between the presence of antibody and protective immunity and have a long DOI (Duration of Immunity). Antibody tests can be used to demonstrate the DOI after vaccination with core vaccines, though not for non-core vaccines.
FVRCP vaccines have also come under scrutiny of late due to possible risks to long term health. A study at Colorado State University noted an association between vaccination with parenteral (injectable) FVRCP vaccinations and development of antibodies against feline kidney tissue. Antibody development is hypothesized to develop when the immune system reacts to protein contaminants from the cell line used to cultivate vaccinial viruses. The cell line in question, the Crandell-Rees Feline Kidney (CRFK) cell line, was derived from a cat kidney. It is currently unknown whether this antibody development can lead to renal disease, though a recent follow-up study demonstrated evidence of inflammation on re-biopsy samples from some of the study cats.
Although no specific treatment for acute infection with SuHV1 is available, vaccination can alleviate clinical signs in pigs of certain ages. Typically, mass vaccination of all pigs on the farm with a modified live virus vaccine is recommended. Intranasal vaccination of sows and neonatal piglets one to seven days old, followed by intramuscular (IM) vaccination of all other swine on the premises, helps reduce viral shedding and improve survival. The modified live virus replicates at the site of injection and in regional lymph nodes. Vaccine virus is shed in such low levels, mucous transmission to other animals is minimal. In gene-deleted vaccines, the thymidine kinase gene has also been deleted; thus, the virus cannot infect and replicate in neurons. Breeding herds are recommended to be vaccinated quarterly, and finisher pigs should be vaccinated after levels of maternal antibody decrease. Regular vaccination results in excellent control of the disease. Concurrent antibiotic therapy via feed and IM injection is recommended for controlling secondary bacterial pathogens.
In 2012, the World Health Organization estimated that vaccination prevents 2.5 million deaths each year. If there is 100% immunization, and 100% efficacy of the vaccines, one out of seven deaths among young children could be prevented, mostly in developing countries, making this an important global health issue. Four diseases were responsible for 98% of vaccine-preventable deaths: measles, "Haemophilus influenzae" serotype b, pertussis, and neonatal tetanus.
The Immunization Surveillance, Assessment and Monitoring program of the WHO monitors and assesses the safety and effectiveness of programs and vaccines at reducing illness and deaths from diseases that could be prevented by vaccines.
Vaccine-preventable deaths are usually caused by a failure to obtain the vaccine in a timely manner. This may be due to financial constraints or to lack of access to the vaccine. A vaccine that is generally recommended may be medically inappropriate for a small number of people due to severe allergies or a damaged immune system. In addition, a vaccine against a given disease may not be recommended for general use in a given country, or may be recommended only to certain populations, such as young children or older adults. Every country makes its own vaccination recommendations, based on the diseases that are common in its area and its healthcare priorities. If a vaccine-preventable disease is uncommon in a country, then residents of that country are unlikely to receive a vaccine against it. For example, residents of Canada and the United States do not routinely receive vaccines against yellow fever, which leaves them vulnerable to infection if travelling to areas where risk of yellow fever is highest (endemic or transitional regions).
The virus’s transmission cycle in the wild is similar to the continuous sylvatic cycle of yellow fever and is believed to involve wild primates (monkeys) as the reservoir and the tree-canopy-dwelling "Haemagogus" species mosquito as the vector. Human infections are strongly associated with exposure to humid tropical forest environments. Chikungunya virus is closely related, producing a nearly indistinguishable, highly debilitating arthralgic disease. On February 19, 2011, a Portuguese-language news source reported on a recent survey which revealed Mayaro virus activity in Manaus, Amazonas State, Brazil. The survey studied blood samples from 600 residents of Manaus who had experienced a high fever; Mayaro virus was identified in 33 cases. Four of the cases experienced mild hemorrhagic (bleeding) symptoms, which had not previously been described in Mayaro virus disease. The report stated that this outbreak is the first detected in a metropolitan setting, and expressed concern that the disease might be adapting to urban species of mosquito vectors, which would make it a risk for spreading within the country. A study published in 1991 demonstrated that a colonized strain of Brazilian "Aedes albopictus" was capable of acquiring MAYV from infected hamsters and subsequently transmitting it and a study published in October 2011 demonstrated that "Aedes aegypti" can transmit MAYV, supporting the possibility of wider transmission of Mayaro virus disease in urban settings.
Rabies can be contracted in horses if they interact with rabid animals in their pasture, usually being bitten on the muzzle or lower limbs. Signs include aggression, incoordination, head-pressing, circling, lameness, muscle tremors, convulsions, colic and fever. Horses that experience the paralytic form of rabies have difficulty swallowing, and drooping of the lower jaw due to paralysis of the throat and jaw muscles. Incubation of the virus may range from 2–9 weeks. Death often occurs within 4–5 days of infection of the virus. There are no effective treatments for rabies in horses. Veterinarians recommend an initial vaccination as a foal at three months of age, repeated at one year and given an annual booster.
SuHV1 can be used to analyze neural circuits in the central nervous system (CNS). For this purpose the attenuated (less virulent) Bartha SuHV1 strain is commonly used and is employed as a retrograde and anterograde transneuronal tracer. In the retrograde direction, SuHV1-Bartha is transported to a neuronal cell body via its axon, where it is replicated and dispersed throughout the cytoplasm and the dendritic tree. SuHV1-Bartha released at the synapse is able to cross the synapse to infect the axon terminals of synaptically connected neurons, thereby propagating the virus; however, the extent to which non-synaptic transneuronal transport may also occur is uncertain. Using temporal studies and/or genetically engineered strains of SuHV1-Bartha, second, third, and higher order neurons may be identified in the neural network of interest.
Rabies is a viral zoonotic neuroinvasive disease which causes inflammation in the brain and is usually fatal. Rabies, caused by the rabies virus, primarily infects mammals. In the laboratory it has been found that birds can be infected, as well as cell cultures from birds, reptiles and insects. Animals with rabies suffer deterioration of the brain and tend to behave bizarrely and often aggressively, increasing the chances that they will bite another animal or a person and transmit the disease. Most cases of humans contracting the disease from infected animals are in developing nations. In 2010, an estimated 26,000 people died from rabies, down from 54,000 in 1990.
The current clinical case definition of diphtheria used by the United States' Centers for Disease Control and Prevention is based on both laboratory and clinical criteria.
Yellow fever is most frequently a clinical diagnosis, made on the basis of symptoms and the diseased person's whereabouts prior to becoming ill. Mild courses of the disease can only be confirmed virologically. Since mild courses of yellow fever can also contribute significantly to regional outbreaks, every suspected case of yellow fever (involving symptoms of fever, pain, nausea and vomiting six to 10 days after leaving the affected area) is treated seriously.
If yellow fever is suspected, the virus cannot be confirmed until six to 10 days after the illness. A direct confirmation can be obtained by reverse transcription polymerase chain reaction where the genome of the virus is amplified. Another direct approach is the isolation of the virus and its growth in cell culture using blood plasma; this can take one to four weeks.
Serologically, an enzyme linked immunosorbent assay during the acute phase of the disease using specific IgM against yellow fever or an increase in specific IgG-titer (compared to an earlier sample) can confirm yellow fever. Together with clinical symptoms, the detection of IgM or a fourfold increase in IgG-titer is considered sufficient indication for yellow fever. Since these tests can cross-react with other flaviviruses, like dengue virus, these indirect methods cannot conclusively prove yellow fever infection.
Liver biopsy can verify inflammation and necrosis of hepatocytes and detect viral antigens. Because of the bleeding tendency of yellow fever patients, a biopsy is only advisable "post mortem" to confirm the cause of death.
In a differential diagnosis, infections with yellow fever must be distinguished from other feverish illnesses like malaria. Other viral hemorrhagic fevers, such as Ebola virus, Lassa virus, Marburg virus, and Junin virus, must be excluded as cause.
Outbreaks of zoonoses have been traced to human interaction with and exposure to animals at fairs, petting zoos, and other settings. In 2005, the Centers for Disease Control and Prevention (CDC) issued an updated list of recommendations for preventing zoonosis transmission in public settings. The recommendations, developed in conjunction with the National Association of State Public Health Veterinarians, include educational responsibilities of venue operators, limiting public and animal contact, and animal care and management.
The WHO lists 25 diseases for which vaccines are available:
1. Measles
2. Rubella
3. Cholera
4. Meningococcal disease
5. Influenza
6. Diphtheria
7. Mumps
8. Tetanus
9. Hepatitis A
10. Pertussis
11. Tuberculosis
12. Hepatitis B
13. Pneumoccocal disease
14. Typhoid fever
15. Hepatitis E
16. Poliomyelitis
17. Tick-borne encephalitis
18. Haemophilus influenzae type b
19. Rabies
20. Varicella and herpes zoster (shingles)
21. Human papilloma-virus
22. Rotavirus gastroenteritis
23. Yellow fever
24. Japanese encephalitis
25. Malaria
26. Dengue fever
Contact with farm animals can lead to disease in farmers or others that come into contact with infected animals. Glanders primarily affects those who work closely with horses and donkeys. Close contact with cattle can lead to cutaneous anthrax infection, whereas inhalation anthrax infection is more common for workers in slaughterhouses, tanneries and wool mills. Close contact with sheep who have recently given birth can lead to clamydiosis, or enzootic abortion, in pregnant women, as well as an increased risk of Q fever, toxoplasmosis, and listeriosis in pregnant or the otherwise immunocompromised. Echinococcosis is caused by a tapeworm which can be spread from infected sheep by food or water contaminated with feces or wool. Bird flu is common in chickens. While rare in humans, the main public health worry is that a strain of bird flu will recombine with a human flu virus and cause a pandemic like the 1918 Spanish flu. In 2017, free range chickens in the UK were temporarily ordered to remain inside due to the threat of bird flu. Cattle are an important reservoir of cryptosporidiosis and mainly affects the immunocompromised.
Vaccination is recommended for those traveling to affected areas, because non-native people tend to develop more severe illness when infected. Protection begins by the 10th day after vaccine administration in 95% of people, and had been reported to last for at least 10 years. WHO now states that a single dose of vaccination is sufficient to confer lifelong immunity against yellow fever disease." The attenuated live vaccine stem 17D was developed in 1937 by Max Theiler. The World Health Organization (WHO) recommends routine vaccinations for people living in affected areas between the 9th and 12th month after birth.
Up to one in four people experience fever, aches, and local soreness and redness at the site of injection. In rare cases (less than one in 200,000 to 300,000), the vaccination can cause yellow fever vaccine–associated viscerotropic disease, which is fatal in 60% of cases. It is probably due to the genetic morphology of the immune system. Another possible side effect is an infection of the nervous system, which occurs in one in 200,000 to 300,000 cases, causing yellow fever vaccine-associated neurotropic disease, which can lead to meningoencephalitis and is fatal in less than 5% of cases.
The Yellow Fever Initiative, launched by WHO in 2006, vaccinated more than 105 million people in 14 countries in West Africa. No outbreaks were reported during 2015. The campaign was supported by the GAVI Alliance, and governmental organizations in Europe and Africa. According to the WHO, mass vaccination cannot eliminate yellow fever because of the vast number of infected mosquitoes in urban areas of the target countries, but it will significantly reduce the number of people infected.
In March 2017, WHO launched a vaccination campaign in Brazil with 3.5 million doses from an emergency stockpile. In March 2017 the WHO recommended vaccination for travellers to certain parts of Brazil.
Some conventional parasitological techniques (CPT) such as wet blood film, and stained blood smears are used because so far, the best identifier is looking at the blood of the potentially infected host. Other tissues can be looked at, but the gold standard is identifying trypanosomes in the blood. Before the infection becomes severe, it is difficult to catch as many times these cryptic infections are undetectable by direct microscopy. Since CPT is not very sensitive, it cannot be used as a sole method of diagnosis.
The Haematocrit Centrifugation Technique (HCT) is a much better alternative. Using HCT trypanosomes can be detected in the blood even in field conditions. Buffy coat can be used to increase detection. Detection with this method is approx 85 trypanosomes per millilitre.
Rather than using live animals as test subjects, Canada used serological tests such as complement fixation tests to detect trypanosomes, and have been very successful. Other tests used look at detecting antibodies generated by the host species against T.evansi antigens. This is done using the enzyme-linked immunosorbent assays (ELISA) method. Now polymerase chain reaction (PCR) and DNA probes are being used to detect Surra in animals.
The diagnosis is aided by obtaining a history of the circumstances surrounding the bite. The time the bite was experienced, the location of the bite, and examination of the bite is noted. The person may have drainage from the site of the bite. They may also be febrile. Swelling may also occur. Because the wound from the bite may have healed over the punctures, the wound it may be opened and explored. The site is anesthetized prior to exploration of the wound for is examined for damage. Neurovascular status is assessed. Immune status may determine treatment as does
the presence of transplanted tissue or organs, rheumatic disease, diabetes, HIV/AIDS and sickle cell disease.
Swollen glands (lymph nodes) and red streaks radiating upward may be evident.
The diagnosis of a cat with rabies is evident by observing the cat. Cats with rabies may also appear restless, pant, and attack other animals, people, or objects. Animals with rabies typically die within a few days of appearing sick. Vaccination of the cat can prevent rabies being transmitted by the cat through a bite. If the cat is suspected of being infected with rabies, the person begins treatment with rabies vaccine.
Empirical treatment should generally be started in a patient in whom suspicion of diphtheria is high.
The main methods of controlling surra has been chemotherapy, and chemoprophylaxis in animals.