Measures to reduce contact between the vesper mouse and humans may have contributed to limiting the number of outbreaks, with no cases identified between 1973 and 1994. Although there are no cures or vaccine for the disease, a vaccine developed for the genetically related Junín virus which causes Argentine hemorrhagic fever has shown evidence of cross-reactivity to Machupo virus, and may therefore be an effective prophylactic measure for people at high risk of infection. Post infection (and providing that the person survives the infection), those that have contracted BHF are usually immune to further infection of the disease.

Investigational vaccines exist for Argentine hemorrhagic fever and RVF; however, neither is approved by FDA or commonly available in the United States.

The structure of the attachment glycoprotein has been determined by X-ray crystallography and this glycoprotein is likely to be an essential component of any successful vaccine.

Severe disease is more common in babies and young children, and in contrast to many other infections, it is more common in children who are relatively well nourished. Other risk factors for severe disease include female sex, high body mass index, and viral load. While each serotype can cause the full spectrum of disease, virus strain is a risk factor. Infection with one serotype is thought to produce lifelong immunity to that type, but only short-term protection against the other three. The risk of severe disease from secondary infection increases if someone previously exposed to serotype DENV-1 contracts serotype DENV-2 or DENV-3, or if someone previously exposed to DENV-3 acquires DENV-2. Dengue can be life-threatening in people with chronic diseases such as diabetes and asthma.

Polymorphisms (normal variations) in particular genes have been linked with an increased risk of severe dengue complications. Examples include the genes coding for the proteins known as TNFα, mannan-binding lectin, CTLA4, TGFβ, DC-SIGN, PLCE1, and particular forms of human leukocyte antigen from gene variations of HLA-B. A common genetic abnormality, especially in Africans, known as glucose-6-phosphate dehydrogenase deficiency, appears to increase the risk. Polymorphisms in the genes for the vitamin D receptor and FcγR seem to offer protection against severe disease in secondary dengue infection.

Preventing Omsk Hemorrhagic Fever consists primarily in avoiding being exposed to tick. Persons engaged in camping, farming, forestry, hunting (especially the Siberian muskrat) are at greater risk and should wear protective clothing or use insect repellent for protection. The same is generally recommended for persons at sheltered locations.

Yellow fever is common in tropical and subtropical areas of South America and Africa. Worldwide, about 600 million people live in endemic areas. The WHO estimates 200,000 cases of disease and 30,000 deaths a year occur; the number of officially reported cases is far lower.

About 15–20% of hospitalized Lassa fever patients will die from the illness. The overall mortality rate is estimated to be 1%, but during epidemics, mortality can climb as high as 50%. The mortality rate is greater than 80% when it occurs in pregnant women during their third trimester; fetal death also occurs in nearly all those cases. Abortion decreases the risk of death to the mother. Some survivors experience lasting effects of the disease, and can include partial or complete deafness.

Because of treatment with ribavirin, fatality rates are continuing to decline.

Five families of RNA viruses have been recognised as being able to cause hemorrhagic fevers.

- The family "Arenaviridae" include the viruses responsible for Lassa fever (Lassa virus), Lujo virus, Argentine (Junin virus), Bolivian (Machupo virus), Brazilian (Sabiá virus), Chapare hemorrhagic fever (Chapare virus) and Venezuelan (Guanarito virus) hemorrhagic fevers.

- The family "Bunyaviridae" include the members of the "Hantavirus" genus that cause hemorrhagic fever with renal syndrome (HFRS), the Crimean-Congo hemorrhagic fever (CCHF) virus from the "Nairovirus" genus, Garissa virus and Ilesha virus from the "Orthobunyavirus" and the Rift Valley fever (RVF) virus from the "Phlebovirus" genus.

- The family "Filoviridae" include Ebola virus and Marburg virus.

- The family "Flaviviridae" include dengue, yellow fever, and two viruses in the tick-borne encephalitis group that cause VHF: Omsk hemorrhagic fever virus and Kyasanur Forest disease virus.

- In September 2012 scientists writing in the journal PLOS Pathogens reported the isolation of a member of the "Rhabdoviridae" responsible for 2 fatal and 2 non-fatal cases of hemorrhagic fever in the Bas-Congo district of the Democratic Republic of Congo. The non-fatal cases occurred in healthcare workers involved in the treatment of the other two, suggesting the possibility of person-to-person transmission. This virus appears to be unrelated to previously known Rhabdoviruses.

The pathogen that caused the cocoliztli epidemics in Mexico of 1545 and 1576 is still unknown.

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.

AHF is a grave acute disease which may progress to recovery or death in 1 to 2 weeks. The incubation time of the disease is between 10 and 12 days, after which the first symptoms appear: fever, headaches, weakness, loss of appetite and will. These intensify less than a week later, forcing the infected to lie down, and producing stronger symptoms such as vascular, renal, hematological and neurological alterations. This stage lasts about 3 weeks.

If untreated, the mortality of AHF reaches 15–30%. The specific treatment includes plasma of recovered patients, which, if started early, is extremely effective and reduces mortality to 1%.

Ribavirin also has shown some promise in treating arenaviral diseases.

The disease was first detected in the 1950s in the Junín Partido in Buenos Aires, after which its agent, the Junín virus, was named upon its identification in 1958. In the early years, about 1,000 cases per year were recorded, with a high mortality rate (more than 30%). The initial introduction of treatment serums in the 1970s reduced this lethality.

Omsk hemorrhagic fever is caused by the Omsk hemorrhagic fever virus (OHFV), a member of the Flavivirus family. The virus was discovered by Mikhail Chumakov and his colleagues between 1945 and 1947 in Omsk, Russia. The infection is found in western Siberia, in places including Omsk, Novosibirsk, Kurgan, and Tyumen. The virus survives in water and is transferred to humans via contaminated water or an infected tick.

Prevention depends on control of and protection from the bites of the mosquito that transmits it. The World Health Organization recommends an Integrated Vector Control program consisting of five elements:

1. Advocacy, social mobilization and legislation to ensure that public health bodies and communities are strengthened;

2. Collaboration between the health and other sectors (public and private);

3. An integrated approach to disease control to maximize use of resources;

4. Evidence-based decision making to ensure any interventions are targeted appropriately; and

5. Capacity-building to ensure an adequate response to the local situation.

The primary method of controlling "A. aegypti" is by eliminating its habitats. This is done by getting rid of open sources of water, or if this is not possible, by adding insecticides or biological control agents to these areas. Generalized spraying with organophosphate or pyrethroid insecticides, while sometimes done, is not thought to be effective. Reducing open collections of water through environmental modification is the preferred method of control, given the concerns of negative health effects from insecticides and greater logistical difficulties with control agents. People can prevent mosquito bites by wearing clothing that fully covers the skin, using mosquito netting while resting, and/or the application of insect repellent (DEET being the most effective). However, these methods appear not to be sufficiently effective, as the frequency of outbreaks appears to be increasing in some areas, probably due to urbanization increasing the habitat of "A. aegypti". The range of the disease appears to be expanding possibly due to climate change.

Treatment is similar to hepatitis B, but due to its high lethality, more aggressive therapeutic approaches are recommended in the acute phase. In absence of a specific vaccine against delta virus, the vaccine against HBV must be given soon after birth in risk groups.

The disease was first reported in the town of in Buenos Aires province, Argentina in 1958, giving it one of the names by which it is known. Various theories about its nature were proposed: it was Weil's disease, leptospirosis, caused by chemical pollution. It was associated with fields containing stubble after the harvest, giving it another of its names.

The endemic area of AHF covers approximately 150,000 km², compromising the provinces of Buenos Aires, Córdoba, Santa Fe and La Pampa, with an estimated risk population of 5 million.

The vector, a small rodent known locally as "ratón maicero" ("maize mouse"; "Calomys musculinus"), suffers from chronic asymptomatic infection, and spreads the virus through its saliva and urine. Infection is produced through contact of skin or mucous membranes, or through inhalation of infected particles. It is found mostly in people who reside or work in rural areas; 80% of those infected are males between 15 and 60 years of age.

Control of the "Mastomys" rodent population is impractical, so measures focus on keeping rodents out of homes and food supplies, encouraging effective personal hygiene, storing grain and other foodstuffs in rodent-proof containers, and disposing of garbage far from the home to help sustain clean households . Gloves, masks, laboratory coats, and goggles are advised while in contact with an infected person, to avoid contact with blood and body fluids. These issues in many countries are monitored by a department of public health. In less developed countries, these types of organizations may not have the necessary means to effectively control outbreaks.

Researchers at the USAMRIID facility, where military biologists study infectious diseases, have a promising vaccine candidate. They have developed a replication-competent vaccine against Lassa virus based on recombinant vesicular stomatitis virus vectors expressing the Lassa virus glycoprotein. After a single intramuscular injection, test primates have survived lethal challenge, while showing no clinical symptoms.

The VHF viruses are spread in a variety of ways. Some may be transmitted to humans through a respiratory route. According to Soviet defector Ken Alibek, Soviet scientists concluded China may have tried to weaponise a VHF virus during the late 1980's but discontinued to do so after an outbreak . The virus is considered by military medical planners to have a potential for aerosol dissemination, weaponizaton, or likelihood for confusion with similar agents that might be weaponized.

The disease develops from March to September, with the highest infections occurring in June. The disease is found almost exclusively in the western United States and Canada, mostly in high mountain areas such as Colorado and Idaho. The CTFV was first isolated from human blood in 1944.

It is estimated that seven to ten million people are infected by leptospirosis annually. One million cases of severe leptospirosis occur annually, with 58,900 deaths. Annual rates of infection vary from 0.02 per 100,000 in temperate climates to 10 to 100 per 100,000 in tropical climates. This leads to a lower number of registered cases than likely exists.

The number of new cases of leptospirosis is difficult to estimate since many cases of the disease go unreported. There are many reasons for this, but the biggest issue is separating the disease from other similar conditions. Laboratory testing is lacking in many areas.

In context of global epidemiology, the socioeconomic status of many of the world’s population is closely tied to malnutrition; subsequent lack of micronutrients may lead to increased risk of infection and death due to leptospirosis infection. Micronutrients such as iron, calcium, and magnesium represent important areas of future research.

Outbreaks that occurred after the 1940's have happened mostly in the late summer seasons, which happens to be the driest part of the year. The people at the highest risk for leptospirosis are young people whose age ranges from 5-16 years old, and can also range to young adults.

The amount of cases increase during the rainy season in the tropics and during the late summer or early fall in Western countries. This happens because leptospires survive best in fresh water, damp alkaline soil, vegetation, and mud with temperatures higher that 22° C. This also leads to increased risk of exposure to populations during flood conditions, and leptospire concentrations to peak in isolated pools during drought. There is no evidence of leptospirosis having any effect on sexual and age-related differences. However, a major risk factor for development of the disease is occupational exposure, a disproportionate number of working-aged males are affected. There have been reported outbreaks where more than 40% of people are younger than 15. “Active surveillance measures have detected leptospire antibodies in as many as 30% of children in some urban American populations.” Potential reasons for such cases include children playing with suspected vectors such as dogs or indiscriminate contact with water.

Brazilian hemorrhagic fever (BzHF) is an infectious disease caused by the Sabiá virus, an Arenavirus. The Sabiá virus is one of the arenoviruses from South America to cause hemorrhagic fever. It shares a common progenitor with the Junin virus, Machupo virus, Tacaribe virus, and Guanarito virus. It is an enveloped RNA virus and is highly infectious and lethal. Very little is known about this disease, but it is thought to be transmitted by the excreta of rodents.

There have only been three documented infections of the Sabiá virus, only one of which occurred naturally and the other two cases occurred in the clinical setting. The only naturally occurring case was in 1990, when a female agricultural engineer who was staying in the neighborhood of Jardim Sabiá near São Paulo, Brazil contracted the disease. She presented with hemorrhagic fever and died. Her autopsy showed liver necrosis. A virologist who was studying the woman's disease contracted the virus but survived. Ribavirin was not given in these first two cases. Four years later, in 1994, a researcher was exposed to the virus in a level 3 biohazard facility at Yale University when a centrifuge bottle cracked, leaked, and released aerosolized virus particle. He was successfully treated with ribavirin.

Ribavirin is thought to be effective in treating the illness, similar to other arenaviruses. Compared to the patients who did not receive ribavirin, the patient who was treated with it had a shorter and less severe clinical course. Symptomatic control such as fluids to address dehydration and bleeding may also be required.

The Sabiá virus is a Biosafety Level 4 pathogen.

This virus has also been implicated as a means for bioterrorism, as it can be spread through aerosols.

Prevention strategies include reducing the breeding of midges through source reduction (removal and modification of breeding sites) and reducing contact between midges and people. This can be accomplished by reducing the number of natural and artificial water-filled habitats and encourage the midge larvae to grow.

Oropouche fever is present in epidemics so the chances of one contracting it after being exposed to areas of midgets or mosquitoes is rare.

Lábrea fever is a coinfection or superinfection of hepatitis D or delta virus and hepatitis B (HBV). The infection by delta virus may occur in a patient who already has the HBV, or both viruses may infect at the same time a previously uninfected patient. Delta virus can only multiply in the presence of HBV, therefore vaccination against HBV prevents infection. Thus, American and Brazilian scientists have determined that the delta virusa, virus, which is a small circular RNA virus, is normally unable to cause illness by itself, due to a defect. When it is combined with HBV, Lábrea hepatitis may ensue. The main discovery of delta virus and HBV association was done by Dr. Gilberta Bensabath, a leading tropical virologist of the Instituto Evandro Chagas, of Belém, state of Pará, and her collaborators.

Infected patients show extensive destruction of liver tissue, with steatosis of a particular type (microsteatosis, characterized by small fat droplets inside the cells), and infiltration of large numbers of inflammatory cells called "morula cells", comprised mainly by macrophages containing delta virus antigens.

In the 1987 Boca do Acre study, scientists did an epidemiological survey and reported delta virus infection in 24% of asymptomatic HBV carriers, 29% of acute nonfulminant hepatitis B cases, 74% of fulminant hepatitis B cases, and 100% of chronic hepatitis B cases. The delta virus seems to be endemic in the Amazon region.

Doxycycline has been provided once a week as a prophylaxis to minimize infections during outbreaks in endemic regions. However, there is no evidence that chemoprophylaxis is effective in containing outbreaks of leptospirosis, and use of antibiotics increases antibiotics resistance. Pre-exposure prophylaxis may be beneficial for individuals traveling to high-risk areas for a short stay.

Effective rat control and avoidance of urine contaminated water sources are essential preventive measures. Human vaccines are available only in a few countries, such as Cuba and China. Animal vaccines only cover a few strains of the bacteria. Dog vaccines are effective for at least one year.

Venezuelan hemorrhagic fever (VHF) is a zoonotic human illness first identified in 1989. The disease is most prevalent in several rural areas of central Venezuela and is caused by the Guanarito virus (GTOV) which belongs to the Arenaviridae family. The short-tailed cane mouse ("Zygodontomys brevicauda") is the main host for GTOV which is spread mostly by inhalation of aerosolized droplets of saliva, respiratory secretions, urine, or blood from infected rodents. Person-to-person spread is possible, but uncommon.

A vaccine has been conditionally approved for use in animals in the US. It has been shown that knockout of the NSs and NSm nonstructural proteins of this virus produces an effective vaccine in sheep as well.

One study has focused on identifying OROV through the use of RNA extraction from reverse transcription-polymerase chain reaction. This study revealed that OROV caused central nervous system infections in three patients. The three patients all had meningoencephalitis and also showed signs of clear lympho-monocytic cellular pattern in CSF, high protein, and normal to slightly decreased glucose levels indicating they had viral infections. Two of the patients already had underlying infections that can effect the CNS and immune system and in particular one of these patients has HIV/AIDS and the third patient has neurocysticercosis. Two patients were infected with OROV developed meningitis and it was theorized that this is due to them being immunocompromised. Through this it was revealed that it's possible that the invasion of the central nervous system by the oropouche virus can be performed by a pervious blood-brain barrier damage.

HFRS is primarily a Eurasian disease, whereas HPS appears to be confined to the Americas. The geography is directly related to the indigenous rodent hosts and the viruses that coevolved with them.