The Menace Of Bolivian Hemorrhagic Fever Explained

Bolivian Hemorrhagic Fever (BHF) is a high-mortality febrile illness with a mortality rate of 5-35%. The disease was first identified in 1963 and is caused by the Machupo mammarenavirus, which is transmitted to humans by exposure to the excreta and secretions of wild native rodents in Bolivia. BHF has three phases: prodromal, hemorrhagic, and convalescent. The first phase involves unspecific symptoms such as fever, malaise, headache, and myalgia. In the second phase, patients experience severe hemorrhagic manifestations, including bleeding from the nose and gums. The final phase is a slow convalescent period. There is currently no cure or vaccine for BHF, and treatment focuses on providing supportive care and proper administration of fluids.

Transmission

The route of spread of the Machupo virus from C. callosus to humans is believed to be similar to other South American hemorrhagic arenaviruses; through breathing in aerosolized excreta or secreta from the rodent reservoir, consumption of contaminated food, or through direct mucus membrane contact with infectious particles. Person-to-person transmission of BHF is believed to be rare but has been observed in familial or nosocomial settings, likely via direct contact with infectious body fluids. Transmission by intimate contact during convalescence is also possible.

BHF tends to be a seasonal disease, with more cases occurring in the dry season, at the peak of agricultural activity. Epidemics in towns may occur during epizootic conditions when rodent densities reach unusually high levels and rodents invade human settlements. In 1963 to 1964, a BHF epidemic occurred in the village of San Joaquin, resulting in 637 cases and 113 deaths among the town's 3000 residents. Under these conditions, transmission to humans is likely from the inhalation of infectious aerosols within confined spaces.

The outbreak in San Joaquin was also linked to an increase in the rodent population due to the extermination of mosquitoes using DDT, which led to a shortage of cats in the village. This resulted in a mouse plague, which contributed to the spread of the disease.

Symptoms

The symptoms of Bolivian Hemorrhagic Fever (BHF) are divided into three phases: prodromal, hemorrhagic, and convalescent.

During the prodromal phase, patients experience non-specific symptoms such as fever, malaise, myalgia, headache, and anorexia. This can develop into more severe symptoms, including vomiting, hypersensitivity, and early signs of vascular damage. Laboratory findings during this phase include leukopenia, thrombocytopenia, and proteinuria.

In the hemorrhagic phase, which occurs within a week of the prodromal phase in about one-third of patients, symptoms include flushing of the head and torso, petechiae, hypotension, bleeding from the nose and gums, epistaxis, blood in vomit and stool, delirium, convulsions, tremors, coma, and death.

The convalescent phase can last up to eight weeks, and survivors may experience fatigue, dizziness, and hair loss. The cause of the neurological issues observed in this phase is currently unknown.

Diagnosis

The diagnosis of Bolivian Hemorrhagic Fever (BHF) is primarily clinical and epidemiological. The disease is characterised by three phases: prodromal, hemorrhagic, and convalescent.

During the prodromal phase, patients experience non-specific symptoms such as fever, malaise, myalgia, headache, and anorexia. This develops into more severe symptoms, including vomiting, hypersensitivity, and early signs of vascular damage. Laboratory findings during this phase include leukopenia, thrombocytopenia, and proteinuria.

In the hemorrhagic phase, patients may exhibit flushing of the head and torso, petechiae, hypotension, bleeding from the nose and gums, epistaxis, tremors, delirium, convulsions, and bleeding in the vomit and stool.

The convalescent phase can last up to eight weeks and is associated with fatigue, dizziness, and hair loss.

BHF can be diagnosed through laboratory tests, such as enzyme-linked immunosorbent assays (ELISAs) of IgM and IgG, and reverse transcription polymerase chain reaction (RT-PCR) tests. Virus isolation from blood and tissue samples can also be used for diagnosis, but this method is time-consuming and requires personal protective equipment (PPE).

Diagnostic challenges may arise in non-endemic countries as BHF cases among travellers increase with the rise in tourism and travel to Bolivia.

Treatment

There is currently no cure or vaccine for Bolivian Hemorrhagic Fever (BHF). Treatment options are limited to supportive care and proper administration of fluids. However, there are some potential treatments that have been proposed or are under development:

Convalescent Immune Plasma

Following the isolation of the Machupo virus, convalescent immune plasma from survivors has been used to treat BHF. This approach has been employed similarly to the treatment for Argentine hemorrhagic fever.

Human Immunoglobulin

Administration of human immunoglobulin against the Machupo virus has shown to be protective in rhesus monkeys when given a few hours before or after exposure to the virus. However, no clinical trials have been conducted in human patients to confirm its efficacy and safety.

Ribavirin

Ribavirin is a broad-spectrum antiviral agent that has been effective against human Lassa fever and several arenavirus diseases in animal models. It has been used to treat a limited number of human BHF cases, but the small sample size has prevented clinical trials from being conducted to determine its effectiveness.

Candid#1 Vaccine

The Candid#1 vaccine, developed for the closely related Junín virus, has shown evidence of cross-reactivity to the Machupo virus. It may be an effective prophylactic measure for people at high risk of infection, but further testing is needed to confirm its efficacy.

Rodent Population Control

Measures to reduce contact between humans and the large vesper mouse (Calomys callosus), the primary vector of the Machupo virus, have proven effective in limiting the number of BHF outbreaks.

Prevention

Bolivian Hemorrhagic Fever (BHF) is a viral hemorrhagic fever that is endemic to Bolivia. The disease is caused by the Machupo virus, which is transmitted to humans by exposure to the excreta and secretions of wild native rodents, specifically the large vesper mouse (Calomys callosus), a rodent indigenous to northern Bolivia. Infected animals are asymptomatic and shed the virus in their excreta, thereby infecting humans. Evidence of person-to-person transmission of BHF also exists but is believed to be rare.

To prevent BHF, measures must focus on reducing contact between the vesper mouse and humans. This can include implementing rodent control measures and systematic trapping of rodents in populated urban areas, as well as increasing the domestic feline population to control the rodent population.

Additionally, public health education is crucial to raise awareness about the disease and promote preventive measures. People living in or travelling to endemic areas should be informed about the risks and advised to avoid contact with rodents and their excreta. They should also be encouraged to seek medical attention promptly if they develop any symptoms suggestive of BHF.

Furthermore, healthcare workers and laboratory personnel should adhere to strict infection control measures when handling potentially infectious materials, as BHF requires Biosafety Level Four conditions, the highest level. This is due to the high pathogenicity of the Machupo virus and the risk of laboratory-acquired infections.

Finally, although there is currently no vaccine or cure for BHF, ongoing research and development of vaccines and antiviral therapies are crucial to prevent future outbreaks.

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