Date: Fri 5 Jul 2019
Source: GIDEON (Global Infectious Disease Epidemiology Network) [edited]
<http://www.gideononline.com>

Re: ProMED-mail Undiagnosed illness - Bolivia (02): (LP) Bolivian haemorrhagic fever conf. http://promedmail.org/post/20190704.6551379

In 2019, a small outbreak of Bolivian haemorrhagic fever was reported at a hospital in La Paz [department], Bolivia. The following background data on Bolivian haemorrhagic fever are abstracted from Gideon www.GideonOnline.com and the Gideon e-book series.[1,2] Primary references are available from the author.

Bolivian haemorrhagic fever (BHF) is caused by Machupo virus (Arenaviridae, Tacaribe complex, _Mammarenavirus_). The disease was initially described in 1959 as a sporadic hemorrhagic illness in rural areas of Beni department, eastern Bolivia, and the virus itself was 1st identified in 1963. BHF is most common during April to July in the upper savanna region of Beni. Principal exposure occurs through rodents ([the large vesper mouse] _Calomys callosus_), which enter homes in endemic areas.

BHF is one of several human _Arenavirus_ diseases reported in the Americas: Argentine haemorrhagic fever (Junin virus), Brazilian haemorrhagic fever (Sabia virus), lymphocytic choriomeningitis, Venezuelan haemorrhagic fever (Guanarito virus) and Whitewater Arroyo virus infection. (At least 2 related diseases are reported in Africa: Lassa fever and Lujo virus infection.)

Infection of _C. callosus_ results in asymptomatic viral shedding in saliva, urine, and feces; 50% of experimentally infected _C. callosus_ are chronically viremic and shed virus in their bodily excretions or secretions. _C. callosus_ acquires the virus after birth, and start shedding it through their urine and saliva while suckling. When mice acquire the virus as adults, they may develop immunity and no longer shed the virus.

Although the infectious dose of Machupo virus in humans is unknown, exposed persons may become infected by inhaling virus in aerosolized secretions or excretions of infected rodents, ingestion of food contaminated with rodent excreta, or by direct contact of excreta with abraded skin or oropharyngeal mucous membranes. Nosocomial and human-to-human spread have been documented. Hospital contact with a patient has resulted in person-to-person spread of Machupo virus to nursing and pathology laboratory staff.

In 1994, fatal secondary infection of 6 family members in Magdalena, Bolivia from a single naturally acquired infection further suggested the potential for person-to-person transmission.

During December 2003 to January 2004, a small focus of haemorrhagic fever was reported in the area of Cochabamba. A 2nd _Arenavirus_, Chapare virus, was recovered from one patient with fatal infection.

Early clinical manifestations consist of nonspecific signs and symptoms, including fever, headache, fatigue, myalgia, and arthralgia. Within 7 days, patients may develop hemorrhagic signs, including bleeding from the oral and nasal mucosa and from the bronchopulmonary, gastrointestinal, and genitourinary tracts. Case fatality rates range from 5% to 30%.

Ribavirin has been used successfully in several cases of BHF. The recommended adult regimen is 2.0 g intravenously (IV), followed by 1.0 g IV every 6 hours for 4 days, and then 0.5 g every 8 hours for 6 days.

Note that the etiologic agent and clinical features of BHF are similar to those of Argentine hemorrhagic fever (AHF). Neurological signs are more common in AHF, while hemorrhagic diatheses are more common in BHF. A vaccine available for AHF could theoretically be effective against BHF as well.

References
1. Berger S. American hemorrhagic fevers: global status, 2019. Gideon e-books.
<https://www.gideononline.com/ebooks/disease/american-hemorrhagic-fevers-global-status/>
2. Berger S. Infectious diseases of Bolivia, 2019. 342 pages, 87 graphs, 495 references.
<https://www.gideononline.com/ebooks/country/infectious-diseases-of-bolivia/>
-----------------------------------------
Communicated by:
Steve Berger
Geographic Medicine
Tel Aviv Medical Center, Israel
steve@gideononline.com
=======================
[ProMED-mail thanks Dr. Berger for the overview of Bolivian haemorrhagic fever presented above. As noted in the previous comment, and above, Bolivian haemorrhagic fever, caused by Machupo virus, occurs sporadically in lowland Bolivia, especially in Beni department. There was a case there in 2013, and in 2012 ProMED-mail reported that 13 people had been infected with Machupo virus and 7 had died as a consequence of the disease. In Beni department at that time, 5 municipalities, including Magdalena, were reported to have had large populations of _Calomys callosus_ mice, the reservoir host of Machupo virus, which can persistently infect the mice. It is not surprising to find cases in lowland areas of La Paz department again, where the current cases are occurring. The drylands vesper mouse, _C. musculinus_ mentioned in the previous post, although present in southern Bolivia, is unlikely to be the reservoir rodent involved in the current cases. _C. callosus_ mice are the recognized reservoir hosts of Machupo virus. Health officials can provide information about rodent control and assist in implementing it to reduce the risk of exposure to Machupo virus, but effective long-term implementation of rodent control ultimately rests with local residents.

An image of _C. callosus_, the large vesper mouse and reservoir host of Machupo virus, can be seen at
<http://www.faunaparaguay.com/calomyscallosus.html>. - ProMED Mod.TY]

[HealthMap/ProMED-mail map:
Bolivia: <http://healthmap.org/promed/p/5>]
Date: Wed 3 Jul 2019 11:53 BOT
Source: La Razon [in Spanish trans. ProMED Mod.TY, edited]
<http://www.la-razon.com/sociedad/Virus-salud-arenavirus-medicos-La_Paz-muerte-interna_0_3177282262.html>

[The Ministry of] Health confirmed that a virus that killed a hospitalized patient and 2 physicians from La Paz is an arenavirus transmitted by rodents. The disease, after 7 days, causes haemorrhagic fever, a symptom presented by the patients hospitalized in intensive care in 2 health centers in La Paz.

One of the viruses in this family is Machupo that causes Bolivian hemorrhagic fever, a disease that, according to hypotheses, is affecting the patients that are under observation, La Razon reported this [Wed 3 Jul 2019] in its printed edition.

"In laboratory terms, from national laboratories such as INLASA [Instituto Nacional de Laboratorios de Salud; National Institute of Health Laboratories] and CENTROP, [Centro de Enfermedades Tropicales; Tropical Diseases Center] they have identified an arenavirus," said Gabriela Montano in a press conference.

The report is also backed by a report from the [US] Centers for Disease Control and Prevention in Atlanta [CDC], Georgia, USA.

"We have a preliminary result from the CDC in Atlanta that also mentions an arenavirus. All of these elements together allow us to provide this information to the public today," the official added.

This virus is transmitted by rodents, specifically called the corn rat or _Calomys musculinus_, and it may also be transmitted person-to-person.  [Byline: Ruben Arinez]
=========================
[Bolivian haemorrhagic fever, caused by Machupo virus, an arenavirus, occurs sporadically in lowland Bolivia, especially in Beni department. There was a case there in 2013 and in 2012, ProMED-mail reported that 13 people had been infected with Machupo virus and 7 had died as a consequence of the disease. In Beni department at that time, 5 municipalities, including Magdalena, were reported to have had large populations of _Calomys callosus_ mice, the reservoir host of Machupo virus, which can cause persistent infections in the mice. It would not be surprising to find cases in lowland areas of La Paz department as well, where the current cases are occurring. The drylands vesper mouse, _C. musculinus_ mentioned above, although present in southern Bolivia, is unlikely to be the reservoir rodent involved in these cases. _C. callosus_ mice are the recognized reservoir hosts of Machupo virus. Health officials can provide information about rodent control and assist in implementing it, but effective long-term implementation ultimately rests with local residents.

An image of _C. callosus_, the large vesper mouse and reservoir host of Machupo virus can be seen at
<http://www.faunaparaguay.com/calomyscallosus.html>.

An image of _C. musculinus_, the drylands vesper mouse, can be seen at
<http://www.faunaparaguay.com/calomysmusculinus.html>. - ProMED Mod.TY]

[HealthMap/ProMED-mail map of Bolivia:
<http://healthmap.org/promed/p/10123>]
Date: Mon 1 Jul 2019
Source: Eje Central Mexico [in Spanish, trans. ProMED Mod.MPP, edited]
<http://www.ejecentral.com.mx/alertan-por-enfermedad-viral-no-identificada-en-bolivia/>

An unknown disease that led to the death of an internal medicine physician and that has another 2 in serious condition has led to the activation of health protocols in Bolivia, requesting assistance from international medical teams in order to identify the aetiology of the disease, it was announced on Mon 1 Jul 2019 by the Minister of Health, Gabriela Montano.

Initial diagnostic tests indicated a "viral disease," but through the analysis of the physician who died and the 2 other professionals who are in intensive care, "they have discarded influenza and other viral diseases," such as dengue, according to Montano.

In the last hours, Montano increased the number of infected individuals to 5.  "We have 3 suspected cases in addition to the 1st 2 cases, the doctors; the other 3 are in the same hospital (in La Paz) as the original 2 cases," the Minister of Health said at a press conference.  "Two of the 3 new cases had contact with the 2 doctors who were infected. The 3rd person did not have contact with the professionals, but presented similar symptoms," said Montano.

In order to establish the origin of the disease, an infectious disease specialist from Brasil and another 2 specialists from Atlanta, United States [the Centers for Disease Control and Prevention, CDC], will help the national teams in the investigation.  The health authorities have not declared a state of epidemiologic emergency, while the representative from the Pan American Health Organization [PAHO/OPS] in Bolivia, Alfonso Tenorio, asked to follow protocols in order to "be calm."  "Bolivia has "the equipment and personnel fully trained in order to take the appropriate diagnostic steps, treatment, clinical management, and epidemiologic control," said Tenorio at a press conference.

As part of these protocols, the Ministry of Health ordered the mandatory use of masks and latex gloves in local hospitals.  At the end of last year [2018], Caranavi, the semitropical zone in the northeast of La Paz, where the deceased doctor was infected, reported a dengue outbreak that claimed the lives of 5 people.
Date: Mon 20 May 2019
Source: El Pais [in Spanish, trans. Mod.TY, edited]
<https://elpais.bo/reportan-un-nuevo-caso-de-hantavirus-en-padcaya/>

Tarija Departmental Health Services (SEDES) reported a new case of hantavirus [infection] in Padcaya municipality. The number of patients with this illness is within what is expected, because this season is when more people acquire the disease. Epidemiological surveillance is continuing in Arce province. The person who acquired this illness is male and is under medical care until his recuperation.

The head of the Epidemiological Unit of SEDES, Claudia Montenegro, stated that the patient is hospitalized in the San Juan de Dios Regional Hospital in Tarija awaiting his recuperation. The physician said that in Bermejo and Padcaya municipalities, the harvest of citrus fruit and sugar cane for production of sugar has begun, so there is a trend for the cases of this illness to increase. This is due to the large number of families that move to the countryside where the rodent (long tail) is present that transmits this disease [virus].

"In contrast to previous seasons, this year [2019], there were positives for this disease in Gran Chaco province, including fatalities," Montenegro commented. "Epidemiological surveillance there is being implemented, as well as in areas such as Padcaya and Bermejo."

The official explained that in these localities, the rodent that transmits the disease [virus] to families is present, and with agricultural activities, [people] move into places where this animal lives, and so new cases of patients with hantavirus [infections] are registered every year.

In order to prevent this illness, it is recommended that rodent control campaigns be done to reduce their populations, openings in houses be sealed, and that residents reduce the possibility for rodents to make nests within a radius of 30 meters [100 ft] around the house, and eliminate items that could attract these animals near the house (food, grain, garbage). Workers should employ protective measures during agricultural tasks and cleaning work.

Initial symptoms include fatigue, fever and muscle pain, especially in the thighs, hips and back. Also, patients may present with headache, dizziness, chills, nausea, vomiting, diarrhea and abdominal pain. [These symptoms may progress rapidly to respiratory difficulty requiring mechanical ventilation (hantavirus cardio pulmonary syndrome). Death can occur. - ProMED Mod.TY]
=====================
[The hantavirus involved in the above cases is not mentioned. Cases of hantavirus infections in Tarija department are not new. Tarija department is endemic for hantaviruses, and cases occur there sporadically. Last year (2018), there were 11 cases. The previouslyreported 2015 cases of hantavirus pulmonary syndrome (HPS) that occurred in Tarija department were confirmed. As noted in the previous comments, earlier cases of hantavirus pulmonary syndrome have been reported from tropical, lowland areas of Bolivia, including 7 cases in Tarija during 2014. The specific hantaviruses involved in these or previous cases in Bolivia were not given.

In the lowland Amazon Basin of Bolivia, the rodent hosts of the hantavirus that might be involved in these hantavirus pulmonary syndrome (HPS) cases, with their images, include the following: - Laguna Negra virus (_Calomys laucha_ <http://www.faunaparaguay.com/images/Calomys%20laucha%20enciso%2031aug2011.jpg> and _C. callosus_ <https://eee.uci.edu/clients/bjbecker/PlaguesandPeople/Calomyscallosusb.jpg>); - Bermejo (Chaco rice rat _Oligoryzomys chacoensis_ <http://www.faunaparaguay.com/oligorizomyschacoensis.html>); and - Oran (_O. longicaudatus_ <http://calphotos.berkeley.edu/imgs/512x768/0000_0000/0711/1203.jpeg>).

Since previous cases in Tarija department have occurred in Bermejo, perhaps Bermejo hantavirus was involved.

Dr. Jan Clement commented that there is a need to be able to differentiate Seoul (SEOV) as a causative agent, but that is hampered by the fact that most current commercial ELISA or WB formats do not contain (anymore) a SEOV antigen, so that a preliminary presumption of a hantavirus infection can even be missed in non-research laboratories (ibidem, and: Reynes J-M, Carli D, Bour J-B, Boudjeltia S, Dewilde A, Gerbier G, et al. Seoul virus infection in humans, France, 2014-2016. Emerg Infect Dis. 2017;23:973-7;  <https://wwwnc.cdc.gov/eid/article/23/6/16-0927_article>.

SEOV is widely distributed around the world in the brown rat and is likely found in Tarija department. - ProMED Mod.TY]

[HealthMap/ProMED map available at:
Tarija, Tarija, Bolivia: <http://healthmap.org/promed/p/12643>]
Date: Mon 29 Apr 2019
Source: El Deber [in Spanish, trans., ProMED Mod.TY, edited]
<https://www.eldeber.com.bo/santacruz/Reportan-un-caso-de-hantavirus-en-Postrervalle-20190428-9511.html>

A suspected case of [a] hantavirus [infection] in Postrervalle last week mobilized personnel of the medical centre of this municipality and the Office of Health of Vallegrande. The ill individual, a 17 year old, who works as a cowboy in the Mosqueras area, went to the [health] center, presenting with symptoms of [a] hantavirus [infection]. He was taken to Vallegrande where a corresponding chart was initiated and related tests were done that confirmed the 1st case of [a] hantavirus [infection] in the area. Due to the seriousness of the case, on [Fri 26 Apr 2019] the patient was transferred to Santa Cruz where he received treatment. It is believed that the patient was infected when he was in a rural property in Moroco, close to Mosqueras.

The Moroco - Mosqueras area is forested with high humidity due to the constant rains. There are several cattle ranches in the area. Rodrigo García, Chief of Health in Vallegrande, stated that they went immediately to the areas and established an [epidemiological] focal blockade and began to train people about management of the disease. Today [Mon 29 Apr 2019] a new team went into the place in order to verify the presence of long-tail rats that transmit the virus. A hantavirus outbreak was reported recently in [nearby] Tarija [department]. [Byline: Juan Carlos Aguilar F.]
========================
[The condition of the patient is reported as serious, prompting his transfer to Santa Cruz city where more advanced facilities are available. The seriousness of the case suggests that he may have developed hantavirus cardiopulmonary syndrome although no mention is made of the use of mechanical ventilation. The hantavirus involved in this case is not specified. The Moroco - Mosqueras area is an inter-Andean valley.

The report above indicates that it is forested area but the presence of cattle ranches indicates that extensive open areas of pasture must be present as well; making it difficult to determine which of several hantaviruses may be involved. Andes hantavirus has not been reported present in Bolivia.

In the lowland Amazon Basin of Bolivia, the rodent hosts of the hantavirus that might be involved in these cases, with their images, include the following:
- Laguna Negra virus (_Calomys laucha_ <http://www.faunaparaguay.com/images/Calomys%20laucha%20enciso%2031aug2011.jpg>
and _C. callosus_ <http://www.faunaparaguay.com/calomyscallosus.html>);
- Bermejo (Chaco rice rat _Oligoryzomys chacoensis_ <http://www.faunaparaguay.com/oligorizomyschacoensis.html>); and
- Oran (_O. longicaudatus_ <http://calphotos.berkeley.edu/imgs/512x768/0000_0000/0711/1203.jpeg>).

As Dr. Jan Clement pointed out previously, a battery of hantavirus diagnostic agents, including SEOV antigens is required to reach a definitive diagnosis. - ProMED Mod.TY]

[HealthMap/ProMED map available at: Bolivia: <http://healthmap.org/promed/p/5>]
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