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Outbreak of hantavirus pulmonary syndrome, Los Santos, Panama, 1999-2000.


An outbreak of hantavirus pulmonary syndrome hantavirus pulmonary syndrome An often fatal RTI caused by a hantavirus; the first cluster occurred in the Four Corners region of Southwestern US Epidemiology Mean age 32, 61% ♀, 72% Native American Case definition Unexplained bilateral interstitial  occurred in the province of Los Santos, Panama, in late 1999 and early 2000. Eleven cases were identified; 9 were confirmed by serology Serology

The division of biological science concerned with antigen-antibody reactions in serum. It properly encompasses any of these reactions, but is often used in a limited sense to denote laboratory diagnostic tests, especially for syphilis.
. Three cases were fatal; however, no confirmed case-patient died. Case-neighborhood serologic se·rol·o·gy  
n. pl. se·rol·o·gies
1. The science that deals with the properties and reactions of serums, especially blood serum.

2.
 surveys resulted in an overall hantavirus hantavirus, any of a genus (Hantavirus) of single-stranded RNA viruses that are carried by rodents and transmitted to humans when they inhale vapors from contaminated rodent urine, saliva, or feces. There are many strains of hantavirus.  antibody prevalence of 13% among household and neighborhood members from the outbreak foci. Epidemiologic investigations did not suggest person-to-person transmission of hantavirus infection. By use of Sin Nombre virus The Sin Nombre virus (literally "unnamed virus" in Spanish) (SNV) is the prototypical etiologic agent of hantavirus cardiopulmonary syndrome (HCPS). It was first isolated from rodents collected near the home of one of the initial patients with hantavirus pulmonary syndrome  antigen, hantavirus antibodies were detected in Oligoryzomys fulvescens and Zygodontomys brevicauda cherriei. This outbreak resulted in the first documented cases of human hantavirus infections Hantavirus Infections Definition

Hantavirus infection is caused by a group of viruses that can infect humans with two serious illnesses: hemorrhagic fever with renal syndrome (HFRS), and Hantavirus pulmonary syndrome (HPS).
 in Central America.

**********

Hantavirus pulmonary syndrome (HPS See Seer*HPS. ) is an infectious disease Infectious disease

A pathological condition spread among biological species. Infectious diseases, although varied in their effects, are always associated with viruses, bacteria, fungi, protozoa, multicellular parasites and aberrant proteins known as prions.
 typically characterized by fever, myalgia myalgia /my·al·gia/ (mi-al´jah) muscular pain.myal´gic

epidemic myalgia  see under pleurodynia.


my·al·gia
n.
, and headache and followed by dyspnea dyspnea /dysp·nea/ (disp-ne´ah) labored or difficult breathing.dyspne´ic

paroxysmal nocturnal dyspnea
, noneardiogenic pulmonary edema Pulmonary Edema Definition

Pulmonary edema is a condition in which fluid accumulates in the lungs, usually because the heart's left ventricle does not pump adequately.
, hypotension hypotension
 or low blood pressure

Condition in which blood pressure is abnormally low. It may result from reduced blood volume (e.g., from heavy bleeding or plasma loss after severe burns) or increased blood-vessel capacity (e.g., in syncope).
, and shock (1,2). Common laboratory findings include elevated hematocrit Hematocrit Definition

The hematocrit measures how much space in the blood is occupied by red blood cells. It is useful when evaluating a person for anemia.
Purpose

Blood is made up of red and white blood cells, and plasma.
, leukocytosis Leukocytosis Definition

Leukocytosis is a condition characterized by an elevated number of white cells in the blood.
Description

Leukocytosis is a condition that affects all types of white blood cells.
 with the presence of immunoblasts, and thrombocytopenia Thrombocytopenia Definition

Thrombocytopenia is an abnormal drop in the number of blood cells involved in forming blood clots. These cells are called platelets.
 (3,4). The case-fatality rate can be as high as 52% (5). The etiologic agent of HPS is any one of several hantaviruses carried by rodent hosts belonging to the family Muridae, subfamily subfamily /sub·fam·i·ly/ (sub´fam-i-le) a taxonomic division between a family and a tribe.

sub·fam·i·ly
n.
A taxonomic category ranking between a family and a genus.
 Sigmodontinae (6). Hantaviruses are most often transmitted to humans through the inhalation of infectious rodent feces, urine, or saliva. However, strain-specific virus transmission may occur fl-ore person to person (7-9).

HPS was first recognized in 1993 during an outbreak of severe respiratory disease in the Four Corners Region of the United States (10,11). Since then, 363 cases of HPS have been confirmed in the United States (12). Sin Nombre virus (SNV SNV Synovus Financial Corp. (stock symbol)
SNV Schweizerische Normenvereinigung (Swiss standards body)
SNV Stichting Nederlandse Vrijwilligers (Netherlands Development Organization) 
) was the first HPS-causing pathogen identified; its primary rodent reservoir host reservoir host
n.
A host that serves as a source of infection and potential reinfection of humans and as a means of sustaining a parasite when it is not infecting humans.
 is the deer mouse, Peromyscus maniculatus (13,14). However, four other hantaviruses, Bayou virus, Black Creek Canal virus, New York New York, state, United States
New York, Middle Atlantic state of the United States. It is bordered by Vermont, Massachusetts, Connecticut, and the Atlantic Ocean (E), New Jersey and Pennsylvania (S), Lakes Erie and Ontario and the Canadian province of
 virus, and Monongahela virus, each with a different rodent reservoir, have been characterized in the United States and associated with HPS (6,15-21).

Since 1993, HPS has also been reported and confirmed in six countries in South America--Argentina, Bolivia, Brazil, Chile, Paraguay, and Uruguay (6,9,22-30). Several distinct hantaviruses have been associated with HPS, including Andes virus (Argentina, Bolivia, Chile, and Uruguay), Bermejo virus (Bolivia), Juquitiba virus (Brazil), Laguna Negra virus (Bolivia, Paraguay), Lechiguanas virus (Argentina), and Oran virus (Argentina) (22,23,25,28,30,31).

Before 2000, no human hantavirus infections had been reported in Central America. However, in February 2000, health officials in Panama reported a cluster of acute respiratory illnesses in residents of the district of Las Tablas Tab·las  

An island of the central Philippines east of Mindoro. It is the largest of the Romblon Islands.
 in Los Santos Province Los Santos is a province of Panama. The capital city is Las Tablas, which is famous for its carnivals, the Festival Nacional de la Pollera (National Festival of the Pollera), and the Festival of the Patron Santa Librada; and the Festival Nacional de la Mejorana en Guarare .  from late December 1999 to February 2000 (32). Human illness was characterized by a febrile febrile /feb·rile/ (feb´ril) pertaining to or characterized by fever.

feb·rile
adj.
Of, relating to, or characterized by fever; feverish.
 prodrome prodrome /pro·drome/ (pro´drom) a premonitory symptom; a symptom indicating the onset of a disease.prodro´malprodro´mic

pro·drome
n. pl.
 with rapid progression to moderate-to-severe respiratory distress Respiratory distress
A condition in which patients with lung disease are not able to get enough oxygen.

Mentioned in: Lung Cancer, Non-Small Cell
. Serum specimens from three of four patients had immunoglobulin (Ig) M and IgG antibodies to SNV. In February and March 2000, an outbreak investigation by the Panamanian Ministry of Health, Gorgas Memorial Institute for Health Studies (Panama City), the U.S. Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center.  (Atlanta, GA), and the Pan American Health Organization The Pan American Health Organization (PAHO) is an international public health agency with 100 years of experience in working to improve health and living standards of the countries of the Americas. It serves as the specialized organization for health of the Inter-American System.  was conducted in collaboration with local medical and public health officials. Sequence analysis of virus genome from human serum samples and rodent tissue led to the identification of a novel hantavirus, Choclo virus, as the cause of HPS in this outbreak (33). This report summarizes the clinical, epidemiologic, and environmental findings of the investigation.

Materials and Methods

Case Definition

A suspected case of HPS was defined as fever (temperature [greater than or equal to] 38.3[degrees]C) and unexplained acute respiratory distress requiring supplemental oxygen, with radiographic radiographic (rā´dēōgraf´ik),
adj relating to the process of radiography, the finished product, or its use.
 evidence of acute respiratory distress syndrome acute respiratory distress syndrome
n.
See adult respiratory distress syndrome.
 or bilateral interstitial pulmonary infiltrates (34). A suspected case was also defined as an unexplained respiratory illness resulting in death, with a postmortem examination postmortem examination
n.
See autopsy.
 indicating noncardiogenic pulmonary edema without identifiable cause (34). A confirmed case of HPS was defined as a clinically compatible illness plus the presence of one of the following; 1) hantavirus-specific IgM antibodies in acute-phase serum, 2) hantavirus-specific nucleic acid nucleic acid, any of a group of organic substances found in the chromosomes of living cells and viruses that play a central role in the storage and replication of hereditary information and in the expression of this information through protein synthesis.  sequences by reverse transcriptase Reverse transcriptase

Any of the deoxyribonucleic acid (DNA) polymerases present in particles of retroviruses which are able to carry out DNA synthesis using an RNA template.
 polymerase chain reaction polymerase chain reaction (pŏl`ĭmərās') (PCR), laboratory process in which a particular DNA segment from a mixture of DNA chains is rapidly replicated, producing a large, readily analyzed sample of a piece of DNA; the process is  (RT-PCR RT-PCR

reverse transcriptase-polymerase chain reaction. See PCR1.
), or 3) hantavirus-specific antigen by immunohistochemistry (34).

Case Finding and Characterization

At visits to two hospitals in Panama Here is a list of hospitals in Panama.
  • Hospital Nacional (National Hospital) - State-of-the-art private hospital in Panama City, Panamá Province .
  • Hospital Santo Tomas - The biggest Ministry of Health Hospital in the country, located in Panama City, Panamá Province
 City and one in the Las Tablas District that admitted patients with suspected HPS, hospitalized patients were examined and interviewed when possible, and medical charts were reviewed. To identify past HPS patients, retrospective chart reviews were conducted on admissions dating back to August 1999 at these hospitals. In addition, medical records of any previous or current suspected HPS patients admitted to other district hospitals in the Las Tablas Province were obtained and reviewed. Clinical case information was collected on a standard abstraction form.

To monitor the spread of disease in Las Tablas and other areas of Los Santos Province, an outbreak communications center was established at the Ministry of Health in Panama City and staffed by physicians, public health officials, and health educators. Operations of this center included 1) passive surveillance for suspected cases of HPS, 2) a public hotline that addressed symptoms and signs of HPS and methods of prevention, and 3) nationwide distribution of HPS educational materials. Staff physicians also called hospitals throughout Panama to promote awareness of HPS among medical providers.

Community Surveys

Surveys for hantavirus antibodies were conducted on March 5, 2000, in six neighborhoods in the Las Tablas District and one in the Guarare District in which confirmed HPS patients resided. The primary objectives of the surveys were to determine the prevalence of hantavirus infection within households and neighborhoods of case-patients and the frequency of mild and asymptomatic infection.

Approximately 10-15 households, including the case-patient household, were sampled in each of the seven neighborhoods. Teams composed of public health officials, nurses, and phlebotomists visited each neighborhood. The day before the survey, pamphlets explaining the survey in Spanish were given to each household that had agreed to participate. All participants were administered a standard questionnaire that asked about demographic characteristics, illness history, and rodent exposure. Team members were familiarized with the questionnaire before the survey started. A 10-mL blood specimen (3-5 mL for children) for hantavirus serologic testing was collected from each interviewed participant.

Hospital Survey

A hospital survey was conducted March 9-10, 2000, among healthcare workers who cared for confirmed HPS patients at a major hospital in Panama City. This hospital received most of its cases from Las Tablas. The objectives of the survey were to 1) serologically determine exposure to hantavirus among doctors, nurses, respiratory therapists, physiotherapists, and nurses' aides who provided direct care to confirmed HPS patients and 2) assess whether person-to-person transmission occurred. Medical staff who provided direct medical care (i.e., [less than or equal to] 1 m from the patient) to infected patients in the emergency room and medical intensive care unit were compared with those in the coronary or neurologic intensive care units who had no exposure to case-patients. A standard self-administered questionnaire was used to inquire about timing and amount of exposures, specific types of exposures, and precautionary measures taken. A 10-mL blood specimen for hantavirus serologic testing was collected from each surveyed participant.

Rodent Investigation

Small mammals were sampled to determine potential hantavirus reservoir hosts. Primary sampling methods were trapping and collecting small mammals around households of confirmed and suspected HPS patients and from two uninhabited locations in Los Santos. The habitat of each trapping area was described. Small mammals were initially identified in the field on the basis of external characteristics and standard keys for the region. Definitive identification that used cranial cranial /cra·ni·al/ (-al)
1. pertaining to the cranium.

2. toward the head end of the body; a synonym of superior in humans and other bipeds.


cra·ni·al
adj.
 characteristics was performed at the Museum of Southwest Biology, University of New Mexico The University of New Mexico (UNM) is a public university in Albuquerque, New Mexico. It was founded in 1889. It also offers multiple bachelor's, master's, doctoral, and professional degree programs in all areas of the arts, sciences, and engineering. , where voucher specimens from these small mammals are currently archived. Liver, kidney, spleen, lung, heart, and a whole blood sample were collected from each trapped rodent for diagnostic testing Diagnostic testing
Testing performed to determine if someone is affected with a particular disease.

Mentioned in: Von Willebrand Disease
, and carcasses were preserved for rodent speciation speciation

Formation of new and distinct species, whereby a single evolutionary line splits into two or more genetically independent ones. One of the fundamental processes of evolution, speciation may occur in many ways.
. Trapping and sampling were performed according to established safety protocols (35). Panamanian team members were trained to trap and observe safety precautions when handling potentially infectious rodents.

Diagnostic Testing

All available serum specimens from suspected HPS patients were tested for IgM antibodies by using an IgM-capture format and inactivated inactivated

rendered inactive; the activity is destroyed.


inactivated viruses
treated so that they are no longer able to produce evidence of growth or damaging effect on tissue.
 SNV antigen and for IgG antibodies by an indirect enzyme-linked immunosorbent assay enzyme-linked immunosorbent assay
n.
ELISA.


Enzyme-linked immunosorbent assay (ELISA)
A diagnostic blood test used to screen patients for AIDS or other viruses.
 (ELISA ELISA (e-li´sah) Enzyme-Linked Immuno-Sorbent Assay; any enzyme immunoassay using an enzyme-labeled immunoreactant and an immunosorbent.

ELISA
n.
) as previously described (11). Serum samples from survey participants, rodents, and other small mammals were tested for IgG antibodies by using SNV antigens. IgG-positive survey participants were also tested for IgM antibodies by use of SNV antigens. Positive findings with SNV antigens in the IgG- or IgM-capture ELISAs indicate infections with New World hantaviruses rather than with SNV specifically.

Results

Characteristics of HPS Patients

Eleven case-patients with suspected HPS were identified and reported to the Panamanian Ministry of Health from December 25, 1999, to February 29, 2000 (Figure 1). Three patients (25%) died; neither serum nor tissue samples were available for diagnostic testing from these three patients. The remaining eight cases were confirmed by the presence of IgM against hantavirus in at least two separate serum specimens from patients; all eight also had IgG antibodies, with five demonstrating IgG seroconversion seroconversion /se·ro·con·ver·sion/ (-con-ver´zhun) the change of a seronegative test from negative to positive, indicating the development of antibodies in response to immunization or infection.  after the first specimen. One additional patient, whose onset of illness was August 24, 1999, was identified retrospectively. Although acute-phase clinical specimens were not available for testing, review of medical records indicated that her illness was clinically compatible with HPS, and her IgG titer in February 2000 was elevated (6,400). She was subsequently confirmed as the ninth HPS patient.

The median age of the 12 patients was 42 years (range 26-58 years); seven (58%) were women. The primary occupation of patients was as follows: secretary (2), housewife (2), truck driver/transporter (2), electrician (1), field pump worker (1), seamstress (1), teacher (1), security guard (1), and unidentified (1).

All cases occurred in the Las Tablas, Guarare, and Tonosi Districts of Los Santos Province. In Las Tablas and Guarare, eight towns had at least one patient with suspected HPS, and seven had one or more confirmed patients (Table 1). Two cases, one suspected and one confirmed, were identified in Tonosi. No clustering of cases occurred at the household level.

Two patients denied handling or cleaning up rodent excreta excreta /ex·cre·ta/ (eks-kret´ah) excretion (2).

ex·cre·ta
pl.n.
Waste matter, such as sweat or feces, discharged from the body.
 before their illnesses, while a third admitted frequently killing and handling rodents. In interviews, family members of all case-patients from Las Tablas District noted marked increases in the number of rodents in and around the home from November 1999 to February 2000.

Clinical Description of Confirmed HPS Patients

The spectrum of preadmission symptoms of the nine confirmed patients is documented in Table 2. The mean temperature on admission was 38.0[degrees]C (n = 6, range 37.3[degrees]C-39.6[degrees]C). The median systolic Systolic
The phase of blood circulation in which the heart's pumping chambers (ventricles) are actively pumping blood. The ventricles are squeezing (contracting) forcefully, and the pressure against the walls of the arteries is at its highest.
 and diastolic blood pressure Diastolic blood pressure
Blood pressure when the heart is resting between beats.

Mentioned in: Hypertension
 values were 100 mm Hg (n = 9, range 80-130) and 63 mm Hg (n = 9, range 50-80), respectively. The median pulse rate pulse rate
n.
The rate of the pulse as observed in an artery, expressed as beats per minute.
 was 102/min (n = 8, range 60-172). The median respiratory rate respiratory rate,
n the normal rate of breathing at rest, about 12 to 20 inspirations per minute.

systemic inflammatory response syndrome A term that '
 was 23/min (n = 8, range 14-36). No patient was unconscious or cyanotic Cyanotic
Marked by bluish discoloration of the skin due to a lack of oxygen in the blood. It is one of the types of congenital heart disease.

Mentioned in: Congenital Heart Disease
 on admission. A temperature of [greater than or equal to] 38.5[degrees]C was documented in all patients at some time during hospitalization. Seven of nine patients were hypotensive hypotensive /hy·po·ten·sive/ (-ten´siv) marked by low blood pressure or serving to reduce blood pressure.

hy·po·ten·sive
adj.
1. Of or characterized by low blood pressure.

2.
 during their illness (median lowest systolic blood pressure Systolic blood pressure
Blood pressure when the heart contracts (beats).

Mentioned in: Hypertension
 = 90, range 50-100), and three required inotropic inotropic /in·o·tro·pic/ (in´o-tro?pik) affecting the force of muscular contractions.

in·o·trop·ic
adj.
Affecting the contraction of muscle, especially heart muscle.
 therapy.

Laboratory values at admission and during hospitalization are listed in Table 3. Eight of nine patients were thrombocytopenic thrombocytopenic

of the nature of or pertaining to thrombocytopenia.
 either on admission or at some time during hospitalization. Five of nine had hematuria hematuria

Blood in the urine. It usually indicates injury or disease of the kidney or another structure of the urinary system or possibly, in males, the reproductive system. It may result from infection, inflammation, tumours, kidney stones, or other disorders.
 (urine erythroctyes > 10 per high power field, while four of nine had moderate proteinuria proteinuria /pro·tein·uria/ (-ur´e-ah) an excess of serum proteins in the urine, as in renal disease or after strenuous exercise.proteinu´ric

pro·tein·u·ri·a
n.
1.
 ([less than or equal to] 2+ on urine dipstick dipstick /dip·stick/ (dip´stik) a strip of cellulose chemically impregnated to render it sensitive to protein, glucose, or other substances in the urine. ). Evidence of renal function abnormalities was present in three of nine patients whose serum creatinine levels were >2.0 mg/dL.

Three of nine patients had aspartate aminotransferase aspartate aminotransferase
n. Abbr. AST
See SGOT.



aspartate aminotransferase

an enzyme that catalyzes the reversible transfer of an amino group:

$$\eqalign $$
 >500 U/L U/L Upload
U/L Uplink
U/L Universal/Local
U/L Units/Litre
, alanine aminotransferase alanine aminotransferase /al·a·nine ami·no·trans·fer·ase/ (ah-me?no-trans´fer-as) alanine transaminase.

alanine aminotransferase
n. Abbr. ALT
See SGPT.
 >300 U/L, total bilirubin Bilirubin

The predominant orange pigment of bile. It is the major metabolic breakdown product of heme, the prosthetic group of hemoglobin in red blood cells, and other chromoproteins such as myoglobin, cytochrome, and catalase.
 >1.5 mg/dL, and direct bilirubin >1.0 mg/dL. Two patients had clinical evidence of liver disease--one with hepatomegaly hepatomegaly /hep·a·to·meg·a·ly/ (hep?ah-to-meg´ah-le) enlargement of the liver.

hep·a·to·meg·a·ly
n.
The abnormal enlargement of the liver. Also called megalohepatia.
 and the other with seleral icterus icterus /ic·ter·us/ (ik´ter-us) [L.] jaundice.icter´ic

icterus neonato´rum  jaundice in newborn children.


ic·ter·us
n.
See jaundice.
. Hematemesis hematemesis /he·ma·tem·e·sis/ (he?mah-tem´e-sis) the vomiting of blood.

he·ma·tem·e·sis
n.
The vomiting of blood.
, melena melena /me·le·na/ (me-le´nah) the passage of dark stools stained with altered blood.

me·le·na
n.
, and coagulopathy (prothrombin time Prothrombin Time Definition

The prothrombin time test belongs to a group of blood tests that assess the clotting ability of blood. The test is also known as the pro time or PT test.
 = 22 s, partial thromboplastin time Partial Thromboplastin Time Definition

The partial thromboplastin time (PTT) test is a blood test that is done to investigate bleeding disorders and to monitor patients taking an anticlotting drug (heparin).
 = 167 s, fibrinogen Fibrinogen

The major clot-forming substrate in the blood plasma of vertebrates. Though fibrinogen represents a small fraction of plasma proteins (normal human plasma has a fibrinogen content of 2–4 mg/ml of a total of 70 mg protein/ml), its conversion
 = 161 mg/dL) also developed in one patient. Two of the three patients also had elevated serum amylase amylase (ăm`əlās'), enzyme having physiological, commercial, and historical significance, also called diastase. It is found in both plants and animals. Amylase was purified (1835) from malt by Anselme Payen and Jean Persoz.  values (294 and 437 U/dL).

Seven of nine patients had chest x-ray chest x-ray,
n an examination of the chest using x-rays. Routinely performed in patients complaining of chest pain to rule out respiratory or heart disease.

chest X-ray Chest film, see there
 examinations on admission. All had evidence of bilateral infiltrates, and one of seven had a radiographic pattern suggestive of suggestive of Decision making adjective Referring to a pattern by LM or imaging, that the interpreter associates with a particular–usually malignant lesion. See Aunt Millie approach, Defensive medicine.  pulmonary edema. Two patients who did not have chest x-ray examinations on admission subsequently were found to have bilateral interstitial infiltrates radiographically. Pulmonary edema of varying severity developed in four patients during the course of their illnesses; pleural effusions also occurred in three of these patients, and they were intubated within 24 to 72 hours after admission.

Community Survey

Interviews and serum specimens were obtained from 311 (83%) of 376 residents of seven different neighborhoods of Las Tablas and Guarare Districts in which confirmed HPS patients were identified. These 311 survey participants represented 119 households. A minimum of one blood specimen was obtained from each household. Forty (13%) of 311 survey participants had IgG against hantavirus. By sex, 25 (14%) of 178 females and 15 (11%) of 133 males had IgG antibodies. The median age of the 40 antibody-positive participants was 31.5 years (range 1-79). Age group prevalence estimates ranged from 9% (5/53, >61 years of age) to 21% (6/28, 51-60 years of age). Of 47 children, 5 (11%) [less than or equal to] 10 years of age had IgG antibodies. Antibody prevalences among patients' neighborhoods ranged from 6% to 31% (Table 4). Two of 10 household members of confirmed patients had IgG antibodies. Six (15%) of the 40 infected participants had visited a confirmed HPS patient.

Of 119 households surveyed, 31 (26%) had at least one member who had IgG against hantavirus (Table 4). Eight (8%) of 96 households had two or more antibody-positive members, while 1 (2%) of 54 households had three or more antibody-positive members. Prevalence of antibody-positive households (i.e., one or more antibody-positive members) per neighborhood ranged from 8% to 73%.

Among the 40 antibody-positive participants, occupations of those with the highest antibody prevalences were students (14%), secretaries (13%), agricultural workers (13%), livestock or vegetable farmers (12%), and housewives (11%). Among the 40 infected participants, 33 (82.5%) touched rodents, 31 (77.5%) cleaned up rodent droppings (e.g., sweeping, mopping), and 29 (72.5%) killed rodents after December 1, 1999. Fifteen (37.5%) noted increased numbers of peridomestic rodents compared with previous years.

Only five (12.5%) of 40 antibody-positive participants recalled fever or myalgia since December 1, 1999. In contrast, the most common symptoms reported were upper respiratory in nature, such as rhinorrhea (45%), sore throat Sore Throat Definition

Sore throat, also called pharyngitis, is a painful inflammation of the mucous membranes lining the pharynx. It is a symptom of many conditions, but most often is associated with colds or influenza.
 (35%), and cough (22%). Moreover, of two participants who bad both IgM and IgG antibodies, one experienced only a cough without fever, while the other was asymptomatic.

Hospital Serosurvey

Questionnaires and serum samples were obtained from 38 directly exposed and 39 unexposed healthcare workers. No IgM antibodies were present in the 77 workers. Only one of 38 exposed workers had IgG antibodies. This person, a medical resident, directly cared for five confirmed HPS patients (each healthcare worker cared for an average of 4 patients, range 1-5) for a total of approximately 15 patient-care days (group mean 43, range 1-70). His first exposure occurred in late December 1999. While caring for patients, he wore gloves, gown, and mask most of the time and was not directly exposed to respiratory secretions. He denied any travel to Los Santos Province after December 1999 and had no history of exposure to rodents. However, he was uncertain about whether he had visited Los Santos Province before December 1999. He denied having any febrile illness after late December 1999. Of the remaining 37 healthcare workers who cared for HPS patients, four (11%) were directly exposed to respiratory secretions in the eye, nose, or mouth; 26 (70%) wore gloves, gowns, and masks most of the time.

One unexposed worker, an operating room operating room
n. Abbr. OR
A room equipped for performing surgical operations.
 assistant, also had IgG against hantavirus. She denied travel to Los Santos Province, exposure to rodents, or febrile illness after December 1999. However, history of travel to Los Santos Province before December 1999 was again uncertain.

Rodent Investigation

Rodent traps were set at 13 sites, l0 of which were homes and immediate surroundings of patients with confirmed and suspected HPS. One of the three remaining sites was the home of a patient previously suspected to have HPS who did not have antibodies to hantavirus. The other two locations were a rural agricultural area in the Pocri District of Los Santos Province and a late secondary forest area (two subsites) near the town of Portabelo, Montijo District, Veraguas Province. In all, 120 rodents representing nine species and seven opossums (two species) were captured (Table 5). Of the 120 rodents, 52 (43%) were caught from the 10 patient household areas. A trap success of approximately 5% was achieved at these homes. Only one of the six antibody-positive rodents (Oligozyzomy fulvescens) was captured at the household of a confirmed HPS case-patient (Las Tablas town); five were captured in the Pocri District.

Discussion

We have documented the first human cases of hantavirus infection in Central America. A novel Panamanian hantavirus, Choclo virus, was subsequently characterized and is thought to be responsible for HPS during the outbreak (33). Virus genetic sequences of Choclo virus from case-patients were identical to those from O. fulvescens (33).

The clinical spectrum of pulmonary disease among HPS patients in Panama varied widely from severe disease requiring intubation intubation /in·tu·ba·tion/ (in?too-ba´shun) the insertion of a tube into a body canal or hollow organ, as into the trachea.

endotracheal intubation
 and cardiovascular support to mild pulmonary involvement with a benign clinical course. Extrapulmonary manifestations, such as hepatobiliary disease, hemorrhage, and central nervous system sequelae sequelae Clinical medicine The consequences of a particular condition or therapeutic intervention , were also present. The case-fatality rate (0% among 9 confirmed cases; 25% among 12 total suspected and confirmed cases) was noticeably lower than that described in Paraguay (12%), Chile (54%), and the United States (52%) in confirmed cases (5,9,29).

We found an antibody prevalence of 13% among household and neighborhood members of all ages from the outbreak foci. This figure is comparable to that found in Paraguay, but higher than in Chile and the United States (9,29,36). The percentages of hantavirus antibody-positive persons and households were particularly high in San Jose, the only town with two confirmed case-patients. Clustering of cases of HPS was not observed, and household clustering of antibody-positive persons was infrequent. Only 13% of hantavirus antibody-positive persons had a febrile illness after early December 1999, and none had an illness compatible with HPS, which suggests that mild infections occurred, as documented with other hantaviruses in the United States and Chile (9,36-38).

Person-to-person transmission of hantavirus infection was not demonstrated during the outbreak. Inlkequent clustering of antibody-positive serosurvey participants by household probably reflected common exposures to infect ed rodent excreta peridomestically. Furthermore, only I of 38 medical care workers who cared for HPS patients had IgG antibodies, while none had IgM antibodies. Similarly, 1 of 39 workers who did not care for HPS patients had IgG antibodies. Thus far, person-to-person transmission has only been suggested during outbreaks caused by Andes virus in Argentina and Chile (7-9).

Climate data from Los Santos Province clearly demonstrated a two- to threefold increase in rainfall in September and October 1999 when compared to similar periods in the previous 4 years (Figure 2). Such atypical rainfall patterns may have led to increases in rodent populations, which led to more frequent contact between infected rodents and humans and subsequent human infection. Many residents of patient-neighborhoods of Las Tablas reported an unusually large number of rodents from December 1999 through January 2000. Similar patterns of environmental change followed by outbreaks of human disease have been observed in the United States and South America (29,39,40).

Ecologic observations in Los Santos provided an impression of a dry, open, and deforested region. Long-term commercial logging, agriculture (primarily com and sugarcane), and animal husbandry animal husbandry, aspect of agriculture concerned with the care and breeding of domestic animals such as cattle, goats, sheep, hogs, and horses. Domestication of wild animal species was a crucial achievement in the prehistoric transition of human civilization from  practices (mainly cattle and horses) have contributed to the deforestation deforestation

Process of clearing forests. Rates of deforestation are particularly high in the tropics, where the poor quality of the soil has led to the practice of routine clear-cutting to make new soil available for agricultural use.
 process. The rodent species most closely associated with corn and sugarcane fields, Zygodontomys brevicauda cherriei, is a likely reservoir host for a new hantavirus, Calabazo virus (33). O. fulvescens, the likely reservoir for Choclo virus, was found in grass of varying heights near human habitation and in cattle and horse pastures. Given the observed habitat associations of these two species, agriculture and animal husbandry practices in the Los Santos regions may have had a positive effect on populations of rodents associated with hantaviruses and may continue to augment the risk for HPS as the human population increases.

The social and economic impact of this outbreak was substantial. The cancellation of Carnival, one of Panama's most celebrated festivals, had financial effects on residents of Las Tablas. Nevertheless, the public health impact of holding Carnival could also have been substantial, given the potential for rodent exposure among thousands of visitors and participants.

In conclusion, this outbreak resulted in the first documented cases of human hantavirus infections in Central America. Although cases were not reported from other districts of Los Santos or other provinces of Panama during the investigation, surveillance for HPS nationwide should continue, as serologic testing capabilities have since been implemented in Panama. More extensive sampling of rodent populations would help identify other areas in Panama with large numbers of O. fulvescens that could place residents at risk for Choclo virus infection. Longitudinal studies longitudinal studies,
n.pl the epidemiologic studies that record data from a respresentative sample at repeated intervals over an extended span of time rather than at a single or limited number over a short period.
 of rodents, particularly those species implicated im·pli·cate  
tr.v. im·pli·cat·ed, im·pli·cat·ing, im·pli·cates
1. To involve or connect intimately or incriminatingly: evidence that implicates others in the plot.

2.
 as reservoir hosts, will be necessary to monitor the fluctuation and distribution of rodent population numbers over time and their correlation with human infection (41). Educational campaigns promoting risk reduction, such as proper clean-up of rodent excrement excrement /ex·cre·ment/ (eks´kri-mint)
1. feces.

2. excretion (2).


ex·cre·ment
n.
Waste matter or any excretion cast out of the body, especially feces.
, sealing homes against the entry of rodents, and other rodent-proofing techniques, should continue as additional cases of HPS are reported in Panama.
Table 1. Geographic distribution of suspected and confirmed HPS cases,
Los Santos Province, Panama, August 1999-February 2000 (a)

                               No. confirmed    No. suspected
Town              District          cases            cases

El Cocal         Las Tablas          1                0
La Tronosa       Las Tablas          0                1
Las Tablas       Las Tablas          1                0
Los Angeles      Las Tablas          1                0
San Jose         Las Tablas          2                0
Santo Domingo    Las Tablas          1                0
Bella Vista       Guarare            1                0
La Enea           Guarare            1                1
Las Llanas        Tonosi             1                1

(a) HPS, hantavirus pulmonary syndrome.

Table 2. Symptoms on admission in nine patients with
laboratory-confirmed hantavirus pulmonary syndrome, Los Santos
Province, Panama, August 1999-February 2000

Symptom                     No. (%)

Fever                       9 (100)
Dyspnea                     8 (89)
Myalgia                     8 (89)
Cough                       7 (78)
Malaise                     6 (67)
Vomiting                    5 (56)
Nausea                      4 (44)
Headache                    4 (44)
Arthralgia                  4 (44)
Weakness                    4 (44)
Lower back pain             3 (33)
Abdominal pain              2 (22)
Chest pain                  2 (22)
Dizziness                   2 (22)
Diarrhea                    1 (11)
Dysuria                     1 (11)
Lower extremity edema       1 (11)

Table 3. Laboratory values of confirmed HPS patients on admission
and during hospitalization (a)

                                               Median
                                 No. of        value
Test                             cases      (admission)        Range

Leukocyte count                    7             6.4          3.6-14.1
(x1,000/[mm.sup.3])
Hematocrit (%)                     7            39.7         35.1-44.2
Platelet (x1,000/[mm.sup.3])       7            84             47-186
BUN (mg/dL)                        2             7              5-9
Creatinine (mg/dL)                 3             0.8          0.6-1.0
CPK (IU/L)
LDH (U/L)                          1           219            219 (b)
Albumin (g/dL)
AST (U/L)                          2            42             40-43
ALT (U/L)                          2            33             31-35
Bilirubin, total (mg/dL)
Bilirubin, direct (mg/dL)
Amylase (U/L)
PT (s)                             1            11.7         11.7-11.7
PTT (s)                            1            31.2         31.2 (b)
Urine leukocyte count              5             9              6-35
(/hpf)
Urine erythrocyte count            4            12              4-25
(/hpf)

                                               Median
                                              maximum
                                               value
                                 No. of     (admission +
Test                             cases    hospitalization)     Range

Leukocyte count                    9            11.4          5.7-28.1
(x1,000/[mm.sup.3])
Hematocrit (%)                     9            41.0         31.4-52.4
Platelet (x1,000/[mm.sup.3])       9
BUN (mg/dL)                        8             26            1-56
Creatinine (mg/dL)                 8            2.2           1.0-3.3
CPK (IU/L)                         6            240          38-12,840
LDH (U/L)                          7            1028         32-3,775
Albumin (g/dL)                     7
AST (U/L)                          7            223           46-983
ALT (U/L)                          7            168           32-570
Bilirubin, total (mg/dL)           7            1.1          0.8-8.0
Bilirubin, direct (mg/dL)          7            0.6          0.1-6.5
Amylase (U/L)                      6             74           38-437
PT (s)                             4            13.7        11.3-22.0
PTT (s)                            4             28           27-167
Urine leukocyte count              9              8            1-35
(/hpf)
Urine erythrocyte count            9             10            1-35
(/hpf)

                                               Median
                                           minimum value
                                            (admission +
Test                                      hospitalization)     Range

Leukocyte count
(x1,000/[mm.sup.3])
Hematocrit (%)
Platelet (x1,000/[mm.sup.3])                     60            26-429
BUN (mg/dL)
Creatinine (mg/dL)
CPK (IU/L)
LDH (U/L)
Albumin (g/dL)                                   2.5           1.2-3.2
AST (U/L)
ALT (U/L)
Bilirubin, total (mg/dL)
Bilirubin, direct (mg/dL)
Amylase (U/L)
PT (s)
PTT (s)
Urine leukocyte count
(/hpf)
Urine erythrocyte count
(/hpf)

(a) HPS, hantavirus pulmonary syndrome; ALT, alanine aminotransferase;
AST, aspartate aminotransferase; BUN, blood urea nitrogen; CPK,
creatinine phosphokinase; LDH, lactate dehydrogenase; PT, prothrombin
time; PTT, partial thromboplastin time; hpf, high power field.

(b) There was only one case for this laboratory category.

Table 4. Hantavirus IgG antibody-positive findings of survey
participants and households by neighborhood, town, and district
of confirmed HPS patients, Los Santos Province (a)

Neighborhood                                        No. of persons
(case no.)            Town            District          tested

2                  Los Angeles       Las Tablas           45
4                   San Jose         Las Tablas           34
7                  Bella Vista        Guarare             50
8                   San Jose         Las Tablas           48
9                 Santo Domingo      Las Tablas           43
11                 Las Tablas        Las Tablas           41
12                  El Cocal         Las Tablas           50

Total                                                     311

                                       No. of           No. (%)
Neighborhood     No. (%) persons     households       households
(case no.)      antibody positive      tested      antibody positive

2                    4 (8.9)             18             4 (22.2)
4                    5 (14.7)            11             3 (27.3)
7                    3 (6.0)             24             2 (8.3)
8                   15 (31.3)            15            11 (73.3)
9                    6 (14.0)            15             4 (26.7)
11                   4 (9.8)             15             4 (26.7)
12                   3 (6.0)             21             3 (14.3)

Total               40 (12.9)           119            31 (26.1)

(a) IgG, immunoglobulin G; HPS, hantavirus pulmonary syndrome.

Table 5. List of species of rodents and opossums captured at 13
trapping sites in Los Santos and Veraguas Provinces, Panama,
February-March 2000, and antibody results

                                             No.       No. hantavirus
Rodent species (common name)               captured   antibody-positive

Zygodontomys brevicauda cherriei
  (cane rat)                                  50              4
Sigmodon hispidus (hispid cotton rat)         20              0
Oligoryzomys fulvescens (fulvous pigmy
  rice rat)                                   15              2
Oryzomys couesi (Coues's rice rat)            14              0
Mus musculus (house mouse)                    9               0
Liomys adspersus (Panamanian spiny
  pocket mouse)                               8               0
Oryzomys concolor (colored rice rat)          2               0
Proechimys semispinosus
  (silky spiny rat)                           1               0
Rattus rattus (black rat)                     1               0
Marmosa mexicana. (Mexican mouse
  opossum)                                    4               0
Marmosa robinsoni (Robinson's mouse
  opossum)                                    3               0


Acknowledgments

We thank Jose Manuel Teran Sitton, Amalia Rodrigues, Pedro Rios, Mario I Avila Diaz, Ivan Alexis Villalaz, Francisco A. Crespo Perez, Bienvenido Munoz Cano, Esteban Morales, Cornelio Campos, Justo Serrano, Eric Pinilla, Luis Bravo, Luis Castellanos, Lillian Reneau-Vernon, Joni C. Young, Amy Corneli, Kimberly Dills, Amera Khan, Patrick Stockton, Linda Pezzanti, and Terry Yates for their assistance during the investigation, and Kathleen Murray for her helpful review of this manuscript.

Dr. Bayard is an epidemiologist with the Gorgas Memorial Institute for Health Studies in Panama City. He is also a professor of epidemiology with the Faculty of Medicine, University of Panama. His research interests include the epidemiology of emerging infectious diseases.

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Hidalgo thäl`gō), state (1990 pop. 1,888,366), 8,058 sq mi (20,870 sq km), central Mexico. Pachuca de Soto is the capital.
 NTR NTR Normal Trade Relations (international economic term; Most Favored Nation, MFN)
NTR Nitro (Nintendo DS codename)
NTR National Trauma Registry (Canada)
NTR Non-Traditional Revenue
, Veiga APR APR

See: Annual Percentage Rate
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Vicente Bayard, * ([dagger]) Paul T. Kitsutani, ([double dagger]) Eduardo O. Barria, * Luis A. Ruedas, ([section]) David S. Tinnin, ([paragraph]) Carlos Munoz, (#) Itza B. de Mosca, (#) Gladys Guerrero, ** Rudick Kant, ([dagger][dagger]) Arsenio Garcia, * Lorenzo Caceres, * Fernando G. Gracia, * Evelia Quiroz, * Zoila de Castillo, * Bias Armien, * Marlo Libel, ([dagger][dagger]) James N. Mills, ([double dagger]) Ali S. Khan, ([double dagger]) Stuart T. Nichol, ([double dagger]) Pierre E. Rollin, ([double dagger]) Thomas G Ksiazek, ([double dagger]) and Clarence J. Peters ([double dagger][double dagger])

* Gorgas Memorial Institute for Health Studies, Panama City, Panama; ([dagger]) University of Panama, Panama City, Panama; ([double dagger]) Centers for Disease Control and Prevention, Atlanta, Georgia, USA; ([section]) University of Wisconsin, Madison, Wisconsin, USA; ([paragraph]) University of New Mexico, Albuquerque, New Mexico “Albuquerque” redirects here. For other uses, see Albuquerque (disambiguation).
Albuquerque (pronounced [ˈæl.bə.kɚ.kiː], Spanish: [al.βu.
, USA; (#) Ministry of Health, Panama City, Panama; ** Complejo Hospital A.A.M., Panama City, Panama; ([dagger][dagger]) Pan American Health Organization, Washington DC, USA; and ([double dagger][double dagger]) University of Texas, Galveston, Texas, USA

Address for correspondence: Paul T. Kitsutani, National Institute of infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo, 162-8640 Japan; fax: 81-3-5285-1129; e-mail: kitsu@nih.go.jp
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