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  • 2009 Houston rabies case poses new questions about age-old illness

    Source: http://www.businessweek.com/lifestyl...ay/636424.html

    Texas Girl Recovers From Rabies Without Intensive Care
    Natural defense against the disease could be more common than thought, experts say

    THURSDAY, Feb. 25 (HealthDay News) -- The seemingly miraculous recovery from rabies of a 17-year-old Texas girl -- diagnosed months after a suspected bat bite -- is leaving doctors scratching their heads and wondering if such cases might be less rare than is believed.

    The case "suggests the rare possibility that abortive rabies can occur in humans and might go unrecognized," write a team of researchers reporting in this week's issue of Morbidity and Mortality Weekly Report, a publication of the U.S. Centers for Disease and Control and Prevention.

    As noted in the report, rabies -- typically transferred to humans via the bites of infected animals such as dogs, raccoons or bats -- is largely fatal if left untreated, and only six such patients have been known to survive worldwide.

    In late February of 2009, the girl in question was brought to a Texas hospital, disoriented and in serious pain. She received treatment and within three days her symptoms cleared up and she was sent home. On March 6, however, she was admitted to another hospital with severe headache, rash and weakness in the limbs. This time, she received a diagnosis of encephalitis -- swelling of the brain. She received a barrage of drugs including the antiviral acyclovir (Zovirax) and the antibacterial drug isoniazid (Nydrazid).

    However, by March 10 the girl became sicker, weaker and "combative," wrote the team led by Dr. Galit Holzmann-Pazgal, an assistant professor of pediatrics at the University of Texas School of Medicine, in Houston. At this time, the girl mentioned that she had been brushed by flying bats in a cave during a hiking trip more than two months earlier, although she did not recall being bitten.

    Tests performed the next day showed antibodies to the rabies virus and on March 14 the girl received one dose of rabies vaccine. She did not get the full round of doses because it was feared it would spur a dangerous immune response.

    During all of this, the patient did not require intensive care. In fact, her symptoms resolved so well that she was discharged on March 22. She subsequently returned (on an outpatient basis) complaining of headache on March 29 and then again on April 3. But the headaches went away and she has not since needed hospital care.

    This case of "abortive" human rabies appears to be a first, the researchers said. They noted that her illness seemed to follow the typical rabies pattern: An acute encephalopathy about two months after bat exposure is about right for the virus' known incubation period. The girl's symptoms also seemed compatible with rabies, as well, and no other diagnosis appears plausible.

    And yet, unlike typical human rabies, in this case "the clinical manifestation was relatively mild," suggesting "more limited" viral spread and "less apparent stimulation of the immune system," according to an editorial comment in the journal. Along with the researchers, the editorial speculates that, in rare cases, humans might develop a mild form of rabies infection from which recovery without intensive care might be possible.

    More information

    Learn the warning signs of rabies at the U.S. Centers for Disease Control and Prevention.

    -- E.J. Mundell

    SOURCE: Feb. 26, 2010, Morbidity and Mortality Weekly Report

  • #2
    Re: Texas Girl Recovers From Rabies Without Intensive Care

    This is EXTREMELY unusual. Doctors scratching their heads sounds about right. I wonder if an MMWR is forthcoming. I think a ProMED post is definitely coming.

    The only other possibility I can think of is that her illness was some other form of encephalitis, and the rabies virus she had been infected with had not yet caused any symptoms. The vaccine she was given would then have prevented the development of rabies, and she would then have recovered from whatever encephalitis virus was making her ill.

    Sounds bizarre, but I think if milder cases of rabies existed, we'd have seen them before now. We have seen in the past few years a couple (one in Wisconsin, one in Brazil) rabies survivors, but they required a special treatment regimen, and months in the ICU.

    Comment


    • #3
      Re: Texas Girl Recovers From Rabies Without Intensive Care

      The MMWR. The red text below indicates that antibodies to rabies were not found until after the vaccine was given. But the testing at the bottom of the article rules out just about any other etiology I could think of (although a lot of encephalitis never gets a causative agent found).



      Morbidity and Mortality Weekly Report (MMWR)MMWR
      Text size:smlxl
      Add this to...
      FavoritesDel.icio.usDiggFacebookGoogle BookmarksYahoo MyWeb Presumptive Abortive Human Rabies --- Texas, 2009
      Weekly
      February 26, 2010 / 59(07);185-190


      Rabies is a serious zoonotic disease. Recovery has been well documented in only six human patients worldwide (1,2). Five of those patients had received rabies vaccinations before illness; one had not received rabies vaccination but survived infection after prolonged intensive care. In most of these survivors, moderate to profound neurologic sequelae occurred (2,3). In all six survivors, rabies was diagnosed based on exposure history, compatible clinical symptoms, and detection of rabies virus-neutralizing antibodies (VNA). This report describes the clinical course and laboratory findings of an adolescent girl with encephalitis who had not had rabies vaccination and who had been exposed to bats 2 months before illness. Antibodies to rabies virus were detected in specimens of the girl's serum and cerebrospinal fluid (CSF) by indirect fluorescent antibody test (IFA). However, the presence of rabies VNA was not detected until after she had received single doses of rabies vaccine and human rabies immune globulin (HRIG). Although the patient required multiple hospitalizations and follow-up visits for recurrent neurologic symptoms, she survived without intensive care. No alternate etiology was determined, and abortive human rabies (defined in this report as recovery from rabies without intensive care) was diagnosed. Public education should emphasize avoiding exposure to bats and other potentially rabid wildlife and seeking prompt medical attention after exposure to such animals. Rabies is preventable if rabies immune globulin and vaccine are administered soon after an exposure; however, this case also suggests the rare possibility that abortive rabies can occur in humans and might go unrecognized.

      Case Report

      On February 25, 2009, an adolescent girl aged 17 years went to a community hospital emergency department with severe frontal headache, photophobia, emesis, neck pain, dizziness, and paresthesia of face and forearms. The headaches had begun approximately 2 weeks before she went to the hospital (Figure). Her examination was significant for intermittent disorientation, with a Glasgow Coma Score of 14, nuchal rigidity, and fever to 102.0oF (38.9oC). Computed tomography of her head was normal. A lumbar puncture (LP) was performed and revealed a white blood cell (WBC) count of 163/mm3, no red blood cells (RBC), 97% lymphocytes, 3% monocytes, and glucose of 61 mg/dL (Table 1). The patient was treated with intravenous ceftriaxone and dexamethasone, but when CSF bacterial cultures produced no growth, these medications were discontinued. After 3 days in the hospital, the girl's symptoms resolved, and she was discharged home.

      Subsequently, her headaches recurred and intensified; on March 6, she went to another local hospital with photophobia, emesis, and myalgias, particularly of the neck and back. Magnetic resonance imaging (MRI) of her head demonstrated enlarged lateral ventricles for her age; another LP was performed and revealed a protein level of 160 mg/dL, WBC count of 185/mm3, and RBC count of 1/mm3 with 95% lymphocytes and 5% macrophages (Table 1). She was transferred to a tertiary-care children's hospital that same day.

      On admission to the hospital (Figure), she was afebrile, alert, and oriented. Fundoscopic examination demonstrated a blurring of disk margins bilaterally. She was photophobic with transient limitation of vision in the left visual field. Initially, she had decreased strength of the left lower and upper extremities, but it resolved during subsequent examinations. She also had a new papular pruritic rash on her arms and back. She received a diagnosis of suspected infectious encephalitis and was treated during the hospitalization with intravenous acyclovir, ceftriaxone, ethambutol, isoniazid, pyrazinadmide, and rifapmin. On March 10, the girl reported loss of sensation and strength of the right extremities, and weakness was confirmed on examination. Emesis increased, and she became agitated and combative. But these symptoms resolved the next day. Repeat LP demonstrated increased intracranial pressure (Table 1).

      An extensive workup for potential etiologies of encephalitis/aseptic meningitis was performed, but no definitive etiology was determined (Table 2). On March 10, the medical team elicited a history of bat exposure, and rabies was considered in the differential diagnosis. The patient recalled that approximately 2 months before her headaches began she had entered a cave while on a camping trip in Texas and came into contact with flying bats. Although several bats hit her body, she did not notice any bites or scratches. The patient also reported owning pet ferrets and a dog; all were in good health and under routine veterinary care.

      The patient reportedly had never received rabies prophylaxis. On March 11, serologic tests of serum and CSF for antirabies virus antibodies, polymerase chain reaction (PCR) tests of saliva and nuchal skin biopsy for the presence of rabies virus RNA, and direct fluorescent antibody tests of the nuchal biopsy for rabies virus antigen were performed at CDC. No rabies virus antigens or RNA were detected. However, four serum and CSF samples tested positive for rabies virus antibodies by IFA. Serum immunoglobulin G (IgG) reactivity increased to a peak dilution of 1:8192 and immunoglobulin M (IgM) to 1:32. The CSF IgG was positive up to dilution 1:32 through March 19 and by April 3 had decreased to 1:8. The CSF IgM remained negative (Table 1). The positive IFA results were corroborated by a Western blot assay performed in blinded fashion by an independent investigator. Although rabies virus can crossreact serologically with other members of the Lyssavirus genus, Kern Canyon virus (KCV) is the only other rhabdovirus associated with bats in North America that potentially could demonstrate a limited serologic crossreactivity with rabies virus. KCV RNA was not detected in the patient's skin biopsy, saliva, and CSF by nested PCR.

      On March 14, after notification of positive rabies serology results, the girl received 1 dose of rabies vaccine and 1,500 IU of HRIG. Additional doses of vaccine were not administered because of concern over possible adverse effects from potentiating the immune response. On March 19 and March 29, the patient's serum tested positive for rabies VNA by the rapid fluorescent focus inhibition test (RFFIT), whereas her CSF remained negative for rabies VNA (Table 1).

      The patient was managed supportively and never required intensive care. She was discharged on March 22 with clinical symptom resolution but returned to the emergency department on March 29 with recurring headache. She left before an LP could be performed, but returned to the emergency department again on April 3 with headache and emesis. At that time, an LP was performed, and her CSF opening pressure was still elevated (Table 1). After the LP, her headache resolved. She was not rehospitalized and did not return for follow up in the outpatient clinic.

      Questionnaires were administered to close friends and family members of the girl and to health-care workers to assess indications for postexposure prophylaxis (PEP). Only the girl's boyfriend met the criteria and received PEP (4). The current clinical status of the patient or her boyfriend is unknown.

      Reported by
      G Holzmann-Pazgal, MD, A Wanger, PhD, G Degaffe, MD, C Rose, MD, G Heresi, MD, R Amaya MD, Univ of Texas School of Medicine Dept of Pediatrics; A Eshofonie, MD, H Lee-Han, PhD, A Awosika-Olumo, MD, Bur of Epidemiology, Office of Surveillance and Public Health Preparedness, Houston Dept of Health and Human Svcs, Houston, Texas. I Kuzmin, MD, PhD, CE Rupprecht, VMD, PhD, Div of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases, CDC.

      Editorial Note
      This is the first reported case in which certain clinical and serologic findings indicate abortive human rabies and in which, despite an extensive medical investigation, no alternate etiology for the illness was determined. The patient's positive serologic results offer evidence of rabies virus infection; IFA and Western blot assays indicated the presence of antibodies capable of binding to rabies virus antigens before the patient received rabies PEP. Rabies virus can crossreact serologically with other members of the Lyssavirus genus, distributed in Australia, Eurasia, and Africa (5) or, theoretically, with as yet uncharacterized rhabdoviruses. However, this patient had no history of foreign travel and no evidence of infection with KCV, the only other rhabdovirus associated with bats in North America.

      Laboratory diagnosis of rabies antemortem is based typically on routine detection of viral antigen in a full-thickness skin biopsy, viral RNA in the skin biopsy or saliva, or antibodies in serum and CSF. Only antibodies were found in this patient. However, viral antigen and RNA often are not detected in infected humans antemortem because of limited virus replication and intermittent viral excretion in saliva (1,4,6). Notably, the diagnosis of rabies in all human survivors has been based solely on serologic findings, including the presence of VNA, but without virus isolation or detection of viral antigens or RNA (2,6).

      Certain other clinical and laboratory findings also support a diagnosis of abortive rabies in the patient described in this report. First, the onset of acute encephalopathy approximately 2 months after exposure to bats is compatible with documented incubation periods after rabies virus exposure. Second, central nervous system (CNS) findings (e.g., fever, photophobia, emesis, neck pain, dizziness, paresthesia, limitation of visual field, and altered behavior with agitation and combativeness) are compatible with clinical aspects of rabies. Although this patient did not have classic symptoms such as laryngeal spasms (manifested as hydrophobia) or autonomic instability, the lack of such symptoms has been documented in other rabies patients (1,2,6). Finally, despite an extensive medical workup, no alternate infectious etiology was identified for the patient's neurologic symptoms, increased intracranial pressure, and CSF pleocytosis.

      In animal models, both cellular and humoral immune responses are important indicators in survivorship after rabies virus infection (7--9). In this report, the patient's serologic profile suggests that her immune system cleared the rabies virus before production of VNA. This might help explain the patient's atypical (i.e., waxing and waning) neurologic course. In more typical rabies cases, infected persons who have not received rabies PEP experience a rapid neurologic decline, resulting in death. Human survivors of rabies have demonstrated a vigorous immune response to the virus, as measured by serum and CSF antibody levels (2,4). However, CSF IgG in the patient in this report never exceeded a dilution of 1:32, with serum IgG reaching 1:8192, not nearly as high as values reported in previous survivors (1). Another patient, given experimental treatment, showed evidence for neurologic recovery, with high serum but low CSF VNA, but died shortly after therapy (10).

      Detection of viral antibodies in serum can be indicative of previous vaccination or exposure to a lyssavirus, but does not necessarily indicate the development of disease. Contact with virus does not ultimately constitute a productive infection (e.g., the virus can be inactivated by the host innate response or by other means before replication in host cells). Similarly, a productive infection does not necessarily result in transportation of virus to the CNS. An abortive infection can occur outside the CNS, with limited replication of the virus at the exposure site and further clearance by the host immune system (7,8).

      Rabies virus is a highly neurotropic pathogen, transported from the exposure site to the CNS by peripheral nerves without significant local replication and avoiding or impairing the host immune response during the incubation period. Thereafter, when the virus reaches higher concentrations in the CNS and spreads peripherally, specific antibodies can be detected as the clinical course evolves. Typically, the detection of specific virus antibodies in the CSF indicates a CNS infection. Based on evidence to date with U.S. rabies patients, antibodies to the abundant viral nucleocapsid antigens detected by IFA are registered first, whereas VNA, directed to the outer viral glycoprotein, are only detected later by RFFIT, if VNA are detected at all. The patient described in this report did not have detectable rabies VNA in the serum until after receiving rabies vaccine and HRIG.

      In all previous human survivors, rabies was diagnosed based on exposure histories, compatible clinical symptoms, and detection of rabies virus antibodies. However, in all of those patients, the clinical courses were substantially longer, with more severe neurologic compromise and more prominent stimulation of the immune system, including the induction of VNA. In the case presented here, the clinical manifestation was relatively mild, which might imply variables associated with viral dose, route, and type, with a more limited virus replication and less apparent stimulation of the immune system. Clinicians treating possible cases of human rabies, indicated by acute, progressive infectious encephalitis, a compatible exposure history, and serologic evidence of a specific lyssavirus response, even in the absence of detectable VNA or fulminant neurologic decline, should contact their state health department for engagement with CDC.

      Acknowledgments
      This report is based, in part, on contributions by J Murphy, PhD, I Butler, MD, C Dreyer, MD, B Aalbers, MD, Univ of Texas School of Medicine; R Arafat, MD, Office of Surveillance and Public Health Preparedness, D Persse, MD, Houston Dept of Health and Human Svcs; P Grunenwald, DVM, Texas Dept of State Health Svcs, Region 6/5 South; C Kilborn, MPH, Harris County Public Health and Environmental Svcs, Houston; T Sidwa, DVM, Texas Dept of State Health Svcs, Austin, Texas; J Blanton, MPH, R Franka, DVM, PhD, M Niezgoda, MS, L Orciari, MS, A Velasco-Villa, PhD, X Wu, DVM, PhD, and P Yager, Div of Viral and Rickettsial Diseases, National Center for Emerging and Zoonotic Diseases, CDC.

      References
      1.Willoughby RE, Tieves KS, Hoffman GM, et al. Survival after treatment of rabies with induction of coma. N Engl J Med 2005;352:2508--14.
      2.Hattwick MA, Weis TT, Stechschulte CJ, Baer GM, Gregg MB. Recovery from rabies: a case report. Ann Intern Med 1972;76:931--42.
      3.Jackson AC, Warrell MJ, Rupprecht CE, et al. Management of rabies in humans. Clin Infect Dis 2003;36:60--3.
      4.CDC. Human rabies prevention---United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR 2008;57(No. RR-3).
      5.Calisher CH, Karabatsos N, Zeller H, et al. Antigenic relationships among rhabdoviruses from vertebrates and hematophagous arthropods. Intervirology 1989;30:241--57.
      6.World Health Organization. WHO expert consultation on rabies: first report. WHO Technical Report Series 931. Geneva, Switzerland: World Health Organization; 2005. Available at http://www.who.int/rabies/trs931_%2006_05.pdf . Accessed February 22, 2010.
      7.Lodmell DL, Ewalt LC. Pathogenesis of street rabies virus infections in resistant and susceptible strains of mice. J Virol 1985;55:788--95.
      8.Bell JF. Abortive rabies infection: experimental production in white mice and general discussion. J Infect Dis 1964;114:249--57.
      9.Perry LL, Lodmell DL. Role of CD4 and CD8 T cells in murine resistance to street rabies virus. J Virol 1991;65:3429--34.
      10.Rubin J, David D, Willoughby RE, Jr., et al. Applying the Milwaukee Protocol to treat canine rabies in Equatorial Guinea. Scand J Infect Dis 2009;41:372--5.
      What is already known on this topic?

      Only six human rabies survivors have been well documented after clinical onset, and none of the survivors had abortive rabies (i.e., recovery without intensive care).

      What is added by this report?

      This is the first reported case in which certain clinical and serologic findings indicate abortive human rabies and in which, despite an extensive medical investigation, no alternate etiology for the illness was determined.

      What are the implications for public health practice?

      Clinicians treating possible human rabies, indicated by acute, progressive infectious encephalitis, a compatible exposure history, and serologic evidence of a specific lyssavirus response, should contact their state health department for engagement with CDC; public education should continue to stress the importance of avoiding exposure to bats and seeking prompt medical attention after exposure to any potentially rabid animals.



      FIGURE. Timeline of course for a patient with presumptive abortive human rabies --- Texas, 2009


      * Approximate date.

      † Indirect fluorescent antibody.

      Alternate Text: The figure above shows the timeline of course for a patient with presumptive abortive human rabies in Texas in 2009. On February 25, 2009, an adolescent girl aged 17 years went to a community hospital emergency department with severe frontal headache, photophobia, emesis, neck pain, dizziness, and paresthesia of face and forearms. The headaches had begun approximately 2 weeks before she went to the hospital.

      TABLE 1. Cerebrospinal fluid (CSF) and rabies virus antibody test results for a patient with presumptive abortive human rabies --- Texas, 2009

      CSF
      Serum

      Date
      WBC/mm3*
      WBC differential†
      RBC/mm3§
      Glucose (mg/dL&#182
      Protein (mg/dL**)
      Opening pressure

      (cm H20††)
      Rabies IFA IgG/IgM§§
      Rabies VNA (RFFIT)¶¶
      Rabies IFA IgG/IgM
      Rabies VNA (RFFIT)

      February 25
      163
      97% lymphocytes

      3% monocytes
      0
      61
      NP***
      NP
      NP
      NP
      NP
      NP

      March 6
      185
      95% lymphocytes

      5% macrophages
      1
      56
      160
      NP
      NP
      NP
      NP
      NP

      March 9
      318
      95% lymphocytes

      5% monocytes
      0
      50
      152
      28
      NP
      NP
      NP
      NP

      March 10
      500
      2% neutrophils

      89% lymphocytes

      9% monocytes
      350
      58
      146
      38
      NP
      NP
      NP
      NP

      March 11
      254
      7% neutrophils

      79% lymphocytes

      14% monocytes
      1775
      55
      164
      23
      1:32/negative
      <1:5
      1:2048/8
      <1:5

      March 15
      395
      95% lymphocytes

      5% monoctyes
      37
      51
      198
      NP
      1:32/negative
      <1:5
      1:8192/8
      <1:5

      March 19
      82
      89% lymphocytes

      11% monocytes
      80
      62
      146
      25
      1:32/negative
      <1:5
      1:8192/32
      1:14

      March 29
      NP
      NP
      NP
      NP
      NP
      NP
      NP
      NP
      1:8192/32
      >1:5

      April 3
      63
      96% lymphocytes

      4% monocytes
      3
      60
      53
      29
      1:8/negative
      <1:5
      NP
      NP

      * Normal: white blood cells 0--5/mm3.

      † Normal: neutrophils: 0--6%, lymphocytes 40%--80%, monocytes 15%--45%, macrophages (no reference range).

      &#167; Normal: red blood cells 0/mm3.

      &#182; Normal: 45--80 mg/dL.

      ** Normal: 15--45 mg/dL.

      †† Normal: <20 cm H20.

      &#167;&#167; Indirect fluorescent antibody test (serum or CSF dilutions); immunoglobulin G/immunoglobulin M.

      &#182;&#182; Viral neutralizing antibodies (serum or CSF dilutions); rapid fluorescent focus inhibition test.

      *** Not performed.




      TABLE 2. Results of diagnostic testing for causative agents of encephalitis/aseptic meningitis in a patient with presumptive abortive human rabies --- Texas, 2009

      Test
      Date
      Result

      Cerebrospinal fluid (CSF)

      Herpes simplex virus PCR*
      March 6
      Negative

      Enterovirus PCR
      March 6
      Negative

      Epstein Barr virus PCR
      March 10
      Negative

      Cytomegalovirus PCR
      March 15
      Negative

      Varicella zoster virus PCR
      March 15
      Negative

      VDRL†
      March 6
      Nonreactive

      Bacterial culture (five specimens)
      March 6, 9, 10, 15, 19
      No growth

      AFB&#167; culture (five specimens)
      March 6, 9, 10, 15, 19
      No growth

      Fungal culture (five specimens)
      March 6, 9, 10, 15, 19
      No growth

      Protein electrophoresis

      IgG&#182; index
      March 9
      No oligoclonal process

      0.5 (normal)

      Cytopathology
      March 9
      Negative for malignancy

      Serum

      HIV 1/HIV 2** antibodies
      March 7
      Negative

      HIV 1 RNA PCR
      March 7
      Negative

      Rapid plasma reagin
      March 7
      Nonreactive

      West Nile virus

      IgM††

      IgG
      March 7
      Negative

      0.00

      0.00

      Epstein Barr virus

      IgM

      IgG

      Nuclear antigen
      March 8
      0.15 (negative)

      3.42 (positive)

      6.53 (positive)

      Arboviruses

      St. Louis encephalitis

      Eastern equine encephalitis

      Western equine encephalitis

      California encephalitis
      March 11
      Negative

      <1:16&#167;&#167;

      <1:16

      <1:16

      <1:16

      Borrelia burgdorferi
      March 16
      Negative

      Human T-lymphotropic virus 1 and 2
      March 16
      Negative

      Mycoplasma IgM

      Mycoplasma IgG
      March 16
      0.12 (negative)

      0.79 (positive)

      Ehrlichia PCR
      March 16
      Negative

      Fungal

      Coccidiomycosis

      Blasomycosis

      Histoplasmosis
      March 11
      <1:2 (negative)

      <1:8 (negative)

      <1:8 (negative)

      Quantiferon-TB Gold
      March 12
      Negative

      Antinuclear antibody

      Anti-double stranded DNA

      Anti-Ro antigen

      Anti-Smith antigen
      March 11
      Negative

      Negative

      Negative

      Negative

      Other

      Viral culture (nasal wash)
      March 6
      No growth

      Viral culture (oral sore)
      March 10
      No growth

      Purified protein derivative (intradermal inoculation)
      March 8

      March 13
      6 mm

      0 mm

      * Polymerase chain reaction.

      † Venereal disease research laboratory.

      &#167; Acid-fast bacilli.

      &#182; Immunoglobulin G.

      ** Human immunodeficiency virus.

      †† Immunoglobulin M.

      &#167;&#167; Dilution.



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      Comment


      • #4
        Re: Texas Girl Recovers From Rabies Without Intensive Care

        I am reading the table at the bottom of the MMWR (that the above post seems to mangle). It seems that the girl tested positive for IgM and IgG to Epstein-Barr virus (although negative to the virus by PCR), as well as positive by IgG to Mycoplasma.

        Epstein-Barr virus is the cause of mononucleiosis, which would explain the recurrent nature of her symptoms.

        Either way, very puzzling.

        Comment


        • #5
          Re: Texas Girl Recovers From Rabies Without Intensive Care

          The text of this ProMED post is the MMWR text, with the comment below.

          It not not that we don't trust the CDC; this is just an extraordinary claim, being the first ever such case discovered, with no real evidence of anything similar ever happening before. Extraordinary claims require extraordinary proof.



          The clinical data and the time course of the illness are tabulated and
          illustrated graphically in the original text.

          Only 6 human rabies survivors have been well documented after clinical
          onset, and none of the survivors had abortive rabies (that is, recovery
          without intensive care). This is the 1st reported case in which certain
          clinical and serologic findings indicate abortive human rabies and in
          which, despite an extensive medical investigation, no alternate etiology
          for the illness was determined.

          It is unfortunate that no viral genomic RNA was obtained during this
          investigation, which could have verified the source of the infection. The
          presumed contact with an infected bat is no more than circumstantial. Not
          all strains of rabies virus are pathogenic in humans, for example the SAD/B
          attenuated strains which have been used to vaccinate wildlife in Central
          Europe. - Mod.CP
          ]

          Comment


          • #6
            2009 Houston rabies case poses new questions about age-old illness

            Source: http://www.statesman.com/news/texas/...inglePage=true

            Houston rabies case poses new questions about age-old illness
            By Brenda Bell
            AMERICAN-STATESMAN STAFF
            Updated: 8:56 p.m. Saturday, March 31, 2012
            Published: 8:28 p.m. Saturday, March 31, 2012

            At the U.S. Centers for Disease Control and Prevention, she's called the "Texas wild child."

            She was a 17-year-old who had run away from home when she walked into a Houston hospital with a fever and puzzling neurological symptoms.

            Her name is veiled by medical privacy laws, as is the identity of her family back in Missouri; exactly how she was exposed to the virus that sickened her three years ago is a mystery. Where she is now, no one seems to know.

            Her disappearance is part of one of the area's most intriguing medical mysteries: The CDC says she is the only known person in the U.S. to survive rabies after the onset of clinical symptoms, and without prior vaccination or intensive hospital care...

            Comment


            • #7
              Re: 2009 Houston rabies case poses new questions about age-old illness

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              Published Date: 2012-04-03 09:34:46
              Subject: PRO/AH/EDR> Rabies, human, presumed abortive, 2009 - USA: (TX) unresolved, RFI
              Archive Number: 20120403.1088994

              RABIES, HUMAN, PRESUMED ABORTIVE 2009 - USA: (TEXAS) UNRESOLVED OUTCOME, REQUEST FOR INFORMATION
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              Date: Mon 2 Apr 2012
              Source: The Austin American-Statesman [edited]



              Houston rabies case poses new questions about age-old illness
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              At the US Centers for Disease Control and Prevention [CDC], she's called the "Texas wild child." She was a 17-year-old who had run away from home when she walked into a Houston hospital with a fever and puzzling neurological symptoms. Her name is veiled by medical privacy laws, as is the identity of her family back in Missouri; exactly how she was exposed to the virus that sickened her 3 years ago is a mystery. Where she is now, no one seems to know. Her disappearance is part of one of the area's most intriguing medical mysteries: The CDC says she is the only known person in the US to survive rabies after the onset of clinical symptoms, and without prior vaccination or intensive hospital care.

              "Obviously we're dying to know what happened to her," said Dr Charles Rupprecht, who leads the CDC's rabies program in Atlanta. "We made calls to the numbers she gave us, but she's dropped off the grid." To Rupprecht, the Texas case is "the door that's been opened" to questioning the age-old paradigm of rabies. What if the one thing we thought we knew about this disease -- once contracted, it is a certain death sentence -- isn't true? "Rabies is one of the few diseases that we thought we understood, and now we have to undo that," said Dr Carol Glaser, who leads the special investigations division of the California Department of Public Health. "When you think about it, no other infection has a 100 percent mortality rate. Why should this?"

              There have always been clues. Veterinarians know that not all animals die after exposure -- usually from a bite -- to the rabies virus, which is carried in saliva and other bodily fluids. Much depends on how much of the virus is transmitted, the severity and location of the bite, and the immune system of the bitten animal. "Abortive rabies is not unusual in research animals -- it happens spontaneously all the time," Rupprecht said. [For example, see: Hamir AN, Niezgoda M, Rupprecht CE: Recovery from and clearance of rabies virus in a domestic ferret. J Am Assoc Lab Anim Sci. 2011 Mar; 50(2): 248-51; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3061427. - Mod.CP] Rupprecht said the blood of certain human populations -- maybe 1 percent of raccoon hunters, for example -- also tests positive for rabies antibodies, indicating they have been exposed to the virus without becoming acutely ill. In the Amazon, where indigenous tribes are at daily risk of rabies from vampire bats, "it could be in the 10 percent or more range," he said.

              The rabies vaccine, injected in a series of 5 doses, prevents onset of the disease if given soon enough after exposure. About 35 000 people receive the expensive shots -- the series costs about USD 1600 -- in the US each year. Seldom do more than a handful of people die from rabies in a year. But once rabies symptoms appear, the vaccine is no help. "We don't have poster children. In our field, 99.9 percent of our cases are in the ground," Rupprecht said. In that grim fact lies the significance of the unidentified Texas teenager. The CDC published her case in February 2010, calling it the 1st reported instance of abortive human rabies [Presumptive abortive human rabies - Texas, 2009. MMWR Morb Mortal Wkly Rep. 2010 Feb 26; 59(7): 185-90. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5907a1.htm. See Abstract reproduced below. - Mod.CP] Though her blood and cerebral spinal fluid tested positive for rabies exposure, she never became critically ill, and never even needed extraordinary treatment. She recovered and left Children's Memorial Hermann Hospital in Houston under her own steam. "Nobody does that. She broke an immunological rule," said Dr Rodney Willoughby of Children's Hospital of Wisconsin. "It's almost liberating." Dr Tom Sidwa, who heads the Texas Health Department's rabies program, said public health authorities must now view possible rabies cases differently. "Prior to this girl in Houston, anything that suggested improvement, they said, 'That ain't rabies,'?" he said. "They can't say that anymore."

              Rabies is [caused by] a lyssavirus, a zoonotic brain infection -- meaning it can pass from animals to humans and vice versa -- that is so old and so feared, it has its own mythology. Lyssa was the Greek goddess of rage and mad dogs; scholars have noted the parallels between vampire legends and symptoms of rabies in humans, such as biting, extreme sensitivity to light, and occasionally, hypersexuality. The disease figures in popular novels (think "Cujo" and "Old Yeller") and movies (for instance, "Rage" in 1966 and the 2010 Israeli horror film, "Kalavet"). "This is something out of your nightmares -- it's very primal," Rupprecht said. "Rabies and horror are deeply ingrained in our psyche."

              Until Louis Pasteur developed a vaccine in 1885, there was no prevention. There is still no cure for rabies, which has an uncommon ability to subvert the body's immune system until infection is so far advanced that death is inevitable. The World Health Organization estimates that rabies kills 50 000 people annually, most of them bitten by mad dogs in Africa and Asia. Thanks to widespread vaccination of pets, there have been only 108 cases of human rabies in the US in the past 50 years. Texas and California, with 19 and 20 cases respectively, have had the most. Before the Houston case in 2009, there were just 6 well-documented survivors of rabies worldwide, according to the CDC. 5 received vaccinations before becoming ill. All were left with some degree of neurological damage.

              The 6th, most famous survivor is Willoughby's former patient, J.G. A month after being bitten by a bat in Fond du Luc, Wisconsin, in 2004, the 15-year-old girl was hospitalized with vomiting, slurred speech, tremors, and excessive salivating. The CDC confirmed rabies-specific antibodies in her spinal fluid. It was too late for the vaccine. Willoughby, a pediatric infectious disease specialist, had seen rabid dogs while growing up in South America, but never a human with the disease until she "just landed in my lap," he said. He had only hours to read up on rabies on the Internet. Scrolling through medical journal articles from all over the world, he saw that post-mortem exams often showed surprisingly little evidence of damage to the brain from rabies. The killing thing seemed to be violent disturbances of brain function that had caused the autonomic nervous system to go haywire. "It was a software problem," Willoughby said. He reasoned that if he shut down the nervous system long enough to prevent a meltdown, it might buy time for the "cavalry" -- the immune response -- to arrive. "It's such a simple concept you wonder why no one had thought of that before," he said. He told the girl's parents they could put their daughter in hospice care to await certain death, or allow her to be drugged into a coma, hooked up to life support, and a cocktail of antiviral medicines -- an untested regimen that was likely to fail. It was an easy choice.

              The girl became the 1st unvaccinated survivor of rabies the world has known. She suffered minimal neurological effects, and in 2010 she graduated from college. Yet, no sooner had Willoughby published her case than physicians worldwide questioned whether his radical treatment -- now called the Milwaukee protocol -- made sense. Doctors in developing countries have seen thousands of rabies patients and lost them all. They were skeptical of a single rogue case in the US that relied on a dream team of specialists and high-tech supportive care. What proved that the medical coma had worked? Where were the animal studies that supported it? What if the Wisconsin girl never had full-blown rabies to begin with? Since that 1st success, 4 other people around the world -- all of them young and unvaccinated -- have contracted rabies and survived after medically-induced comas, Willoughby said. The latest was an 8-year-old girl in Humboldt County, California, who fell ill last year [2011]. But 32 other rabies victims who were subjected to the protocol have died, including a 16-year-old high school football player in Humble who was bitten by a bat in 2006. The most recent is a 63-year-old man in Cape Cod, Massachusetts, who succumbed in January [2012], also after a bat bite. "We made something up and it worked," Willoughby said. "Getting it to work again -- that's been much harder. Either we're doing something right, or we're just lucky."

              The wisdom -- and extraordinary expense -- of the Milwaukee protocol has been challenged in the very places where rabies is rampant. In Southeast Asia, where an estimated 24 000 people die each year from the virus, doctors tried it on a single patient without success in 2006. "The cost for caring for this patient by a multi-specialist team at a university hospital in Thailand could have provided pre-exposure rabies vaccination ... for at least 16 000 slum-dwelling children in Bangkok," they wrote in the journal of the Royal Society of Tropical Medicine and Hygiene. The doctors decided not to subject future patients "to intensive therapeutic measures, including respiratory and cardiovascular support. Symptomatic and comfort care ... will be the primary goal for many patients." "We're on the horns of an ethical dilemma," Rupprecht said. "But whenever you get the phone call from someone who says, 'Please save my child,' what are you going to do?"

              For centuries, Europeans knew rabies as a disease primarily spread by dogs, wolves, and other canines. Not until the 1950s did scientists discover that the virus is carried by insect-eating North American bats (including the Mexican free-tail bats that nest by the millions in Central Texas, not the vampire bats of South America), which are now the most common cause of human exposure to rabies in the state and much of the US.

              The story of that discovery is told in "The Incurable Wound," a 1957 New Yorker article that is a classic among medical students and infectious disease specialists. It begins with a West Texas farmer's wife who died of rabies after being bitten by a bat she found lying in the road. It ends with another Texas casualty, a state health department epidemiologist named George Menzies who succumbed to the disease after collecting bat specimens from caves in the Hill Country.

              Despite the frequency of rabies in Texas ? in 2010 and 2011 Texas led the nation in reported cases in animals ? no one initially thought of the disease in March 2009 as Houston doctors puzzled over their 17-year-old patient, a few blocks from another hospital where a boy her age had died of rabies three years earlier. The girl had severe headaches, neck pain and vomiting. Light hurt her eyes. She was agitated and combative.

              The tentative diagnosis: infectious encephalitis, a brain inflammation of uncertain origin. Under questioning by her doctors, she revealed she had been camping somewhere between Austin and San Antonio two months before, and had entered a cave where flying bats had brushed against her. She didn't think she had been bitten, but samples of her blood and spinal fluid were rushed to the CDC anyway.

              Four samples tested positive for rabies antibodies. Doctors gave her a single dose of rabies vaccine before halting the series of five shots, afraid the vaccine would complicate her own immune response.

              Slowly but surely, their patient got better and was discharged three weeks later, seemingly recovered. Over the next few days, she returned twice more to the emergency room with headaches, but her symptoms again resolved and she was not readmitted.

              It was the last they were to see of her. During her treatment, the young woman turned 18 and so by law was then an adult in charge of her own medical care. According to Dr. Anthony Eshofonie, an epidemiologist who was working for the Houston Health Department at the time, she rebuffed attempts by medical personnel to keep track of her.

              "She and her boyfriend were more concerned about their privacy than their health consequences," he said.

              "She changed her phone, changed her email. She's what we call ?lost to follow-up,' " Rupprecht said.

              Attempts by the American-Statesman to reach her physician at Children's Memorial also failed. A hospital spokesperson said doctors cannot comment on cases without patient consent.

              Asked why the CDC did not try harder to find someone who could alter the scientific understanding of rabies, Rupprecht said the agency's hands were tied. "We're big believers in states' rights and personal freedom. The patient has the right to be left alone."

              Twenty miles from the hospital where she was treated, at the University of Texas Medical Branch in Galveston, research is now under way to test the effectiveness of the treatment credited with Jeanna Giese's recovery from rabies. The test animals are ferrets, in which rabies closely mimics the form seen in humans.

              The idea is to standardize the Milwaukee protocol ? what length of coma to induce, which antivirals to use ? so that it could be used anywhere, said Dr. Nigel Bourne, the researcher in charge of the project, which is funded by the National Institutes of Health.

              But progress has been slow. It's hard to anesthetize ferrets for days at a time without killing them, and each animal must be monitored 24 hours a day, as if it were in intensive care. "I would like to tell you we've solved all the problems, but we haven't," he said.

              In the parts of the world where rabies is most prevalent, children are most often the victims. "I'm in pediatrics ? that's one of the reasons we're doing this work," Bourne said.

              Meanwhile, in Wisconsin, Willoughby still takes calls from doctors around the globe. Sometimes they send Willoughby videos of their patients, dark-eyed children with only days to live. Desperately thirsty, they choke violently when they try to drink a cup of water and push it away. Involuntary throat spasms are a telltale sign of rabies and the origin of its scientific name, hydrophobia ? fear of water.

              You can see some of these videos on YouTube. They are disturbing, heartbreaking. They show that far from being lost to madness, victims are conscious of their surroundings and what is happening to them. And they help explain the desire to pull out all the stops to save even one of the thousands of doomed patients, wherever they are.

              "It is terrible, truly terrible," Willoughby said. "I hate this disease."

              [Byline: Brenda Bell]

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              [A description of the "Texas wild child" case was published in MMWR Morb Mortal Wkly Rep. 2010 Feb 26; 59(7): 185-90; http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5907a1.htm. Entitled " Presumptive abortive human rabies - Texas, 2009," the abstract is reproduced below.

              "Rabies is a serious zoonotic disease. Recovery has been well documented in only 6 human patients worldwide. 5 of those patients had received rabies vaccinations before illness; one had not received rabies vaccination but survived infection after prolonged intensive care. In most of these survivors, moderate to profound neurologic sequelae occurred. In all 6 survivors, rabies was diagnosed based on exposure history, compatible clinical symptoms, and detection of rabies virus-neutralizing antibodies (VNA). This report describes the clinical course and laboratory findings of an adolescent girl with encephalitis who had not had rabies vaccination and who had been exposed to bats 2 months before illness. Antibodies to rabies virus were detected in specimens of the girl's serum and cerebrospinal fluid (CSF) by indirect fluorescent antibody test (IFA). However, the presence of rabies VNA was not detected until after she had received single doses of rabies vaccine and human rabies immune globulin (HRIG). Although the patient required multiple hospitalizations and follow-up visits for recurrent neurologic symptoms, she survived without intensive care. No alternate etiology was determined, and abortive human rabies (defined in this report as recovery from rabies without intensive care) was diagnosed. Public education should emphasize avoiding exposure to bats and other potentially rabid wildlife and seeking prompt medical attention after exposure to such animals. Rabies is preventable if rabies immune globulin and vaccine are administered soon after an exposure; however, this case also suggests the rare possibility that abortive rabies can occur in humans and might go unrecognised."

              The Austin American-Statesman article above provides a useful summary of the present state of knowledge concerning abortive rabies virus infection, and which may elicit further information concerning the enigma of the Texas patient. - Mod.CP

              A HealthMap/ProMED-mail map can be accessed at: http://healthmap.org/r/276D.]

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