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Complicaciones de la Vacuna BCG en ni os con infecci HIV

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Complicaciones de la Vacuna BCG en ni os con infecci HIV Powered By Docstoc
					                                                      
Delayed complications of Bacillus
Calmette- Guérin (BCG) vaccination in
HIV-infected children

        Fallo A, Torrado L, Sánchez A, Cerqueiro C,
                  Schargrodsky L, López EL.1



  1   Children’s Hospital “Ricardo Gutiérrez”
             Buenos Aires, Argentina
 Introduction
•Tuberculosis is a leading cause of mortality in
developing countries.

•Bacillus Calmette-Guérin, an attenuated strain of
Mycobacterium bovis is extensively used
throughout the world as immunoprophylaxis
against severe tuberculosis disease.

• The World Health Organization and UNICEF
encourage BCG vaccination in developing
countries.
 Introduction
• In Argentina intradermally BCG vaccine is given
to all children in the first month of life

•Localized adverse events of BCG vaccine in
normal hosts is an entity known since a long time
ago, with almost 400 cases/million doses reported

• Disseminated infections were reported in 0.2
cases/million doses.

•Risk is increased for immunodeficient patients.
Objective
       To report the risk of BCG
 complications in perinatally HIV-
 infected children followed up at a
 Children’s Hospital .
Material and Methods I
A retrospective study in 310 BCG
 vaccinated patients of 374 perinatally
 HIV -infected children.

Period: 1992 - 2004.
Material and Methods II
 Definitions:

•   Localized Adverse Event: Abscess at the site of
    vaccination and/or ipsilateral adenitis.

•   Disseminated Form: other sites involved beyond
    the satellite node.

 Biochemical identification of M.bovis-BCG was
  performed at The National Reference Laboratory
  (Instituto Malbrán).
Results: Study Population

                 374
         HIV- infected patients


              310 (83%)
            BCG vaccinated


               28 (9%)
          BCG complications
Tuberculosis in HIV-infected children*
                   n = 51/374 (12.5%)

 NON - VACCINATED 64                  BCG VACCINATED: 310
  89%                                      86%



              7                                            44


                  11%
                                                                14%

                              TB disease

                  11 % vs 14%           p= NS
            *Fallo et al. Presented in part at 38th Annual Meeting of the
            Infectious Diseases Society of America (IDSA2001) Abstract # 788. .
   BCG Vaccinated Patients
       n= 310
                           With           Without
                        Complications   Complications    p=
                           N= 28          N= 246
Mean time follow-up     5.9 ± 5 years   6.2 ± 6 years    NS

Category C (CDC)            61%             48%          NS
Mean Viral Load (log)     5.2 ± 0.3        4.9 ± 1       NS
Mean CD4 %               13.6 ± 11        20 ± 12       < 0.01
       Study Population
           General Findings
N= 28/ 310 (9%)
Mean age at onset       8.6 ± 7 mo
Range                    3-31 mo
Category C (CDC)           71%

Median CD4 %              11%
Range                    1- 46%
Median viral load         5.1 log
ARV therapy < 3 mo            89%
 BCG Complications
N= 28
                          Disseminated Complications
                                    14%
                                4



                24


        86%

Localized Complications
 Localized complications : 24 (86%)
      – Abscess at the site of vaccination :4
      – Axillary Lymphadenitis :            6
      – Chronic Suppurative Lymphadenitis: 14 (58%)

                       Simple          Chronic
                      Adenitis       Suppurative     p=
                        n= 9        Adenitis n=14
Mean age              8 ± 9 mo         7 ± 3mo       NS
Category C (CDC)         4                 9         NS
Mean viral load        5±1             5.6 ± 0.3     NS
Mean CD4 %             21 ± 9           11 ± 7      < 0,02
      Disseminated cases:                       4 (14%)
                                            TB                    Response
     Age       CD4        Clinical                     BCG
Case                                    Histologic                  to TB
     (mo)       %         Findings                    Culture
                                         pattern                   drugs #
                       Multiple bones
 1*     29      1         Spleen            +        Bones +        Bad
                       Mesenteric LN
                        Cervical and                 Cervical
 2      10      10       Mediastinal        +         lymph        Good
                        lymph nodes                  node +
                        Pneumonitis                   Gastric
 3      5       9       Suppurative         /         fluid +      Good
                          adenitis                   Adenitis +
                        Pneumonitis                   Gastric
 4      5       21      Suppurative         /         fluid +     Relapsed
                          adenitis                   Adenitis +

 *Fallo et al. IJID 2005; 9: 96-103.                    # INH, RMP, EMB
   Localized vs. Disseminated Cases

                    Localized   Disseminated
                                               p=
                       24            4
Mean age (months)     8±6          11 ± 6      NS
Category C (CDC)       13             4        NS
Mean viral load      4.9 ± 1       5.4 ± 1     NS
Mean CD4 %           15 ± 11       10 ± 8      NS
Discussion: Literature
      BCG                       INCIDENCE *                    INCIDENCE
  Adverse Event           GENERAL POPULATION                  Present Study
                                 (Age < 1 year)
                         /millon doses        %                    %
LOCALIZED                     387             0.04%               7.7%

DISSEMINATED                  0.1-2         0.0001 %              1.3%




•Milstien, JB Gibson JJ Bull WHO 1990; 68:93-108.
•Lotte A et al Bull Int Union Tuber Lung Dis 1988; 63:47-57
Adverse Events associated with BCG vaccination in HIV-infected children *
    Author        Year of     Country     Study         Adverse Events
                 Publication            Population Localized Disseminated
Blanche               1986        France          18                         17%
Bregere               1988        France          67           10%
Hira                  1989         Zaire          42           13%
Lallemant             1991        Congo           21           24%
MMWR                  1991       Rwanda           37            5%
Green                 1992         Zaire          21             0
Ryder                 1993         Zaire          48           10%
Besnard               1993        France          68           10%            3%
O’Brien               1995         Haiti          13           31%
Thaithumyanon         2000       Thailand         26             0
Current study         2005       Argentina        310          7.7%          1.3%

  * At least other 12 case reports about disseminated BCG infections are published.
Conclusions
 No differences in frequency of TB disease
between vaccinated and non-vaccinated patients
were found


 a high frequency of complications (9%) and an
increased risk of severe disease was observed in
our population of perinatally HIV-infected children,
specially in patients with lower CD4.
  Conclusions
       Therefore, taking into account this and other
similar reports, we believe that BCG vaccination
should be reconsidered in children at risk of HIV
infection, specially in countries where early
diagnosis and adequate control of HIV infection is
possible.