A STUDY OF AVIAN INFLUENZA (H5N1) INFECTION IN EGYPTIAN CHILDREN

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A STUDY OF AVIAN INFLUENZA (H5N1) INFECTION IN
EGYPTIAN CHILDREN

• By Dr. Nasser Abdou Kolkailah
• MD pediatrics, Benha University
• Ministry Of health consultant of Avian Influenza
  in pediatrics.
• E-mail nasserkolkailah_at_yahoo.com

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When you want something, all the universe
conspires in helping you to achieve it.

• Paulo Coelho
• The Alchemist

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Avian Influenza

• Recent cluster of severe infection with Avian
  Influenza virus was first documented in Hong Kong
  in 1997.

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• The global number of H5N1 cases is 554 out of
  whom 324 died.
• Egypt confirmed the 1st case of H5N1 virus in its
  domestic poultry on February 17th , 2006 and the
  1st human case on March 17th , 2006. Since then,
  there have been 144 cases, among whom 48 died.

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• This can be explained by the fact that young
  children often treat poultry as pets. Children
  often care for domestic poultry by feeding them,
  cleaning pans and gathering eggs.

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• In children, sex predominance has not been noted.
  In adults, females have been more infected (54
  cases) than males (17 cases) with a P value of lt
  0.01, which is statistically highly significant
  and reassures that those backyards still remain
  the main source of infection.

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Figure3 Annual distribution of human avian
influenza cases by age group in Egypt
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• This may be attributed to the efforts exerted by
  the Egyptian Ministry of Health in controlling
  farms as a main source of infection in adults.
  Nevertheless, there are difficulties faced in
  combating backyards which represent the main
  source of infection in children who play with
  apparently healthy poultry during the early
  infectivity period.
• Another assumption is the possibility of sub
  clinical infection in adults.

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• In 2010 2011 the rates were reversed.
• This may be due to failure of the ministry of
  health and ministry of agriculture in limiting
  the trading of live poultry.

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Figure 4 Seasonal predilection of H5N1 human
infection in Egypt
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Figure 5 Worldwide seasonal predilection of H5N1
human infection
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Descriptive Data for H5N1 infection in Egyptian
Children
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• All cases had an obvious history of close contact
  with infected poultry. There have been 2 affected
  sibs and 2 affected cousins. The exposure to a
  common source of infection is rather a stronger
  explanation than human to human transmission.
• The duration between the exposure to dead birds
  and the appearance of symptoms ranged from 3 to
  10 days.

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Clinical Data

• 49 cases presented with symptoms and signs of
  upper respiratory catarrh and they were stable.
• 10 cases presented with dyspnea grade II and
  clinical examination revealed acute bronchitis.
• 14 cases were suffering from severe
  bronchopneumonia hepatomegaly was a finding in 5
  of them.

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Laboratory results

• RT- PCR confirmed the diagnosis of H5N1 infection
  in all cases.
• Our results have shown anemia in 20 cases,
  leucopenia in 14, lymphopenia in 7 and
  thrombocytopenia in 10.
• There have been 8 cases that developed secondary
  bacterial infection proved by leucocytosis,
  rising titre of CRP, while blood culture was ve
  in 3 cases.
• Mild elevation of liver enzymes has been noted in
  12 cases and mild elevation of serum creatinine
  in 6.

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Radiological Findings

• Increased bronchovascular markings in 10 cases
  denoting acute bronchitis.
• Bronchopneumonia was found in 14 cases (figures
  5-10).
• CT scan was requested for 2 cases of pneumonia
  (figures 11-12).

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Figure 6 Plain chest X-Ray of case number 18
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Figure 7 Plain chest X-Ray of case number 20
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Figure 8 Plain chest X-Ray of case number 21
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Figure 9 Plain chest X-Ray of case number 22
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Figure 10 Plain chest X-Ray of case number 28
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Figure 11 A Plain chest X-Ray of case number 34
2/4/2009
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Figure 11B Plain chest X-Ray of case number 34
3/4/2009
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Figure 11C Plain chest X-Ray of case number 34
11/4/2009
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Figure 11D Plain chest X-Ray of case number 34
21/4/2009
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Figure 12 A Chest CT scans of case number 18

• 22/6/2007
• Sizable areas of pneumonic consolidation process
  seen at right middle lobe and left basal lower
  segments, with fine air broncogram at site.
• The left basal segment pneumonic area showed
  small 1 cm cavity for follow up, left basal
  pleuro-pulmonary reaction, patent main
  tracheo-bronchial tree, fine left basal
  atelectatic bands, and no evidence of hilar
  masses or mediastinal lymphadenopathy

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Figure 12 B Chest CT scans of case number 18

• 22/7/2007
• Improvement of the consolidative process
  previously noted at both lower lobes mainly
  affecting the apical and anterior basal segment
  of right lower lobe and the posterior and
  anteromedial basal segments of the left lower
  lobe.

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Figure 12 C Chest CT scans of case number 18

• 21/8/2007
• Regression of the previously noted bilateral
  lower lobe subsegmental air space consolidation
  changes with areas of ground glass opacities are
  still noticed

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Figure 13 Chest CT scans of case number 28

• Multiple areas of pneumonic patches of chest
  infection.
• Segmental collapse area of right middle lobe.
• Areas of fine basal atelectatic bands.

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• Our management plan is to eradicate the virus and
  to prevent and treat body systems dysfunction.
• Tamiflu has been given to all cases according to
  the standard dose regimen.
• The start of Tamiflu ranged from the 1st day to
  the 6th day after the onset of symptoms.
• One case started therapy 2 weeks after the onset
  of symptoms due to a delayed etiological
  diagnosis.
• Course of therapy ranged from 5 to 33 days.

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• In addition to the standard therapy of Tamiflu,
  10 cases received polyclonal IVIG
• 7 cases received it on the 1st day of admission
  as they suffered from severe bronchopneumonia.
• The 8th and 9th cases were stable and received
  polyclonal IVIG due to persistent positive
  cultures after Tamiflu therapy.
• The 10th case developed respiratory failure as a
  complication of pneumonia and received
  polyclonal IVIG two weeks after the onset of
  symptoms due to delayed etiological diagnosis.

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• All cases have shown progressive improvement
  except 7 pneumonic cases.
• The 1st case deteriorated clinically and
  developed circulatory collapse which was treated
  by inotropics (Dopamine) and has fully recovered.
  
• The 2nd case deteriorated clinically and
  developed cardio respiratory failure and was
  mechanically ventilated for four days and has
  eventually recovered.

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• The 3rd case was mechanically ventilated as he
  developed respiratory failure and ARDS, but
  unfortunately died.
• 4 cases have developed respiratory failure and
  died before being referred to our center.

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Figure 14 Human Avian Influenza (H5N1) cases by
age group and outcome in Egypt (May 2011)
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Why clinical course and outcome among Egyptian
children were better compared to other countries?

• 1- Early suspicion of Avian Influenza.
• 2- Meticulous prevention of secondary bacterial
  infection.
• 3- Administration of polyclonal IVIG in severe
  cases.

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My considerations of adding polyclonal IVIG to
the standard therapy regimen in the 1st case

• The possibility of unresponsiveness to Tamiflu
  as it was started 5 days after the onset of
  symptoms.

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• Apoptosis may play a major role in the
  pathogenesis of influenza (H5N1) virus in humans
  by destroying alveolar epithelial cells. Whether
  apoptosis is a direct result of the viral
  replication or a consequence of an over
  activation of the immune system (cytokine storm)
  has not been clearly elucidated. Polyclonal IVIG
  has proved to have a dual action. It functions as
  an antiviral therapy neutralizing the virus and
  immunomodulating agent suppressing various
  inflammatory mediators including cytokines,
  chemokines, and metalloproteinases.

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The evidence of polyclonal IVIG being greatly
effective in recovery

• The case has been purely viral with no secondary
  bacterial infection, Thus the antibiotics given
  were not the reason for recovery.

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• The role of Tamiflu is doubtful due to
• a. The therapy started 5 days after the
  onset of symptoms, which was rather late.
• b. The severe systemic hypoperfusion could
  affect the intestinal absorption of the drug.

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• The case developed life threatening pneumonia
  denoting her immunodeficient state. Thus her
  innate immunity was not the key for recovery.

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• Due to all the facts mentioned before, we started
  polyclonal IVIG for six severe cases with
  bronchopneumonia on the first day of therapy and
  they fully recovered.

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More evidence supporting the effectiveness of
polyclonal IVIG

• An eight-year-old boy received Tamiflu for 5 days
  before being referred to the designed hospital in
  an advanced stage of severe bronchopneumonia and
  huge hepatomegaly. He was given IVIG for 5 days
  as an adjuvant therapy, which resulted in full
  recovery after 5 days.

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• Four stable cases among the 2009 cluster and
  one case in the 2011 cluster, showed a delayed
  sero-conversion for more than 20 days and
  received Tamiflu only. On the contrary, the use
  of Polyclonal IVIG as an adjuvant therapy in
  three critical cases of severe bronchopneumonia
  and respiratory failure achieved both a good
  clinical response and a complete eradication of
  the virus in less than 10 days.

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Conclusion

• Backyards represent the major source of infection
  in Egypt. Thus, H5N1 infection targets mainly
  young children and housewives.

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• There is a seasonal predilection of H5N1 in both
  winter and early spring .

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• No evidence has supported human to human
  transmission till now.

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• The early seeking of medical advice represents an
  important contribution to a better prognosis in
  children.

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• The early administration of oseltamivir within 3
  days of onset of the symptoms is associated with
  excellent prognosis.

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• Strong infection control policies play a highly
  favorable role in the outcome of most avian
  influenza cases.

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• The availability of detailed descriptive clinical
  data will assist in further comparative studies
  between affected countries.

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• Polyclonal IVIG proved to be an effective
  therapeutic tool in the management of critical
  H5N1 cases.

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Thank You