alexa Severe Pneumonia in HIV-infected Infants-Clinical and Immunological Correlates. Trying to Improve Diagnosis and thereby Survival | Open Access Journals
ISSN: 1948-5964
Journal of Antivirals & Antiretrovirals
Like us on:
Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

Severe Pneumonia in HIV-infected Infants-Clinical and Immunological Correlates. Trying to Improve Diagnosis and thereby Survival

Robin John Green*, Adele Pentz and Refiloe Masekela

Department of Pediatrics and Child Health, University of Pretoria, South Africa

*Corresponding Author:
Robin J Green
Associate Professor
Department of Pediatrics and Child Health
University of Pretoria, South Africa
Tel: 082-851-1904
E-mail: [email protected]

Received Date: November 08, 2013; Accepted Date: November 08, 2013; Published Date: November 12, 2013

Citation: Green RJ (2013) Severe Pneumonia in HIV-infected Infants–Clinical and Immunological Correlates. Trying to Improve Diagnosis and thereby Survival. J Antivir Antiretrovir 5: xxx-xxxi. doi: 10.4172/jaa.1000e114

Copyright: © 2013 Green RJ. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Journal of Antivirals & Antiretrovirals

Severe pneumoniain infants who are HIV-infected is a common problem in many parts of the developing world, especially sub-Saharan Africa. It has emerged that the condition of severe hypoxic pneumonia in early infancy is a disease of many causes, most occurring together in the individual patient [1-3]. A frequent cause of severe pneumonia in infants is Pneumocystis jiroveci. This condition is usually diagnosed clinically and managed as ‘Pneumocystis pneumonia’ in the regions of the world where HIV-infected children live. Only in the last few years, has it become possible to make a microbiologicaldiagnosis of Pneumocystis jiroveci based on Polymerase Chain Reaction (PCR) testing of airway secretions. However, in the developing world, such testing is largely unavailable and the clinical condition still poses an enormous problem.

Pneumocystis jiroveci is a fungal organism that has a predilection for the immune-compromised host, and is a common pathogen in HIV-infected infants. The term PCP (pneumocystis pneumonia) was retained when Pneumocystis carinii was taxonomically renamed jiroveci [4]. Since the earliest reports of HIV infection, PCP has been recognized as a severe form of acute pneumonia. The disease may occur at any age, but is particularly common in early infancy [5]. PCP is recognized clinically by a distinct set of common criteria; hypoxic pneumonia, few pulmonary crackles, a reticular-nodular appearance on chest radiographs and an elevated lactate dehydrogenase (>500 U/l) [6,7]. The case fatality rate from PCP approaches 100% if not treated with trimethoprim-sulphamethoxazole (TMP-SMX) [8]. However, where TMP-SMX prophylaxis is employed alone, mortality is not significantly reduced [9]. Because the disease often causes severe hypoxia, these children would benefit from Paediatric Intensive Care admission. Admitting infants with PCP to an intensive care unit, in a resource limited setting, has created a number of ethical dilemmas for pediatricians, including the historical poor outcome for these patients and the pressure on scarce resources [10].

Cytomegalovirus(CMV) is now recognized as an important copathogen of severe pneumonia in infants, and may be the organism driving mortality in this form of pneumonia [1-3]. Treatment of this form of severe pneumonia with a combination of antiprotozoaland antiviral agents has had mixed success [1-3]. Some studies report improved survival with use of the antiviral agent ganciclovir [2,3]. Despite the presence of Pneumocystis jiroveci and CMV, a number of other pathogens also cause and contribute to severe hypoxic pneumonia in infants. What has been missing from previous studies of severe pneumonia in HIV-infected infants, however, is a description of the host inflammatory response and cytokine/chemokine profile that accompanies this disease. It is hoped that a better understanding of the host response and associated clinical correlates may aid in seeking better therapeutic options for these very ill children who frequently die.

In a study of HIV-infected infants with severe hypoxic pneumonia conducted in Pretoria, South Africa, findings of the immunological profile suggest that IL-10 and IP-10 are associated with acute severe lung disease that would be described as PCP. IL-10 is a cytokinethat has important anti-inflammatory properties [11]. Coded for by the IL-10 gene, this cytokine is produced mainly by monocytes and to some extent by lymphocytes[12]. It has a major function in down-regulating the expression of Th1 cytokines [11]. There is a paucity of data on the presence of IL-10 in pediatric lung disease, especially pneumonia. However, in a study of children with severe sepsis or pneumonia, IL-10 was found to be elevated in serum of the children with severe sepsis, but not pneumonia [13]. In other pediatric pulmonary conditions, there is evidence that IL-10 is elevated in respiratory syncytial virus infection [14], bronchopulmonary dysplasia [15] and Mycoplasma pneumoniae pneumonia [16]. An adult study of patients with community-acquired pneumonia suggests that IL-10 functions as an acute phase reactant [17]. The finding of elevated sputum and serum IL-10 in the current study of infants with severe pneumonia is a new finding and suggests that the anti-inflammatory defenses of the HIV-infected infant are mobilized early after the onset of severe pneumonic pathology.

IP-10 is a chemokine that is secreted by several cell types, including monocytes, endothelial cells and fibroblasts, in response to INF-y [18]. It functions as a chemoattractant for macrophages, T-cells, NK cells and dendritic cells and also has a number of newly identified functions, including promotion of T cell adhesion to endothelial cells, antitumor activity and inhibition of angiogenesis [19,20]. It has not previously been associated with a specific form of pneumonia in children. High levels of this chemokine have been shown to be associated with a poorer outcome in HIV-infected individuals with hepatitis C viral co-infection [21]. IP-10 has been documented as a better test than both interferon gamma-based QuantiFERON TB Gold assays and tuberculin skin tests for diagnosing TB in HIV-infected individuals [22]. HCV was not measured in the Pretoria study, but all children had normal levels of liver enzymes. TB was not seen in the children. Elevation of this chemokine in infants with severe pneumonia may reflect that significant stimulation of monocytes, in keeping with the elevated values of IL-10. It may have pro- or anti-inflammatory activity in this disease state. These functions, however, require more extensive study.

Previous studies have attempted to characterize the cytokine profile of P. jiroveci-infected individuals. These studies suggest that the actual cause of the immunosuppressionpredisposing to the infection may have as much impact on the cytokine profile as the organism itself [23,24]. This latter study suggests that P. jiroveci infection is associated with reduced macrophages in alveoli and elevated IL-6. However IP-10 was not measured in that study.

IL-1β and TNFα are found to be lower in infants with severe pneumonia in the Pretoria study, as compared to a group of children with bronchiectasis. The reason for this finding is unknown and should be investigated further.

Conclusion

PCP remains a devastating disease in the developed world were HIV infections still occur. A greater sense of clarity in management of this condition is being achieved, and it is hoped that further immunological evidence will contribute to better outcomes.

References

Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Recommended Conferences

Article Usage

  • Total views: 11526
  • [From(publication date):
    December-2013 - Aug 19, 2017]
  • Breakdown by view type
  • HTML page views : 7757
  • PDF downloads :3769
 

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords