A recent study
that described Clinical and Laboratory features of infants with pneumonia
demonstrated an elevated fatality rate in severely malnourished children
compared to well-nourished infants [Chisti, M. J.; et al., 2010]. A study
examining the prevalence of respiratory infections to the prevalence f
malnutrition in children under 5 years of age. Found that acute upper
respiratory infections were most prevalent among children with acute
malnutrition. However, lower respiration infections were most prevalent among
children with either acute or chronic malnutrition. As most previous studies
did not examine the effect of malnutrition acute upper and lower respiratory
infections separately, these result provide additional information to this
complex
area of study [Cunha, A. L. 2000].
To identify potential differences in etiology of pneumonia between
children with and without severe malnutrition, Chisti et al [Chisti, M. J.; et al., 2009] conducted an excellent
review study to quantify the degree by which moderate and severe degree of
malnutrition, increases the mortality risk in pneumonia. They found that
children wit pneumonia and moderate or severe malnutrition showed a higher
mortality risk. For severe malnutrition, reported relative ranged from 29 to
121.2; odds ratios ranged from 2.5 to 5.1 for moderate malnutrition, relative
risk ranged from 1.2 to 36.5. These results show a significant association
between moderate severe malnutrition among children with pneumonia.
Further more studies have demonstrated that pneumonia is
more common among children with Marasmic-kwashiorkor
than among other types of malnourishment [Adegbola, R. A.; et al., 1994]. Additionally, in children under the age 2 years, malnutrition is associated with a significant increase ARi morbidity also, saves pneumonia
is associated to increase the mortality rate [Tupasi, T. E.; et al., 1990], [Nantanda R.; et al., 2008]. In a study performed with severely
malnourished children, the mortality in children with kwashiorkor was 13-4%.
Mortality was 28% in children with Maramus and 48.3% in children with
classified malnutrition. The main cases of death in children younger than 18
month of age were dehydration and pneumonia: in children from 19 to 60 month of
age, it was pneumonia [WHO Clinical Management, 1981].
The data currently available suggest that the spectrum and
frequency of causative agents of bacteria pneumonia is severely malnourished
children may differ from that observed in children without severe malnutrition
[Chisti, M. J.; et al., 2009].
Streptococcus
pneumonia and Haemophilus influenzae
were the two microorganism isolated most frequently from the blood, lung or
pleura fluid from well –nourished (33%) and malnourished children (11%) with
pneumonia [Selwgn, BJ. 1990],[ Berman, S. 1991]. However according to Chisti et al [Chisti, M. J.; et al., 2009] Kelbsiella spp and S. aureus were the most causative
organism in severely malnourished children. These findings suggest that Klebsiella
spp and S. aureus are probably the main bacterial causes of
pneumonia in malnourished children. Additionally, pathogenic viruses have been
isolated form malnourished children with pneumonia. Although mycobacterium
tuberculosis detected in 18% of malnourished with pneumonia [Adegbola, R. A.; et al., 1997], the role of mycobacterium
tuberculosis presenting as an acute lower respiratory infection in severely
malnourished children has not been well studied.
A perspective study of Staphylococcal
lower respiratory infection in children aged 1-48 month reported that’s 68% of
the cases were diagnosed as brochopneamonia. Of the 9.7% of parents in the
study that died, they were all malnourished children who did not receive
antibiotics prior to disease presentation. Further, they all exhibit
bronchopneumonia and Staphylococcus
aureus positive blood cultures [Aderele, W. I.; et al., 1994]. In the absence of an organized and
effective immune response, antibiotics alone are usually incapable of
eradicating bacteria pathogens [Ambrus, J. L; Sr.; and Ambrus, J. L.; Jr. 2004]; therefore antibiotic only have slight
effect on early mortality from bacteramia and sepsis due to Streptococus pneumoniea [Hedlund,
J. 1995]. As we mentioned above, the
innate immune response provides a first line of defense against infection. It
has been eliminated that innate immune system provides protection against 98%
of encountered pathogens [Jones, G. E.
2000]. The upper respiratory tract is the ecological niche for many
bacterial species. S. Pneumoniae is
part of the commensal flora of the upper respiratory tract, as mentioned above.
Together with Haemophilus influenzae,
Staphylococcis aureus, M. Catarr haus, and various hemolytic Streptococcu S, pneumoniae colonizes the
nasopharyngeal tract [Paton, J. C.; et
al., 1993].
Effective respiratory tract host defense against pathogens
depends on the interaction of types = specific antibodies, complement, and
neutrophils or other phagocytic cell [Gordon, S. B.; et al., 2000], [Gingles, N. A.; et al., 2001]. If pathogens
overcome these defenses and gain entry into the blood stream, systemic
protection is mediated by anticapsular antibodies [Anttua, M.; et al.,
1999]. A reduced mucosal immune
response might lead to persistent and recurrent colonization and subsequent
infection, whereas and efficient local immune response to the pathogen
eliminates colonization and prevents recolonization.
The pneumococcal cell wall is highly immunogenic, it is the
cause of the intense inflammatory reaction that a companies pneumococcal
infection; It stimulates the influx of inflammatory cells activates the
complement cascade and increases cytokine production [Brugn, M; et al., 1999]. In general, the mucas
immune system develops faster than the systematic immune system and functions
from the age of 6 months. IgG and secretory IgA antibodies directed against
carular polysaccharides and surface-associated proteins have been observed in
saliva of children under five years in response to colonization with S. pneumoniae [Bogard, D; et al., 2004].
There is evidence that the susceptibility of malnourished
children to respiratory infections caused by encapsulated bacteria is due to
defects in the production of IgG antibodies. However, malnutrition produces a
profound depression on acquired cell- mediated immune competence, where as
humoral competence is less predictably affected. In contrast in a resent study
examined the effect of under, nutrition on the humoral immune profile in
children less than 60 months of age with pneumonia. The children were a united
to hospital with moderate. Severe pneumonia, and under nutrition was associated
with hypoabuminemia and reduced humoral Immune responses [Cripps, A. W.; et al.,
2008].
Immunoglobulin
levels of malnourished children have been reported by various researchers to be
comparable to well nourished children; however IgA level are decreased in
Malnutrition [Reckly, V.; et al., 1976].
In addition, previous report show that the main percentage of TL 4-producing
T-cells are increased in malnourished children; compared to well nourished
children [Rodrguez, L.; et al., 2005]. Moreover, high levels of serum 12-4 have been
found in malnourished children [Hagel, I.; et al., 1995]. The high level of 1L-4 could
contribute to the elevated level of serum immounoglobulin reported in malnourished
children [Roddy, V.; et al., 1976]. The secretory IgA is a principal
component of the mucosal immune response that protects the upper respiratory
track against infection with pathogenic organism; therefore the diminished IgA
level observed in malnourished children may be responsible for diminished IgA
level observed in malnourished children may be responsible for diminished
immune responses against respiratory infections.
In general acute bacterial infection such as such as Streptococcus pneumonia, are
characterized by the predominance of neutrophus in the inflammatory reaction
[Mizgerd, J. P.; et al., 1995]. Chemokines are likely to play a major role in
this type of immune response. A significant reduction of phagocytic
capabilities and diminished killing capabilities of neutrophils in malnourished
children has been reported [Bhaskam, P. 1992], furthermore in malnourished patients a
though there is a close-to-normal neutrophil chemitaxis and phagocytosis, minor
defect in the generation of reactive oxygen intermediates and bacteria killing
have been demonstrated [Keusch, G. I.; and Farthing, M.J. 1986]. Several
investigators have demonstrated that malnutrition results in impaired
macrophage phagocytosis, impaired superoxide a noon production and reduced
cytokine production [Redmond, H.; et al., 1995]. Moreover, malnutrition has been shown
to cause retarded macrophage differentiation [Honda, Y.; et al., 1995].
However, protection against bacterial respiratory infection
is also mediated by opsonin-dependent phagocytosis. Antibody-initiated
complement-dependent opsonization which activates the classic complement pathway
is taught to be the main immune mechanism protecting the host against S. pneumonia infection [Paten, J. C.; et al., 1993]. In several studies,
complement, were significantly lower in malnourished children [Olusic, O.; et al.,
1986], [Magadees an, V.; and Reddy, V. 1975]. In particular, C3 and
factor B were depressed in malnourished patient [Chandra, R. K. 1975] over all, complement production in
response to infection and inflammation is inadequate in malnourish individuals
[Ambrus, J. L.; Sr.; and Ambrus, J. L.; Jr, 2004]. These data suggest that a
relative complement deficiency with decreased resistance to infections sexist
in malnourished children.
Malnourished mice infected with Streptococcus pnenumoniae exhibited more lung injuries, impaired
leukocyte recruitment and reduced antibody and cytokines play an important role
in the nutrition-infection complex [Gonalez,C; et al.,1997 ] . According, an
impairment of cytokine production has been reported in malnutrition [Gonzalez,
C.; et al., 1997] , [Grombie, R. 1990]
Macrophages from protein malnourished animals produces less
TNF- in response to infection [Black, R.
E.; et al., 2003], [Moore, K.; et al., 1994]. Particularly, phagocytes
in the respiratory tract of infected malnourished mice showed reduced TNF- production and activity
compered to infected malnourished mice [Chan,j,; et al., 1997].In contrast, other studies have shown that TNF- production by PBMC from malnourished children did not differ
compered to well nourished children.[Palacio,A,; et al.,2002].Consistent with this,IL-6 production in malnourished
children was similar to a well nourished children. However, this result differ
from those of luDohelty et al. [Dorherty,;J.F;
et al., 1994] who reported a diminished IL6 production in severely malnourished child
Incontrast,other studies
found that IL6level were significantly increased in super-permanent of
phytohemagglutinia(PHA)-stimulated culture from malnourished children compered to well nourished
children.[Malave, I.; et al., 1998], [Cedeholm,T,;
et al., 1997].
In more more
recent study from our laboratory [ Rodriguez,L; et al., 2005] ,Production of IL-2,IFN-Y,-IL-4 and IL-10)Were evaluated in
CD4+ and CD8+T cells from malnourished children showed reduced IL-2 and IFN-Y, production has also been observed in
other studies[Chandra,R.K.1991], [Chamelers ,H.; et al., 1998]
An
important increase in percentages of CD4+ and CD8+IL 10- expressing cell is
evident in malnourished children [Rodriguez,L; et al., 2005]. IL-10, which
is produced by variety of cells including T lymphocytes, B lymphocytes,
and monocytes has been identified as a cytokine with important
anti-inflammatory and immune suppressive properties [Moore ,K; et al., 200I].IL-10 is a major cause of
infective anti-pathogen immune response, as inhibits many of the individual
steps in anti-microbial immunity[Moore, K,; et
al.,2001]. Therefore, IL-10 may be an important immunosuppressive factor
related to the impaired immune response observed in malnourished children.
Altered levels of the proinflammatory cytokines
granulocyte-macrophage colony stimulatory factors (CM-SCF), IL-8 and IL-8 have
been observed in culture supernatant of PBMCs isolated from malnourished
children. Specifically GM-CSF levels were lower in malnourished children
compared to well nourished children, while IL-8 and IL-6 levels were higher in
malnourished children compared to well nourished children. These altered
cytokine responses in PBMCs from malnourished children suggests severely
impaired inflammatory responses [Abo-Shouma, S.; et al., 2008].
When malnourished mice were challenged with S. Pneumonia, lung colonization and
bacteremia were significantly greater in malnourished mice. The malnourished
mice showed diminished number of leukocyte and neutrophils in the blood and in
bronchoaliveolar lavages. Although a moderate increases of leukocytes was
observed after challenge with S.
pneumoniae, there was a decrease of leukocytes on day 5 post-infection,
must likely due to affected cells release from the bone marrow [Willenu,
J.; et
al., 2009]. Reduce capacity of leucocytes to kill ingested microorganism
and decreased ability and lymphocytes to replicate, coupled with lower
concentrations of the cell responsible for cell-mediated for the immunity,
result in higher morbidity due to infectious diseases [Deshmula, P. R.; et al.,
2009]. Another problem explanation for the reduced bacterial clearance
and increased mortality observed in malnourished children with pneumonia is
defected alveolar macrophage function.
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