The Impact of Co-morbidities and

Immune Diseases in Infants

Community-Acquired Pneumonia
The actuality
Pneumonia represents the cause of death for more than 2 million children
annually, which is about 20% of all infant deaths. (UNICEF, 2009).
According to the WHO, pneumonia is the leading cause of infant mortality in
the world. Annual deaths of pneumonia among infants is greater than those
caused by the infection of HIV/AIDS, tuberculosis and malaria together.
Global registers show more than 155 million cases of pneumonia in children, 1.5
million of them will manifests complications of different severity.
Prevalence of pneumonia in Moldova is 140-150 per 1,000 children.
WHO's priority strategy and perspective for 2013-2025 period is pneumonia and
diarrhea.

According to WHOs estimates, the mortality caused by herpes infection is in
the second place (15.8%) from the group of viral infections after influenza
(35,8%).
Thanks to development of screening methods, imunofluoriscent method
determined the immunoglobulin antibodies to CMV at 33% of children up to 2
years in high socioeconomic developed countries. And in developing countries
were discovered 69%.
The mortality from CMV in children is estimated at 30%, and in 80-100% of
survivors will develop sequelae like: progressive deafness, mental retardation,
microcephaly. (C. l., Spanu Brc 2006)
The damage of respiratory system in children with CMV infection is estimated
at 49%, clinically manifested by distress respiratory syndrome and pneumonia
with severe evolution.


The aim of this work
The implementation of the risk factors and establishing the clinical and
immunological particularities of community acquired pneumonia at the
child, associated with persistent viral infection.
The objectives of the study
Estimation of the risk factors in the development of community acquired
pneumonia at a child with comorbidities.
Determination of the clinical and immunological markers in suspicion of
recurrent viral infection.
Clinical and immunological particularities of the CAP associated with
recurrent viral infection in the acute and latent phase of the disease.
Diagnostic aspects of CAP associated with recurrent viral infection.
Materials and methods the study research


Examination of medical files (medical history, clinical examination; objective
systems examination).
Paraclinical examination (complete blood count, blood biochemical
examination, examination of immunological characteristics by Mancini
method of IgA, G, M; serological examination of anti-CMV-IgM, anti-CMV-
IgG).
Screening methods: chest radiography, ultrasonography of the internal
organs.
Specialists consultation: infecionist, psychoneurologist, allergist,
gastroenterologist, a radiologist.
Research data were processed statistically by methods of variation and
descriptive analysis, with application of the Microsoft Excel, which enables us
to analyze more profoundly the individual and group characteristics of signs.
Discussion of the obtained results
The study material was collected during the 2012 and 106 children were selected under
the age of 5, with the diagnosis of community-acquired pneumonia
All patients in the study were examined for serological determination of anti-CMV IgM
antibodies, anti-CMV IgG antibodies and persistent viral positive history in both groups
which served as a condition for the formation of examination groups.
106 children with CAP
I group
anti-CMV IgM +
anti-CMV IgG +
31 children
II group
anti-CMV IgM -
anti-CMV IgG +
44 children
III group
anti-CMV IgM -
anti-CMV IgG -
31 children
In each group we obtained next structure of age: from 1 to
6 months, 6-12 months, 1-3 years 3-5 years. The distribution
into the study groups by age was identical with control
groups.
Positive herpetic anamnesis -
61,33%.
Negative herpetic anamnesis -
38,67%
Congenital pneumonia were discovered in over 1/3 of the patients from the II group; in I group
about 19,35 2.5% (p < 0,05)
Acquired pneumonia was identified in half of children from II group, in 1/3 from I group and nearly
10% in the control group.
Obstructive bronchitis was identified in all lots of research but prevails in groups with aggravated
allergic anamnesis.
Acute recurrent respiratory infection (II group-40,9 4.3%, (p < 0.005), I group-22,58 3.8% (p <
0.005)).

The structure of morbidity in children with CAP associated
with CMV
Pathologies I group II group III group
Pneumonia 1/year 12,9% 13,63% 9,67%
2/year 12,9% 27,27% 3,22%
3/year 6,45% 9,09% -
Obstructive bronchitis
1/year
12,9% 13,63% 16,12%
2/year 12,9% 15,9% 3,22%
3/year 16,12% 18,18% -
Recurrent respiratory
infections ( 6/year)
22,58% 40,9% -
Allergic reactions 25,8% 18,18% 32,25%
Digestive system diseases 22,58% 22,72% -
CNS diseases 12,9% 25% 6,45%
Thymomegaly 9,67% 13,6% -
The pre-hospital duration of the disease
During the first week of the disease were addressed most children from the control
group - 41,93%, which showed an acute onset of the disease.
While in the other groups only of the cases were addressed up to 7 days after onset.
Duration up to 2 weeks occupies roughly the same rate at all lots - 27,12 2.1%.
Addressing up to 1 month is observed in 19,35% cases in the I lot, with a decrease in
other lots (18,18%; 16,12%).
1/3 of children from the I group have been addressed over 1 month from the debut and
more than from the II group. In control group only 12.9%.
The share of serious health condition in the study
At patients examination was determined that children with serious health condition were
admitted in 25,21 1.6% of cases.
The proportion of patients with serious health condition, especially in the I group (35,48 1.4%, (p
< 0,05)), II group (27,27 1.3%, (p < 0.01)).
The main causes of severe evolution of CAP at these children are late visits to the doctor, the
presence of concomitant diseases, and last but not least, the opportunistic viral infection associated
to the disease.

Complaints at the hospitalization
CNS damage was detected in all groups, but the children from the I group being over 90%, were
characterized as agitated in 70,96% of cases and the rest as flaccid in 19,35% of cases.
Food refusing and loss of appetite were determined at over 80%, while vomiting just in 22,58%.
Fever have presented over 50% of patients with medium values of 38,5 1.2C.
Dyspnoea was presented in 87,09% of cases with predominance of aspiratory type and stridulating in
the 74,4%.

Cough particularity
According to the complaints at hospitalization was determined that cough was presented
in 100% of cases in all groups of research.
Dry cough (61,29%) and spastic cough (45,16%) has maximal incidence in I group.
The hard productive cough was determined in all groups of research, but the highest
frequency - 50%,in group with anti-CMV IgG positive, what could be explained by the fact
that the CMV has increased tropism to the epithelial glandular cells, with increasing viscosity
secrecy.
The variety of skin changes
The mottled skin colour was determined in children from I and II lot with
approximately the same rate - 10%.
Peri-oral and peri-orbital cyanosis indicate about childs hypoxemia,
which was manifested in 64,51% of children from the I group, the II group
reached more than half of children (54,54%), while in control group
cyanosis manifested 45,16% children.

Clinical signs structure in childs pneumonia from the
research
According to the criteria for assessing the severity of respiratory diseases established by
Practical Clinical Pediatric Guide The management of community-acquired pneumonia in
children by American society, October 2012, it has been determined that the patients
from I group have more severe pneumonia evolution with the manifestation of clinical
signs of respiratory failure at over 80%.
Inflammatory markers
In this study, leukocytosis is observed experimentally with 40,56% rate: I group - 41,93 2.6% (p <
0.001), II group - 43,18 1.8% (p < 0.001).
Deviation to the left is determined by the maximum of 93,54% in control group because the
pneumonia has bacterial etiology.
In the I group deviation to the left is determined in 61,25 1.4% (p < 0,05) and in II group - 79,54
2,01% (p < 0.05). So we can deduce that the etiology is mixed viral and bacterial.
Lymphocytosis was observed in 29,03% (p < 0,05) in the I group and in 20,04% (p < 0,005) in II
group.
Monocytosis was found in 11,36 1.17% (p < 0.005) in II group and in 9,67 0,97% (p < 0,01) in I
group.
Accelerated ESR was observed in all groups of study.
The intensity and variety of pathogens in research
IgA structure in the research
IgA's examination in groups of research has been found that the largest share of the
low immunoglobulins in II group - 93,33 3.6%, (p < 0.01), I group - 83,33 2.7%, (p <
0.05), which is explained by the impact of the opportunistic infection on the immune
system with suppression of humoral immunity.
IgG structure in the research
Significant congenital or acquired declines of IgG grow individual susceptibility to
bacterial infections.
In researched groups were resulted low levels of IgG. Mainly in II group - 83.3 2.8%, (p <
0,05) in I group - 72,2 1.6% (p < 0.01), III group - 83,87%.
It is determined by the massiveness of the inflammatory process and immune system
imbalance.
IgM structure in the research
In the III group high values of IgM were determined in 61,29 4,8%, (p < 0,05), low values
of IgM only at 12.9 1.4%, (p < 0,01).
While in II group, increased level of IgM is determined at 43.3 M 2.7% of children having
the same quota as decreased IgM.
In I group,the acute infectious process is represented by increased values of the IgM -
44,44 1.4% (p < 0.001).
Structure of total serum IgE and circulating immune
complexes in the research

Increased levels of IgE are largely found in the control group - 85,71 3.2% (p < 0,05), in II
group - 81,81 3.8% (p < 0,05), in I group - 75 25%, (p < 0,005).
Circulating immune complexes is determined in reverse proportion to the maximum in I
group - 63,63 1.45% (p < 0,05), in II group - 61,20 1.6% (p < 0.01), in III group -
56,661,3%, (p<0,01). They are formed as a result of continuous immune response
In I and II groups we have children with an immune deficiency confirmed by elevated
levels of CIC.
Radiological confirmation of respiratory affectation in the study
Radiological
confirmation
I group II group III group
polisegmental
pneumonia
- 7,45% 3,22%
bilateral
bronchopneumonia
32,25% 38,63% 35,48%
right basal
bronchopneumonia
58,06% 29,54% 45,16%
right lobar pneumonia 3,22% 2,27% 3,22%
right focal
bronchopneumonia
6,45% 11,36% 3,22%
right segmental
pneumonia
3,22% 4,54% 3,22%
left segmental
bronchopneumonia
3,22% 9,09% 3,22%
Structure changes at ultrasound
Hepatomegaly was confirmed in 38,7 2.45% (p<0,05 ) cases from the I group, with a
gradual decrease in the other groups: II group - 27,27 1.19% (p < 0,01); III group -22,58
2.09% (p < 0,05)).
The infection of the gallbladder was fully confirmed in the I group - 16,12%, the other
being at the same rate of 6.45%.
The signs of pancreatitis were detected in all groups, but the maximum was found in II
group being about 27,27 1,67% (p < 0,05).
Classification of pneumonia forms
It is observed that about 1/3 of children from each group of research have supported the
bilateral pneumonia, while right bronchopneumonia has an incidence of 55,68 5,46% (p <
0,05), left bronchopneumonia has a lower incidence of 1.23 6.25% (p < 0.05), and
polisegmental damage is determined in children aged over 1 year in II and III groups.
The diversity of complications in the study groups
Respiratory failure in the study groups was at its peak.
In the I group was found 2.35 83,8% (p < 0.005) of RF, 19,35% of children had II degree
of RF.
In the II group was observed the highest level of RF 95 1.06% (p < 0,05), including
22,72% of children with II degree of RF.
In the control group, RF was diagnosed in 67,74% of cases and it is only I degree of RF.
Accompanying diseases determined in the study groups in
children with CAP
Accompanying diseases I group II group III group
congenital CMV infection 32,2% 18,18% -
acquired CMV infection 67,74% 81,82% -
toxic hepatitis 64,51% 84,09% 16,12%
pancreatic insufficiency 12,9% 18,18% 3,22%
biliary dyskinesia 16,12% 6,81% 6,45%
malnutrition 9,67% 15,9% 3,22%
gastroesophageal reflux 3,22% 4,54% -
EPHI 19,35% 27,27% 6,45%
epilepsy - 6,81% -
allergic dermatitis 38,7% 25% 58,06%
I-II degree anemia 45,16% 54,54% 48,38%
MCC 6,45% 15,9% 6,45%
thymomegaly 3,22% 4,54% -
The average time of treatment in the study
The average length of inpatient treatment was 11.5 2.4 days.
The duration of treatment in I group was 12,38 2.6 days, because it was CAP
complicated with respiratory failure, obstructive bronchitis, expressed toxic infectious
syndrome, associated with CMV infection in acute phase. It warrants the longest duration
of treatment in the study.
Conclusions
The risk factors that determines severe evolution of CAP at children with
positive herpes IgM or IgG are the ones with positive herpes familiar anamnesis
in 61,3% cases, especially those with CMV in 43,07% cases.
Clinical markers in diagnosis of persistent viral infection are: positive family viral
anamnesis, congenital pneumonia, prolonged neonatal jaundice, presence of
antenatal risk factors, toxic hepatitis.
The association of CAP with IgM positive herpes infection appreciates the
severity of the disease (35,48 1.4%, (p < 0,05)), duration of the disease (more
than 1 month, 2 weeks of hospitalization) and the presence of complications
(83,8 2.35% (p < 0,005) and co morbidities in these children.
Persistent herpes infection may be qualified as a public health problem by its
expansion, distribution,co morbidities and the severity of the clinical and
immunological manifestations.