36   WITS SPECIAL EDITION JOurNAL 2013

Research

Article

BURDEN OF RESPIRATORY DISEASE 
AMONG PAEDIATRIC PATIENTS 

INFECTED WITH HIV

Correspondence Author:
Mrs CRM Humphries
Physiotherapy Department, 
Khanya Block
University of the Witwatersrand
7 York Road
Parktown 2193
South Africa
Email: Carolyn.humphries@wits.ac.za

ABSTRACT:  The effects of paediatric HIV on the respiratory system are 
seen daily in paediatric wards. The nature of respiratory disease and the 
needs of HIV-positive patients have changed subsequent to the introduction 
of anti-retrovirals to South Africa in 2004.  

One hundred and twenty five children admitted to the paediatric wards 
under the age of seven years were recruited for this study. The pur-
pose of this study was to understand the disease profile of children with  
HIV/AIDS, their health status, presenting respiratory conditions, and need 
for chest physiotherapy.

The most common respiratory conditions included bacterial pneumo-
nia (66.4%), tuberculosis (48%) and pneumocystis jirovecii pneumonia 
(23.2%) (n=125). Two thirds of the children (68.8%) presented with a high burden of disease. Forty percent (40.8%) 
of the children were taking anti-retrovirals with an average length of use of 9.81 months (±SD=11.61).  Analysis of  
immune status revealed a mean CD4 percentage of 17.33% (±SD=10.96), CD4 absolute 631.36 cell/mm3 (±SD=610.36) 
and viral load 2.6 million copies /ml (±SD=9.08 million copies/ml). 

This study highlights the characteristics and prevalence of respiratory disease burden among children with HIV in a 
South African setting in a post highly active antiretroviral era.

KEY WORDS:  RESPIRATORY DISEASE; CHILDREN; HIV; ANTIRETROVIRAL THERAPY; PHYSIOTHERAPY.

Da Cunha NCP, 
MSc Paediatric Physiotherapy1;

Potterton JL, PhD Physiotherapy1;
Humphries CRM, 

MSc Paediatric Physiotherapy1
 
 1 University of the Witwatersrand, 
  Department of Physiotherapy.

INTRODUCTION
Sub­Saharan Africa remains the re­
gion of the world most heavily affected 
by HIV.  In 2011, sub­Saharan Africa  
accounted for 69% of HIV infections 
worldwide.  Mother­to­child transmis­
sion continues to account for a substan­
tial portion of new HIV infections in 
many African countries. In 2011, more 
than 90% of children were newly in­
fected in sub­Saharan Africa (UNAIDS, 
2012).  Respiratory disease remains a 
major cause of morbidity and morta lity 

and pulmonary tuberculosis (PTB) are 
among the most common opportunistic 
infections (Parker et al, 1998). In 
children with HIV infection, lymphoid 
interstitial pneumonitis (LIP) has been 
designated as an AIDS­defining illness 
by the US Centres for Disease Control 
and Prevention (1994). Pulmonary 
infec tion may develop chronicity. This is 
illustrated by the significant occurrence 
of bronchiectasis in children with AIDS, 
particularly in children developing LIP, 
recurrent pneumonia and unresolved 
pneumonia (Sheikh et al, 1997). 

There are many other factors which 
may contribute towards the prevalence 
of acute and chronic respiratory condi­
tions including age and health status 
(Graham, 2007). Survival rates have  
increased with improved treatment strat­
egies (Graham, 2007).  The CD4 count 
is a good immunological marker of  
disease progression.  Thus, a CD4 count 
of more than 25% shows that there is 

amongst HIV­infected children (Zar, 
2008).  Zar and Mulholland reported in 
2003 that of more than one and a half 
million HIV infected children, 90% will 
develop a respiratory illness sometime 
in the course of their HIV condition. 

The management of HIV has made 
progress in South Africa and therefore, 
the incidence of acute and opportunistic 
respiratory infections has declined while 
HIV­associated chronic lung disease 
has increasingly emerged (Zar, 2008).  
The incidence of acute pneumonia 
is much higher in HIV infected than 
uninfected children (Madhi et al, 2000) 
and chronic lung diseases are much 
more common owing to a wider range 
of pulmonary diseases (Graham, 2005). 
Pneumocystis jirovecii pneumonia (PJP) 
is by far the most common opportunistic 
infection and serves as an HIV marker 
and many other studies have shown 
that PJP, cytomegalovirus (CMV), 
mycobacterium avium complex (MAC) 

Research Article

BURDEN OF RESPIRATORY DISEASE AMONG PAEDIATRIC PATIENTS 
INFECTED WITH HIV
Authors: Da Cunha NCP, Potterton JL, Humphries CRM 36

Research Article

FACTORS WHICH ARE PREDICTIVE OF RETURN TO WORK AFTER 
STROKE
Authors: Ntsiea MV, Van Aswegen H, Olorunju S 42

Research Article

THE IMPACT OF LOWER LIMB AMPUTATION ON COMMUNITY 
REINTEGRATION OF A POPULATION IN JOHANNESBURG: A 
QUALITATIVE PERSPECTIVE
Authors: Godlwana LL, Stewart AV 48

Research Article

AN AUDIT OF THE PHYSIOTHERAPY MANAGEMENT OF PARAPLEGIC 
PATIENTS WITH SACRAL PRESSURE SORES
Authors: Pather D, Mudzi W 55

Research Article

PAEDIATRIC HIV - LOOKING BEYOND CD4 COUNTS
Authors: Potterton J, Hilburn N, Stewart A, Humphries C 62

Research Article

CAREGIVER STRAIN AND QUALITY OF LIFE 
6 TO 36 MONTHS POST STROKE
Authors: Hilton J, Mudzi W, Ntsiea V, Olorunju S 66

Research Article

THE EFFECT OF TRIGGER POINT THERAPY AND MEDICINE BALL 
EXERCISES VS TRIGGER POINT THERAPY AND STRETCHING ON HIP 
ROTATIONAL BIOMECHANICS OF THE GOLF SWING
Authors: Quinn SL, Olivier B, Wood W, Naidoo V 73



37   WITS SPECIAL EDITION JOurNAL 2013 

the combination of ARVs administered, 
length of drug use, patient history of 
ARV drug combination use, whether the 
mother was on ARVs, the necessity for 
physiotherapy intervention and the rea­
son for physiotherapy intervention.

Statistical analysis
The data were reviewed and statistically 
analysed.  The relationship between the 
respiratory categories and influencing 
factors was investigated using logistic 
or polytomous logistic regression.  The 
relationship between length of stay and 
the influencing factors employed time  
to event analysis.  Interpretation was 
performed at a 0.05 level of significance 
using. 

RESULTS
The results of the study showed the 
average age of all the children under 

little immune suppression; 15–24% 
moderate suppression and less than 15% 
severe suppression (World Health Orga­
nisation, 2005). 

Prior to the introduction of antire­
troviral therapy (ART) in 2004 in South 
Africa, respiratory tract infections were 
found in over 90% of HIV infected  
African children post mortem (Zwi et 
al, 2000).  Respiratory tract infection 
accounted for 30­40% of paediatric in­
patient admissions in HIV endemic re­
gions with case fatality rates of between 
15­28% (Zwi et al, 2000). Thus the high 
prevalence of respiratory conditions may 
have been partly attributable to many 
children not receiving highly active  
antiretroviral therapy (HAART) or hav­
ing had an undiagnosed HIV infection.  

A study by Cowburn et al (2004) 
completed in Cape Town raised an 
issue that health care workers cannot 
adopt a deontological approach or see 
treatment of those infected with HIV as 
an obligation due to “a high incidence 
of HIV infection and lack of access 
to HAART, coupled with resource 
constraints”. Jeena (2005) discusses that 
in developing countries a much more 
utilitarian view has to apply until such 
time that resources to practise at optimum 
levels become available. Research with 
regard to HIV and respiratory care is 
scant and is thus required in order to 
develop data upon which policies can 
be built; and is required to guide policy, 
resource allocation and ethical decision 
making in South Africa. This study aims 
to determine the burden of disease with 
regard to the prevalence of respiratory 
conditions among paediatric patients 
infected with HIV/AIDS and to establish 
the need for chest physiotherapy.

METHODS
Study setting and participants
One hundred and twenty five children 
admitted to the paediatric wards at Steve 
Biko Academic Hospital (Pretoria) 
and Chris Hani Baragwanath Hospital 
(Johannesburg), Gauteng, South Africa 
were recruited for this study.  Children 
included were those under the age of 
seven years diagnosed with a respiratory 
condition and infected with HIV/AIDS 
already confirmed by polymerase chain 
reaction (PCR) testing.  

Ethical Considerations
Ethical approval was obtained from 
the Human Research Medical Ethics 
Committee at the University of the 
Witwatersrand and from the Faculty 
of Health Sciences Research Ethics 
Committee at the University of Pretoria.  
Consent was obtained from the parent  
or guardian and assent from the child 
where applicable, prior to data collection.

Procedure
Upon consent, patient files were used to 
complete a data collection form. The data 
collection form was completed two days 
post admission, five to seven days post 
admission and repeatedly five to seven 
days later until discharge and finally at 
discharge.  Data collected included: age, 
gender, length of hospital stay, diag nosis 
of the respiratory conditions, the pa­
tients’ CD4 count, viral load, ARV use, 

Figure 1: Outcome distribution post admission

Figure 2: Distribution of respiratory conditions (n=239 conditions)



38   WITS SPECIAL EDITION JOurNAL 2013

seven years (84 months) to be 21 
months (±SD=23.64). Fifty­five per­
cent of patients were boys. The average 
length of stay in hospital was 19 days 
(±SD=19.19).

The outcome of the sample (n=125) 
after admission is presented in Figure 1.

The distribution of respiratory con­
ditions was collated and categorised  

Figure 3: Distribution of the percentage of conditions presented

Figure 4: Breakdown of reasons for the status of ARV use

Table 1: Immunological status

Mean SD Median IQR

CD 4 Percentage 17.33 10.96 16.7 8.94 ­ 21.3 

CD 4 Absolute 
(cell/mm³)

631.36 610.36 417 233.5 – 811.5

Viral Load 
(copies/mL)

2664420 9080406 350000 33000 – 
1550000

* SD – standard deviation
** IQR – Inter­quartile range

into eight groups. This is shown in  
Figure 2. ‘Bacterial pneumonia’ inclu­
ded all forms of bronchopneumonia, 
pneu monia, community and hospital  
acquired. ‘Viral pneumonia’ included 
bronchiolitis and all types of influenza.  
The ‘Other’ group included interstitial 
lung disease, emphyema, pleural effu­
sion, laryngomalacia, bronchopul mo­

nary, dysplasia, mycobacterium avium 
com plex (MAC), swine flu (H1N1) and 
lung fibrosis.

Patients presented with one to four 
respiratory conditions as depicted in 
Figure 3.

These were then categorised as a ‘Low 
burden’ (only one condition) or a ‘High 
Burden’ (more than one condition).  Two 
thirds (69%) of all the patients were 
classified as having a high burden of 
respiratory disease.

The number of children taking anti­
retroviral medication was 51 (41%).  
Figure 4 demonstrates the breakdown of 
ARV use.

The average length of anti­retroviral 
use for the 36 patients that were already 
taking ARVs prior to admission was 10 
months (±SD=11.61).

Of all the mothers there were only 31 
(24.8%) who were involved in a PMTCT 
programme.

Information regarding the immunity 
of the children is included in table 1.

The level of immune suppression was 
categorised into four stages (figure 5)  
according to the WHO staging, which 
accounts for age and CD4 percentage 
(for children under 5 years) or CD4  
absolute count (for children 5 years and 
older).

The burden of respiratory disease 
was regarded as low or high burden as 
described above. The influencing factors 
include: anti­retroviral use, CD4 count, 
viral load, age and gender.  A relationship 
was shown to exist with ARV use, CD4 
count and gender (table 2). 

In conclusion: there is a higher 
burden of disease among patients 
using anti­retrovirals, as the level of 
immunosuppression increases so does 
the burden of respiratory disease, and 
there is a higher burden of disease 
among female patients. 

Using the Kaplan Meier survival 
curves there was a marginally significant 
difference (p = 0.06) between a low 
burden of disease and high burden with 
respect to mortality. The low burden 
group died earlier but had a shorter length 
of stay; the high burden group died later 
but had a longer length of stay. This 
relationship between burden of disease 
and the length of hospital stay was also 
statistically significant (p=0.029). 



39   WITS SPECIAL EDITION JOurNAL 2013 

DISCUSSION
Lower respiratory tract infections 
(LRTIs) are a major cause of morbidity 
and mortality in children aged less 
than five years in developing countries 
(Madhi et al, 2000; Zar and Mulholland, 
2003). This study population consisted 
of 125 children all diagnosed with 
perinatally acquired HIV and respiratory 
illness with an average age of just under 
two years.  The distribution of males to 
females was similar.

The length of hospital stay was 
approximately two and a half weeks 
with an 80% discharge rate. Madhi 
et al (2000) found in a South African 
based study that the average length of 
hospitalisation was less than seven days 
with mortality lower than 10%. Further 
South African studies show mortalities 
of up to 16% (Ojikutu et al, 2008).

Of the twelve patients who died 
three were taking ARVs. These three 
had only started medication during the 
study; essentially making all children 
who died ARV naive, highlighting 

the problems arising as a result of late 
initiation of ARVs. Nine of the twelve 
children who died were under the age 
of six months. Pneumonia, PJP, CMV 
pneumonitis and TB were the diagnosed 
respiratory illnesses in these children, 
concurring with a 2004 Zambian study 
by Kouakoussui et al (2004). 

Although Zar (2008) discusses a shift 
from acute to chronic exacerbations 
of respiratory disease, this state is not 
clearly depicted in this study due to the 
young population age. This study may 
offer more insight into acute respiratory 
diseases. 

Pneumocystis jirovecii pneumonia 
occurred in 10% and 17% of children 
according to a study by Jeena (2005); 
however is represented by 23% of 
children in this study. Graham (2003) 
reports that PJP presents with severe 
pneumonia, usually in infants between 
two and seven months old. Of the 
twenty­nine children, 27 were seven 
months or younger. This demonstrates 
PJP’s early presentation confirming the 

need or proper ante­natal HIV testing  
and PJP prophylaxis post­natally.  
Bacterial pneumonia was found in 
two thirds of all patients in this study.   
Current PJP prophylaxis has, however, 
lowered this infection rate by three 
times, making bacterial pneumonia a 
more common acute respiratory illness, 
as shown in this study and that conducted 
by Graham (2005).  CMV pneumonitis, 
often associated with PJP (Graham, 
2003) was found in 18.4% of children  
in this study. 

Viral pneumonia (including bron­
chiolitis and influenza viruses) was 
not very common with only an eight 
percent presentation. This group remains 
important as repeated viral infections 
may result in chronic lung disease 
of which HIV infected children are 
susceptible (Zar, 2008). 

This study found a low percentage of 
cases of LIP due to a number of  reasons: 
the young study population, improved 
care of acute respiratory exacerbations, 
which in the long term may reduce the 
occurrence of chronic lung diseases and  
the under diagnosis of LIP as a result 
of high prevalence of TB, since the 
presenting features are very similar.  

Half of the cases presented with 
tuberculosis. Tuberculosis remains 
a major disease in South Africa and 
its management of importance due to 
its co­infection with HIV resulting in 
more rapid deterioration of immune 
dysfunction, viral replication, and HIV 
progression; and more frequently other 
severe infections (Zar, 2008).  

Bronchiectasis is a common presenting 
condition among children infected with 
HIV and occurs as a result of repeated 
lung tissue damage. It occurs in up to 
16% of children (Rabie et al, 2007).  
Just over 11% of children in this study 
presented with bronchiectasis.  Sheikh  
et al (1997) had similar results however 
the children had a mean age of seven and 
a half years. 

The number of respiratory diseases 
presented in this study was classified 
as low burden when only one condition 
was present and a high burden when two 
or more conditions were present.  This is 
clearly demonstrated with a 69% rate of 
high disease burden.  

Figure 5: Level of immune suppression

Table 2: Summary of Findings

Risk of increased 
Burden

Crudes odd 
ratio

P value

ARV non-users 1/2 0.54 0.13 

Mild 
immunosuppression

1 1/2 1.66 0.50

Advanced / Severe
immunosuppression

2 2.01 0.20

Females 2 2.23 0.05



40   WITS SPECIAL EDITION JOurNAL 2013

A higher burden of disease among 
patients using ARVs was found. This 
result seems to be contradictory as 
the use of ARVs is known to improve 
immune status. Children receiving ARVs 
for a short and a long period of time were 
analysed in the same group, possibly 
masking the effect of ARVs in those who 
had been taking them for a longer time. It 
may also be that the children presenting 
with more conditions had been referred 
to the tertiary hospitals by secondary or 
primary institutions for more specialised 
care of complicated conditions, therefore 
the study only recruited children with 
a higher burden of disease, due to the 
tertiary institutions chosen.

The relationship between the level 
of immune suppression and the burden 
of disease showed that as the level of 
immunity decreased children were 
predisposed to infection. Children 
infected with HIV have a lower 
immunity and are thus more susceptible 
to infection and to having a number of 
co­existing conditions. 

The results showed that girls are twice 
as likely to develop a higher burden of 
disease as boys. This contrasts findings 
by Kristensen and Olsen (2006) that 
girls tended to be better protected 
against acute respiratory infections  
than boys.  Further study is needed to 
clarify this discrepancy.  

This study sought to find whether 
a relationship between the burden of 
disease and the length of hospital stay 
and with respect to mortality exists. 
With regard to mortality the children 
with a low burden of disease died at 
earlier stages after hospital admission.  
The patients with a high burden of 
disease were admitted for longer and 
displayed incidents of mortality much 
later. Children admitted with only 
one condition such as pneumocystis 
jirovecii pneumonia, aggressive in its 
presentation, demised at an early stage 
of admission. The children identified 
to have a higher burden of disease may 
have had conditions less aggressive,  
may have received a more intense  
pro gramme of care thus lengthening 
their hospital stay. No relationship 
between the age of the child and the 
point of hospital stay at which mortality 

occurred was found. Mortality was rather 
influenced by the number of conditions 
presented. 

Of the sample only 36 were already 
taking ARVs, prior to admission, 
for an average length of 10 months 
(±SD=11.61). Sixty two patients were 
only diagnosed with HIV during hospital 
admission, and thus were still awaiting 
initiation of ARV treatment. The most 
commonly administrated drugs inclu­
ded: Stavudine, Lamivudine and Kaletra. 
In 2010, the National Department 
of Health in South Africa published 
“Guidelines for the Management of  
HIV in Children” suggesting that all 
diagnosed children under the age of 
one start ARVs immediately.  Children 
between one and five years are eligible 
to start treatment if they are symptomatic 
(stage III or IV), have a CD4 count less 
than 750 cells/mm3 or percentage CD4 
count below 25%. Children over five 
years of age may start ARV’s when 
they too are symptomatic or have 
CD4 counts less than 350 cells/mm3.  
Studies show that early anti­retroviral 
treatment initiation lowers viral load and 
thus reduces the risk of opportunistic 
infections (Eley et al, 2006). The 
initiation of early ARV use has shown 
a 69­94% reduction in mortality and 
reduced early mortality rates within the 
first six months (Kitahata et al, 2009).

The proportion of current maternal 
anti­retroviral use was not evaluated; 
however it is an important factor 
influencing the burden of childhood 
disease. Maternal death is a major 
risk factor for poor survival in HIV­
exposed infants (Graham, 2005).
Seven intervention trials from sub­
Saharan Africa in largely breastfeeding 
populations demonstrated that the death 
of children by age one is approximately 
seven times greater when the mothers 
are HIV infected compared to non­
infected (Newell et al, 2004). 

One hundred and twenty of the total 
number of patients (n=125) required 
physiotherapy mostly due to excess 
secretions and decreased air entry. The 
need for physiotherapy for each child 
was based upon the need to provide 
treatment due to excess secretions, 
decreased air entry, weak cough, poor 

exercise endurance, poor positioning or 
posture, poor breathing control or need 
for a home programme and caregiver 
education in the event of chronic lung 
diseases. Of the 120 patients the average 
need for physiotherapy was thirteen days. 
There are no studies, both nationally 
and internationally, that have been done 
before to investigate the length of time 
that physiotherapy is required.

CONCLUSION
This study aimed to determine the 
burden of disease with regard to the 
prevalence of respiratory conditions 
among paediatric patients infected with 
HIV/AIDS. The younger age group 
selected showed a predominance of  
acute respiratory disorders. Of the 
125 children perinatally infected with 
HIV, there was a mortality rate of just 
under 10% due to pneumonia, PJP, 
CMV pneumonitis and TB infection.  
Conditions observed were similar to 
previous studies, highlighting that PJP, 
bacterial and viral pneumonia, TB, LIP, 
CMV pneumonitis and bronchiectasis 
remain common conditions among chil­
dren with HIV. This study substantiates 
a shift seen in increased bacterial 
pneumonia rather than PJP diagnoses, 
due to improved prophylactic measures. 

The relationships between the bur­
den of disease and its influencing 
factors showed that a higher burden 
of disease was related to the use of 
ARVs, a higher immuno­suppression, 
longer length of hospital stay, longer 
life span and in female patients.  
Despite six years of anti­retroviral 
therapy roll­out many children’s HIV 
status remains undiagnosed leading to 
delayed initiation of ARVs and interim 
respiratory conditions.



41   WITS SPECIAL EDITION JOurNAL 2013 

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