Oral Presentations / Paediatric Respiratory Reviews 12S1 (2011) S1–S66 S43

CF center in Gaza. The establishment of a CF center located in

a hospital in Gaza should provide the full spectrum of health

services for CF patients including diagnostic capabilities, appropriate

consultative services and treatment modalities, and the ability to

provide psychosocial support. Establishment of such a CF center

would open new opportunities for physicians, nurses and other

health care personnel to train in CF centers outside of Gaza in order

to obtain expertise and specialization with this disease.

Methods: The CF center team at Hadassah Hebrew University

Medical Center, Jerusalem, Israel was the only program that

answered this international plea for help. The CF center at Hadassah

established a 1-year training program funded by the Peres Center

for Peace to train a team of 3 physicians, a nurse and physiotherapist

from Gaza that volunteered to participate in this project. The

training took place at Hadassah Hospital in Jerusalem, Israel with

trainees living in Jerusalem during the week and commuting home

to Gaza during the weekends.

Results: After the year-long training period, a CF center was opened

in Gaza. A database was established to register all known CF

patients. We are currently aware of 80 patients with CF in the Gaza

strip. Based on population projections, it is estimated that there

are between 140–300 patients with CF in Gaza, a large number of

which have not been diagnosed and others whom have died of CF

complications without an established diagnosis.

Limited resources under the current Hamas government continue

to be problematic. Medications are still in short supply and

are available mainly by private donations. Prior to the arrival

of the trained CF team, the medical staff frequently dosed

those medications that were available such as pancreatic

enzymes incorrectly. Trained personnel are still unable to

provide physiotherapy to many patients. Appropriate and effective

inhalation machines are not available and have been replaced

by cheaper, less efficient units. Hypertonic Saline is the standard

mucolytic/secretion clearance treatment. Families are preparing this

at home by mixing 15% Hypertonic Saline with 0.9% Normal Saline.

Inhaled antibiotics such as TOBI are not available and are replaced by

inhalation of intravenous solutions such as Gentamicin. Nutritional

supplements are rarely available and again, only by private donation.

Food enrichment is done by families by mixing cereal with oil.

Appropriate next steps in the evolution of the CF program in Gaza

are to work with health authorities to understand the importance

of providing basic therapies to patients.

Conclusions: In resource poor countries, treatment of CF patients

should begin with the establishment of a center with dedicated and

specialized team members. Creative and less expensive therapies

can be used including saline mixtures and inhalation of intravenous

antibiotics. Likewise, appropriately trained family members can

provide physiotherapy. Lobbying governments unwilling to dedicate

appropriate resources to treat patients is not always effective.

IV.4. Infection, Inflammation & Other Topics – Childhood

respiratory infections: the new frontiers

IV.4.1

Pneumococcal conjugate vaccines as a probe for better

understanding pneumococcal respiratory infections

R. Dagan. Pediatric Infectious Disease Unit, Soroka University Medical

Center and the Faculty of Health Sciences, Ben-Gurion University of

the Negev, Beer-Sheva, Israel

Respiratory infections are the leading cause of morbidity and

mortality in young infants and young children globally. Streptococcus

pneumoniae (Pnc) is the leading bacterial pathogen in respiratory

infections and a major cause of deaths in children <5 years of

age (~11% of all deaths in this age group [1]). Around 14.5 million

episodes of serious pneumococcal disease occurred in the year

2000 in children <5 years with ~825,000 estimated deaths, due to

serious pneumococcal disease. 95% of these serious pneumococcal

disease cases and mortality were attributed to pneumonia [1]. Most

serious diseases caused by pneumococcal respiratory disease occur

in only 10 countries in Africa and Asia, but pneumococcal respiratory

infections are a serious problem globally [1]. Thus it is clear that

preventing pneumococcal severe respiratory infections is one of the

main global goals [2]. However, what is pneumococcal respiratory

disease? The tradition wisdom that pneumococcal pneumonia

presenting as alveolar (or lobar) pneumonia is shown to be wrong,

although this entity is definitely enriched with bacterial pathogens

in general and Pnc in particular.

Using any diagnostics tools detects a bacterial pathogen in only a

low proportion of LRI and pneumonia. On the other hand, series

of efficacy studies with pneumococcal conjugate vaccine in the

US, South Africa, the Gambia and the Philippines showed that the

use of pneumococcal conjugate vaccines (PCVs) reduced alveolar

pneumonia by ~33%, pointing clearly to an important role of Pnc

in alveolar pneumonia [3]. However, other endpoints, such as

any severe pneumonia (efficacy of 21%) and any clinical pneumonia

(efficacy of 8%) were all affected by PCVs, suggesting that Pnc has

a role even in the less “classical” pneumonia. Furthermore, the less

specific entities were far more common than the classical alveolar

pneumonia endpoint, thus a smaller percentage of efficacy in the

“non-specific” pneumococcal cases led to a much higher vaccine

attributable reduction (VAR) of disease. Thus, for each episode of

culture-proven pneumococcal pneumonia, 7 radiologically-proven

pneumococcal pneumonia episodes and 19 “clinical pneumonia”

episodes could be prevented [3].

Even more surprising findings were that PCVs could reduce what

was considered until recently as “pure” viral infections. The first

work was from Israel, where a PCV could reduce 20% of bronchiolitis

episodes in daycare center toddlers attendees [4]. Later, in a

series of studies, Madhi and Klugman showed in South Africa

that hospitalization due to virus-positive pneumonia including RSV,

human metapneumovirus, parainfluenza 1–3 and influenza A and

B, were significantly reduced by a PCV [5]. This was the proof of the

concept that viral infections often represent in fact a common viral-

bacterial co-infection was proven. By reducing the pneumococcal

component, severity of the viral infections can be reduced, resulting

in a significant reduction in the proportion of the children ending

up being hospitalized.

After the introduction of the 7-valent PCV (PCV7) to various

countries, a reduction in overall outcomes in respiratory infections

could be observed. In the US, <30% of hospitalizations due to all-

cause pneumonia was seen in the post PCV7 in children <2 years of

age. However, at the same time, a 20% reduction of hospitalization

due to non-pneumonia LRIs was seen [6] showing that for each

case of invasive pneumococcal disease prevented, hospitalization of

14 cases of respiratory infections was prevented by PCV7.

The series of studies reviewed above contributed on the one hand to

our understanding of the role of pneumocococci in respiratory tract

infections, but on the other hand showed that the use of PCV was

associated with much greater than expected reduction in respiratory

disease. The insights acquired on pneumococcal role in the overall

respiratory disease burden and the insights acquired on the PCV role

in the reduction of such disease lead to the term “vaccine probe”

which means that the use of vaccine can show us its unexpected

benefit and teach us about pathogens and epidemiology.

We also learned that some serotypes not included in the PCV7 are

important, especially for the complicated (or complex) pneumonia,

namely pleuropneumonia (or empyema). The most important

serotypes are 1, 3, 5, 7F, 14 and 19A, of which only serotype

14 is included in the PCV7. Thus, no one should be surprised

that empyema was not reduced after the introduction of PCV7,

especially given the fact that another non-Pnc pathogen responsible

for this complex entity was MRSA. In fact, an increase in this entity

was observed worldwide regardless of PCV7 administration. On

the other hand, the new generation PCV10 and PCV13 vaccines

S44 Oral Presentations / Paediatric Respiratory Reviews 12S1 (2011) S1–S66

contain the “empyema serotypes” and thus after switching from

PCV7 to PCV13, we are expecting reduction of empyema. However,

the effectiveness of the new PCVs has still to be proven, following

vaccine implementation.

In summary, the vaccine probe studies has taught us how important

PCVs are and that the widespread use of these vaccines can reduce

mortality and morbidity. Much more can be learned if additional

high quality surveillance programs are set up in countries adopting

the vaccine.

References

[1] O’Brien KL, Wolfson LJ, Watt JP, et al. Burden of disease caused by

Streptococcus pneumoniae in children younger than 5 years: global

estimates. Lancet 2009; 374: 893–902.

[2] World Health Organization. Pneumococcal conjugate vaccine for child-

hood immunization – WHO position paper. Weekly Epidemiological

Record. No. 12, 2007, 82, 93–104 (www.who.int/wer).

[3] Madhi SA, Kuwanda L, Cutland C,Klugman KP. The impact of a 9-valent

pneumococcal conjugate vaccine on the public health burden of

pneumonia in HIV-infected and -uninfected children. Clin Infect Dis

2005; 40: 1511–8.

[4] Dagan R, Sikuler-Cohen M, Zamir O, Janco J, Givon-Lavi N,Fraser D. Effect

of a conjugate pneumococcal vaccine on the occurrence of respiratory

infections and antibiotic use in day-care center attendees. Pediatr Infect

Dis J 2001; 20: 951–8.

[5] Madhi SA, Klugman KP. Efficacy and Safety of Conjugate Pneumococcal

Vaccine in the Prevention of Pneumonia. In: Siber GR, Klugman PK,

Makela H, eds. Pneumococcal Vaccines: The impact of Conjugate

Vaccine. Washington, DC, ASM Press, 2008: ch. 22, pp. 327–346.

[6] CDC. Pneumonia hospitalizations among young children before and

after introduction of pneumococcal conjugate vaccine – United States,

1997–2006. MMWR 2009; 6: 1–4.

IV.4.2

How to manage complicated pneumonia

I.M. Balfour-Lynn. Royal Brompton Hospital, London, UKCorrespondence: i.balfourlynn@ic.ac.uk

In previously healthy children, community-acquired pneumonia

is normally treated easily and without complications using

intravenous or oral antibiotics [1]. However sometimes

complications may be encountered which require tertiary

respiratory care:

• Parapneumonic effusion / empyema

• Lung abscess

• Necrotising pneumonia

• Pneumatocoeles

• Pneumothorax

• Atelectasis

Another complications is failure to improve in the usual timeframe,

and this may require further investigations such as bronchoscopy,

CT chest scan etc.

The mainstay of treatment is administration of intravenous

antibiotics and it is important to pick the right one(s), especially

in the absence of microbial isolation. Supportive therapy may

also be necessary, for example oxygen, intravenous fluids or even

ventilatory support.

Further intervention may be required for example an intercostal

chest drain for fluid or air. Management options for an empyema

are well described [2]. However where possible it is best to stay

out of the chest cavity especially in the presence of necrotising

pneumonia, a lung abscess or pneumatocoeles.

Follow up is also important to exclude an underlying cause such as

a congenital thoracic malformation or immunodeficiency. Prognosis

and long term outcomes are usually excellent.

References

[1] British Thoracic Society Standards of Care Committee. British Thoracic

Society Guidelines for the Management of Community Acquired

Pneumonia in Childhood. Thorax. 2002;57 Suppl 1:i1–24.

[2] Balfour-Lynn IM, Abrahamson E, Cohen G, Hartley J, King S, Parikh D,

Spencer D, Thomson AH, Urquhart D. BTS Guidelines for the

Management of Pleural Infections in Children. Thorax 2005;60 Suppl

1:i1–21.

IV.4.3

Pneumonia in HIV-infected children

H.J. Zar. Department of Paediatrics and Child Health, Red Cross War

Memorial Children’s Hospital, University of Cape Town, South Africa

Pneumonia is a major cause of mortality and hospitalization in

HIV-infected children, particularly in Sub-Saharan Africa, where the

paediatric HIV epidemic is concentrated. HIV-infected children have

a higher risk of developing pneumonia and of more severe disease,

including bacteraemic illness compared to immunocompetent

children. Although early use of highly active anti-retroviral therapy

(HAART) can substantially reduce the incidence and severity of

pneumonia in HIV-infected children, pneumonia remains the major

cause of morbidity in these children. Bacterial pathogens especially

S. pneumoniae, S. aureus and Gram negative bacteria predominate

with rising rates of antimicrobial resistance. More widespread

availability of the conjugate vaccines, HiB and pneumococcal

conjugate vaccine (PCV) can impact on the epidemiology and

aetiology of pneumonia with reduced incidence of these bacterial

pathogens and reduced hospitalisations for severe pneumonia. In

high TB prevalence areas, M. tuberculosis causes acute pneumonia,

often with associated bacterial coinfection. Pneumocystis jirovecii

(PCP) remains an important cause of severe pneumonia especially in

infants who have not yet been diagnosed with HIV-infection, are not

on HAART or who are not taking chemoprophylaxis. Viral infections,

especially CMV-associated pneumonia are common; CMV disease

has been frequently found in fatal pneumonia. Polymicrobial

infection is common and associated with an exponential increased

risk of mortality as the number of pathogens increases. HIV-exposed

but uninfected children have an increased risk of pneumonia and a

poorer outcome than HIV-unexposed children.

Standard case management guidelines are effective to reduce

pneumonia-specific and overall mortality but require adaptation

for high HIV prevalence areas. Broad spectrum antibiotics should

be used as empiric therapy. Infants or children who are not taking

pneumocystis prophylaxis should be treated for PCP. Oxygen is

indicated for hypoxic children. Treatment for CMV pneumonitis

should be initiated in children with severe pneumonia in whom

CMV testing is positive.

A number of effective preventive strategies are available. Early

use of highly antiretroviral therapy (HAART) at the time of HIV

diagnosis, is highly effective for reducing pneumonia incidence

and severity. Pathogen specific immunizations are protective but

have reduced efficacy in children not on HAART. Pneumococcal

conjugate vaccine is an effective strategy for reducing pneumonia

incidence and severity; immunogenicity is similar in HIV-uninfected

and HIV-infected children on HAART. However, booster doses may

be need in children not on HAART as efficacy wanes over time.

Prophylaxis against PCP is indicated for all HIV-infected infants but

may be stopped once immune reconstitution is well established in

children over 2 years of age on HAART. Isoniazid prophylaxis for

M. tuberculosis is a potentially effective intervention especially for

HIV-infected children who are not taking HAART and who live in

high TB prevalence areas.

Greater access to the available, effective preventative and treatment

strategies especially PCP prophylaxis, pneumococcal conjugate

vaccine and HAART are urgently needed in areas of high childhood

HIV prevalence where they are still not widely available.