- Email: [email protected]
Pneumococcal conjugate vaccines as a probe for better understanding pneumococcal respiratory infections
Oral Presentations / Paediatric Respiratory Reviews 12S1 (2011) S1–S66
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 Appropriate and effective inhalation machines are not available and have been replaced by cheaper, less efficient units.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
S43
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 viralbacterial 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 allcause 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 childhood 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, UK Correspondence: [email protected]
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.
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
S43
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 viralbacterial 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 allcause 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 childhood 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, UK Correspondence: [email protected]
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.