Tuberculosis and pneumonia in HIV-infected children: an overview

Fowler MG, Qin M, Fiscus SA et al. PROMISE: Efficacy and safety of 2 strategies to prevent perinatal HIV transmission. CROI 2015. 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015), 23–26 February 2015, Seattle. Oral abstract 31LB.

World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. Geneva: World Health Organization; 2013.

Evans C, Jones CE, Prendergast AJ. HIV-exposed, uninfected infants: new global challenges in the era of paediatric HIV elimination. Lancet Infect Dis. 2016;16(6).

World Health Organization. Global update on the health sector response to HIV. 2014. http://www.who.int/hiv/pub/progressreports/update2014-executive-summary/en/.

Newell ML, Coovadia H, Cortina-Borja M, Rollins N, Gaillard P, Dabis F. Mortality of infected and uninfected infants born to HIV infected mothers in Africa: a pooled analysis. Lancet. 2004;364:1236–43.

Ferrand RA, Corbett EL, Wood R, et al. AIDS among older children and adolescents in Southern Africa: projecting the time course and magnitude of the epidemic. AIDS. 2009;23:2039–46.

Theodoratou E, McAllister DA, Reed C, et al. Global, regional, and national estimates of pneumonia burden in HIV infected children in 2010: a meta-analysis and modelling study. Lancet Infect Dis. 2014;14(12):1250–8.

Venturini E, Turkova A, Chiappini E, Galli L, de Martino M, Thorne C. Tuberculosis and HIV co-infection in children. BMC Infect Dis. 2014;14 Suppl 1:S5.

Bates M, Mudenda V, Mwaba P, Zumla A. Deaths due to respiratory tract infections in Africa: a review of autopsy studies. Curr Opin Pulm Med. 2013;19(3):229–37.

Chintu C, Mudenda V, Lucas S, et al. Lung diseases at necropsy in African children dying from respiratory illnesses: a descriptive necropsy study. Lancet. 2002;360:985.

Gupta RK, Lucas SB, Fielding KL, Lawn SD. Prevalence of tuberculosis in post-mortem studies of HIV infected adults and children in resource-limited settings: a systematic review and meta-analysis. AIDS. 2015;29(15):1987–2002.

World Health Organization. Global tuberculosis report. Contract No.: WHO/HTM/TB/2014.08. 2014. http://www.who.int/tb/publications/global_report/en/.

Dodd PJ, Gardiner E, Coghlan R, Seddon JA. Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modeling study. Lancet Glob Health. 2014;2(8):e453_9.

Hesseling AC, Cotton MF, Jennings T, et al. High Incidence of Tuberculosis among HIV infected Infants: Evidence from a South African population-based study highlights the need for improved tuberculosis control strategies. Clin Infect Dis. 2009;48:10.

Walters E, Cotton MF, Rabie H, Schaaf HS, Walters LO, Marais BJ. Clinical presentation and outcome of tuberculosis in human immunodeficiency virus infected children on antiretroviral therapy. BMC Pediatr. 2008;8:1.

Madhi SA, Nachman S, Violari A, et al. Effect of primary isoniazid prophylaxis against tuberculosis in HIV-exposed children. N Eng J Med. 2011;365:21–31.

Cohen JM, Whittaker E, Walters S, Lyall H, Tudor-Williams G, Kampmann B. Presentation, diagnosis and management of tuberculosis in HIV infected children in the UK. HIV Med. 2008;9(5):277–84.

Ferrand RA, Bandason T, Musvaire P, et al. Causes of acute hospitalization in adolescence: burden and spectrum of HIV-related morbidity in a country with an early-onset and severe HIV epidemic: a prospective survey. PLoS Med. 2010;7(2):e1000178.

Cotton MF, Slogrove A, Rabie H. Infections in HIV-exposed Uninfected Children With Focus on Sub-Saharan Africa. Pediatr Infect Dis J. 2014;33(10):1085–6.

Lawn SD, Churchyard G. Epidemiology of HIV-associated tuberculosis. Curr Opin HIV AIDS. 2009;4:325–33.

Lawn SD, Bekker LG, Middelkoop K, Myer L, Wood R. Impact of HIV infection on the epidemiology of tuberculosis in a peri-urban community in South Africa: the need for age-specific interventions. Clin Infect Dis. 2006;42:1040–7.

Wood R, Johnstone-Robertson S, Uys P, et al. Tuberculosis transmission to young children in a South African community: modeling household and community infection risks. Clin Infect Dis. 2010;51:401–8.

Cotton MF, Schaaf HS, Lottering G, Weber HL, Coetzee J, Nachman S. Tuberculosis exposure in HIV-exposed infants in a high-prevalence setting. Int J Tuberc Lung Dis. 2008;12:225–7.

Gupta A, Bhosale R, Kinikar A, et al. Maternal tuberculosis: a risk factor for mother-to-child transmission of human immunodeficiency virus. J Infect Dis. 2011;203:358–63.

Tostmann A, Kik SV, Kalisvaart NA, et al. Tuberculosis transmission by patients with smear-negative pulmonary tuberculosis in a large cohort in the Netherlands. Clin Infect Dis. 2008;47:1135–42.

Lawn SD, Edwards D, Wood R. Tuberculosis transmission from patients with smear-negative pulmonary tuberculosis in sub-Saharan Africa. Clin Infect Dis. 2009;48:496–7.

Marais BJ, Gie RP, Schaaf HS, et al. The natural history of childhood intra-thoracic tuberculosis: a critical review of literature from the pre-chemotherapy era. Int J Tuberc Lung Dis. 2004;8(4):392–402.

Walters E, Duvenhage J, Draper HR, et al. Severe manifestations of extrapulmonary tuberculosis in HIV infected children initiating antiretroviral therapy before 2 years of age. Arch Dis Child. 2014;99(11):998–1003.

Violari A, Cotton MF, Gibb DM, et al. Early antiretroviral therapy and mortality among HIV infected infants. N Engl J Med. 2008;359:2233–44.

Turkova A, Chappell E, Judd A, et al. Prevalence, incidence, and associated risk factors of tuberculosis in children with HIV living in the UK and Ireland (CHIPS): a cohort study. Lancet HIV. 2015;2(12):e530–9. doi:10.1016/S2352-3018(15)00200-3. Epub 2015 Oct 29.

Orikiiriza J, Bakeera-Kitaka S, Musiime V, Mworozi EA, Mugyenyi P, Boulware DR. The clinical pattern, prevalence, and factors associated with immune reconstitution inflammatory syndrome in Ugandan children. AIDS. 2010;24:2009–17.

Bakeera-Kitaka S, Conesa-Botella A, Dhabangi A, et al. Tuberculosis in human immunodeficiency virus infected Ugandan children starting on antiretroviral therapy. Int J Tuberc Lung Dis. 2011;15:1082–6.

Koller M, Patel K, Chi BH, et al. Immunodeficiency in children starting antiretroviral therapy in low-, middle-, and high-income countries. J Acquir Immune Defic Syndr. 2015;68:62–72.

Dangor Z, Izu A, Hillier K, et al. Impact of the antiretroviral treatment program on the burden of hospitalization for culture-confirmed tuberculosis in South African Children: a time-series analysis. Pediatr Infect Dis J. 2013;32:972–7.

UNAIDS. 90–90–90 An ambitious treatment target to help end the AIDS epidemic. UNAIDS/JC2684. 2014. Available from: http://www.unaids.org/sites/default/files/media_asset/90-90-90_en_0.pdf. [cited 2015 Feb 13].

Pretorius C, Menzies NA, Chindelevitch L, et al. The potential effects of changing HIV treatment policy on tuberculosis outcomes in South Africa: results from three tuberculosis-HIV transmission models. AIDS. 2014;28 Suppl 1:S25–34. doi:10.1097/QAD.0000000000000085.

Zar HJ, Cotton MF, Strauss S, et al. Effect of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV: randomised controlled trial. BMJ. 2007;334:136.

Frigati LJ, Kranzer K, Cotton MF, Schaaf HS, Lombard CJ, Zar HJ. The impact of isoniazid preventive therapy and antiretroviral therapy on tuberculosis in children infected with HIV in a high tuberculosis incidence setting. Thorax. 2011;66:496–501.

Hesseling AC, Kim S, Madhi S, Nachman S, et al. High prevalence of drug resistance amongst HIV-exposed and -infected children in a tuberculosis prevention trial. Int J Tuberc Lung Dis. 2012;16:192–5.

Seddon JA, Hesseling AC, Finlayson H, et al. Preventive therapy for child contacts of multidrug-resistant tuberculosis: a prospective cohort study. Clin Infect Dis. 2013;57(12):1676–84.

Seddon JA, Hesseling AC, Willemse M, Donald PR, Schaaf HS. Culture-confirmed multidrug-resistant tuberculosis in children: clinical features, treatment, and outcome. Clin Infect Dis. 2012;54(2):157–66.

Hicks RM, Padayatchi N, Shah NS, et al. Malnutrition associated with unfavorable outcome and death among South African MDR-TB and HIV co-infected children. Int J Tuberc Lung Dis. 2014;18(9):1074–83.

Fairlie L, Beylis NC, Reubenson G, Moore DP, Madhi SA. High prevalence of childhood multi-drug resistant tuberculosis in Johannesburg, South Africa: a cross sectional study. BMC Infect Dis. 2011;11:28.

Seddon JA, Hesseling AC, Godfrey-Faussett P, Schaaf HS. High treatment success in children treated for multidrug-resistant tuberculosis: an observational cohort study. Thorax. 2014;69(5):458–64.

Isaakidis P, Casas EC, Das M, Tseretopoulou X, Ntzani EE, Ford N. Treatment outcomes for HIV and MDR-TB co-infected adults and children: systematic review and meta-analysis. Int J Tuberc Lung Dis. 2015;19(8):969–78.

Dangor Z, Izu A, Moore DP, et al. Temporal association in hospitalizations for tuberculosis, invasive pneumococcal disease and influenza virus illness in South African children. PLoS One. 2014;9(3):e91464.

Moore DP, Klugman KP, Madhi SA. Role of Streptococcus pneumoniae in hospitalization for acute community-acquired pneumonia associated with culture-confirmed Mycobacterium tuberculosis in children: a pneumococcal conjugate vaccine probe study. Pediatr Infect Dis J. 2010;1(2):1099–04.

Crook AM, Turkova A, Musiime V, et al. Tuberculosis incidence is high in HIV infected African children but is reduced by co-trimoxazole and time on antiretroviral therapy. BMC Med. 2016;14:50.

Madhi SA, Huebner RE, Doedens L, Aduc T, Wesley D, Cooper PA. HIV-1 co-infection in children hospitalised with tuberculosis in South Africa. Int J Tuberc Lung Dis. 2000;4:448–54.

Marais BJ, Schaaf HS. Tuberculosis in children. Cold Spring Harb Perspect Med. 2014;4(9):a017855. doi:10.1101/cshperspect.a017855.

Schaaf HS, Marais BJ, Whitelaw A, et al. Culture-confirmed childhood tuberculosis in Cape Town, South Africa: a review of 596 cases. BMC Infect Dis. 2007;7:140.

Hesseling AC, Schaaf SH, Westra AE, et al. Outcome of HIV infected children with culture-confirmed tuberculosis. Arch Dis Child. 2005;90:1171–4.

Maritz E, Liu L, Montepierda G, et al. Timing of tuberculosis sourse case contact information and tuberculosis in HIV infected and HIV-exposed non-infected children from southern Africa: IMPAACT 1041. 43rd Union World Conference on Lung Health 2012 Nov 13–17; Kuala Lumpur, Malaysia. Abstract PC 640 17.

Jeena PM, Pillay P, Pillay T, Coovadia HM. Impact of HIV-1 co-infection on presentation and hospital-related mortality in children with culture proven pulmonary tuberculosis in Durban, South Africa. Int J Tuberc Lung Dis. 2002;6:672–8.

Ren Y, Nuttall JJ, Eley BS, et al. Effect of rifampicin on efavirenz pharmacokinetics in HIV infected children with tuberculosis. J Acquir Immune Defic Syndr. 2009;50(5):439–43.

Ren Y, Nuttall JJ, Egbers C, et al. Effect of Rifampicin on Lopinavir Pharmacokinetics in HIV infected children with tuberculosis. J Acquir Immune Defic Syndr. 2008;47:566–9.

Oudijk JM, McIlleron H, Mulenga V, et al. Pharmacokinetics of nevirapine in HIV infected children under 3 years on rifampicin-based antituberculosis treatment. AIDS. 2012;26(12):1523–8.

Yapa HM, Boffito M, Pozniak A. Critical Review: What dose of rifabutin is recommended with antiretroviral therapy? J Acquir Immune Defic Syndr. 2016;72:138-52.

World Health Organization. Guidelines for the programmatic management of drug-resistant tuberculosis: Emergency Update 2008. 2008. http://whqlibdoc.who.int/publications/2008/9789241547581_eng.pdf.

Seddon JA, Hesseling AC, Marais BJ, et al. Paediatric use of second-line anti-tuberculosis agents: a review. Tuberculosis (Edinb). 2012;92(1):9–17. 3.

Coyne KM, Pozniak AL, Lamorde M, Boffito M. Pharmacology of second-line antituberculosis drugs and potential for interactions with antiretroviral agents. AIDS. 2009;23(4):437–46. 10.

Frohoff C, Moodley M, Fairlie L, et al. Antiretroviral therapy outcomes in HIV infected children after adjusting protease inhibitor dosing during tuberculosis treatment. PloS one. 2011;6:e17273. doi:10.1371/journal.pone.001727.

Meyers T, Sawry S, Wong JY, et al. Virologic failure among children taking lopinavir/ritonavir-containing first-line antiretroviral therapy in South Africa. Pediatr Infect Dis J. 2014:1.

Reitz C, Coovadia A, Ko S, et al. Initial response to protease-inhibitor-based antiretroviral therapy among children less than 2 years of age in South Africa: effect of cotreatment for tuberculosis. J Infect Dis. 2010;201:1121–31.

World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2013. Available from: http://www.who.int/publications/guidelines/en/. [cited 2015 Feb 13].

Arrow Trial Team. Routine versus clinically driven laboratory monitoring and first-line antiretroviral therapy strategies in African children with HIV (ARROW): a 5-year open-label randomised factorial trial. Lancet. 2013;381(9875):1391–403.

Bahr N, Boulware DR, Marais S, Scriven J, Wilkinson RJ, Meintjes G. Central nervous system immune reconstitution inflammatory syndrome. Curr Infect Dis Rep. 2013;15:583–93.

van Toorn R, Rabie H, Dramowski A, Schoeman JF. Neurological manifestations of TB-IRIS: a report of 4 children. Eur J Paediatr Neurol. 2012;16:676–82.

Rabie H, Frigati L, Hesseling AC, Garcia-Prats AJ. Tuberculosis: opportunities and challenges for the 90-90-90 targets in HIV infected children. J Int AIDS Soc. 2015;18 Suppl 6:20236.

Liu L, Oza S, Hogan D, et al. Global, regional, and national causes of child mortality in 2000–13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet. 2015;385(9966):430–40. published online Oct 1. http://dx.doi.org/10.1016/S0140-6736(14)61698-6.

Rudan I, O’Brien KL, Nair H, et al. Epidemiology and etiology of childhood pneumonia in 2010: estimates of incidence, severe morbidity, mortality, underlying risk factors and causative pathogens for 192 countries. J Glob Health. 2013;3:10401.

Nair H, Simoes EA, Rudan I, et al. Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis. Lancet. 2013;381:1380–90.

Gray DM, Zar HJ. Community-acquired pneumonia in HIV infected children: a global perspective. Curr Opin Pulm Med. 2010;16(3):208–16.

McNally LM, Jeena PM, Gajee K, et al. Effect of age, polymicrobial disease, and maternal HIV status on treatment response and cause of severe pneumonia in South African children: a prospective descriptive study. Lancet. 2007;369:1440–51.

George R, Andronikou S, Theron S, et al. Pulmonary infections in HIV. Pediatr Radiol. 2009;39(6):545–54. doi:10.1007/s00247-009-1194-9.

Sawicki GS, Lu FL, Valim C, Cleveland RH, Colin AA. Necrotising pneumonia is an increasingly detected complication of pneumonia in children. Eur Respir J. 2008;31(6):1285–91.

Edinburgh KJ, Jasmer RM, Huang L, et al. Multiple pulmonary nodules in AIDS: usefulness of CT in distinguishing among potential causes. Radiology. 2000;214:427–32.

El-Atrouni W, Berbari E, Temesgen Z. HIV-associated opportunistic infections. Bacterial infections. J Med Liban. 2006;54:80–3.

Bliss SJ, O'Brein KL, Janoff EN. The evidence for using conjugate vaccines to protect HIV infected children against pneumococcal disease. Lancet Infect Dis. 2008;8:67–80.

Nunes MC, von Gottberg A, de Gouveia L, et al. The impact of antiretroviral treatment on the burden of invasive pneumococcal disease in South African children: a time series analysis. AIDS. 2011;25(4):453–62.

Madhi SA, Izu A, Nunes MC, et al. Longitudinal study on Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus nasopharyngeal colonization in HIV infected and -uninfected infants vaccinated with pneumococcal conjugate vaccine. Vaccine. 2015;33(23):2662–9.

Fletcher MA, Schmitt HJ, Syrochkina M, Sylvester G. Pneumococcal empyema and complicated pneumonias: global trends in incidence, prevalence, and serotype epidemiology. Eur J Clin Microbiol Infect Dis. 2014;33:879–910.

Cohen C, Walaza S, Moyes J, et al. Epidemiology of viral-associated acute lower respiratory tract infection among children <5 years of age in a high HIV prevalence setting, South Africa, 2009–2012. Pediatr Infect Dis J. 2015;34(1):66–72.

Cohen C, Walaza S, Moyes J, et al. Epidemiology of severe acute respiratory illness (SARI) among adults and children aged ≥5 years in a high HIV-prevalence setting, 2009–2012. PLoS One. 2015;10(2):e0117716.

Nunes MC, Kuschner Z, Rabede Z, et al. Clinical epidemiology of bocavirus, rhinovirus, two polyomaviruses and four coronaviruses in HIV infected and HIV-uninfected South African children. PLoS One. 2014;9(2):e86448.

Shi T, Balsells E, Wastnedge E, et al. Risk factors for respiratory syncytial virus associated with acute lower respiratory infection in children under five years: systematic review and meta-analysis. J Glob Health. 2015;5(2):020416.

Moyes J, Cohen C, Pretorius M, et al. Epidemiology of respiratory syncytial virus-associated acute lower respiratory tract infection hospitalizations among HIV infected and HIV-uninfected South African children, 2010–2011. J Infect Dis. 2013;208 Suppl 3:S217–26.

Madhi SA, Schoub B, Simmank K, Blackburn N, Klugman KP. Increased burden of respiratory viral associated severe lower respiratory tract infections in children infected with human immunodeficiency virus type-1. J Pediatr. 2000;137(1):78–84.

Madhi SA, Ramasamy N, Bessellar TG, Saloojee H, Klugman KP. Lower respiratory tract infections associated with influenza A and B viruses in an area with a high prevalence of pediatric human immunodeficiency type 1 infection. Pediatr Infect Dis J. 2002;21:291–7.

Madhi SA, Kuwanda L, Venter M, Violari A. Prospective cohort study comparing seasonal and H1N1(2009) pandemic influenza virus illnesses in HIV infected children during 2009. Pediatr Infect Dis J. 2014;33(2):174–6.

Giannattasio A, Lo Vecchio A, Russo MT, et al. Pandemic flu: a comparative evaluation of clinical, laboratory, and radiographic findings in HIV-positive and negative children. AIDS. 2010;24(14):2292–4.

Cerevalolo A, Orsi A, Parodi V, Ansaldi F. Influenza vaccination in HIV-positive subjects: latest evidence and future perspective. J Prev Med Hyg. 2013;54(1):1–10.

Jeena PM, Coovadia HM, Chrystal V. Pneumocystis carinii and cytomegalovirus infections in severely ill, HIV infected African infants. Ann Trop Paediatr. 1997;76:124–8.

Williams AJ, Duong T, McNally LM, et al. Pneumocystis carinii pneumonia and cytomegalovirus infection in children with vertically acquired HIV infection. Aids. 2001;15:335–9.

Gumbo H, Chasekwa B, Church JA, et al. Congenital and postnatal CMV and EBV acquisition in HIV infected Zimbabwean infants. PLoS One. 2014;9(12):e114870.

Chang TS, Wiener J, Dollard SC, et al. Effect of cytomegalovirus infection on breastfeeding transmission of HIV and on the health of infants born to HIV infected mothers. AIDS. 2015;29(7):831–6.

Goussard P, Kling S, Gie RP, Nel ED, Heyns L, Rossouw GJ, Janson JT. CMV pneumonia in HIV infected ventilated infants. Pediatr Pulmonol. 2010;45:650–5.

Zampoli M, Morrow B, Hsiao NY, Whitelaw A, Zar HJ. Prevalence and outcome of cytomegalovirus-associated pneumonia in relation to human immunodeficiency virus infection. Pediatr Infect Dis J. 2011;30(5):413–7.

Hsiao NY, Zampoli M, Morrow B, Zar HJ, Hardie D. Cytomegalovirus viraemia in HIV exposed and infected infants: prevalence and clinical utility for diagnosing CMV pneumonia. J Clin Virol. 2013;58(1):74–8.

Moss WJ, Griffin DE. Measles. Lancet. 2012;379:153–64.

Moss WJ, Monze M, Ryon JJ, Quinn TC, Griffin DE, Cutts F. Prospective study of measles in hospitalized, human immunodeficiency virus (HIV)-infected and HIV-uninfected children in Zambia. Clin Infect Dis. 2002;35:189–96.

le Roux DM, le Roux SM, Nuttall JJ, Eley BS. South African measles outbreak 2009–2010 as experienced by a paediatric hospital. S Afr Med J. 2012;102:760–4.

Measles vaccines: WHO position paper. Wkly Epidemiol Rec 2009;84:349–60.

Moss WJ, Fisher C, Scott S, et al. HIV type 1 infection is a risk factor for mortality in hospitalized Zambian children with measles. Clin Infect Dis. 2008;46:523–7.

Mussi-Pinhata MM, Freimanis L, Yamamoto AY, et al. Infectious disease morbidity among young HIV-1-exposed but uninfected infants in Latin American and Caribbean countries: the National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study. Pediatrics. 2007;119:e694–704.

Slogrove AL, Cotton MF, Esser MM. Severe infections in HIV-exposed uninfected infants: clinical evidence of immunodeficiency. J Trop Pediatr. 2010;56(2):75–81.

Pitcher RD, Daya R, Beningfield SJ, Zar HJ. Chest radiographic presenting features and radiographic progression of pneumocystis pneumonia in South African children. Pediatr Pulmonol. 2011;46(10):1015–22.

Morrow BM, Samuel CM, Zampoli M, Whitelaw A, Zar HJ. Pneumocystis pneumonia in South African children diagnosed by molecular methods. BMC Res Notes. 2014;7:26.

Chintu C, Bhat GJ, Walker AS, et al. Co-trimoxazole as prophylaxis against opportunistic infections in HIV infected Zambian children (CHAP): a double-blind randomised placebo-controlled trial. Lancet. 2004;364(9448):1865–71.

Berman DM, Mafut D, Djokic B, Scott G, Mitchell C. Risk factors for the development of bronchiectasis in HIV infected children. Pediatr Pulmonol. 2007;42(10):871 5.

Sheikh S, Madiraju K, Steiner P, Rao M. Bronchiectasis in pediatric AIDS. Chest. 1997;112(5):1202. 7.

McHugh G, Rylance J, Mujuru H, et al. Chronic morbidity among older children and adolescents at diagnosis of HIV infection. J Acquir Immune Defic Syndr. 2016. [Epub ahead of print].