India had around 21 lakh people living with HIV in 2017, among whom 56% were accessing antiretroviral therapy 7. The development of highly active antiretroviral therapy (HAART) and prophylaxis therapy for opportunistic infections has significantly decreased the viral load (and thus HIV related morbidity and mortality) in adults as well as in pediatric populations. However, pulmonary infections remain the first cause of hospital admission in HIV-infected children even in the HAART era. 5

In present study, majority of children (51.11%) were in age group > 10 years to 15 years, 22.22% were between 5 and 10 years, 17.78% were < 5 years, and 8.89% were > 15–18 years of age. The male to female ratio was 2.75:1.

Pulmonary manifestations, viz. fever & cough, were seen in 95.56% of the patients at time of presentation.

In present study, 30 (66.67%) out of 45 patients were on ART and 15 (33.33%) patients did not receive ART (Table 8). It was observed that the patients receiving ART had better CD4 counts as compared to patients not receiving ART (pre-ART patients).

Bacterial Infection. Frontal chest radiograph (CXR) in a 12-year-old HIV-positive male reveals diffuse consolidation (arrow in A) involving left lung field. After start of antibiotics, the consolidation showed gradual resolution (arrow in B), with appearance of two oval cystic lucencies (arrows in C) in left upper & mid zones suggesting pneumatocele formation. CT chest (sagittal plane in lung window) confirmed presence of pneumatoceles in left upper lobe (arrows in D). Axial CT in soft tissue window (E) showed enlarged pulmonary artery (thick arrow) suggestive of pulmonary hypertension, and few calcified mediastinal/hilar lymph nodes (thin arrows). Patient’s CD4 count was 354 cells/cu.mm. Sputum isolated pneumococcus. Patient showed complete clinical and radiological improvement after a course of antibiotic with non-visualization of pneumatoceles on follow-up CXR (F)

Bacterial Infection. Frontal CXR in a 13-year-old HIV-positive female shows right lower lobe consolidation involving mid and lower zones, causing silhouetting of adjacent right hemi-diaphragm (arrows in A & B). Sputum could not isolate any microorganism. CD4 count was 301 cells/cu.mm. Patient was put on antibacterial antibiotics and improved clinically & radiologically (C) over a period of 4 weeks

Bacterial Infection. An 18-month-old male child reveals consolidation/haziness in bilateral upper & mid zones (thick vertical arrows), with hyperinflation in left lower zone (thin horizontal arrow), on frontal CXR (A). CT chest (axial, lung window) shows subsegmental consolidation in RUL (arrow in B), GGO in bilateral lower lobes (asterisks) and consolidation with hyperinflation of lateral basal segment of LLL (arrow in C). Sputum could not isolate any microorganism. BAL isolated Klebsiella species. CD4 count was 406 cells/cu.mm. Patient responded to antibacterial antibiotics and improved clinically & radiologically (D) over a period of 4 weeks

Bacterial Infection. CXR (PA view) in a 12-year-old HIV-positive child reveals inhomogeneous opacity in right para-cardiac region (arrow in A). CT chest (lung window) shows presence of consolidation (white arrow in B) in medial segment of RML, along with centrilobular nodules (black arrows in B) in bilateral lung fields on axial image, and collapse of anterior segment of RUL on sagittal image (arrow in C). Sputum could not isolate any microorganism. CD4 count was 400 cells/cu.mm. Patient was given antibacterial antibiotics and improved clinically & radiologically (D) over a period of 3 weeks

Bacterial Infection. A 10-year-old male, presented with cough and fever since last 2 days. Chest X-ray (PA view) reveals bilateral LZ haziness (arrows) (A). CT chest (axial view) shows subsegmental GGO in RUL (arrow) (B) and nodular air-space opacity in LLL (black arrow) along with bronchiectatic changes and peribronchial thickening in B/L LL (white arrows) (C). Sputum could not isolate any microorganism. CD4 count was 95 cells/cu.mm. Patient was given antibacterial antibiotics and improved clinically and radiologically (D) over a period of 4 weeks

Bacterial Infection. An 11-year-old-HIV-positive male patient presented with cough & fever since 15 days. CXR-posteroanterior (PA) view reveals a homogenous opacity involving left lower zone causing silhouetting of left cardiac border and left hemi-diaphragm (arrow, A). CT chest shows left lower lobe and lingular atelecto-bronchiectatic changes (arrow in B,C) with ipsilateral mediastinal shift and upward displacement of the left hemi-diaphragm. Sputum could not isolate any microorganism. CD4 count was 248 cells/cu.mm. Patient was given antibacterial antibiotics and improved clinically over a period of 2 weeks

Bacterial Infection. Frontal CXR in a 6-year-old HIV-positive female reveals focal area of consolidation in right para-cardiac region (arrow, A), later progressing into frank cavitation (arrow, B). Sputum could not isolate any microorganism. CD4 count was 400 cells/cu.mm. Patient was given antibacterial antibiotics and improved clinically and radiologically (C) over a period of 4 weeks

Bacterial Infection. CXR-PA view in a 13-year-old HIV-positive female shows bilateral mid-zone triangular patchy opacities causing silhouetting of adjacent cardiac borders (arrows, A). CT chest shows right middle lobe (RML) and lingular atelecto-brochiectatic changes (arrows in B, lung window), and mediastinal lymphadenopathy (arrow in C, soft issue window). Sputum could not isolate any microorganism. CD4 count was 1001cells/cu.mm. Patient was given antibacterial antibiotics and improved clinically and radiologically (D) over a period of 4 weeks

A total of 27 (60%) out of 45 patients were diagnosed with bacterial infections in our study (Table 1). Similar increased incidence of bacterial pneumonia has been reported by Afessa et al. (42% in an autopsy series of 233 HIV-infected individuals) and supported by others. 8, 9

Fever, productive cough & tachypnea were the most common presenting complaints, followed by breathlessness and chest pain.

In the present study, microorganisms isolated in four (8.89%) patients were Pneumococcus, Staphylococcus, Pseudomonas and Klebsiella. In 23 patients, no microorganism could be isolated in sputum/BAL/gastric aspirate/blood culture. They were diagnosed as probable bacterial patients on the basis of clinical and radiological findings and all of them showed clinical and radiological improvement with antibacterial antibiotics.

Thirteen (48.15%) out of 27 patients had CD4 count > 500 cells/mm3, 12 (44.44%) patients had CD4 count > 200–500 cells/mm3, and only two patients had CD4 count < 200 cells/mm3 (Table 5). The present study observed that bacterial infections tend to occur in early stages of HIV infection when immune status is relatively preserved. Hirschtick et al. described similar correlation of CD4 count with bacterial infections. They stated that although bacterial pneumonia often occurs in early stages of HIV infection, the risk of bacterial infection increases steadily with declining CD4 lymphocyte counts. 9

Eighteen (66.67%) out of 27 patients with bacterial infection were on ART (Table 7), and 11 (61.11%) of these had CD4 count > 500 cells/mm3, and 38.89% had CD4 count in the range of 200–500 cells/mm3 suggesting better immune status of patients on ART with bacterial infections. In comparison with this, seven out of nine patients (i.e., 77.78%) of bacterial infection not receiving ART had CD4 counts of 500 cells/mm3 or less.

CXR was done in all 27 (100%) patients, while CT chest was done in 16 (59.26%) patients (Table 1). On CXR, consolidation (Figs. 1, 2, 3, 4, 5, 6, 7, 8) was the most common finding, seen in 24 (88.89%) patients, being predominantly focal in 20 patients and diffuse in four patients. Boiselle et al. also observed the presence of focal consolidation on CXR in 45–60% patients with bacterial pneumonia 13. The focal segmental/subsegmental consolidation was seen in 15 (93.75%) out of 16 patients in our study in whom CT scan was done. Focal segmental consolidation, usually associated with bacterial infection, was also observed by Sider et al. in their study. 10

Bacterial pneumonia may also present as solitary or multiple pulmonary nodules. Nodular air-space opacities were observed as ill-defined lesions ranging from 1 to 3 cm in size in four (14.81%) out of 27 patients on CXR. Besides these, in six (37.5%) out of 16 patients, CT chest was able to diagnose smaller opacities (micronodules) ranging from 3 mm to 1 cm size that were beyond the resolution of CXR. Jasmer et al. reported bacterial pneumonia to be the most important cause of pulmonary nodules followed by tuberculosis in HIV-infected patients. 11

Cavitation within consolidation was observed in two (7.41%) patients which resolved with antibiotics on follow-up CXR. Cavitary pulmonary lesions are often associated with bacterial pneumonia in HIV-infected patients, confirmed by Aviram et al. in 85% patients. 12

CXR did not show any hilar or mediastinal lymphadenopathy (LAP). CT scan done in 16 patients revealed hilar LAP (Fig. 8) in two (12.5%) patients and mediastinal LAP in five (31.25%) patients. Calcification was seen in one hilar and one mediastinal lymph node; however, no necrosis was evident. This is supported by Boiselle et al. observation that although intrathoracic lymph node enlargement is usually not evident on CXR, mildly enlarged nodes are frequently seen on CT scans of patients with bacterial pneumonia. 13

CT scan done in 16 patients revealed subsegmental collapse in three (18.75%) patients and lobar collapse in one (6.25%) patient (Fig. 4, 8). Paraseptal emphysema was seen in two (12.5%) patients and pneumatocele in one (6.25%) patient (Fig. 1). Pulmonary arterial hypertension (PAH) was also detected in one (6.25%) (Fig. 1) patient having enlarged pulmonary artery segment with distal pruning of vessels later confirmed on echocardiography.

Tubercular Infection. Frontal chest radiograph in a 9-year-old HIV-positive male demonstrates confluent ill-defined nodular air-space opacities involving left lower zone (arrow, A). Ultrasound abdomen shows multiple mesenteric & retroperitoneal lymph nodes (arrow, B), some of which showed conglomeration and necrosis. His CD4 count was 256 cells/cu.mm, and Mantoux was strongly positive. Sputum could not isolate any microbe. On the basis of combined clinico-radiological findings, positive Mantoux test and CD4 count, antitubercular therapy (ATT) was started and patient improved both clinically and radiologically, showing complete resolution of the lesion (arrow, C)

Tubercular Infection. A 13-year-old HIV-positive male presented with fever of 2 weeks’ duration. Frontal chest radiograph (A) was normal. CT chest (axial view, lung window) revealed patchy areas of consolidation & ground-glass opacity in bilateral lung parenchyma (arrow in B,C,D). Conglomerate, mildly enhancing mediastinal lymph nodes were noted in subcarinal location (arrow, E) on mediastinal window. Patient’s CD4 count was 425 cells/cu.mm. BAL isolated Mycobacterium, and Mantoux test was positive. Patient started on ATT on the basis of these findings and showed significant clinical improvement

Tubercular Infection. Frontal chest radiograph in a 14-year-old male, a K/C/O HIV/AIDS, reveals diffuse ill-defined nodular air-space opacities throughout bilateral lung fields (arrows, A), few of them showing areas of confluence and calcification. Ultrasound abdomen in same patient shows calcified granulomas in liver (arrow, B), spleen (arrow, C) and conglomerated mesenteric lymph nodes with discrete calcifications (arrow, D). Patient’s CD4 count was 655 cells/cu.mm. BAL isolated MDR-TB, Mantoux test was positive. Patient was put on ATT on the basis of these findings and showed significant clinical improvement. Follow-up (after 6 months) CXR shows resolution of nodular opacities and presence of multiple calcific lesions in bilateral lungs (arrows, E)

Tubercular Infection. A 17-year-old HIV-positive female presented with cough & fever for 7 days. CXR shows patchy consolidation (white arrow, A) in right lower zone, and prominent right hilum with lobulated lateral margin (black arrow, A). CECT CHEST (axial view) reveals consolidated posterior segment of RUL (black arrow, B), and multiple ill-defined centrilobular nodules in anterior segment of RUL (white arrows, B). Precarinal/subcarinal (black arrows, C) and right hilar (white arrow in C, just lateral to truncus anterior) lymph nodes, with subtle internal areas of necrosis, are seen on mediastinal window. Patient’s Mantoux test was positive. Her CD4 count during this episode was 657 cells/mm3. Sputum and BAL could not isolate any microorganism. On the basis of these findings, ATT was started and patient showed clinical and radiological improvement (D) on completion of the therapy

Tubercular Infection. Chest radiograph (A) was normal in this 12-year-old HIV-positive male, who presented with fever since 4 days. CECT chest (B,C,D) was then done, which showed subsegmental area of GGO along with ill-defined centrilobular nodules in RUL, predominantly involving posterior segment (arrows in B,C). Ultrasound abdomen revealed multiple mesenteric lymph nodes, some of which showed central necrosis (not shown). Sputum could not isolate any microorganism, BAL isolated Mycobacterium tuberculosis. CD4 count was 150 cells/cu.mm. On basis of these findings, ATT was started and patient showed clinical improvement within 10 days of start of ATT

Tubercular Infection (followed by polymicrobial infection). CXR in a 4-year-old female child, with complaints of chest pain, cough & low-grade fever for 2 weeks, shows left pleural effusion (arrow, A). Pleural tap was done and it revealed significantly raised LDH. However, no microorganism could be isolated. ATT was started and patient responded over a period of 4 months B). Later, she developed focal consolidation in right upper zone (arrow, C). CD4 count was 280 cells/mm3. BAL specimen isolated Pseudomonas and pneumococcus was isolated in sputum. She was given a course of antibiotics and her clinico-radiological profile improved (D) over a period of 4 weeks

Tubercular Infection. A 13-year-old HIV-positive male presented with cough and fever for 3 weeks. CXR (PA view) reveals right lower zone haze and bilateral central peribronchial thickening and bronchiectatic changes (A). Axial CECT chest (lung window) shows patchy areas of GGO involving bilateral lungs, centrilobular nodules in right lung (black arrows, B), and centrilobular nodules arranged in typical tree-in-bud appearance in left lower lobe (white arrow, B). Central cylindrical bronchiectasis with peribronchial thickening is also seen. The main pulmonary artery (arrowhead, C) is prominent as compared to ascending aorta suggesting pulmonary hypertension. Conglomerate mediastinal and hilar lymphadenopathy (with some of the nodes showing central necrosis) is also seen (arrows in C,D). CD4 count was 285 cells/cu.mm. BAL/sputum could not isolate any microorganism. ATT was started and the patient improved thereafter clinically

The prevalence of tuberculosis as opportunistic infection in HIV-infected children has been reported as 11–40% in various series. Pulmonary tuberculosis was reported in 32–60% patients and extrapulmonary (abdominal, CNS, disseminated) tuberculosis in 7–45% patients. 13,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15

The present study, conducted on HIV-infected Indian children with chest manifestations, diagnosed 14 patients with pulmonary tuberculosis. Mycobacterium could be isolated only in three out of 14 patients from BAL specimen. Of these three patients, one had Mantoux negative tuberculosis, while other two had Mantoux positive multi-drug resistant tuberculosis (MDR-TB). Hence, our study detected MDR-TB in two (14.29%) out of the 14 patients as compared to five (5.4%) out of 93% patients as reported by Hessling et al.16 In 11 patients, no mycobacterium could be isolated in sputum/BAL/gastric aspirate. Six of these patients were Mantoux positive and showed radiological evidence of tuberculosis in the form of necrotic mediatinal/hilar lymph nodes with/without parenchymal lesion. All these 11 patients diagnosed as tuberculosis showed clinical and radiological improvement with antitubercular treatment (ATT).

Positive Mantoux test in eight (57.14%) out of 14 patients suggests that in early HIV disease tuberculin skin test is usually positive; however, as the degree of immunosuppression progresses, only 20–40% may demonstrate a positive skin test for tuberculosis. 15

In present study, eight (80%) out of 10 patients on ART and two patients with pre-ART status had CD4 counts > 200–500 cells/mm3, whereas two (20%) patients on ART had CD4 count < 200cells/mm3, and two patients with pre-ART status had CD4 count > 500 cells/mm3. Thus, it is observed that tuberculosis is common in HIV children with CD4 count in the range of 200–500 cells/mm3 (Table 5, 7).

The sputum positivity in HIV patients ranges from 15.4 to 85% depending on immune status of the patients. Chance of acid-fast bacillus (AFB) isolation remains high in patients with mild immunosuppression compared to those with advanced disease. Highly immunosuppressed patients have only subacute symptoms and infected with lower colony count of M. tuberculosis, and hence, the diagnosis may be more difficult in immunosuppressed than in immunocompetent patients.

CXR was done in all 14 (100%) patients, while CT chest was done in 11 (78.57%) of these patients (Table 2). Radiographic appearance of tuberculosis (TB) in AIDS differs from that in immunocompetent host, having more diffuse and lower zone disease, miliary disease, lymphadenopathy and increased incidence of normal CXR 17, 18. Similar findings have been observed in our study. Parenchymal abnormality was seen in 10 (71.43%) patients. Out of these, six patients showed predominantly middle & lower zone involvement and only one patient had predominantly upper & mid-zone involvement. Diffuse involvement was seen in three patients.

Endobronchial tuberculosis manifests as normal chest X-ray and has been observed in 15% patients with tuberculosis by Leung et al. 18 The air-space nodular lesions, especially centrilobular opacities, characteristic of endobronchial spread of tuberculosis are usually better picked up on CT due to inherent spatial resolution of CT as compared to CXR. In present study, three patients with normal CXR had conglomerate/necrotic mediastinal/hilar lymph nodes, and one patient with normal CXR had endobronchial tuberculosis evident as multiple ill-defined nodular air-space opacities (3 mm–1 cm size), centrilobular distribution and focal GGO in right upper lobe on CT scan (Fig. 13).

On CXR, consolidation was the most common finding, seen in seven (50%) patients, being predominantly focal in six patients and diffuse in one patient. CT done in 11 out of 14 patients showed subsegmental consolidation in seven (63.64%) out of 11 patients (Figs. 8, 12). Leung et al.18, in their study, noted consolidation in 43% patients of HIV-positive patients with pulmonary tuberculosis. Higher percentage noted in our study could be contributed to small sample size and selective inclusion of patients with chest manifestations suspected clinically or on CXR. Cavitation has been reported in HIV patients with tuberculosis having CD4 counts > 200 cells/mm3. 19 In present study, one (7.14%) patient with CD4 counts 285 cells/mm3 had cavitation on CECT chest. Centrilobular distribution of nodules was seen in six patients (Figs. 12, 13) with tree-in-bud appearance (Fig. 15) in two of these patients. Nodules size ranged from 1 to 3 cm in four patients and 3 mm–1 cm (micronodules) in two patients. Similar pattern of nodular opacities has been reported by other authors also. 18, 19

On CXR, lymphadenopathy was observed only in three (21.43%) patients, two hilar and one mediastinal in location. Contrast-enhanced CT (CECT) revealed mediastinal lymphadenopathy in eight (72.73%) patients, with central necrosis and rim enhancement seen in six (54.55%) patients. Four of these patients had associated hilar lymphadenopathy on CECT (Figs. 10, 12, 15). Hilar and/or mediastinal lymph nodes with central areas of low attenuation (necrosis) and peripheral rim enhancement on contrast enhanced CT are highly suggestive of active tubercular infection. 18

Pleural effusion (Fig. 14) and pulmonary hypertension (Fig. 15) were observed each in one patient, both on CXR and CT scan. Pericardial effusion was detected only on CT scan in one patient. Leung et al. detected pleural effusion in 21% of HIV-positive tubercular patients 18. Variation in our study may be due to small study group, differences in severity of infection and host immunity.

Fungal Infection. Frontal CXR in an 18-month-old HIV-positive male child, presented with recurrent episodes of cough & fever for last 3 weeks, reveals inhomogeneous nodular opacities involving bilateral upper lung and right lower zone (arrows, A). CECT chest (axial, lung window) showed GGO in posterior part of bilateral upper lobes & posterior basal segment of LLL (black arrows in B,C), and dense consolidation involving apical, medial basal and posterior basal segments of RLL (white arrow, C). CD4 count was 172 cells/mm3. Neutrophil count was 20%. BAL isolated Pneumocystis jiroveci and Candida species. Serial follow-up radiographs showed persistence of findings (D). Patient soon expired