Bronchiectasis and other chronic lung diseases in adolescents living with HIV.

: The incidence of pulmonary infections has declined dramatically with improved access to antiretroviral therapy (ART) and cotrimoxazole prophylaxis, but chronic lung disease (CLD) is an increasingly recognized but poorly understood complication in adolescents with perinatally acquired HIV. : There is a high prevalence of chronic respiratory symptoms, abnormal spirometry and chest radiographic abnormalities among HIV-infected adolescents in sub-Saharan Africa, wherein 90% of the world's HIV-infected children live. The incidence of lymphocytic interstitial pneumonitis, the most common cause of CLD in the pre-ART era, has declined with increased ART access. Small airways disease, particularly constrictive obliterative bronchiolitis and bronchiectasis, are emerging as leading causes of CLD among HIV-infected adolescents in low-income and middle-income countries. Asthma may be more common in high-income settings. Likely risk factors for CLD include recurrent pulmonary infections, air pollution, HIV-related immune dysfunction, and untreated HIV infection, particularly during critical stages of lung development. : Globally, the importance of HIV-associated CLD as a cause of morbidity and mortality is increasing, especially as survival has improved dramatically with ART and growing numbers of children living with HIV enter adolescence. Further research is urgently needed to elucidate the natural history and pathogenesis of CLD, and to determine optimal screening, diagnostic and treatment strategies.<br/

Extensive cerebrovascular disease and stroke with prolonged prodromal symptoms as first presentation of perinatally-acquired human immunodeficiency virus infection in a young adult.

A 26-year-old black African woman presented with an acute onset of hemiparesis and visual symptoms. This had been preceded several months by symptoms which were apparently psychiatric in nature. She had no apparent risk for cerebrovascular disease. Neurological evaluation revealed a striking burden of cerebrovascular disease for her age, including the rare stroke syndrome of basilar artery occlusion. Human immunodeficiency virus (HIV) infection was identified during clinical assessment. This was judged to be perinatally acquired, as there was no history of sexual debut or blood transfusion; her mother was taking antiretroviral therapy and she had facial planar warts and underlying bronchiectasis. Therefore, it has been concluded that presentation of stroke should prompt HIV testing in young people and perinatally-acquired infection can present in adulthood

Stool Xpert® MTB/RIF test for the diagnosis of childhood pulmonary tuberculosis at primary clinics in Zimbabwe.

OBJECTIVE: To evaluate the diagnostic performance of Xpert® MTB/RIF on stool samples from children with clinical suspicion of pulmonary tuberculosis (PTB) at primary care clinics. DESIGN: A cross-sectional diagnostic evaluation enrolling 5-16 year olds from whom one induced sputum (IS) sample was tested for microbiological TB confirmation. Results of a single stool sample tested using Xpert were compared against microbiologically confirmed TB, defined as a positive result on sputum microscopy and/or culture and/or IS Xpert. RESULTS: Of 222 children enrolled, 218 had complete microbiological results. The median age was 10.6 years (interquartile range 8-13). TB was microbiologically confirmed in 19/218 (8.7%) children. Of these, respectively 5 (26%), 9 (47%) and 15 (79%) were smear-, culture- and IS Xpert-positive. Stool Xpert was positive in 13/19 (68%) microbiologically confirmed cases and 4/199 (2%) microbiologically negative cases. Stool Xpert detected 76.9% (10/13) of human immunodeficiency virus (HIV) infected and 50% (3/6) of non-HIV-infected children with microbiologically confirmed TB (P = 0.241). CONCLUSION: Stool Xpert is a potential alternative screening test for children with suspected TB if sputum is unavailable. Strategies to optimise the diagnostic yield of stool Xpert assay need further study

Cardiac Disease in Adolescents With Delayed Diagnosis of Vertically Acquired HIV Infection

Background. At least one-third of human immunodeficiency virus (HIV)–infected infants survive to adolescence even without antiretroviral therapy (ART), but are at high risk of complications including cardiac disease. We investigated the characteristics of cardiac disease among adolescents with HIV infection diagnosed in late childhood who were receiving ambulatory HIV care in Harare, Zimbabwe. / Methods. Consecutive adolescents with vertically acquired HIV attending 2 HIV outpatient treatment clinics were studied. Assessment included clinical history and examination, and 2-dimensional, M-mode, pulsed- and continuous-wave Doppler echocardiography. / Results. Of 110 participants (47% male; median age, 15 years; interquartile range, 12–17 years), 78 (71%) were taking ART. Exertional dyspnea, chest pain, palpitations, and ankle swelling were reported by 47 (43%), 43 (39%), 10 (9%), and 7 (6%), respectively. The New York Heart Association score was ≥2 in 41 participants (37%). Echocardiography showed that 74 participants (67%) had left ventricular (LV; septal and/or free wall) hypertrophy and 27 (24%) had evidence of impaired LV relaxation or restrictive LV physiology. The estimated pulmonary artery systolic pressure (ePASP) was >30 mm Hg in 4 participants (3.6%); of these 2 also had right ventricular (RV) dilatation. Another 32 participants (29%), without elevated ePASP, had isolated RV dilatation. / Conclusions. A significant burden of cardiac disease was seen among adolescents with vertically acquired HIV infection. More than half were asymptomatic yet had significant echocardiographic abnormalities. These findings highlight the need to screen this population in order to better define the geography, natural history, etiopathogenic mechanisms, and management (including the timing and choice of optimal therapeutic ART and cardiac drug interventions) to prevent development and/or progression of HIV-associated cardiac disease

Chronic lung disease in HIV-infected children established on antiretroviral therapy.

Respiratory disease is a major cause of morbidity and mortality in HIV-infected children. Despite antiretroviral therapy (ART), children suffer chronic symptoms. We investigated symptom prevalence, lung function, and exercise capacity among older children established on ART, and an age-matched HIV-uninfected group. A cross-sectional study in Zimbabwe of: 1) HIV-infected children aged 6-16 years receiving ART for over six months; 2) HIV-uninfected children attending primary health clinics from the same area. Standardised questionnaire, spirometry, Incremental Shuttle Walk Testing (ISWT), CD4 count, HIV viral load, and sputum culture for tuberculosis were performed. 202 HIV-infected and 150 uninfected participants (median age 11.1 years in each group) were recruited. Median age at HIV diagnosis and ART initiation was 5.5 (IQR 2.8-7.5) and 6.1 years (IQR 3.6-8.4) respectively. Median CD4 count was 726 cells/μl, and 79% had HIV viral load&lt;400copies/ml. Chronic respiratory symptoms were rare in HIV-uninfected children (n = 1 [0.7%]), but common in HIV-infected participants (51 [25%]), especially cough (30 [15%]) and dyspnoea (30 [15%]). HIV-infected participants were more commonly previously treated for tuberculosis (76 [38%] versus 1 [0.7%], p &lt; 0.001), had lower exercise capacity (mean ISWT distance 771m versus 889m respectively, p &lt; 0.001), and more frequently abnormal spirometry (43 [24.3%] versus 15 [11.5%], p = 0.003) compared to HIV-uninfected participants. HIV diagnosis at an older age was associated with lung function abnormality (p = 0.025). No participant tested positive for M. tuberculosis. In children, despite ART, HIV is associated with significant respiratory symptoms and functional impairment. Understanding pathogenesis is key, as new treatment strategies are urgently required

The impact of Vitamin D supplementation on musculoskeletal health outcomes in children, adolescents, and young adults living with HIV: A systematic review

Objective: HIV-positive children, adolescents, and young adults are at increased risk poor musculoskeletal outcomes. Increased incidence of vitamin D deficiency in youth living with HIV may further adversely affect musculoskeletal health. We investigated the impact of vitamin D supplementation on a range of musculoskeletal outcomes among individuals aged 0–25 years living with HIV. Methods: A systematic review was conducted using databases: PubMed/Medline, CINAHL, Web of Knowledge, and EMBASE. Interventional randomised control trials, quasi-experimental trials, and previous systematic reviews/meta-analyses were included. Outcomes included: BMD, BMC, fracture incidence, muscle strength, linear growth (height-for-age Z-score [HAZ]), and biochemical/endocrine biomarkers including bone turnover markers. Results: Of 497 records, 20 studies met inclusion criteria. Thirteen studies were conducted in North America, one in Asia, two in Europe, and four in Sub-Saharan Africa. High-dose vitamin D supplementation regimens (1,000–7,000 IU/day) were successful in achieving serum 25-hydroxyvitamin-D (25OHD) concentrations above study-defined thresholds. No improvements were observed in BMD, BMC, or in muscle power, force and strength; however, improvements in neuromuscular motor skills were demonstrated. HAZ was unaffected by low-dose (200–400 IU/day) supplementation. A single study found positive effects on HAZ with high-dose supplementation (7,000 vs 4,000IU/day). Conclusions: Measured bone outcomes were unaffected by high-dose vitamin D supplementation, even when target 25OHD measurements were achieved. This may be due to: insufficient sample size, follow-up, intermittent dosing, non-standardised definitions of vitamin D deficiency, or heterogeneity of enrolment criteria pertaining to baseline vitamin D concentration. High-dose vitamin D may improve HAZ and neuromuscular motor skills. Adequately powered trials are needed in settings where HIV burden is greatest

The impact of long-term azithromycin on antibiotic resistance in HIV-associated chronic lung disease

Selection for resistance to azithromycin (AZM) and other antibiotics such as tetracyclines and lincosamides remains a concern with long-term AZM use for treatment of chronic lung diseases (CLD). We investigated the impact of 48 weeks of AZM on the carriage and antibiotic resistance of common respiratory bacteria among children with HIV-associated CLD. Nasopharyngeal (NP) swabs and sputa were collected at baseline, 48 and 72 weeks from participants with HIV-associated CLD randomised to receive weekly AZM or placebo for 48 weeks and followed postintervention until 72 weeks. The primary outcomes were prevalence and antibiotic resistance of Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI) and Moraxella catarrhalis (MC) at these timepoints. Mixed-effects logistic regression and Fisher’s exact test were used to compare carriage and resistance, respectively. Of 347 (174 AZM, 173 placebo) participants (median age 15 years (IQR 13–18), female 49%), NP carriage was significantly lower in the AZM (n=159) compared to placebo (n=153) arm for SP (18% versus 41%, p<0.001), HI (7% versus 16%, p=0.01) and MC (4% versus 11%, p=0.02); SP resistance to AZM (62% (18 out of 29) versus 13% (8 out of 63), p<0.0001) or tetracycline (60% (18 out of 29) versus 21% (13 out of 63), p<0.0001) was higher in the AZM arm. Carriage of SA resistant to AZM (91% (31 out of 34) versus 3% (1 out of 31), p<0.0001), tetracycline (35% (12 out of 34) versus 13% (4 out of 31), p=0.05) and clindamycin (79% (27 out of 34) versus 3% (1 out of 31), p<0.0001) was also significantly higher in the AZM arm and persisted at 72 weeks. Similar findings were observed for sputa. The persistence of antibiotic resistance and its clinical relevance for future infectious episodes requiring treatment needs further investigation