Disease In HIV-infected Children Research Articles

The risk of disseminated Bacille Calmette-Guerin (BCG) disease in HIV-infected children

Objectives Bacille Calmette-Guerin (BCG), a live attenuated Mycobacterium bovis vaccine, poses a risk to human immunodeficiency virus (HIV)-infected children; this risk has not been well quantified. We estimate the risk of disseminated BCG disease in HIV-infected children in a setting highly endemic for tuberculosis and HIV. Design and methods We conducted a prospective hospital-based surveillance study in the Western Cape Province, South Africa. Clinical and laboratory-confirmed cases of disseminated BCG disease in children <1 year of age from January 2002 to December 2004 at a referral hospital were used as numerator data. Denominator data for calculations of disseminated BCG risk were obtained through estimating the total number of HIV-infected infants receiving BCG based on the known vaccination coverage in the study setting, combined with population data on the total number of children <1 year of age, the known HIV prevalence amongst women attending public antenatal care facilities and different scenarios (5–15%) for the rate of vertical HIV transmission. Results Nine cases of disseminated BCG disease were identified over the study period, seven of these were in HIV-infected infants. The estimated risk for HIV-infected infants to develop disseminated BCG disease, given a 95% BCG coverage and an HIV prevalence of 12.4–15.4% amongst women, were as follows for different scenarios of vertical HIV transmission: 329–417/100,000 vaccinees (assuming 5% vertical HIV transmission), 164–208/100,000 vaccinees (assuming 10% vertical HIV transmission) and 110–139/100,000 vaccinees (assuming 15% vertical HIV transmission). Conclusions The risk of disseminated BCG disease is increased several hundred fold in HIV-infected infants compared to the documented risk in HIV-uninfected infants. Data on the protective effect of BCG in HIV-exposed and infected children is lacking. Population- and hospital-based surveillance is vitally important to more accurately estimate the safety and benefits of BCG in HIV-exposed and infected infants.

Heart disease among children with HIV/AIDS attending the paediatric infectious disease clinic at Mulago Hospital.

There are very few published studies of heart disease in HIV infected children living in sub-Saharan Africa, a region with more than 50% of the world's population of HIV infected patients. To determine the prevalence, and describe the type and clinical presentation of heart disease among children with HIV attending an ambulatory clinic. Two hundred and thirty (230) HIV infected children attending the Paediatric Infectious Disease Clinic at Mulago hospital were recruited by simple random sampling in a cross-sectional study. The children were evaluated clinically, and investigated by electrocardiography and echocardiography. Thirty-two children (13.9%) had asymptomatic HIV disease, 156 (67.8%) had AIDS related complex while 42 (18.3%) had AIDS. Heart abnormalities were detected in 51% of the children (40.0% by echocardiography alone and 26.5% by electrocardiography alone). Heart abnormalities were most prevalent in children with AIDS (76.2%) and least prevalent in children with asymptomatic HIV disease (25.0%). The abnormalities included; Sinus tachycardia (21%), left ventricular systolic dysfunction (17%), right ventricular dilatation (14%), congenital heart disease (4.8%), dilated cardiomyopathy (3.0%), pericarditis (2.2%) and cor pulmonale (1.3%). Children with left ventricular systolic dysfunction significantly had easy fatigability, dyspnoea on exertion and tachypnoea. Other heart abnormalities presented with non-specific clinical features. Heart abnormalities were common especially in children with symptomatic HIV disease and included sinus tachycardia, left ventricular systolic dysfunction and right ventricular dilatation. The detected heart abnormalities, except left ventricular systolic dysfunction, had non-specific clinical features.

Varicella zoster as a manifestation of immune restoration disease in HIV-infected children

BackgroundExacerbation of opportunistic infections in HIV-infected patients shortly after initiation of highly active antiretroviral therapy (HAART) has been named immune restoration disease (IRD). Thus far, IRD has not been reported in children. ObjectiveWe describe the clinical and immune characteristics of IRD in HIV-infected children treated with HAART. MethodsA historical cohort study was conducted in a tertiary HIV center in perinatally HIV-infected children who were started on a first stable HAART between January 1996 and July 2002. The incidence of opportunistic infections, newly AIDS-defining events or death after initiation of HAART, and virologic and immunologic information was evaluated at baseline and every 3 months post-HAART. ResultsSixty-one perinatally HIV-infected children were started and maintained on HAART for >6 months. Seven episodes of IRD occurred. All were cutaneous herpes zoster (HZ). Children who developed HZ had significantly lower baseline CD4+ and CD8+ T-cell numbers compared with children who did not. HZ occurred only in children (7 of 34 subjects) with virological and immunological success to HAART. In children with a previous history of varicella infection, the risk of developing HZ after HAART was higher in those without a protective level of varicella-specific IgG (50%, or 5 of 10 subjects) compared with those with seroprotection (10%, or 2 of 20). ConclusionHerpes zoster is a common manifestation of IRD in HIV-infected children after the initiation of HAART. Risks for developing HZ include no protective varicella-specific antibody despite previous varicella infection, severe immunodeficiency at baseline, and vigorous immunologic and virologic responses to HAART.

Progression of disease in HIV infected children slowed after the first year of life

The European Collaborative Study. Fluctuations in symptoms in human immunodeficiency virus-infected children: the first 10 years of life. Pediatrics2001 Jul; 108 : 116 –22 [OpenUrl][1][Abstract/FREE Full Text][2] QUESTION: In children...

Progression of disease in HIV infected children slowed after the first year of life

Source Citation The European Collaborative Study. Fluctuations in symptoms in human immunodeficiency virus-infected children: the first 10 years of life. Pediatrics. 2001 Jul;108:116-22. 11433063

Progression of disease in HIV-infected children slowed after the first year of life

Progression of disease in HIV-infected children slowed after the first year of life

Thymic size on chest radiograph and rapid disease progression in human immunodeficiency virus 1-infected children.

Early infection of the thymus, an organ central to the ontogeny of the immune system, has been proposed as a cause of rapid progression in pediatric HIV disease. To test the hypothesis that small thymic volume is associated with rapid disease progression in HIV-infected children. Three pediatric radiologists established criteria for rating the size of the thymic profile on chest radiographs. All available baseline chest radiographs were reviewed in a random sequence, with radiologists blinded to study subjects' clinical status. A consensus was reached on whether the thymus was normal or small for age. A prospective multicenter study of the natural history of HIV-1 infection in children, the Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted Human Immunodeficiency Virus Infection (P2C2) Study. Fifty-eight HIV-infected children and 38 control children (uninfected but born to HIV-infected women) for whom chest radiographs in the first year of life were available. Rapid progression of HIV disease, defined as CDC Clinical Category C (severely symptomatic) or Immunologic Category 3 (severe immunosuppression) by 1 year of age. The mean age at the time of chest radiography was 3.5 months. Ten (17%) HIV-infected children had reduced thymic profile size, whereas no controls did (P = 0.006). Of the 58 (59%) HIV-infected children 34 were classified as rapid progressors, and 9 (26%) of them had reduced thymus size, compared with 1 (4%) of the non-rapid progressor children [odds ratio, 8.28; 95% confidence interval (CI), 1.0, 70.5; P = 0.035]. Baseline mean CD4+ count was 1642 (95% CI 1322 to 2009) cells/microl for those with normal thymus and 740 (95% CI 380 to 1275) cells/microl for those with reduced thymus (P = 0.007). Early thymic involution is associated with rapidly progressive disease in HIV-infected children.

Cardiac complications in children with human immunodeficiency virus infection. Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection (P2C2 HIV) Study Group, National Heart, Lung, and Blood Institute.

Although numerous cardiac abnormalities have been reported in HIV-infected children, precise estimates of the incidence of cardiac disease in these children are not well-known. The objective of this report is to describe the 2-year cumulative incidence of cardiac abnormalities in HIV-infected children. Prospective cohort (Group I) and inception cohort (Group II) study design. A volunteer sample from 10 university and public hospitals. Group I consisted of 205 HIV vertically infected children enrolled at a median age of 22 months. This group was comprised of infants and children already known to be HIV-infected at the time of enrollment in the study. Most of the children were African-American or Hispanic and 89% had symptomatic HIV infection at enrollment. The second group included 611 neonates born to HIV-infected mothers, enrolled during fetal life or before 28 days of age (Group II). In contrast to the older Group I children, all the Group II children were enrolled before their HIV status was ascertained. According to the study protocol, children underwent a series of cardiac evaluations including two-dimensional echocardiogram and Doppler studies of cardiac function every 4 to 6 months. They also had a 12- or 15-lead surface electrocardiogram (ECG), 24-hour ambulatory ECG monitoring, and a chest radiograph every 12 months. Main outcome measures were the cumulative incidence of an initial episode of left ventricular (LV) dysfunction, cardiac enlargement, and congestive heart failure (CHF). Because cardiac abnormalities tended to cluster in the same patients, we also determined the number of children who had cardiac impairment which we defined as having either left ventricular fractional shortening (LV FS) </=25% after 6 months of age, CHF, or treatment with cardiac medications. CARDIAC ABNORMALITIES: In Group I children (older cohort), the prevalence of decreased LV function (FS </=25%) was 5.7% and the 2-year cumulative incidence (excluding prevalent cases) was 15.3%. The prevalence of echocardiographic LV enlargement (LV end-diastolic dimension z score >2) at the time of the first echocardiogram was 8. 3%. The cumulative incidence of LV end-diastolic enlargement was 11. 7% after 2 years. The cumulative incidence of CHF and/or the use of cardiac medications was 10.0% in Group I children. There were 14 prevalent cases of cardiac impairment (LV FS </=25% after 6 months of age, CHF, or treatment with cardiac medications) in Group I. After excluding these prevalent cases, the 2-year cumulative incidence of cardiac impairment was 19.1% among Group I children and 80.9% remained free of cardiac impairment after 2 years of follow-up. Within Group II (neonatal cohort), the 2-year cumulative incidence of decreased LV FS was 10.7% in the HIV-infected children compared with 3.1% in the HIV-uninfected children. LV dilatation was also more common in Group II infected versus uninfected children (8.7% vs 2.1%). The cumulative incidence of CHF and/or the use of cardiac medications was 8.8% in Group II infected versus 0.5% in uninfected subjects. The 1- and 2-year cumulative incidence rates of cardiac impairment for Group II infected children were 10.1% and 12.8%, respectively, with 87.2% free of cardiac impairment after the first 2 years of life. In the Group I cohort, the 2-year cumulative death rate from all causes was 16.9% [95% CI: 11.7%-22. 1%]. The 1- and 2-year mortality rates after the diagnosis of CHF (Kaplan-Meier estimates) were 69% and 100%, respectively. In the Group II cohort, the 2-year cumulative death rate from all causes was 16.3% [95% CI: 8.8%-23.9%] in the HIV-infected children compared with no deaths among the 463 uninfected Group II children. Two of the 4 Group II children with CHF died during the 2-year observation period and 1 more died within 2 years of the diagnosis of CHF. The 2-year mortality rate after the

Unexpected non-HIV causes of death in children born to HIV-infected mothers. Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection Study Group.

A high incidence of sudden, unexplained deaths in infants born to HIV-infected mothers has been noted in several epidemiologic studies. During the course of a prospective study of heart and lung disease in children born to HIV-infected mothers, we noted that of 5 unexpected non-HIV-related deaths, 4 were attributed to traumatic events. The Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection (P2C2) study is a multicenter, prospective investigation of the incidence of heart and lung disease in HIV-infected children. A total of 805 children were enrolled and followed for 5 to 7 years with serial immunologic, pulmonary and cardiac function studies. During the study, a multidisciplinary committee was formed to review the cause of death for those patients who died. The committee used results of pulmonary, cardiac, and laboratory tests, hospital summaries, as well as autopsy and coroners' reports. The committee formed a consensus about the underlying and contributing causes of death for each subject using the definitions from the 1989 US Standard Certificate of Death. A total of 121 deaths occurred during the course of the P2C2 study. Of the 121 deaths, 5 were traumatic or sudden and unexpected and judged by the Mortality Review Committee to be unrelated to HIV infection. The median age at the time of death was 1.3 months and ranged from 1.2 to 37.8 months. Two infants died of trauma: a skull fracture and subdural hematoma in 1 infant and multiple skeletal fractures consistent with battered child syndrome in the other infant. The third infant died of accidental suffocation at home at 1.2 months of age. The fourth infant died suddenly and unexpectedly at home at 1.3 months of age. The autopsy showed no sign of HIV or other infection and was consistent with sudden unexpected death or SIDS. One non-HIV-related death occurred when a 38-month-old child died together with the mother in an unwitnessed drowning. The cumulative mortality rate attributable to trauma and sudden death at 4 months of age was 0.95% (95% CI: 0.02-1. 87%) and the infant mortality rate was 9.5/1000 live births. Three children were born prematurely at 30, 33, and 36 weeks' gestational age, respectively, and 3 mothers admitted using recreational drugs before or during pregnancy. These traumatic and sudden non-HIV-related deaths accounted for 4.1% (5/121) of the deaths during the entire P2C2 study period and for 20% (4/20) of the deaths in the first year of life. Four deaths were attributable to accidental and nonaccidental trauma rather than to other common causes of infant death. One death was a sudden unexpected death, similar to SIDS, a leading cause of infant death in the United States. The majority of previously reported non-HIV-related deaths in infants born to HIV-infected mothers have been attributed to SIDS or to unexplained sudden death. In contrast with other reports, 4 of the 5 children in our series died of accidental or nonaccidental trauma and only 1 was a sudden unexplained death. It is unlikely that HIV exposure is related directly to the deaths described in this report; however, maternal HIV infection may be a marker for factors that place the child at risk for sudden or traumatic death. This report suggests that children born to HIV-infected mothers may be at increased risk for traumatic or sudden, unexplained, non-HIV-related death. These children seem to be at risk regardless of their own HIV infection status. Furthermore, 4 of the deaths in our study occurred within the first few months of life, suggesting that this is a period of increased vulnerability. Studies to identify associated risk factors for non-HIV-related deaths are needed to identify these high-risk infants. Children born to HIV-infected mothers may be more vulnerable than was recognized previously and may be in need of increased social services, especially in early infancy.

Randomised trial of intradermal Mycobacterium vaccae or intradermal hepatitis B immunisation in children with HIV infection

This study assessed the safety of inactivated Mycobacterium vaccae as a candidate vaccine to prevent disseminated mycobacterial disease in children with HIV infection. 35 children ages 1–8 with CD4 counts ≥300/mm 3 in New Hampshire, Boston and Chicago were randomised in a 2:1 schedule to receive a 3-dose series of intradermal M. vaccae vaccine (MV) or hepatitis B vaccine (HBV) at 2-month intervals. Immunisation was safe and well tolerated; 2-day median vaccine site induration was 5 mm in MV recipients and 0 mm in HBV recipients ( p<0.001). There were no significantly different changes in viral load or CD4 count between the two vaccine groups. No PPD skin test conversions occurred after immunisation. MV is safe and well tolerated and deserves further evaluation as a vaccine to prevent mycobacterial disease in HIV-infected children.

Correlation of clinical parameters and immunological function with human immunodeficiency virus plasma viremia in children.

Studies of immune function in human immunodeficiency virus (HIV)-infected children are important, because functional abnormalities can precede CD4+ T-cell loss and are associated with the development of opportunistic and bacterial infections. We sought to correlate clinical parameters and immunological function with HIV RNA plasma levels in 20 children. HIV RNA levels were measured by a polymerase chain reaction assay. We analyzed T-cell responses to mitogens (phytohemagglutinin, concanavalin A, and pokeweed [PWM]) and antigens (tetanus toxoid and Candida albicans); T-cell suppressor activity; and humoral immunity to Haemophilus influenzae, hepatitis B, tetanus, and diphtheria vaccines. The median age of the children was 6 years. Eight children had HIV RNA levels less than 200 to 9621 copies per milliliter (group I). Four children had 37,970 to 82,630 copies per milliliter (group II). Eight children had 102,100 to 191,200 copies per milliliter (group III). There were no differences in the HIV-related complications between group I and II children. Group I/II children had significantly higher CD4+ T-cell counts (P = 0.02), less symptomatic HIV disease (P = 0.005), and more detectable protective vaccine immunity (P = 0.014) compared with group III children. Responses to mitogens were conserved in most children. Group I children tended to have higher responses to tetanus toxoid than group II children and significantly higher responses than group III children (P = 0.01). Group I had significantly higher responses to C. albicans than groups II (P = 0.016) and III (P = 0.001). Group I/II children tended to have lower suppressor activity compared with group III children (median, 0 vs 64%). We demonstrated that humoral and cellular immune dysfunction exists at all stages of disease in HIV-infected children but was most severe in children with greater than or equal to 100,000 HIV RNA copies per milliliter. Function was the most intact in children with less than 10,000 copies per milliliter.

Invasive pneumococcal infections in children infected with HIV are not associated with splenic dysfunction.

Children infected with HIV-1 are more likely to acquire infections associated with the encapsulated bacterial pathogens of childhood than their non-HIV-infected peers. The goal of the current study was to determine what proportion of community-acquired, invasive pneumococcal disease in HIV-infected children could be attributed to splenic dysfunction, as measured by enumerating the number of pocked red blood cells (RBCs) in peripheral blood. Splenic reticuloendothelial function was assessed semiquantitatively by examining the morphology of the RBCs of 84 children born to HIV-infected mothers using phase interference microscopy. Surveillance of medical records, and a review of the Yale-New Haven Hospital Clinical Microbiology computerized database, revealed that all of the bacterial cultures of blood and cerebrospinal fluid from these patients were positive. Of the 84 children assessed, 70 were infected with HIV (median age 66 months) and 14 were uninfected seroreverters (controls). Sixty-one of the 70 HIV-infected children met the CDC criteria for moderate or severe immunodeficiency and/or moderate or severe symptomatic conditions. Seventeen of the 70 HIV-infected children experienced 23 invasive bacterial infections. Streptococcus pneumoniae was responsible for all 23 infections. The median age at the time of first infection among these 17 subjects was 20 months (range, 10-58 months). There were no episodes of invasive bacterial infections in the remaining 53 HIV-infected children nor among the 14 controls. All 84 children studied, including those with invasive pneumococcal disease, had normal proportions (i.e., < 2%) of pocked erythrocytes in peripheral blood. Splenic dysfunction, as measured by the pocked RBC count, does not account for the increased occurrence of invasive pneumococcal disease found in children infected with HIV.

INVASIVE PNEUMOCOCCAL INFECTIONS IN CHILDREN INFECTED WITH HIV-1 ARE NOT ASSOCIATED WITH SPLENIC DYSFUNCTION. † 976

Children infected with human immunodeficiency virus type 1 (HIV) are more likely to acquire infections with encapsulated bacterial pathogens of childhood than their non-HIV-infected peers. It has been shown thatStreptococcus pneumoniae (pneumococcus) accounts for 35% of the bacterial isolates from blood and cerebrospinal fluid in this group of children. We wished to learn what proportion (if any) of the incidence of community-acquired, invasive pneumococcal disease in HIV-infected children could be attributed to splenic dysfunction, as measured quantitatively by enumerating the number of pocked red blood cells in peripheral blood (Pearsonet al Pediatrics 1985; 76:392).

Pulmonary Disease in HIV-Infected Children

Pulmonary Disease in HIV-Infected Children

IgA nephropathy in a child with human immunodeficiency virus type 1 infection

Infection with the human immunodeficiency virus type 1 (HIV-1) can cause a spectrum of renal disease, termed acquired immunodeficiency syndrome (AIDS) nephropathy. The most common clinical manifestations of kidney involvement in HIV-1-infected patients are proteinuria and/or nephrotic syndrome, and the histopathological pattern usually reveals focal segmental glomerulosclerosis. We describe an 8-year-old child with AIDS who presented with recurrent gross hematuria. A kidney biopsy demonstrated IgA nephropathy. This unique case indicates that the range of kidney disease in HIV-infected children may be broader than originally thought, and that these patients warrant a complete evaluation of any renal abnormality.