Cutaneous sarcoma: a review and practical approach to management.

Sarcomas arising in the skin are rare but potentially fatal. These tumours originate from mesenchymal cells and can be divided between those that arise in soft tissue and those arising from bone. General guidelines exist for the management of soft-tissue sarcomas; however, there are no specific guidelines for cutaneous sarcomas. Current literature was reviewed for management of seven cutaneous sarcomas including atypical fibroxanthoma, pleomorphic dermal sarcoma, dermal and subcutaneous leiomyosarcoma, dermatofibroma sarcoma protuberans, Kaposi sarcoma, cutaneous angiosarcoma and malignant peripheral nerve sheath tumour. All suspected sarcomas should be discussed in a sarcoma multidisciplinary team meeting. This article is not a clinical guideline but should serve as a practical summary of how these tumours present, how they are recognized histologically, and how best to manage and follow-up patients. The aim is to support clinicians and facilitate the best and most evidence-based standard of care available.

Evaluation of a serum-based antigen test for tuberculosis in HIV-exposed infants: a diagnostic accuracy study.

BACKGROUND: Non-sputum methods are urgently needed to improve tuberculosis diagnosis and treatment monitoring in children. This study evaluated the ability of a serum assay quantifying a species-specific peptide of the Mycobacterium tuberculosis CFP-10 virulence factor via nanotechnology and matrix-assisted laser desorption ionization time-of-flight mass spectrometry to diagnose tuberculosis in HIV-infected and HIV-uninfected infants. METHODS: Serum CFP-10 peptide signal was blinded evaluated in cryopreserved sera of 519 BCG-immunized, HIV-exposed infants (284 HIV-infected, 235 HIV-uninfected) from a multi-center randomized placebo-controlled isoniazid prophylaxis trial conducted in southern Africa between 2004 and 2008, who were followed up to 192 weeks for Mtb infection and TB. Children were classified as confirmed, unconfirmed, or unlikely tuberculosis cases using 2015 NIH diagnostic criteria for pediatric TB. RESULTS: In HIV-infected infants, CFP-10 signal had 100% sensitivity for confirmed TB (5/5, 95% CI, 47.8-100) and 83.7% sensitivity for unconfirmed TB (36/43, 95% CI 69.3-93.2), with 93.1% specificity (203/218, 95% CI 88.9-96.1). In HIV-uninfected infants, CFP-10 signal detected the single confirmed TB case and 75.0% of unconfirmed TB cases (15/20; 95% CI 50.9-91.3), with 96.2% specificity (177/184, 95% CI, 92.3-98.5). Serum CFP-10 achieved 77% diagnostic sensitivity for confirmed and unconfirmed TB (13/17, 95% CI, 50-93%) at ≤ 24 weeks pre-diagnosis, and both CFP-10-positivity and concentration declined following anti-TB therapy initiation. CONCLUSIONS: Serum CFP-10 signal exhibited high diagnostic sensitivity and specificity for tuberculosis in HIV-infected and HIV-uninfected infants and potential utility for early TB detection and monitoring of anti-TB treatment responses.

Rapid diagnosis of new and relapse tuberculosis by quantification of a circulating antigen in HIV-infected adults in the Greater Houston metropolitan area.

BACKGROUND: HIV-associated immune defects inhibit tuberculosis (TB) diagnosis, promote development of extrapulmonary TB and paucibacillary pulmonary TB cases with atypical radiographic features, and increase TB relapse rates. We therefore assessed the diagnostic performance of a novel assay that directly quantitates serum levels of the Mycobacterium tuberculosis (Mtb) virulence factor 10-kDa culture filtrate protein (CFP-10) to overcome limitations associated with detecting Mtb bacilli in sputum or tissue biopsies. METHODS: This study analyzed HIV-positive adults enrolled in a large, population-based TB screening and surveillance project, the Houston Tuberculosis Initiative, between October 1995 and September 2004, and assigned case designations using standardized criteria. Serum samples were trypsin-digested and immunoprecipitated for an Mtb-specific peptide of CFP-10 that was quantified by liquid chromatography-mass spectrometry for rapid and sensitive TB diagnosis. RESULTS: Among the 1053 enrolled patients, 110 met all inclusion criteria; they included 60 tuberculosis cases (12 culture-negative TB), including 9 relapse TB cases, and 50 non-TB controls, including 15 cases with history of TB. Serum CFP-10 levels diagnosed 89.6% (77.3-96.5) and 66.7% (34.9-90.1) of culture-positive and culture-negative TB cases, respectively, and exhibited 88% (75.7-95.5) diagnostic specificity in all non-TB controls. Serum antigen detection and culture, respectively, identified 85% (73.4-92.9) and 80.0% (67.3-88.8) of all 60 TB cases. CONCLUSIONS: Quantitation of the Mtb virulence factor CFP-10 in serum samples of HIV-infected subjects diagnosed active TB cases with high sensitivity and specificity and detected cases missed by the gold standard of Mtb culture. These results suggest that serum CFP-10 quantitation holds great promise for the rapid diagnosis of suspected TB cases in patients who are HIV-infected.

Predictors of resolution and persistence of renal laboratory abnormalities in pediatric HIV infection.

BACKGROUND: Among human immunodeficiency virus (HIV)-infected youth, the role of renal disease (RD) and its management has become increasingly important as these children/adolescents mature into young adults. The identification of predictors of abnormal renal laboratory events (RLE) may be helpful in the management of their HIV infection and its associated renal complications. METHODS: Data collected from HIV-infected youth followed for ≥ 48 months were analyzed to identify predictors of resolution versus persistence of RLE and determine the utility of RLE to predict the onset of RD. Analysis included descriptive and inferential methods using a multivariable extended Cox proportional hazards model. RESULTS: Of the 1,874 at-risk children enrolled in the study, 428 (23 %) developed RLE, which persisted in 229 of these (54 %). CD4 percentages of <25 % [hazard ratio (HR) 0.63, p < 0.002) and an HIV viral load of >100,000 copies/ml (HR 0.31, p < 0.01) were associated with reduced rates of resolution, while in most cases exposure to highly active antiretroviral therapy (HAART)/nephrotoxic HAART prior to or subsequent to RLE were not. Persistence of RLE was 88 % sensitive for identifying new RD. Negative predictive values for RD were >95 % for both the at-risk cohort and those with RLE. CONCLUSIONS: Advanced HIV disease predicted persistence of RLE in HIV-infected youth. Persistent RLE were useful for identifying RD.

Chronic kidney disease associated with perinatal HIV infection in children and adolescents.

BACKGROUND: This study describes the incidence, clinical and demographic characteristics, and spectrum of chronic kidney disease (CKD) in youths with perinatal HIV-1 infection. METHODS: Retrospective analysis between May 1993 and December 2006 of subjects with renal disease followed in the Pediatric AIDS Clinical Trials Group 219/219C multicenter study examining the long-term consequences of perinatal HIV infection. Diagnosis confirmation was made utilizing a questionnaire mailed to research sites. Participants with CKD of other etiology than HIV were excluded. Outcome measures were biopsy-diagnosed CKD and, in the absence of biopsy, HIV-associated nephropathy (HIVAN) using established clinical criteria. RESULTS: Questionnaires on 191 out of 2,102 participants identified 27 cases of CKD: 14 biopsy-diagnosed and 6 clinical cases of HIVAN, and 7 biopsy-diagnosed cases of immune complex-mediated kidney disease (lupus-like nephritis, 3; IgA nephropathy, 2; membranous nephropathy, 2). Incidence rates for CKD associated with HIV in pre-highly active antiretroviral therapy (HAART) (1993-1997) and HAART (1998-2002, 2003-2006) eras were 0.43, 2.84, and 2.79 events per 1,000 person years respectively. In multivariate analysis, black race and viral load ≥100,000 copies/mL (rate ratios 3.28 and 5.05, p ≤ 0.02) were associated with CKD. CONCLUSIONS: A variety of immune complex-mediated glomerulonephritides and HIVAN occurs in this population. Black race and uncontrolled viral replication are risk factors for CKD associated with HIV.

Diagnosis of paediatric tuberculosis by optically detecting two virulence factors on extracellular vesicles in blood samples.

Sensitive and specific blood-based assays for the detection of pulmonary and extrapulmonary tuberculosis would reduce mortality associated with missed diagnoses, particularly in children. Here we report a nanoparticle-enhanced immunoassay read by dark-field microscopy that detects two Mycobacterium tuberculosis virulence factors (the glycolipid lipoarabinomannan and its carrier protein) on the surface of circulating extracellular vesicles. In a cohort study of 147 hospitalized and severely immunosuppressed children living with HIV, the assay detected 58 of the 78 (74%) cases of paediatric tuberculosis, 48 of the 66 (73%) cases that were missed by microbiological assays, and 8 out of 10 (80%) cases undiagnosed during the study. It also distinguished tuberculosis from latent-tuberculosis infections in non-human primates. We adapted the assay to make it portable and operable by a smartphone. With further development, the assay may facilitate the detection of tuberculosis at the point of care, particularly in resource-limited settings.

The Zambia Children's KS-HHV8 Study: rationale, study design, and study methods.

The epidemic of human immunodeficiency virus in Zambia has led to a dramatic rise in the incidence of human herpesvirus-8 (HHV-8)-associated Kaposi's sarcoma in both adults and children. However, there is a paucity of knowledge about the routes of HHV-8 transmission to young children. The Zambia Children's KS-HHV8 Study, a large, prospective cohort study in Lusaka, Zambia, was launched in 2004 to investigate the role of household members as a source of HHV-8 infection in young children and social behaviors that may modify the risk of HHV-8 acquisition. This cohort is distinct from other epidemiologic studies designed to investigate HHV-8 incidence and transmission because it recruited and followed complete households in the urban central African context. Between July 2004 and March 2007, 1,600 households were screened; 368 households comprising 464 children and 1,335 caregivers and household members were enrolled. Follow-up of this population continued for 48 months postrecruitment, affording a unique opportunity to study horizontal transmission of HHV-8 and understand the routes and sources of transmission to young children in Zambia. The authors describe the study rationale, design, execution, and characteristics of this cohort, which provides critical data on the epidemiology and transmission of HHV-8 to young children in Zambia.

Primary gamma-herpesviral infection in Zambian children.

BACKGROUND: HHV-8 is closely related to Epstein-Barr virus (EBV), but the clinical presentations of these two infections in early childhood are not well understood. Also, it is not known whether infection by one virus correlates with another. Here, we compare the natural history of infection by these two viruses along with the clinical manifestations and risk factors that are associated with early childhood infection in Zambia, which is an endemic area for HHV-8. METHODS: This study was conducted in a cohort of 12 month old Zambian children (N = 677). Data on socio-economic status and a wide range of clinical manifestations were collected. Logistic regression was used to test for significant associations between the collected variables and HHV-8 or EBV serostatus at 12 months of age. RESULTS: We observed a significantly higher seroprevalence for EBV (58.9%) as compared to HHV-8 (13.4%). HIV-1 infected children had at a significantly higher risk of being infected with HHV-8 (Odds ratio [OR] 3.69, 95% confidence interval [CI] 1.64 - 8.32). HIV-1 infection of the mothers was a significant risk factor for increased acquisition of EBV but not HHV-8 by children (OR 1.86, 05% CI 1.20 - 2.87). Self reported rash was marginally associated with primary infection for HHV-8 and EBV. CONCLUSIONS: These results suggest that there is no correlation between EBV and HHV-8 infections. Infection by one does not increase the susceptibility for the second virus. Primary HHV-8 and EBV infection in early childhood may clinically present as rash but remains largely asymptomatic and may remain undetected in this population. HIV infection in the mother or child are important risk factors that contribute to EBV or HHV-8 infection.

Pharmacokinetics and tolerability of once- versus twice-daily lopinavir/ritonavir treatment in HIV-1-infected children.

BACKGROUND: Once-daily lopinavir/ritonavir (LPV/r) is not approved for treatment of HIV paediatric patients. Once daily treatment in children might serve the same goals of patient comfort and adherence as in adults. METHODS: HIV type-1-infected children aged 6 months to 18 years, who were virologically suppressed on an LPV/r-containing regimen, were eligible. Treatment 1 consisted of once-daily LPV/r 460/115 mg/m(2), plus two nucleoside reverse transcriptase inhibitors (NRTIs). Treatment 2 consisted of twice-daily LPV/r 230/57.5 mg/m(2) plus two NRTIs. Patients were randomized either to start with treatment 1 followed by treatment 2 or vice versa. Full pharmacokinetic profiles were analysed for lopinavir and ritonavir with a validated HPLC tandem mass spectrometry assay. RESULTS: Seven patients (five girls and two boys) were included in the study. Median age was 9.8 years (range 5.8-15.5). For the once-daily treatment, the median (range) lopinavir 24 h area under the plasma -concentration-time curve (AUC(24 h)), maximum plasma concentration (C(max)) and 24 h plasma concentration (C(24 h)) were 214.6 h*mg/l (114.2-289.2), 13.5 mg/l (8.3-17.5) and 3.4 mg/l (0.6-7.4), respectively. For the twice-daily treatment the median (range) lopinavir 12 h area under the plasma concentration-time curve (AUC(12 h)), C(max) and 12 h plasma concentration (C(12 h)) were 80.9 h*mg/l (23.3-135.9), 9.8 mg/l (3.4-15.2) and 5.7 mg/l (1.7-9.7), respectively. CONCLUSIONS: This study suggests that the pharmacokinetics of lopinavir after twice-daily and once-daily dosing are similar, with no observable difference in tolerability, in this group of patients between 5 and 15 years old.

Predicting Viral Failure in Human Immunodeficiency Virus Perinatally Infected Youth With Persistent Low-Level Viremia on Highly Active Antiretroviral Therapy.

BACKGROUND: Less than optimal adherence with antiretroviral therapy occurs commonly among human immunodeficiency virus HIV)-infected youth. In this study, our object was to identify patterns in the prefailure measurement of viral load (VL) that can reliably predict virological failure (VF) in HIV perinatally infected youth on highly active antiretroviral therapy (HAART). METHODS: We conducted a retrospective chart review of HIV-infected youth with low-level viremia (LLV), defined as an HIV VL between the lower limits of detection (20-75 copies/mL) and 1000 copies/mL. All patients were perinatally infected, under 22 years of age, observed for at least 24 months of consecutive follow-up between May 2008 and July 2014, and received their HIV care at the University of Miami Miller School of Medicine. Of the 349 subjects screened, 100 were eligible for analysis. Virological failure was defined as 3 or more consecutive VLs greater than 1000 copies/mL. Multiple logistic regression and receiver operator characteristic curves were used to identify patterns in VL that ultimately resulted in VF. RESULTS: Fifteen of the 100 patients experienced VF. Higher log10 mean VL, positive slope of the VL (log10 copies/mL per day), and fewer clinic visits were associated with a higher probability of VF. Sensitivity and specificity were .87 and .95, respectively. Resistance was not found in 12 of 15 patients with VF. CONCLUSIONS: Patients with LLV that had fewer clinic visits and a trend toward increasing VLs had an increased risk of VF. Noncompliance seems to be a major component of VF. Physicians should emphasize the critical nature of medication adherence.

Early childhood infection by human herpesvirus 8 in Zambia and the role of human immunodeficiency virus type 1 coinfection in a highly endemic area.

Kaposi's sarcoma occurs at high incidence among Zambian adults and children, but there is a paucity of data on human herpesvirus 8 (HHV-8) incidence and routes of infection, especially in children. Between 1998 and 2004, the authors conducted a prospective study of viral transmission in a cohort of 684 children in Lusaka, Zambia, to estimate the annual incidence of HHV-8 from birth through 48 months of age. Maternal and pediatric human immunodeficiency virus type 1 (HIV-1) infection status was also determined. The results, based on 1,532 child-years of follow-up, showed that HHV-8 seroconversion occurs early in life. The incidence rate of HHV-8 seroconversion was 13.8 infections per 100 child-years by 48 months of age. HIV-1-infected children were at substantially higher risk for HHV-8 seroconversion (adjusted hazard ratio = 4.60, 95% confidence interval: 2.93, 7.22). Maternal HIV-1 and HHV-8 infection status were not independently associated with risk of HHV-8 seroconversion in the child. HHV-8 antibody titers in children followed at all consecutive time points revealed sero-reversion of HHV-8 antibodies, with undetectable titers in some children at one or more time points after seroconversion. These results demonstrate that cross-sectional serologic screening probably underestimates true HHV-8 seroprevalence in young Zambian children because of fluctuations in detectable antibody titers.

Mortality among HIV-1- and human herpesvirus type 8-affected mother-infant pairs in Zambia.

OBJECTIVE: To determine the respective trends in mortality of Zambian mother-infant pairs based on maternal infection with HIV-1 and human herpesvirus type 8 (HHV-8). METHODS: A prospective cohort study was done on Zambian mother-infant pairs, stratified by maternal serologic status and followed from 6 weeks postdelivery for 48 months. Statistical analysis of the differences in the calculated mortality rates among the four groups was done using Stata 7.0. Kaplan-Meier analysis and Cox proportional hazard models were used to measure subject survival time. RESULTS: Between September 1998 and March 2002, a total of 1,425 mother-infant pairs were enrolled. The crude mortality rate among children born to dually infected mothers was approximately 9 times higher (245.90 deaths per 1,000 live births) when compared with the death ratio of children born to seronegative mothers (24.63 deaths per 1,000 live births). The incidence rate for death was 0.34/1,000 in infants of co-infected mothers in comparison with 0.32/1,000 among HIV-1-infected mothers, 0.0336/1,000 among uninfected mothers, and 0.0403/1,000 among HHV-8-infected mothers (chi(2) = 154.56; P < 0.01). Infants of co-infected mothers had a comparable risk of death in comparison with infants infected with HIV-1 alone [hazard ratio, 9.91 [95% confidence interval (95% CI), 5.08-19.37] for co-infected versus 9.26 [95% CI, 4.75-18.07] for HIV-1-infected alone]. Infants of mothers infected only with HHV-8 also had comparable survival in comparison with uninfected infants (hazard ratio, 1.21; 95% CI, 0.56-2.61). CONCLUSION: Infants born to mothers dually infected with both HIV-1 and HHV-8 have comparable survival with infants exposed to HIV-1 alone. Infants born to mothers infected only with HHV-8 have comparable survival with uninfected infants.

Proteinuria in children infected with the human immunodeficiency virus.

OBJECTIVES: To determine the prevalence of proteinuria in a large cohort of children infected with the human immunodeficiency virus (HIV) and their longitudinal progression during treatment with highly active antiretroviral therapy. STUDY DESIGN: In a retrospective cohort study, 286 children infected with HIV were monitored with quantitative assays of proteinuria from January 1998 through January 2007, with monitoring of viral load, lymphocyte profiles, kidney function, and mortality rates. Proteinuria was quantitated by urine protein to creatinine ratio (Upr/cr). RESULTS: Ninety-four (33%) had proteinuria at baseline. Of these, 32 (11.2%) had nephrotic range proteinuria (Upr/cr > or = 1.0). Initial screening was at 11 +/- 0.3 years of age, with an average follow-up of 5.6 +/- 0.1 years. The mortality rate was significantly greater in those with proteinuria. During the period of observation, 15 patients with nephrotic proteinuria died or had development of end-stage renal disease, and 16 showed improvement. Of those with intermediate range proteinuria (Upr/cr > or = 0.2 < 1.0), 3 progressed to nephrotic range proteinuria, and 39 (63%) showed resolution of the proteinuria (Upr/cr < 0.2). Improvement in proteinuria was correlated with decreasing viral load (r = 0.5; P < .01). CONCLUSIONS: Control of viral load with highly active antiretroviral therapy appears to prevent the progression of HIV-associated renal disease and improve survival rates in infected children.

Microbial Translocation and Immune Activation in HIV-1 Infected Pregnant Women.

BACKGROUND: Immune Activation (IA) has been previously documented in both pregnant (PG) and non-PG HIV-1 infected (HIV+) women as well as in HIV- uninfected PG women; the latter as a result of the fetal allograft. To determine whether the combined effects of HIV and pregnancy result in increased IA and whether IA is associated with Microbial Translocation (MT), we performed a prospective, longitudinal, controlled study during pregnancy and the postpartum (PP) period. METHODS: HIV+ PG women had biomarkers of IA and MT tested at 12-20 weeks (T1), and 24-36 weeks (T2) of pregnancy and at 6-8 weeks Postpartum (T3). HIV+, non-PG women were tested at comparable time points. HIV- PG women were tested at T1 only. HIV+ women were not started on antiretroviral therapy (ART) until T1. Biomarkers of IA assessed included: CD4DR+, CD4CD38+, CD4DR+CD38+, CD8DR+, CD8CD38+, and CD8DR+CD38+. Biomarkers of MT included LPS, sCD14, and 16SrDNA. RESULTS: 30 HIV+PG women, 18 HIV+ non-PG and 10 HIV-PG were enrolled. In the HIV+ women, there were no differences in median age, viral load, % or absolute CD4 at entry. Significant differences between T1 and T2 and between T1 and T3 were noted in CD8DR+CD38+ in HIV+PG women after ART. CD4DR+, CD4DR+CD38+, and CD8DR+ decreased post ART in HIV+PG women but a decline in IA was less evident in HIV+ non-PG. LPS decreased post ART by T3 in both HIV+PG and HIV+ non-PG groups; 16SrDNA was elevated at all time points in both groups when compared to control values, and declined post ART in the HIV+PG group. A subgroup of HIV-PG at T1 had IA and MT as evidenced by several IA markers and increased LPS. CONCLUSION: The degree of IA and MT was similar among HIV+PG and HIV+ non-PG women followed longitudinally. There was no incremental increase due to the combined effects of HIV and pregnancy. Several markers of IA and MT (LPS, 16SrDNA) decreased post ART. IA and MT occurred in a subgroup of HIV-PG women during the 1st trimester. Further study must be done to confirm whether MT consistently occurs in some healthy women during PG.

Characterization of HIV-1 subtype C envelope glycoproteins from perinatally infected children with different courses of disease.

BACKGROUND: The causal mechanisms of differential disease progression in HIV-1 infected children remain poorly defined, and much of the accumulated knowledge comes from studies of subtype B infected individuals. The applicability of such findings to other subtypes, such as subtype C, remains to be substantiated. In this study, we longitudinally characterized the evolution of the Env V1-V5 region from seven subtype C HIV-1 perinatally infected children with different clinical outcomes. We investigated the possible influence of viral genotype and humoral immune response on disease progression in infants. RESULTS: Genetic analyses revealed that rapid progressors (infants that died in the first year of life) received and maintained a genetically homogeneous viral population throughout the disease course. In contrast, slow progressors (infants that remained clinically asymptomatic for up to four years) also exhibited low levels variation initially, but attained higher levels of diversity over time. Genetic assessment of variation, as indicated by dN/dS, showed that particular regions of Env undergo selective changes. Nevertheless, the magnitude and distribution of these changes did not segregate slow and rapid progressors. Longitudinal trends in Env V1-V5 length and the number of potential N-glycosylation sites varied among patients but also failed to discriminate between fast and slow progressors. Viral isolates from rapid progressors and slow progressors displayed no significant growth properties differences in vitro. The neutralizing activity in maternal and infant baseline plasma also varied in its effectiveness against the initial virus from the infants but did not differentiate rapid from slow progressors. Quantification of the neutralization susceptibility of the initial infant viral isolates to maternal baseline plasma indicated that both sensitive and resistant viruses were transmitted, irrespective of disease course. We showed that humoral immunity, whether passively acquired or developed de novo in the infected children, varied but was not predictive of disease progression. CONCLUSION: Our data suggest that neither genetic variation in env, or initial maternal neutralizing activity, or the level of passively acquired neutralizing antibody, or the level of the de novo neutralization response appear to be linked to differences in disease progression in subtype C HIV-1 infected children.

Evidence for Placental HPV Infection in Both HIV Positive and Negative Women.

Human papillomaviruses (HPVs) have previously been reported to infect epithelial trophoblast cells of the placenta. To investigate this possibility, 200 placental samples from Zambian women were separated into HIV+ and HIV- groups and tested for HPV by redundant primer PCR, using GP5+/GP6+ and CPI/CPII primer sets. Three HPV genotypes (HPV6, 16 and 90) were detected in placental samples. Whereas, 20 different HPV genotypes were detected in vaginal sampling of the same patients, suggesting that compartment specific sub-populations of HPV may exist. The incidence of HPV16 in placental samples was almost 2-fold greater in HIV+ women compared to HIV- (p = 0.0241). HPV16 L1 expression, detected by immunochemistry, was significantly higher in HIV+ than HIV- samples (p = 0.0231). HPV16 DNA was detected in the nuclei of trophoblast cells by in situ hybridization. Overall, these results suggest that HPVs infect the placenta and that HIV significantly influences these infections.

Risk factors for early childhood infection of human herpesvirus-8 in Zambian children: the role of early childhood feeding practices.

BACKGROUND: Human herpesvirus-8 (HHV-8) infection in early childhood is common throughout sub-Saharan Africa with prevalence increasing throughout childhood. Specific routes of transmission have not been clearly delineated, though HHV-8 is present in high concentrations in saliva. METHODS: To understand the horizontal transmission of HHV-8 within households to children, we enrolled for cross-sectional analysis, 251 households including 254 children, age two and under, in Lusaka, Zambia. For all children, plasma was screened for HHV-8 and HIV type I (HIV-1) and health and behavioral questionnaires were completed. Multilevel logistic regression analysis was conducted to assess independent factors for HHV-8 infection in children. RESULTS: Risk factors for HHV-8 infection included increasing number of HHV-8-positive household members [OR = 2.5; 95% confidence interval (CI), 1.9-3.3; P < 0.01] and having a primary caregiver who tested the temperature of food with their tongue before feeding the child (OR = 2.4; 95% CI, 1.93-3.30; P = 0.01). Breastfeeding was protective against infection with HHV-8 for children (OR = 0.3; 95% CI, 0.16-0.72; P < 0.01). CONCLUSIONS: These results indicate that exposure to HHV-8 in the household increases risk for early childhood infection, with specific feeding behaviors likely playing a role in transmission. IMPACT: Interventions to protect children from infection should emphasize the possibility of infection through sharing of foods.

The pharmacogenetics of NAT2 enzyme maturation in perinatally HIV exposed infants receiving isoniazid.

The roles of the NAT2 genotype and enzyme maturation on isoniazid pharmacokinetics were investigated in South African infants with perinatal HIV exposure enrolled in a randomized, double-blind, controlled trial of isoniazid for prevention of tuberculosis disease and latent infection. Plasma concentration-time measurements of isoniazid from 151 infants (starting at 3-4 months of age) receiving isoniazid 10 to 20 mg/kg/d orally during the course of the 24-month study were incorporated in a population analysis along with NAT2 genotype, body weight, age, and sex. The results showed a different NAT2 enzyme maturation profile for each of the 3 acetylation groups, with the 70-kg body weight-normalized typical apparent clearance for the fast and intermediate acetylators increasing from 14.25 L/h and 10.88 L/h at 3 months of age to 22.84 L/h and 15.58 L/h at 24 months of age, respectively, with no significant change in the apparent clearance of the slow group during this period. A hypothesis is proposed to explain the genotype-dependent enzyme maturation processes for the NAT2 enzyme.

Premastication as a route of pediatric HIV transmission: case-control and cross-sectional investigations.

BACKGROUND: Three cases of pediatric HIV transmission attributed to the feeding practice of premasticating food for children have been reported. The degree of risk that premastication poses for pediatric HIV transmission and the prevalence of this behavior among HIV-infected caregivers is unknown. METHODS: During December 2009 to February 2010, we conducted a case-control investigation of late-diagnosed HIV infection in children at 6 HIV clinics using in-person and telephone interviews. A cross-sectional investigation of premastication was conducted in concert with this case-control investigation. RESULTS: We compared 11 case-patients to 35 HIV-exposed controls of similar age. Sixteen (35%) of 46 children were fed premasticated food, 10 (22%) by an HIV-infected caregiver. Twenty-seven percent of case-patients received premasticated food from an HIV-infected caregiver compared with 20% of controls (odds ratio = 1.5; 95% confidence interval = 0.3 to 7.1). In the cross-sectional investigation, 48 (31%) of 154 primary caregivers of children aged ≥6 months reported the children received premasticated food from themselves or someone else. The prevalence of premastication decreased with increasing caregiver age and had been used to feed children aged 1-36 months. CONCLUSIONS: Premastication, a potential route of HIV transmission to children, was a common practice of caregivers. Public health officials and health care providers should educate the public about the potential risk of disease transmission via premastication.