Immunodeficiency in children starting antiretroviral therapy in low-, middle-, and high-income countries.

BACKGROUND The CD4 cell count or percent (CD4%) at the start of combination antiretroviral therapy (cART) is an important prognostic factor in children starting therapy and an important indicator of program performance. We describe trends and determinants of CD4 measures at cART initiation in children from low-, middle-, and high-income countries. METHODS We included children aged <16 years from clinics participating in a collaborative study spanning sub-Saharan Africa, Asia, Latin America, and the United States. Missing CD4 values at cART start were estimated through multiple imputation. Severe immunodeficiency was defined according to World Health Organization criteria. Analyses used generalized additive mixed models adjusted for age, country, and calendar year. RESULTS A total of 34,706 children from 9 low-income, 6 lower middle-income, 4 upper middle-income countries, and 1 high-income country (United States) were included; 20,624 children (59%) had severe immunodeficiency. In low-income countries, the estimated prevalence of children starting cART with severe immunodeficiency declined from 76% in 2004 to 63% in 2010. Corresponding figures for lower middle-income countries were from 77% to 66% and for upper middle-income countries from 75% to 58%. In the United States, the percentage decreased from 42% to 19% during the period 1996 to 2006. In low- and middle-income countries, infants and children aged 12-15 years had the highest prevalence of severe immunodeficiency at cART initiation. CONCLUSIONS Despite progress in most low- and middle-income countries, many children continue to start cART with severe immunodeficiency. Early diagnosis and treatment of HIV-infected children to prevent morbidity and mortality associated with immunodeficiency must remain a global public health priority.

Accuracy of tidal breathing measurement of FloRight compared to an ultrasonic flowmeter in infants.

INTRODUCTION Monitoring breathing pattern is especially relevant in infants with lung disease. Recently, a vest-based inductive plethysmograph system (FloRight®) has been developed for tidal breathing measurement in infants. We investigated the accuracy of tidal breathing flow volume loop (TBFVL) measurements in healthy term-born infants and infants with lung disease by the vest-based system in comparison to an ultrasonic flowmeter (USFM) with a face mask. We also investigated whether the system discriminates between healthy infants and those with lung disease. METHODS Floright® measures changes in thoracoabdominal volume during tidal breathing through magnetic field changes generated by current-carrying conductor coils in an elastic vest. Simultaneous TBFVL measurements by the vest-based system and the USFM were performed at 44 weeks corrected postmenstrual age during quiet unsedated sleep. TBFVL parameters derived by both techniques and within both groups were compared. RESULTS We included 19 healthy infants and 18 infants with lung disease. Tidal volume per body weight derived by the vest-based system was significantly lower with a mean difference (95% CI) of -1.33 ml/kg (-1.73; -0.92), P < 0.001. Respiratory rate and ratio of time to peak tidal expiratory flow over total expiratory time (tPTEF/tE) did not differ between the two techniques. Both systems were able to discriminate between healthy infants and those with lung disease using tPTEF/tE. CONCLUSION FloRight® accurately measures time indices and may discriminate between healthy infants and those with lung disease, but demonstrates differences in tidal volume measurements. It may be better suited to monitor breathing pattern than for TBFVL measurements.

Clinical factors associated with growth and mortality of pediatric patients on HAART at Mulago PIDC, Uganda, 2003--2006

The global social and economic burden of HIV/AIDS is great, with over forty million people reported to be living with HIV/AIDS at the end of 2005; two million of these are children from birth to 15 years of age. Antiretroviral therapy has been shown to improve growth and survival of HIV-infected individuals. The purpose of this study is to describe a cohort of HIV-infected pediatric patients and assess the association between clinical factors, with growth and mortality outcomes. ^ This was a historical cohort study. Medical records of infants and children receiving HIV care at Mulago Pediatric Infectious Disease Clinic (PIDC) in Uganda between July 2003 and March 2006 were analyzed. Height and weight measurements were age and sex standardized to Centers for Disease Control and prevention (CDC) 2000 reference. Descriptive and logistic regression analyses were performed to identify covariates associated with risk of stunting or being underweight, and mortality. Longitudinal regression analysis with a mixed model using autoregressive covariance structure was used to compare change in height and weight before and after initiation of highly active antiretroviral therapy (HAART). ^ The study population was comprised of 1059 patients 0-20 years of age, the majority of whom were aged thirteen years and below (74.6%). Mean height-for-age before initiation of HAART was in the 10th percentile, mean weight-for-age was in the 8th percentile, and the mean weight-for-height was in the 23rd percentile. Initiation of HAART resulted in improvement in both the mean standardized weight-for-age Z score and weight-for-age percentiles (p <0.001). Baseline age, and weight-for-age Z score were associated with stunting (p <0.001). A negative weight-for-age Z score was associated with stunting (OR 4.60, CI 3.04-5.49). Risk of death decreased from 84% in the >2-8 years age category to 21% in the >13 years age category respectively, compared to the 0-2 years of age (p <0.05). ^ This pediatric population gained weight significantly more rapidly than height after starting HAART. A low weight-for-age Z score was associated with poor survival in children. These findings suggest that age, weight, and height measurements be monitored closely at Mulago PIDC. ^

Maternal nutrition and oral health factors in early childhood caries

Background. Early Childhood Caries (ECC) is the most common chronic infectious disease of childhood worldwide. Seven of ten American children have one or more decayed or filled primary teeth by age five. ECC prevalence is especially high in lower socio-economic ethnic populations. Commonly recognized as a diet-induced disease, focal etiological factors include cariogenic bacteria, fermentable carbohydrates, and a susceptible newly erupted tooth. Sequencing of breast and/or bottle feeding and introduction of beikost come at a time when children's defense mechanisms and, perhaps maternal direction of children's dietary patterns, are not yet fully developed or mature. To date, most research has examined biological factors, while maternal factors, especially psychosocial ones, have received scant attention. Objective. To examine the association of psychosocial factors in terms of maternal nutrition and oral health knowledge, attitudes, and beliefs, as well as social support and self-efficacy (KABS2) in a population of socio-economically disadvantaged infants and young children. A secondary aim was to describe ECC prevalence in this population. Methods. This study examined cross-sectionally the relationship between selected maternal psychosocial variables and ECC in a convenience sample of Mexican-American women and very young children participating in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) in San Antonio, Texas. Mothers were surveyed by use of a criteria- and content-valid, reliable questionnaire, and dental examinations were conducted on 191 children, aged 5 to 47 months old. Results. Thirty-nine percent of the children had ECC. As assessed on a 30-question scale, women in whose children were diagnosed with ECC were found to demonstrate lower Knowledge ( p=0.03), Attitudes (p=0.02), Beliefs (p=0.04), and Social Support (p<0.01) scores, compared to women whose children were found to be caries-free. No differences in Self-Efficacy scores were found between the groups. Conclusions. These data indicate that current etiological model depicting relevant factors associated with ECC in Mexican-American infants and children of low socio-economic status should be broadened to include consideration of maternal psychosocial factors such as nutrition and oral health knowledge, attitudes, beliefs, and social support, and that these factors should be considered when planning educational approaches to reduce the occurrence of ECC. ^

Helicobacter pylori infection and the effect on growth in a cohort of children in the US/Mexico border

Helicobacter pylori (H. pylori) is an S-shaped or curved gram-negative bacterium that is mostly found in the human stomach. H. pylori causes gastritis in adults and children, which can lead to gastric ulcers or risk of cancer. Transmission of this bacterial infection remains to be unknown but is mostly acquired during childhood. Little is known about the effect H. pylori has on growth in children. Although some studies have reported that H. pylori is associated with subnormal growth, the association of H. pylori with growth retardation and malnutrition is poorly described. Data from this study comes from The Pasitos Cohort Study which draws its population from three border communities which include Socorro and San Elizario in Texas, as well as Ciudad Juarez, Chihuahua, Mexico. Birth documentation was obtained for 803 infants and 472 entered follow-up. This cohort study allowed us to assess the growth of children from 6 months to the seventh anniversary, and describe the prevalence of underweight, short stature and overweight in the study population. We also tested the hypothesis that children in the Pasitos Cohort Study who were ever infected with H. pylori show an increased risk of growth retardation or malnutrition at 66 months of age. Using the 2000 CDC Growth Reference, we found that the mean BMI of the study population increased as children grew older, while the mean of their height for age decreased slightly. The proportion of children who were classified as of short stature was under 5%, while those considered underweight were less than 10% at selected six-months of age intervals. Using the subset of children who were 66 months of age we found that the risk of underweight was higher among those who ever tested positive for H. pylori infection using the urea breath test; however, due to small numbers of children with 'wasting' this difference was not statistically significant. Moreover, since the six cases of under weight occurred among children of low socio-economic status we could not rule out potential confounding. The risk of developing short stature was not different among those ever infected and those who never tested positive for H. pylori infection. ^

The relationship between enterotoxigenic {\it Escherichia coli\/} infection and environmental risk factors in Bilbeis, Egypt, 1981--1983

Diarrheal disease associated with enterotoxigenic Escherichia coli (ETEC) infection is one of the major public health problems in many developing countries, especially in infants and young children. Because tests suitable for field laboratories have been developed only relatively recently, the literature on the environmental risk factors associated with ETEC is not as complete as for many other pathogens or for diarrhea of unspecified etiology.^ Data from a diarrheal disease surveillance project in rural Egypt in which stool samples were tested for a variety of pathogens, and in which an environmental questionnaire was completed for the same study households, provided an opportunity to test for an association between ETEC and various risk factors present in those households. ETEC laboratory-positive specimens were compared with ETEC laboratory-negative specimens for both symptomatic and asymptomatic children less than three years of age at the individual and household level using a case-comparison design.^ Individual children more likely to have LT infection were those who lived in HHs that had cooked food stored for subsequent consumption at the time of the visit, where caretakers used water but not soap to clean an infant after a diarrheal stool, and that had an indoor, private water source. LT was more common in HHs where the caretaker did not clean an infant with soap after a diarrheal stool, and where a sleeping infant was not covered with a net. At both the individual and HH level, LT was significantly associated with good water supply in terms of quantity and storage.^ ST was isolated more frequently at the individual level where a sleeping infant was covered with a net, where large animals were kept in or around the house, where water was always available and was not potable, and where the water container was not covered. At the HH level, the absence of a toilet or latrine and the indiscriminate disposal of animal waste decreased risk. Using animal feces for fertilizer, the presence of large animals, and poor water quality were associated with ST at both the individual and HH level.^ These findings are mostly consistent with those of other studies, and/or are biologically plausible, with the obvious exception of those from this study where poorer water supplies are associated with less infection, at least in the case of LT. More direct observation of how animal ownership and feces disposal relates to different types of water supply and usage might clarify mechanisms through which some ETEC infection could be prevented in similar settings. ^

Parenting and survival in anthropoid primates: Caretakers live longer

Most anthropoid primates are slow to develop, their offspring are mostly single births, and the interbirth intervals are long. To maintain a stable population, parents must live long enough to sustain the serial production of a sufficient number of young to replace themselves while allowing for the death of offspring before they can reproduce. However, in many species there is a large differential between the sexes in the care provided to offspring. Therefore, we hypothesize that in slowly developing species with single births, the sex that bears the greater burden in the care of offspring will tend to survive longer. Males are incapable of gestating infants and lactating, but in several species fathers carry their offspring for long periods. We predict that females tend to live longer than males in the species where the mother does most or all of the care of offspring, that there is no difference in survival between the sexes in species in which both parents participate about equally in infant care, and that in the species where the father does a greater amount of care than the mother, males tend to live longer. The hypothesis is supported by survival data for males and females in anthropoid primate species.

Respiratory syncytial virus (RSV) SH and G proteins are not essential for viral replication in vitro: Clinical evaluation and molecular characterization of a cold-passaged, attenuated RSV subgroup B mutant

A live, cold-passaged (cp) candidate vaccine virus, designated respiratory syncytial virus (RSV) B1 cp-52/2B5 (cp-52), replicated efficiently in Vero cells, but was found to be overattenuated for RSV-seronegative infants and children. Sequence analysis of reverse-transcription–PCR-amplified fragments of this mutant revealed a large deletion spanning most of the coding sequences for the small hydrophobic (SH) and attachment (G) proteins. Northern blot analysis of cp-52 detected multiple unique read-through mRNAs containing SH and G sequences, consistent with a deletion mutation spanning the SH:G gene junction. Immunological studies confirmed that an intact G glycoprotein was not produced by the cp-52 virus. Nonetheless, cp-52 was infectious and replicated to high titer in tissue culture despite the absence of the viral surface SH and G glycoproteins. Thus, our characterization of this negative-strand RNA virus identified a novel replication-competent deletion mutant lacking two of its three surface glycoproteins. The requirement of SH and G for efficient replication in vivo suggests that selective deletion of one or both of these RSV genes may provide an alternative or additive strategy for developing an optimally attenuated vaccine candidate.

Nonlinear control of heart rate variability in human infants.

Nonlinear analyses of infant heart rhythms reveal a marked rise in the complexity of the electrocardiogram with maturation. We find that normal mature infants (gestation greater than or equal to 35 weeks) have complex and distinctly nonlinear heart rhythms (consistent with recent reports for healthy adults) but that such nonlinearity is lacking in preterm infants (gestation > or = to 27 weeks) where parasympathetic-sympathetic interaction and function are presumed to be less well developed. Our study further shows that infants with clinical brain death and those treated with atropine exhibit a similar lack of nonlinear feedback control. These three lines of evidence support the hypothesis championed by Goldberger et al. [Goldberger, A.L., Rigney, D.R. & West, B.J. (1990) Sci. Am. 262, 43-49] that autonomic nervous system control underlies the nonlinearity and possible chaos of normal heart rhythms. This report demonstrates the acquisition of nonlinear heart rate dynamics and possible chaos in developing human infants and its loss in brain death and with the administration of atropine. It parallels earlier work documenting changes in the variability of heart rhythms in each of these cases and suggests that nonlinearity may provide additional power in characterizing physiological states.

Maternal plasma human immunodeficiency virus type 1 RNA level: a determinant and projected threshold for mother-to-child transmission.

To prevent mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission, it is important to identify its determinants. Because HIV-1 RNA levels can be reduced by antiviral therapy, we examined the role of maternal plasma HIV-1 RNA level in mother-to-child transmission. We used quantitative competitive PCR to measure HIV-RNA in 30 infected pregnant women and then followed their infants prospectively; 27% of the women transmitted HIV-1 to their infants and maternal plasma HIV-1 RNA level correlated strikingly with transmission. Eight of the 10 women with the highest HIV-1 RNA levels at delivery (190,400-1,664,100 copies per ml of plasma) transmitted, while none of the 20 women with lower levels (500-155,800 copies per ml) did (P = 0.0002). Statistical analysis of the distribution of HIV-1 RNA loads in these 30 women projected a threshold for mother-to-child transmission in a larger population; the probability of a woman with a viral RNA level of < or = 100,000 copies per ml not transmitting is predicted to be 97%. Examination of serial HIV-1 RNA levels during pregnancy showed that viral load was stable in women who did not initiate or change antiviral therapy. These data identify maternal plasma HIV-1-RNA level as a major determinant of mother-to-child transmission and suggest that quantitation of HIV-1 RNA may predict the risk of transmission.

Major histocompatibility complex class II DR alleles DRB1*1501 and those encoding HLA-DR13 are preferentially associated with a diminution in maternally transmitted human immunodeficiency virus 1 infection in different ethnic groups: determination by an automated sequence-based typing method.

Transmission of human immunodeficiency virus 1 (HIV-1) from an infected women to her offspring during gestation and delivery was found to be influenced by the infant's major histocompatibility complex class II DRB1 alleles. Forty-six HIV-infected infants and 63 seroreverting infants, born with passively acquired anti-HIV antibodies but not becoming detectably infected, were typed by an automated nucleotide-sequence-based technique that uses low-resolution PCR to select either the simpler Taq or the more demanding T7 sequencing chemistry. One or more DR13 alleles, including DRB1*1301, 1302, and 1303, were found in 31.7% of seroreverting infants and 15.2% of those becoming HIV-infected [OR (odds ratio) = 2.6 (95% confidence interval 1.0-6.8); P = 0.048]. This association was influenced by ethnicity, being seen more strongly among the 80 Black and Hispanic children [OR = 4.3 (1.2-16.4); P = 0.023], with the most pronounced effect among Black infants where 7 of 24 seroreverters inherited these alleles with none among 12 HIV-infected infants (Haldane OR = 12.3; P = 0.037). The previously recognized association of DR13 alleles with some situations of long-term nonprogression of HIV suggests that similar mechanisms may regulate both the occurrence of infection and disease progression after infection. Upon examining for residual associations, only only the DR2 allele DRB1*1501 was associated with seroreversion in Caucasoid infants (OR = 24; P = 0.004). Among Caucasoids the DRB1*03011 allele was positively associated with the occurrence of HIV infection (P = 0.03).

Effect of mode of delivery on early oral colonization and childhood dental caries: a systematic review

Background: Oral colonization starts at birth by vertical transmission. Objective: To determine whether mode of delivery influences the oral colonization of infants and contributes to the risk of childhood dental caries. Methods: A systematic review was conducted in the electronic database Web of Science for articles published from January 1995 to December 2015 by using a set of keywords. Results: From 2,644 citations identified through electronic search, ten studies met the inclusion criteria. According to the studies mode of delivery influences oral microbial density, oral microbial profile and the timing of oral colonization by cariogenic microbiota. However, there are no consistent results concerning either the prevalence of children harboring cariogenic microbiota or the prevalence of early childhood caries by mode of delivery. Conclusion: Mode of delivery influences early oral colonization. However, it seems that other determinants rather than mode of delivery could be major contributors to the development of early childhood caries. Keywords: Early childhood caries, early oral colonization, acquisition of oral microflora, mode of delivery

Infant formula rebates and the Illinois WIC program.

Caption title: Infant formula rebate.

Collectaneous epitaphs : chiefly designed to assist surviving relations in fixing upon suitable inscriptions, for the tombs and grave-stones of deceased friends ... /

Includes index.

Maternal, fetal, and infant nutrition, 1973<[-1974] >. Hearings, Ninety-third Congress, first[-second] session ...

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