The relationship of maternal and child HIV infection to security of attachment among Ugandan infants.

This study was designed to examine the relationship of maternal and child human immunodeficiency virus (HIV) infection to the security of attachment of Ugandan infants. The attachment patterns of two groups of Ugandan mother-infant pairs: 35 HIV-positive mothers and their infants and 25 HIV-negative mothers and their infants were compared. We tested the hypothesis that infants of HIV-positive mothers would demonstrate less secure attachment as measured by the Waters Attachment Q-set than infants of HIV-negative mothers. No differences were found in the security of attachment of infants of HIV-positive versus HIV-negative mothers. Infants of HIV-positive mothers with Acquired Immunodeficiency Syndrome (AIDS) were less securely attached than infants of mothers without AIDS. These findings underscore the relationship of infant security of attachment to maternal HIV infection in the presence of AIDS-related symptoms but not to asymptomatic maternal HIV infection.

Infant feeding practices in complex emergencies: a case study approach.

The majority of deaths associated with complex emergencies are attributed to infants and children under the age of five years. Most of these deaths are related to preventable diseases such as malnutrition, diarrhea, and malaria. Infant feeding emergencies have emerged as a major factor in complex emergencies. This paper reviews the current information relative to infant feeding, and uses four case studies as educational tools for the management of infant feeding emergencies. Child mortality rates in refugee population have been linked directly to protein-energy malnutrition (PEM). Breast feeding has many advantages over all other forms of feeding for children up to the age of two years of age. These advantages are discussed in detail in this paper. In addition, the appropriate and inappropriate uses of breast-milk substitutes (BMS) are discussed. Breast feeding also may play a role in the spread of HIV infections from the mother to the infant. However, in the setting of complex emergencies in the developing world, the risk of an infant dying of malnutrition and infection when not breastfed is likely to be greater than is the risk of death due to HIV acquisition through breastfeeding. The physiology of lactation is reviewed with particular reference to the roles of prolactin, oxytocin, and the feedback inhibitor of lactation (FIL) hormone. No medications have been demonstrated to augment milk production that can be used in a practical sense in complex emergencies. Lastly, the principles promulgated by the WHO and UNHCR for the feeding of infants and children in emergencies and for milk powder distribution are summarized.

Neurodevelopmental outcomes of Ugandan infants with HIV infection: an application of growth curve analysis.

Neurodevelopmental outcomes of human immunodeficiency virus Type 1 (HIV-1)-infected infants of non-drug-using mothers were assessed in a controlled, prospective study from birth to 24 months with 3 groups: 61 infants of HIV-infected mothers, 234 uninfected infants of HIV-infected mothers (seroreverters), and 115 uninfected infants of uninfected mothers. Compared with seroreverters and uninfected infants, HIV-infected infants demonstrated lower mental and motor development on the Bayley Scales and greater deceleration in their rate of motor development. HIV-infected infants with abnormal neurologic exams had lower motor and mental test scores and lower rates of motor Bayley Scales scores than their HIV-infected counterparts with normal neurologic exams. Contrary to prediction, no group differences in mean performance or growth rates were found on visual information processing on the Fagan Test of Infant Intelligence.

Human immunodeficiency virus status and delayed-type hypersensitivity skin testing in Ugandan children.

BACKGROUND: In previous studies, delayed-type hypersensitivity (DTH) skin testing has been shown to be affected by several factors including nutritional status, intercurrent infection, host immune status, and previous exposure to the antigen being used. OBJECTIVE: To determine the effect of human immunodeficiency virus type 1 (HIV-1) status on DTH skin testing in a cohort of HIV-1-infected and noninfected Ugandan children followed prospectively from birth. DESIGN: Nested case-control study. SETTING: Primary care clinic serving study participants at Mulago Hospital, Makerere University, Kampala, Uganda. PARTICIPANTS: Thirty HIV-1-infected children and 30 age-matched, HIV-1-noninfected children. METHODS: After completion of history and physical, each child underwent Mantoux skin testing with both Candida and purified protein derivative (PPD). Results of skin testing were read in 48 to 72 hours. Complete chart reviews were performed on all children. CD4 lymphocyte counts were obtained on all HIV-1-infected children at the time the skin testing was read. RESULTS: The average age of participants was 67 months (range, 51-92 months). HIV-1-infected children (mean CD4 lymphocyte count, 1069 mL-1; range, 86-3378 mL-1), compared with noninfected, age-matched peers, developed significantly smaller PPD reaction size (mean, 1.18 mm +/- 4.3 vs 3.6 mm +/- 7.6, respectively). Candida responses were not different between the two groups of children. Among HIV-1-infected children, there was a larger Candida reaction size in children who had recently received chloroquine treatment. There was no significant correlation between Candida reactivity and PPD reactivity, progressive HIV-1 disease, or CD4 lymphocyte count. The six children diagnosed clinically with active tuberculosis had lower absolute CD4 lymphocyte counts than children without tuberculosis. Lack of reaction to PPD was associated with lower CD4 lymphocyte counts and progressive HIV-1 disease. CONCLUSIONS: In HIV-1-infected Ugandan children, DTH skin testing was influenced by the choice of antigen selected, HIV-1 infection, and recent treatment with chloroquine. Based on these findings, we believe that further prospective, longitudinal investigation into the role of chloroquine in HIV-1-infected children is needed. We emphasize the limitations of DTH skin testing in HIV-infected children as an adjunct in the diagnosis of active tuberculosis.

Mast cell activation in children with migraine before and after training in self-regulation.

Migraine may affect as many as 9% of all schoolchildren and often presents with abdominal symptoms of pain, nausea, and vomiting. Even though the pathophysiology of migraine remains unknown, self-regulation techniques appear to be more effective in prevention of childhood migraine than conventional pharmacotherapy which is often associated with adverse effects. Mast cells have been implicated in the pathogenesis of migraine in adults, but have not been previously studied in children with migraine. Mast cells are found close to the vessels and nerves in the meninges where they can release multiple vasoactive, neurosensitizing, and pro-inflammatory mediators. Therefore, we investigated whether children with migraine may have increased urinary levels of mast cell mediators and whether practicing relaxation imagery exercises has an effect on the frequency of headache, as well as on mast cell activation. Urine was collected for 24 hours from children with and without migraine after a 5-day amine-restricted diet. Children with migraine also collected urine during migraine episodes. The mean levels of urinary histamine, its main metabolite, methylhistamine, and the mast cell enzyme, tryptase, were higher in children than generally found in adults, but they did not differ statistically in any of the categories studied. However, in 8 of 10 children who practiced relaxation imagery techniques and successfully reduced the number of migraines, the urine tryptase levels were also significantly lower. There was no relationship between successful practice and sex or age of the child. These results suggest that stress may activate mast cells which could be involved in the pathophysiology of migraine.

Relaxation training and breast milk secretory IgA.

OBJECTIVE: To evaluate the hypothesis that breast-feeding women who participate in relaxation training will have increased secretory IgA (sIgA) levels in their breast milk compared with women not receiving training. DESIGN: Nonrandomized control trial of a convenience sample. SETTING: Women were recruited from the postpartum floor of a university teaching hospital. The intervention took place in the women's homes. PARTICIPANTS: Women in the first 48 hours after delivery who were planning to breast-feed their healthy newborn infants for at least 8 weeks were approached for enrollment. Women were excluded if they had previous experience with relaxation training. At 4 to 6 weeks postpartum, we enrolled 38 women still breast-feeding their infants. INTERVENTIONS: Women were allocated into 3 groups. Women in group 1 were taught relaxation and had breast milk samples collected before and after the teaching. Women in group 2 had conversation with similar breast milk sample collection, and women in group 3 had 1 breast milk sample collected. Women in group 1 were encouraged to practice the relaxation once or twice a day for 2 weeks, and a second visit was made to all mothers with repeated breast milk collections. Women who were still breast-feeding at 6 to 8 weeks after study end had a final breast milk sample collected. Breast milk was analyzed for secretory IgA levels. Stress was assayed using the Symptom Checklist-90-R and open-ended questions. RESULTS: There was no difference in sIgA levels among the 3 groups at any time. Women who reported stress present between visit 1 and visit 2 increased their sIgA levels at the final sample collection (+0.16 g/L) compared with women who reported no stress (-0.09 g/L; P= .03). The ratings of success in relaxation in women in group 1 were related to the following sIgA levels in sample 4: poor relaxation, 0.67 g/L; fair relaxation, 0.41 g/L; good relaxation, 0.35 g/L; and very good, 0.30 g/L (P= .006). CONCLUSIONS: Self-reported stress appears to increase breast milk sIgA levels. Success at relaxation was inversely related to sIgA levels in the group learning relaxation.

Effects of malaria infection in human immunodeficiency virus type 1-infected Ugandan children.

BACKGROUND: Malaria causes severe morbidity and mortality in many areas of Africa where HIV-1 infection is also prevalent. Immunosuppression is associated with both diseases but most reports do not find significant interactions between them. METHODS: A collaborative study of HIV-1 infection in Ugandan women and their infants was established between the Ministry of Health, Makerere University, Kampala, and Case Western Reserve University in 1988. Four hundred fifty-eight infants, including 77 HIV-1-infected, 232 seroreverter and 125 control children born to HIV-1-negative mothers and 24 of indeterminate status were followed closely from birth for 4 years. Data on these infants were reviewed with respect to episodes of general illness and infections, suspected and confirmed episodes of malaria, onset and frequency of malaria, use of chloroquine and occurrence of selected illnesses after episodes of febrile illnesses. Thick and thin blood smears for malaria were obtained from children with fever. RESULTS: There was no association between occurrence of febrile illnesses and childrens' HIV-1 category. The relative rates of occurrence were 1.0 (95% confidence interval (CI), 0.8 to 1.2) and 1.1 (95% CI 0.9 to 1.4) for the HIV seroreverter and control children compared with the HIV-infected children. Although there was no association (P = 0.83) between HIV-1 status and a smear being taken during a febrile episode, there was an increase in smears positive for malaria parasitemia among seroreverter (risk ratio, 1.5; 95% CI 1.1 to 1.9) and control infants (risk ratio, 1.6; 95% CI 1.2 to 2.2) compared with HIV-1-infected infants. The level of parasitemia was similar in each group. A greater proportion of malaria episodes among the HIV-infected group than among the control groups resulted in hospitalizations (P = 0.001) and blood transfusions (P = 0.02). There was a positive association between time to clinical AIDS and absence of malaria (adjusted for follow-up age) in infected children (P = 0.02). Use of chloroquine was similarly high in each HIV-1 category (80%). CONCLUSIONS: In this group of HIV-infected children there was no significant increase in malarial episodes as compared with their HIV-negative controls. The results suggest a possibility that malaria may offer some protection against HIV-1 progression or that chloroquine used to treat malaria may have a direct effect against the HIV-1 virus.

PIP: A prospective study of 458 infants from Kampala, Uganda, who were followed from birth to 48 months of age, documented a reduced risk of malaria in children infected with HIV-1. Included in the analysis were 77 HIV-infected children, 232 seroreverters, 125 HIV-negative children born to uninfected mothers, and 24 children of indeterminate HIV status. Thick and thin blood smears for malaria were obtained from children with fever. 51% of all children had at least 1 positive malaria smear during the study period, for a total of 653 documented malaria episodes. HIV-infected children had 3.5 episodes of malaria per 100 child months of observation compared with 5.0 episodes among seroreverters and 5.5 episodes among seronegative children. The relative rates of occurrence of malaria were 1.0 (95% confidence interval [CI], 0.8-1.2) in seroreverters and 1.1 (95% CI, 0.9-1.4) There was an increase in smears positive for malaria parasitemia among seroreverters (risk ratio, 1.5; 95% CI, 1.1-1.9) and HIV-negative controls (risk ratio, 1.6; 95% CI, 1.2-2.2) compared with HIV-infected children. Parasitemia levels during episodes of malaria were not significantly different between groups. Although the HIV-infected children had fewer episodes of malaria, they had a greater percentage of severe malaria episodes than controls and more frequent hospitalizations and blood transfusions per acute malarial episode. Within the HIV-positive group, mortality and progression to AIDS were delayed (although not significantly) among children who had malaria compared with those without malaria. It is possible that HIV-1 suppresses Plasmodium infection by creating a milieu that is suboptimal for parasite growth.

Neurodevelopmental outcomes of Ugandan infants with human immunodeficiency virus type 1 infection.

BACKGROUND: The neurodevelopmental outcomes of human immunodeficiency virus type 1 (HIV-1)-infected Ugandan infants of nondrug-using mothers were studied using controlled, prospective methodology. METHOD: The sample of 436 full-term infants included 79 HIV-infected infants of HIV-1-infected mothers, 241 uninfected infants of HIV-1-infected mothers (seroreverters), and 116 uninfected infants born to HIV-negative mothers. Neurologic status, information processing ability, and motor and mental development were assessed from 6 to 24 months of age. Observations of caretaker-child interaction and home environments were made at 6 and 12 months. All evaluators were blinded to the HIV status of the child and family. RESULTS: Compared with seroreverters and uninfected infants, HIV-infected infants demonstrated greater deficits in motor development and neurologic status, and more frequent and earlier onset of motor and neurologic abnormalities. Compared with controls, HIV-infected infants had more abnormalities in mental development at 6 and 18 months and an earlier onset of abnormalities. By 12 months, 30% of HIV-infected infants demonstrated motor abnormalities and 26% cognitive abnormalities as compared with 11% and 6% among seroreverters and 5% and 6% among seronegative infants. HIV-infected infants (62%) demonstrated a higher probability of developing an abnormal neurologic examination by 12 months, compared with seroreverters (17%) or seronegative infants (15%). Information-processing abilities did not differ as a function of HIV infection. Home environments and infants' interactions with caretakers were similar across groups. CONCLUSION: We conclude that HIV infection results in more frequent and earlier abnormalities in infants' neurologic status and motor development that are not attributable to other biological and environmental risk factors. More frequent mental developmental abnormalities were evident at several ages. However, information-processing abilities, such as recognition memory, may be spared from HIV-related deficits.

Growth failure as a prognostic indicator of mortality in pediatric HIV infection.

OBJECTIVE: To study the effect of perinatally acquired human immunodeficiency virus (HIV) on somatic growth and examine the relationship of nutritional status to mortality in HIV-infected infants. METHOD: Pregnant women attending the antenatal clinic at Mulago hospital in Kampala, Uganda, were enrolled. All live-born babies born to HIV-1 seropositive (HIV+) women, and to every fourth age-matched HIV-1 seronegative (HIV-) woman, were followed for 25 months. RESULTS: The mean weight-for-age and length-for-age curves of HIV+ children were significantly lower than those of HIV- controls and seroeverters. Forty-five (54%) of the 84 HIV+ infants died before their second birthday, as compared with a 1.6% and 5.6% mortality in HIV- and seroeverters. HIV+ infants with an average weight-for-age Z-score below -1.5 in the first year of life have a nearly fivefold risk of dying before 25 months of age compared with noninfected controls. CONCLUSION: Perinatally acquired HIV infection is associated with early and progressive growth failure. The severity of growth failure is associated with an increased risk of mortality. The effect of early, aggressive nutritional intervention in delaying HIV progression and mortality should be evaluated by controlled intervention studies.

Clinical and demographic characteristics of migraine in urban children.

OBJECTIVE: To establish the frequency, symptoms, duration, and treatment methods of childhood migraine in an urban area. DESIGN: Self-administered questionnaire survey. The questionnaire was designed according to criteria suggested by the International Headache Society (IHS). PARTICIPANTS: In 1994, with the help of school officials in 41 elementary and middle schools in the Greater Cleve-land Area, 18,000 questionnaires were distributed to the parents of schoolchildren who ranged in age from 5 to 13 years. RESULTS: Of the total 2572 respondents, 222 children (8.6%) met the IHS criteria for migraine. Male to female ratio was 1:1.2 (99:120), 65.8% had a positive family history of migraine, 30.6% had onset of migraine at 4 to 5 years of age, and 54.1% reported having an aura (71% of these were visual aura). The headaches were mostly pulsating, poorly localized, lasted about 2 to 12 hours, and were aggravated by motion, noise, and bright light. The associated symptoms were nausea, vomiting, photophobia, and phonophobia. During the attack, 43% of the migraineurs had to stay in bed, and 27% were unable to attend school. Only 19.8% of the migraineurs were diagnosed to have migraine by their physicians, and most of these had not received treatment. CONCLUSION: This study in an urban area indicates that childhood migraine is a common, often underdiagnosed disorder that causes significant suffering for children and their families.

Effects of self-induced mental imagery on autonomic reactivity in children.

The purposes of this research study were: (1) to determine whether changes in cardiac rate, skin temperature, and/or electrodermal activity occur as children change mental imagery and (2) to determine whether such changes are related to age, sex, or other variables. Children who were evaluated in this study had no previous experience with hypnosis or biofeedback training and were in good health with no learning disabilities. Thirty-eight boys and 38 girls ranging in age from 5 to 15 years were studied in a comfortable setting with a constant room temperature and biofeedback equipment. A Procomp 5DX computer software unit was used to measure autonomic reactivity during baseline and mental processing periods. After baseline monitoring indicated stabilization of autonomic measures, each child was asked to think about being in a quiet, pleasant place for 120 seconds. Pulse rate, skin temperature, and electrodermal activity were recorded. A resting period followed, and each child was then asked to think about an exciting activity, such as a preferred sports activity, for another 120 seconds. At the end of this monitoring, each child was asked to describe what had been his/her mental imagery during the two monitoring periods. Data analysis used paired t tests and repeated measures analysis of variance. For all children, the pulse rates showed significant decreases (p < .001) during quiet and relaxing imagery and significant increases (p < .001) during active imagery. Skin temperatures increased significantly (p < .001) during quiet imagery and active imagery, whereas electrodermal activity decreased (p < .001) during active imagery. Observed changes did not relate to age or sex. The results confirm our clinical observations that deliberate changing of mental imagery by children results in immediate autonomic changes. Questions evolving from this study and similar studies done in adults are: (1) Do average-thinking processes impact on autonomic changes over long periods of time and (2) do these changes ultimately impact on health, such as cardiovascular status?

Detection of human immunodeficiency virus type 1 (HIV-1) DNA and p24 antigen in breast milk of HIV-1-infected Ugandan women and vertical transmission.

OBJECTIVE: To determine the correlation between the detection of human immunodeficiency virus type 1 (HIV-1) in breast milk, the duration of breastfeeding, and vertical transmission of HIV-1 infection in Ugandan women. METHODS: A prospective study of HIV-1 infection in pregnant Ugandan women and their infants has been ongoing since 1990 with follow-up of mother-infant pairs for at least 2 years. Expressed breast milk specimens were collected from 201 HIV-1-seropositive and 86 HIV-1-seronegative Ugandan women approximately 6 weeks after delivery. The presence of HIV-1 DNA in the cellular fraction of the breast milk was detected by polymerase chain reaction (PCR), and HIV-1 p24 antigen was detected in the cell-free breast milk supernatant using p24 antigen enzyme immunoassay (EIA) after immune complex dissociation (ICD). The duration of breastfeeding and the clinical status of the mothers and their children were recorded. HIV-1 EIA, Western blot, PCR, or p24 antigen detection were used for the determination of the HIV-1 infection status of the children. RESULTS: Of the 201 HIV-1-infected women studied, 47 had HIV-1-infected children, 143 had children who seroreverted, and 11 had children of indeterminate status. Breast milk supernatants were available for ICD p24 antigen testing from 188 of the HIV-1-infected women and none had detectable p24 antigen. Breast milk cell pellets were available and contained amplifiable DNA in 125 of the HIV-1-infected women (20 transmitters, 104 nontransmitters, 1 indeterminate). HIV-1 DNA was detected by PCR in 72% (75/104) of nontransmitters and 80% (16/20) of the transmitters. The duration of breastfeeding by transmitter mothers (15.8 months) was not significantly different from nontransmitter mothers (14.4 months). CONCLUSIONS: No correlation was found between the detection of HIV-1 in breast milk or the duration of breastfeeding and transmission of HIV-1 infection in this study of Ugandan women.

Directional changes in neutrophil adherence following passive resting versus active imagery.

This study was designed to determine whether increases or decreases in neutrophil adherence could be achieved following a self-regulation (relaxation/imagery) intervention. Fifteen subjects were randomly assigned to one of three conditions. Two experimental groups employed imagery focussed on either increasing or decreasing neutrophil adherence. Subjects had two weeks of self-regulation practice (4 total training sessions) prior to blood drawings. A third group of control subjects had the same number of resting sessions without imagery training. All subjects had blood samples collected before and after either 30 minutes of self-regulation or resting practice for two sessions. Pulse and peripheral finger temperature measures were taken before and after the blood samples. Both experimental groups demonstrated decreases in neutrophil adherence, and the control showed a tendency toward increases in this measure. The psychophysiologic data for the control group was suggestive of a relaxation response. The experimental group that attempted to increase neutrophil adherence demonstrated psychophysiologic responses that were contrary to relaxation. We concluded that an active cognitive exercise or process is associated with decreases in neutrophil adherence irrespective of the exercise. In contrast, relaxation without an active imagery exercise was associated with increases in neutrophil adherence. The results of this study are discussed in terms of behavioral engineering of directional immune changes.

Maternal HIV-1 RNA serum levels at delivery and vertical transmission in Uganda.

OBJECTIVE: To evaluate the clinical utility of maternal HIV-1 RNA serum levels at delivery in predicting the rate of HIV-1 vertical transmission. DESIGN AND METHODS: HIV-1 RNA levels were determined by the Roche Amplicor Monitor assay in serum specimens collected at the time of delivery from 94 transmitting and 107 nontransmitting infected mothers and 12 seronegative mothers in Uganda. Nonparametric Wilcoxon-Rank sum tests were used to identify significant differences in medians and RNA level distributions by transmission status. RESULTS: Mean HIV-1 RNA copies/mL for transmitters was 3419 +/- 7489 copies/mL versus 2483 +/- 8954 copies/mL for nontransmitters. There was a significant difference in medians and HIV-1 RNA serum level distributions between transmitting and nontransmitting mothers (p = 0.0039). However, the predictive value for any given HIV-1 RNA level for HIV-1 vertical transmission was poor. CONCLUSION: Maternal HIV-1 RNA serum levels at delivery are significantly higher in transmitting mothers versus nontransmitting mothers, but appear to be of limited value in predicting HIV-1 vertical transmission using the Roche Amplicor Monitor assay in Uganda.

An educational intervention to increase faculty publication productivity.

BACKGROUND: Writing is an essential skill for academic family physicians. It is essential in all of the academic physicians' roles, and publications are critical for promotion and tenure. This study describes a three-part faculty development instructional program designed to teach writing skills. The instructional program was repeated over a 3-year period involving two different institutions with departments of family medicine. METHODS: Educational interventions included seminars, workshops, and independent practice, with feedback from senior advisors. The practice and feedback sections centered on the faculty members' own written products. RESULTS: This series resulted in the publication of 16 papers from 13 of the 40 faculty participants. CONCLUSIONS: Our experience suggests that a writing series is one effective method that departments of family medicine may use to facilitate the writing productivity of faculty.

Lack of association between anti-V3 loop antibodies and perinatal transmission of HIV-1 in Kampala, Uganda.

This study evaluated the association between reactivity of maternal antibody to human immunodeficiency virus type 1 (HIV-1) V3 loop peptides and perinatal transmission in Uganda. Plasma from 40 HIV-1-infected mothers (20 transmitting and 20 nontransmitting mothers) and 31 uninfected mothers in Uganda were tested for reactivity and antibody titer to synthetic peptides representing V3 loop sequences from HIV-1 strains MN, SF2, LAI, ZR6, and CM235 and consensus peptides CA, CB, and CD. No significant differences were found between 20 transmitting mothers and 20 nontransmitting mothers in terms of percent reactivity or titer of antibody to any of the V3 loop peptides tested. Use of a multivariable logistic model to adjust for beta-2 microglobulin level as a confounding variable of stage of infection did not help demonstrate an association except possibly for the ZR6 peptide. These data suggest that neither reactivity nor maternal antibody titer to V3 loop peptides are protective against perinatal transmission of HIV-1 in Uganda.