Risk factors associated with first symptomatic infection of {\it Cryptosporidium parvum\/} in an infant population in Bilbeis, Egypt

Diarrhea disease is a leading cause of morbidity and mortality, especially in children in developing countries. An estimate of the global mortality caused by diarrhea among children under five years of age was 3.3 million deaths per year. Cryptosporidium parvum was first identified in 1907, but it was not until 1970 that this organism was recognized as a cause of diarrhea in calves. Then it was as late as 1976 that the first reported case of human Cryptosporidiosis occurred. This study was conducted to ascertain the risk factors of first symptomatic infection with Cryptosporidium parvum in a cohort of infants in a rural area of Egypt. The cohort was followed from birth through the first year of life. Univariate and multivariate analyses of data demonstrated that infants greater than six months of age had a two-fold risk of infection compared with infants less than six months of age (RR = 2.17; 95% C.I. = 1.01-4.82). When stratified, male infants greater than six months of age were four times more likely to become infected than male infants less than six months of age. Among female infants, there was no difference in risk between infants greater than six months of age and infants less than six months of age. Female infants less than six months of age were twice more likely to become infected than male infants less than six months of age. The reverse occurred for infants greater than six months of age, i.e., male infants greater than six months of age had twice the risk of infection compared to females of the same age group. Further analysis of the data revealed an increased risk of Cryptosporidiosis infection in infants who were attended in childbirth by traditional childbirth attendants compared to infants who were attended by modern childbirth attendants (nurses, trained midwives, physicians) (RR = 4. 18; 95% C.I. = 1.05-36.06). The final risk factor of significance was the number of people residing in the household. Infants in households which housed more than seven persons had an almost two-fold risk of infection compared with infants in homes with fewer than seven persons. Other risk factors which suggested increased risk were lack of education among the mothers, absence of latrines and faucets in the homes, and mud used as building material for walls and floors in the homes. ^

Birth defects among surviving children under seven years of age in Tianjin, China

Birth defects are a leading cause of infant mortality in the developed countries. They are also of increasing concern in many developing countries, such as China. However, prevalence and causes of birth defects in China are inadequately understood.^ The purpose of the present study was to estimated prevalence of birth defects in surviving children under seven years of age in Tianjin, China and investigate determinants of birth defects in the study area.^ The present study took place in Tianjin, China in 1986, involving 22,081 surviving children under seven years of age. Children with birth defects were ascertained through physical examinations by physicians during household visits and ascertainment of birth defects was verified through multiple sources. Of 22,081 surviving children, 524 had birth defects (23.7 per 1,000). The study noted a striking discrepancy in the prevalence of birth defects between urban and rural area. The prevalence of birth defects was 16.3 per 1,000 in the urban and 33.2 per 1,000 in the rural area.^ Using cases of birth defects ascertained from surviving children, a case-control study was carried out. The study observed that first-trimester maternal flu was associated with increased risk of both major and minor birth defects in children after controlling for other maternal factors (adjusted odds ratio (OR) = 8.7, 95% confidence interval (CI) = 4.3-17.3; OR = 3.6, 95% CI = 1.7-7.5). This association could be biased by different reporting of exposure between mothers of children with birth defects and mothers of children without defects. This study indicated that maternal flu was also associated with congenital heart defects and polydactyly after controlling for other maternal factors (adjusted OR = 32.3, 95% CI = 13.3-78.3; adjusted OR = 5.5, 95% CI = 1.1-27.7). The associations remained when affected controls (children with similar birth defects other than congenital heart defects or polydactyly) were used (adjusted OR = 4.3, 95% CI = 1.2-15.3; OR = 1.4, 95% CI = 1.4-7.9). A weak association between first-trimester vaginal bleeding and selected groups of birth defects was found in this study, but the association may be confounded by other factors. Maternal smoking during pregnancy was modestly associated with cleft lip with or without cleft palate (OR = 1.4, 95% = 0.4-4.9), but the association may be due to chance. Some major limitations in this study warrant caution in interpretation of the findings, especially the causal relation. ^

Source of health insurance and immunization rates: Findings from the 1996 Texas immunization survey

This study was a further investigation of the 1996 Texas Immunization Survey conducted by the Associateship for Disease Control and Prevention of the Texas Department of Health. The 1996 survey was conducted through 4,599 completed telephone interviews of families with a child between the ages of 3–35 months concerning the immunization status of Texas children. The present study determined differences in immunization rates for children aged 3–35 months for the last shot in the immunization series that should be completed before 2 years of age, a total of four shots, both overall and for different health insurance groups. Life tables were used to determine the percentage and distribution over time of completed vaccination rates for each shot. Emphasis was placed on the proportion of children that were immunized at the end of the recommended range of the immunization schedule, and at 2 years of age. Univariate and multivariate analysis was also performed in order to ascertain which risk factors predict whether or not a child will be immunized. RESULTS: Between 80–90% were immunized for the last shot of Hepatitis B; Measles, Mumps, and Rubella; and Polio at 2 years of age. Approximately 2/3 of the sample was immunized for Diphtheria, Pertussis, and Tetanus. Most of the children were immunized by the end of the recommended range of the immunization schedule except for Measles, Mumps, and Rubella. Children of parents with private indemnity insurance were significantly more likely to have received two of the four shots; children of uninsured parents were significantly less likely to have received three of the four shots. In multivariate analysis, maternal education was the only variable that consistently predicted immunization status for the different shots. Results indicate that a substantial gap exists for immunization rates between children with private insurance and uninsured children, despite recent policy changes to provide immunizations free of charge. Health care providers should pay extra attention to the poor and uninsured to make sure that all children receive timely immunizations. ^

Can infant lung function predict respiratory morbidity during the first year of life in preterm infants?

Compared with term-born infants, preterm infants have increased respiratory morbidity in the first year of life. We investigated whether lung function tests performed near term predict subsequent respiratory morbidity during the first year of life and compared this to standard clinical parameters in preterms.The prospective birth cohort included randomly selected preterm infants with and without bronchopulmonary dysplasia. Lung function (tidal breathing and multiple-breath washout) was measured at 44 weeks post-menstrual age during natural sleep. We assessed respiratory morbidity (wheeze, hospitalisation, inhalation and home oxygen therapy) after 1 year using a standardised questionnaire. We first assessed the association between lung function and subsequent respiratory morbidity. Secondly, we compared the predictive power of standard clinical predictors with and without lung function data.In 166 preterm infants, tidal volume, time to peak tidal expiratory flow/expiratory time ratio and respiratory rate were significantly associated with subsequent wheeze. In comparison with standard clinical predictors, lung function did not improve the prediction of later respiratory morbidity in an individual child.Although associated with later wheeze, noninvasive infant lung function shows large physiological variability and does not add to clinically relevant risk prediction for subsequent respiratory morbidity in an individual preterm.

Dexamethasone aggravates hippocampal apoptosis and learning deficiency in pneumococcal meningitis in infant rats.

In an infant rat model of pneumococcal meningitis the effect of dexamethasone on neuronal injury in the hippocampus and on learning disability after recovery from the disease was examined. Treatment with dexamethasone or vehicle was started 18 h after infection, concomitant with antibiotics. Neuronal apoptosis in the hippocampal dentate gyrus 34 h after infection was significantly aggravated by dexamethasone treatment compared with vehicle controls (p = 0.02). Three weeks after acute pneumococcal meningitis, learning capacity of animals was assessed in the Morris water maze. The results showed a significantly impaired learning performance of infected animals treated with dexamethasone compared with vehicle controls (p = 0.01). Dexamethasone had no effect on hippocampal injury or learning in uninfected controls. Thus, dexamethasone as adjuvant therapy increased hippocampal cell injury and reduced learning capacity in this model of pneumococcal meningitis in infant rats.

Bacterial meningitis causes two distinct forms of cellular damage in the hippocampal dentate gyrus in infant rats.

Bacterial meningitis causes neurological sequelae in up to 50% of survivors. Two pathogens known for their propensity to cause severe neurological damage are Streptococcus pneumoniae and group B streptococci. Some forms of neuronal sequelae, such as learning and memory deficits, have been associated with neuronal injury in the hippocampus. To learn more about hippocampal injury in meningitis, we performed a comparative study in bacterial meningitis due to S. pneumoniae and group B streptococcus, in which 11-day-old infant rats were infected intracisternally with either of the two pathogens. Histopathological examination of the neuronal injury in the dentate gyrus of the hippocampus showed that S. pneumoniae caused predominantly classical apoptotic cell death. Cells undergoing apoptosis were located only in the subgranular zone and stained positive for activated caspase-3 and TUNEL. Furthermore, dividing progenitor cells seemed particularly sensitive to this form of cell death. Group B streptococcus was mainly responsible for a caspase-3-independent (and TUNEL-negative) form of cell death. Compared with the morphological features found in apoptosis (e.g., apoptotic bodies), this form of neuronal death was characterized by clusters of uniformly shrunken cells. It affected the dentate gyrus throughout the blade, showing no preferences for immature or mature neurons. Thus, depending on the infecting agent, bacterial meningitis causes two distinct forms of cell injury in the dentate gyrus.

Reactive oxygen intermediates contribute to necrotic and apoptotic neuronal injury in an infant rat model of bacterial meningitis due to group B streptococci.

Reactive oxygen intermediates (ROI) contribute to neuronal injury in cerebral ischemia and trauma. In this study we explored the role of ROI in bacterial meningitis. Meningitis caused by group B streptococci in infant rats led to two distinct forms of neuronal injury, areas of necrosis in the cortex and neuronal loss in the dentate gyrus of the hippocampus, the latter showing evidence for apoptosis. Staining of brain sections with diaminobenzidine after perfusion with manganese buffer and measurement of lipid peroxidation products in brain homogenates both provided evidence that meningitis led to the generation of ROI. Treatment with the radical scavenger alpha-phenyl-tert-butyl nitrone (PBN) (100 mg/kg q8h i.p.) beginning at the time of infection completely abolished ROI detection and the increase in lipidperoxidation. Cerebral cortical perfusion was reduced in animals with meningitis to 37.5+/-21.0% of uninfected controls (P < 0.05), and PBN restored cortical perfusion to 72.0+/-8.1% of controls (P < 0.05 vs meningitis). PBN also completely prevented neuronal injury in the cortex and hippocampus, when started at the time of infection (P < 0.02), and significantly reduced both forms of injury, when started 18 h after infection together with antibiotics (P < 0.004 for cortex and P < 0.001 for hippocampus). These data indicate that the generation of ROI is a major contributor to cerebral ischemia and necrotic and apoptotic neuronal injury in this model of neonatal meningitis.

Parasite- and predator-induced maternal effects in the great tit (Parus major)

Both predators and parasites can elicit behavioral and physiological responses in prey and hosts, respectively. These responses may involve the reallocation of resources and may thus limit each other. We investigated the effects of concurrent pre-laying exposure of great tit females (Parus major) to both a simulated predation risk and a nest-based ectoparasite, the hen flea (Ceratophyllus gallinae), on nestling growth and development. We manipulated perceived predation risk using models and vocalizations of sparrowhawks (Accipiter nisus). At the start of incubation, we swapped whole clutches between treated and untreated nests to separate pre-laying maternal effects from posthatching effects. Since costs and benefits of maternal responses to parasites need to be assessed under parasite pressure, we infested half of the rearing nests with hen fleas. Parasites had negative effects on mass gain and wing growth, both via maternal effects and via direct exposure of nestlings, whereas maternal predation risk had no significant effect. The interaction between predator and parasite treatments was not significant and, thus, suggests the absence of a trade-off between the 2 stressors operating at the level of maternal effects. Alternatively, the complexity of the design, despite a relatively large sample size, may have limited the power for detection of this expected trade-off.

A tick-borne encephalitis model in infant rats infected with langat virus

Tick-borne encephalitis virus (TBEV) is the causative agent of human TBE, a severe infection that can cause long-lasting neurologic sequelae. Langat virus (LGTV), which is closely related to TBEV, has a low virulence for human hosts and has been used as a live vaccine against TBEV. Tick-borne encephalitis by natural infection of LGTV in humans has not been described, but one of 18,500 LGTV vaccinees developed encephalitis. The pathogenetic mechanisms of TBEV are poorly understood and, currently, no effective therapy is available. We developed an infant rat model of TBE using LGTV as infective agent. Infant Wistar rats were inoculated intracisternally with 10 focus-forming units of LGTV and assessed for clinical disease and neuropathologic findings at Days 2, 4, 7, and 9 after infection. Infection with LGTV led to gait disturbance, hypokinesia, and reduced weight gain or weight loss. Cerebrospinal fluid concentrations of RANTES, interferon-γ, interferon-β, interleukin-6, and monocyte chemotactic protein-1 were increased in infected animals. The brains of animals with LGTV encephalitis exhibited characteristic perivascular inflammatory cuffs and glial nodules; immunohistochemistry documented the presence of LGTV in the thalamus, hippocampus, midbrain, frontal pole, and cerebellum. Thus, LGTV meningoencephalitis in infant rats mimics important clinical and histopathologic features of human TBE. This new model provides a tool to investigate disease mechanisms and to evaluate new therapeutic strategies against encephalitogenic flaviviruses.