Internally Displaced “Victims of Armed Conflict” in Colombia: The Trajectory and Trauma Signature of Forced Migration

While conflict-induced forced migration is a global phenomenon, the situation in Colombia, South America, is distinctive. Colombia has ranked either first or second in the number of internally displaced persons for 10 years, a consequence of decades of armed conflict compounded by high prevalence of drug trafficking. The displacement trajectory for displaced persons in Colombia proceeds through a sequence of stages: (1) pre-expulsion threats and vulnerability, (2) expulsion, (3) migration, (4) initial adaptation to relocation, (5) protracted resettlement (the end point for most forced migrants), and, rarely, (6) return to the community of origin. Trauma signature analysis, an evidence-based method that elucidates the physical and psychological consequences associated with exposures to harm and loss during disasters and complex emergencies, was used to identify the psychological risk factors and potentially traumatic events experienced by conflict-displaced persons in Colombia, stratified across the phases of displacement. Trauma and loss are experienced differentially throughout the pathway of displacement.     

Mother-to-Child Transmission of Chagas Disease in El Salvador

To estimate the incidence (any mother to child) and rate (from seropositive mother to child) of mother-to-child transmission of Trypanosoma cruzi, a serological census was conducted, targeting pregnant women and infants born to seropositive mothers, in four municipalities of El Salvador. Of 943 pregnant women, 36 (3.8%) were seropositive for T. cruzi. Of 36, 32 proceeded to serological tests of their infants when they became 6–8 months of age. Six infants seropositive at the age of 6–8 months further proceeded to second-stage serological test at the age of 9–16 months. As the result, one infant was congenitally infected. Thus, serological tests at the age of 6–8 months produced five false positives. To ensure earlier effective medication only for true positives, identification of seropositive infants at the age of 9–16 months is crucial. Incidence and rate of mother-to-child transmission were 0.14 (per 100 person-years) and 4.0%, respectively. Estimated number of children infected through mother-to-child transmission in El Salvador (170 per year) was much higher than that of human immunodeficiency virus (HIV; seven per year). It is recommended that serological testing for T. cruzi be integrated into those for HIV and syphilis as part of antenatal care package.     

The fitness of citrus tristeza virus defective RNAs is affected by the lengths of their 5'- and 3'-termini and by the coding capacity

Populations of the Closterovirus Citrus tristeza virus (CTV) generally contain defective RNAs (dRNAs) that vary in size, abundance, and sequence. The variation in abundance of the different dRNAs in a population suggests selection for those of higher fitness. To examine factors affecting fitness of dRNAs, we investigated a series of in vitro constructed dRNAs for their ability to be amplified in protoplasts by an efficiently replicated CTV deletion mutant. The minimal sequences required for accumulation of the dRNAs were within the genomic 5' proximal approximately 1 kb and the 3' 270 nucleotides. However, other factors were involved, because a dRNA with only the minimal sequences failed to be replicated. Rescue of a nonviable dRNA by insertion of nonviral sequences between the termini suggested that "spacing" between terminal cis-acting signals influenced fitness. A continuous open reading frame (ORF) through most of the sequences derived from the 5' of the genome was a requirement for dRNA amplification. In general, insertions, deletions, or nucleotide substitutions were tolerated in the dRNAs as long as an ORF was retained, whereas dRNAs with mutations that prematurely terminated the ORF were not viable. To discriminate between a requirement for an essential protein and ribosomal travel, perhaps to present replication signals to the replicase complex, mutations were made to modify the potential protein but still maintain an ORF. Deletions, insertions of nonviral sequences, or switching of reading frames that altered the amino acid sequence of the protein, except the N-terminal 161 amino acids, did not destroy the fitness of the dRNAs. Yet termination of the ORF in the middle of nonviral sequences did destroy the ability of the dRNAs to be amplified. These results suggest that even though a continuous ORF was needed for fitness, its protein product did not affect the amplification of the dRNAs.     

CD8+-dependent CNS demyelination following ocular infection of mice with a recombinant HSV-1 expressing murine IL-2

Demyelinating diseases comprise a spectrum of immunopathologic syndromes in which myelin, the fatty covering of nerve cell fibers in the brain and spinal cord, is destroyed. In this study, we have shown for the first time that ocular infection of BALB/c mice with a recombinant herpes simplex virus type 1 (HSV-1) expressing IL-2 (HSV-IL-2) results in CNS demyelination as determined by light microscopy and EM. The demyelinated lesions involve periventricular white matter, brain stem, and spinal cord white matter. Demyelination was detected in the CNS of infected mice up to 75 days (the longest time point tested) post HSV-IL-2 infection. In contrast, mice infected with HSV-IFN-gamma or HSV-IL-4, which are identical to HSV-IL-2 but express IFN-gamma or IL-4 instead of IL-2, did not exhibit demyelination. Control mice infected with wild-type HSV-1 or parental virus also remained free of these symptoms. During early times (days 3-7), post-infection with HSV-IL-2 virus, a T(H)1 + T(H)2 pattern of cytokines was produced by lymphocytes of infected mice while mice infected with HSV-IFN-gamma or control viruses produced a T(H)1 pattern of cytokine. By day 21 post-infection, all infected groups exhibited a T(H)1 pattern of response. Immunohistochemistry and FACS analyses of infiltrates in the brains and spinal cords of HSV-IL-2-infected mice showed elevations in CD4+ and CD8+ T cells and macrophages. However, T cell depletion studies suggest that only central memory CD8+ T cells are directly involved in the demyelination process, with macrophages being involved through a bystander effect.     

Maternal activating mutation of the calcium-sensing receptor: implications for calcium metabolism in the neonate

Two infants were studied born of a mother with autosomal dominant hypocalcemia who is heterozygous for an activating mutation in the calcium-sensing receptor gene. Both infants had serum calcium levels in the low-normal range and parathyroid hormone levels in the high-normal range and were healthy. The mother's hypocalcemia had been treated with calcium carbonate and calcitriol and she has nephrocalcinosis and mild renal insufficiency. By genetic testing, both infants were shown to have normal calcium-sensing receptor gene alleles, i.e., they had not inherited the activating mutation from their mother. This provided reassurance to the family and ensured that treatment to correct apparent hypocalcemia would not be necessary. The fact that the infants had high normal parathyroid hormone levels with normal calcium may be due to the fact that with a normal calcium-sensing receptor their parathyroid glands responded in utero to the maternal hypocalcemia with an increase in parathyroid hormone.