Voluntary HIV counseling and testing: experience among the sexually active population in Bangui,Central African Republic

OBJECTIVES: In July 1997, the National Reference Center for Sexually Transmitted Diseases of Bangui, Central African Republic (CAR), was expanded by the creation of an anonymous and voluntary counseling and testing (VCT) unit for HIV infection, the Anonymous Surveillance Unit (Unité de Dépistage Anonyme [UDA]). The goal of the UDA was to initiate and promote voluntary HIV testing in the general adult population of Bangui. We carried out an observational and comprehensive survey over a 4-year period to document and analyze the experience of VCT in the UDA, with special attention to risk factors associated with HIV infection. METHODS: All clients for VCT were given adequate pretest counseling by trained counselors focused on knowledge about HIV infection and sexually transmitted infections, individual risks of acquiring HIV, and anticipation of the client's attitude about test results. After consent was obtained, a blood sample was drawn and tested for HIV by two ELISAs in parallel. The client paid a standard cost of $1.20 at the initial visit. After a week, test results were given to the client during the posttest visit, at which time HIV-seropositive individuals received emotional support and were referred to specific social or medical structures. Seronegative clients received reinforcement of prevention messages and were asked to come back for serologic follow-up free of charge after 3 (M3) and 12 (M12) months. RESULTS: From July 1997 to March 2001, 5686 individuals aged 14 to 65 years (mean age, 27 years) had an initial visit for VCT (V1). Peaks of UDA visitation (250-450 clients) were observed on the annual AIDS Day in the CAR, at which time HIV serologic testing was offered free of charge. A total of 5060 (89%) clients came back for a second visit (V2) to receive test results. Among those, 18.3% were infected with HIV type 1. Multivariate analysis of risk factors demonstrated marked association of HIV seropositivity with age, female gender, widowed/divorced women, poor or low education level, occupations such as civil servants or merchants, presence of symptoms of sexually transmitted infections, and lack of systematic condom use. Single young women were at higher risk for HIV infection compared with men of the same age (OR = 7.7 for women aged 15-24 years, 95% CI: 4.0-14.0; OR = 2.8 for women aged 25-34 years, 95% CI: 1.7-4.5). Widowed women older than 44 years of age were more likely to be HIV-seropositive than men (OR = 10.0; 95% CI: 1.7-83.6). A total of 885 (21%) HIV-seronegative individuals returned for follow-up at 3 months (M3; 0.45% rate of seroconversion). Seventy-nine (9%) individuals returned at 12 months (M12), without any new cases of HIV infection. HIV-negative clients consulting at M3 and M12 showed a significant reduction in unprotected intercourse with occasional sexual partners. CONCLUSION: This experience demonstrates that VCT for HIV infection is feasible in Central Africa.     

Comparison of CHROMagar Salmonella medium and xylose-lysine-desoxycholate and Salmonella-Shigella agars for isolation of Salmonella strains from stool samples

The growth and appearance of 115 stock Salmonella isolates on a new formulation of CHROMagar Salmonella (CAS) medium were compared to those on xylose-lysine-desoxycholate agar (XLD), Salmonella-Shigella agar (SS), and Hektoen enteric agar (HEA) media. CAS medium was then compared prospectively to XLD and SS for the detection and presumptive identification of Salmonella strains in 500 consecutive clinical stool samples. All stock Salmonella isolates produced typical mauve colonies on CAS medium. Nine Salmonella strains were isolated from clinical specimens. The sensitivities for the detection of salmonellae after primary plating on CAS medium and the combination of XLD and SS after enrichment were 100%. The specificity for the detection of salmonellae after primary plating on CAS medium (83%) was significantly (P < 0.0001) higher than that after primary plating on the combination of SS and XLD media (55%) (a 28% difference in rates; 95% confidence interval, 23.0 to 34%). Twenty-nine non-Salmonella organisms produced mauve colonies on CAS medium, including 17 Candida spp. (59%) and 8 Pseudomonas spp. (28%). These were easily excluded as salmonellae by colony morphology, microscopic examination of a wet preparation, or oxidase testing. One biochemically inert Escherichia coli isolate required further identification to differentiate it from Salmonella spp. The use of plating on CAS medium demonstrated high levels of sensitivity and specificity and reduced the time to final identification of Salmonella spp., resulting in substantial cost savings. It can be recommended for use for the primary isolation of Salmonella spp. from stool specimens. Other media (e.g., XLD) are required to detect Shigella spp. concurrently.     

The role of CD45+CD4+CD3– cells in lymphoid organ development

Summary: In the last 10 years the continuing search for gene function has yielded many mutant mice that unexpectedly showed a complete lack of lymph nodes and/or Peyer's patches. With the realization that all these functionally highly diverse genes are involved at some point in the development of lymphoid organs, the challenge now is to assign a function to the molecules involved in lymphoid organ development. It will be important to determine the sequence of molecular events and assign this to the cellular events that lead to an accumulation of hematopoietic cells in one location, ultimately forming an organized lymphoid organ. Here we will focus on CD45⁺CD4⁺CD3^– cells that are the early colonizing cells in lymph nodes and Peyer's patches and develop a hypothetical model of their contribution to the creation of organized lymphoid structures.     

Characterization of unusual bacteria isolated from respiratory secretions of cystic fibrosis patients and description of Inquilinus limosus gen. nov., sp. nov

Using a polyphasic approach (including cellular protein and fatty acid analysis, biochemical characterization, 16S ribosomal DNA sequencing, and DNA-DNA hybridizations), we characterized 51 bacterial isolates recovered from respiratory secretions of cystic fibrosis (CF) patients. Our analyses showed that 24 isolates belong to taxa that have so far not (or only rarely) been reported from CF patients. These taxa include Acinetobacter sp., Bordetella hinzii, Burkholderia fungorum, Comamonas testosteroni, Chryseobacterium sp., Herbaspirillum sp., Moraxella osloensis, Pandoraea genomospecies 4, Ralstonia gilardii, Ralstonia mannitolilytica, Rhizobium radiobacter, and Xanthomonas sp. In addition, one isolate most likely represents a novel Ralstonia species, whereas nine isolates belong to novel taxa within the alpha-PROTEOBACTERIA: Eight of these latter isolates are classified into the novel genus Inquilinus gen. nov. as Inquilinus limosus gen. nov., sp. nov., or as Inquilinus sp. The remaining 17 isolates are characterized as members of the family ENTEROBACTERIACEAE: The recovery of these species suggests that the CF lung is an ecological niche capable of supporting the growth of a wide variety of bacteria rarely seen in clinical samples. Elucidation of the factors that account for the association between these unusual species and the respiratory tract of CF patients may provide important insights into the pathophysiology of CF infection. Because accurate identification of these organisms in the clinical microbiology laboratory may be problematic, the present study highlights the utility of reference laboratories capable of identifying unusual species recovered from CF sputum.     

The human genome browser at UCSC

As vertebrate genome sequences near completion and research refocuses to their analysis, the issue of effective genome annotation display becomes critical. A mature web tool for rapid and reliable display of any requested portion of the genome at any scale, together with several dozen aligned annotation tracks, is provided at http://genome.ucsc.edu. This browser displays assembly contigs and gaps, mRNA and expressed sequence tag alignments, multiple gene predictions, cross-species homologies, single nucleotide polymorphisms, sequence-tagged sites, radiation hybrid data, transposon repeats, and more as a stack of coregistered tracks. Text and sequence-based searches provide quick and precise access to any region of specific interest. Secondary links from individual features lead to sequence details and supplementary off-site databases. One-half of the annotation tracks are computed at the University of California, Santa Cruz from publicly available sequence data; collaborators worldwide provide the rest. Users can stably add their own custom tracks to the browser for educational or research purposes. The conceptual and technical framework of the browser, its underlying MYSQL database, and overall use are described. The web site currently serves over 50,000 pages per day to over 3000 different users.     

Influence of resistance to antidepressant pharmacotherapy on short-term response to electroconvulsive therapy

BACKGROUND: Few studies assessing the influence of resistance to antidepressant pharmacotherapy on the response to subsequent electroconvulsive therapy (ECT) are found in the literature. Results are somewhat conflicting and may not be applicable to the population of depressed patients in The Netherlands. The aim of this study is to assess the influence of medication resistance on the short-term response to ECT in a population of severely depressed inpatients in The Netherlands, where ECT is an exceptional treatment, often used as a final treatment option. METHODS: We reviewed the records of 41 consecutive inpatients with major depression according to DSM-III-R criteria and rated each patients' antidepressant pharmacotherapy prior to ECT. We examined the extent to which medication resistance was related to short-term response to ECT. RESULTS: When a reduction of at least 50% on the Hamilton Rating Scale for Depression (HRSD) post-ECT compared to pre-ECT (partial remission) is used as response criterion, medication resistant patients and patients without established medication resistance were equally likely to respond to subsequent ECT. When a post-ECT HRSD score < or = 7 (full remission) is used as response criterion, medication resistant patients were less likely to respond to subsequent ECT (8/29=27.6%) than patients who did not receive adequate antidepressant pharmacotherapy prior to ECT (6/12=50.0%), although the difference in response rate was not statistically significant. LIMITATIONS: This study has a retrospective nature and a relatively small sample size. CONCLUSION: Antidepressant medication resistance does not seem to have an influence on the short-term response to subsequent ECT. However, when the number of patients achieving full remission is concerned, a substantial percentage of antidepressant medication resistant patients respond to ECT, although their response rate was nearly half compared to that of patients without prior adequate treatment with antidepressants. This difference in response rate was not statistically significant. ECT seems to be an effective treatment for both patients with and without prior adequate treatment with antidepressants in this Dutch population.     

Clinical,biochemical, and genetic features of four patients with short‐chain enoyl‐CoA hydratase (ECHS1) deficiency

Short‐chain enoyl‐CoA hydratase (SCEH or ECHS1) deficiency is a rare inborn error of metabolism caused by biallelic mutations in the gene ECHS1 (OMIM 602292). Clinical presentation includes infantile‐onset severe developmental delay, regression, seizures, elevated lactate, and brain MRI abnormalities consistent with Leigh syndrome (LS). Characteristic abnormal biochemical findings are secondary to dysfunction of valine metabolism. We describe four patients from two consanguineous families (one Pakistani and one Irish Traveler), who presented in infancy with LS. Urine organic acid analysis by GC/MS showed increased levels of erythro‐2,3‐dihydroxy‐2‐methylbutyrate and 3‐methylglutaconate (3‐MGC). Increased urine excretion of methacrylyl‐CoA and acryloyl‐CoA related metabolites analyzed by LC‐MS/MS, were suggestive of SCEH deficiency; this was confirmed in patient fibroblasts. Both families were shown to harbor homozygous pathogenic variants in the ECHS1 gene; a c.476A > G (p.Gln159Arg) ECHS1variant in the Pakistani family and a c.538A > G, p.(Thr180Ala) ECHS1 variant in the Irish Traveler family. The c.538A > G, p.(Thr180Ala) ECHS1 variant was postulated to represent a Canadian founder mutation, but we present SNP genotyping data to support Irish ancestry of this variant with a haplotype common to the previously reported Canadian patients and our Irish Traveler family. The presence of detectable erythro‐2,3‐dihydroxy‐2‐methylbutyrate is a nonspecific marker on urine organic acid analysis but this finding, together with increased excretion of 3‐MGC, elevated plasma lactate, and normal acylcarnitine profile in patients with a Leigh‐like presentation should prompt consideration of a diagnosis of SCEH deficiency and genetic analysis of ECHS1. ECHS1 deficiency can be added to the list of conditions with 3‐MGA.     

Clinical spectrum of KIAA2022 pathogenic variants in males: Case report of two boys with KIAA2022 pathogenic variants and review of the literature

KIAA2022 is an X‐linked intellectual disability (XLID) syndrome affecting males more severely than females. Few males with KIAA2022 variants and XLID have been reported. We present a clinical report of two unrelated males, with two nonsense KIAA2022 pathogenic variants, with profound intellectual disabilities, limited language development, strikingly similar autistic behavior, delay in motor milestones, and postnatal growth restriction. Patient 1, 19‐years‐old, has long ears, deeply set eyes with keratoconus, strabismus, a narrow forehead, anteverted nares, café‐au‐lait spots, macroglossia, thick vermilion of the upper and lower lips, and prognathism. He has gastroesophageal reflux, constipation with delayed rectosigmoid colonic transit time, difficulty regulating temperature, several musculoskeletal issues, and a history of one grand mal seizure. Patient 2, 10‐years‐old, has mild dysmorphic features, therapy resistant vomiting with diminished motility of the stomach, mild constipation, cortical visual impairment with intermittent strabismus, axial hypotonia, difficulty regulating temperature, and cutaneous mastocytosis. Genetic testing identified KIAA2022 variant c.652C > T(p.Arg218*) in Patient 1, and a novel nonsense de novo variant c.2707G > T(p.Glu903*) in Patient 2. We also summarized features of all reported males with KIAA2022 variants to date. This report not only adds knowledge of a novel pathogenic variant to the KIAA2022 variant database, but also likely extends the spectrum by describing novel dysmorphic features and medical conditions including macroglossia, café‐au‐lait spots, keratoconus, severe cutaneous mastocytosis, and motility problems of the GI tract, which may help physicians involved in the care of patients with this syndrome. Lastly, we describe the power of social media in bringing families with rare medical conditions together.     

Modelling foetal growth in a bi-ethnic sample: results from the Born in Bradford (BiB) birth cohort

Background: Attempts to explain the increased risk for metabolic disorders observed in South Asians have focused on the “South Asian” phenotype at birth and subsequent post-natal growth, with little research on pre-natal growth.

Aim: To identify whether divergent growth patterns exist for foetal weight, head (HC) and abdominal circumferences (AC) in a sample of Pakistani and White British foetuses.

Subjects and methods: Models were based on 5553 (weight), 5154 (HC) and 5099 (AC) foetuses from the Born in Bradford birth cohort. Fractional polynomials and mixed effects models were employed to determine growth patterns from ～15 weeks of gestation-birth.

Results: Pakistani foetuses were significantly smaller and lighter as early as 20 weeks. However, there was no ethnic difference in the growth patterns of weight and HC. For AC, Pakistani foetuses displayed a trend for reduced growth in the final trimester.

Conclusion: As the pattern of weight and HC growth was not significantly different during the period under investigation, the mechanism culminating in the reduced Pakistani size at birth may act earlier in gestation. Reduced AC growth in Pakistanis may represent reduced growth of the visceral organs, with consequences for post-natal liver metabolism and renal function.