Fatal disseminated Acanthamoeba infection in a liver transplant recipient immunocompromised by combination therapies for graft-versus-host disease.

Immunosuppressed solid organ transplant recipients are at increased risk for acquisition of opportunistic pathogens, with potentially fatal consequences. With the introduction of novel immunosuppressive agents used to prevent organ rejection and to treat the sequelae of transplantation, severity and rates of infection with unusual opportunistic pathogens may increase. Various monoclonal antibodies are now being used in the treatment of severe, acute graft-versus-host disease (GVHD), including rituximab, daclizumab, and alemtuzumab. These therapies, particularly when used in combination and with other traditional forms of immunosuppression, may have profound effects on the immune system. Acanthamoeba species are ubiquitous, free-living protozoa that rarely cause disseminated disease in the immunocompromised host. We report a fatal case of disseminated Acanthamoeba infection with a dramatic cutaneous presentation in a liver transplant recipient severely immunocompromised by sequential standard and novel therapies used to successfully treat life-threatening acute GVHD. This case illustrates the current major limitation of these therapies, discusses the cutaneous findings in disseminated acanthamoebiasis, and highlights the need to maintain vigilance for the presence of unusual infection in patients receiving similar therapeutic regimens.

Integrating tuberculosis and HIV care in rural Rwanda.

SETTING: Rwanda has generalised human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics. The Rwandan Ministry of Health approved a policy on TB-HIV collaborative activities in 2005. The present study is a report on the results of the integrated TB and HIV activities at a rural health care site between July 2005 and June 2006. METHODS: Activities included provider-initiated HIV testing and counselling (PITC) of TB patients and the implementation of a standardised TB screening questionnaire for in-patients on medical wards and HIV-infected out-patients. RESULTS: Of a total 259 TB patients registered, 87% with unknown HIV status or who were HIV-negative accepted PITC. Overall, 48% (125/259) of TB patients were HIV-infected. The proportion of TB patients ever tested for HIV increased from 82% (138/169) in 2004-2005 to 93% (240/259) in 2005-2006 (P < 0.001). Of the 770 in-patients screened for TB, 162 (21%) tested positive, of whom 53 (33%) were diagnosed with TB; 39 (76%) of these were HIV co-infected. Three hundred out-patients with HIV were screened for TB; 80 (27%) tested positive, of whom 11 (14%) were diagnosed with TB. DISCUSSION: Activities integrating TB and HIV were feasible in a rural health care setting. PITC was successful in TB patients and unrecognised TB was common, particularly among HIV-infected in-patients.

Results of a tuberculosis-specific IFN-gamma assay in children at high risk for tuberculosis infection.

The specificity of the tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection (LTBI) is adversely affected by bacille Calmette-Guérin (BCG) vaccination and infection with non-tuberculous mycobacteria. Interferon-gamma release assays (IGRAs) using TB-specific antigens promise higher specificity. We compared a new IGRA and TST in 184 schoolchildren at high risk for LTBI. The IGRA and TST were positive in 33.2% and 43.5% of the children, respectively (P < 0.001). If studies confirm that this difference is due to higher specificity of this IGRA, it may have an important role to play in the diagnosis of LTBI and identification of children at true risk for TB.

Linkage disequilibrium analysis of G-olf alpha (GNAL) in bipolar affective disorder.

This study examines G-olf alpha as a possible candidate gene for susceptibility to bipolar affective disorder (BPAD) using the Transmission Disequilibrium Test (TDT). G-olf alpha, which encodes a subunit of a G-protein involved in intracellular signaling, maps within a region of chromosome 18 that has been implicated by two different linkage studies as a potential site of BPAD susceptibility loci. The expression pattern of G-olf alpha in the brain, its coupling to dopamine receptors, and the effects of lithium salts on G-proteins all support G-olf alpha as a candidate gene for BPAD. Our study population consisted of 106 probands and sibs with bipolar I disorder, with a median age-at-onset of 21.5 years ascertained from the United States. There was no evidence of linkage disequilibrium between BPAD and any of the observed G-olf alpha alleles in our sample. Division of families based on sex of the transmitting parent did not significantly change the results. This sample had good power (78%) to detect linkage disequilibrium with alleles conferring a relative risk equal to that estimated for the putative 18p locus (2.58). Our results do not support a major role for G-olf alpha as a susceptibility locus for BPAD in a substantial portion of our sample. Other genes lying near G-olf alpha within the linked region on chromosome 18 cannot be excluded by our data. This study illustrates the use of the TDT in evaluating candidate genes within linked chromosome regions.