Fever and Ulcerative Skin Lesions in a Patient Referred for Altered Mental Status: Clinical and Microbiological Diagnosis of Ulceroglandular Tularemia

Background: Tularemia is a devastating disease that affects multiple organ systems and can have several different presentations. In its most frequent form—that of ulceroglandular tularemia—a detailed history and physical examination can enable a physician to make the diagnosis clinically, leading to the prompt initiation of the appropriate antibiotic treatment. Detailed Case Description: A 63-year-old man was brought by ambulance to the emergency department for an evaluation of an altered mental status noted by his psychiatrist at a telehealth appointment. A physical examination revealed a fever and two ulcerative lesions with a central eschar on his left leg (of which the patient was unaware) with ipsilateral tender inguinal lymphadenopathy. When asked, the patient recalled visiting Martha’s Vineyard and having removed ticks from his legs. Gentamicin was administered on the clinical suspicion of ulceroglandular tularemia. Blood and skin lesion cultures grew Gram-negative rods, which were confirmed to be Francisella tularensis on hospital day eight, and the patient fully recovered. Conclusion: This case highlights the importance of clinician perception of altered mental status as a key alarm sign, the necessity of a thorough physical exam independent of the chief compliant in the emergency department, and the essential role of pattern recognition by front-line providers for the appropriate management of uncommon but serious infections such as tularemia

Gag-p6 Tsg101 Binding Site Duplications in Maternal–Infant HIV Infection

Prevalence and patterns of HIV p6 duplications in HIV-1 mother-to-baby transmission are examined. Resistance genotyping was performed in a multisite U.S. study of antiretroviral resistance in vertical transmission. Sequence data were used in secondary analyses of HIV genetic variation. Two hundred sixty HIV viral RNA samples from HIV-infected pregnant women and their infants were analyzed with a commercial resistance genotyping kit. Chromatograms were examined for variability in the 3\u27 region of gag. From 103 mother-baby sets, 190 samples gave readable p6 sequence. Of 103 mother-baby sets, 20 (19%) showed duplication of between 3 and 12 codons ending at the PTAPP motif of p6. When maternal p6 duplication was present and the p6 sequence was available from both maternal and infant isolates, all (seven of seven) infants had p6 duplications, but two cases showed discordancies between maternal and infant sequences. The prevalence of p6 duplication varied among geographical sites, ranging from 4 of 43 families (9%, Puerto Rico and New York sites) to 16 of 60 families (27%, Massachusetts, Texas, and Illinois). The presence of p6 duplication was not associated with differences in transmission, viral load, or disease progression in the infants, but showed a trend toward association with lower maternal CD4 count. Substantial p6 variation data are generated by resistance genotyping. PTAP duplication is prevalent in this group of HIV-infected women and infants. The duplication is efficiently transmitted from mother to infant, is present at variable prevalence at different geographic sites, and shows no clear association with vertical transmission risks

Time Trends for HIV-1 Antiretroviral Resistance Among Antiretroviral-Experienced and Naive Pregnant Women in New York City During 1991 to Early 2001

Time trends in the prevalence of drug resistance to antiretroviral therapy (ART) in pregnant women have not been studied. Treatment and prophylactic efficacy could be compromised by drug-resistant HIV strains. We conducted a repeated cross-sectional study of antiretroviral resistance mutations to nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) and of major mutations to protease inhibitors (PIs) in virus isolates from 300 HIV-infected pregnant women in New York City from 1991 to early 2001. The overall prevalence of mutations for NRTIs from 1991 to early 2001 was higher for ART-experienced (25.6% [95% confidence interval (CI): 19.1% to 32.1%]) than ART-naive (8.6% [95% CI: 3.7% to 13.4%]) mothers (P \u3c 0.002). For NNRTIs, the overall prevalence of mutations was somewhat higher among ART-experienced (5.8% [95% CI: 2.3% to 9.3%]) versus ART-naive (1.6% [95% CI: 0% to 3.7%]) women (P = 0.06), and increased over time for ART-naive women (0%-7.4%; P = 0.03) and ART-experienced women (0%-19.4%; P = 0.0002). The prevalence of PI-associated mutations was also higher overall among ART-experienced mothers (5.8% [95% CI: 2.3% to 9.3%] vs. 1.6% [95% CI: 0% to 3.7%]; P = 0.06), with increases over time seen for ART-naive women (0%-7.4%; P = 0.03) and ART-experienced women (0%-16.1%; P = 0.0008). The increasing prevalence of drug resistance in pregnant women, including those who are drug-naive, underscores the necessity for resistance testing to guide treatment to achieve suppression of the mother\u27s virus

Antiretroviral Resistance in Viral Isolates from HIV-1-transmitting Mothers and Their Infants

OBJECTIVE: To characterize concordance of resistance mutations to antiretroviral drugs (ART) in mother-infant pairs. DESIGN: Case series of HIV-transmitting mothers and infants in the Women and Infants Transmission Study, where delivery occurred between April 1994 and December 1999. METHODS: Reverse transcriptase and protease genes were sequenced in stored viral isolates from 32 mother-infant pairs. Mutations were coded as pure mutants where only mutant virus was detected or as mixtures where a mixed mutant/wild-type population was identified. ART resistance mutations were compared for concordance between mothers and their infants. RESULTS: Maternal mutations associated with resistance to nucleoside reverse transcriptase inhibitor (NRTI) and minor protease inhibitor (PI) drugs were typically concordant with that of infant, while those associated with non-nucleoside reverse transcriptase inhibitors (NNRTI) and major PI drugs were not. Of five NRTI-associated maternal mutations observed, three pure mutants corresponded with mutant in the infant, while two wild-type-predominant mixtures corresponded with infant wild type. The only NNRTI-associated mutation observed, K103N, was not transmitted, nor were the two major PI-associated mutations, L90M and V82I/V. Transmission of minor PI-associated mutations was consistent with the sole observed or dominant variant for 20 of 21 mutations. CONCLUSIONS: For NRTI- and minor PI-associated mutations, transmission was consistent with relative quantity of variants in maternal virus. However, where NNRTI- and major PI-associated mutations were present in three cases, they were not transmitted, even where only mutant virus was detectable in maternal isolates. This is consistent with evidence of loss of transmission with resistance to NNRTI and PI drugs

Identification and Functional Evaluation of Cellular and Viral Factors Involved in the Alteration of Nuclear Architecture during Herpes Simplex Virus 1 Infection

Herpes simplex virus 1 (HSV-1) replicates in the nucleus of host cells and radically alters nuclear architecture as part of its replication process. Replication compartments (RCs) form, and host chromatin is marginalized. Chromatin is later dispersed, and RCs spread past it to reach the nuclear edge. Using a lamin A-green fluorescent protein fusion, we provide direct evidence that the nuclear lamina is disrupted during HSV-1 infection and that the UL31 and UL34 proteins are required for this. We show nuclear expansion from 8 h to 24 h postinfection and place chromatin rearrangement and disruption of the lamina in the context of this global change in nuclear architecture. We show HSV-1-induced disruption of the localization of Cdc14B, a cellular protein and component of a putative nucleoskeleton. We also show that UL31 and UL34 are required for nuclear expansion. Studies with inhibitors of globular actin (G-actin) indicate that G-actin plays an essential role in nuclear expansion and chromatin dispersal but not in lamina alterations induced by HSV-1 infection. From analyses of HSV infections under various conditions, we conclude that nuclear expansion and chromatin dispersal are dispensable for optimal replication, while lamina rearrangement is associated with efficient replication

Zidovudine Resistance Phenotype and Risk of Perinatal HIV-1 Transmission in Zidovudine Monotherapy-Treated Mothers With Moderately Advanced Disease

The association of phenotypic zidovudine resistance with perinatal transmission was evaluated in 74 zidovudine-treated mothers enrolled in the Women and Infants Transmission Study through September 1994. Women in the sample had moderately advanced disease, with a median CD4+ cell count of 271/microL and a median plasma HIV-1 RNA level of 39,811 copies/mL. Factors independently associated with zidovudine resistance at delivery (50% inhibitory concentration [IC50], \u3e/=0.1 microM) in multiple logistic regression included prepregnancy zidovudine use, high log plasma HIV-1 RNA level, and low CD4+ cell count. Of 74 mothers, 16 (22%) transmitted HIV-1 to their infants. After adjustment for duration of membrane rupture and CD8+ cell count, zidovudine resistance (IC50 range, 0.01-2.2 microM) was associated with an increased odds of transmission (ORadj, 1.25 per 0.1 microM; 95% confidence interval, 1.01-1.54), suggesting a decreased effect of prenatal zidovudine on preventing transmission in mothers infected with zidovudine-resistant virus. However, when the analysis was limited only to those mothers infected with virus containing zidovudine resistance mutations, no association between phenotypic resistance and transmission remained, indicating that phenotype may not provide significant additional information in predicting transmission where resistance genotype is known