Diagnosis and Genotyping of Coxiella burnetii Endocarditis in a Patient with Prosthetic Pulmonary Valve Replacement Using Next-Generation Sequencing of Plasma Microbial Cell-Free DNA.
Open forum infectious diseases
2019; 6 (6): ofz242
Combining Phylogenetic and Network Approaches to Identify HIV-1 Transmission Links in San Mateo County, California.
Frontiers in microbiology
2018; 9: 2799
Determining the causative etiology of culture-negative endocarditis can be challenging. We performed next-generation sequencing of plasma microbial cell-free DNA to facilitate rapid diagnosis and genotyping of Coxiella burnetii in a patient with culture-negative endocarditis of a prosthetic pulmonary valve, enabling early targeted treatment prior to valve replacement surgery.
View details for DOI 10.1093/ofid/ofz242
View details for PubMedID 31249846
View details for PubMedCentralID PMC6580995
Placental Malaria and Mother-to-Child Transmission of Human Immunodeficiency Virus-1 in Rural Rwanda
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
2011; 85 (2): 202-206
The HIV epidemic in San Mateo County is sustained by multiple overlapping risk groups and is an important hub for HIV transmission in northern California. Limited access to care has led historically to delayed clinical presentation, higher rates of opportunistic infections, and an increased prevalence of antiretroviral drug resistance. The virologic and clinical consequences of treatment within these multiple ethnic and behavioral groups are poorly understood, highlighting the need for efficient surveillance strategies that are able to elucidate transmission networks and drug resistance patterns. We obtained sequence data from a group of 316 HIV-positive individuals in the San Mateo AIDS Program over a 14-year period and integrated epidemiologic, phylogenetic, and network approaches to characterize transmission clusters, risk factors and drug resistance. Drug resistance mutations were identified using the Stanford HIV Drug Resistance Database. A maximum likelihood tree was inferred in RAxML and subjected to clustering analysis in Cluster Picker. Network analysis using pairwise genetic distances was performed in HIV-TRACE. Participants were primarily male (60%), white Hispanics and non-Hispanics (32%) and African American (20.6%). The most frequent behavior risk factor was male-male sex (33.5%), followed by heterosexual (23.4%) and injection drug use (9.5%). Nearly all sequences were subtype B (96%) with subtypes A, C, and CRF01_AE also observed. Sequences from 65% of participants had at least one drug resistance mutation. Clustered transmissions included a higher number of women when compared to non-clustered individuals and were more likely to include heterosexual or people who inject drugs (PWID). Detailed analysis of the largest network (N = 47) suggested that PWID played a central role in overall transmission of HIV-1 as well as bridging men who have sex with men (MSM) transmission with heterosexual/PWID among primarily African American men. Combined phylogenetic and network analysis of HIV sequence data identified several overlapping risk factors in the epidemic, including MSM, heterosexual and PWID transmission with a disproportionate impact on African Americans and a high prevalence of drug resistance.
View details for PubMedID 30574123
Viral Sequence Analysis from HIV-Infected Mothers and Infants: Molecular Evolution, Diversity, and Risk Factors for Mother-To-Child Transmission
CLINICS IN PERINATOLOGY
2010; 37 (4): 739-?
We conducted a nested case-control study of placental malaria (PM) and mother-to-child transmission (MTCT) of human immunodeficiency virus-1 (HIV-1) within a prospective cohort of 627 mother-infant pairs followed from October 1989 until April 1994 in rural Rwanda. Sixty stored placentas were examined for PM and other placental pathology, comparing 20 HIV-infected mother-infant (perinatal transmitter) pairs, 20 HIV-uninfected pairs, and 20 HIV-infected mothers who did not transmit to their infant perinatally. Of 60 placentas examined, 45% showed evidence of PM. Placental malaria was associated with increased risk of MTCT of HIV-1 (adjusted odds ratio [aOR] = 6.3; 95% confidence interval [CI] = 1.4-29.1), especially among primigravidae (aOR = 12.0; 95% CI = 1.0-150; P < 0.05). Before antiretroviral therapy or prophylaxis, PM was associated with early infant HIV infection among rural Rwandan women living in a hyper-endemic malaria region. Primigravidae, among whom malaria tends to be most severe, may be at higher risk.
View details for DOI 10.4269/ajtmh.2011.10-0589
View details for Web of Science ID 000293613000004
View details for PubMedID 21813835
View details for PubMedCentralID PMC3144813
Environmental Enrichment Reduces Neuronal Intranuclear Inclusion Load But Has No Effect on Messenger RNA Expression in a Mouse Model of Huntington Disease
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
2010; 69 (8): 817-827
Great progress has been made in understanding the pathogenesis, treatment, and transmission of HIV and the factors influencing the risk of mother-to-child transmission (MTCT). Many questions regarding the molecular evolution and genetic diversity of HIV in the context of MTCT remain unanswered. Further research to identify the selective factors governing which variants are transmitted, how the compartmentalization of HIV in different cells and tissues contributes to transmission, and the influence of host immunity, viral diversity, and recombination on MTCT may provide insight into new prevention strategies and the development of an effective HIV vaccine.
View details for DOI 10.1016/j.clp.2010.08.003
View details for Web of Science ID 000285485400005
View details for PubMedID 21078447
View details for PubMedCentralID PMC3175486
Detection of HIV-1 in Saliva: Implications for Case-Identification, Clinical Monitoring and Surveillance for Drug Resistance.
The open virology journal
2010; 4: 88-93
Huntington disease (HD) is a fatal neurodegenerative disease with no effective treatment. In the R6/1 mouse model of HD, environmental enrichment delays the neurologic phenotype onset and prevents cerebral volume loss by unknown molecular mechanisms. We examined the effects of environmental enrichment on well-characterized neuropathological parameters in a mouse model of HD. We found a trend toward preservation of downregulated neurotransmitter receptors in striatum of environmentally enriched mice and assessed possible enrichment-related modifications in gene expression using microarrays. We observed similar gene expression changes in R6/1 and R6/2 transgenic mice but found no specific changes in enrichment-related microarray expression profiles in either transgenic or wild-type mice. Furthermore, specific corrections in transprotein-induced transcriptional dysregulation in R6/1 mice were not detected by microarray profiling. However, gene-specific analyses suggested that long-term environmental enrichment may beneficially modulate gene expression dysregulation. Finally, environmental enrichment significantly decreased neuronal intranuclear inclusion load, despite unaffected transgene expression levels. Thus, the therapeutic effects of environmental enrichment likely contribute to decreasing aggregated polyglutamine protein levels without exerting strong effects on gene expression.
View details for DOI 10.1097/NEN.0b013e3181ea167f
View details for Web of Science ID 000280478800005
View details for PubMedID 20613636
Evolution and molecular epidemiology of subtype C HIV-1 in Zimbabwe
2009; 23 (18): 2523-2532
Saliva tests that detect antibodies are used to diagnose HIV infection. The goal of this study was to determine whether saliva could be used for nucleic acid-based tests to measure HIV-1 virus load (VL) and detect drug resistance.69 HIV infected individuals provided 5-10 ml of saliva and blood samples. Viral RNA was isolated from saliva and dried blood spots using the Nuclisens extraction. Saliva VL was measured using a modified Amplicor assay, and genotyping was performed using an in-house RT-PCR/sequencing protocol. Plasma VLs were obtained from concurrently drawn clinical tests.Thirty-six of 47 (77%) plasma viremic patients had measurable saliva HIV-1 RNA. Paired plasma and saliva HIV RNA levels were significantly correlated (Spearman's correlation = .6532, p<.0001), but saliva VL was typically lower. Three of 22 patients with undetectable plasma VL (<50 copies/ml) had detectable saliva HIV RNA. Eleven of 30 patients with undetectable saliva RNA had detectable plasma HIV-1 RNA. Comparison of the protease and reverse transcriptase gene sequences from paired saliva and plasma of 20 patients showed less than 1% difference overall, and few resistance-related amino acid differencesMost patients with plasma virus >50 copies/mL had detectable saliva HIV RNA, and the genotypic data was highly concordant between saliva and plasma. In patients with high levels of plasma HIV RNA, saliva might be useful in identifying viremia and evaluating drug resistance.
View details for DOI 10.2174/1874357901004010088
View details for PubMedID 21673840
View details for PubMedCentralID PMC3111737
To investigate the origins and evolutionary history of subtype C HIV-1 in Zimbabwe in a context of regional conflict and migration.HIV-1C pol sequence datasets were generated from four sequential cohorts of antenatal women in Harare, Zimbabwe sampled over 15 years (1991-2006).One hundred and seventy-seven HIV-1C pol sequences were obtained from four successive cohorts in Zimbabwe. Maximum-likelihood methods were used to explore phylogenetic relationships between Zimbabwean HIV-1C sequences and subtype C strains from other regions. A Bayesian coalescent-based framework was used to estimate evolutionary parameters for HIV-1C in Zimbabwe, including origin and demographic growth patterns.Zimbabwe HIV-1C pol demonstrated increasing sequence divergence over the 15-year period. Nearly all Zimbabwe sequences clustered phylogenetically with subtype C strains from neighboring countries. Bayesian evolutionary analysis indicated a most recent common ancestor date of 1973 with three epidemic growth phases: an initial, slow phase (1970s) followed by exponential growth (1980s), and a linearly expanding epidemic to the present. Bayesian trees provided evidence for multiple HIV-1C introductions into Zimbabwe during 1979-1981, corresponding with Zimbabwean national independence following a period of socio-political instability.The Zimbabwean HIV-1C epidemic likely originated from multiple introductions in the late 1970s and grew exponentially during the 1980s, corresponding to changing political boundaries and rapid population influx from neighboring countries. The timing and phylogenetic clustering of the Zimbabwean sequences is consistent with an origin in southern Africa and subsequent expansion. HIV-1 sequence data contain important epidemiological information, which can help focus treatment and prevention strategies in light of more recent political volatility in Zimbabwe.
View details for DOI 10.1097/QAD.0b013e3283320ef3
View details for Web of Science ID 000272135800017
View details for PubMedID 19770693
View details for PubMedCentralID PMC2923658