Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-26 (of 26 Records) |
Query Trace: Nieto A[original query] |
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Reply to Rasmussen and Ringwald, "Continued Low Efficacy of Artemether-Lumefantrine in Angola?"
Dimbu PR , Horth R , Cândido ALM , Ferreira CM , Caquece F , Garcia LEA , André K , Pembele G , Jandondo D , Bondo BJ , Nieto Andrade B , Labuda S , Ponce de León G , Kelley J , Patel D , Svigel SS , Talundzic E , Lucchi N , Morais JFM , Fortes F , Martins JF , Pluciński MM . Antimicrob Agents Chemother 12/28/2021 65 (6) We thank Rasmussen and Ringwald for further highlighting the importance of routine monitoring of antimalarial drug efficacy in sub-Saharan Africa, including Angola (1). Longitudinal monitoring is critical to identify potential new, persistent, and/or expanding foci of parasite resistance to available drugs. In 3 of the last 4 rounds, artemether-lumefantrine (AL) was estimated to have an efficacy of <90% at one of the three sentinel sites in Angola. To our knowledge, in sub-Saharan Africa, only Angola and Burkina Faso (2) have shown AL efficacy of <90% across multiple therapeutic efficacy study (TES) rounds. Thus, we chose a title to highlight this persistent concern. | | We concur that the significance of the high rates of day 2 slide positivity in Lunda Sul Province is not fully known, and as pointed out, there may be various explanations for this finding. Measuring drug levels is resource intensive and not feasible every year, but this could help rule out underdosing in future studies. However, we believe our study procedures, as described in this and previous studies, are robust and thus make systematic underdosing unlikely. We have always strictly adhered to WHO guidelines, including hemoglobin criteria and analysis of day 1 severe cases, to inform our classifications. |
Therapeutic response to four artemisinin-based combination therapies in Angola, 2021
Dimbu PR , Labuda S , Ferreira CM , Caquece F , André K , Pembele G , Pode D , João MF , Pelenda VM , Nieto Andrade B , Horton B , Kennedy C , Svigel SS , Zhou Z , Morais JFM , Rosário Jd , Fortes F , Martins JF , Plucinski MM . Antimicrob Agents Chemother 2024 e0152523 Monitoring antimalarial efficacy is important to detect the emergence of parasite drug resistance. Angola conducts in vivo therapeutic efficacy studies (TESs) every 2 years in its fixed sentinel sites in Benguela, Lunda Sul, and Zaire provinces. Children with uncomplicated Plasmodium falciparum malaria were treated with artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), dihydroartemisinin-piperaquine (DP), or artesunate-pyronaridine (ASPY) and followed for 28 (AL and ASAQ) or 42 days (DP and ASPY) to assess clinical and parasitological response to treatment. Two drugs were sequentially assessed in each site in February-July 2021. The primary indicator was the Kaplan-Meier estimate of the PCR-corrected efficacy at the end of the follow-up period. A total of 622 patients were enrolled in the study and 590 (95%) participants reached a study endpoint. By day 3, ≥98% of participants were slide-negative in all study sites and arms. After PCR correction, day 28 AL efficacy was 88.0% (95% CI: 82%-95%) in Zaire and 94.7% (95% CI: 90%-99%) in Lunda Sul. For ASAQ, day 28 efficacy was 92.0% (95% CI: 87%-98%) in Zaire and 100% in Lunda Sul. Corrected day 42 efficacy was 99.6% (95% CI: 99%-100%) for ASPY and 98.3% (95% CI: 96%-100%) for DP in Benguela. High day 3 clearance rates suggest no clinical evidence of artemisinin resistance. This was the fourth of five rounds of TES in Angola showing a corrected AL efficacy <90% in a site. For Zaire, AL has had an efficacy <90% in 2013, 2015, and 2021. ASAQ, DP, and ASPY are appropriate choices as artemisinin-based combination therapies in Angola. |
Comparing genomic variant identification protocols for Candida auris
Li X , Muñoz JF , Gade L , Argimon S , Bougnoux ME , Bowers JR , Chow NA , Cuesta I , Farrer RA , Maufrais C , Monroy-Nieto J , Pradhan D , Uehling J , Vu D , Yeats CA , Aanensen DM , d'Enfert C , Engelthaler DM , Eyre DW , Fisher MC , Hagen F , Meyer W , Singh G , Alastruey-Izquierdo A , Litvintseva AP , Cuomo CA . Microb Genom 2023 9 (4) Genomic analyses are widely applied to epidemiological, population genetic and experimental studies of pathogenic fungi. A wide range of methods are employed to carry out these analyses, typically without including controls that gauge the accuracy of variant prediction. The importance of tracking outbreaks at a global scale has raised the urgency of establishing high-accuracy pipelines that generate consistent results between research groups. To evaluate currently employed methods for whole-genome variant detection and elaborate best practices for fungal pathogens, we compared how 14 independent variant calling pipelines performed across 35 Candida auris isolates from 4 distinct clades and evaluated the performance of variant calling, single-nucleotide polymorphism (SNP) counts and phylogenetic inference results. Although these pipelines used different variant callers and filtering criteria, we found high overall agreement of SNPs from each pipeline. This concordance correlated with site quality, as SNPs discovered by a few pipelines tended to show lower mapping quality scores and depth of coverage than those recovered by all pipelines. We observed that the major differences between pipelines were due to variation in read trimming strategies, SNP calling methods and parameters, and downstream filtration criteria. We calculated specificity and sensitivity for each pipeline by aligning three isolates with chromosomal level assemblies and found that the GATK-based pipelines were well balanced between these metrics. Selection of trimming methods had a greater impact on SAMtools-based pipelines than those using GATK. Phylogenetic trees inferred by each pipeline showed high consistency at the clade level, but there was more variability between isolates from a single outbreak, with pipelines that used more stringent cutoffs having lower resolution. This project generated two truth datasets useful for routine benchmarking of C. auris variant calling, a consensus VCF of genotypes discovered by 10 or more pipelines across these 35 diverse isolates and variants for 2 samples identified from whole-genome alignments. This study provides a foundation for evaluating SNP calling pipelines and developing best practices for future fungal genomic studies. |
Molecular Markers of Sulfadoxine-Pyrimethamine Resistance in Samples from Children with Uncomplicated Plasmodium falciparum at Three Sites in Angola in 2019.
Rosillo SR , Dimbu PR , Cândido ALM , Oh JM , Ferreira CM , Nieto Andrade B , Labuda S , Horth R , Kelley J , Morais JFM , Fortes F , Martins JF , Talundzic E , Pluciński MM . Antimicrob Agents Chemother 2023 67 (4) e0160122 Sulfadoxine-pyrimethamine (SP) is used for prevention of malaria in pregnant women in Angola. We sequenced the Plasmodium falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes, implicated in SP resistance, in samples collected during a 2019 study of artemisinin-based combination therapy efficacy in Benguela, Lunda Sul, and Zaire provinces. A total of 90 day 0 and day of failure samples were individually sequenced, while 508 day 0 samples from participants without recurrent parasitemia were pooled after DNA extraction into 61 pools. The N51I, C59R, and S108N pfdhfr mutations and A437G pfdhps mutations were present at high proportions in all provinces (weighted allele frequencies, 62% to 100%). The K540E pfdhps mutation was present at lower proportions (10% to 14%). The A581G pfdhps mutation was only observed in Zaire, at a 4.6% estimated prevalence. The I431V and A613S mutations were also only observed in Zaire, at a prevalence of 2.8% to 2.9%. The most common (27% to 66%) reconstructed haplotype in all three provinces was the canonical quadruple pfdhfr pfdhps mutant. The canonical quintuple mutant was absent in Lunda Sul and Benguela and present in 7.9% of samples in Zaire. A single canonical sextuple (2.6%) mutant was observed in Zaire Province. Proportions of the pfdhps K540E and A581G mutations were well below the World Health Organization thresholds for meaningful SP resistance (prevalence of 95% for K540E and 10% for A581G). Samples from therapeutic efficacy studies represent a convenient source of samples for monitoring SP resistance markers. |
Genomic Epidemiology Linking Nonendemic Coccidioidomycosis to Travel.
Monroy-Nieto J , Gade L , Benedict K , Etienne KA , Litvintseva AP , Bowers JR , Engelthaler DM , Chow NA . Emerg Infect Dis 2023 29 (1) 110-117 Coccidioidomycosis is a fungal infection endemic to hot, arid regions of the western United States, northern Mexico, and parts of Central and South America. Sporadic cases outside these regions are likely travel-associated; alternatively, an infection could be acquired in as-yet unidentified newly endemic locales. A previous study of cases in nonendemic regions with patient self-reported travel history suggested that infections were acquired during travel to endemic regions. We sequenced 19 Coccidioides isolates from patients with known travel histories from that earlier investigation and performed phylogenetic analysis to identify the locations of potential source populations. Our results show that those isolates were phylogenetically linked to Coccidioides subpopulations naturally occurring in 1 of the reported travel locales, confirming that these cases were likely acquired during travel to endemic regions. Our findings demonstrate that genomic analysis is a useful tool for investigating travel-related coccidioidomycosis. |
High Level of Pretreatment and Acquired Human Immunodeficiency Virus Drug Resistance in El Salvador: A Nationally Representative Survey, 2018-2019.
Girón-Callejas A , García-Morales C , Mendizabal-Burastero R , Quezada A , Ruiz L , Arguera N , Sorto S , Nieto AI , Tapia-Trejo D , López-Sánchez DM , Pérez-García M , Cruz L , Andino R , Sajquim E , Juárez SI , Farach N , Ravasi G , Northbrook S , Reyes-Terán G , Ávila-Ríos S . Open Forum Infect Dis 2022 9 (11) ofac580 BACKGROUND: Human immunodeficiency virus drug resistance (HIVDR) can negatively impact the effectiveness of antiretroviral therapy (ART). We aimed to estimate the prevalence of pretreatment HIVDR (PDR) among ART initiators and the prevalence of viral load (VL) suppression and acquired HIVDR among individuals receiving ART for 12 ± 3 months (ADR12) and ≥48 months (ADR48) in El Salvador. METHODS: Nationally representative cross-sectional PDR, ADR12 and ADR48 surveys were conducted among adults with HIV from October 2018 to August 2019, following World Health Organization-recommended methods. Demographic and clinic data and blood specimens were collected. RESULTS: Two hundred sixty participants were enrolled in the PDR survey, 230 in ADR12 and 425 in ADR48. Twenty-seven percent (95% confidence interval [CI], 17.1%-39.9%) of ART initiators had PDR to efavirenz or nevirapine. The prevalence of VL suppression was 88.8% (95% CI, 83.1%-92.8%) in ADR12 and 80.5% (95% CI, 76.6%-84.0%) in ADR48 surveys. Among people with HIV receiving a first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART regimens and with unsuppressed VL, the prevalence of ADR to efavirenz or nevirapine was 72.0% (95% CI, 32.3%-93.3%) and 95.0% (68.5%-99.4%) in the ADR12 and ADR28 surveys, respectively. ADR12 to boosted protease inhibitors (PI/r) or integrase strand transfer inhibitors (INSTIs) was not observed. ADR48 was 1.3% (95% CI, 0.2%-9.6%) and 2.1% (0.3%-13.7%), respectively. CONCLUSIONS: Programmatic improvements in ART delivery are urgently needed in El Salvador to address the high levels of resistance to efavirenz or nevirapine among ART initiators and the low VL suppression prevalence among individuals on treatment. |
Exposure to 1,3-Butadiene in the U.S. Population: National Health and Nutrition Examination Survey 2011-2016
Nieto A , Zhang L , Bhandari D , Zhu W , Blount BC , De Jesús VR . Biomarkers 2021 26 (4) 1-40 1,3-Butadiene is a volatile organic compound with a gasoline-like odor that is primarily used as a monomer in the production of synthetic rubber. The International Agency for Research on Cancer has classified 1,3-butadiene as a human carcinogen. We assessed 1,3-butadiene exposure in the U.S. population by measuring its urinary metabolites N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (34HBMA), N-acetyl-S-(1-hydroxymethyl-2-propenyl)-L-cysteine (1HMPEMA), N-acetyl-S-(2-hydroxy-3-butenyl)-L-cysteine (2HBEMA), and N-acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine (t4HBEMA). Urine samples from the 2011-2016 National Health and Nutrition Examination Survey were analyzed for 1,3-butadiene metabolites using ultrahigh-performance liquid chromatography/tandem mass spectrometry. 34HBMA and t4HBEMA were detected in >96% of the samples; 1HMPEMA and 2HBEMA were detected in 0.66% and 9.84% of the samples, respectively. We used sample-weighted linear regression models to examine the influence of smoking status (using a combination of self-reporting and serum-cotinine data), demographic variables, and diet on biomarker levels. The median t4HBEMA among exclusive smokers (31.5 µg/g creatinine) was higher than in non-users (4.11 µg/g creatinine). Similarly, the median 34HBMA among exclusive smokers (391 µg/g creatinine) was higher than in non-users (296 µg/g creatinine). Furthermore, smoking 1-10, 11-20, and >20 cigarettes per day (CPD) was associated with 475%, 849%, and 1,143% higher t4HBEMA (p < 0.0001), respectively. Additionally, smoking 1-10, 11-20, and >20 CPD was associated with 33%, 44%, and 102% higher 34HBMA (p < 0.0001). These results provide significant baseline data for 1,3-butadiene exposure in the U.S. population, and demonstrate that tobacco smoke is a major exposure source. |
Continued low efficacy of artemether-lumefantrine in Angola, 2019.
Dimbu PR , Horth R , Cândido ALM , Ferreira CM , Caquece F , Garcia LEA , André K , Pembele G , Jandondo D , Bondo BJ , Nieto Andrade B , Labuda S , Ponce de León G , Kelley J , Patel D , Svigel SS , Talundzic E , Lucchi N , Morais JFM , Fortes F , Martins JF , Pluciński MM . Antimicrob Agents Chemother 2020 65 (2) BACKGROUND: Biennial therapeutic efficacy monitoring is a crucial activity for ensuring efficacy of currently used artemisinin-based combination therapy in Angola. METHODS: Children with acute uncomplicated P. falciparum infection in sentinel sites in Benguela, Zaire, and Lunda Sul Provinces were treated with artemether-lumefantrine (AL) or artesunate amodiaquine (ASAQ) and followed for 28 days to assess clinical and parasitological response. Molecular correction was performed using seven microsatellite markers. Samples from treatment failures were genotyped for the pfk13, pfcrt, and pfmdr1 genes. RESULTS: Day 3 clearance rates were ≥95% in all arms. Uncorrected Day-28 Kaplan-Meier efficacy estimates ranged from 84.2 to 90.1% for the AL arms, and 84.7 to 100% for the ASAQ arms. Corrected Day-28 estimates were 87.6% (95% Confidence interval [CI]: 81-95%) for the AL arm in Lunda Sul, 92.2% (95%CI: 87-98%) for AL in Zaire, 95.6% (95%CI: 91-100%) for ASAQ in Zaire, 98.4% (95%CI: 96-100%) for AL in Benguela, and 100% for ASAQ in Benguela and Lunda Sul. All 103 analyzed samples had wildtype pfk13 sequences. The 76T pfcrt allele was found in most (92%, 11/12) ASAQ late failure samples but only 16% (4/25) of AL failure samples. The N86 pfmdr1 allele was found in 97% (34/35) of treatment failures. CONCLUSION: AL efficacy in Lunda Sul was below the 90% World Health Organization threshold, the third time in four rounds that this threshold was crossed for an AL arm in Angola. In contrast, observed ASAQ efficacy has not been below 95% to date in Angola, including this latest round. |
Malaria Risk and Prevention in Asian Migrants to Angola.
Martins JF , Marques C , Nieto-Andrade B , Kelley J , Patel D , Nace D , Herman C , Barratt J , Ponce de Leon G , Talundzic E , Rogier E , Halsey ES , Plucinski MM . Am J Trop Med Hyg 2020 103 (5) 1918-1926 The number of Asian migrants working in sub-Saharan developing countries like Angola has been increasing. Their malaria risk, prevention, and care-seeking practices have not been characterized. A cross-sectional survey was conducted in 733 Chinese and Southeast Asian migrants in Angola. Respondents were interviewed and provided blood samples. Samples were analyzed to detect Plasmodium antigen and characterize host anti-Plasmodium response. Positive samples were genotyped using the pfs47 marker. Most respondents (72%; 95% CI: 68-75) reported using bed nets, but less than 1% reported using chemoprophylaxis. Depending on the assay, 1-4% of respondents had evidence of active malaria infection. By contrast, 55% (95% CI: 52-59) were seropositive for Plasmodium antibodies. Most infections were Plasmodium falciparum, but infection and/or exposure to Plasmodium vivax and Plasmodium malariae was also detected. Seroprevalence by time in Angola showed most exposure occurred locally. One respondent had sufficiently high parasitemia for pfs47 genotyping, which showed that the infection was likely locally acquired despite recent travel to home country. Asian migrants to Angola are at substantial risk of malaria. Employers should consider enhanced malaria prevention programs, including chemoprophylaxis; embassies should encourage prevention practices. Angolan healthcare workers should be aware of high malaria exposure in Asian migrants. |
Rhizopus microsporus infections associated with surgical procedures, Argentina, 2006-2014
Bowers JR , Monroy-Nieto J , Gade L , Travis J , Refojo N , Abrantes R , Santander J , French C , Dignani MC , Hevia AI , Roe CC , Lemmer D , Lockhart SR , Chiller T , Litvintseva AP , Clara L , Engelthaler DM . Emerg Infect Dis 2020 26 (5) 937-944 Rhizopus spp. fungi are ubiquitous in the environment and a rare but substantial cause of infection in immunosuppressed persons and surgery patients. During 2005-2017, an abnormally high number of Rhizopus infections in surgery patients, with no apparent epidemiologic links, were reported in Argentina. To determine the likelihood of a common source of the cluster, we performed whole-genome sequencing on samples collected during 2006-2014. Most isolates were separated by >60 single-nucleotide polymorphisms, and we found no evidence for recombination or nonneutral mutation accumulation; these findings do not support common source or patient-to-patient transmission. Assembled genomes of most isolates were ≈25 Mbp, and multiple isolates had substantially larger assembled genomes (43-51 Mbp), indicative of infections with strain types that underwent genome expansion. Whole-genome sequencing has become an essential tool for studying epidemiology of fungal infections. Less discriminatory techniques may miss true relationships, possibly resulting in inappropriate attribution of point source. |
Progressive vaccinia acquired through zoonotic transmission in a patient with HIV/AIDS, Colombia
Laiton-Donato K , Avila-Robayo P , Paez-Martinez A , Benjumea-Nieto P , Usme-Ciro JA , Pinzon-Narino N , Giraldo I , Torres-Castellanos D , Nakazawa Y , Patel N , Wilkins K , Li Y , Davidson W , Burgado J , Satheshkumar PS , Styczynski A , Mauldin MR , Gracia-Romero M , Petersen BW . Emerg Infect Dis 2020 26 (3) 601-605 In March 2015, a patient in Colombia with HIV/AIDS was hospitalized for disseminated ulcers after milking cows that had vesicular lesions on their udders. Vaccinia virus was detected, and the case met criteria for progressive vaccinia acquired by zoonotic transmission. Adherence to an optimized antiretroviral regimen resulted in recovery. |
Serologic assessment for exposure to spotted fever group rickettsiae in dogs in the Arizona-Sonora border region
Yaglom HD , Nicholson WL , Casal M , Nieto NC , Adams L . Zoonoses Public Health 2018 65 (8) 984-992 Rocky Mountain spotted fever (RMSF) is a severe tick-borne rickettsial illness. In the south-western United States and Mexico, RMSF displays unique epidemiologic and ecologic characteristics, including Rhipicephalus sanguineus sensu lato (brown dog tick) as the primary vector. Expansion and spread of the disease from hyperendemic regions of Arizona or Mexico to new areas is a key public health concern. Dogs are thought to play an important role in the emergence and circulation of R. rickettsii in these regions and are often one of earliest indicators of RMSF presence. A canine serosurvey was conducted in 2015 among owned and stray dogs at rabies clinic and animal shelters in three southern Arizona counties where RMSF had not previously been identified. Of the 217 dogs sampled, 11 (5.1%) tested positive for spotted fever group rickettsia (SFGR) IgG antibodies, with seropositivity ranging from 2.9% to 12.2% across the three counties. Large dogs were significantly more likely than small dogs to have positive titres reactive with R. rickettsii; no additional statistically significant relationships were observed between seropositivity of canine age, sex, neuter or ownership status. In addition, 17 (7.8%) dogs had ticks attached at the time of sampling, and stray dogs were significantly more likely to have ticks present than owned dogs (p < 0.001). All 57 ticks collected were identified as Rh. sanguineus s.l., and four (7%) had DNA evidence of genera-wide Rickettsia species. The results of this project demonstrated canine seroprevalence levels lower than those previously reported from dogs in highly endemic areas, indicating a low risk of SFGR transmission to humans in the southern Arizona border region at this time. Continued surveillance is critical to identify SFGR emergence in new geographic regions and to inform prevention efforts for humans and dogs in those areas. |
Efficacy and safety of artemether-lumefantrine, artesunate-amodiaquine, and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in three provinces in Angola, 2017.
Davlantes E , Dimbu PR , Ferreira CM , Florinda Joao M , Pode D , Felix J , Sanhangala E , Andrade BN , Dos Santos Souza S , Talundzic E , Udhayakumar V , Owens C , Mbounga E , Wiesner L , Halsey ES , Martins JF , Fortes F , Plucinski MM . Malar J 2018 17 (1) 144 BACKGROUND: The Angolan government recommends three artemisinin-based combinations for the treatment of uncomplicated Plasmodium falciparum malaria: artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), and dihydroartemisinin-piperaquine (DP). Due to the threat of emerging anti-malarial drug resistance, it is important to periodically monitor the efficacy of artemisinin-based combination therapy (ACT). This study evaluated these medications' therapeutic efficacy in Benguela, Lunda Sul, and Zaire Provinces. METHODS: Enrollment occurred between March and July 2017. Study participants were children with P. falciparum monoinfection from each provincial capital. Participants received a 3-day course of a quality-assured artemisinin-based combination and were monitored for 28 (AL and ASAQ arms) or 42 days (DP arm). Each ACT was assessed in two provinces. The primary study endpoints were: (1) follow-up without complications and (2) failure to respond to treatment or development of recurrent P. falciparum infection. Parasites from each patient experiencing recurrent infection were genotyped to differentiate new infection from recrudescence of persistent parasitaemia. These parasites were also analysed for molecular markers associated with ACT resistance. RESULTS: Of 608 children enrolled in the study, 540 (89%) reached a primary study endpoint. Parasitaemia was cleared within 3 days of medication administration in all participants, and no early treatment failures were observed. After exclusion of reinfections, the corrected efficacy of AL was 96% (91-100%, 95% confidence interval) in Zaire and 97% (93-100%) in Lunda Sul. The corrected efficacy of ASAQ was 100% (97-100%) in Benguela and 93% (88-99%) in Zaire. The corrected efficacy of DP was 100% (96-100%) in Benguela and 100% in Lunda Sul. No mutations associated with artemisinin resistance were identified in the pfk13 gene in the 38 cases of recurrent P. falciparum infection. All 33 treatment failures in the AL and ASAQ arms carried pfmdr1 or pfcrt mutations associated with lumefantrine and amodiaquine resistance, respectively, on day of failure. CONCLUSIONS: AL, ASAQ, and DP continue to be efficacious against P. falciparum malaria in these provinces of Angola. Rapid parasite clearance and the absence of genetic evidence of artemisinin resistance are consistent with full susceptibility to artemisinin derivatives. Periodic monitoring of in vivo drug efficacy remains a priority routine activity for Angola. |
Tick-Borne Relapsing Fever Outbreak Among a High School Football Team at an Outdoor Education Camping Trip, Arizona, 2014.
Jones JM , Hranac CR , Schumacher M , Horn K , Lee DM , Terriquez J , Engelthaler DM , Peoples M , Corrigan J , Replogle A , Souders N , Komatsu KK , Nieto NC . Am J Trop Med Hyg 2016 95 (3) 546-50 During August 2014, five high school students who had attended an outdoor education camp were hospitalized with a febrile illness, prompting further investigation. Ten total cases of tick-borne relapsing fever (TBRF) were identified-six cases confirmed by culture or visualization of spirochetes on blood smear and four probable cases with compatible symptoms (attack rate: 23%). All patients had slept in the campsite's only cabin. Before the camp, a professional pest control company had rodent proofed the cabin, but no acaricides had been applied. Cabin inspection after the camp found rodents and Ornithodoros ticks, the vector of TBRF. Blood samples from a chipmunk trapped near the cabin and from patients contained Borrelia hermsii with identical gene sequences (100% over 630 base pairs). Health departments in TBRF endemic areas should consider educating cabin owners and pest control companies to apply acaricides during or following rodent proofing, because ticks that lack rodents for a blood meal might feed on humans. |
Notes from the field: tickborne relapsing fever outbreak at an outdoor education camp - Arizona, 2014
Jones JM , Schumacher M , Peoples M , Souders N , Horn K , Fox L , Scott M , Brady S , Weiss J , Komatsu K , Nieto N . MMWR Morb Mortal Wkly Rep 2015 64 (23) 651-652 Tickborne relapsing fever (TBRF) is a bacterial infection characterized by recurring episodes of fever, headache, muscle and joint aches, and nausea. In North America, TBRF primarily is caused by Borrelia hermsii spirochetes transmitted by Ornithodoros hermsii ticks. Once infected, these soft ticks are infectious for life and transmit the spirochete to sleeping humans quickly (possibly within 30 seconds) during short feeds (15-90 minutes). On August 10, 2014, the Coconino County Public Health Services District in Arizona was notified by a local hospital that five high school students who attended the same outdoor education camp had been hospitalized with fever, headache, and myalgias. Hantavirus infection initially was suspected because of reported exposure to rodent droppings, but after detecting spirochetes on peripheral blood smears from all five hospitalized students, TBRF was diagnosed. The camp was instructed to close immediately, and the health department, in collaboration with local university experts, investigated to identify additional cases, determine the cause, and prevent further infections. A total of 11 cases (six confirmed and five probable) were identified. |
Performance and comparison of self-reported STI symptoms among high-risk populations - MSM, sex workers, persons living with HIV/AIDS - in El Salvador
Shah NS , Kim E , de Maria Hernandez Ayala F , Escobar ME , Nieto AI , Kim AA , Paz-Bailey G . Int J STD AIDS 2014 25 (14) 984-91 BACKGROUND: Resource-limited countries have limited laboratory capability and rely on syndromic management to diagnose sexually transmitted infections (STI). We aimed to estimate the sensitivity, specificity and positive predictive value (PPV) of STI syndromic management when used as a screening method within a study setting. METHODS: Men who have sex with men (MSM), female sex workers (FSWs) and people living with HIV/AIDS (PLWHA) participated in a behavioural surveillance study. Data were obtained on demographics, sexual behaviours, STI history and service utilisation. Biological specimens were tested for genital inflammatory infections (Neisseria gonorrhoeae [GC], Chlamydia trachomatis [CT], Mycoplasma genitalium [MG], Trichomonas vaginalis [TV]) and genital ulcerative infection (syphilis and Herpes simplex virus-2). RESULTS: There was a high prevalence of Herpes simplex virus-2 (MSM 48.1%, FSW 82.0% and PLWHA 84.4%). Most participants reported no ulcerative symptoms and the majority of men reported no inflammatory symptoms. Sensitivity and PPV were poor for inflammatory infections among PLWHA and MSM. Sensitivity for FSWs inflammatory infections was 75%. For ulcerative infections, sensitivity was poor, but specificity and PPV were high. CONCLUSIONS: Reliance on self-reported symptoms may not be an effective screening strategy for these populations. STI prevention studies should focus on symptom recognition and consider routine screening and referral for high-risk populations. |
HIV and STI control in El Salvador: results from an integrated behavioural survey among men who have sex with men
Creswell J , Guardado ME , Lee J , Nieto AI , Kim AA , Monterroso E , Paz-Bailey G . Sex Transm Infect 2012 88 (8) 633-8 OBJECTIVE: This cross-sectional study investigates HIV, other sexually transmitted infections (STI), and risk behaviours among men who have sex with men (MSM) in two cities in El Salvador. METHODS: Respondent-driven sampling (RDS) was used to recruit MSM in the cities of San Salvador and San Miguel, El Salvador. Participants responded to questions about HIV risk behaviours; and blood, urine and anal swabs were collected. Blood samples were tested for herpes simplex type 2, syphilis and HIV infection. Urine and anal samples were tested by polymerase chain reaction (PCR) for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and Mycoplasma genitalium. HIV-positive samples were tested with the BED capture enzyme immunoassay to distinguish recent from longstanding HIV infection. We estimated population-adjusted prevalence of behavioural variables, STI and HIV, and identified risk factors for HIV. RESULTS: The final sample included 596 and 195 MSM in San Salvador and San Miguel, respectively. Consistent condom use was low across all partner types as was recent HIV testing. RDS-adjusted HIV prevalence was 10.8% (95% CI 7.4% to 14.7%) in San Salvador, and 8.8% (95% CI 4.2% to 14.5%) in San Miguel. The proportion of recent testing among HIV-positive samples was 20%. Prevalence of any bacterial STI by PRC testing was 12.7% (95% CI 8.2% to 17.5%) in San Salvador, and 9.6% (95% CI 4.9% to 15.4%) in San Miguel. CONCLUSIONS: We found a high prevalence of HIV, high levels of recent infection, and low condom usage. In El Salvador, targeted interventions towards MSM are needed to promote condom use, as well as to diagnose, treat and prevent HIV and other STIs. |
Risk behaviors and STI prevalence among people with HIV in El Salvador
Paz-Bailey G , Shah N , Creswell J , Guardado M , Nieto A , Estrada M , Cedillos R , Pascale J , Monterroso E . Open AIDS J 2012 6 205-12 To date, there are no studies from El Salvador among people with HIV to inform prevention programs. We conducted a study in El Salvador in 2008 among people with HIV using audio computer-assisted interviews on risk behaviors and access to health care. Blood was tested for syphilis and herpes simplex type 2 (HSV-2). Active syphilis was defined as RPR titer ≥1:8. Genital specimens were tested for other sexually transmitted infections (STI) by PCR. We evaluated factors associated with unprotected sex with last stable partner of HIV-negative or unknown status among those reporting a stable partner. A total of 811 HIV-positive individuals participated: 413 men and 398 women. Prevalence of Chlamydia and gonorrhea was low (≤1%), while prevalence of other STI was high: Mycoplasma genitalium (14%), syphilis (15% seropositivity, active syphilis 3%) and HSV-2 (85%). In multivariate analysis, disclosing HIV status to partner (OR 0.2, 95% CI: 0.1-0.3, p<0.001), participation in HIV support groups (OR 0.3, 95% CI: 0.1-0.8, p=0.01), easy access to condoms (OR 0.4, 95% CI: 0.2-0.9, p=0.04) were protective factors for unprotected sex. Reporting a casual partner in the last 12 months (OR 3.6, 95% CI: 1.5-8.5, p=0.004). and having an STI (OR 2.6, 95% CI:1.3-5.5, p=0.02) were associated with an increased odds of unprotected sex. Prevention interventions among HIV-positives in El Salvador should focus on increasing condom access, promoting HIV disclosure and couples testing and reducing the number of partners. The positive role of support groups should be used to enhance behavioral change. |
Correlates of bisexual behaviors among men who have sex with men in El Salvador
Kim EJ , Creswell J , Guardado ME , Shah N , Kim AA , Nieto AI , de Maria Hernandez-Ayala F , Monterroso E , Paz-Bailey G . AIDS Behav 2012 17 (4) 1279-87 Bisexual behaviors may increase transmission pathways of HIV and sexually transmitted infections (STIs) from a higher prevalence group to lower prevalence groups in El Salvador. In 2008, men who have sex with men (MSM) were recruited in San Salvador and San Miguel using respondent driven sampling. Participants were interviewed and tested for HIV and STIs. Sixteen seeds and 797 MSM participated; 34.9% in San Salvador and 58.8% in San Miguel reported bisexual behavior. Bisexual behavior was associated with drug use (adjusted odds ratio (AOR) = 2.57, 95% CI: 1.30-5.06) and insertive anal sex (AOR = 5.45, 95% CI: 3.01-9.87), and inversely associated with having a stable male partner (AOR = 0.47, 95% CI: 0.26-0.84) and disclosing MSM behavior to family (AOR = 0.41, 95% CI: 0.22-0.75). Bisexual behavior was associated with risk behaviors with male and female partners that may be associated with HIV and STI transmission. Bisexual men displayed a distinct identity calling for tailored interventions. |
Social network characteristics and HIV vulnerability among transgender persons in San Salvador: identifying opportunities for HIV prevention strategies
Barrington C , Wejnert C , Guardado ME , Nieto AI , Bailey GP . AIDS Behav 2012 16 (1) 214-24 The purpose of this study is to improve understanding of HIV vulnerability and opportunities for HIV prevention within the social networks of male-to-female transgender persons in San Salvador, El Salvador. We compare HIV prevalence and behavioral data from a sample of gay-identified men who have sex with men (MSM) (n=279), heterosexual or bisexual identified MSM (n=229) and transgender persons (n=67) recruited using Respondent Driven Sampling. Transgender persons consistently reported higher rates of HIV risk behavior than the rest of the study population and were significantly more likely to be involved in sex work. While transgender persons reported the highest rates of exposure to HIV educational activities they had the lowest levels of HIV-related knowledge. Transgender respondents' social networks were homophilous and efficient at recruiting other transgender persons. Findings suggest that transgender social networks could provide an effective and culturally relevant opportunity for HIV prevention efforts in this vulnerable population. |
Evaluation of two rK39 dipstick tests, direct agglutination test, and indirect fluorescent antibody test for diagnosis of visceral leishmaniasis in a new epidemic site in highland Ethiopia
Canavate C , Herrero M , Nieto J , Cruz I , Chicharro C , Aparicio P , Mulugeta A , Argaw D , Blackstock AJ , Alvar J , Bern C . Am J Trop Med Hyg 2011 84 (1) 102-106 We assessed the performance characteristics of two rK39 immunochromatographic tests, a direct agglutination test (DAT), and an indirect immunofluorescent antibody test (IFAT) in the site of a new epidemic of visceral leishmaniasis (VL) in northwestern Ethiopia. The study population was composed of 179 patients with suspected VL and 67 controls. The sensitivities of Kalazar Detect((R)), DiaMed-IT Leish((R)), DAT, and IFAT in 35 polymerase chain reaction-confirmed VL cases were 94.3%, 91.4%, 91.4%, and 100%, respectively, and the specificities were 98.5%, 94%, 98.5%, and 98.5%, respectively. In a Bayesian latent class analysis of all 246 specimens, the estimated sensitivities were 90.5%, 89%, 88.8%, and 96% for Kalazar Detect((R)), DiaMed-IT Leish((R)), DAT, and IFAT, respectively; DAT showed the highest estimated specificity (97.4%). Both rK39 immunochromatographic tests perform as well as DAT, and are suitable for VL diagnosis in first-level health centers in this area of Ethiopia. |
Human peripheral blood B-cell compartments: A crossroad in B-cell traffic
Perez-Andres M , Paiva B , Nieto WG , Caraux A , Schmitz A , Almeida J , Vogt Jr RF , Marti GE , Rawstron AC , Van Zelm MC , Van Dongen JJ , Johnsen HE , Klein B , Orfao A . Cytometry B Clin Cytom 2010 78 Suppl 1 S47-60 A relatively high number of different subsets of B-cells are generated through the differentiation of early B-cell precursors into mature B-lymphocytes in the bone marrow (BM) and antigen-triggered maturation of germinal center B-cells into memory B-lymphocytes and plasmablasts in lymphoid tissues. These B-cell subpopulations, which are produced in the BM and lymphoid tissues, recirculate through peripheral blood (PB), into different tissues including mucosa and the BM, where long-living plasma cells produce antibodies. These circulating PB B-cells can be classified according to their maturation stage into i) immature/transitional, ii) naive, and iii) memory B-lymphocytes, and iv) plasmablasts/plasma cells. Additionally, unique subsets of memory B-lymphocytes and plasmablasts/plasma cells can be identified based on their differential expression of unique Ig-heavy chain isotypes (e.g.: IgM, IgD, IgG, IgA). In the present paper, we review recent data reported in the literature about the distribution, immunophenotypic and functional characteristics of these cell subpopulations, as well as their distribution in PB according to age and seasonal changes. Additional information is also provided in this regard based on the study of a population-based cohort of 600 healthy adults aged from 20 to 80 years, recruited in the Salamanca area in western Spain. Detailed knowledge of the distribution and traffic of B-cell subsets through PB mirrors the immune status of an individual subject and it may also contribute to a better understanding of B-cell disorders related to B-cell biology and homeostasis, such as monoclonal B-cell lymphocytosis (MBL). |
Commentary: Comparison of current flow cytometry methods for monoclonal B cell lymphocytosis detection
Nieto WG , Almeida J , Teodosio C , Abbasi F , Allgood SD , Connors F , Rachel JM , Ghia P , Lanasa MC , Rawstron AC , Orfao A , Caporaso NE , Hanson CA , Shim YK , Vogt RF , Marti GE . Cytometry B Clin Cytom 2010 78 Suppl 1 S4-9 Monoclonal B cell lymphocytosis (MBL) is now recognized as the B-lymphocyte analogue of a monoclonal gammopathy of unknown significance. MBL can be the precursor of chronic lymphocytic leukemia or associated with non-Hodgkin's lymphoma. It may be associated with an autoimmune abnormality or be related to aging (immunosenescence). The combination of available new fluorochrome-conjugated monoclonal antibody reagents, multilaser instrumentation, and improved software tools have led to a new level of multicolor analysis of MBL. Presently, several centers, including the University of Salamanca (Spain), Duke University (Durham, NC), Mayo Clinic (Rochester, MN), and the National Cancer Institute (Bethesda, MD) in conjunction with the Genetics and Epidemiology of Familial chronic lymphocytic leukemia Consortium, the Food and Drug Administration (Bethesda, MD), and the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry (Atlanta, GA) in collaboration with Saint Luke's Hospital (Kansas City, MO), the Universita Vita-Salute San Raffaele in Milan (Italy), and Leeds Teaching Hospital (UK) are all actively conducting studies on MBL. This commentary is an updated summary of the current methods used in these centers. It is important to note the diversity of use in reagents, instruments, and methods of analysis. Despite this diversity, there is a consensus in what constitutes the diagnosis of MBL and its subtypes. There is also an emerging consensus on what the next investigative steps should be. |
Comparison of two immunochromatographic assays and the indirect immunofluorescence antibody test for diagnosis of Trypanosoma cruzi infection in dogs in south central Louisiana
Nieto PD , Boughton R , Dorn PL , Steurer F , Raychaudhuri S , Esfandiari J , Goncalves E , Diaz J , Malone JB . Vet Parasitol 2009 165 241-7 Two rapid tests evaluated in dogs considered to be of high risk of infection with the Chagas parasite Trypanosoma cruzi using two immunochromatographic assays: Trypanosoma Detect for canine, InBios, Seattle, WA and CHAGAS STAT-PAK assay, Chembio Diagnostic Systems, Medford, NY, in south central Louisiana. For this purpose a serological survey was carried out in a total of 122 dogs and a serum bank was created. These 122 animals were first tested by IFAT that was used as the standard test. From the serum bank 50 samples were tested using the two rapid Chagas assays and results compared to the standard test IFAT. The serological survey using IFAT showed a prevalence of T. cruzi infection in 22.1% of the tested dogs. In the immunochromatographic assays, 13 and 11 animals were positive on rapid assay: Trypanosoma Detect for canine, InBios and CHAGAS STAT-PAK, Chembio Diagnostic Systems, respectively compared to 11 positive by IFAT. These two immunochromatographic tests have shown high susceptibility and specificity compared to our standard method IFAT. The rapid, easy and accurate screening assays used in conjunction with confirmatory tests, would be an excellent tool for veterinarians to diagnose T. cruzi infection. Early detection of T. cruzi infection may prevent complications through an effective treatment. Greater awareness by veterinarians of the risk, clinical findings, history along with diagnostic methods will contribute greatly to an understanding of the true prevalence of Chagas disease in dogs in Louisiana. |
Risk factors for visceral leishmaniasis in a new epidemic site in Amhara Region, Ethiopia
Bashaye S , Nombela N , Argaw D , Mulugeta A , Herrero M , Nieto J , Chicharro C , Canavate C , Aparicio P , Velez ID , Alvar J , Bern C . Am J Trop Med Hyg 2009 81 (1) 34-9 We conducted a case-control study to evaluate risk factors for visceral leishmaniasis during an epidemic in a previously unaffected district of Ethiopia. We also collected blood and bone marrow specimens from dogs in the outbreak villages. In multivariable analyses of 171 matched case-control pairs, dog ownership, sleeping under an acacia tree during the day, and habitually sleeping outside at night were associated with significantly increased risk. Specimens from 7 (3.8%) dogs were positive by immunofluorescent antibody test (IFAT) and both enzyme-linked immunosorbent assays (ELISAs), whereas Leishmania DNA was detected in 5 (2.8%) bone marrow aspirates (from 3 seropositive and 2 seronegative dogs). Insecticide-treated nets may only protect a portion of those at risk. Further research on the vectors, the role of the dog in the transmission cycle, and the effect of candidate interventions are needed to design the best strategy for control. |
Attenuated strains of influenza A viruses do not induce degradation of RNA polymerase II
Rodriguez A , Perez-Gonzalez A , Hossain MJ , Chen LM , Rolling T , Perez-Brena P , Donis R , Kochs G , Nieto A . J Virol 2009 83 (21) 11166-74 We have previously shown that infection with laboratory-passaged strains of influenza virus causes both specific degradation of the largest subunit of the RNA polymerase II complex (RNAP II) and inhibition of host cell transcription. When infection with natural human and avian isolates belonging to different antigenic subtypes was examined, we observed that all these viruses efficiently induce the proteolytic process. To evaluate if this process is a general feature of non-attenuated viruses, we studied the behavior of the influenza virus strains A/PR8/8/34 (PR8) and the cold-adapted A/Ann Arbor/6/60 (AA), which are currently used as the donor strains for vaccine seeds due to their attenuated phenotype. We have observed that upon infection with these strains, degradation of the RNAP II does not occur. Moreover, by run-off experiments we observe that PR8 has a reduced ability to inhibit cellular mRNA transcription. In addition, a hyper-virulent PR8 (hvPR8) variant that multiplies much faster than standard PR8 (lvPR8) in infected cells and is more virulent in mice than the parental PR8 virus, efficiently induces RNAP II degradation. Studies with reassortant viruses containing defined genome segments of both hvPR8 and lvPR8 indicate that PA and PB2 subunits individually contribute to the ability of influenza virus to degrade the RNAP II. In addition, recently it has been reported that the inclusion of PA or PB2 from hvPR8 in lvPR8 recombinant viruses, highly increases their pathogenicity. Together, the data indicate that the capacity of the influenza virus to degrade RNAP II and inhibit the host-cell transcription machinery is a feature of influenza A viruses that might contribute to their virulence. |
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