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1.
AIDS Behav ; 26(7): 2363-2375, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35061117

RESUMO

Sexual minority men (SMM) in Nigeria have been disproportionately affected by HIV. Pre-exposure prophylaxis (PrEP) reduces risk for HIV acquisition among SMM by over 90%. The current study investigated the association between demographics, socioeconomic marginalization, sexual health and willingness to use long-acting injectable (LAI-) PrEP and preferences for other PrEP modalities in a sample of HIV-negative SMM in Nigeria. Between March and June 2019, SMM residing in Abuja, Delta, Lagos, and Plateau completed a quantitative survey. To examine willingness to use LAI-PrEP and PrEP modality preferences, multivariable binomial and multinomial logistic regression models were fit. We found that 88% were willing to use LAI-PrEP and 44% preferred LAI-PrEP to other PrEP modalities. Participants who reported interest in LAI-PrEP were more likely to be single, engage in inconsistent condom use, and report having a primary care provider. Compared to participants who preferred daily oral PrEP, participants who preferred other PrEP modalities had higher odds of having some university education/university degree or higher and reporting low financial hardship. It is imperative that SMM in Nigeria are prioritized for access to new HIV prevention interventions, as they bear a disproportionate burden of HIV and are especially vulnerable to HIV infection.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Nigéria/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde
2.
J Antimicrob Chemother ; 76(3): 710-717, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33294914

RESUMO

BACKGROUND: Treatment options are limited for TB/HIV-coinfected children who require PI-based ART. Rifabutin is the preferred rifamycin for adults on PIs, but the one study evaluating rifabutin with PIs among children was stopped early due to severe neutropenia. METHODS: We evaluated rifabutin safety and plasma pharmacokinetics among coinfected children 3-15 years of age receiving rifabutin 2.5 mg/kg daily with standard doses of lopinavir/ritonavir. The AUC0-24 at 2, 4 and 8 weeks after rifabutin initiation was described using intensive sampling and non-compartmental analysis. Clinical and laboratory toxicities were intensively monitored at 12 visits throughout the study. RESULTS: Among 15 children with median (IQR) age 13.1 (10.9-14.0) years and weight 25.5 (22.3-30.5) kg, the median (IQR) rifabutin AUC0-24 was 5.21 (4.38-6.60) µg·h/mL. Four participants had AUC0-24 below 3.8 µg·h/mL (a target for the population average exposure) at week 2 and all had AUC0-24 higher than 3.8 µg·h/mL at the 4 and 8 week visits. Of 506 laboratory evaluations during rifabutin, grade 3 and grade 4 abnormalities occurred in 16 (3%) and 2 (0.4%) instances, respectively, involving 9 (60%) children. Specifically, grade 3 (n = 4) and grade 4 (n = 1) neutropenia resolved without treatment interruption or clinical sequelae in all patients. One child died at week 4 of HIV-related complications. CONCLUSIONS: In children, rifabutin 2.5 mg/kg daily achieved AUC0-24 comparable to adults and favourable HIV and TB treatment outcomes were observed. Severe neutropenia was relatively uncommon and improved with ongoing rifabutin therapy. These data support the use of rifabutin for TB/HIV-coinfected children who require lopinavir/ritonavir.


Assuntos
Coinfecção , Infecções por HIV , Tuberculose , Adolescente , Adulto , Criança , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Lopinavir/efeitos adversos , Rifabutina/efeitos adversos , Ritonavir/efeitos adversos , Tuberculose/complicações , Tuberculose/tratamento farmacológico
3.
BMC Microbiol ; 20(1): 17, 2020 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959116

RESUMO

BACKGROUND: We identified a HIV-positive cohort in virologic failure (VF) who re-suppressed without drug switch. We characterized their drug resistance mutations (DRM) and adherence profiles to learn how to better manage HIV drug resistance. A retrospective cohort study utilizing clinical data and stored samples. Patients received ART at three Nigerian treatment centres. Plasma samples stored when they were in VF were genotyped. RESULT: Of 126 patients with samples available, 57 were successfully genotyped. From ART initiation, the proportion of patients with adherence ≥90% increased steadily from 54% at first high viral load (VL) to 67% at confirmed VF, and 81% at time of re-suppressed VL. Sixteen (28%) patients had at least one DRM. Forty-six (81%) patients had full susceptibility to the three drugs in their first-line (1 L) regimen. Thirteen (23%) were resistant to at least one antiretroviral drug but three were resistant to drugs not used in Nigeria. Ten patients had resistance to their 1 L drug(s) and six were fully susceptible to the three drugs in the recommended second-line regimen. CONCLUSION: This cohort had little drug resistance mutations. We conclude that if adherence is not assured, patients could exhibit virologic failure without having developed mutations associated with drug resistance.


Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Mutação , Adulto , Feminino , Genótipo , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Humanos , Masculino , Nigéria , Cooperação do Paciente , Estudos Retrospectivos , Carga Viral
4.
J Antimicrob Chemother ; 74(9): 2707-2715, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31139825

RESUMO

BACKGROUND: TB is the leading cause of death among HIV-infected children, yet treatment options for those who require PI-based ART are suboptimal. Rifabutin is the preferred rifamycin for adults on PI-based ART; only one study has evaluated its use among children on PIs and two of six children developed treatment-limiting neutropenia. METHODS: Since 2009, rifabutin has been available for HIV/TB-coinfected children requiring PI-based ART in the Harvard/APIN programme in Nigeria. We retrospectively analysed laboratory and clinical toxicities at baseline and during rifabutin therapy, and examined HIV/TB outcomes. RESULTS: Between 2009 and 2015, 48 children received rifabutin-containing TB therapy with PI (lopinavir/ritonavir)-based ART: 50% were female with a median (IQR) baseline age of 1.7 (0.9-5.0) years and a median (IQR) CD4+ cell percentage of 15% (9%-25%); 52% were ART experienced. Eighty-five percent completed the 6 month rifabutin course with resolution of TB symptoms and 79% were retained in care at 12 months. Adverse events (grade 1-4) were more common at baseline (27%) than during rifabutin treatment (15%) (P = 0.006). Absolute neutrophil count was lower during rifabutin compared with baseline (median = 1762 versus 2976 cells/mm3, respectively), but only one instance (2%) of grade 3 neutropenia occurred during rifabutin treatment. CONCLUSIONS: With clinical and laboratory monitoring, our data suggest that rifabutin is a safe option for TB therapy among children on PI-based ART. By contrast with the only other study of this combination in children, severe neutropenia was rare. Furthermore, outcomes from this cohort suggest that rifabutin is effective, and a novel option for children who require PI-based ART. Additional study of rifabutin plus PIs in children is urgently needed.


Assuntos
Antibióticos Antituberculose/uso terapêutico , Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Lopinavir/uso terapêutico , Rifabutina/uso terapêutico , Ritonavir/uso terapêutico , Tuberculose/tratamento farmacológico , Antibióticos Antituberculose/administração & dosagem , Antibióticos Antituberculose/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Biomarcadores , Interações Medicamentosas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Infecções por HIV/virologia , Humanos , Masculino , Estudos Retrospectivos , Rifabutina/administração & dosagem , Rifabutina/efeitos adversos , Resultado do Tratamento , Tuberculose/microbiologia
5.
J Virol ; 92(7)2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29321308

RESUMO

Recent studies on the role of T cells in Zika virus (ZIKV) infection have shown that T cell responses to Asian ZIKV infection are important for protection, and that previous dengue virus (DENV) exposure amplifies the protective T cell response to Asian ZIKV. Human T cell responses to African ZIKV infection, however, remain unexplored. Here, we utilized the modified anthrax toxin delivery system to develop a flavivirus enzyme-linked immunosorbent spot (ELISPOT) assay. Using human ZIKV and DENV samples from Senegal, West Africa, our results demonstrate specific and cross-reactive T cell responses to nonstructural protein 3 (NS3). Specifically, we found that T cell responses to NS3 protease are ZIKV and DENV specific, but responses to NS3 helicase are cross-reactive. Sequential sample analyses revealed immune responses sustained many years after infection. These results have important implications for African ZIKV/DENV vaccine development, as well as for potential flavivirus diagnostics based on T cell responses.IMPORTANCE The recent Zika virus (ZIKV) epidemic in Latin America and the associated congenital microcephaly and Guillain-Barré syndrome have raised questions as to why we have not recognized these distinct clinical diseases in Africa. The human immunologic response to ZIKV and related flaviviruses in Africa represents a research gap that may shed light on the mechanisms contributing to protection. The goal of our study was to develop an inexpensive assay to detect and characterize the T cell response to African ZIKV and DENV. Our data show long-term specific and cross-reactive human immune responses against African ZIKV and DENV, suggesting the usefulness of a diagnostic based on the T cell response. Additionally, we show that prior flavivirus exposure influences the magnitude of the T cell response. The identification of immune responses to African ZIKV and DENV is of relevance to vaccine development.


Assuntos
Vírus da Dengue/imunologia , Dengue/imunologia , Proteínas não Estruturais Virais/imunologia , Infecção por Zika virus/imunologia , Zika virus/imunologia , África Ocidental/epidemiologia , Reações Cruzadas , Dengue/diagnóstico , Dengue/epidemiologia , ELISPOT , Feminino , Humanos , RNA Helicases/imunologia , Serina Endopeptidases/imunologia , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia
6.
J Infect Dis ; 215(10): 1546-1550, 2017 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-28398562

RESUMO

First identified in 1947 in Uganda, Zika virus (ZIKV) has remained largely unstudied until the recent outbreak in Latin America. This study aimed to measure the prevalence of ZIKV in febrile patients in Senegal and Nigeria in samples collected from 1992 to 2016. The seroprevalence of ZIKV was 6.2% based on ZIKV immunoglobulin M and negative for dengue reactivity. ZIKV envelope was amplified from 4 samples. Phylogenetic analysis showed that the ZIKVs belonged to the African lineage, grouping with either the Nigerian or MR766 sublineages. This study provides evidence that ZIKV has been silently circulating in West Africa for 2 decades.


Assuntos
Infecção por Zika virus/epidemiologia , Infecção por Zika virus/virologia , Zika virus/genética , Adolescente , Adulto , Idoso , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Lactente , Malária/complicações , Malária/epidemiologia , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , RNA Viral/sangue , RNA Viral/genética , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Senegal/epidemiologia , Estudos Soroepidemiológicos , Adulto Jovem , Zika virus/classificação , Infecção por Zika virus/complicações , Infecção por Zika virus/transmissão
9.
AIDS Res Ther ; 14(1): 58, 2017 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-29029637

RESUMO

BACKGROUND: For patients on antiretroviral therapy (ART), treatment interruptions can impact patient outcomes and result in the accumulation of drug resistance mutations leading to virologic failure. There are minimal published data on the impact of an ART stock shortage on development of drug resistance mutations (DRMs). In this report, we evaluate data from patients enrolled in the Government of Nigeria National ART Program that were receiving treatment at the time of a national drug shortage in late 2003. METHODS: We conducted a cross-sectional evaluation of samples collected between December 2004 and August 2005 from ART patients in virologic failure that either had a treatment interruption or did not during the late 2003 drug shortage period at the Jos University Teaching Hospital (JUTH). Plasma virus was genotyped, sequence data were edited and analyzed, and mutation profiles were categorized to evaluate predicted drug susceptibility. Data were analyzed to examine factors associated with development of resistance mutations. A genotypic sensitivity score to the alternate recommended regimen was computed to assess drug susceptibility if regimens were changed. RESULTS: A total of 56 patients were included in this evaluation (28 interrupted, 28 uninterrupted). Patients in the interrupted group had more DRMs than those in the uninterrupted group (p < 0.001); interrupted patients were more likely than uninterrupted patients to have one or more TAM-2 mutations (57.1% interrupted vs. 21.3% uninterrupted; p = 0.04). There was a statistically significant difference in resistance to both d4T (53.7% interrupted vs. 17.9 uninterrupted; p = 0.011) and AZT (64.3% interrupted vs. 25.0% uninterrupted; p = 0.003) by drug interruption status. Examining genotypic sensitivity scores, we found that 67.9% of the interrupted patients, as compared to 25.0% of the uninterrupted patients, did not have full susceptibility to one drug in the regimen to which guidelines recommended they be switched (p = 0.001). DISCUSSION: In this small observational study, we found evidence of a difference in resistance profiles and ART susceptibility between those that were stocked-out of drug versus those that were not. We believe that these data are relevant for many other low- and middle-income countries (LMIC) that also experienced similar ART shortages as they rapidly scaled up their national programs.


Assuntos
Fármacos Anti-HIV/provisão & distribuição , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Adulto , Estudos Transversais , Feminino , HIV-1/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria , Resultado do Tratamento , Carga Viral/efeitos dos fármacos
10.
Clin Infect Dis ; 62(4): 512-8, 2016 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-26561532

RESUMO

BACKGROUND: Despite sparse efficacy data, tenofovir-emtricitabine or tenofovir-lamivudine plus nevirapine is used in many resource-constrained settings. METHODS: This retrospective cohort study included patients initiating nevirapine-based antiretroviral therapy (ART) with either tenofovir-emtricitabine or lamivudine (tenofovir group) or zidovudine-lamivudine (zidovudine group). Clinical, virologic, and immunologic evaluations were performed at baseline and every 6 months. Virologic failure was defined as 2 consecutive human immunodeficiency virus (HIV)-RNA values >1000 copies/mL. Patients were included from ART initiation until time of failure, regimen switch, discontinuation, or last HIV-RNA measurement. Cox proportional hazards regression was used to model factors influencing time to failure. Bias due to dependent censoring was investigated via inverse probability weighted pooled logistic regression. RESULTS: A total of 5547 patients were evaluated; 1484 (26.8%) were in the tenofovir group and 4063 (73.2%) were in the zidovudine group. In the adjusted model, tenofovir regimen (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.21-1.79) and higher baseline log10 HIV-RNA (HR, 1.15; 95% CI, 1.03-1.28) were associated with virologic failure. Higher baseline log10 CD4+ cell count (HR, 0.50; 95% CI, .40-.63) and increasing age (HR, 0.98; 95% CI, .97-.99) decreased the risk of virologic failure. Inverse probability weighting results were consistent with the primary analysis. CONCLUSIONS: Compared with zidovudine-lamivudine, the use of tenofovir-lamivudine or emtricitabine in combination with nevirapine was a strong predictor of virologic failure in our cohort, which was not explained by other risk factors or criteria for regimen selection.


Assuntos
Antirretrovirais/administração & dosagem , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , Nevirapina/administração & dosagem , Tenofovir/administração & dosagem , Zidovudina/administração & dosagem , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Carga Viral , Adulto Jovem
11.
J Infect Dis ; 207 Suppl 2: S70-7, 2013 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-23687292

RESUMO

BACKGROUND: The World Health Organization Antiretroviral Treatment Guidelines recommend phasing-out stavudine because of its risk of long-term toxicity. There are two mutational pathways of stavudine resistance with different implications for zidovudine and tenofovir cross-resistance, the primary candidates for replacing stavudine. However, because resistance testing is rarely available in resource-limited settings, it is critical to identify the cross-resistance patterns associated with first-line stavudine failure. METHODS: We analyzed HIV-1 resistance mutations following first-line stavudine failure from 35 publications comprising 1,825 individuals. We also assessed the influence of concomitant nevirapine vs. efavirenz, therapy duration, and HIV-1 subtype on the proportions of mutations associated with zidovudine vs. tenofovir cross-resistance. RESULTS: Mutations with preferential zidovudine activity, K65R or K70E, occurred in 5.3% of individuals. Mutations with preferential tenofovir activity, ≥ two thymidine analog mutations (TAMs) or Q151M, occurred in 22% of individuals. Nevirapine increased the risk of TAMs, K65R, and Q151M. Longer therapy increased the risk of TAMs and Q151M but not K65R. Subtype C and CRF01_AE increased the risk of K65R, but only CRF01_AE increased the risk of K65R without Q151M. CONCLUSIONS: Regardless of concomitant nevirapine vs. efavirenz, therapy duration, or subtype, tenofovir was more likely than zidovudine to retain antiviral activity following first-line d4T therapy.


Assuntos
Antirretrovirais/administração & dosagem , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , HIV-1/genética , RNA Viral/análise , Inibidores da Transcriptase Reversa/administração & dosagem , Adenina/administração & dosagem , Adenina/análogos & derivados , Alcinos , Benzoxazinas/administração & dosagem , Ciclopropanos , Bases de Dados Factuais , Farmacorresistência Viral/genética , Quimioterapia Combinada , Genótipo , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Humanos , Mutação de Sentido Incorreto , Nevirapina/administração & dosagem , Organofosfonatos/administração & dosagem , RNA Viral/genética , Estavudina/administração & dosagem , Tenofovir , Zidovudina/administração & dosagem
12.
AIDS ; 38(3): 309-316, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37916471

RESUMO

BACKGROUND: Compared with HIV-1 infection, HIV-2 infection is associated with a slower progression to AIDS. Understanding the persistence of HIV-2 infection might inform the mechanisms responsible for differences in the pathogenicity of HIV-2 versus HIV-1. METHODS: In this study, we analyzed the genetic composition of the proviral reservoir in archived blood samples collected from 13 untreated HIV-2-infected adults from Senegal. We used single-genome, near-full-length individual proviral sequencing (FLIP-Seq) to assess the relative frequency of intact and defective proviruses. RESULTS: Ten out of 13 (77%) study participants demonstrated virologic suppression (<90 HIV RNA copies/ml) while the remaining 3 (23%) had detectable HIV RNA. We obtained 363 proviral sequences from peripheral blood mononuclear cells (PBMCs) from the 13 study participants. Within these sequences, 342 (94%) defective proviruses were detected. Twenty-one (6%) intact proviruses were detected from three study participants, with one study participant displaying a large clone consisting of 16 genome-intact sequences. CONCLUSION: This data suggests that similar to HIV-1 infection, the proviral landscape of HIV-2 is dominated by defective proviruses.


Assuntos
Infecções por HIV , Provírus , Adulto , Humanos , Provírus/genética , HIV-2/genética , Leucócitos Mononucleares , Carga Viral , RNA , Linfócitos T CD4-Positivos
13.
Diagn Microbiol Infect Dis ; 109(3): 116282, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38663335

RESUMO

The effect of freeze-thaw on SARS-CoV-2 viral viability is not well established. We isolated virus from 31 split clinical samples cultured fresh or after a 7- or 17/18-day freeze. We found that freeze-thaw did not significantly affect viral culture isolation. Therefore, frozen samples may be used to assess SARS-CoV-2 infectiousness.


Assuntos
COVID-19 , Congelamento , SARS-CoV-2 , Humanos , COVID-19/virologia , Manejo de Espécimes/métodos , Viabilidade Microbiana , Cultura de Vírus/métodos , Criopreservação
14.
Open Forum Infect Dis ; 11(3): ofae092, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38464491

RESUMO

We determined pretreatment and acquired human immunodeficiency virus (HIV) drug resistance among children with HIV type 1 (HIV-1) in Jos, Nigeria. The majority (71%) of those who failed first-line antiretroviral therapy were on a nevirapine-containing regimen. The prevalence of pretreatment (48%) and acquired (76%) HIV drug resistance mutations was high in our study. Wider access to HIV drug resistance testing after treatment failure is necessary to optimize second-line treatment options among children with HIV in Nigeria.

15.
Int J Infect Dis ; 139: 92-100, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38056689

RESUMO

OBJECTIVES: Chikungunya virus (CHIKV), a reemerging global public health concern, which causes acute febrile illness, rash, and arthralgia and may affect both mothers and infants during pregnancy. Mother-to-child transmission (MTCT) of CHIKV in Africa remains understudied. METHODS: Our cohort study screened 1006 pregnant women with a Zika/dengue/CHIKV rapid test at two clinics in Nigeria between 2019 and 2022. Women who tested positive for the rapid test were followed through their pregnancy and their infants were observed for 6 months, with a subset tested by reverse transcription-polymerase chain reaction (RT-PCR) and neutralization, to investigate seropositivity rates and MTCT of CHIKV. RESULTS: Of the 1006, 119 tested positive for CHIKV immunoglobulin (Ig)M, of which 36 underwent detailed laboratory tests. While none of the IgM reactive samples were RT-PCR positive, 14 symptomatic pregnant women were confirmed by CHIKV neutralization test. Twelve babies were followed with eight normal and four abnormal outcomes, including stillbirth, cleft lip/palate with microcephaly, preterm delivery, polydactyly with sepsis, and jaundice. CHIKV IgM testing identified three possible antepartum transmissions. CONCLUSION: In Nigeria, we found significant CHIKV infection in pregnancy and possible CHIKV antepartum transmission associated with birth abnormalities.


Assuntos
Febre de Chikungunya , Vírus Chikungunya , Fenda Labial , Fissura Palatina , Dengue , Infecção por Zika virus , Zika virus , Lactente , Recém-Nascido , Humanos , Feminino , Gravidez , Vírus Chikungunya/genética , Gestantes , Estudos de Coortes , Nigéria/epidemiologia , Fenda Labial/complicações , Transmissão Vertical de Doenças Infecciosas , Fissura Palatina/complicações , Febre de Chikungunya/diagnóstico , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/complicações , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia , Natimorto , Imunoglobulina M
16.
Emerg Microbes Infect ; 13(1): 2301666, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38163752

RESUMO

In the past few decades, several emerging/re-emerging mosquito-borne flaviviruses have resulted in disease outbreaks of public health concern in the tropics and subtropics. Due to cross-reactivities of antibodies recognizing the envelope protein of different flaviviruses, serosurveillance remains a challenge. Previously we reported that anti-premembrane (prM) antibody can discriminate between three flavivirus infections by Western blot analysis. In this study, we aimed to develop a serological assay that can discriminate infection or exposure with flaviviruses from four serocomplexes, including dengue (DENV), Zika (ZIKV), West Nile (WNV) and yellow fever (YFV) viruses, and explore its application for serosurveillance in flavivirus-endemic countries. We employed Western blot analysis including antigens of six flaviviruses (DENV1, 2 and 4, WNV, ZIKV and YFV) from four serocomplexes. We tested serum samples from YF-17D vaccinees, and from DENV, ZIKV and WNV panels that had been confirmed by RT-PCR or by neutralization assays. The overall sensitivity/specificity of anti-prM antibodies for DENV, ZIKV, WNV, and YFV infections/exposure were 91.7%/96.4%, 91.7%/99.2%, 88.9%/98.3%, and 91.3%/92.5%, respectively. When testing 48 samples from Brazil, we identified multiple flavivirus infections/exposure including DENV and ZIKV, DENV and YFV, and DENV, ZIKV and YFV. When testing 50 samples from the Philippines, we detected DENV, ZIKV, and DENV and ZIKV infections with a ZIKV seroprevalence rate of 10%, which was consistent with reports of low-level circulation of ZIKV in Asia. Together, these findings suggest that anti-prM antibody is a flavivirus serocomplex-specific marker and can be employed to delineate four flavivirus infections/exposure in regions where multiple flaviviruses co-circulate.


Assuntos
Vírus da Dengue , Dengue , Infecções por Flavivirus , Flavivirus , Infecção por Zika virus , Zika virus , Animais , Flavivirus/genética , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia , Zika virus/genética , Vírus da Dengue/genética , Estudos Soroepidemiológicos , Anticorpos Antivirais , Infecções por Flavivirus/diagnóstico , Infecções por Flavivirus/epidemiologia , Vírus da Febre Amarela , Reações Cruzadas
17.
Arch Gynecol Obstet ; 288(6): 1365-70, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23700253

RESUMO

BACKGROUND: Cervical cancer is strongly linked to high-risk human papillomavirus (HR-HPV) and is typically preceded by cytological abnormalities. Less is known in patients with normal cervical cytology (NCC). We investigated the epidemiology of HR-HPV among HIV-infected women with NCC. METHODOLOGY: We conducted a cross-sectional study between January and June 2011 among HIV-infected women with NCC at an adult HIV clinic in Jos, Nigeria. Cervical sampling and analysis for HR-HPV by hybrid capture (HC2) with signal amplification was done to determine presence of one or more of the following HR-HPV types: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 or 68. Epidemiologic factors associated with HR-HPV were determined using bivariate statistics and multivariate logistic regression. RESULTS: We evaluated 103 HIV-infected women with Pap cytology. The median age of the women was 32 years (range 21-49). Ninety-seven (94.2%) had NCC. Cervical samples for HR-HPV DNA testing were available from 89/97 (91.8%) of the HIV-infected women with NCC. Of the 89 women with cervical samples for HR-HPV DNA testing, 40 (44.9%) had detectable HR-HPV by HC2 giving a HR-HPV prevalence of 44.9% (95% CI 33.9-55.5%). Age < 30 years was associated with HR-HPV (OR 2.69 [95% CI 1.05-6.91, p = 0.039]) while history of previous abortion showed an inverse association with HR-HPV (OR 0.33[95% CI 0.15-0.94, p = 0.039]). CONCLUSION: The prevalence of HR-HPV is seemingly high among HIV-infected women with NCC in our clinical setting. These data provide support for further investigation of the clinical implications of positive HR-HPV among HIV-infected women with NCC report in cervical cancer prevention programs in Nigeria.


Assuntos
Infecções por HIV/complicações , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Adulto , Idoso , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Testes de DNA para Papilomavírus Humano , Humanos , Pessoa de Meia-Idade , Nigéria/epidemiologia , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Projetos Piloto , Gravidez , Prevalência , Fatores Socioeconômicos , Inquéritos e Questionários , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/patologia
18.
Afr J Reprod Health ; 17(4 Spec No): 138-45, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24689325

RESUMO

HIV testing during labour and delivery provides a critical opportunity for administering appropriate interventions to prevent mother-to-child-transmission (PMTCT). We studied current HIV rates and infection trend among women tested during delivery following scale-up of PMTCT and antiretroviral therapy (ART) programs in Jos, north central Nigeria. Between March 2010 and January 2012, provider-initiated HIV testing and counselling was offered in early labour. Women were recruited from a government tertiary health centre, a faith-based hospital, and a private health centre. Those who previously tested HIV negative during antenatal care (ANC) and those who presented at the labour ward with unknown HIV status were tested. A total of 944 subjects (727 re-tested for HIV infection and 217 with unknown HIV status) were enrolled and tested during labour. The HIV incidence and sero-conversion rates during pregnancy among women who repeated HIV testing at delivery was 1.7 per 100 person-years of observation (pyo) and 0.6% (4/727), respectively, while the rate among those who tested for the first time in labour was 1.8% (4/217). Women who accessed ANC were older and had achieved a higher educational status than those who did not access ANC. A 3- to 5-fold decline in HIV incidence and prevalence rates was detected among women tested at delivery when compared to data from a report in 2004. It is not certain whether the decline in maternal HIV infection is due to the major state-wide scale-up of PMTCT and HIV treatment programs. A broader and purposefully designed evaluation study would be required to verify observed occurrence.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Fatores Etários , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/transmissão , Humanos , Programas de Rastreamento , Nigéria/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Cuidado Pré-Natal , Fatores Socioeconômicos
19.
Clin Microbiol Infect ; 29(1): 94-100, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35863629

RESUMO

OBJECTIVE: To define the relationship of SARS-CoV-2 antigen, viral load determined by RT-qPCR, and viral culture detection. Presumptively, viral culture can provide a surrogate measure for infectivity of sampled individuals and thereby inform how and where to most appropriately deploy antigen and nucleic acid amplification-based diagnostic testing modalities. METHODS: We compared the antigen testing results from three lateral flow and one microfluidics assay to viral culture detection and viral load determination performed in parallel in up to 189 nasopharyngeal swab samples positive for SARS-CoV-2. Sample viral loads, determined by RT-qPCR, were distributed across the range of viral load values observed in our testing population. RESULTS: Antigen tests were predictive of viral culture positivity, with the LumiraDx microfluidics method showing enhanced sensitivity (90%; 95% CI 83-94%) compared with the BD Veritor (74%, 95% CI 65-81%), CareStart (74%, 95% CI 65-81%) and Oscar Corona (74%, 95% CI 65-82%) lateral flow antigen tests. Antigen and viral culture positivity were also highly correlated with sample viral load, with areas under the receiver operator characteristic curves of 0.94 to 0.97 and 0.92, respectively. A viral load threshold of 100 000 copies/mL was 95% sensitive (95% CI, 90-98%) and 72% specific (95% CI, 60-81%) for predicting viral culture positivity. Adjusting for sample dilution inherent in our study design, sensitivities of antigen tests were ≥95% for detection of viral culture positive samples with viral loads >106 genome copies/mL, although specificity of antigen testing was imperfect. DISCUSSION: Antigen testing results and viral culture were correlated. For culture positive samples, the sensitivity of antigen tests was high at high viral loads that are likely associated with significant infectivity. Therefore, our data provides support for use of antigen testing in ruling out infectivity at the time of sampling.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Carga Viral , COVID-19/diagnóstico , Testes Sorológicos , Reação em Cadeia da Polimerase , Sensibilidade e Especificidade
20.
J Clin Virol Plus ; 3(3): 100156, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37388808

RESUMO

Background: Early evidence suggested that the impact of the COVID-19 pandemic was less severe in Africa compared to other parts of the world. However, more recent studies indicate higher SARS-CoV-2 infection and COVID-19 mortality rates on the continent than previously documented. Research is needed to better understand SARS-CoV-2 infection and immunity in Africa. Methods: In early 2021, we studied the immune responses in healthcare workers (HCWs) at Lagos University Teaching Hospital (n = 134) and Oxford-AstraZeneca COVID-19 vaccine recipients from the general population (n = 116) across five local government areas (LGAs) in Lagos State, Nigeria. Western blots were used to simultaneously detect SARS-CoV-2 spike and nucleocapsid (N) antibodies (n = 250), and stimulation of peripheral blood mononuclear cells with N followed by an IFN-γ ELISA was used to examine T cell responses (n = 114). Results: Antibody data demonstrated high SARS-CoV-2 seroprevalence of 72·4% (97/134) in HCWs and 60·3% (70/116) in the general population. Antibodies directed to only SARS-CoV-2 N, suggesting pre-existing coronavirus immunity, were seen in 9·7% (13/134) of HCWs and 15·5% (18/116) of the general population. T cell responses against SARS-CoV-2 N (n = 114) were robust in detecting exposure to the virus, demonstrating 87·5% sensitivity and 92·9% specificity in a subset of control samples tested. T cell responses against SARS-CoV-2 N were also observed in 83.3% of individuals with N-only antibodies, further suggesting that prior non-SARS-CoV-2 coronavirus infection may provide cellular immunity to SARS-CoV-2. Conclusions: These results have important implications for understanding the paradoxically high SARS-CoV-2 infection with low mortality rate in Africa and supports the need to better understand the implications of SARS-CoV-2 cellular immunity.

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