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2.
JAC Antimicrob Resist ; 5(3): dlad057, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37206308

RESUMEN

Objectives: C-reactive protein (CRP) and procalcitonin (PCT) are widely used biomarkers in high-income countries. However, evidence for their use in low- and middle-income countries (LMICs) is scant. Because many factors, including rates of endemic disease, comorbidities and genetics, may influence biomarkers' behaviour, we aimed to review available evidence generated in LMICs. Methods: We searched the PubMed database for relevant studies within the last 20 years that originated in regions of interest (Africa, Latin America, Middle East, South Asia or South East Asia), and full-text articles involving diagnosis, prognostication and evaluation of therapeutic response with CRP and/or PCT in adults (n = 88) were reviewed and categorized in 12 predefined focus areas. Results: Overall, results were highly heterogeneous, at times conflicting, and often lacking clinically useful cut-off values. However, most studies demonstrated higher levels of CRP/PCT in patients with bacterial versus other infections. HIV and TB patients had consistently higher levels of CRP/PCT versus controls. In addition, higher CRP/PCT levels at baseline and follow-up in HIV, TB, sepsis and respiratory tract infections were associated with poorer prognosis. Conclusions: Evidence generated from LMIC cohorts suggests that CRP and PCT may have potential to become effective clinical guiding tools particularly in respiratory tract infections, sepsis and HIV/TB. However, more studies are needed to define potential scenarios for use and cost-effectiveness. Consensus across stakeholders regarding target conditions, laboratory standards and cut-off values would support the quality and applicability of future evidence.

3.
BMC Cardiovasc Disord ; 21(1): 486, 2021 10 09.
Artículo en Inglés | MEDLINE | ID: mdl-34627153

RESUMEN

INTRODUCTION: Multi-parameter diagnostic devices can simplify cardiometabolic disease diagnosis. However, existing devices may not be suitable for use in low-resource settings, where the burden of non-communicable diseases is high. Here we describe the development of a target product profile (TPP) for a point-of-care multi-parameter device for detection of biomarkers for cardiovascular disease and metabolic disorders, including diabetes, in primary care settings in low- and middle-income countries (LMICs). METHODS: A draft TPP developed by an expert group was reviewed through an online survey and semi-structured expert interviews to identify device characteristics requiring refinement. The draft TPP included 41 characteristics with minimal and optimal requirements; characteristics with an agreement level for either requirement of ≤ 85% in either the survey or among interviewees were further discussed by the expert group and amended as appropriate. RESULTS: Twenty people responded to the online survey and 18 experts participated in the interviews. Twenty-two characteristics had an agreement level of ≤ 85% in either the online survey or interviews. The final TPP defines the device as intended to be used for basic diagnosis and management of cardiometabolic disorders (lipids, glucose, HbA1c, and creatinine) as minimal requirement, and offering an expanded test menu for wider cardiometabolic disease management as optimal requirement. To be suitable, the device should be intended for level 1 healthcare settings or lower, used by minimally trained healthcare workers and allow testing using self-contained cartridges or strips without the need for additional reagents. Throughput should be one sample at a time in a single or multi-analyte cartridge, or optimally enable testing of several samples and analytes in parallel with random access. CONCLUSION: This TPP will inform developers of cardiometabolic multi-parameter devices for LMIC settings, and will support decision makers in the evaluation of existing and future devices.


Asunto(s)
Análisis Químico de la Sangre/instrumentación , Enfermedades Cardiovasculares/diagnóstico , Diabetes Mellitus/diagnóstico , Síndrome Metabólico/diagnóstico , Sistemas de Atención de Punto , Pruebas en el Punto de Atención , Atención Primaria de Salud , Tiras Reactivas , Biomarcadores/sangre , Glucemia/análisis , Enfermedades Cardiovasculares/sangre , Consenso , Creatinina/sangre , Técnica Delphi , Diabetes Mellitus/sangre , Diseño de Equipo , Hemoglobina Glucada/análisis , Humanos , Lípidos/sangre , Ensayo de Materiales , Síndrome Metabólico/sangre , Valor Predictivo de las Pruebas
4.
PLoS One ; 15(1): e0227773, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31940418

RESUMEN

INTRODUCTION: High quality diagnostic imaging can provide increased diagnostic accuracy and help guide medical decision-making and management, however challenges for radiology in resource-limited settings are numerous. Diagnostic imaging and teleradiology have financial and logistical implications, so evidence of impact is crucial. We sought to test the hypothesis that the implementation of computed radiography with teleradiology consultation support will significantly change diagnoses and treatment plans in a resource limited setting. METHOD: Paired before-after study to determine the therapeutic impact of an add-on diagnostic test. 'Preliminary Plan' and 'Final Plan' forms allowed direct comparison of diagnosis and treatment plans at initial consultation and following radiography and teleradiology. Consecutive consenting patients were included until the sample size (600) was reached. Changes in both diagnosis and treatment plan were analysed in the whole cohort, with sub-analyses of children aged <5 years, and cases of chest radiography. RESULTS: Final analysis included 536 cases. Diagnosis changed following radiography and teleradiology in 62% of cases, and treatment plans changed in 61%. In chest radiography cases, 70% of diagnoses and 62% of treatment plans changed, while in children <5 years 66% of diagnoses and 58% of treatment plans changed. Reduced final treatment plans were most common for exploratory surgery (72% decrease), surgical orthopaedic intervention (62% decrease), and TB treatment (52% decrease), allowing more conservative medical or surgical management in 61 cases. Increased final treatment plans were highest in the orthopaedic and interventional surgery and referral categories. Of 42 cases requiring interventional surgery in the final plan, 26 (62%) were identified only after radiography and teleradiology. 16 additional cases were indicated for orthopaedic surgery, 10 cases required patient transfer, and TB treatment was indicated in 45 cases. A change in the original prescription plan occurred in 41% of 536 cases, with one or more prescriptions stopped in 28% of all cases. CONCLUSION: We found that computed radiography with teleradiology had significant clinical value in this resource-limited setting, with the potential to affect both patient outcomes and treatment costs through providing improved diagnostics and avoiding unnecessary treatments and medications.


Asunto(s)
Radiografía , Telerradiología , Tórax/diagnóstico por imagen , Preescolar , Estudios de Cohortes , República Democrática del Congo , Manejo de la Enfermedad , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Radiografía/métodos , Telerradiología/métodos
5.
BMJ Glob Health ; 4(Suppl 2): e001105, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30815285

RESUMEN

Diagnostics play a central role in the early detection and control of outbreaks and can enable a more nuanced understanding of the disease kinetics and risk factors for the Middle East respiratory syndrome-coronavirus (MERS-CoV), one of the high-priority pathogens identified by the WHO. In this review we identified sources for molecular and serological diagnostic tests used in MERS-CoV detection, case management and outbreak investigations, as well as surveillance for humans and animals (camels), and summarised the performance of currently available tests, diagnostic needs, and associated challenges for diagnostic test development and implementation. A more detailed understanding of the kinetics of infection of MERS-CoV is needed in order to optimise the use of existing assays. Notably, MERS-CoV point-of-care tests are needed in order to optimise supportive care and to minimise transmission risk. However, for new test development, sourcing clinical material continues to be a major challenge to achieving assay validation. Harmonisation and standardisation of laboratory methods are essential for surveillance and for a rapid and effective international response to emerging diseases. Routine external quality assessment, along with well-characterised and up-to-date proficiency panels, would provide insight into MERS-CoV diagnostic performance worldwide. A defined set of Target Product Profiles for diagnostic technologies will be developed by WHO to address these gaps in MERS-CoV outbreak management.

6.
BMJ Glob Health ; 4(Suppl 2): e001112, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30899573

RESUMEN

Ebolaviruses and Marburg virus (MARV) both belong to the family Filoviridae and cause severe haemorrhagic fever in humans. Due to high mortality rates and potential for spread from rural to urban regions, they are listed on the WHO R&D blueprint of high-priority pathogens. Recent ebolavirus outbreaks in Western and Central Africa have highlighted the importance of diagnostic testing in epidemic preparedness for these pathogens and led to the rapid development of a number of commercially available benchtop and point-of-care nucleic acid amplification tests as well as serological assays and rapid diagnostic tests. Despite these advancements, challenges still remain. While products approved under emergency use licenses during outbreak periods may continue to be used post-outbreak, a lack of clarity and incentive surrounding the regulatory approval pathway during non-outbreak periods has deterred many manufacturers from seeking full approvals. Waning of funding and poor access to samples after the 2014-2016 outbreak also contributed to cessation of development once the outbreak was declared over. There is a need for tests with improved sensitivity and specificity, and assays that can use alternative sample types could reduce the need for invasive procedures and expensive equipment, making testing in field conditions more feasible. For MARV, availability of diagnostic tests is still limited, restricted to a single ELISA test and assay panels designed to differentiate between multiple pathogens. It may be helpful to extend the target product profile for ebolavirus diagnostics to include MARV, as the viruses have many overlapping characteristics.

7.
PLoS One ; 14(3): e0212113, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30845203

RESUMEN

BACKGROUND: Without an effective vaccine, as was the case early in the 2014-2016 Ebola Outbreak in West Africa, disease control depends entirely on interrupting transmission through early disease detection and prompt patient isolation. Lateral Flow Immunoassays (LFI) are a potential supplement to centralized reference laboratory testing for the early diagnosis of Ebola Virus Disease (EVD). The goal of this study was to assess the performance of commercially available simple and rapid antigen detection LFIs, submitted for review to the WHO via the Emergency Use Assessment and Listing procedure. The study was performed in an Ebola Treatment Centre laboratory involved in EVD testing in Sierra Leone. In light of the current Ebola outbreak in May 2018 in the Democratic Republic of Congo, which highlights the lack of clarity in the global health community about appropriate Ebola diagnostics, our findings are increasingly critical. METHODS: A cross-sectional study was conducted to assess comparative performance of four LFIs for detecting EVD. LFIs were assessed against the same 328 plasma samples and 100 whole EDTA blood samples, using the altona RealStar Filovirus Screen real-time RT-PCR as the bench mark assay. The performance of the Public Health England (PHE) in-house Zaire ebolavirus-specific real time RT-PCR Trombley assay was concurrently assessed. Statistical analysis using generalized estimating equations was conducted to compare LFI performance. FINDINGS: Sensitivity and specificity varied between the LFIs, with specificity found to be significantly higher for whole EDTA blood samples compared to plasma samples in at least 2 LFIs (P≤0.003). Using the altona RT-PCR assay as the bench mark, sensitivities on plasma samples ranged from 79.53% (101/127, 95% CI: 71.46-86.17%) for the DEDIATEST EBOLA (SD Biosensor) to 98.43% (125/127, 95% CI: 94.43-99.81%) for the One step Ebola test (Intec). Specificities ranged from 80.20% (158/197, 95% CI: 74.07-88.60%) for plasma samples using the ReEBOV Antigen test Kit (Corgenix) to 100.00% (98/98, 95% CI: 96.31-100.00%) for whole blood samples using the DEDIATEST EBOLA (SD Biosensor) and SD Ebola Zaire Ag (SD Biosensor). Results also showed the Trombley RT-PCR assay had a lower limit of detection than the altona assay, with some LFIs having higher sensitivity than the altona assay when the Trombley assay was the bench mark. INTERPRETATION: All of the tested EVD LFIs may be considered suitable for use in an outbreak situation (i.e. rule out testing in communities), although they had variable performance characteristics, with none possessing both high sensitivity and specificity. The non-commercial Trombley Zaire ebolavirus RT-PCR assay warrants further investigation, as it appeared more sensitive than the current gold standard, the altona Filovirus Screen RT-PCR assay.


Asunto(s)
Fiebre Hemorrágica Ebola/diagnóstico , Inmunoensayo/métodos , Adulto , Antígenos Virales/sangre , Estudios Transversales , Brotes de Enfermedades/prevención & control , Ebolavirus/genética , Epidemias , Femenino , Fiebre Hemorrágica Ebola/epidemiología , Humanos , Pruebas Inmunológicas , Masculino , Sistemas de Atención de Punto , ARN Viral/sangre , Juego de Reactivos para Diagnóstico/virología , Sensibilidad y Especificidad , Sierra Leona
8.
J Antimicrob Chemother ; 73(7): 1737-1749, 2018 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-29514279

RESUMEN

Low- and middle-income countries (LMICs) shoulder the bulk of the global burden of infectious diseases and drug resistance. We searched for supranational networks performing antimicrobial resistance (AMR) surveillance in LMICs and assessed their organization, methodology, impacts and challenges. Since 2000, 72 supranational networks for AMR surveillance in bacteria, fungi, HIV, TB and malaria have been created that have involved LMICs, of which 34 are ongoing. The median (range) duration of the networks was 6 years (1-70) and the number of LMICs included was 8 (1-67). Networks were categorized as WHO/governmental (n = 26), academic (n = 24) or pharma initiated (n = 22). Funding sources varied, with 30 networks receiving public or WHO funding, 25 corporate, 13 trust or foundation, and 4 funded from more than one source. The leading global programmes for drug resistance surveillance in TB, malaria and HIV gather data in LMICs through periodic active surveillance efforts or combined active and passive approaches. The biggest challenges faced by these networks has been achieving high coverage across LMICs and complying with the recommended frequency of reporting. Obtaining high quality, representative surveillance data in LMICs is challenging. Antibiotic resistance surveillance requires a level of laboratory infrastructure and training that is not widely available in LMICs. The nascent Global Antimicrobial Resistance Surveillance System (GLASS) aims to build up passive surveillance in all member states. Past experience suggests complementary active approaches may be needed in many LMICs if representative, clinically relevant, meaningful data are to be obtained. Maintaining an up-to-date registry of networks would promote a more coordinated approach to surveillance.


Asunto(s)
Países en Desarrollo/estadística & datos numéricos , Farmacorresistencia Microbiana , Salud Global , Vigilancia en Salud Pública , Programas de Gobierno/organización & administración , Programas de Gobierno/estadística & datos numéricos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Malaria/tratamiento farmacológico , Malaria/epidemiología , Pobreza , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Organización Mundial de la Salud
9.
NPJ Vaccines ; 3: 11, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29581897

RESUMEN

Lassa fever (LF) is a zoonotic disease associated with acute and potentially fatal hemorrhagic illness caused by the Lassa virus (LASV), a member of the family Arenaviridae. It is generally assumed that a single infection with LASV will produce life-long protective immunity. This suggests that protective immunity induced by vaccination is an achievable goal and that cell-mediated immunity may play a more important role in protection, at least following natural infection. Seropositive individuals in endemic regions have been shown to have LASV-specific T cells recognizing epitopes for nucleocapsid protein (NP) and glycoprotein precursor (GPC), suggesting that these will be important vaccine immunogens. The role of neutralizing antibodies in protective immunity is still equivocal as recent studies suggest a role for neutralizing antibodies. There is extensive genetic heterogeneity among LASV strains that is of concern in the development of assays to detect and identify all four LASV lineages. Furthermore, the gene disparity may complicate the synthesis of effective vaccines that will provide protection across multiple lineages. Non-human primate models of LASV infection are considered the gold standard for recapitulation of human LF. The most promising vaccine candidates to date are the ML29 (a live attenuated reassortant of Mopeia and LASV), vesicular stomatitis virus (VSV) and vaccinia-vectored platforms based on their ability to induce protection following single doses, high rates of survival following challenge, and the use of live virus platforms. To date no LASV vaccine candidates have undergone clinical evaluation.

10.
J Infect Dis ; 217(7): 1060-1068, 2018 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-29294035

RESUMEN

Epidemics of dengue, Zika, and other arboviral diseases are increasing in frequency and severity. Current efforts to rapidly identify and manage these epidemics are limited by the short diagnostic window in acute infection, the extensive serologic cross-reactivity among flaviviruses, and the lack of point-of-care diagnostic tools to detect these viral species in primary care settings. The Partnership for Dengue Control organized a workshop to review the current landscape of Flavivirus diagnostic tools, identified current gaps, and developed strategies to accelerate the adoption of promising novel technologies into national programs. The rate-limiting step to bringing new diagnostic tools to the market is access to reference materials and well-characterized clinical samples to facilitate performance evaluation. We suggest the creation of an international laboratory-response consortium for flaviviruses with a decentralized biobank of well-characterized samples to facilitate assay validation. Access to proficiency panels are needed to ensure quality control, in additional to in-country capacity building.


Asunto(s)
Anticuerpos Antivirales/sangre , Dengue/diagnóstico , Infección por el Virus Zika/diagnóstico , Anticuerpos Antivirales/inmunología , Seguridad de Productos para el Consumidor , Dengue/historia , Dengue/virología , Virus del Dengue/genética , Virus del Dengue/inmunología , Virus del Dengue/aislamiento & purificación , Ensayo de Inmunoadsorción Enzimática/historia , Ensayo de Inmunoadsorción Enzimática/métodos , Ensayo de Inmunoadsorción Enzimática/tendencias , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Vigilancia de la Población , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/historia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/tendencias , Sensibilidad y Especificidad , Virus Zika/genética , Virus Zika/inmunología , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/historia , Infección por el Virus Zika/virología
12.
PLoS One ; 11(8): e0161721, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27559728

RESUMEN

Acute fever is one of the most common presenting symptoms globally. In order to reduce the empiric use of antimicrobial drugs and improve outcomes, it is essential to improve diagnostic capabilities. In the absence of microbiology facilities in low-income settings, an assay to distinguish bacterial from non-bacterial causes would be a critical first step. To ensure that patient and market needs are met, the requirements of such a test should be specified in a target product profile (TPP). To identify minimal/optimal characteristics for a bacterial vs. non-bacterial fever test, experts from academia and international organizations with expertise in infectious diseases, diagnostic test development, laboratory medicine, global health, and health economics were convened. Proposed TPPs were reviewed by this working group, and consensus characteristics were defined. The working group defined non-severely ill, non-malaria infected children as the target population for the desired assay. To provide access to the most patients, the test should be deployable to community health centers and informal health settings, and staff should require <2 days of training to perform the assay. Further, given that the aim is to reduce inappropriate antimicrobial use as well as to deliver appropriate treatment for patients with bacterial infections, the group agreed on minimal diagnostic performance requirements of >90% and >80% for sensitivity and specificity, respectively. Other key characteristics, to account for the challenging environment at which the test is targeted, included: i) time-to-result <10 min (but maximally <2 hrs); ii) storage conditions at 0-40°C, ≤90% non-condensing humidity with a minimal shelf life of 12 months; iii) operational conditions of 5-40°C, ≤90% non-condensing humidity; and iv) minimal sample collection needs (50-100µL, capillary blood). This expert approach to define assay requirements for a bacterial vs. non-bacterial assay should guide product development, and enable targeted and timely efforts by industry partners and academic institutions.


Asunto(s)
Infecciones Bacterianas/diagnóstico , Fiebre/diagnóstico , Técnicas de Diagnóstico Molecular/normas , Juego de Reactivos para Diagnóstico/normas , Consenso , Países en Desarrollo , Diagnóstico Diferencial , Humanos , Técnicas de Diagnóstico Molecular/economía , Técnicas de Diagnóstico Molecular/métodos , Guías de Práctica Clínica como Asunto , Juego de Reactivos para Diagnóstico/economía , Sensibilidad y Especificidad
13.
Curr Opin Infect Dis ; 29(4): 381-7, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27257796

RESUMEN

PURPOSE OF REVIEW: Humanitarian medical organizations focus on vulnerable patients with increased risk for healthcare-associated infections (HAIs) and are obligated to minimize them in inpatient departments (IPDs). However, in doing so humanitarian groups face considerable obstacles. This report will focus on approaches to reducing common HAIs that the authors have found to be helpful in humanitarian settings. RECENT FINDINGS: HAIs are common in humanitarian contexts but there are few interventions or guidelines adapted for use in poor and conflict-affected settings to improve prevention and guide surveillance. Based on existing recommendations and studies, it appears prudent that all humanitarian IPDs introduce a basic infection prevention infrastructure, assure high adherence to hand hygiene with wide accessibility to alcohol-based hand rub, and develop pragmatic surveillance based on clinically evident nosocomial infection. Although microbiology remains out of reach for most humanitarian hospitals, rapid tests offer the possibility of improving the diagnosis of HAIs in humanitarian hospitals in the decade ahead. SUMMARY: There is a dearth of new studies that can direct efforts to prevent HAIs in IPDs in poor and conflict-affected areas and there is a need for practical, field-adapted guidelines from professional societies, and international bodies to guide infection prevention efforts in humanitarian environments.


Asunto(s)
Altruismo , Infección Hospitalaria/prevención & control , Higiene de las Manos/métodos , Hospitales Especializados , Infección Hospitalaria/transmisión , Higiene de las Manos/organización & administración , Humanos
14.
Emerg Infect Dis ; 22(2): 210-6, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26812466

RESUMEN

Rapid diagnostic methods are essential in control of Ebola outbreaks and lead to timely isolation of cases and improved epidemiologic surveillance. Diagnosis during Ebola outbreaks in West Africa has relied on PCR performed in laboratories outside this region. Because time between sampling and PCR results can be considerable, we assessed the feasibility and added value of using the Xpert Ebola Assay in an Ebola control program in Guinea. A total of 218 samples were collected during diagnosis, treatment, and convalescence of patients. Median time for obtaining results was reduced from 334 min to 165 min. Twenty-six samples were positive for Ebola virus. Xpert cycle thresholds were consistently lower, and 8 (31%) samples were negative by routine PCR. Several logistic and safety issues were identified. We suggest that implementation of the Xpert Ebola Assay under programmatic conditions is feasible and represents a major advance in diagnosis of Ebola virus disease without apparent loss of assay sensitivity.


Asunto(s)
Ebolavirus/genética , Fiebre Hemorrágica Ebola/diagnóstico , Fiebre Hemorrágica Ebola/virología , Tipificación Molecular/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Genes Virales , Guinea , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Tipificación Molecular/normas , ARN Viral , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto Joven
15.
PLoS One ; 10(12): e0145772, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26717411

RESUMEN

The increasing prevalence of acquired and transmitted HIV-1 drug resistance is an obstacle to successful antiretroviral therapy (ART) in the low- and middle-income countries (LMICs) hardest hit by the HIV-1 pandemic. Genotypic drug resistance testing could facilitate the choice of initial ART in areas with rising transmitted drug resistance (TDR) and enable care-providers to determine which individuals with virological failure (VF) on a first- or second-line ART regimen require a change in treatment. An inexpensive near point-of-care (POC) genotypic resistance test would be useful in settings where the resources, capacity, and infrastructure to perform standard genotypic drug resistance testing are limited. Such a test would be particularly useful in conjunction with the POC HIV-1 viral load tests that are currently being introduced in LMICs. A POC genotypic resistance test is likely to involve the use of allele-specific point mutation assays for detecting drug-resistance mutations (DRMs). This study proposes that two major nucleoside reverse transcriptase inhibitor (NRTI)-associated DRMs (M184V and K65R) and four major NNRTI-associated DRMs (K103N, Y181C, G190A, and V106M) would be the most useful for POC genotypic resistance testing in LMIC settings. One or more of these six DRMs was present in 61.2% of analyzed virus sequences from ART-naïve individuals with intermediate or high-level TDR and 98.8% of analyzed virus sequences from individuals on a first-line NRTI/NNRTI-containing regimen with intermediate or high-level acquired drug resistance. The detection of one or more of these DRMs in an ART-naïve individual or in a individual with VF on a first-line NRTI/NNRTI-containing regimen may be considered an indication for a protease inhibitor (PI)-containing regimen or closer virological monitoring based on cost-effectiveness or country policy.


Asunto(s)
Farmacorresistencia Viral/genética , Técnicas de Genotipaje/métodos , VIH-1/genética , Mutación/genética , Sistemas de Atención de Punto , Sulfato de Atazanavir/farmacología , Sulfato de Atazanavir/uso terapéutico , Darunavir/farmacología , Darunavir/uso terapéutico , Quimioterapia Combinada , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Humanos , Lopinavir/farmacología , Lopinavir/uso terapéutico , Inhibidores de Proteasas/farmacología , Inhibidores de Proteasas/uso terapéutico , Inhibidores de la Transcriptasa Inversa/farmacología , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Ritonavir/farmacología , Ritonavir/uso terapéutico , Insuficiencia del Tratamiento
18.
Ann Acad Med Singap ; 42(7): 350-3, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23949264

RESUMEN

There is a lack of representative samples to provide reliable and accurate seroprevalence of sexually transmitted infections (STIs) and human immunodeficiency virus (HIV) as well as behavioural information among men who have sex with men (MSM) in Singapore. We used respondent driven sampling (RDS) to recruit MSM. Participants completed a survey used by Asian Internet MSM Sex Survey (AIMSS) and were tested for HIV and syphilis. We compared the characteristics of the RDS participants with STI diagnosis against those who did not have any STI diagnosis in the past 6 months. We compared RDS participants with AIMSS participants. Of 72 MSM recruited, 1 was positive for HIV (1.3%) and 4 (5.5%) tested positive for syphilis. Median age was 30 years and majority was Chinese (69.4%). RDS participants who had any STI diagnosis reported to have more use of recreational drugs (P = 0.006), and lower condom use (P = 0.054). Comparing RDS participants (n = 72) with the AIMSS participants (n = 2075), RDS respondents had ≥1 male partner in the past 6 months (P = 0.003), more casual sex partners (P = 0.012) and more STI symptoms (P = 0.019). There was no difference in terms of HIV testing and recreational drug use. The HIV and syphilis seroprevalence rates from our study are similar to previous reports conducted in high-risk MSM. In contrast to other settings, RDS did not work well among MSM in Singapore. The public health implications of our study highlight the challenges in obtaining data for HIV surveillance in assessing prevalence and risk behaviours among MSM.


Asunto(s)
Infecciones por VIH , Homosexualidad Masculina , Conducta Sexual , Sífilis , Adulto , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/psicología , Alfabetización en Salud/métodos , Encuestas Epidemiológicas , Homosexualidad Masculina/psicología , Homosexualidad Masculina/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Asunción de Riesgos , Estudios Seroepidemiológicos , Parejas Sexuales/psicología , Singapur/epidemiología , Sífilis/diagnóstico , Sífilis/epidemiología , Sífilis/psicología
19.
BMC Infect Dis ; 13: 90, 2013 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-23421710

RESUMEN

BACKGROUND: Recent studies suggest HIV-1 inter-subtype differences in co-receptor usage. We examined the correlation between HIV-1 subtype and co-receptor usage among treatment-naïve HIV-1 subjects in Singapore. Additionally, we investigated whether the subtype co-receptor association was influenced by stage of infection. METHODS: V3 sequences of HIV-1 envelope protein gp120 were obtained from 110 HIV treatment-naïve patients and genotypic co-receptor tropism determination was performed using Geno2pheno. Two false-positive rate (FPR) cut-offs, 10% and 5.75% were selected for tropism testing. RESULTS: Subtype assignment of viral strains from 110 HIV-infected individuals based on partial sequencing of HIV-1 pol, gp120 and gp41 were as follows: 27 subtype B, 64 CRF01_AE, 10 CRF51_01B, and 9 other subtypes. At FPR=10%, 10 (100%) CRF51_01B-infected subjects and 26 (40.6%) CRF01_AE-infected subjects had CXCR4-using virus, compared to 7 (25.9%) subtype B subjects and 1 (11.1%) CRF33_01B-infected subject (P < 0.001). At FPR=5.75%, 10 (100%) CRF51_01B-infected subjects and 20 (31.3%) CRF01_AE-infected subjects had CXCR4-using virus, compared to 4 (14.8%) subtype B and 1 (11.1%) CRF33_01B-infected subjects (P < 0.001). Among those with evidence of seroconversion within 2 years prior to study enrolment, 100% of CRF51_01B-infected subjects had CXCR4-using virus, independent of Geno2pheno FPR. CONCLUSION: CRF51_01B and CRF01_AE-infected individuals have higher prevalence of CXCR4-usage compared to subtype B infected individuals. Further studies examining these differences could help optimise the use of CCR5-antagonist in populations with these subtypes, and increase our understanding of HIV-1 biology.


Asunto(s)
Genotipo , Infecciones por VIH/virología , VIH-1/genética , Receptores CXCR4/metabolismo , Adolescente , Adulto , Niño , Femenino , Proteína gp120 de Envoltorio del VIH/genética , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , VIH-1/clasificación , VIH-1/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Receptores CCR5/metabolismo , Singapur/epidemiología , Tropismo Viral , Adulto Joven
20.
Ann Acad Med Singap ; 42(12): 667-73, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24463828

RESUMEN

INTRODUCTION: Chronic bacterial, viral and parasitic infections contribute to the morbidity and mortality associated with human immunodeficiency virus (HIV) infection. This study investigated risk factors and time-trends of the seroprevalence of cytomegalovirus (CMV), toxoplasmosis and hepatitis A total antibody; and co-infection with syphilis, hepatitis B and hepatitis C among newly diagnosed HIV individuals in Singapore. MATERIALS AND METHODS: This was a cross-sectional study. A random sample of 50% of HIV infected patients who visited the Communicable Disease Centre (CDC), Singapore for first-time care from January 2006 to December 2011 were analysed. RESULTS: Among the 793 study subjects, 93.4% were male; 77.9% of them were of Chinese ethnicity; mean age at HIV diagnosis was 41.4 years; and the mean baseline CD4+ T-cell count was 222 cells/mm³. The prevalence of sero-reactivity for CMV was 96.8%; hepatitis A: 40.9%; and toxoplasmosis: 23.7%. Co-infection with syphilis was identified in 12.3%; hepatitis B: 8.1%; and hepatitis C: 2%. Among those co-infected with hepatitis C, 73.3% of them were intravenous drug user (IVDU). Syphilis co-infection was significantly more common among men who have sex with men (MSM) (multivariate OR: 2.53, 95% CI, 1.31 to 4.90, P = 0.006). CONCLUSION: This study described the baseline rates of HIV co-infection with syphilis, hepatitis B and C in Singapore, and sero-reactivity to CMV, toxoplasmosis and hepatitis A. The increased rates compared to the general population may have important consequences for disease progression, response to antiretroviral treatment and long-term general health.


Asunto(s)
Infecciones por Citomegalovirus/epidemiología , Infecciones por VIH/epidemiología , Hepatitis Viral Humana/epidemiología , Sífilis/epidemiología , Toxoplasmosis/epidemiología , Adulto , Coinfección/epidemiología , Estudios Transversales , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/sangre , Femenino , Hepacivirus/aislamiento & purificación , Hepatitis Viral Humana/sangre , Humanos , Masculino , Oportunidad Relativa , Factores de Riesgo , Estudios Seroepidemiológicos , Singapur/epidemiología , Sífilis/sangre , Factores de Tiempo , Toxoplasmosis/sangre
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