83 research outputs found
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A portable device for nucleic acid quantification powered by sunlight, a flame or electricity.
A decentralized approach to diagnostics can decrease the time to treatment of infectious diseases in resource-limited settings. Yet most modern diagnostic tools require stable electricity and are not portable. Here, we describe a portable device for isothermal nucleic-acid quantification that can operate with power from electricity, sunlight or a flame, and that can store heat from intermittent energy sources, for operation when electrical power is not available or reliable. We deployed the device in two Ugandan health clinics, where it successfully operated through multiple power outages, with equivalent performance when powered via sunlight or electricity. A direct comparison between the portable device and commercial qPCR (quantitative polymerase chain reaction) machines for samples from 71 Ugandan patients (29 of which were tested in Uganda) for the presence of Kaposi's sarcoma-associated herpesvirus DNA showed 94% agreement, with the four discordant samples having the lowest concentration of the herpesvirus DNA. The device's flexibility in power supply provides a needed solution for on-field diagnostics
T cell immunosenescence is associated with the presence of Kaposi’s sarcoma in antiretroviral treated human immunodeficiency virus-infected persons
Impact of R-CHOP dose intensity on survival outcomes in diffuse large B-cell lymphoma:a systematic review
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Implementation of an Ultraviolet Phototherapy Service at a National Referral Hospital in Western Kenya: Reflections on Challenges and Lessons Learned.
IntroductionIn order to manage skin conditions at a national referral hospital level in Kenya, specialized dermatology services, such as dermatologic surgery, dermatopathology, phototherapy, and sub-specialty care, should be offered, as is typically available in referral hospitals around the world. A Kenyan patient with prurigo nodularis, whose severe itch remitted after phototherapy treatment at the University of California, San Francisco (UCSF), inspired the development of a phototherapy service at Academic Model Providing Access to Healthcare (AMPATH), a partnership in Western Kenya between Moi Teaching and Referral Hospital, Moi University College of Health Sciences, and a consortium of North American academic medical centers.MethodsInitial project funds were raised through a crowdfunding campaign and fundraising events. A new narrowband ultraviolet B phototherapy unit and replacement bulbs were donated and air shipped to Eldoret, Kenya. A team of dermatologists and phototherapy nurses from UCSF conducted a 2-day training session. US-based dermatologists affiliated with AMPATH provide ongoing support through regular communication and on-site visits.ResultsEarly in implementation, challenges faced included training clinical staff with limited experience in phototherapy and improving communication between nurses and clinicians. More recent challenges include frequent rotation of specialty clinic nurses in the dermatology clinic, adaptation of phototherapy guidelines to balance patient volume with service delivery capacity, and training assessment of disease activity in darkly pigmented skin.ConclusionStrategies that have been helpful in addressing implementation challenges include: increasing on-site and remote training opportunities for clinicians and nurses, developing a tiered payment schema, educating patients to combat misconceptions about phototherapy, dynamic phototherapy referral guidelines to accommodate service delivery capacity, and prioritizing the engagement of a multidisciplinary team
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A prospective ascertainment of cancer incidence in sub-Saharan Africa: The case of Kaposi sarcoma.
In resource-limited areas, such as sub-Saharan Africa, problems in accurate cancer case ascertainment and enumeration of the at-risk population make it difficult to estimate cancer incidence. We took advantage of a large well-enumerated healthcare system to estimate the incidence of Kaposi sarcoma (KS), a cancer which has become prominent in the HIV era and whose incidence may be changing with the rollout of antiretroviral therapy (ART). To achieve this, we evaluated HIV-infected adults receiving care between 2007 and 2012 at any of three medical centers in Kenya and Uganda that participate in the East Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortium. Through IeDEA, clinicians received training in KS recognition and biopsy equipment. We found that the overall prevalence of KS among 102,945 HIV-infected adults upon clinic enrollment was 1.4%; it declined over time at the largest site. Among 140,552 patients followed for 319,632 person-years, the age-standardized incidence rate was 334/100,000 person-years (95% CI: 314-354/100,000 person-years). Incidence decreased over time and was lower in women, persons on ART, and those with higher CD4 counts. The incidence rate among patients on ART with a CD4 count >350 cells/mm(3) was 32/100,000 person-years (95% CI: 14-70/100,000 person-years). Despite reductions over time coincident with the expansion of ART, KS incidence among HIV-infected adults in East Africa equals or exceeds the most common cancers in resource-replete settings. In resource-limited settings, strategic efforts to improve cancer diagnosis in combination with already well-enumerated at-risk denominators can make healthcare systems attractive platforms for estimating cancer incidence
An expanded population of CD8dim T cells with features of mitochondrial dysfunction and senescence is associated with persistent HIV-associated Kaposi’s sarcoma under ART
HIV-associated Kaposi’s sarcoma (KS), which is caused by Kaposi’s sarcoma-associated herpesvirus, usually arises in the context of uncontrolled HIV replication and immunosuppression. However, disease occasionally occurs in individuals with durable HIV viral suppression and CD4 T cell recovery under antiretroviral therapy (ART). The underlying mechanisms associated with this phenomenon are unclear. Suppression of viral infections can be mediated by CD8 T cells, which detect infected cells via their T cell receptor and the CD8 coreceptor. However, CD8 T cells exhibit signs of functional exhaustion in untreated HIV infection that may not be fully reversed under ART. To investigate whether KS under ART was associated with phenotypic and functional perturbations of CD8 T cells, we performed a cross-sectional study comparing HIV-infected individuals with persistent KS under effective ART (HIV+ KS+) to HIV-infected individuals receiving effective ART with no documented history of KS (HIV+ KSneg). A subset of T cells with low cell surface expression of CD8 (“CD8dim T cells”) was expanded in HIV+ KS+ compared with HIV+ KSneg participants. Relative to CD8bright T cells, CD8dim T cells exhibited signs of senescence (CD57) and mitochondrial alterations (PGC-1α, MitoTracker) ex vivo. Mitochondrial activity (MitoTracker) was also reduced in proliferating CD8dim T cells. These findings indicate that an expanded CD8dim T cell population displaying features of senescence and mitochondrial dysfunction is associated with KS disease under ART. CD8 coreceptor down-modulation may be symptomatic of ongoing disease
Prospective evaluation of the impact of potent antiretroviral therapy on the incidence of Kaposi’s Sarcoma in East Africa: findings from the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortium
The burden of co-existing dermatological disorders and their tendency of being overlooked among patients admitted to muhimbili national hospital in Dar es Salaam, Tanzania
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Skin diseases are underestimated and overlooked by most clinicians despite being common in clinical practice. Many patients are hospitalized with co-existing dermatological conditions which may not be detected and managed by the attending physicians. The objective of this study was to determine the burden of co-existing and overlooked dermatological disorders among patients admitted to medical wards of Muhimbili National hospital in Dar es Salaam. A hospital-based descriptive cross-sectional study conducted at Muhimbili National hospital in Dar es Salaam, Tanzania. Patients were consecutively recruited from the medical wards. Detailed interview to obtain clinico-demographic characteristics was followed by a complete physical examination. Dermatological diagnoses were made mainly clinically. Appropriate confirmatory laboratory investigations were performed where necessary. Data was analyzed using the 'Statistical Package for Social Sciences' (SPSS) program version 10.0. A p-value of < 0.5 was statistically significant. Three hundred and ninety patients admitted to medical wards were enrolled into the study of whom, 221(56.7%) were females. The mean age was 36.7 ± 17.9 (range 7-84 years). Overall, 232/390 patients (59.5%) had co-existing dermatological disorders with 49% (191/390) having one, 9% (36/390) two and 5 patients (1%) three. A wide range of co-existing skin diseases was encountered, the most diverse being non-infectious conditions which together accounted for 36.4% (142/390) while infectious dermatoses accounted for 31.5% (123/390). The leading infectious skin diseases were superficial fungal infections accounting for 18%. Pruritic papular eruption of HIV/AIDS (PPE) and seborrheic eczema were the most common non-infectious conditions, each accounting for 4.3%. Of the 232/390 patients with dermatological disorders, 191/232 (82.3%) and 154/232 (66.3%) had been overlooked by their referring and admitting doctors respectively. Dermatological disorders are common among patients admitted to medical wards and many are not detected by their referring or admitting physicians. Basic dermatological education should be emphasized to improve knowledge and awareness among clinicians.\u
The public health control of scabies: priorities for research and action.
Scabies is a parasitic disease of the skin that disproportionately affects disadvantaged populations. The disease causes considerable morbidity and leads to severe bacterial infection and immune-mediated disease. Scientific advances from the past 5 years suggest that scabies is amenable to population-level control, particularly through mass drug administration. In recognition of these issues, WHO added scabies to the list of neglected tropical diseases in 2017. To develop a global control programme, key operational research questions must now be addressed. Standardised approaches to diagnosis and methods for mapping are required to further understand the burden of disease. The safety of treatments for young children, including with ivermectin and moxidectin, should be investigated. Studies are needed to inform optimum implementation of mass treatment, including the threshold for intervention, target, dosing, and frequency. Frameworks for surveillance, monitoring, and evaluation of control strategies are also necessary
Psoriasis Patients Are Enriched for Genetic Variants That Protect against HIV-1 Disease
An important paradigm in evolutionary genetics is that of a delicate balance between genetic variants that favorably boost host control of infection but which may unfavorably increase susceptibility to autoimmune disease. Here, we investigated whether patients with psoriasis, a common immune-mediated disease of the skin, are enriched for genetic variants that limit the ability of HIV-1 virus to replicate after infection. We analyzed the HLA class I and class II alleles of 1,727 Caucasian psoriasis cases and 3,581 controls and found that psoriasis patients are significantly more likely than controls to have gene variants that are protective against HIV-1 disease. This includes several HLA class I alleles associated with HIV-1 control; amino acid residues at HLA-B positions 67, 70, and 97 that mediate HIV-1 peptide binding; and the deletion polymorphism rs67384697 associated with high surface expression of HLA-C. We also found that the compound genotype KIR3DS1 plus HLA-B Bw4-80I, which respectively encode a natural killer cell activating receptor and its putative ligand, significantly increased psoriasis susceptibility. This compound genotype has also been associated with delay of progression to AIDS. Together, our results suggest that genetic variants that contribute to anti-viral immunity may predispose to the development of psoriasis
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