Prospective evaluation of diagnostic accuracy of dried blood spots from finger prick samples for determination of HIV-1 load with the NucliSENS Easy-Q HIV-1 version 2.0 assay in Malawi.

HIV-1 viral load (VL) testing is not widely available in resource-limited settings. The use of finger prick dried blood spot (FP-DBS) samples could remove barriers related to sample collection and transport. Measurement of VL using DBS from EDTA venous blood (VB-DBS) in place of plasma has previously been validated using the NucliSENS Easy-Q HIV-1 v2.0 assay, but information on the accuracy of FP-DBS samples for measuring VL is limited. This prospective study, conducted at Thyolo District Hospital in southern Malawi, compared VL levels measured on FP-DBS samples and plasma using the NucliSENS Easy-Q HIV-1 v2.0 assay. Comparability was assessed by means of agreement and correlation (131 patients with VLs of ≥100 copies/ml), sensitivity, and specificity (612 patients on antiretroviral treatment [ART]). Samples of EDTA venous blood and FP-DBS from 1,009 HIV-infected individuals were collected and prepared in the laboratory. Bland-Altman analysis found good agreement between plasma and FP-DBS VL levels, with a mean difference of -0.35 log10, and 95% limits of agreement from -1.26 to 0.55 log10. FP-DBS had a sensitivity of 88.7% (95% confidence interval [CI], 81.1 to 94.4%) and a specificity of 97.8% (95% CI, 96.1 to 98.9%) using a 1,000-copies/ml cut point and a sensitivity of 83.0% (95% CI, 73.4 to 90.1%) and a specificity of 100% (95% CI, 99.3 to 100%) using a 5,000-copies/ml cut point. This study shows that FP-DBS is an acceptable alternative to plasma for measuring VL using the NucliSENS Easy-Q HIV-1 v2.0. We are conducting a second study to assess the proficiency of health workers at preparing FP-DBS in primary health care clinics.

Prevalence of tinea pedis, tinea unguium of toenails and tinea capitis in school children from Barcelona.

OBJECTIVE: To evaluate the prevalence of tinea capitis, tinea pedis, and tinea unguium in children from several schools of Barcelona city. METHODS: During the period of 2003-2004, a prospective cross-sectional study was carried out in 1,305 children (9% immigrant population) between the ages 3 and 15 in 17 schools in Barcelona. A systematic examination of the feet, (including nails and scalp), was performed to identify lesions compatible with tinea. Cultures of scalp and feet samples were done and analysis of environmental samples was performed for dermatophyte isolation. RESULTS: Dermatophytes were isolated in 2.9% of the samples with a prevalence of 2.5% in feet, 0.23% in scalp, and 0.15% in nails of the feet. The predominant etiologic agents in feet were Trichophyton mentagrophytes in 45.7% of the cases and Trichophyton rubrum in 31.4%. In the nails, T. rubrum and Trichophyton tonsurans were isolated, while T. mentagrophytes (2 cases) and Trichophyton violaceum (1 case) were identified in scalp samples. Forty-five per cent of dermatophytes were isolated from healthy feet, the majority of cases in children 13- 15-years-old (p < 0.05). Microsporum gypseum was the only agent identified in the environmental samples, and was also found in one of the cases of tinea pedis. CONCLUSION: The results of this study demonstrate a low prevalence of tinea capitis and tinea unguium in school children of Barcelona. On the contrary, high prevalence of dermatophytes in feet was found. It highlights the high prevalence of healthy carriers of dermatophytes in feet.

Antibiotic treatment for ocular toxoplasmosis: a systematic review and meta-analysis: study protocol.

BACKGROUND: Ocular toxoplasmosis (OT) is the most common cause of posterior uveitis, leading to visual impairment in a high proportion of patients. Antibiotics and corticosteroids lower the risk of permanent visual impairment by reducing the size of the retinochoroidal scar, the risk of recurrence, and the severity and duration of acute symptoms. Although OT is a very common cause of infectious posterior uveitis, its treatment remains controversial. Through our systematic review and meta-analysis, we aim to provide the best possible evidence-based information on the safety and effectiveness of the different antibiotic regimes for OT. METHODS: This systematic review protocol has been developed based on PRISMA-P guidelines for reporting systematic reviews evaluating health care interventions. We will include all published and unpublished randomized controlled trials (RCTs) comparing different antibiotics used for the treatment of OT. We will consider changes in visual acuity, number of recurrences, improvement or worsening of ocular inflammation, size of lesion, and adverse effects as our outcomes. Screening, data extraction, and quality assessment will be undertaken by two reviewers with disagreements resolved through discussion. Studies that compared antibiotics with placebo will be excluded. The reviews will be assessed for quality and relevance. We will assess the risk of bias in five domains according to Cochrane group's tool. The type of data will dictate measures of treatment effect. We will use a random-effects model to calculate our meta-analysis, as eligible studies represent clinically varied populations of participants. DISCUSSION: The strength of our study will lie in the exhaustive and systematic nature of the literature search, as well as in its methods for assessing quality and analyzing RCT data. Considering the controversial efficacy of the treatment for OT, our study will contribute to improving the existing evidence on the effectiveness of different antibiotics. Future studies may be conducted to increase physicians' awareness of antibiotic therapies, improving the health of patients with OT. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018085468.

First Natural Endocranial Cast of a Fossil Snake (Cretaceous of Patagonia, Argentina).

In this study, we describe a natural endocranial cast included in a partially preserved medium-sized skull of the Upper Cretaceous South American snake Dinilysia patagonica. The endocast is composed of sedimentary filling of the cranial cavity in which the posterior brain, the vessels, the cranial nerves, and the inner ear surrounded by delicate semicircular canals, are represented. It is simple in form, with little differentiation between the three main areas (Forebrain, Midbrain, and Hindbrain), and without flexures. The nervous system is well preserved. The posterior brain surface is smooth, except for two small prominences that make up the cerebellum. A large inner ear is preserved on the right side; it consists of a voluminous central mass, the vestibule, which occupies most of the space defined by the three semicircular canals. In particular, the lateral semicircular canal is very close to the vestibule. This characteristic, in combination with the medium to large body size of Dinilysia, its large skull and dorsally exposed orbits, and vertebrae bearing a rather high neural spine on a depressed neural arch, suggests that this snake would have had a semifossorial lifestyle. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 301:9-20, 2018. © 2017 Wiley Periodicals, Inc.

Renal safety of a tenofovir-containing first line regimen: experience from an antiretroviral cohort in rural Lesotho.

INTRODUCTION: Current guidelines contraindicate TDF use when creatinine clearance (CrCl) falls below 50 ml/min. We report prevalence of abnormal renal function at baseline and factors associated with abnormal renal function from a community cohort in Lesotho. METHODS: We calculated changes in CrCl from baseline for patients initiated on TDF at 6 and 12 months and the proportion of patients initiated on TDF who developed renal impairment. Screening algorithms were developed using risk factors determined by multivariate analysis. RESULTS: Among 933 adults for whom baseline creatinine was available, 176 (18.9%) presented with a baseline CrCl <50 ml/min. Renal function improved during follow-up. 19 patients who developed renal toxicity during follow up remained on TDF; renal function improved (CrCl≥50 ml/min) in all but 3 of these patients. Among 15 patients with a baseline CrCl <50 ml/min were started in error, none developed severe renal impairment. CONCLUSION: In this setting TDF-associated renal toxicity is rare and mainly transient. Further studies to assess TDF safety at lower CrCl thresholds are warranted.

Implementing a tenofovir-based first-line regimen in rural Lesotho: clinical outcomes and toxicities after two years.

BACKGROUND: The latest World Health Organization guidelines recommend replacing stavudine with tenofovir or zidovudine in first-line antiretroviral therapy in resource-limited settings. We report on outcomes and toxicities among patients on these different regimens in a routine treatment cohort in Lesotho. METHODS: All adult patients initiating antiretroviral therapy from January 1, 2008, to December 31, 2008, were included in the analysis and followed until December 31, 2009. Choice of regimen was determined by clinical criteria. RESULTS: Of 1124 patient records analyzed, median age was 39 years, and the majority (67.7%) were women. Five hundred eighty-seven patients were started on tenofovir, 255 on zidovudine, and 282 on stavudine. Patients on zidovudine were more than twice as likely to experience a toxicity-driven regimen substitution compared with tenofovir (adjusted hazard ratio: 2.32, 95% confidence interval: 1.23 to 4.40); for patients on stavudine, the risk of a toxicity-driven regimen switch was almost 6 times higher than tenofovir (adjusted hazard ratio: 5.43, 95% confidence interval: 3.31 to 8.91). CONCLUSIONS: Our findings support the latest World Health Organization Guidelines, in particular the adoption of tenofovir in first line, given the advantages in terms of tolerability and availability as a once-daily formulation.

Cost and cost-effectiveness of switching from d4T or AZT to a TDF-based first-line regimen in a resource-limited setting in rural Lesotho.

BACKGROUND: Latest World Health Organization guidelines recommend shifting away from Stavudine (d4T)-based regimens due to severe side effects. However, widespread replacement of d4T by Tenofovir (TDF) or Zidovudine (AZT) is hampered by cost concerns. METHODS: We established the cost-effectiveness of alternative first-line regimens using primary utilization, cost, and outcome data from a program in a rural district in Lesotho. We calculated cost per patient-year, incremental costs, and incremental cost-effectiveness ratios per life year, and per Quality Adjusted Life Year gained. Uncertainty was assessed using multiway and probabilistic sensitivity analyses. RESULTS: Our study included 1260 patients representing 1635 patient-years on antiretroviral therapy (ART). Six hundred eight patients were on TDF, 290 were on AZT, and 362 were on d4T. Patients on d4T experienced more toxicities; toxicities with the biggest impact on quality of life were moderate neuropathy and severe lipodystrophy. The cost per patient-year ranged from US $266 on d4T to US $353 on TDF. Inpatient care and essential drug costs were higher for patients on d4T than on AZT or TDF. Incremental cost-effectiveness ratio results suggest that AZT-based ART is weakly dominated by a combination of d4T- and TDF-based ART. DISCUSSION: This is one of the first analyses to investigate the cost-effectiveness of TDF using primary data in a resource-poor setting. Although TDF-based first-line ART is more costly than d4T, it is also more effective. Political pressure should be exerted to encourage further price reductions and additional generic manufacturing for TDF and partner drugs such as Efavirenz. This should be met by a commitment from donors and implementers to ensure that supply is met by a clear demand.

Early initiation of antiretroviral therapy and associated reduction in mortality, morbidity and defaulting in a nurse-managed, community cohort in Lesotho.

INTRODUCTION: The latest WHO guidelines recommend initiating antiretroviral therapy (ART) at CD4 cell counts less than 350 cells/µl. However, donors and national governments are reluctant to support implementation owing to uncertainty regarding feasibility and relative benefit. Lesotho has supported earlier initiation since 2008. We assessed outcomes comparing early (CD4 cell counts >200 cells/µl) and late (CD4 cell counts ≤200 cells/µl) initiation. METHODS: We describe survival probability among patients initiating ART at CD4 cell counts 200 or less and more than 200 cells/µl and assess associations between baseline CD4 cell counts and mortality, morbidity, loss to follow-up and hospitalization using Cox regression adjusting for confounders identified a priori. RESULTS: Our analysis included 1177 patients; median age was 38 years and the majority (67%) were women. Median time on ART for the overall cohort was 506 days (interquartile range 396-608). Five hundred and thirty eight patients initiated ART at a CD4 cell count 200 cells/µl or less (interquartile range 54-160) and 639 patients initiated at CD4 cell count more than 200 cells/µl (interquartile range 238-321). In multivariate analysis, we found that patients initiating at CD4 cell count more than 200 cells/µl were 68% less likely to die (adjusted hazard ratio 0.32, 95% confidence interval 0.20-0.50), and 39% less likely to be lost to follow-up (adjusted hazard ratio 0.61, 95% confidence interval 0.43-0.87). Initiating ART at CD4 cell count more than 200 cells/µl was also associated with a 27% reduction in the rate of incident morbidity (adjusted hazard ratio 0.73, 95% confidence interval 0.65-0.82) and a 63% decreased rate of hospitalization (adjusted hazard ratio 0.37, 95% confidence interval 0.19-0.73). CONCLUSION: Earlier initiation is feasible in a low resource, high HIV prevalence setting, and provides important benefits in terms of reduced mortality, morbidity, retention and hospitalization. Donors should fully support the implementation of the latest WHO recommendations.

Trends in loss to follow-up among migrant workers on antiretroviral therapy in a community cohort in Lesotho.

BACKGROUND: The provision of antiretroviral therapy (ART) to migrant populations raises particular challenges with respect to ensuring adequate treatment support, adherence, and retention in care. We assessed rates of loss to follow-up for migrant workers compared with non-migrant workers in a routine treatment programme in Morjia, Lesotho. DESIGN: All adult patients (≥18 years) initiating ART between January 1, 2008, and December 31, 2008, and followed up until the end of 2009, were included in the study. We described rates of loss to follow-up according to migrant status by Kaplan-Meier estimates, and used Poisson regression to model associations between migrant status and loss to follow-up controlling for potential confounders identified a priori. RESULTS: Our cohort comprised 1185 people, among whom 12% (148) were migrant workers. Among the migrant workers, median age was 36.1 (29.6-45.9) and the majority (55%) were male. We found no statistically significant differences between baseline characteristics and migrant status. Rates of lost to follow up were similar between migrants and non-migrants in the first 3 months but differences increased thereafter. Between 3 and 6 months after initiating antiretroviral therapy, migrants had a 2.78-fold increased rate of defaulting (95%CI 1.15-6.73); between 6 and 12 months the rate was 2.36 times greater (95%CI 1.18-4.73), whereas after 1 year the rate was 6.69 times greater (95%CI 3.18-14.09). CONCLUSIONS: Our study highlights the need for programme implementers to take into account the specific challenges that may influence continuity of antiretroviral treatment and care for migrant populations.

Prevalence of tinea pedis, tinea unguium of toenails and tinea capitis in school children from Barcelona

ObjetivoEvaluar la prevalencia de tinea capitis, tinea pedis y tinea unguium en niños de diferentes escuelas de la ciudad de Barcelona.MétodoDurante el periodo 2003–2004 se efectuó un estudio prospectivo en 1.305 niños (9% de inmigrantes) de edades comprendidas entre los 3 y los 15 años, en 17 escuelas de dos distritos de la ciudad de Barcelona. Se realizó un examen sistemático de los pies, uñas de los pies y cuero cabelludo de todos los niños, seguido de la toma y posterior cultivo de muestras del cuero cabelludo y pies, así como de muestras ambientales para aislar e identificar la presencia de hongos dermatofitos.ResultadosSe aisló un 2,9% de dermatofitos de las muestras clínicas, correspondiéndose con una prevalencia del 2,5% en pies, 0,23% en cuero cabelludo y 0,15% en uñas de pies. Las especies predominantes fueron Trichophyton mentagrophytes en el 45% de los casos y Trichophyton rubrum en el 31,4%. En uñas se cultivó T. rubrum y Trichophyton tonsurans, mientras que en cuero cabelludo se aisló T. mentagrophytes (dos casos) y Trichophyton violaceum (un caso). El 45% de los dermatofitos se aislaron de niños aparentemente sanos, la mayoría de los cuales se encontraban entre los 13 y los 15 años de edad (p<0,05). Microsporum gypseum fue el único dermatofito aislado del medio ambiente, encontrándose también en un caso de tinea pedis.ConclusiónLos resultados de este estudio demuestran una baja prevalencia de tinea capitis y tinea unguium en escolares de Barcelona. Destaca la elevada prevalencia de aislamientos de dermatofitos en pies, con gran proporción de portadores sanos(AU)

ObjectiveTo evaluate the prevalence of tinea capitis, tinea pedis, and tinea unguium in children from several schools of Barcelona city.MethodsDuring the period of 2003–2004, a prospective cross-sectional study was carried out in 1,305 children (9% immigrant population) between the ages 3 and 15 in 17 schools in Barcelona. A systematic examination of the feet, (including nails and scalp), was performed to identify lesions compatible with tinea. Cultures of scalp and feet samples were done and analysis of environmental samples was performed for dermatophyte isolation.ResultsDermatophytes were isolated in 2.9% of the samples with a prevalence of 2.5% in feet, 0.23% in scalp, and 0.15% in nails of the feet. The predominant etiologic agents in feet were Trichophyton mentagrophytes in 45.7% of the cases and Trichophyton rubrum in 31.4%. In the nails, T. rubrum and Trichophyton tonsurans were isolated, while T. mentagrophytes (2 cases) and Trichophyton violaceum (1 case) were identified in scalp samples. Forty-five per cent of dermatophytes were isolated from healthy feet, the majority of cases in children 13–15 years old (p<0.05). Microsporum gypseum was the only agent identified in the environmental samples, and was also found in one of the cases of tinea pedis.ConclusionThe results of this study demonstrate a low prevalence of tinea capitis and tinea unguium in school children of Barcelona. On the contrary, high prevalence of dermatophytes in feet was found. It highlights the high prevalence of healthy carriers of dermatophytes in feet(AU)