Outcomes of Reflex Cryptococcal Antigen (CrAg) Screening in Human Immunodeficiency Virus (HIV)-Positive Patients With CD4 Counts of 100-200 Cells/µL in Botswana.

Increasing the CD4-count threshold for cryptococcal antigen (CrAg) screening from ≤100 to ≤200 cells/µL resulted in a 3-fold increase in numbers screened. CrAg-prevalence was 3.5% at CD4 101-200 and 6.2% ≤100 cells/µL. Six-month mortality was 21.4% (9/42) in CrAg-positive CD4 ≤100 cells/µL and 3.2% (1/31) in CrAg-positive CD4 101-200 cells/µL.

Fuel types misrepresent forest structure and composition in interior British Columbia: a way forward.

Background: A clear understanding of the connectivity, structure, and composition of wildland fuels is essential for effective wildfire management. However, fuel typing and mapping are challenging owing to a broad diversity of fuel conditions and their spatial and temporal heterogeneity. In Canada, fuel types and potential fire behavior are characterized using the Fire Behavior Prediction (FBP) System, which uses an association approach to categorize vegetation into 16 fuel types based on stand structure and composition. In British Columbia (BC), provincial and national FBP System fuel type maps are derived from remotely sensed forest inventory data and are widely used for wildfire operations, fuel management, and scientific research. Despite their widespread usage, the accuracy and applicability of these fuel type maps have not been formally assessed. To address this knowledge gap, we quantified the agreement between on-site assessments and provincial and national fuel type maps in interior BC. Results: We consistently found poor correspondence between field assessment data and both provincial and national fuel types. Mismatches were particularly frequent for (i) dry interior ecosystems, (ii) mixedwood and deciduous fuel types, and (iii) post-harvesting conditions. For 58% of field plots, there was no suitable match to the extant fuel structure and composition. Mismatches were driven by the accuracy and availability of forest inventory data and low applicability of the Canadian FBP System to interior BC fuels. Conclusions: The fuel typing mismatches we identified can limit scientific research, but also challenge wildfire operations and fuel management decisions. Improving fuel typing accuracy will require a significant effort in fuel inventory data and system upgrades to adequately represent the diversity of extant fuels. To more effectively link conditions to expected fire behavior outcomes, we recommend a fuel classification approach and emphasis on observed fuels and measured fire behavior data for the systems we seek to represent. Supplementary Information: The online version contains supplementary material available at 10.1186/s42408-024-00249-z.

Antecedentes: Un entendimiento claro sobre la conectividad, estructura, y composición de los combustibles vegetales es esencial para un manejo efectivo de los incendios de vegetación. Sin embargo, la tipificación y mapeo de los combustibles son aspectos desafiantes debido a la amplia diversidad de las condiciones de los combustibles y su variabilidad espacial y temporal. En Canadá, los tipos de combustibles y el comportamiento potencial del fuego están caracterizados por el uso del Sistema de Predicción del Comportamiento del Fuego (Fire Behavior Prediction System, FBP), el cual usa una "aproximación asociada" para categorizar la vegetación en 16 tipos de combustibles basados en la estructura y composición de los rodales. En la Columbia Británica (BC) los mapas del sistema provincial y nacional de FBP son derivados de datos de inventarios tomados mediante sensores remotos, que son ampliamente usados para operaciones de incendios de vegetación, manejo de combustibles, e investigación científica. A pesar de su amplio uso, la exactitud y aplicabilidad de esos mapas de tipos de combustibles no han sido adecuadamente comprobadas. Para determinar este vacío en el conocimiento, cuantificamos la concordancia entre las determinaciones in situ y los mapas de combustibles provinciales y nacionales en el interior de BC. Resultados: Encontramos consistentemente una pobre correspondencia entre las determinaciones de los datos de campo y los tipos de combustibles provinciales y nacionales. Los desfasajes fueron particularmente frecuentes para: i) los ecosistemas secos del interior, ii) bosques mixtos y tipos de combustibles en bosques deciduos, y iii) condiciones de postcosecha. Para el 58% de las parcelas a campo, no hubo una concordancia adecuada entre la estructura y composición existentes. Estos desajustes fueron derivados de la exactitud y disponibilidad de datos del inventario forestal, y la baja aplicabilidad del Sistema FBP a los combustibles del interior de la Columba Británica. Conclusiones: Los desajustes en la determinación de los tipos de combustibles que nosotros identificamos pueden limitar la investigación científica, pero también es un desafío para las decisiones en las operaciones de incendios y en el manejo de los combustibles. El mejoramiento de la exactitud en la determinación de tipos de combustibles requerirá de un esfuerzo significativo en el inventario de datos y sistemas mejorados para representar adecuadamente la diversidad de los combustibles existentes. Para ligar más efectivamente las condiciones a los resultados del comportamiento, recomendamos una aproximación a la clasificación de los combustibles y énfasis en datos de los combustibles observados y del comportamiento medido para los sistemas que pretendemos representar.

Retrospective Assessment of a National Reflex Cryptococcal Antigen Screening Program in South Africa Through Interlaboratory Comparison of Lateral Flow Assay Results.

OBJECTIVE: Reflex cryptococcal antigen (CrAg) screening of blood specimens with a CD4 count of <100 cells/µL was performed at 45 South African CD4 laboratories using a lateral flow assay (LFA). Our objective was to evaluate the reliability of routine LFA results through comparative interlaboratory testing. METHODS: All CrAg-positive and a selected number of CrAg-negative samples from the CD4 laboratories were retested at paired microbiology laboratories using the same LFA. Samples with discordant results were tested at a reference laboratory, using the LFA (with CrAg titers). RESULTS: During interlaboratory testing, 12,502 samples were retested, with 93 (0.7%) discordant results and a between-laboratory agreement of 99.3% (Cohen's kappa, 0.98). The proportion of retested samples with discordant results ranged from 0.17% to 5.31% per laboratory pair (median 0.28%), with 3 reporting >3% of results as discordant. CONCLUSION: Routine CrAg screening results were reliable, with <1% of samples having discordant results, mainly due to interpretation and transcription errors.

Improved detection and management of advanced HIV disease through a community adult TB-contact tracing intervention with same-day provision of the WHO-recommended package of care including ART initiation in a rural district of Mozambique.

INTRODUCTION: AIDS-mortality remains unacceptably high in sub-Saharan Africa, largely driven by advanced HIV disease (AHD). We nested a study in an existing tuberculosis (TB) contact-tracing intervention (Xpatial-TB). The aim was to assess the burden of AHD among high-risk people living with HIV (PLHIV) identified and to evaluate the provision of the WHO-recommended package of care to this population. METHODS: All PLHIV ≥14 years old identified between June and December 2018 in Manhiça District by Xpatial-TB were offered to participate in the study if ART naïve or had suboptimal ART adherence. Consenting individuals were screened for AHD. Patients with AHD (CD4 < 200 cells/µL or WHO stage 3 or 4) were offered a package of interventions in a single visit, including testing for cryptococcal antigen (CrAg) and TB-lipoarabinomannan (TB-LAM), prophylaxis and treatment for opportunistic infections, adherence support or accelerated ART initiation. We collected information on follow-up visits carried out under routine programmatic conditions for six months. RESULTS: A total of 2881 adults were identified in the Xpatial TB-contact intervention. Overall, 23% (673/2881) were HIV positive, including 351 TB index (64.2%) and 322 TB contacts (13.8%). Overall, 159/673 PLHIV (24%) were ART naïve or had suboptimal ART adherence, of whom 155 (97%, 124 TB index and 31 TB-contacts) consented to the study and were screened for AHD. Seventy percent of TB index-patients (87/124) and 16% of TB contacts (5/31) had CD4 < 200 cells/µL. Four (13%) of the TB contacts had TB, giving an overall AHD prevalence among TB contacts of 29% (9/31). Serum-CrAg was positive in 4.6% (4/87) of TB-index patients and in zero TB contacts. All ART naïve TB contacts without TB initiated ART within 48 hours of HIV diagnosis. Among TB cases, ART timing was tailored to the presence of TB and cryptococcosis. Six-month mortality was 21% among TB-index cases and zero in TB contacts. CONCLUSIONS: A TB contact-tracing outreach intervention identified undiagnosed HIV and AHD in TB patients and their contacts, undiagnosed cryptococcosis among TB patients, and resulted in an adequate provision of the WHO-recommended package of care in this rural Mozambican population. Same-day and accelerated ART initiation was feasible and safe in this population including among those with AHD.

Evaluation of a national cryptococcal antigen screening program for HIV-infected patients in Uganda: A cost-effectiveness modeling analysis.

BACKGROUND: Cryptococcal meningitis accounts for 15% of AIDS-related mortality. Cryptococcal antigen (CrAg) is detected in blood weeks before onset of meningitis, and CrAg positivity is an independent predictor of meningitis and death. CrAg screening for patients with advanced HIV and preemptive treatment is recommended by the World Health Organization, though implementation remains limited. Our objective was to evaluate costs and mortality reduction (lives saved) from a national CrAg screening program across Uganda. METHODS: We created a decision analytic model to evaluate CrAg screening. CrAg screening was considered for those with a CD4<100 cells/µL per national and international guidelines, and in the context of a national HIV test-and-treat program where CD4 testing was not available. Costs (2016 USD) were estimated for screening, preemptive therapy, hospitalization, and maintenance therapy. Parameter assumptions were based on large prospective CrAg screening studies in Uganda, and clinical trials from sub Saharan Africa. CrAg positive (CrAg+) persons could be: (a) asymptomatic and thus eligible for preemptive treatment with fluconazole; or (b) symptomatic with meningitis with hospitalization. RESULTS: In the base case model for 1 million persons with a CD4 test annually, 128,000 with a CD4<100 cells/µL were screened, and 8,233 were asymptomatic CrAg+ and received preemptive therapy. Compared to no screening and treatment, CrAg screening and treatment in the base case cost $3,356,724 compared to doing nothing, and saved 7,320 lives, for a cost of $459 per life saved, with the $3.3 million in cost savings derived from fewer patients developing fulminant meningitis. In the scenario of a national HIV test-and-treat program, of 1 million HIV-infected persons, 800,000 persons were screened, of whom 640,000 returned to clinic, and 8,233 were incident CrAg positive (CrAg prevalence 1.4%). The total cost of a CrAg screening and treatment program was $4.16 million dollars, with 2,180 known deaths. Conversely, without CrAg screening, the cost of treating meningitis was $3.09 million dollars with 3,806 deaths. Thus, despite the very low CrAg prevalence of 1.4% in the general HIV-infected population, and inadequate retention-in-care, CrAg screening averted 43% of deaths from cryptococcal meningitis at a cost of $662 per death averted. CONCLUSION: CrAg screening and treatment programs are cost-saving and lifesaving, assuming preemptive treatment is 77% effective in preventing death, and could be adopted and implemented by ministries of health to reduce mortality in those with advanced HIV disease. Even within HIV test-and-treat programs where CD4 testing is not performed, and CrAg prevalence is only 1.4%, CrAg screening is cost-effective.

Fate of methoprene in temperate salt marsh ditches following aerial applications.

Aerial applications of liquid methoprene are used in salt marshes to control mosquitoes by preventing adult emergence. Despite concern about toxicity to non-target organisms, little is known about environmental concentrations after applications, nor methoprene's persistence in salt marsh environments. Aqueous and sediment samples were collected from two marshes receiving weekly applications. Aqueous samples were collected as early as 30 min after applications and as long as nine days afterwards; sediment samples were taken within hours of application and as long as 19 days post-application. Use of time-of-flight liquid chromatography - mass spectral analysis allowed for ultra-low detection limits (0.5 ng/L) in water samples. The data show loss of nearly all methoprene from 1 m deep marsh ditches within 1 day and presence but not accumulation of methoprene in marsh sediments despite repeated applications. Methoprene concentrations observed in salt-marsh mosquito ditches were below those found to be of toxicological significance in other studies.

Trachomatous Scarring and Infection With Non-Chlamydia Trachomatis Bacteria in Women in Kongwa, Tanzania.

Purpose: To assess for an association between conjunctival infection with nonchlamydial bacterial species and the presence of trachomatous scarring (TS) in women in central Tanzania. Methods: Cross-sectional data were collected from a random sample of women ages 18 and older in 47 trachoma-endemic communities in Kongwa, Tanzania. Each participant completed a survey, provided a conjunctival swab sample, and received an ocular exam to assess for TS. Biologic samples were cultured for bacterial growth and speciation. Contingency tables were used to assess the associations between TS and bacterial carriage. Results: Complete data was provided by 3882 women (80.7% of invitees). Of all samples, 14% resulted in a positive bacterial isolate. There was no association between TS and nonchlamydial bacterial carriage, whether assessed by species, pathogenicity, or in aggregate. There was a significant association between increasing age and TS severity, but not between age and bacterial carriage. No Corynebacterium was found in the swabs. Conclusions: This study found no association between TS and nonchlamydial ocular infections, although associations with Corynebacterium cannot be ruled out.

Brief Report: Geographical Variation in Prevalence of Cryptococcal Antigenemia Among HIV-Infected, Treatment-Naive Patients in Nigeria: A Multicenter Cross-Sectional Study.

OBJECTIVE: Worldwide, HIV-associated cryptococcal meningitis affects approximately 1 million persons and causes 600,000 deaths each year mostly in sub-Saharan Africa. Limited data exist on cryptococcal meningitis and antigenemia in Nigeria, and most studies are geographically restricted. We determined the prevalence of cryptococcal antigenemia (CrAg) among HIV-infected, treatment-naive individuals in Nigeria. DESIGN/METHODS: This was a retrospective, cross-sectional study across 4 geographic regions in Nigeria. We performed CrAg testing using a lateral flow immunoassay on archived whole-blood samples collected from HIV-infected participants at US President's Emergency Plan for AIDS Relief (PEPFAR)-supported sites selected to represent the major geographical and ethnic diversity in Nigeria. Eligible samples were collected from consenting patients (>15 years) naive to antiretroviral therapy with CD4 count less than 200 cells per cubic millimeter and were stored in an -80°C freezer. RESULTS: A total of 2752 stored blood samples were retrospectively screened for CrAg. Most of the samples were from participants aged 30-44 years (57.6%), and 1570 (57.1%) were from women. The prevalence of CrAg positivity in specimens with CD4 <200 cells per cubic millimeter was 2.3% (95% confidence interval: 1.8% to 3.0%) and varied significantly across the 4 regions (P < 0.001). At 4.4% (3.2% to 5.9%), the South East contained the highest prevalence. CONCLUSIONS: The significant regional variation in CrAg prevalence found in Nigeria should be taken into consideration as plans are made to integrate routine screening into clinical care for HIV-infected patients.

Screening HIV-Infected Patients with Low CD4 Counts for Cryptococcal Antigenemia prior to Initiation of Antiretroviral Therapy: Cost Effectiveness of Alternative Screening Strategies in South Africa.

BACKGROUND: In 2015 South Africa established a national cryptococcal antigenemia (CrAg) screening policy targeted at HIV-infected patients with CD4+ T-lymphocyte (CD4) counts <100 cells/ µl who are not yet on antiretroviral treatment (ART). Two screening strategies are included in national guidelines: reflex screening, where a CrAg test is performed on remnant blood samples from CD4 testing; and provider-initiated screening, where providers order a CrAg test after a patient returns for CD4 test results. The objective of this study was to compare costs and effectiveness of these two screening strategies. METHODS: We developed a decision analytic model to compare reflex and provider-initiated screening in terms of programmatic and health outcomes (number screened, number identified for preemptive treatment, lives saved, and discounted years of life saved) and screening and treatment costs (2015 USD). We estimated a base case with prevalence and other parameters based on data collected during CrAg screening pilot projects integrated into routine HIV care in Gauteng, Free State, and Western Cape Provinces. We conducted sensitivity analyses to explore how results change with underlying parameter assumptions. RESULTS: In the base case, for each 100,000 CD4 tests, the reflex strategy compared to the provider-initiated strategy has higher screening costs ($37,536 higher) but lower treatment costs ($55,165 lower), so overall costs of screening and treatment are $17,629 less with the reflex strategy. The reflex strategy saves more lives (30 lives, 647 additional years of life saved). Sensitivity analyses suggest that reflex screening dominates provider-initiated screening (lower total costs and more lives saved) or saves additional lives for small additional costs (< $125 per life year) across a wide range of conditions (CrAg prevalence, patient and provider behavior, patient survival without treatment, and effectiveness of preemptive fluconazole treatment). CONCLUSIONS: In countries with substantial numbers of people with untreated, advanced HIV disease such as South Africa, CrAg screening before initiation of ART has the potential to reduce cryptococcal meningitis and save lives. Reflex screening compared to provider-initiated screening saves more lives and is likely to be cost saving or have low additional costs per additional year of life saved.

Assessment of a Novel Approach to Identify Trichiasis Cases Using Community Treatment Assistants in Tanzania.

BACKGROUND: Simple surgical intervention advocated by the World Health Organization can alleviate trachomatous trichiasis (TT) and prevent subsequent blindness. A large backlog of TT cases remain unidentified and untreated. To increase identification and referral of TT cases, a novel approach using standard screening questions, a card, and simple training for Community Treatment Assistants (CTAs) to use during Mass Drug Administration (MDA) was developed and evaluated in Kongwa District, a trachoma-endemic area of central Tanzania. METHODOLOGY/PRINCIPAL FINDINGS: A community randomized trial was conducted in 36 communities during MDA. CTAs in intervention villages received an additional half-day of training and a TT screening card in addition to the training received by CTAs in villages assigned to usual care. All MDA participants 15 years and older were screened for TT, and senior TT graders confirmed case status by evaluating all screened-positive cases. A random sample of those screened negative for TT and those who did not present at MDA were also evaluated by the master graders. Intervention CTAs identified 5.6 times as many cases (n = 50) as those assigned to usual care (n = 9, p < 0.05). While specificity was above 90% for both groups, the sensitivity for the novel screening tool was 31.2% compared to 5.6% for the usual care group (p < 0.05). CONCLUSIONS/SIGNIFICANCE: CTAs appear to be viable resources for the identification of TT cases. Additional training and use of a TT screening card significantly increased the ability of CTAs to recognize and refer TT cases during MDA; however, further efforts are needed to improve case detection and reduce the number of false positive cases.

Geospatial distribution and clustering of Chlamydia trachomatis in communities undergoing mass azithromycin treatment.

PURPOSE: We detected spatial clustering of households with Chlamydia trachomatis infection (CI) and active trachoma (AT) in villages undergoing mass treatment with azithromycin (MDA) over time. METHODS: We obtained global positioning system (GPS) coordinates for all households in four villages in Kongwa District, Tanzania. Every 6 months for a period of 42 months, our team examined all children under 10 for AT, and tested for CI with ocular swabbing and Amplicor. Villages underwent four rounds of annual MDA. We classified households as having ≥1 child with CI (or AT) or having 0 children with CI (or AT). We calculated the difference in the K function between households with and without CI or AT to detect clustering at each time point. RESULTS: Between 918 and 991 households were included over the 42 months of this analysis. At baseline, 306 households (32.59%) had ≥1 child with CI, which declined to 73 households (7.50%) at 42 months. We observed borderline clustering of households with CI at 12 months after one round of MDA and statistically significant clustering with growing cluster sizes between 18 and 24 months after two rounds of MDA. Clusters diminished in size at 30 months after 3 rounds of MDA. Active trachoma did not cluster at any time point. CONCLUSIONS: This study demonstrates that CI clusters after multiple rounds of MDA. Clusters of infection may increase in size if the annual antibiotic pressure is removed. The absence of growth after the three rounds suggests the start of control of transmission.

A novel prospective approach to evaluate trauma recidivism: the concept of the past trauma history.

BACKGROUND: The purpose of this study was to determine the incidence and burden of trauma recidivism at a regional Level 1 trauma center by incorporating the concept of the past trauma history (PTHx) into the general trauma history. METHODS: All trauma patients who met prehospital trauma criteria and activated the trauma team during a 13-month period were asked about their PTHx, that is, their history of injury in the previous 5 years. A recidivist presented more than once for separate severe injuries. Recurrent recidivists presented multiple times during the study period. RESULTS: Of the 4,971 trauma activations during the study period, 1,246 (25.2%) were identified as recidivists. Recidivists were 75% male, 62% white, 36% unemployed, 26% uninsured, and 90% unmarried. The recidivism rate among admitted patients was 23.4% compared with 29.3% in those discharged from the emergency department. The highest recidivism rates were noted in patients who reported alcohol or illegal drug use on the day of injury and in victims of interpersonal violence (IPV), defined as those who sustained gunshot wounds, stab wounds, or assaults, Those involved in IPV were more likely to have been involved in IPV at the previous trauma than those with other trauma mechanisms. Key risk factors for recidivism among all patients were male sex and single marital status. Seventy-three patients (1.5%) were recurrent recidivists, representing 157 unique encounters. CONCLUSION: This is the highest trauma recidivism rate reported on a large population of all consecutive trauma activations at a regional Level 1 trauma center. These data illustrate the tremendous burden of recidivism in the modern era, more than previously recognized. Efforts specifically targeting those involved in IPV may reduce recidivism rates. Incorporating the concept of the PTHx into the general history of the trauma patient is feasible and provides valuable information to the provider. LEVEL OF EVIDENCE: Prognostic study, level II.