Ann C. Miller

Excellent clinical outcomes and high retention in care among adults in a community-based HIV treatment program in rural Rwanda.

Background: Access to antiretroviral therapy (ART) has rapidly expanded; as of the end of 2010, an estimated 6.6 million people are receiving ART in low-income and middle-income countries. Few reports have focused on the experiences of rural health centers or the use of community health workers. We report clinical and programatic outcomes at 24 months for a cohort of patients enrolled in a community-based ART program in southeastern Rwanda under collaboration between Partners In Health and the Rwandan Ministry of Health. Methods and Findings A retrospective medical record review was performed for a cohort of 1041 HIV+ adult patients initiating community-based ART between June 1, 2005, and April 30, 2006. Key programatic elements included free ART with direct observation by community health worker, tuberculosis screening and treatment, nutritional support, a transportation allowance, and social support. Among 1041 patients who initiated community-based ART, 961 (92.3%) were retained in care, 52 (5%) died and 28 (2.7%) were lost to follow-up. Median CD4 T-cell count increase was 336 cells per microliter [interquartile range: (IQR): 212–493] from median 190 cells per microliter (IQR: 116–270) at initiation. Conclusions: A program of intensive community-based treatment support for ART in rural Rwanda had excellent outcomes in 24-month retention in care. Having committed to improving access to HIV treatment in sub-Saharan Africa, the international community, including country HIV programs, should set high programmatic outcome benchmarks.

ReEBOV Antigen Rapid Test kit for point-of-care and laboratory-based testing for Ebola virus disease: a field validation study

BACKGROUND At present, diagnosis of Ebola virus disease requires transport of venepuncture blood to field biocontainment laboratories for testing by real-time RT-PCR, resulting in delays that complicate patient care and infection control efforts. Therefore, an urgent need exists for a point-of-care rapid diagnostic test for this disease. In this Article, we report the results of a field validation of the Corgenix ReEBOV Antigen Rapid Test kit. METHODS We performed the rapid diagnostic test on fingerstick blood samples from 106 individuals with suspected Ebola virus disease presenting at two clinical centres in Sierra Leone. Adults and children who were able to provide verbal consent or assent were included; we excluded patients with haemodynamic instability and those who were unable to cooperate with fingerstick or venous blood draw. Two independent readers scored each rapid diagnostic test, with any disagreements resolved by a third. We compared point-of-care rapid diagnostic test results with clinical real-time RT-PCR results (RealStar Filovirus Screen RT-PCR kit 1·0; altona Diagnostics GmbH, Hamburg, Germany) for venepuncture plasma samples tested in a Public Health England field reference laboratory (Port Loko, Sierra Leone). Separately, we performed the rapid diagnostic test (on whole blood) and real-time RT-PCR (on plasma) on 284 specimens in the reference laboratory, which were submitted to the laboratory for testing from many clinical sites in Sierra Leone, including our two clinical centres. FINDINGS In point-of-care testing, all 28 patients who tested positive for Ebola virus disease by RT-PCR were also positive by fingerstick rapid diagnostic test (sensitivity 100% [95% CI 87·7-100]), and 71 of 77 patients who tested negative by RT-PCR were also negative by the rapid diagnostic test (specificity 92·2% [95% CI 83·8-97·1]). In laboratory testing, all 45 specimens that tested positive by RT-PCR were also positive by the rapid diagnostic test (sensitivity 100% [95% CI 92·1-100]), and 214 of 232 specimens that tested negative by RT-PCR were also negative by the rapid diagnostic test (specificity 92·2% [88·0-95·3]). The two independent readers agreed about 95·2% of point-of-care and 98·6% of reference laboratory rapid diagnostic test results. Cycle threshold values ranged from 15·9 to 26·3 (mean 22·6 [SD 2·6]) for the PCR-positive point-of-care cohort and from 17·5 to 26·3 (mean 21·5 [2·7]) for the reference laboratory cohort. Six of 16 banked plasma samples from rapid diagnostic test-positive and altona-negative patients were positive by an alternative real-time RT-PCR assay (the Trombley assay); three (17%) of 18 samples from individuals who were negative by both the rapid diagnostic test and altona test were also positive by Trombley. INTERPRETATION The ReEBOV rapid diagnostic test had 100% sensitivity and 92% specificity in both point-of-care and reference laboratory testing in this population (maximum cycle threshold 26·3). With two independent readers, the test detected all patients who were positive for Ebola virus by altona real-time RT-PCR; however, this benchmark itself had imperfect sensitivity. FUNDING Abundance Foundation.

Estimated Costs of False Laboratory Diagnoses of Tuberculosis in Three Patients

We estimated direct medical and nonmedical costs associated with a false diagnosis of tuberculosis (TB) caused by laboratory cross-contamination of Mycobacterium tuberculosis cultures in Massachusetts in 1998 and 1999. For three patients who received misdiagnoses of active TB disease on the basis of laboratory cross-contamination, the costs totaled U.S.

Genotyping analyses of tuberculosis cases in U.S.- and foreign-born Massachusetts residents.

32,618. Of the total, 97% was attributed to the public sector (local and state health departments, public health hospital and laboratory, and county and state correctional facilities); 3% to the private sector (physicians, hospitals, and laboratories); and <1% to the patient. Hospitalizations and inpatient tests, procedures, and TB medications accounted for 69% of costs, and outpatient TB medications accounted for 18%. The average cost per patient was

Performance of the GeneXpert Ebola Assay for Diagnosis of Ebola Virus Disease in Sierra Leone: A Field Evaluation Study

10,873 (range,

Impact of Genotyping of Mycobacterium Tuberculosis on Public Health Practice in Massachusetts

1,033-

Strengthening Health Systems While Responding to a Health Crisis: Lessons Learned by a Nongovernmental Organization During the Ebola Virus Disease Epidemic in Sierra Leone

21,306). Reducing laboratory cross-contamination and quickly identifying patients with cross-contaminated cultures can prevent unnecessary and potentially dangerous treatment regimens and anguish for the patient and financial burden to the health-care system.

Hepatotoxicity during treatment for multidrug-resistant tuberculosis: occurrence, management and outcome.

We used molecular genotyping to further understand the epidemiology and transmission patterns of tuberculosis (TB) in Massachusetts. The study population included 983 TB patients whose cases were verified by the Massachusetts Department of Public Health between July 1, 1996, and December 31, 2000, and for whom genotyping results and information on country of origin were available. Two hundred seventy-two (28%) of TB patients were in genetic clusters, and isolates from U.S-born were twice as likely to cluster as those of foreign-born (odds ratio [OR] 2.29, 95% confidence interval [CI] 1.69, 3.12). Our results suggest that restriction fragment length polymorphism analysis has limited capacity to differentiate TB strains when the isolate contains six or fewer copies of IS6110, even with spoligotyping. Clusters of TB patients with more than six copies of IS6110 were more likely to have epidemiologic connections than were clusters of TB patients with isolates with few copies of IS6110 (OR 8.01, 95%; CI 3.45,18.93).

Baseline population health conditions ahead of a health system strengthening program in rural Madagascar

Background Throughout the Ebola virus disease (EVD) epidemic in West Africa, field laboratory testing for EVD has relied on complex, multi-step real-time reverse transcription PCR (RT-PCR) assays; an accurate sample-to-answer RT-PCR test would reduce time to results and potentially increase access to testing. We evaluated the performance of the Cepheid GeneXpert Ebola assay on clinical venipuncture whole blood (WB) and buccal swab (BS) specimens submitted to a field biocontainment laboratory in Sierra Leone for routine EVD testing by RT-PCR (“Trombley assay”). Methods and Findings This study was conducted in the Public Health England EVD diagnostic laboratory in Port Loko, Sierra Leone, using residual diagnostic specimens remaining after clinical testing. EDTA-WB specimens (n = 218) were collected from suspected or confirmed EVD patients between April 1 and July 20, 2015. BS specimens (n = 71) were collected as part of a national postmortem screening program between March 7 and July 20, 2015. EDTA-WB and BS specimens were tested with Xpert (targets: glycoprotein [GP] and nucleoprotein [NP] genes) and Trombley (target: NP gene) assays in parallel. All WB specimens were fresh; 84/218 were tested in duplicate on Xpert to compare WB sampling methods (pipette versus swab); 43/71 BS specimens had been previously frozen. In all, 7/218 (3.2%) WB and 7/71 (9.9%) BS samples had Xpert results that were reported as “invalid” or “error” and were excluded, leaving 211 WB and 64 BS samples with valid Trombley and Xpert results. For WB, 22/22 Trombley-positive samples were Xpert-positive (sensitivity 100%, 95% CI 84.6%–100%), and 181/189 Trombley-negative samples were Xpert-negative (specificity 95.8%, 95% confidence interval (CI) 91.8%–98.2%). Seven of the eight Trombley-negative, Xpert-positive (Xpert cycle threshold [Ct] range 37.7–43.4) WB samples were confirmed to be follow-up submissions from previously Trombley-positive EVD patients, suggesting a revised Xpert specificity of 99.5% (95% CI 97.0%–100%). For Xpert-positive WB samples (n = 22), Xpert NP Ct values were consistently lower than GP Ct values (mean difference −4.06, 95% limits of agreement −6.09, −2.03); Trombley (NP) Ct values closely matched Xpert NP Ct values (mean difference −0.04, 95% limits of agreement −2.93, 2.84). Xpert results (positive/negative) for WB sampled by pipette versus swab were concordant for 78/79 (98.7%) WB samples, with comparable Ct values for positive results. For BS specimens, 20/20 Trombley-positive samples were Xpert-positive (sensitivity 100%, 95% CI 83.2%–100%), and 44/44 Trombley-negative samples were Xpert-negative (specificity 100%, 95% CI 92.0%–100%). This study was limited to testing residual diagnostic samples, some of which had been frozen before use; it was not possible to test the performance of the Xpert Ebola assay at point of care. Conclusions The Xpert Ebola assay had excellent performance compared to an established RT-PCR benchmark on WB and BS samples in a field laboratory setting. Future studies should evaluate feasibility and performance outside of a biocontainment laboratory setting to facilitate expanded access to testing.

Baseline Predictors of Treatment Outcomes in Children With Multidrug-Resistant Tuberculosis: A Retrospective Cohort Study.

Massachusetts was one of seven sentinel surveillance sites in the National Tuberculosis Genotyping and Surveillance Network. From 1996 through 2000, isolates from new patients with tuberculosis (TB) underwent genotyping. We describe the impact that genotyping had on public health practice in Massachusetts and some limitations of the technique. Through genotyping, we explored the dynamics of TB outbreaks, investigated laboratory cross-contamination, and identified Mycobacterium tuberculosis strains, transmission sites, and accurate epidemiologic links. Genotyping should be used with epidemiologic follow-up to identify how resources can best be allocated to investigate genotypic findings.