Repeat assessment of examination signs among children in Malawi with fast-breathing pneumonia.

BACKGROUND: As part of a randomised controlled trial of treatment with placebo versus 3 days of amoxicillin for nonsevere fast-breathing pneumonia among Malawian children aged 2-59 months, a subset of children was hospitalised for observation. We sought to characterise the progression of fast-breathing pneumonia among children undergoing repeat assessments to better understand which children do and do not deteriorate. METHODS: Vital signs and physical examination findings, including respiratory rate, arterial oxygen saturation measured by pulse oximetry (S pO2 ), chest indrawing and temperature were assessed every 3 h for the duration of hospitalisation. Children were assessed for treatment failure during study visits on days 1, 2, 3 and 4. RESULTS: Hospital monitoring data from 436 children were included. While no children had S pO2 90-93% at baseline, 7.4% (16 of 215) of children receiving amoxicillin and 9.5% (21 of 221) receiving placebo developed S pO2 90-93% during monitoring. Similarly, no children had chest indrawing at enrolment, but 6.6% (14 of 215) in the amoxicillin group and 7.2% (16 of 221) in the placebo group went on to develop chest indrawing during hospitalisation. CONCLUSION: Repeat monitoring of children with fast-breathing pneumonia identified vital and physical examination signs not present at baseline, including S pO2 90-93% and chest indrawing. This information may support providers and policymakers in developing guidance for care of children with nonsevere pneumonia.

Pooled nucleic acid testing to detect antiretroviral treatment failure in Mexico.

BACKGROUND: Similar to other resource-limited settings, cost restricts availability of viral load monitoring for most patients receiving antiretroviral therapy in Tijuana, Mexico. We evaluated if a pooling method could improve efficiency and reduce costs while maintaining accuracy. METHODS: We evaluated 700 patient blood plasma specimens at a reference laboratory in Tijuana for detectable viremia, individually and in 10 × 10 matrix pools. Thresholds for virologic failure were set at ≥500, ≥1000 and ≥1500 HIV RNA copies per milliliter. Detectable pools were deconvoluted using pre-set algorithms. Accuracy and efficiency of the pooling method were compared with individual testing. Quality assurance (QA) measures were evaluated after 1 matrix demonstrated low efficiency relative to individual testing. RESULTS: Twenty-two percent of the cohort had detectable HIV RNA (≥50 copies/mL). Pooling methods saved approximately one third of viral load assays over individual testing, while maintaining negative predictive values of >90% to detect samples with virologic failure (≥50 copies/mL). One matrix with low relative efficiency would have been detected earlier using the developed QA measures, but its exclusion would have only increased relative efficiency from 39% to 42%. These methods would have saved between $13,223 and $14,308 for monitoring this cohort. CONCLUSIONS: Despite limited clinical data, high prevalence of detectable viral loads and a contaminated matrix, pooling greatly improved efficiency of virologic monitoring while maintaining accuracy. By improving cost-effectiveness, these methods could provide sustainability of virologic monitoring in resource-limited settings, and incorporation of developed QA measures will most likely maximize pooling efficiency in future uses.

Pooled nucleic acid testing to identify antiretroviral treatment failure during HIV infection.

BACKGROUND: Pooling strategies have been used to reduce the costs of polymerase chain reaction-based screening for acute HIV infection in populations in which the prevalence of acute infection is low (less than 1%). Only limited research has been done for conditions in which the prevalence of screening positivity is higher (greater than 1%). METHODS AND RESULTS: We present data on a variety of pooling strategies that incorporate the use of polymerase chain reaction-based quantitative measures to monitor for virologic failure among HIV-infected patients receiving antiretroviral therapy. For a prevalence of virologic failure between 1% and 25%, we demonstrate relative efficiency and accuracy of various strategies. These results could be used to choose the best strategy based on the requirements of individual laboratory and clinical settings such as required turnaround time of results and availability of resources. CONCLUSIONS: Virologic monitoring during antiretroviral therapy is not currently being performed in many resource-constrained settings largely because of costs. The presented pooling strategies may be used to significantly reduce the cost compared with individual testing, make such monitoring feasible, and limit the development and transmission of HIV drug resistance in resource-constrained settings. They may also be used to design efficient pooling strategies for other settings with quantitative screening measures.

The use of pooled viral load testing to identify antiretroviral treatment failure.

BACKGROUND: To develop less costly methods to virologically monitor patients receiving antiretroviral therapy, we evaluated methods that use pooled blood samples and quantitative information available from viral load assays to monitor a cohort of patients on first-line antiretroviral therapy for virologic failure. METHODS: We evaluated 150 blood samples collected after 6 months of therapy from participants enrolled in a San Diego primary infection program between January 1998 and January 2007. Samples were screened for virologic failure with individual viral load testing, 10 x 10 matrix pools and minipools of five samples. For the pooled platforms (matrix and minipools), we used a search and retest algorithm based on the quantitative viral load data to resolve samples that remained ambiguous for virologic failure. Viral load thresholds were more than 500 and more than 1500 copies/ml for the matrix and more than 250 and more than 500 copies/ml for the minipool. Efficiency, accuracy and result turnaround times were evaluated. RESULTS: Twenty-three percent of cohort samples were detectable at more than 50 HIV RNA copies/ml. At an algorithm threshold of more than 500 HIV RNA copies/ml, both minipool and matrix methods used less than half the number of viral load assays to screen the cohort, compared with testing samples individually. Both pooling platforms had negative predictive values of 100% for viral loads of more than 500 HIV RNA copies/ml and at least 94% for viral loads of more than 250 HIV RNA copies/ml. CONCLUSION: In this cohort, both pooling methods improved the efficiency of virologic monitoring over individual testing with a minimal decrease in accuracy. These methods may allow for the induction and sustainability of the virologic monitoring of patients receiving antiretroviral therapy in resource-limited settings.