Viewpoint: Evaluating the impact of malaria control efforts on mortality in sub-Saharan Africa

OBJECTIVE To describe an approach for evaluating the impact of malaria control efforts on malaria-associated mortality in sub-Saharan Africa, where disease-specific mortality trends usually cannot be measured directly and most malaria deaths occur among young children. METHODS Methods for evaluating changes in malaria-associated mortality are examined; advantages and disadvantages are presented. RESULTS All methods require a plausibility argument - i.e., an assumption that mortality reductions can be attributed to programmatic efforts if improvements are found in steps of the causal pathway between intervention scale-up and mortality trends. As different methods provide complementary information, they can be used together. We recommend following trends in the coverage of malaria control interventions, other factors influencing childhood mortality, malaria-associated morbidity (especially anaemia), and all-cause childhood mortality. This approach reflects decreases in malaria's direct and indirect mortality burden and can be examined in nearly all countries. Adding other information can strengthen the plausibility argument: trends in indicators of malaria transmission, information from demographic surveillance systems and sentinel sites where malaria diagnostics are systematically used, and verbal autopsies linked to representative household surveys. Health facility data on malaria deaths have well-recognized limitations; however, in specific circumstances, they could produce reliable trends. Model-based predictions can help describe changes in malaria-specific burden and assist with program management and advocacy. CONCLUSIONS Despite challenges, efforts to reduce malaria-associated mortality in Africa can be evaluated with trends in malaria intervention coverage and all-cause childhood mortality. Where there are resources and interest, complementary data on malaria morbidity and malaria-specific mortality could be added

Indicators Measuring the Performance of Malaria Programs Supported by the Global Fund in Asia, Progress and the Way Forward

INTRODUCTION: In 2010, the Global Fund provided more than 75% of external international financing for malaria control. The Global Fund uses performance based funding in the grants it finances. This paper analyses the indicators used to measure the performance of Global Fund supported malaria grants in Asia. METHODS: Indicators used in the performance frameworks for all Global Fund supported malaria grants in Asia were retrieved from grant database and grouped into impact, outcome, output and input categories and categorized by service delivery areas. Indicators of each group were compared over rounds. Indicators used in performance frameworks were compared with internationally adopted indicators included in the Monitoring and Evaluation Toolkit developed by the Global Fund and international technical agencies. RESULTS: Between 2002 and 2010, 1,434 indicators were included in the performance frameworks of the 48 malaria grants awarded in Asia, including 229 impact and 227 outcome indicators, 437 output and 541 input indicators, with an average of 29.9 indicators per grant. The proportion of impact and outcome indicators increased over rounds, with that of input indicators declining from 44.1% in Round 1 to 22.7% in Round 9. CONCLUSIONS: Input indicators, which have predominated the performance frameworks of the Global Fund supported malaria programs in Asia have declined between Rounds 1 and 9. However, increased alignment with internationally adopted indicators included in the Monitoring and Evaluation Toolkit is needed to improve the validity of reported results

Improving pneumonia case-management in Benin: a randomized trial of a multi-faceted intervention to support health worker adherence to Integrated Management of Childhood Illness guidelines

<p>Abstract</p> <p>Background</p> <p>Pneumonia is a leading cause of death among children under five years of age. The Integrated Management of Childhood Illness strategy can improve the quality of care for pneumonia and other common illnesses in developing countries, but adherence to these guidelines could be improved. We evaluated an intervention in Benin to support health worker adherence to the guidelines after training, focusing on pneumonia case management.</p> <p>Methods</p> <p>We conducted a randomized trial. After a health facility survey in 1999 to assess health care quality before Integrated Management of Childhood Illness training, health workers received training plus either study supports (job aids, non-financial incentives and supervision of workers and supervisors) or "usual" supports. Follow-up surveys were conducted in 2001, 2002 and 2004. Outcomes were indicators of health care quality for Integrated Management-defined pneumonia. Further analyses included a graphical pathway analysis and multivariable logistic regression modelling to identify factors influencing case-management quality.</p> <p>Results</p> <p>We observed 301 consultations of children with non-severe pneumonia that were performed by 128 health workers in 88 public and private health facilities. Although outcomes improved in both intervention and control groups, we found no statistically significant difference between groups. However, training proceeded slowly, and low-quality care from untrained health workers diluted intervention effects. Per-protocol analyses suggested that health workers with training plus study supports performed better than those with training plus usual supports (20.4 and 19.2 percentage-point improvements for recommended treatment [p = 0.08] and "recommended or adequate" treatment [p = 0.01], respectively). Both groups tended to perform better than untrained health workers. Analyses of treatment errors revealed that incomplete assessment and difficulties processing clinical findings led to missed pneumonia diagnoses, and missed diagnoses led to inadequate treatment. Increased supervision frequency was associated with better care (odds ratio for recommended treatment = 2.1 [95% confidence interval: 1.13.9] per additional supervisory visit).</p> <p>Conclusion</p> <p>Integrated Management of Childhood Illness training was useful, but insufficient, to achieve high-quality pneumonia case management. Our study supports led to additional improvements, although large gaps in performance still remained. A simple graphical pathway analysis can identify specific, common errors that health workers make in the case-management process; this information could be used to target quality improvement activities, such as supervision (ClinicalTrials.gov number NCT00510679).</p

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Evaluating health worker performance in Benin using the simulated client method with real children

Abstract Background The simulated client (SC) method for evaluating health worker performance utilizes surveyors who pose as patients to make surreptitious observations during consultations. Compared to conspicuous observation (CO) by surveyors, which is commonly done in developing countries, SC data better reflect usual health worker practices. This information is important because CO can cause performance to be better than usual. Despite this advantage of SCs, the method’s full potential has not been realized for evaluating performance for pediatric illnesses because real children have not been utilized as SCs. Previous SC studies used scenarios of ill children that were not actually brought to health workers. During a trial that evaluated a quality improvement intervention in Benin (the Integrated Management of Childhood Illness [IMCI] strategy), we conducted an SC survey with adult caretakers as surveyors and real children to evaluate the feasibility of this approach and used the results to assess the validity of CO. Methods We conducted an SC survey and a CO survey (one right after the other) of health workers in the same 55 health facilities. A detailed description of the SC survey process was produced. Results of the two surveys were compared for 27 performance indicators using logistic regression modeling. Results SC and CO surveyors observed 54 and 185 consultations, respectively. No serious problems occurred during the SC survey. Performance levels measured by CO were moderately higher than those measured by SCs (median CO – SC difference = 16.4 percentage-points). Survey differences were sometimes much greater for IMCI-trained health workers (median difference = 29.7 percentage-points) than for workers without IMCI training (median difference = 3.1 percentage-points). Conclusion SC surveys can be done safely with real children if appropriate precautions are taken. CO can introduce moderately large positive biases, and these biases might be greater for health workers exposed to quality improvement interventions. Trial number http://clinicaltrials.gov Identifier NCT00510679</p

Gatifloxacin versus chloramphenicol for uncomplicated enteric fever: an open-label, randomised, controlled trial.

BACKGROUND: We aimed to investigate whether gatifloxacin, a new generation and affordable fluoroquinolone, is better than chloramphenicol for the treatment of uncomplicated enteric fever in children and adults. METHODS: We did an open-label randomised superiority trial at Patan Hospital, Kathmandu, Nepal, to investigate whether gatifloxacin is more effective than chloramphenicol for treating uncomplicated enteric fever. Children and adults clinically diagnosed with enteric fever received either gatifloxacin (10 mg/kg) once a day for 7 days, or chloramphenicol (75 mg/kg per day) in four divided doses for 14 days. Patients were randomly allocated treatment (1:1) in blocks of 50, without stratification. Allocations were placed in sealed envelopes opened by the study physician once a patient was enrolled into the trial. Masking was not possible because of the different formulations and ways of giving the two drugs. The primary outcome measure was treatment failure, which consisted of at least one of the following: persistent fever at day 10, need for rescue treatment, microbiological failure, relapse until day 31, and enteric-fever-related complications. The primary outcome was assessed in all patients randomly allocated treatment and reported separately for culture-positive patients and for all patients. Secondary outcome measures were fever clearance time, late relapse, and faecal carriage. The trial is registered on controlled-trials.com, number ISRCTN 53258327. FINDINGS: 844 patients with a median age of 16 (IQR 9-22) years were enrolled in the trial and randomly allocated a treatment. 352 patients had blood-culture-confirmed enteric fever: 175 were treated with chloramphenicol and 177 with gatifloxacin. 14 patients had treatment failure in the chloramphenicol group, compared with 12 in the gatifloxacin group (hazard ratio [HR] of time to failure 0·86, 95% CI 0·40-1·86, p=0·70). The median time to fever clearance was 3·95 days (95% CI 3·68-4·68) in the chloramphenicol group and 3·90 days (3·58-4·27) in the gatifloxacin group (HR 1·06, 0·86-1·32, p=0·59). At 1 month only, three of 148 patients were stool-culture positive in the chloramphenicol group and none in the gatifloxacin group. At the end of 3 months only one person had a positive stool culture in the chloramphenicol group. There were no other positive stool cultures even at the end of 6 months. Late relapses were noted in three of 175 patients in the culture-confirmed chloramphenicol group and two of 177 in the gatifloxacin group. There were no culture-positive relapses after day 62. 99 patients (24%) experienced 168 adverse events in the chloramphenicol group and 59 (14%) experienced 73 events in the gatifloxacin group. INTERPRETATION: Although no more efficacious than chloramphenicol, gatifloxacin should be the preferred treatment for enteric fever in developing countries because of its shorter treatment duration and fewer adverse events. FUNDING: Wellcome Trust