Gene Expression Classification of Colon Cancer into Molecular Subtypes: Characterization, Validation, and Prognostic Value
by Laetitia Marisa, Aurélien de Reyniès, Alex Duval, Janick Selves, Marie Pierre Gaub, Laure Vescovo, Marie-Christine Etienne-Grimaldi, Renaud Schiappa, Dominique Guenot, Mira Ayadi, Sylvain Kirzin, Maurice Chazal, Jean-François Fléjou, Daniel Benchimol, Anne Berger, Arnaud Lagarde, Erwan Pencreach, Françoise Piard, Dominique Elias, Yann Parc, Sylviane Olschwang, Gérard Milano, Pierre Laurent-Puig, Valérie BoigeBackground
Colon cancer (CC) pathological staging fails to accurately predict recurrence, and to date, no gene expression signature has proven reliable for prognosis stratification in clinical practice, perhaps because CC is a heterogeneous disease. The aim of this study was to establish a comprehensive molecular classification of CC based on mRNA expression profile analyses.Methods and Findings
Fresh-frozen primary tumor samples from a large multicenter cohort of 750 patients with stage I to IV CC who underwent surgery between 1987 and 2007 in seven centers were characterized for common DNA alterations, including BRAF, KRAS, and TP53 mutations, CpG island methylator phenotype, mismatch repair status, and chromosomal instability status, and were screened with whole genome and transcriptome arrays. 566 samples fulfilled RNA quality requirements. Unsupervised consensus hierarchical clustering applied to gene expression data from a discovery subset of 443 CC samples identified six molecular subtypes. These subtypes were associated with distinct clinicopathological characteristics, molecular alterations, specific enrichments of supervised gene expression signatures (stem cell phenotype–like, normal-like, serrated CC phenotype–like), and deregulated signaling pathways. Based on their main biological characteristics, we distinguished a deficient mismatch repair subtype, a KRAS mutant subtype, a cancer stem cell subtype, and three chromosomal instability subtypes, including one associated with down-regulated immune pathways, one with up-regulation of the Wnt pathway, and one displaying a normal-like gene expression profile. The classification was validated in the remaining 123 samples plus an independent set of 1,058 CC samples, including eight public datasets. Furthermore, prognosis was analyzed in the subset of stage II–III CC samples. The subtypes C4 and C6, but not the subtypes C1, C2, C3, and C5, were independently associated with shorter relapse-free survival, even after adjusting for age, sex, stage, and the emerging prognostic classifier Oncotype DX Colon Cancer Assay recurrence score (hazard ratio 1.5, 95% CI 1.1–2.1, p = 0.0097). However, a limitation of this study is that information on tumor grade and number of nodes examined was not available.Conclusions
We describe the first, to our knowledge, robust transcriptome-based classification of CC that improves the current disease stratification based on clinicopathological variables and common DNA markers. The biological relevance of these subtypes is illustrated by significant differences in prognosis. This analysis provides possibilities for improving prognostic models and therapeutic strategies. In conclusion, we report a new classification of CC into six molecular subtypes that arise through distinct biological pathways.Please see later in the article for the Editors' Summary
Contribution of H. pylori and Smoking Trends to US Incidence of Intestinal-Type Noncardia Gastric Adenocarcinoma: A Microsimulation Model
by Jennifer M. Yeh, Chin Hur, Deb Schrag, Karen M. Kuntz, Majid Ezzati, Natasha Stout, Zachary Ward, Sue J. GoldieBackground
Although gastric cancer has declined dramatically in the US, the disease remains the second leading cause of cancer mortality worldwide. A better understanding of reasons for the decline can provide important insights into effective preventive strategies. We sought to estimate the contribution of risk factor trends on past and future intestinal-type noncardia gastric adenocarcinoma (NCGA) incidence.Methods and Findings
We developed a population-based microsimulation model of intestinal-type NCGA and calibrated it to US epidemiologic data on precancerous lesions and cancer. The model explicitly incorporated the impact of Helicobacter pylori and smoking on disease natural history, for which birth cohort-specific trends were derived from the National Health and Nutrition Examination Survey (NHANES) and National Health Interview Survey (NHIS). Between 1978 and 2008, the model estimated that intestinal-type NCGA incidence declined 60% from 11.0 to 4.4 per 100,000 men, <3% discrepancy from national statistics. H. pylori and smoking trends combined accounted for 47% (range = 30%–58%) of the observed decline. With no tobacco control, incidence would have declined only 56%, suggesting that lower smoking initiation and higher cessation rates observed after the 1960s accelerated the relative decline in cancer incidence by 7% (range = 0%–21%). With continued risk factor trends, incidence is projected to decline an additional 47% between 2008 and 2040, the majority of which will be attributable to H. pylori and smoking (81%; range = 61%–100%). Limitations include assuming all other risk factors influenced gastric carcinogenesis as one factor and restricting the analysis to men.Conclusions
Trends in modifiable risk factors explain a significant proportion of the decline of intestinal-type NCGA incidence in the US, and are projected to continue. Although past tobacco control efforts have hastened the decline, full benefits will take decades to be realized, and further discouragement of smoking and reduction of H. pylori should be priorities for gastric cancer control efforts.Please see later in the article for the Editors' Summary
Grand Challenges: Improving HIV Treatment Outcomes by Integrating Interventions for Co-Morbid Mental Illness
by Sylvia Kaaya, Eddy Eustache, Ilana Lapidos-Salaiz, Seggane Musisi, Christina Psaros, Lawrence Wissow
Integrating Global and National Knowledge to Select Medicines for Children: The Ghana National Drugs Programme
by David Sinclair, Martha Gyansa-Lutterodt, Brian Asare, Augustina Koduah, Edith Andrews, Paul Garner
by Victoria K. Ngo, Adolfo Rubinstein, Vijay Ganju, Pamela Kanellis, Nasser Loza, Cristina Rabadan-Diehl, Abdallah S. Daar
Effect of Facilitation of Local Maternal-and-Newborn Stakeholder Groups on Neonatal Mortality: Cluster-Randomized Controlled Trial
by Lars Åke Persson, Nguyen T. Nga, Mats Målqvist, Dinh Thi Phuong Hoa, Leif Eriksson, Lars Wallin, Katarina Selling, Tran Q. Huy, Duong M. Duc, Tran V. Tiep, Vu Thi Thu Thuy, Uwe EwaldBackground
Facilitation of local women's groups may reportedly reduce neonatal mortality. It is not known whether facilitation of groups composed of local health care staff and politicians can improve perinatal outcomes. We hypothesised that facilitation of local stakeholder groups would reduce neonatal mortality (primary outcome) and improve maternal, delivery, and newborn care indicators (secondary outcomes) in Quang Ninh province, Vietnam.Methods and Findings
In a cluster-randomized design 44 communes were allocated to intervention and 46 to control. Laywomen facilitated monthly meetings during 3 years in groups composed of health care staff and key persons in the communes. A problem-solving approach was employed. Births and neonatal deaths were monitored, and interviews were performed in households of neonatal deaths and of randomly selected surviving infants. A latent period before effect is expected in this type of intervention, but this timeframe was not pre-specified. Neonatal mortality rate (NMR) from July 2008 to June 2011 was 16.5/1,000 (195 deaths per 11,818 live births) in the intervention communes and 18.4/1,000 (194 per 10,559 live births) in control communes (adjusted odds ratio [OR] 0.96 [95% CI 0.73–1.25]). There was a significant downward time trend of NMR in intervention communes (p = 0.003) but not in control communes (p = 0.184). No significant difference in NMR was observed during the first two years (July 2008 to June 2010) while the third year (July 2010 to June 2011) had significantly lower NMR in intervention arm: adjusted OR 0.51 (95% CI 0.30–0.89). Women in intervention communes more frequently attended antenatal care (adjusted OR 2.27 [95% CI 1.07–4.8]).Conclusions
A randomized facilitation intervention with local stakeholder groups composed of primary care staff and local politicians working for three years with a perinatal problem-solving approach resulted in increased attendance to antenatal care and reduced neonatal mortality after a latent period.Trial registration
Current Controlled Trials ISRCTN44599712Please see later in the article for the Editors' Summary
Setting Research Priorities to Reduce Mortality and Morbidity of Childhood Diarrhoeal Disease in the Next 15 Years
by Kerri Wazny, Alvin Zipursky, Robert Black, Valerie Curtis, Christopher Duggan, Richard Guerrant, Myron Levine, William A. Petri, Mathuram Santosham, Rebecca Scharf, Philip M. Sherman, Evan Simpson, Mark Young, Zulfiqar A. Bhutta
Carriage of Mycoplasma pneumoniae in the Upper Respiratory Tract of Symptomatic and Asymptomatic Children: An Observational Study
by Emiel B. M. Spuesens, Pieter L. A. Fraaij, Eline G. Visser, Theo Hoogenboezem, Wim C. J. Hop, Léon N. A. van Adrichem, Frank Weber, Henriette A. Moll, Berth Broekman, Marjolein Y. Berger, Tineke van Rijsoort-Vos, Alex van Belkum, Martin Schutten, Suzan D. Pas, Albert D. M. E. Osterhaus, Nico G. Hartwig, Cornelis Vink, Annemarie M. C. van RossumBackground
Mycoplasma pneumoniae is thought to be a common cause of respiratory tract infections (RTIs) in children. The diagnosis of M. pneumoniae RTIs currently relies on serological methods and/or the detection of bacterial DNA in the upper respiratory tract (URT). It is conceivable, however, that these diagnostic methods also yield positive results if M. pneumoniae is carried asymptomatically in the URT. Positive results from these tests may therefore not always be indicative of a symptomatic infection. The existence of asymptomatic carriage of M. pneumoniae has not been established. We hypothesized that asymptomatic carriage in children exists and investigated whether colonization and symptomatic infection could be differentiated by current diagnostic methods.Methods and Findings
This study was conducted at the Erasmus MC–Sophia Children's Hospital and the after-hours General Practitioners Cooperative in Rotterdam, The Netherlands. Asymptomatic children (n = 405) and children with RTI symptoms (n = 321) aged 3 mo to 16 y were enrolled in a cross-sectional study from July 1, 2008, to November 30, 2011. Clinical data, pharyngeal and nasopharyngeal specimens, and serum samples were collected. The primary objective was to differentiate between colonization and symptomatic infection with M. pneumoniae by current diagnostic methods, especially real-time PCR. M. pneumoniae DNA was detected in 21.2% (95% CI 17.2%–25.2%) of the asymptomatic children and in 16.2% (95% CI 12.2%–20.2%) of the symptomatic children (p = 0.11). Neither serology nor quantitative PCR nor culture differentiated asymptomatic carriage from infection. A total of 202 children were tested for the presence of other bacterial and viral pathogens. Two or more pathogens were found in 56% (63/112) of the asymptomatic children and in 55.5% (50/90) of the symptomatic children. Finally, longitudinal sampling showed persistence of M. pneumoniae in the URT for up to 4 mo. Fifteen of the 21 asymptomatic children with M. pneumoniae and 19 of the 22 symptomatic children with M. pneumoniae in this longitudinal follow-up tested negative after 1 mo.Conclusions
Although our study has limitations, such as a single study site and limited sample size, our data indicate that the presence of M. pneumoniae in the URT is common in asymptomatic children. The current diagnostic tests for M. pneumoniae are unable to differentiate between asymptomatic carriage and symptomatic infection.Please see later in the article for the Editors' Summary
by Jennifer Bryce, Fred Arnold, Ann Blanc, Attila Hancioglu, Holly Newby, Jennifer Requejo, Tessa Wardlaw, the CHERG Working Group on Improving Coverage MeasurementConsiderable progress has been made in reducing maternal, newborn, and child mortality worldwide, but many more deaths could be prevented if effective interventions were available to all who could benefit from them. Timely, high-quality measurements of intervention coverage—the proportion of a population in need of a health intervention that actually receives it—are essential to support sound decisions about progress and investments in women's and children's health. The PLOS Medicine “Measuring Coverage in MNCH” Collection of research studies and reviews presents systematic assessments of the validity of health intervention coverage measurement based on household surveys, the primary method for estimating population-level intervention coverage in low- and middle-income countries. In this overview of the Collection, we discuss how and why some of the indicators now being used to track intervention coverage may not provide fully reliable coverage measurements, and how a better understanding of the systematic and random error inherent in these coverage indicators can help in their interpretation and use. We draw together strategies proposed across the Collection for improving coverage measurement, and recommend continued support for high-quality household surveys at national and sub-national levels, supplemented by surveys with lighter tools that can be implemented every 1–2 years and by complementary health-facility-based assessments of service quality. Finally, we stress the importance of learning more about coverage measurement to strengthen the foundation for assessing and improving the progress of maternal, newborn, and child health programs. Please see later in the article for the Editors' Summary
Measuring Coverage in MNCH: Challenges in Monitoring the Proportion of Young Children with Pneumonia Who Receive Antibiotic Treatment
by Harry Campbell, Shams el Arifeen, Tabish Hazir, James O'Kelly, Jennifer Bryce, Igor Rudan, Shamim Ahmad QaziPneumonia remains a major cause of child death globally, and improving antibiotic treatment rates is a key control strategy. Progress in improving the global coverage of antibiotic treatment is monitored through large household surveys such as the Demographic and Health Surveys (DHS) and the Multiple Indicator Cluster Surveys (MICS), which estimate antibiotic treatment rates of pneumonia based on two-week recall of pneumonia by caregivers. However, these survey tools identify children with reported symptoms of pneumonia, and because the prevalence of pneumonia over a two-week period in community settings is low, the majority of these children do not have true pneumonia and so do not provide an accurate denominator of pneumonia cases for monitoring antibiotic treatment rates. In this review, we show that the performance of survey tools could be improved by increasing the survey recall period or by improving either overall discriminative power or specificity. However, even at a test specificity of 95% (and a test sensitivity of 80%), the proportion of children with reported symptoms of pneumonia who truly have pneumonia is only 22% (the positive predictive value of the survey tool). Thus, although DHS and MICS survey data on rates of care seeking for children with reported symptoms of pneumonia and other childhood illnesses remain valid and important, DHS and MICS data are not able to give valid estimates of antibiotic treatment rates in children with pneumonia.
Measuring Coverage in MNCH: Tracking Progress in Health for Women and Children Using DHS and MICS Household Surveys
by Attila Hancioglu, Fred ArnoldHousehold surveys are the primary data source of coverage indicators for children and women for most developing countries. Most of this information is generated by two global household survey programmes—the USAID-supported Demographic and Health Surveys (DHS) and the UNICEF-supported Multiple Indicator Cluster Surveys (MICS). In this review, we provide an overview of these two programmes, which cover a wide range of child and maternal health topics and provide estimates of many Millennium Development Goal indicators, as well as estimates of the indicators for the Countdown to 2015 initiative and the Commission on Information and Accountability for Women's and Children's Health. MICS and DHS collaborate closely and work through interagency processes to ensure that survey tools are harmonized and comparable as far as possible, but we highlight differences between DHS and MICS in the population covered and the reference periods used to measure coverage. These differences need to be considered when comparing estimates of reproductive, maternal, newborn, and child health indicators across countries and over time and we discuss the implications of these differences for coverage measurement. Finally, we discuss the need for survey planners and consumers of survey results to understand the strengths, limitations, and constraints of coverage measurements generated through household surveys, and address some technical issues surrounding sampling and quality control. We conclude that, although much effort has been made to improve coverage measurement in household surveys, continuing efforts are needed, including further research to improve and refine survey methods and analytical techniques.
Measuring Coverage in MNCH: Design, Implementation, and Interpretation Challenges Associated with Tracking Vaccination Coverage Using Household Surveys
by Felicity T. Cutts, Hector S. Izurieta, Dale A. RhodaVaccination coverage is an important public health indicator that is measured using administrative reports and/or surveys. The measurement of vaccination coverage in low- and middle-income countries using surveys is susceptible to numerous challenges. These challenges include selection bias and information bias, which cannot be solved by increasing the sample size, and the precision of the coverage estimate, which is determined by the survey sample size and sampling method. Selection bias can result from an inaccurate sampling frame or inappropriate field procedures and, since populations likely to be missed in a vaccination coverage survey are also likely to be missed by vaccination teams, most often inflates coverage estimates. Importantly, the large multi-purpose household surveys that are often used to measure vaccination coverage have invested substantial effort to reduce selection bias. Information bias occurs when a child's vaccination status is misclassified due to mistakes on his or her vaccination record, in data transcription, in the way survey questions are presented, or in the guardian's recall of vaccination for children without a written record. There has been substantial reliance on the guardian's recall in recent surveys, and, worryingly, information bias may become more likely in the future as immunization schedules become more complex and variable. Finally, some surveys assess immunity directly using serological assays. Sero-surveys are important for assessing public health risk, but currently are unable to validate coverage estimates directly. To improve vaccination coverage estimates based on surveys, we recommend that recording tools and practices should be improved and that surveys should incorporate best practices for design, implementation, and analysis.
Measuring Coverage in MNCH: Total Survey Error and the Interpretation of Intervention Coverage Estimates from Household Surveys
by Thomas P. Eisele, Dale A. Rhoda, Felicity T. Cutts, Joseph Keating, Ruilin Ren, Aluisio J. D. Barros, Fred ArnoldNationally representative household surveys are increasingly relied upon to measure maternal, newborn, and child health (MNCH) intervention coverage at the population level in low- and middle-income countries. Surveys are the best tool we have for this purpose and are central to national and global decision making. However, all survey point estimates have a certain level of error (total survey error) comprising sampling and non-sampling error, both of which must be considered when interpreting survey results for decision making. In this review, we discuss the importance of considering these errors when interpreting MNCH intervention coverage estimates derived from household surveys, using relevant examples from national surveys to provide context. Sampling error is usually thought of as the precision of a point estimate and is represented by 95% confidence intervals, which are measurable. Confidence intervals can inform judgments about whether estimated parameters are likely to be different from the real value of a parameter. We recommend, therefore, that confidence intervals for key coverage indicators should always be provided in survey reports. By contrast, the direction and magnitude of non-sampling error is almost always unmeasurable, and therefore unknown. Information error and bias are the most common sources of non-sampling error in household survey estimates and we recommend that they should always be carefully considered when interpreting MNCH intervention coverage based on survey data. Overall, we recommend that future research on measuring MNCH intervention coverage should focus on refining and improving survey-based coverage estimates to develop a better understanding of how results should be interpreted and used.
Measuring Coverage in MNCH: Evaluation of Community-Based Treatment of Childhood Illnesses through Household Surveys
by Elizabeth Hazel, Jennifer Requejo, Julia David, Jennifer BryceCommunity case management (CCM) is a strategy for training and supporting workers at the community level to provide treatment for the three major childhood diseases—diarrhea, fever (indicative of malaria), and pneumonia—as a complement to facility-based care. Many low- and middle-income countries are now implementing CCM and need to evaluate whether adoption of the strategy is associated with increases in treatment coverage. In this review, we assess the extent to which large-scale, national household surveys can serve as sources of baseline data for evaluating trends in community-based treatment coverage for childhood illnesses. Our examination of the questionnaires used in Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) conducted between 2005 and 2010 in five sub-Saharan African countries shows that questions on care seeking that included a locally adapted option for a community-based provider were present in all the DHS surveys and in some MICS surveys. Most of the surveys also assessed whether appropriate treatments were available, but only one survey collected information on the place of treatment for all three illnesses. This absence of baseline data on treatment source in household surveys will limit efforts to evaluate the effects of the introduction of CCM strategies in the study countries. We recommend alternative analysis plans for assessing CCM programs using household survey data that depend on baseline data availability and on the timing of CCM policy implementation.
Measuring Coverage in MNCH: Challenges and Opportunities in the Selection of Coverage Indicators for Global Monitoring
by Jennifer Harris Requejo, Holly Newby, Jennifer BryceGlobal monitoring of intervention coverage is a cornerstone of international efforts to improve reproductive, maternal, newborn, and child health. In this review, we examine the process and implications of selecting a core set of coverage indicators for global monitoring, using as examples the processes used by the Countdown to 2015 for Maternal, Newborn and Child Survival and the Commission on Accountability for Women's and Children's Health. We describe how the generation of data for global monitoring involves five iterative steps: development of standard indicator definitions and measurement approaches to ensure comparability across countries; collection of high-quality data at the country level; compilation of country data at the global level; organization of global databases; and rounds of data quality checking. Regular and rigorous technical review processes that involve high-level decision makers and experts familiar with indicator measurement are needed to maximize uptake and to ensure that indicators used for global monitoring are selected on the basis of available evidence of intervention effectiveness, feasibility of measurement, and data availability as well as programmatic relevance. Experience from recent initiatives illustrates the challenges of striking this balance as well as strategies for reducing the tensions inherent in the indicator selection process. We conclude that more attention and continued investment need to be directed to global monitoring, to support both the process of global database development and the selection of sets of coverage indicators to promote accountability. The stakes are high, because these indicators can drive policy and program development at the country and global level, and ultimately impact the health of women and children and the communities where they live.
Measuring Coverage in MNCH: Population HIV-Free Survival among Children under Two Years of Age in Four African Countries
by Jeffrey S. A. Stringer, Kathryn Stinson, Pius M. Tih, Mark J. Giganti, Didier K. Ekouevi, Tracy L. Creek, Thomas K. Welty, Benjamin H. Chi, Catherine M. Wilfert, Nathan Shaffer, Elizabeth M. Stringer, Francois Dabis, David CoetzeeBackground
Population-based evaluations of programs for prevention of mother-to-child HIV transmission (PMTCT) are scarce. We measured PMTCT service coverage, regimen use, and HIV-free survival among children ≤24 mo of age in Cameroon, Côte D'Ivoire, South Africa, and Zambia.Methods and Findings
We randomly sampled households in 26 communities and offered participation if a child had been born to a woman living there during the prior 24 mo. We tested consenting mothers with rapid HIV antibody tests and tested the children of seropositive mothers with HIV DNA PCR or rapid antibody tests. Our primary outcome was 24-mo HIV-free survival, estimated with survival analysis. In an individual-level analysis, we evaluated the effectiveness of various PMTCT regimens. In a community-level analysis, we evaluated the relationship between HIV-free survival and community PMTCT coverage (the proportion of HIV-exposed infants in each community that received any PMTCT intervention during gestation or breastfeeding). We also compared our community coverage results to those of a contemporaneous study conducted in the facilities serving each sampled community. Of 7,985 surveyed children under 2 y of age, 1,014 (12.7%) were HIV-exposed. Of these, 110 (10.9%) were HIV-infected, 851 (83.9%) were HIV-uninfected, and 53 (5.2%) were dead. HIV-free survival at 24 mo of age among all HIV-exposed children was 79.7% (95% CI: 76.4, 82.6) overall, with the following country-level estimates: Cameroon (72.6%; 95% CI: 62.3, 80.5), South Africa (77.7%; 95% CI: 72.5, 82.1), Zambia (83.1%; 95% CI: 78.4, 86.8), and Côte D'Ivoire (84.4%; 95% CI: 70.0, 92.2). In adjusted analyses, the risk of death or HIV infection was non-significantly lower in children whose mothers received a more complex regimen of either two or three antiretroviral drugs compared to those receiving no prophylaxis (adjusted hazard ratio: 0.60; 95% CI: 0.34, 1.06). Risk of death was not different for children whose mothers received a more complex regimen compared to those given single-dose nevirapine (adjusted hazard ratio: 0.88; 95% CI: 0.45, 1.72). Community PMTCT coverage was highest in Cameroon, where 75 of 114 HIV-exposed infants met criteria for coverage (66%; 95% CI: 56, 74), followed by Zambia (219 of 444, 49%; 95% CI: 45, 54), then South Africa (152 of 365, 42%; 95% CI: 37, 47), and then Côte D'Ivoire (3 of 53, 5.7%; 95% CI: 1.2, 16). In a cluster-level analysis, community PMTCT coverage was highly correlated with facility PMTCT coverage (Pearson's r = 0.85), and moderately correlated with 24-mo HIV-free survival (Pearson's r = 0.29). In 14 of 16 instances where both the facility and community samples were large enough for comparison, the facility-based coverage measure exceeded that observed in the community.Conclusions
HIV-free survival can be estimated with community surveys and should be incorporated into ongoing country monitoring. Facility-based coverage measures correlate with those derived from community sampling, but may overestimate population coverage. The more complex regimens recommended by the World Health Organization seem to have measurable public health benefit at the population level, but power was limited and additional field validation is needed. Please see later in the article for the Editors' Summary
Measuring Coverage in MNCH: A Prospective Validation Study in Pakistan and Bangladesh on Measuring Correct Treatment of Childhood Pneumonia
by Tabish Hazir, Khadija Begum, Shams el Arifeen, Amira M. Khan, M. Hamidul Huque, Narjis Kazmi, Sushmita Roy, Saleem Abbasi, Qazi Sadeq-ur Rahman, Evropi Theodoratou, Mahmuda Shayema Khorshed, Kazi Mizanur Rahman, Sanwarul Bari, M. Mahfuzul Islam Kaiser, Samir K. Saha, A. S. M. Nawshad Uddin Ahmed, Igor Rudan, Jennifer Bryce, Shamim Ahmad Qazi, Harry CampbellBackground
Antibiotic treatment for pneumonia as measured by Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) is a key indicator for tracking progress in achieving Millennium Development Goal 4. Concerns about the validity of this indicator led us to perform an evaluation in urban and rural settings in Pakistan and Bangladesh.Methods and Findings
Caregivers of 950 children under 5 y with pneumonia and 980 with “no pneumonia” were identified in urban and rural settings and allocated for DHS/MICS questions 2 or 4 wk later. Study physicians assigned a diagnosis of pneumonia as reference standard; the predictive ability of DHS/MICS questions and additional measurement tools to identify pneumonia versus non-pneumonia cases was evaluated.Results at both sites showed suboptimal discriminative power, with no difference between 2- or 4-wk recall. Individual patterns of sensitivity and specificity varied substantially across study sites (sensitivity 66.9% and 45.5%, and specificity 68.8% and 69.5%, for DHS in Pakistan and Bangladesh, respectively). Prescribed antibiotics for pneumonia were correctly recalled by about two-thirds of caregivers using DHS questions, increasing to 72% and 82% in Pakistan and Bangladesh, respectively, using a drug chart and detailed enquiry.Conclusions
Monitoring antibiotic treatment of pneumonia is essential for national and global programs. Current (DHS/MICS questions) and proposed new (video and pneumonia score) methods of identifying pneumonia based on maternal recall discriminate poorly between pneumonia and children with cough. Furthermore, these methods have a low yield to identify children who have true pneumonia. Reported antibiotic treatment rates among these children are therefore not a valid proxy indicator of pneumonia treatment rates. These results have important implications for program monitoring and suggest that data in its current format from DHS/MICS surveys should not be used for the purpose of monitoring antibiotic treatment rates in children with pneumonia at the present time.Please see later in the article for the Editors' Summary
Measuring Coverage in MNCH: Accuracy of Measuring Diagnosis and Treatment of Childhood Malaria from Household Surveys in Zambia
by Thomas P. Eisele, Kafula Silumbe, Josh Yukich, Busiku Hamainza, Joseph Keating, Adam Bennett, John M. MillerBackground
To assess progress in the scale-up of rapid diagnostic tests and artemisinin-based combination therapies (ACTs) across Africa, malaria control programs have increasingly relied on standardized national household surveys to determine the proportion of children with a fever in the past 2 wk who received an effective antimalarial within 1–2 d of the onset of fever. Here, the validity of caregiver recall for measuring the primary coverage indicators for malaria diagnosis and treatment of children <5 y old is assessed.Methods and Findings
A cross-sectional study was conducted in five public clinics in Kaoma District, Western Provence, Zambia, to estimate the sensitivity, specificity, and accuracy of caregivers' recall of malaria testing, diagnosis, and treatment, compared to a gold standard of direct observation at the health clinics. Compared to the gold standard of clinic observation, for recall for children with fever in the past 2 wk, the sensitivity for recalling that a finger/heel stick was done was 61.9%, with a specificity of 90.0%. The sensitivity and specificity of caregivers' recalling a positive malaria test result were 62.4% and 90.7%, respectively. The sensitivity and specificity of recalling that the child was given a malaria diagnosis, irrespective of whether a laboratory test was actually done, were 76.8% and 75.9%, respectively. The sensitivity and specificity for recalling that an ACT was given were 81.0% and 91.5%, respectively.Conclusions
Based on these findings, results from household surveys should continue to be used for ascertaining the coverage of children with a fever in the past 2 wk that received an ACT. However, as recall of a malaria diagnosis remains suboptimal, its use in defining malaria treatment coverage is not recommended.Please see later in the article for the Editors' Summary
by Allisyn C. Moran, Kate Kerber, Deborah Sitrin, Tanya Guenther, Claudia S. Morrissey, Holly Newby, Joy Fishel, P. Stan Yoder, Zelee Hill, Joy E. LawnNeonatal mortality accounts for 43% of under-five mortality. Consequently, improving newborn survival is a global priority. However, although there is increasing consensus on the packages and specific interventions that need to be scaled up to reduce neonatal mortality, there is a lack of clarity on the indicators needed to measure progress. In 2008, in an effort to improve newborn survival, the Newborn Indicators Technical Working Group (TWG) was convened by the Saving Newborn Lives program at Save the Children to provide a forum to develop the indicators and standard measurement tools that are needed to measure coverage of key newborn interventions. The TWG, which included evaluation and measurement experts, researchers, individuals from United Nations agencies and non-governmental organizations, and donors, prioritized improved consistency of measurement of postnatal care for women and newborns and of immediate care behaviors and practices for newborns. In addition, the TWG promoted increased data availability through inclusion of additional questions in nationally representative surveys, such as the United States Agency for International Development–supported Demographic and Health Surveys and the United Nations Children's Fund–supported Multiple Indicator Cluster Surveys. Several studies have been undertaken that have informed revisions of indicators and survey tools, and global postnatal care coverage indicators have been finalized. Consensus has been achieved on three additional indicators for care of the newborn after birth (drying, delayed bathing, and cutting the cord with a clean instrument), and on testing two further indicators (immediate skin-to-skin care and applications to the umbilical cord). Finally, important measurement gaps have been identified regarding coverage data for evidence-based interventions, such as Kangaroo Mother Care and care seeking for newborn infection.
Measuring Coverage in MNCH: Current Indicators for Measuring Coverage of Diarrhea Treatment Interventions and Opportunities for Improvement
by Christa L. Fischer Walker, Olivier Fontaine, Robert E. BlackDiarrhea morbidity and mortality remain important child health problems in low- and middle-income countries. The treatment of diarrhea and accurate measurement of treatment coverage are critical if child mortality is going to continue to decline. In this review, we examine diarrhea treatment coverage indicators collected in two large-scale community-based household surveys—the Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS). Current surveys do not distinguish between children with mild diarrhea episodes and those at risk for dehydration. Additional disease severity questions may improve the identification of cases of severe diarrhea but research is needed to identify indicators with the highest sensitivity and specificity. We also review the current treatment indicators in these surveys and highlight three areas for improvement and research. First, specific questions on fluids other than oral rehydration salts (ORS) should be eliminated to refocus the treatment of dehydration on ORS and to prevent confusion between prevention and treatment of dehydration. Second, consistency across surveys and throughout translations is needed for questions about the caregiver behavior of “offering" the sick child fluid and food. Third, breastfeeding should be separated from other fluid and food questions to capture the frequency and duration of nursing sessions offered during the illness. Research is also needed to assess the accuracy of the current zinc indicator to determine if caregivers are correctly recalling zinc treatment for current and recent diarrhea episodes.