The costs of integrated community case management (iCCM) programs: A multi-country analysis.

BACKGROUND: Integrated community case management (iCCM) can be an effective strategy for expanding the provision of diarrhea, pneumonia, and malaria services to children under 5 years old but there are concerns in some countries about the corresponding cost and impact. This paper presents and compares findings from a multi-country analysis of iCCM program costs. METHODS: Data on coverage, utilization, and costs were collected as part of two sets of studies conducted between 2011 and 2013 for iCCM programs in seven sub-Saharan African countries: Cameroon, the Democratic Republic of the Congo, Malawi, Senegal, Sierra Leone, South Sudan and Zambia. The data were used to compare some elements of program performance as well as costs per capita and costs per service (which are key indicators of resource allocation and efficiency). RESULTS: Among the seven countries, iCCM utilization ranged from a total of 0.26 to 3.05 contacts per capita (children 2-59 months) per year for the diseases treated, representing a range of 2.7% to 36.7% of the expected numbers of cases. The total recurrent cost per treatment ranged from US$ 2.44 to US$ 13.71 for diarrhea; from US$ 2.17 to US$ 17.54 for malaria (excluding rapid diagnostic testing); and from US$ 1.70 to US$ 12.94 for pneumonia. In some of the country programs, the utilization of iCCM services was quite low and this, together with significant fixed costs, particularly for management and supervision, resulted in services being quite costly. Given the differences across the countries and programs, however, these results should be treated as indicative and not definitive. CONCLUSION: A comprehensive understanding of iCCM program costs and results can help countries obtain resources and use them efficiently. To be cost-effective and affordable, iCCM programs must be well-utilized while program management and supervision should be organized to minimize costs and ensure quality of care. iCCM programs will not always be low-cost, however, particularly in small, remote villages where supervision and supply challenges are greater. Further research is needed to determine the cost-effectiveness of iCCM programs and corresponding patient and service delivery costs.

Functional genomic analysis of amniotic fluid cell-free mRNA suggests that oxidative stress is significant in Down syndrome fetuses.

To characterize the differences between second trimester Down syndrome (DS) and euploid fetuses, we used Affymetrix microarrays to compare gene expression in uncultured amniotic fluid supernatant samples. Functional pathway analysis highlighted the importance of oxidative stress, ion transport, and G protein signaling in the DS fetuses. Further evidence supporting these results was derived by correlating the observed gene expression patterns to those of small molecule drugs via the Connectivity Map. Our results suggest that there are secondary adverse consequences of DS evident in the second trimester, leading to testable hypotheses about possible antenatal therapy for DS.

Gene expression analysis in pregnant women and their infants identifies unique fetal biomarkers that circulate in maternal blood.

The discovery of fetal mRNA transcripts in the maternal circulation holds great promise for noninvasive prenatal diagnosis. To identify potential fetal biomarkers, we studied whole blood and plasma gene transcripts that were common to 9 term pregnant women and their newborns but absent or reduced in the mothers postpartum. RNA was isolated from peripheral or umbilical blood and hybridized to gene expression arrays. Gene expression, paired Student's t test, and pathway analyses were performed. In whole blood, 157 gene transcripts met statistical significance. These fetal biomarkers included 27 developmental genes, 5 sensory perception genes, and 22 genes involved in neonatal physiology. Transcripts were predominantly expressed or restricted to the fetus, the embryo, or the neonate. Real-time RT-PCR amplification confirmed the presence of specific gene transcripts; SNP analysis demonstrated the presence of 3 fetal transcripts in maternal antepartum blood. Comparison of whole blood and plasma samples from the same pregnant woman suggested that placental genes are more easily detected in plasma. We conclude that fetal and placental mRNA circulates in the blood of pregnant women. Transcriptional analysis of maternal whole blood identifies a unique set of biologically diverse fetal genes and has a multitude of clinical applications.

Array-CGH analysis of cell-free fetal DNA in 10 mL of amniotic fluid supernatant.

BACKGROUND: Previously, we showed that analysis of amniotic fluid (AF) supernatant cell-free fetal (cff) DNA using DNA microarrays (array-CGH) allows for detection of whole chromosome differences between test and reference DNA. Subsequent technical advances have increased both the yield and quality of extracted cffDNA. Here we determined whether array-CGH using smaller volumes of both fresh and frozen AF cffDNA could identify fetal aneuploidy. METHODS: CffDNA was extracted from 10 mL of residual AF supernatant. The test AF samples (n = 10) included one with a normal karyotype, and nine with the following fetal aneuploidies: trisomies 13 (n = 1), 18 (n = 3), 21 (n = 2), trisomy 9 mosaicism (47,XX,+ 9[18]/46,XX[2]), triploidy (69,XXY) and Turner syndrome (45,X). RESULTS: Array-CGH using AF cffDNA from aneuploid fetuses, compared to euploid reference AF cffDNA, detected whole chromosome aneuploidy in 8 of 9 cases tested, including the case of trisomy 9 mosaicism. The case of triploidy was not detected. CONCLUSIONS: CffDNA extracted from 10 mL AF supernatant can be analyzed using array-CGH to correctly identify human chromosome abnormalities. This technology allows for rapid screening of AF samples for whole chromosomal changes by using routinely discarded supernatant, and may augment standard prenatal karyotyping techniques by providing additional molecular information.