Rebuilding human resources for health: a case study from Liberia.

INTRODUCTION: Following twenty years of economic and social growth, Liberia's fourteen-year civil war destroyed its health system, with most of the health workforce leaving the country. Following the inauguration of the Sirleaf administration in 2006, the Ministry of Health & Social Welfare (MOHSW) has focused on rebuilding, with an emphasis on increasing the size and capacity of its human resources for health (HRH). Given resource constraints and the high maternal and neonatal mortality rates, MOHSW concentrated on its largest cadre of health workers: nurses. CASE DESCRIPTION: Based on results from a post-war rapid assessment of health workers, facilities and community access, MOHSW developed the Emergency Human Resources (HR) Plan for 2007-2011. MOHSW established a central HR Unit and county-level HR officers and prioritized nursing cadres in order to quickly increase workforce numbers, improve equitable distribution of workers and enhance performance. Strategies included increasing and standardizing salaries to attract workers and prevent outflow to the private sector; mobilizing donor funds to improve management capacity and fund incentive packages in order to retain staff in hard to reach areas; reopening training institutions and providing scholarships to increase the pool of available workers. DISCUSSION AND EVALUATION: MOHSW has increased the total number of clinical health workers from 1396 in 1998 to 4653 in 2010, 3394 of which are nurses and midwives. From 2006 to 2010, the number of nurses has more than doubled. Certified midwives and nurse aides also increased by 28% and 31% respectively. In 2010, the percentage of the clinical workforce made up by nurses and nurse aides increased to 73%. While the nursing cadre numbers are strong and demonstrate significant improvement since the creation of the Emergency HR Plan, equitable distribution, retention and performance management continue to be challenges. CONCLUSION: This paper illustrates the process, successes, ongoing challenges and current strategies Liberia has used to increase and improve HRH since 2006, particularly the nursing workforce. The methods used here and lessons learned might be applied in other similar settings.

Water and hygiene interventions to reduce diarrhoea in rural Afghanistan: a randomized controlled study.

A randomized controlled trial of four interventions was conducted using tubewells (n=2,486), liquid sodium hypochlorite ('Clorin') distributed with an improved water vessel (n=2,305), hygiene promotion (n=1,877), and a combination of the three (n=2,040) to create an evidence-base for water policy in Afghanistan. A fifth group served as a control (n=2,377). Interventions were randomized across 32 villages in Wardak province. Outcomes were measured through two household surveys separated by one year and twice-weekly household surveillance conducted over 16 months. The households receiving all three interventions showed reduction in diarrhoea compared with the control group, through both longitudinal surveillance data (IRR [95% CI]=0.61 [0.47-0.81]) and cross-sectional survey data (AOR [95% CI]=0.53 [0.30-0.93]). This reduction was significant when all household members were included, but did not reach significance when only children under five were considered. These results suggest multi-barrier methods are necessary where there are many opportunities for water contamination. Surveillance data suggested a greater impact of interventions on reducing diarrhoeal diseases than data from the surveys. Higher economic status as measured through household assets was associated with lower rates of diarrhoea and greater intervention uptake, excepting Clorin. Use of soap was also associated with lower prevalence of diarrhoea.

Impact of intestinal colonization and invasion on the Entamoeba histolytica transcriptome.

A genome-wide transcriptional analysis of Entamoeba histolytica was performed on trophozoites isolated from the colon of six infected mice and from in vitro culture. An Affymetrix platform gene expression array was designed for this analysis that included probe sets for 9435 open reading frames (ORFs) and 9066 5' and 3' flanking regions. Transcripts were detected for > 80% of all ORFs. A total of 523 transcripts (5.2% of all E. histolytica genes) were significantly changed in amebae isolated from the intestine on Days 1 and 29 after infection: 326 and 109 solely on Days 1 and 29, and 88 on both days. Quantitative real-time reverse transcriptase PCR confirmed these changes in 11/12 genes tested using mRNA isolated from an additional six mice. Adaptation to the intestinal environment was accompanied by increases in a subset of cell signaling genes including transmembrane kinases, ras and rho family GTPases, and calcium binding proteins. Significant decreases in mRNA abundance for genes involved in glycolysis and concomitant increases in lipases were consistent with a change in energy metabolism. Defense against bacteria present in the intestine (but lacking from in vitro culture) was suggested by alterations in mRNA levels of genes similar to the AIG1 plant antibacterial proteins. Decreases in oxygen detoxification pathways were observed as expected in the anaerobic colonic lumen. Of the known virulence factors the most remarkable changes were a 20-35-fold increase in a cysteine proteinase four-like gene, and a 2-3-fold decrease in two members of the Gal/GalNAc lectin light subunit family. Control of the observed changes in mRNA abundance in the intestine might potentially rest with four related proteins with DNA binding domains that were down-regulated 6-16-fold in the intestinal environment. In conclusion, the first genome-wide analysis of the transcriptome of E. histolytica demonstrated that the vast majority of genes are transcribed in trophozoites, and that in the host intestine trophozoites altered the expression of mRNAs for genes implicated in metabolism, oxygen defense, cell signaling, virulence, antibacterial activity, and DNA binding.

Targets of the Entamoeba histolytica transcription factor URE3-BP.

The Entamoeba histolytica transcription factor Upstream Regulatory Element 3-Binding Protein (URE3-BP) is a calcium-responsive regulator of two E. histolytica virulence genes, hgl5 and fdx1. URE3-BP was previously identified by a yeast one-hybrid screen of E. histolytica proteins capable of binding to the sequence TATTCTATT (Upstream Regulatory Element 3 (URE3)) in the promoter regions of hgl5 and fdx1. In this work, precise definition of the consensus URE3 element was performed by electrophoretic mobility shift assays (EMSA) using base-substituted oligonucleotides, and the consensus motif validated using episomal reporter constructs. Transcriptome profiling of a strain induced to produce a dominant-positive URE3-BP was then used to identify additional genes regulated by URE3-BP. Fifty modulated transcripts were identified, and of these the EMSA defined motif T[atg]T[tc][cg]T[at][tgc][tg] was found in over half of the promoters (54% p<0.0001). Fifteen of the URE3-BP regulated genes were potential membrane proteins, suggesting that one function of URE3-BP is to remodel the surface of E. histolytica in response to a calcium signal. Induction of URE3-BP leads to an increase in tranwell migration, suggesting a possible role in the regulation of cellular motility.

Resistance to intestinal Entamoeba histolytica infection is conferred by innate immunity and Gr-1+ cells.

Establishment of intestinal infection with Entamoeba histolytica depends on the mouse strain; C57BL/6 mice are highly resistant, and C3H/HeJ mice are relatively susceptible. We found that resistance to intestinal infection was independent of lymphocyte activity or H-2 haplotype and occurred in the first hours to days postchallenge according to in vivo imaging. At 18 h postchallenge, the ceca of resistant C57BL/6 mice were histologically unremarkable, in contrast to the severe inflammation observed in susceptible C3H/HeJ mice. Comparison of cecal gene expression in C3H/HeJ and C57BL/6 mice demonstrated that there was parasite-induced upregulation of proinflammatory and neutrophil chemotaxis transcripts and there was downregulation of transforming growth factor beta signaling molecules. Pretreatment with dexamethasone abrogated the partial resistance of C3H/HeJ or CBA mice through an innate, lymphocyte-independent mechanism, but it had no effect on the high-level resistance of C57BL/6 mice. Similarly, administration of a neutrophil-depleting anti-Gr-1 monoclonal antibody (RB6-8C5) decreased the partial resistance of CBA mice and led to severe pathology compared to control antibody-treated mice, but it had no effect on C57BL/6 resistance. These data indicate that there are discrete mechanisms of innate resistance to E. histolytica depending on the host background and, in contrast to other reports, imply that neutrophils are protective and not damaging in intestinal amebiasis.