Search

IntroductionThe purpose of this study was to evaluate the use of a novel imaging modality, digital tomosynthesis (DT), for identification of predefined anatomic dental and maxillomandibular structures in dogs.MethodsDT images were compared to conventional intraoral dental radiography (DR) for the diagnostic yield regarding the presence and quality of visualization of 35 structures. DT imaging and full mouth DR were obtained on 16 canine cadaver heads and a semi-quantitative scoring system was used to characterize the ability of each imaging method to identify the anatomic structures.ResultsThe results demonstrated that each imaging modality, and orientation, was superior for certain anatomic structures.DiscussionOverall, although one modality did not prove superior to the other, digital tomosynthesis appears to be an appropriate novel tool for identification of specific anatomic structures in the dog skull.

Supplementation with Rhodiola Rosea (RR) and Cordyceps Sinensis (CS) has been shown to improve aerobic performance, but their influence on concurrent training (resistance training plus high intensity interval training) outcomes has not been established. The purpose of this study was to determine the effects of supplementation with a multi-ingredient performance supplement (MIPS) containing RR and CS during a 14-week training and testing program on body composition, weekly exercise training outcomes, overall training and performance outcomes, and hormone profiles. Active college-aged men (N = 21) were stratified into either a MIPS or a placebo (PLA) group. Both groups completed 14 weeks of training and testing. Body composition, overall training outcomes, and blood sample collection occurred at weeks 0, 7, and 14, while training performance was evaluated weekly. Both groups improved (p < 0.05) percent body fat (-1.3%), bench press (+4%) and squat strength (+8%), with no difference between groups. Serum cortisol concentrations significantly decreased (-11%) but there were no differences between groups. No other changes in blood hormone profiles occurred. Weekly exercise performance data suggests that MIPS improved sprint performance, bench press lifting volume, and total workload, but this did not lead to improved overall training performance compared to PLA over the14-week study. Despite MIPS improving certain aspects of weekly training performance, supplementation with MIPS for 14 weeks did not improve body composition, overall training and performance outcomes, or blood biomarkers of health in response to concurrent training in young men compared to PLA. This study was registered with clinicaltrials. gov (NCT02383017). [ABSTRACT FROM AUTHOR]

Retroperitoneal tumors are extremely rare. More than 70% of primary retroperitoneal soft tissue tumors are malignant. The most common sarcomas in the retroperitoneum include liposarcomas and leiomyosarcoma, however other sarcomas, along with benign mesenchymal tumors, can occur. Sarcomas are a heterogenous group of tumors with overlapping microscopic features, posing a diagnostic challenge for the pathologist. Correct tumor classification has become important for prognostication and the evolving targeted therapies for sarcoma subtypes. In this review, the pathology of retroperitoneal soft tissue sarcomas is discussed, which is important to the surgical oncologist. In addition, less common sarcomas and benign mesenchymal tumors of the retroperitoneum, which may mimic sarcoma clinically and pathologically, are also discussed.

Introduction In response to the limited supply of personal protective equipment during the pandemic caused by SARS-CoV-2, recent studies demonstrate that gaseous H2O2 is an effective decontaminant of N95 filtering facepiece respirators to enable reuse of these items in a clinical setting. This paper evaluates the efficacy of the Arca Aerosolized Hydrogen Peroxide Decontamination System (Arca), a novel aerosolized H2O2 decontamination system, using biologic indicator testing. Materials and methods The Arca produces and circulates H2O2 aerosol inside of a sealed stainless steel chamber. The Arca’s decontamination efficacy was evaluated in 8 decontamination trials with 2 H2O2 concentrations (3% and 12%) and 4 decontamination cycle durations (45, 60, 90, and 120 minutes). Efficacy was evaluated by testing: 1) the concentration in parts per million (ppm) of H2O2 produced inside the chamber and the concentration in ppm of H2O2 vented from the chamber, and 2) the decontamination of Mesa Biologic Indicator filter strips (BI) inoculated with Geobacillus Stearothermophilus. Control tests were conducted by submerging BI strips in 3mL of 3% and 12% H2O2 for 120 minutes (negative controls) and by not exposing one BI strip to H2O2 (positive control). Results Greater than 5000 ppm of H2O2 was detected on the concentration strips inside the chamber for each of the eight decontamination trials. No vented H2O2 was detected on the external concentration strips after any decontamination trial. No growth was observed for any of the negative controls after seven days. The positive control was positive for growth. Conclusion The Arca Aerosolized Hydrogen Peroxide Decontamination System is effective at decontaminating bacterial G. Stearothermophilus at a cycle time of 45 minutes utilizing 6mL of 3% H2O2 solution.

The mitotic deacetylase complex (MiDAC) is a recently identified histone deacetylase (HDAC) complex. While other HDAC complexes have been implicated in neurogenesis, the physiological role of MiDAC remains unknown. Here, we show that MiDAC constitutes an important regulator of neural differentiation. We demonstrate that MiDAC functions as a modulator of a neurodevelopmental gene expression program and binds to important regulators of neurite outgrowth. MiDAC upregulates gene expression of pro-neural genes such as those encoding the secreted ligands SLIT3 and NETRIN1 (NTN1) by a mechanism suggestive of H4K20ac removal on promoters and enhancers. Conversely, MiDAC inhibits gene expression by reducing H3K27ac on promoter-proximal and -distal elements of negative regulators of neurogenesis. Furthermore, loss of MiDAC results in neurite outgrowth defects that can be rescued by supplementation with SLIT3 and/or NTN1. These findings indicate a crucial role for MiDAC in regulating the ligands of the SLIT3 and NTN1 signaling axes to ensure the proper integrity of neurite development.

A new species of Lactura is described from Texas: Lactura rubritegula sp. n. Identity of the new species can be reliably determined by both larval and adult characters, CO1 haplotypes, and its late-spring period of flight activity. Male genitalic features overlap with those of L. basistriga (Barnes & McDunnough, 1913), whereas female structures differ markedly between the pair. The new Sideroxylon-feeding species, rare in collections, is found principally in limestone areas in the vicinity San Antonio, Texas, westward through the southern Hill Country. We illustrate the adult and larval stages and male and female genitalia, review available DNA barcode data that support the recognition of the new Lactura, and briefly characterize its life history.

Background: The World Health Report, 2008, contains a global review of primary health care on the 30th anniversary of the Declaration of Alma-Ata. The period covered by the study reported on here corresponds with that of the Report, allowing for a comparison of achievements and challenges in one primary health care centre vis-a-vis the WHO standards. Materials and Methods: This study uses qualitative and quantitative data from a rural primary care facility in Western Maharashtra, collected over three decades. It analyzes the four groups of reforms defined by WHO in the context of the achievements and challenges of the study facility. Results: According to the WHO Report, health systems in developing countries have not responded adequately to people′s needs. However, our in-depth observations revealed substantial progress in several areas, including in family planning, safe deliveries, immunization and health promotion. Satisfaction with services in the study area was high. Conclusion: Adequate primary health care is possible, even when all recommended WHO reforms are not fully in place.

The immunoglobulin heavy chain (IGH) gene rearrangement in chronic lymphocytic leukemia (CLL) provides a unique molecular signature; however, we demonstrate that 26/198 CLL patients (13%) had more than one IGH rearrangement, indicating the power of molecular technology over phenotypic analysis. Single-cell PCR analysis and next-generation immuno-sequencing identified IGH-defined clones. In 23% (18/79) of cases whose clones carried unmutated immunoglobulin heavy chain variable (IGHV) genes (U-CLL), IGH rearrangements were bialleic with one productive (P) and one non-productive (NP) allele. Two U-CLL were biclonal, each clone being monoallelic (P). In 119 IGHV-mutated (M-CLL) cases, one had biallelic rearrangements in their CLL (P/NP) and five had 2-4 distinct clones. Allelic exclusion was maintained in all B-clones analyzed. Based on single-cell PCR analysis, 5/11 partner clones (45%) reached levels of >5x10(9) cells/L, suggesting second CLL clones. Partner clones persisted over years. Conventional IGH characterization and next-generation sequencing of 13 CLL, 3 multiple myeloma, 2 Waldenstrom's macroglobulinemia and 3 age-matched healthy donors consistently identified the same rearranged IGH sequences. Most multiple clones occurred in M-CLL, perhaps indicative of weak clonal dominance, thereby associating with a good prognosis. In contrast, biallelic CLL occurred primarily in U-CLL thus being associated with poor prognosis. Extending beyond intra-clonal diversity, molecular analysis of clonal evolution and apparent subclones in CLL may also reflect inter-clonal diversity.

OBJECTIVE: To compare the quality of public and private first-tier antenatal care services in Dar es Salaam, United Republic of Tanzania, using defined criteria. METHODS: Structural attributes of quality were assessed through a checklist, and process attributes, including interpersonal and technical aspects, through observation and exit interviews. A total of 16 health care providers, and 166 women in the public and 188 in the private sector, were selected by systematic random sampling for inclusion in the study. Quality was measured against national standards, and an overall score calculated for the different aspects to permit comparison. FINDINGS: The results showed that both public and private providers were reasonably good with regard to the structural and interpersonal aspects of quality of care. However, both were poor when it came to technical aspects of quality. For example, guidelines for dispensing prophylactic drugs against anaemia or malaria were not respected, and diagnostic examinations for the assessment of gestation, anaemia, malaria or urine infection were frequently not performed. In all aspects, private providers were significantly better than public ones. CONCLUSION: Approaches to improving quality of care should emerge progressively as a result of regular quality assessments. Changes should be introduced using an incremental approach addressing few improvements at a time, while ensuring participation in, and ownership of, every aspect of the strategy by health personnel, health planners and managers and also the community.

OBJECTIVE: To assess the costs and consequences of a social marketing approach to malaria control in children by means of insecticide-treated nets in two rural districts of the United Republic of Tanzania, compared with no net use. METHODS: Project cost data were collected prospectively from accounting records. Community effectiveness was estimated on the basis of a nested case-control study and a cross-sectional cluster sample survey. FINDINGS: The social marketing approach to the distribution of insecticide-treated nets was estimated to cost US$ 1560 per death averted and US$ 57 per disability-adjusted life year averted. These figures fell to US$ 1018 and US$ 37, respectively, when the costs and consequences of untreated nets were taken into account. CONCLUSION: The social marketing of insecticide-treated nets is an attractive intervention for preventing childhood deaths from malaria.

New initiatives are aiming to reduce the global burden of schistosomiasis, mainly through the large-scale application of chemotherapy. To target chemotherapy effectively, rapid assessment procedures are needed for identifying high-risk communities that are foci for the disease. In this review, we examine the development and validation of simple school questionnaires for screening communities for Schistosoma haematobium and S. mansoni rapidly and inexpensively. The focus is on sub-Saharan Africa, where 85% of the current schistosomiasis burden is concentrated. For more than a decade, the questionnaire approach has been validated in 10 countries, with 133 880 children interviewed in 1282 schools, and with 54 996 children examined for S. haematobium. The questionnaires were well accepted, highly reliable, and of low cost. The success of the questionnaires is explained by the fact that S. haematobium infections were easily perceived through the presence of blood in urine. Evidence from 48 258 children interviewed in 545 schools indicated that reported blood in stools and bloody diarrhoea are valuable indicators for community diagnosis of S. mansoni. However, the diagnostic performance of the questionnaires for S. mansoni was weaker than for S. haematobium, and although these results are encouraging, the questionnaires need additional validation. Recently, questionnaires were extended from community to individual diagnosis and showed considerable promise. Questionnaires are now available for promptly defining the magnitude of schistosomiasis in a large area, which will allow limited resources for morbidity control to be allocated optimally.

Abstract Background The RTS,S/AS malaria candidate vaccine is being developed with the intent to be delivered, if approved, through the Expanded Programme on Immunization (EPI) of the World Health Organization. Safety, immunogenicity and efficacy of the RTS,S/AS02D vaccine candidate when integrated into a standard EPI schedule for infants have been reported over a nine-month surveillance period. This paper describes results following 20 months of follow up. Methods This Phase IIb, single-centre, randomized controlled trial enrolled 340 infants in Tanzania to receive three doses of RTS,S/AS02D or hepatitis B vaccine at 8, 12, and 16 weeks of age. All infants also received DTPw/Hib (diphtheria and tetanus toxoids, whole-cell pertussis vaccine, conjugated Haemophilus influenzae type b vaccine) at the same timepoints. The study was double-blinded to month 9 and single-blinded from months 9 to 20. Results From month 0 to 20, at least one SAE was reported in 57/170 infants who received RTS,S/AS02D (33.5%; 95% confidence interval [CI]: 26.5, 41.2) and 62/170 infants who received hepatitis B vaccine (36.5%; 95% CI: 29.2, 44.2). The SAE profile was similar in both vaccine groups; none were considered to be related to vaccination. At month 20, 18 months after completion of vaccination, 71.8% of recipients of RTS,S/AS02D and 3.8% of recipients of hepatitis B vaccine had seropositive titres for anti-CS antibodies; seroprotective levels of anti-HBs antibodies remained in 100% of recipients of RTS,S/AS02D and 97.7% recipients of hepatitis B vaccine. Anti-HBs antibody GMTs were higher in the RTS,S/AS02D group at all post-vaccination time points compared to control. According to protocol population, vaccine efficacy against multiple episodes of malaria disease was 50.7% (95% CI: -6.5 to 77.1, p = 0.072) and 26.7% (95% CI: -33.1 to 59.6, p = 0.307) over 12 and 18 months post vaccination, respectively. In the Intention to Treat population, over the 20-month follow up, vaccine efficacy against multiple episodes of malaria disease was 14.4% (95% CI: -41.9 to 48.4, p = 0.545). Conclusions The acceptable safety profile and good tolerability of RTS,S/AS02D in combination with EPI vaccines previously reported from month 0 to 9 was confirmed over a 20 month surveillance period in this infant population. Antibodies against both CS and HBsAg in the RTS,S/AS02D group remained significantly higher compared to control for the study duration. Over 18 months follow up, RTS,S/AS02D prevented approximately a quarter of malaria cases in the study population. Clinical trials Gov identifier: NCT00289185

Abstract Background Malaria mortality is mainly a direct consequence of inadequate and/or delayed diagnosis and case management. Some important control interventions (e.g. long-lasting insecticidal nests) have contributed to reduce malaria morbidity and mortality in different parts of the world. Moreover, the development and effective use of rapid diagnostic tests (RDTs) hold promise to further enhance the control and elimination of malaria, particularly in areas where health services are deficient. The aim of this study was to determine knowledge, attitudes, practices and beliefs in relation to RDTs for malaria in rural Côte d’Ivoire. Methods One hundred individuals from Bozi and Yoho who sought care at the health centre in Bozi and were offered an RDT for malaria were interviewed in April 2010 using a pre-tested questionnaire on practice and perceptions in relation to RDTs for malaria. The relationships between acceptance of RDTs and factors related to opinions were identified, using generalized linear mixed models. Qualitative data from open-ended questions complemented the quantitative analysis. Results Only 34 out of 100 patients who were offered an RDT for malaria were willing to undergo the test. People who perceived blood as a sacred body fluid were less likely to comply with an RDT. The concurrent availability and use of RDTs for HIV and malaria was associated with an unwilling attitude towards RDTs for malaria (Fisher’s exact test, p Conclusion Socio-cultural factors might be barriers for accepting RDTs in general health services. There are social representations of malaria and HIV/AIDS, symbolic for blood or experiences in relation to blood taking and blood-related diseases in relation to the introduction and routine use of RDTs. Special attention should be given to these barriers as otherwise the promotion of RDTs for prompt and effective diagnosis and subsequent management of malaria is hampered.

Abstract Background A sound understanding of malaria transmission patterns in the People’s Republic of China (P.R. China) is crucial for designing effective surveillance-response strategies that can guide the national malaria elimination programme (NMEP). Using an established biology-driven model, it is expected that one may design and refine appropriate surveillance-response strategies for different transmission zones, which, in turn, assist the NMEP in the ongoing implementation period (2010–2020) and, potentially, in the post-elimination stage (2020–2050). Methods Environmental data obtained from 676 locations across P.R. China, such as monthly temperature and yearly relative humidity (YRH), for the period 1961–2000 were prepared. Smoothed surface maps of the number of months suitable for parasite survival derived from monthly mean temperature and YRH were generated. For each decade, the final malaria prediction map was overlaid by two masked maps, one showing the number of months suitable for parasite survival and the other the length of YRH map in excess of 60%. Results Considering multiple environmental factors simultaneously, the environmental variables suitable for malaria transmission were found to have shifted northwards, which was especially pronounced in northern P.R. China. The unstable suitable regions (transmission periods between five and six months) showed increased transmission intensity due to prolonged suitable periods, especially in the central part of the country. Conclusion Adequate and effective surveillance-response strategies for NMEP should be designed to achieve the goal of malaria elimination in P.R. China by 2020, especially in the zones predicted to be the most vulnerable for climate change.

Abstract Control and eventual elimination of human parasitic diseases in the People's Republic of China (P.R. China) requires novel approaches, particularly in the areas of diagnostics, mathematical modelling, monitoring, evaluation, surveillance and public health response. A comprehensive effort, involving the collaboration of 188 scientists (>85% from P.R. China) from 48 different institutions and universities (80% from P.R. China), covers this collection of 29 articles published in Parasites & Vectors. The research mainly stems from a research project entitled “Surveillance and diagnostic tools for major parasitic diseases in P.R. China” (grant no. 2008ZX10004-011) and highlights the frontiers of research in parasitology. The majority of articles in this thematic series deals with the most important parasitic diseases in P.R. China, emphasizing Schistosoma japonicum, Plasmodium vivax and Clonorchis sinensis plus some parasites of emerging importance such as Angiostrongylus cantonensis. Significant achievements have been made through the collaborative research programme in the following three fields: (i) development of strategies for the national control programme; (ii) updating the surveillance data of parasitic infections both in human and animals; and (iii) improvement of existing, and development of novel, diagnostic tools to detect parasitic infections. The progress is considerable and warrants broad validation efforts. Combined with the development of improved tools for diagnosis and surveillance, integrated and multi-pronged control strategies should now pave the way for elimination of parasitic diseases in P.R. China. Experiences and lessons learned can stimulate control and elimination efforts of parasitic diseases in other parts of the world.

Abstract Background In Côte d’Ivoire, an estimated 767,000 disability-adjusted life years are due to malaria, placing the country at position number 14 with regard to the global burden of malaria. Risk maps are important to guide control interventions, and hence, the aim of this study was to predict the geographical distribution of malaria infection risk in children aged Methods Using different data sources, a systematic review was carried out to compile and geo-reference survey data on Plasmodium spp. infection prevalence in Côte d’Ivoire, focusing on children aged Plasmodium spp. infection risk for entire Côte d’Ivoire, including uncertainty. Results Overall, 235 data points at 170 unique survey locations with malaria prevalence data for individuals aged Conclusion The malaria risk map at high spatial resolution gives an important overview of the geographical distribution of the disease in Côte d’Ivoire. It is a useful tool for the national malaria control programme and can be utilized for spatial targeting of control interventions and rational resource allocation.

Abstract Background Artemisinin-based combination therapy (ACT) has been promoted as a means to reduce malaria transmission due to their ability to kill both asexual blood stages of malaria parasites, which sustain infections over long periods and the immature derived sexual stages responsible for infecting mosquitoes and onward transmission. Early studies reported a temporal association between ACT introduction and reduced malaria transmission in a number of ecological settings. However, these reports have come from areas with low to moderate malaria transmission, been confounded by the presence of other interventions or environmental changes that may have reduced malaria transmission, and have not included a comparison group without ACT. This report presents results from the first large-scale observational study to assess the impact of case management with ACT on population-level measures of malaria endemicity in an area with intense transmission where the benefits of effective infection clearance might be compromised by frequent and repeated re-infection. Methods A pre-post observational study with a non-randomized comparison group was conducted at two sites in Tanzania. Both sites used sulphadoxine-pyrimethamine (SP) monotherapy as a first-line anti-malarial from mid-2001 through 2002. In 2003, the ACT, artesunate (AS) co-administered with SP (AS + SP), was introduced in all fixed health facilities in the intervention site, including both public and registered non-governmental facilities. Population-level prevalence of Plasmodium falciparum asexual parasitaemia and gametocytaemia were assessed using light microscopy from samples collected during representative household surveys in 2001, 2002, 2004, 2005 and 2006. Findings Among 37,309 observations included in the analysis, annual asexual parasitaemia prevalence in persons of all ages ranged from 11% to 28% and gametocytaemia prevalence ranged from Interpretation The introduction of ACT at fixed health facilities only modestly reduced asexual parasitaemia prevalence. ACT is effective for treatment of uncomplicated malaria and should have substantial public health impact on morbidity and mortality, but is unlikely to reduce malaria transmission substantially in much of sub-Saharan Africa where individuals are rapidly re-infected.

Abstract Background Recent years have seen an unprecedented increase in funds for procurement of health commodities in developing countries. A major challenge now is the efficient delivery of commodities and services to improve population health. With this in mind, we documented staffing levels and productivity in peripheral health facilities in southern Tanzania. Method A health facility survey was conducted to collect data on staff employed, their main tasks, availability on the day of the survey, reasons for absenteeism, and experience of supervisory visits from District Health Teams. In-depth interview with health workers was done to explore their perception of work load. A time and motion study of nurses in the Reproductive and Child Health (RCH) clinics documented their time use by task. Results We found that only 14% (122/854) of the recommended number of nurses and 20% (90/441) of the clinical staff had been employed at the facilities. Furthermore, 44% of clinical staff was not available on the day of the survey. Various reasons were given for this. Amongst the clinical staff, 38% were absent because of attendance to seminar sessions, 8% because of long-training, 25% were on official travel and 20% were on leave. RCH clinic nurses were present for 7 hours a day, but only worked productively for 57% of time present at facility. Almost two-third of facilities had received less than 3 visits from district health teams during the 6 months preceding the survey. Conclusion This study documented inadequate staffing of health facilities, a high degree of absenteeism, low productivity of the staff who were present and inadequate supervision in peripheral Tanzanian health facilities. The implications of these findings are discussed in the context of decentralized health care in Tanzania.

Abstract Background Combination therapy with deferoxamine and oral deferiprone is superior to deferoxamine alone in removing cardiac iron and improving left ventricular ejection fraction (LVEF). The right ventricle (RV) is also affected by the toxic effects of iron and may cause additional cardiovascular perturbation. We assessed the effects of combination therapy on the RV in thalassaemia major (TM) using cardiovascular magnetic resonance (CMR). Methods We retrieved imaging data from 2 treatment trials and re-analyzed the data for the RV responses: Trial 1 was a randomized controlled trial (RCT) of 65 TM patients with mild-moderate cardiac siderosis receiving combination therapy or deferoxamine with placebo; Trial 2 was an open label longitudinal trial assessing combination therapy in 15 TM patients with severe iron loading. Results In the RCT, combination therapy with deferoxamine and deferiprone was superior to deferoxamine alone for improving RVEF (3.6 vs 0.7%, p = 0.02). The increase in RVEF was greater with lower baseline T2* 8-12 ms (4.7 vs 0.5%, p = 0.01) than with T2* 12-20 ms (2.2 vs 0.8%, p = 0.47). In patients with severe cardiac siderosis, substantial improvement in RVEF was seen with open-label combination therapy (10.5% ± 5.6%, p < 0.01). Conclusions In the RCT of mild to moderate cardiac iron loading, combination treatment improved RV function significantly more than deferoxamine alone. Combination treatment also improved RV function in severe cardiac siderosis. Therefore adding deferiprone to deferoxamine has beneficial effects on both RV and LV function in TM patients with cardiac siderosis.

Abstract Background Intermittent Preventive Treatment for malaria control in infants (IPTi) consists of the administration of a treatment dose of an anti-malarial drug, usually sulphadoxine-pyrimethamine, at scheduled intervals, regardless of the presence of Plasmodium falciparum infection. A pooled analysis of individually randomized trials reported that IPTi reduced clinical episodes by 30%. This study evaluated the effect of IPTi on child survival in the context of a five-district implementation project in southern Tanzania. [Trial registration: clinical trials.gov NCT00152204]. Methods After baseline household and health facility surveys in 2004, five districts comprising 24 divisions were randomly assigned either to receive IPTi (n = 12) or not (n = 12). Implementation started in March 2005, led by routine health services with support from the research team. In 2007, a large household survey was undertaken to assess the impact of IPTi on survival in infants aged two-11 months through birth history interviews with all women aged 13-49 years. The analysis is based on an "intention-to-treat" ecological design, with survival outcomes analysed according to the cluster in which the mothers lived. Results Survival in infants aged two-11 months was comparable in IPTi and comparison areas at baseline. In intervention areas in 2007, 48% of children aged 12-23 months had documented evidence of receiving three doses of IPTi, compared to 2% in comparison areas (P < 0.0001). Over the three years of the study there was a marked improvement in survival in both groups. Between 2001-4 and 2005-7, mortality rates in two-11 month olds fell from 34.1 to 23.6 per 1,000 person-years in intervention areas and from 32.3 to 20.7 in comparison areas. In 2007, divisions implementing IPTi had a 14% (95% CI -12%, 49%) higher mortality rate in two-11 month olds in comparison with non-implementing divisions (P = 0.31). Conclusion The lack of evidence of an effect of IPTi on survival could be a false negative result due to a lack of power or imbalance of unmeasured confounders. Alternatively, there could be no mortality impact of IPTi due to low coverage, late administration, drug resistance, decreased malaria transmission or improvements in vector control and case management. This study raises important questions for programme evaluation design.

Abstract Background To improve effectiveness of malaria control interventions, it is essential to deepen the knowledge of contextual factors that govern people's practice for preventive and curative measures. The aim of this study was to determine factors that influence the use of long-lasting insecticidal nets (LLINs) in three rural communities of Côte d'Ivoire, two of which benefited from recent interventions. Methods The study was carried out in 957 households in three villages (Bozi, N'Dakonankro and Yoho) located in central Côte d'Ivoire. Indicators of socioeconomic position (SEP), malaria knowledge and practice, placing special emphasis on LLINs, were investigated during a cross-sectional questionnaire survey. Principal component analysis was used to calculate the SEP of households by means of a list of household assets ownership. The concentration index was used to assess the direction of the association between SEP and a given variable. To compare groups or means, Fisher's exact test, χ2 and Kruskal-Wallis test were used, as appropriate. Results Significant differences were found between SEP and reported malaria symptoms, such as fever or hot body, convulsion, anaemia and jaundice (yellow eyes). Individuals from the least poor group cited more often the use of bed nets and insecticide-treated nets (ITNs) compared to poorer groups. The mean number of individuals reporting the use of bed nets and LLINs was different between groups with different educational level. Moreover, the mean number of LLINs in a household was influenced by the presence of children below five years of age. Conclusion The study not only confirmed that education and SEP play important roles in the prevention and control of malaria and promotion of health in general, but pointed at the basic essential knowledge and the key behavioural elements that should guide education and learning processes among the poorer segments of the population. In turn, such knowledge may change behaviour and lead to an increased utilization of LLINs.

Abstract Background Community engagement and participation has played a critical role in successful disease control and elimination campaigns in many countries. Despite this, its benefits for malaria control and elimination are yet to be fully realized. This may be due to a limited understanding of the influences on participation in developing countries as well as inadequate investment in infrastructure and resources to support sustainable community participation. This paper reports the findings of an atypical systematic review of 60 years of literature in order to arrive at a more comprehensive awareness of the constructs of participation for communicable disease control and elimination and provide guidance for the current malaria elimination campaign. Methods Evidence derived from quantitative research was considered both independently and collectively with qualitative research papers and case reports. All papers included in the review were systematically coded using a pre-determined qualitative coding matrix that identified influences on community participation at the individual, household, community and government/civil society levels. Colour coding was also carried out to reflect the key primary health care period in which community participation programmes originated. These processes allowed exhaustive content analysis and synthesis of data in an attempt to realize conceptual development beyond that able to be achieved by individual empirical studies or case reports. Results Of the 60 papers meeting the selection criteria, only four studies attempted to determine the effect of community participation on disease transmission. Due to inherent differences in their design, interventions and outcome measures, results could not be compared. However, these studies showed statistically significant reductions in disease incidence or prevalence using various forms of community participation. The use of locally selected volunteers provided with adequate training, supervision and resources are common and important elements of the success of the interventions in these studies. In addition, qualitative synthesis of all 60 papers elucidates the complex architecture of community participation for communicable disease control and elimination which is presented herein. Conclusions The current global malaria elimination campaign calls for a health systems strengthening approach to provide an enabling environment for programmes in developing countries. In order to realize the benefits of this approach it is vital to provide adequate investment in the 'people' component of health systems and understand the multi-level factors that influence their participation. The challenges of strengthening this component of health systems are discussed, as is the importance of ensuring that current global malaria elimination efforts do not derail renewed momentum towards the comprehensive primary health care approach. It is recommended that the application of the results of this systematic review be considered for other diseases of poverty in order to harmonize efforts at building 'competent communities' for communicable disease control and optimising health system effectiveness.

Abstract Background The Solomon Islands National Malaria Programme is currently focused on intensified control and progressive elimination. Recent control efforts in Isabel Province have reduced their malaria incidence to 2.6/1,000 population in 2009 1 whereas most neighbouring provinces have much higher incidences. A malaria surveillance-response system that involves testing all travellers entering Isabel Province using rapid diagnostic tests (RDT) to prevent cases being imported had been proposed by local health authorities. This study provides information on the feasibility and acceptability of implementing a new approach of surveillance and response in the context of low levels of indigenous malaria transmission in Isabel Province. Methods A total of 13 focus group discussions (FGD) and 22 key informant interviews (KII) were conducted in Isabel Province, Solomon Islands. Key topics included: the travel patterns of people to, from and within Isabel Province; the acceptability, community perceptions, attitudes and suggestions towards the proposed surveillance programme; and management of suspected malaria cases. This information was triangulated with data obtained from port authorities, airlines and passenger ships travelling to and from Isabel Province in the preceding two years. Results Travel within Isabel Province and to and from other provinces is common with marked seasonality. The majority of inter-provincial travel is done on scheduled public transport; namely passenger ships and aircrafts. In Isabel Province there is a healthy community spirit as well as high concern regarding malaria and its importation and there is currently effective malaria passive case detection and management. Conducting malaria screening at ports and airports would be acceptable to the community. Conclusion A robust surveillance-response system is essential when moving towards malaria elimination. Many factors contribute positively towards the feasibility of an RDT based malaria surveillance system in Isabel Province. Due to financial and logistical restraints local health authorities have concluded that a system of community-based vigilance to identify new arrivals in villages and direct them to have malaria testing is more feasible than formal screening at ports and airports. A surveillance response system to prevent introduction of malaria into Isabel Province can be integrated into the National Malaria Control Programme provided the operational steps are carefully planned with regards to human and financial resources.

Abstract Background Thalassaemia major (TM) patients need regular blood transfusions that lead to accumulation of iron and death from heart failure. Deferiprone has been reported to be superior to deferoxamine for the removal of cardiac iron and improvement in left ventricular (LV) function but little is known of their relative effects on the right ventricle (RV), which is being increasingly recognised as an important prognostic factor in cardiomyopathy. Therefore data from a prospective randomised controlled trial (RCT) comparing these chelators was retrospectively analysed to assess the RV responses to these drugs. Methods In the RCT, 61 TM patients were randomised to receive either deferiprone or deferoxamine monotherapy, and CMR scans for T2* and cardiac function were obtained. Data were re-analysed for RV volumes and function at baseline, and after 6 and 12 months of treatment. Results From baseline to 12 months, deferiprone reduced RV end systolic volume (ESV) from 37.7 to 34.2 mL (p = 0.008), whilst RV ejection fraction (EF) increased from 69.6 to 72.2% (p = 0.001). This was associated with a 27% increase in T2* (p < 0.001) and 3.1% increase in LVEF (p < 0.001). By contrast, deferoxamine showed no change in RVESV (38.1 to 39.1 mL, p = 0.38), or RVEF (70.0 to 69.9%, p = 0.93) whereas the T2* increased by 13% (p < 0.001), but with no change in LVEF (0.32%; p = 0.66). Analysis of between drugs treatment effects, showed significant improvements favouring deferiprone with a mean effect on RVESV of -1.82 mL (p = 0.014) and 1.16% for RVEF (p = 0.009). Using regression analysis the improvement in RVEF at 12 months was shown to be greater in patients with lower baseline EF values (p < 0.001), with a significant difference in RVEF of 3.5% favouring deferiprone over deferoxamine (p = 0.012). Conclusion In this retrospective analysis of a prospective RCT, deferiprone monotherapy was superior to deferoxamine for improvement in RVEF and end-systolic volume. This improvement in the RV volumes and function may contribute to the improved cardiac outcomes seen with deferiprone.

Abstract Background Data on combination antiretroviral therapy (cART) in remote rural African regions is increasing. Methods We assessed prospectively initial cART in HIV-infected adults treated from 2005 to 2008 at St. Francis Designated District Hospital, Ifakara, Tanzania. Adherence was assisted by personal adherence supporters. We estimated risk factors of death or loss to follow-up by Cox regression during the first 12 months of cART. Results Overall, 1,463 individuals initiated cART, which was nevirapine-based in 84.6%. The median age was 40 years (IQR 34-47), 35.4% were males, 7.6% had proven tuberculosis. Median CD4 cell count was 131 cells/μl and 24.8% had WHO stage 4. Median CD4 cell count increased by 61 and 130 cells/μl after 6 and 12 months, respectively. 215 (14.7%) patients modified their treatment, mostly due to toxicity (56%), in particular polyneuropathy and anemia. Overall, 129 patients died (8.8%) and 189 (12.9%) were lost to follow-up. In a multivariate analysis, low CD4 cells at starting cART were associated with poorer survival and loss to follow-up (HR 1.77, 95% CI 1.15-2.75, p = 0.009; for CD4 100 cells/μl). Higher weight was strongly associated with better survival (HR 0.63, 95% CI 0.51-0.76, p < 0.001 per 10 kg increase). Conclusions cART initiation at higher CD4 cell counts and better general health condition reduces HIV related mortality in a rural African setting. Efforts must be made to promote earlier HIV diagnosis to start cART timely. More research is needed to evaluate effective strategies to follow cART at a peripheral level with limited technical possibilities.

Abstract Background Intermittent preventive treatment of malaria in infants (IPTi) consists of the administration of a treatment dose of sulphadoxine-pyrimethamine (SP) at the time of routine vaccinations. The use of routine Health Management and Information Services (HMIS) data to investigate the effect of IPTi on malaria, anaemia, and all-cause attendance in children aged 2-11 months presenting to 11 health centres in southern Tanzania is described. Methods Clinical diagnosis of malaria was confirmed with a positive blood slide reading from a quality assurance laboratory. Anaemia was defined using two thresholds (mild [Hb < 11 g/dL], severe [Hb < 8 g/dL]). Incidence rates between IPTi and non-implementing health centres were calculated using Poisson regression, and all statistical testing was based on the t test due to the clustered nature of the data. Results Seventy two per cent of infants presenting in intervention areas received at least one dose of IPTi- 22% received all three. During March 2006 - April 2007, the incidence of all cause attendance was two attendances per person, per year (pppy), including 0.2 episodes pppy of malaria, 0.7 episodes of mild and 0.13 episodes of severe anaemia. Point estimates for the effect of IPTi on malaria varied between 18% and 52%, depending on the scope of the analysis, although adjustment for clustering rendered these not statistically significant. Conclusions The point estimate of the effect of IPTi on malaria is consistent with that from a large pooled analysis of randomized control trials. As such, it is plausible that the difference seen in health centre data is due to IPTi, even thought the effect did not reach statistical significance. Findings draw attention to the challenges of robust inference of effects of interventions based on routine health centre data. Analysis of routine health information can reassure that interventions are being made available and having desired effects, but unanticipated effects should trigger data collection from representative samples of the target population.

Abstract Background Heart failure remains a major cause of mortality in thalassaemia major. The possible role of cardiac fibrosis in thalassemia major in the genesis of heart failure is not clear. It is also unclear whether cardiac fibrosis might arise as a result of heart failure. Methods We studied 45 patients with thalassaemia major who had a wide range of current cardiac iron loading and included patients with prior and current heart failure. Myocardial iron was measured using T2* cardiovascular magnetic resonance (CMR), and following this, late gadolinium enhancement (LGE) was used to determine the presence of macroscopic myocardial fibrosis. Results The median myocardial T2* in all patients was 22.6 ms (range 5.3-58.8 ms). Fibrosis was detected in only one patient, whose myocardial T2* was 20.1 ms and left ventricular ejection fraction 57%. No fibrosis was identified in 5 patients with a history of heart failure with full recovery, in 3 patients with current left ventricular dysfunction undergoing treatment, or in 18 patients with myocardial iron loading with cardiacT2* < 20 ms at the time of scan. Conclusion This study shows that macroscopic myocardial fibrosis is uncommon in thalassemia major across a broad spectrum of myocardial iron loading. Importantly, there was no macroscopic fibrosis in patients with current or prior heart failure, or in patients with myocardial iron loading without heart failure. Therefore if myocardial fibrosis indeed contributes to myocardial dysfunction in thalassemia, our data combined with the knowledge that the myocardial dysfunction of iron overload can be reversed, indicates that any such fibrosis would need to be both microscopic and reversible.

Abstract Background Geographical Reconnaissance (GR) operations using Personal Digital Assistants (PDAs) and Global Positioning Systems (GPS) have been conducted in the elimination provinces of Temotu, Solomon Islands and Tafea, Republic of Vanuatu. These operations aimed to examine modern approaches to GR to define the spatial distribution of target populations to support contemporary malaria elimination interventions. Methods Three GR surveys were carried out covering the outer islands of Temotu Province (October - November, 2008); Santa Cruz Island, Temotu Province (February 2009) and Tanna Island, Tafea Province (July - September 2009). Integrated PDA/GPS handheld units were used in the field to rapidly map and enumerate households, and collect associated population and household structure data to support priority elimination interventions, including bed net distribution, indoor residual spraying (IRS) and malaria case surveillance. Data were uploaded and analysed in customized Geographic Information System (GIS) databases to produce household distribution maps and generate relevant summary information pertaining to the GR operations. Following completion of field operations, group discussions were also conducted to review GR approaches and technology implemented. Results 10,459 households were geo-referenced and mapped. A population of 43,497 and 30,663 household structures were recorded during the three GR surveys. The spatial distribution of the population was concentrated in coastal village clusters. Survey operations were completed over a combined total of 77 field days covering a total land mass area of approximately 1103.2 km2. An average of 45 households, 118 structures and a population of 184 people were recorded per handheld device per day. Geo-spatial household distribution maps were also produced immediately following the completion of GR fieldwork. An overall high acceptability of modern GR techniques and technology was observed by both field operations staff and communities. Conclusion GR implemented using modern techniques has provided an effective and efficient operational tool for rapidly defining the spatial distribution of target populations in designated malaria elimination zones in Solomon Islands and Vanuatu. The data generated are being used for the strategic implementation and scaling-up of priority interventions, and will be essential for establishing future surveillance using spatial decision support systems.

Abstract Background Neonatal mortality because of low birth weight or prematurity remains high in many developing country settings. This research aimed to estimate the sensitivity and specificity, and the positive and negative predictive values of newborn foot length to identify babies who are low birth weight or premature and in need of extra care in a rural African setting. Methods A cross-sectional study of newborn babies in hospital, with community follow-up on the fifth day of life, was carried out between 13 July and 16 October 2009 in southern Tanzania. Foot length, birth weight and gestational age were estimated on the first day and foot length remeasured on the fifth day of life. Results In hospital 529 babies were recruited and measured within 24 hours of birth, 183 of whom were also followed-up at home on the fifth day. Day one foot length Conclusion Measurement of newborn foot length for home births in resource poor settings has the potential to be used by birth attendants, community volunteers or parents as a screening tool to identify low birth weight or premature newborns in order that they can receive targeted interventions for improved survival

Abstract Background The use of malaria rapid diagnostic tests (RDTs) has been widely advocated to improve Plasmodium falciparum diagnosis, especially in settings where quality microscopy is not available. RDTs based on the detection of histidine-rich protein 2 (HRP-2) can remain positive for several weeks after an infection is cured, due to the persistence of HRP-2 antigens. As a result, test specificity may vary between age groups with different prevalence of P. falciparum infection. Methods A community-based cross-sectional survey, carried out in southern Tanzania in July and August 2004, evaluated the performance of the Paracheck Pf in comparison with microscopy (number of P. falciparum parasites/200 leucocytes). A sample of 598 individuals living in an area of intense malaria transmission had demographic data collected before an RDT was performed. HRP-2 test sensitivity, specificity, positive and negative predictive values were calculated and compared between distinct age groups, using microscopy as "gold standard". Results The overall malaria prevalence was 34.3% according to microscopy and 57.2% according to the HRP-2 test. The HRP-2 test had a sensitivity of 96.1%, a specificity of 63.1%, a positive predictive value of 57.6% and a negative predictive value of 96.9%. The test sensitivity was higher (ranging from 98% to 100%) amongst people less than 25 years of age, but decreased to 81.3% in older adults. The HRP-2 test specificity varied between age groups, ranging from 25% among children of five to nine years of age, to 73% among adults aged 25 or more. The test positive predictive value increased with malaria prevalence, while the negative predictive value was consistently high across age groups. Conclusions These results suggest that the performance of HRP-2 tests in areas of intense malaria transmission varies by age and the prevalence of P. falciparum infection. The particularly low specificity among children will lead to the over-estimation of malaria infection prevalence in this group.

Abstract Background Castration resistant prostate cancer (CRPC) develops as a consequence of hormone therapies used to deplete androgens in advanced prostate cancer patients. CRPC cells are able to grow in a low androgen environment and this is associated with anomalous activity of their endogenous androgen receptor (AR) despite the low systemic androgen levels in the patients. Therefore, the reactivated tumor cell androgen signaling pathway is thought to provide a target for control of CRPC. Previously, we reported that Hedgehog (Hh) signaling was conditionally activated by androgen deprivation in androgen sensitive prostate cancer cells and here we studied the potential for cross-talk between Hh and androgen signaling activities in androgen deprived and androgen independent (AI) prostate cancer cells. Results Treatment of a variety of androgen-deprived or AI prostate cancer cells with the Hh inhibitor, cyclopamine, resulted in dose-dependent modulation of the expression of genes that are regulated by androgen. The effect of cyclopamine on endogenous androgen-regulated gene expression in androgen deprived and AI prostate cancer cells was consistent with the suppressive effects of cyclopamine on the expression of a reporter gene (luciferase) from two different androgen-dependent promoters. Similarly, reduction of smoothened (Smo) expression with siRNA co-suppressed expression of androgen-inducible KLK2 and KLK3 in androgen deprived cells without affecting the expression of androgen receptor (AR) mRNA or protein. Cyclopamine also prevented the outgrowth of AI cells from androgen growth-dependent parental LNCaP cells and suppressed the growth of an overt AI-LNCaP variant whereas supplemental androgen (R1881) restored growth to the AI cells in the presence of cyclopamine. Conversely, overexpression of Gli1 or Gli2 in LNCaP cells enhanced AR-specific gene expression in the absence of androgen. Overexpressed Gli1/Gli2 also enabled parental LNCaP cells to grow in androgen depleted medium. AR protein co-immunoprecipitates with Gli2 protein from transfected 293T cell lysates. Conclusions Collectively, our results indicate that Hh/Gli signaling supports androgen signaling and AI growth in prostate cancer cells in a low androgen environment. The finding that Gli2 co-immunoprecipitates with AR protein suggests that an interaction between these proteins might be the basis for Hedgehog/Gli support of androgen signaling under this condition.

Abstract The launch of a new thematic series of Malaria Journal -- "Towards malaria elimination" -- creates the forum that allows carrying scientific evidence on how to achieve malaria elimination in specific endemic settings and conditions into the circles of scientists, public health specialists, national and global programme managers, funders and decision makers.

Abstract Background Preventing malaria by controlling mosquitoes in their larval stages requires regular sensitive monitoring of vector populations and intervention coverage. The study assessed the effectiveness of operational, community-based larval habitat surveillance systems within the Urban Malaria Control Programme (UMCP) in urban Dar es Salaam, Tanzania. Methods Cross-sectional surveys were carried out to assess the ability of community-owned resource persons (CORPs) to detect mosquito breeding sites and larvae in areas with and without larviciding. Potential environmental and programmatic determinants of habitat detection coverage and detection sensitivity of mosquito larvae were recorded during guided walks with 64 different CORPs to assess the accuracy of data each had collected the previous day. Results CORPs reported the presence of 66.2% of all aquatic habitats (1,963/2,965), but only detected Anopheles larvae in 12.6% (29/230) of habitats that contained them. Detection sensitivity was particularly low for late-stage Anopheles (2.7%, 3/111), the most direct programmatic indicator of malaria vector productivity. Whether a CORP found a wet habitat or not was associated with his/her unfamiliarity with the area (Odds Ratio (OR) [95% confidence interval (CI)] = 0.16 [0.130, 0.203], P < 0.001), the habitat type (P < 0.001) or a fence around the compound (OR [95%CI] = 0.50 [0.386, 0.646], P < 0.001). The majority of mosquito larvae (Anophelines 57.8% (133/230) and Culicines 55.9% (461/825) were not reported because their habitats were not found. The only factor affecting detection of Anopheline larvae in habitats that were reported by CORPs was larviciding, which reduced sensitivity (OR [95%CI] = 0.37 [0.142, 0.965], P = 0.042). Conclusions Accessibility of habitats in urban settings presents a major challenge because the majority of compounds are fenced for security reasons. Furthermore, CORPs under-reported larvae especially where larvicides were applied. This UMCP system for larval surveillance in cities must be urgently revised to improve access to enclosed compounds and the sensitivity with which habitats are searched for larvae.

Abstract Background The objective of this study was to identify demographic, environmental and socioeconomic risk factors and spatial patterns of Plasmodium falciparum parasitaemia in a high endemicity area of Africa, and to specify how this information can facilitate improved malaria control at the district level. Methods A questionnaire was administered to about 4,000 schoolchildren in 55 schools in western Côte d'Ivoire to determine children's socioeconomic status and their habit of sleeping under bed nets. Environmental data were obtained from satellite images, digitized ground maps and a second questionnaire addressed to school directors. Finger prick blood samples were collected and P. falciparum parasitaemia determined under a microscope using standardized, quality-controlled methods. Bayesian variogram models were utilized for spatial risk modelling and mapping of P. falciparum parasitaemia at non-sampled locations, assuming stationary and non-stationary underlying spatial dependence. Results Two-thirds of the schoolchildren were infected with P. falciparum and the mean parasitaemia among infected children was 959 parasites/μl of blood. Age, socioeconomic status, not sleeping under a bed net, coverage rate with bed nets and environmental factors (e.g., normalized difference vegetation index, rainfall, land surface temperature and living in close proximity to standing water) were significantly associated with the risk of P. falciparum parasitaemia. After accounting for spatial correlation, age, bed net coverage, rainfall during the main malaria transmission season and distance to rivers remained significant covariates. Conclusion It is argued that a massive increase in bed net coverage, particularly in villages in close proximity to rivers, in concert with other control measures, is necessary to bring malaria endemicity down to intermediate or low levels.

Abstract Background Although antenatal care coverage in Tanzania is high, worrying gaps exist in terms of its quality and ability to prevent, diagnose or treat complications. Moreover, much less is known about the utilisation of postnatal care, by which we mean the care of mother and baby that begins one hour after the delivery until six weeks after childbirth. We describe the perspectives and experiences of women and health care providers on the use of antenatal and postnatal services. Methods From March 2007 to January 2008, we conducted in-depth interviews with health care providers and village based informants in 8 villages of Lindi Rural and Tandahimba districts in southern Tanzania. Eight focus group discussions were also conducted with women who had babies younger than one year and pregnant women. The discussion guide included information about timing of antenatal and postnatal services, perceptions of the rationale and importance of antenatal and postnatal care, barriers to utilisation and suggestions for improvement. Results Women were generally positive about both antenatal and postnatal care. Among common reasons mentioned for late initiation of antenatal care was to avoid having to make several visits to the clinic. Other concerns included fear of encountering wild animals on the way to the clinic as well as lack of money. Fear of caesarean section was reported as a factor hindering intrapartum care-seeking from hospitals. Despite the perceived benefits of postnatal care for children, there was a total lack of postnatal care for the mothers. Shortages of staff, equipment and supplies were common complaints in the community. Conclusion Efforts to improve antenatal and postnatal care should focus on addressing geographical and economic access while striving to make services more culturally sensitive. Antenatal and postnatal care can offer important opportunities for linking the health system and the community by encouraging women to deliver with a skilled attendant. Addressing staff shortages through expanding training opportunities and incentives to health care providers and developing postnatal care guidelines are key steps to improve maternal and newborn health.