Prevention of Tungiasis and Tungiasis-Associated Morbidity Using the Plant-Based Repellent Zanzarin: A Randomized,Controlled Field Study in Rural Madagascar

Background

Tungiasis, a parasitic skin disease caused by the female sand flea Tunga penetrans, is a prevalent condition in impoverished communities in the tropics. In this setting, the ectoparasitosis is associated with important morbidity. It causes disfigurement and mutilation of the feet. Feasible and effective treatment is not available. So far prevention is the only means to control tungiasis-associated morbidity.

Methodology

In two villages in Central Madagascar, we assessed the efficacy of the availability of closed shoes and the twice-daily application of a plant-based repellent active against sand fleas (Zanzarin) in comparison to a control group without intervention. The study population was randomized into three groups: shoe group, repellent group and control group and monitored for ten weeks. The intensity of infestation, the attack rate and the severity of tungiasis-associated morbidity were assessed every two weeks.

Findings

In the repellent group, the median attack rate became zero already after two weeks. The intensity of the infestation decreased constantly during the observation period and tungiasis-associated morbidity was lowered to an insignificant level. In the shoe group, only a marginal decrease in the intensity of infestation and in the attack rate was observed. At week 10, the intensity of infestation, the attack rate and the severity score for acute tungiasis remained significantly higher in the shoe group than in the repellent group. Per protocol analysis showed that the protective effect of shoes was closely related to the regularity with which shoes were worn.

Conclusions

Although shoes were requested by the villagers and wearing shoes was encouraged by the investigators at the beginning of the study, the availability of shoes only marginally influenced the attack rate of female sand fleas. The twice-daily application of a plant-based repellent active against sand fleas reduced the attack to zero and lowered tungiasis-associated morbidity to an insignificant level.     

Effect of Footwear Modifications on Oscillations at the Achilles Tendon during Running on a Treadmill and Over Ground: A Cross-Sectional Study

Background

Achilles tendon injuries are known to commonly occur in runners. During running repeated impacts are transferred in axial direction along the lower leg, therefore possibly affecting the oscillation behavior of the Achilles tendon. The purpose of the present study was to explore the effects of different footwear modifications and different ground conditions (over ground versus treadmill) on oscillations at the Achilles tendon.

Methods

Oscillations were measured in 20 male runners using two tri-axial accelerometers. Participants ran in three different shoe types on a treadmill and over ground. Data analysis was limited to stance phase and performed in time and frequency space. Statistical comparison was conducted between oscillations in vertical and horizontal direction, between running shoes and between ground conditions (treadmill versus over ground running).

Results

Differences in the oscillation behavior could be detected between measurement directions with peak accelerations in the vertical being lower than those in the horizontal direction, p < 0.01. Peak accelerations occurred earlier at the distal accelerometer than at the proximal one, p < 0.01. Average normalized power differed between running shoes (p < 0.01) with harder damping material resulting in higher power values. Little to no power attenuation was found between the two accelerometers. Oscillation behavior of the Achilles tendon is not influenced by ground condition.

Conclusion

Differences in shoe configurations may lead to variations in running technique and impact forces and therefore result in alterations of the vibration behavior at the Achilles tendon. The absence of power attenuation may have been caused by either a short distance between the two accelerometers or high stiffness of the tendon. High stiffness of the tendon will lead to complete transmission of the signal along the Achilles tendon and therefore no attenuation occurs.     

Barriers and Facilitators of Participation in Sports: A Qualitative Study on Dutch Individuals with Lower Limb Amputation

Introduction

Although individuals with lower limb amputation may benefit from participation in sports, less than 40% do so.

Aim

To identify the barriers and facilitators that influence participation in sports for individuals with lower limb amputation.

Design

Qualitative study.

Participants

Twenty six individuals with lower limb amputation, all originating from the Dutch provinces of Groningen and Drenthe, of which 13 athletes.

Methods

Semi-structured interviews were used to gather information. Following thematic analysis, emerging themes were organized in three categories Technical, Social and Personal.

Results

Sport was perceived as enjoyable activity that would help participants to become and stay healthy, improve the number of social contacts, reduce phantom pain and decrease daily tension. Inadequate facilities, problematic transportation, trivialization from others, poor health and lack of motivation or the lack of a sports partner were barriers commonly mentioned by non-athletes. Remarkably, while all athletes were successful prosthetic users, the majority chose to participate in sports for which prosthesis was neither required nor needed.

Conclusions

Each individual with lower limb amputation needs to be counselled according to the barriers and facilitators he/she personally experiences. Athletes appeared to be more proactive in searching for a solution and also appeared less discouraged by failing.     

Toward an open-access global database for mapping, control, and surveillance of neglected tropical diseases

Background

After many years of general neglect, interest has grown and efforts came under way for the mapping, control, surveillance, and eventual elimination of neglected tropical diseases (NTDs). Disease risk estimates are a key feature to target control interventions, and serve as a benchmark for monitoring and evaluation. What is currently missing is a georeferenced global database for NTDs providing open-access to the available survey data that is constantly updated and can be utilized by researchers and disease control managers to support other relevant stakeholders. We describe the steps taken toward the development of such a database that can be employed for spatial disease risk modeling and control of NTDs.

Methodology

With an emphasis on schistosomiasis in Africa, we systematically searched the literature (peer-reviewed journals and ‘grey literature’), contacted Ministries of Health and research institutions in schistosomiasis-endemic countries for location-specific prevalence data and survey details (e.g., study population, year of survey and diagnostic techniques). The data were extracted, georeferenced, and stored in a MySQL database with a web interface allowing free database access and data management.

Principal Findings

At the beginning of 2011, our database contained more than 12,000 georeferenced schistosomiasis survey locations from 35 African countries available under http://www.gntd.org. Currently, the database is expanded to a global repository, including a host of other NTDs, e.g. soil-transmitted helminthiasis and leishmaniasis.

Conclusions

An open-access, spatially explicit NTD database offers unique opportunities for disease risk modeling, targeting control interventions, disease monitoring, and surveillance. Moreover, it allows for detailed geostatistical analyses of disease distribution in space and time. With an initial focus on schistosomiasis in Africa, we demonstrate the proof-of-concept that the establishment and running of a global NTD database is feasible and should be expanded without delay.     

Neglected Tropical Diseases outside the Tropics

Background

The neglected tropical diseases (NTDs) cause significant morbidity and mortality worldwide. Due to the growth in international travel and immigration, NTDs may be diagnosed in countries of the western world, but there has been no specific focus in the literature on imported NTDs.

Methods

Retrospective study of a cohort of immigrants and travelers diagnosed with one of the 13 core NTDs at a Tropical Medicine Referral Unit in Spain during the period April 1989-December 2007. Area of origin or travel was recorded and analyzed.

Results

There were 6168 patients (2634 immigrants, 3277 travelers and 257 VFR travelers) in the cohort. NTDs occurred more frequently in immigrants, followed by VFR travelers and then by other travelers (p<0.001 for trend). The main NTDs diagnosed in immigrants were onchocerciasis (n = 240, 9.1%) acquired mainly in sub-Saharan Africa, Chagas disease (n = 95, 3.6%) in immigrants from South America, and ascariasis (n = 86, 3.3%) found mainly in immigrants from sub-Saharan Africa. Most frequent NTDs in travelers were: schistosomiasis (n = 43, 1.3%), onchocerciasis (n = 17, 0.5%) and ascariasis (n = 16, 0.5%), and all were mainly acquired in sub-Saharan Africa. The main NTDs diagnosed in VFR travelers were onchocerciasis (n = 14, 5.4%), and schistosomiasis (n = 2, 0.8%).

Conclusions

The concept of imported NTDs is emerging as these infections acquire a more public profile. Specific issues such as the possibility of non-vectorial transmission outside endemic areas and how some eradication programmes in endemic countries may have an impact even in non-tropical western countries are addressed. Recognising NTDs even outside tropical settings would allow specific prevention and control measures to be implemented and may create unique opportunities for research in future.     

Neglected Tropical Diseases: A Systematic Evaluation of Research Capacity in Nigeria

Background

Nigeria carries the highest burden and diversity of neglected tropical diseases (NTDs) in sub-Saharan Africa and is preparing to scale up its efforts to control/eliminate these diseases. To achieve this it will require a range of internal technical support and expertise for mapping, monitoring and evaluating, operational research and documenting its success. In order to begin to evaluate this potential in Nigeria, this study collated and analysed information for lymphatic filariasis (LF), onchocerciasis, schistosomiasis and soil-transmitted helminths (STH), which are currently being targeted with preventive chemotherapy through mass drug administration (MDA).

Methodology/Principal Findings

Information from 299 scientific articles published on the selected NTDs in 179 journals between January 2008 and September 2013 was extracted and systematically compiled into a geo-referenced database for analysis and mapping. The highest number of articles was from the southern geo-political zones of the country. The majority of articles focused on one specific disease, and schistosomiasis and STH were found to have the highest and most wide ranging research output. The main type of study was parasitological, and the least was biotechnological. Nigerian authors were mostly affiliated with universities, and there was a wide range of international co-authors from Africa and other regions, especially the USA and UK. The majority of articles were published in journals with no known impact factor.

Conclusions/Significance

The extensive database and series of maps on the research capacity within Nigeria produced in this study highlights the current potential that exists, and needs to be fully maximized for the control/elimination of NTDs in the country. This study provides an important model approach that can be applied to other low and middle income countries where NTDs are endemic, and NTD programmes require support from the expertise within their own country, as well as internationally, to help raise their profile and importance.     

Do we protect or discriminate? Representation of senior adults in clinical trials

Aim

The analysis of barriers responsible for low recruitment of older patients in clinical trials and presentation of possible solutions are the subject of this review.

Background

Europe''s population is ageing, and the group of people who more frequently develop neoplasms increases. Oncologists are confronted with a new challenge – how to treat cancer in this group of patients, especially considering the lack of Evidence Based Medicine (EBM) guidelines for treatment of cancer in the elderly population.

Materials and methods

Medline search and analysis of studies published between 1999 and 2012, containing key words: senior adults, cancer, elderly in clinical trials.

Results

Detailed analysis of relevant studies demonstrated that senior adults are underrepresented in clinical trials. Moreover, there is a lack of trials exclusively designed for this heterogeneous group of patients. The analysis of reasons for low recruitment of older patients in clinical trials revealed barriers dependent on patient''s and physician''s attitudes as well as institutional and logistic problems.

Conclusions

It is necessary to widen the scale of trials of all phases in the group of seniors with appropriate assessment of toxicity. This will allow a proper stratification and obtaining representative groups for statistical analysis and credible trial results. Another priority is the design of trials dedicated exclusively to the elderly.     

Subspace Identification and Classification of Healthy Human Gait

Purpose

The classification between different gait patterns is a frequent task in gait assessment. The base vectors were usually found using principal component analysis (PCA) is replaced by an iterative application of the support vector machine (SVM). The aim was to use classifyability instead of variability to build a subspace (SVM space) that contains the information about classifiable aspects of a movement. The first discriminant of the SVM space will be compared to a discriminant found by an independent component analysis (ICA) in the SVM space.

Methods

Eleven runners ran using shoes with different midsoles. Kinematic data, representing the movements during stance phase when wearing the two shoes, was used as input to a PCA and SVM. The data space was decomposed by an iterative application of the SVM into orthogonal discriminants that were able to classify the two movements. The orthogonal discriminants spanned a subspace, the SVM space. It represents the part of the movement that allowed classifying the two conditions. The data in the SVM space was reconstructed for a visual assessment of the movement difference. An ICA was applied to the data in the SVM space to obtain a single discriminant. Cohen''s d effect size was used to rank the PCA vectors that could be used to classify the data, the first SVM discriminant or the ICA discriminant.

Results

The SVM base contains all the information that discriminates the movement of the two shod conditions. It was shown that the SVM base contains some redundancy and a single ICA discriminant was found by applying an ICA in the SVM space.

Conclusions

A combination of PCA, SVM and ICA is best suited to extract all parts of the gait pattern that discriminates between the two movements and to find a discriminant for the classification of dichotomous kinematic data.     

Dynamics of Socioeconomic Risk Factors for Neglected Tropical Diseases and Malaria in an Armed Conflict

Background

Armed conflict and war are among the leading causes of disability and premature death, and there is a growing share of civilians killed or injured during armed conflicts. A major part of the civilian suffering stems from indirect effects or collateral impact such as changing risk profiles for infectious diseases. We focused on rural communities in the western part of Côte d''Ivoire, where fighting took place during the Ivorian civil war in 2002/2003, and assessed the dynamics of socioeconomic risk factors for neglected tropical diseases (NTDs) and malaria.

Methodology

The same standardized and pre-tested questionnaires were administered to the heads of 182 randomly selected households in 25 villages in the region of Man, western Côte d''Ivoire, shortly before and after the 2002/2003 armed conflict.

Principal Findings

There was no difference in crowding as measured by the number of individuals per sleeping room, but the inadequate sanitation infrastructure prior to the conflict further worsened, and the availability and use of protective measures against mosquito bites and accessibility to health care infrastructure deteriorated. Although the direct causal chain between these findings and the conflict are incomplete, partially explained by the very nature of working in conflict areas, the timing and procedures of the survey, other sources and anecdotal evidence point toward a relationship between an increased risk of suffering from NTDs and malaria and armed conflict.

Conclusion

New research is needed to deepen our understanding of the often diffuse and neglected indirect effects of armed conflict and war, which may be worse than the more obvious, direct effects.     

Deformation of the Durom Acetabular Component and Its Impact on Tribology in a Cadaveric Model—A Simulator Study

Background

Recent studies have shown that the acetabular component frequently becomes deformed during press-fit insertion. The aim of this study was to explore the deformation of the Durom cup after implantation and to clarify the impact of deformation on wear and ion release of the Durom large head metal-on-metal (MOM) total hips in simulators.

Methods

Six Durom cups impacted into reamed acetabula of fresh cadavers were used as the experimental group and another 6 size-paired intact Durom cups constituted the control group. All 12 Durom MOM total hips were put through a 3 million cycle (MC) wear test in simulators.

Results

The 6 cups in the experimental group were all deformed, with a mean deformation of 41.78±8.86 µm. The average volumetric wear rate in the experimental group and in the control group in the first million cycle was 6.65±0.29 mm³/MC and 0.89±0.04 mm³/MC (t = 48.43, p = 0.000). The ion levels of Cr and Co in the experimental group were also higher than those in the control group before 2.0 MC. However there was no difference in the ion levels between 2.0 and 3.0 MC.

Conclusions

This finding implies that the non-modular acetabular component of Durom total hip prosthesis is likely to become deformed during press-fit insertion, and that the deformation will result in increased volumetric wear and increased ion release.

Clinical Relevance

This study was determined to explore the deformation of the Durom cup after implantation and to clarify the impact of deformation on wear and ion release of the prosthesis. Deformation of the cup after implantation increases the wear of MOM bearings and the resulting ion levels. The clinical use of the Durom large head prosthesis should be with great care.     

Neglected diseases in the news: a content analysis of recent international media coverage focussing on leishmaniasis and trypanosomiasis

Background

Although the pharmaceutical industry''s “neglect” of neglected tropical diseases (NTDs) has been investigated, no study evaluating media coverage of NTDs has been published. Poor media coverage exacerbates the neglect. This study aimed to investigate, describe, and analyse international media coverage of “neglected diseases” in general and three specific NTDs—African trypanosomiasis, leishmaniasis, and Chagas disease—from 1 January 2003 to 1 June 2007.

Methods

Archives of 11 leading international, English-language media were searched. A content analysis was done, coding for media organisation, date, author, type of report, slant, themes, and “frames”. Semi-structured interviews with journalists and key informants were conducted for further insight.

Principal Findings

Only 113 articles in a 53-month time period met the inclusion criteria, with no strong trends or increases in coverage. Overall, the BBC had the highest coverage with 20 results, followed by the Financial Times and Agence France Presse. CNN had the least coverage with one result. The term “neglected diseases” had good media currency and “sleeping sickness” was far more widely used than trypanosomiasis. The disease most covered was leishmaniasis and the least covered was Chagas. Academic researchers were most commonly quoted as a main source, while the World Health Organization (WHO) and pharmaceutical industry were the least quoted. Journalists generally agreed NTDs had not been adequately covered, but said a lack of real news development and the need to cater to domestic audiences were major obstacles for NTD reporting. All journalists said health agencies, particularly WHO, were not communicating adequately about the burden of NTDs.

Conclusions

Public health agencies need to raise priority for NTD advocacy. Innovative strategies, such as reporting grants or creating a network of voices, may be needed.     

Serological Surveillance Development for Tropical Infectious Diseases Using Simultaneous Microsphere-Based Multiplex Assays and Finite Mixture Models

Background

A strategy to combat infectious diseases, including neglected tropical diseases (NTDs), will depend on the development of reliable epidemiological surveillance methods. To establish a simple and practical seroprevalence detection system, we developed a microsphere-based multiplex immunoassay system and evaluated utility using samples obtained in Kenya.

Methods

We developed a microsphere-based immuno-assay system to simultaneously measure the individual levels of plasma antibody (IgG) against 8 antigens derived from 6 pathogens: Entamoeba histolytica (C-IgL), Leishmania donovani (KRP42), Toxoplasma gondii (SAG1), Wuchereria bancrofti (SXP1), HIV (gag, gp120 and gp41), and Vibrio cholerae (cholera toxin). The assay system was validated using appropriate control samples. The assay system was applied for 3411 blood samples collected from the general population randomly selected from two health and demographic surveillance system (HDSS) cohorts in the coastal and western regions of Kenya. The immunoassay values distribution for each antigen was mathematically defined by a finite mixture model, and cut-off values were optimized.

Findings

Sensitivities and specificities for each antigen ranged between 71 and 100%. Seroprevalences for each pathogen from the Kwale and Mbita HDSS sites (respectively) were as follows: HIV, 3.0% and 20.1%; L. donovani, 12.6% and 17.3%; E. histolytica, 12.8% and 16.6%; and T. gondii, 30.9% and 28.2%. Seroprevalences of W. bancrofti and V. cholerae showed relatively high figures, especially among children. The results might be affected by immunological cross reactions between W. bancrofti-SXP1 and other parasitic infections; and cholera toxin and the enterotoxigenic E. coli (ETEC), respectively.

Interpretation

A microsphere-based multi-serological assay system can provide an opportunity to comprehensively grasp epidemiological features for NTDs. By adding pathogens and antigens of interest, optimized made-to-order high-quality programs can be established to utilize limited resources to effectively control NTDs in Africa.     

Barriers to Advance Care Planning in Cancer,Heart Failure and Dementia Patients: A Focus Group Study on General Practitioners' Views and Experiences

Background

The long-term and often lifelong relationship of general practitioners (GPs) with their patients is considered to make them the ideal initiators of advance care planning (ACP). However, in general the incidence of ACP discussions is low and ACP seems to occur more often for cancer patients than for those with dementia or heart failure.

Objective

To identify the barriers, from GPs'' perspective, to initiating ACP and to gain insight into any differences in barriers between the trajectories of patients with cancer, heart failure and dementia.

Method

Five focus groups were held with GPs (n = 36) in Flanders, Belgium. The focus group discussions were transcribed verbatim and analyzed using the method of constant comparative analysis.

Results

Three types of barriers were distinguished: barriers relating to the GP, to the patient and family and to the health care system. In cancer patients, a GP''s lack of knowledge about treatment options and the lack of structural collaboration between the GP and specialist were expressed as barriers. Barriers that occured more often with heart failure and dementia were the lack of GP familiarity with the terminal phase, the lack of key moments to initiate ACP, the patient''s lack of awareness of their diagnosis and prognosis and the fact that patients did not often initiate such discussions themselves. The future lack of decision-making capacity of dementia patients was reported by the GPs as a specific barrier for the initiation of ACP.

Conclusion

The results of our study contribute to a better understanding of the factors hindering GPs in initiating ACP. Multiple barriers need to be overcome, of which many can be addressed through the development of practical guidelines and educational interventions.     

Exploring Gender Dimensions of Treatment Programmes for Neglected Tropical Diseases in Uganda

Background

Gender remains a recognized but relatively unexamined aspect of the potential challenges for treatment programmes for Neglected Tropical Diseases (NTDs). We sought to explore the role of gender in access to treatment in the Uganda National Neglected Tropical Disease Control Programme.

Methodology/Principal Findings

Quantitative and qualitative data was collected in eight villages in Buyende and Kamuli districts, Eastern Uganda. Quantitative data on the number of persons treated by age and gender was identified from treatment registers in each village. Qualitative data was collected through semi-structured interviews with sub-county supervisors, participant observation and from focus group discussions with community leaders, community medicine distributors (CMDs), men, women who were pregnant or breastfeeding at the time of mass-treatment, and adolescent males and females. Findings include the following: (i) treatment registers are often incomplete making it difficult to obtain accurate estimates of the number of persons treated; (ii) males face more barriers to accessing treatment than women due to occupational roles which keep them away from households or villages for long periods, and males may be more distrustful of treatment; (iii) CMDs may be unaware of which medicines are safe for pregnant and breastfeeding women, resulting in women missing beneficial treatments.

Conclusions/Significance

Findings highlight the need to improve community-level training in drug distribution which should include gender-specific issues and guidelines for treating pregnant and breastfeeding women. Accurate age and sex disaggregated measures of the number of community members who swallow the medicines are also needed to ensure proper monitoring and evaluation of treatment programmes.     

Reporting the Reliability of Accelerometer Data with and without Missing Values

Objectives

Participants with complete accelerometer data often represent a low proportion of the total sample and, in some cases, may be distinguishable from participants with incomplete data. Because traditional reliability methods characterize the consistency of complete data, little is known about reliability properties for an entire sample. This study employed Generalizability theory to report an index of reliability characterizing complete (7 days) and observable (1 to 7 days) accelerometer data.

Design

Cross-sectional.

Methods

Accelerometer data from the Study of Early Child Care and Youth Development were analyzed in this study. Missing value analyses were conducted to describe the pattern and mechanism of missing data. Generalizability coefficients were derived from variance components to report reliability parameters for complete data and also for the entire observable sample. Analyses were conducted separately by age (9, 11, 12, and 15 yrs) and daily wear time criteria (6, 8, 10, and 12 hrs).

Results

Participants with complete data were limited (<34%) and, most often, data were not considered to be missing completely at random. Across conditions, reliability coefficients for complete data were between 0.74 and 0.87. Relatively lower reliability properties were found across all observable data, ranging from 0.52 to 0.67. Sample variability increased with longer wear time criteria, but decreased with advanced age.

Conclusions

A reliability coefficient that includes all participants, not just those with complete data, provides a global perspective of reliability that could be used to further understand group level associations between activity and health outcomes.     

A Systematic Approach to Capacity Strengthening of Laboratory Systems for Control of Neglected Tropical Diseases in Ghana,Kenya, Malawi and Sri Lanka

Background

The lack of capacity in laboratory systems is a major barrier to achieving the aims of the London Declaration (2012) on neglected tropical diseases (NTDs). To counter this, capacity strengthening initiatives have been carried out in NTD laboratories worldwide. Many of these initiatives focus on individuals'' skills or institutional processes and structures ignoring the crucial interactions between the laboratory and the wider national and international context. Furthermore, rigorous methods to assess these initiatives once they have been implemented are scarce. To address these gaps we developed a set of assessment and monitoring tools that can be used to determine the capacities required and achieved by laboratory systems at the individual, organizational, and national/international levels to support the control of NTDs.

Methodology and principal findings

We developed a set of qualitative and quantitative assessment and monitoring tools based on published evidence on optimal laboratory capacity. We implemented the tools with laboratory managers in Ghana, Malawi, Kenya, and Sri Lanka. Using the tools enabled us to identify strengths and gaps in the laboratory systems from the following perspectives: laboratory quality benchmarked against ISO 15189 standards, the potential for the laboratories to provide support to national and regional NTD control programmes, and the laboratory''s position within relevant national and international networks and collaborations.

Conclusion

We have developed a set of mixed methods assessment and monitoring tools based on evidence derived from the components needed to strengthen the capacity of laboratory systems to control NTDs. Our tools help to systematically assess and monitor individual, organizational, and wider system level capacity of laboratory systems for NTD control and can be applied in different country contexts.     

Recognising and Treatment Seeking for Acute Bacterial Meningitis in Adults and Children in Resource-Poor Settings: A Qualitative Study

Objective

High mortality burden from Acute Bacterial Meningitis (ABM) in resource-poor settings has been frequently blamed on delays in treatment seeking. We explored treatment-seeking pathways from household to primary health care and referral for ABM in Malawi.

Design

A cross-sectional qualitative study using narrative in-depth interviews, semi-structured interviews and focus group discussions.

Participants

Adults and children with proven and probable acute bacterial meningitis and/or their carers; adults from urban and peri-urban communities; and primary health care workers (HCW).

Setting

Queen Elizabeth Central Hospital (QECH), urban and peri-urban private and government primary health centres and communities in Blantyre District, Malawi.

Results

Whilst communities associated meningitis with a stiff neck, in practice responses focused on ability to recognise severe illness. Misdiagnosis of meningitis as malaria was common. Subsequent action by families depended on the extent to which normal social life was disrupted by the illness and depended on the age and social position of the sufferer. Seizures and convulsions were considered severe symptoms but were often thought to be malaria. Presumptive malaria treatment at home often delayed formal treatment seeking. Further delays in treatment seeking were caused by economic barriers and perceptions of inefficient or inadequate primary health services.

Conclusions

Given the difficulties in diagnosis of meningitis where malaria is common, any intervention for ABM at primary level must focus on recognising severe illness, and encouraging action at the household, community and primary health levels. Overcoming barriers to recognition and social constraints at community level require broad community-based strategies and may provide a route to addressing poor clinical outcomes.     

Integrated Surveys of Neglected Tropical Diseases in Southern Sudan: How Much Do They Cost and Can They Be Refined?

Background

Increasing emphasis on integrated control of neglected tropical diseases (NTDs) requires identification of co-endemic areas. Integrated surveys for lymphatic filariasis (LF), schistosomiasis and soil-transmitted helminth (STH) infection have been recommended for this purpose. Integrated survey designs inevitably involve balancing the costs of surveys against accuracy of classifying areas for treatment, so-called implementation units (IUs). This requires an understanding of the main cost drivers and of how operating procedures may affect both cost and accuracy of surveys. Here we report a detailed cost analysis of the first round of integrated NTD surveys in Southern Sudan.

Methods and Findings

Financial and economic costs were estimated from financial expenditure records and interviews with survey staff using an ingredients approach. The main outcome was cost per IU surveyed. Uncertain variables were subjected to univariate sensitivity analysis and the effects of modifying standard operating procedures were explored. The average economic cost per IU surveyed was USD 40,206 or USD 9,573, depending on the size of the IU. The major cost drivers were two key categories of recurrent costs: i) survey consumables, and ii) personnel.

Conclusion

The cost of integrated surveys in Southern Sudan could be reduced by surveying larger administrative areas for LF. If this approach was taken, the estimated economic cost of completing LF, schistosomiasis and STH mapping in Southern Sudan would amount to USD 1.6 million. The methodological detail and costing template provided here could be used to generate cost estimates in other settings and readily compare these to the present study, and may help budget for integrated and single NTDs surveys elsewhere.     

Association of the Maternal MTHFR C677T Polymorphism with Susceptibility to Neural Tube Defects in Offsprings: Evidence from 25 Case-Control Studies

Background

Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and is involved in DNA methylation, DNA synthesis, and DNA repair. In addition, it is a possible risk factor in neural tube defects (NTDs). The association of the C677T polymorphism in the MTHFR gene and NTD susceptibility has been widely demonstrated, but the results remain inconclusive. In this study, we performed a meta-analysis with 2429 cases and 3570 controls to investigate the effect of the MTHFR C677T polymorphism on NTDs.

Methods

An electronic search of PubMed and Embase database for papers on the MTHFR C677T polymorphism and NTD risk was performed. All data were analysed with STATA (version 11). Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Sensitivity analysis, test of heterogeneity, cumulative meta-analysis, and assessment of bias were performed in our meta-analysis.

Results

A significant association between the MTHFR C677T polymorphism and NTD susceptibility was revealed in our meta-analysis ( TT versus CC: OR  = 2.022, 95% CI: 1.508, 2.712; CT+TT versus CC: OR  = 1.303, 95% CI: 1.089, 1.558; TT versus CC+CT: OR  = 1.716, 95% CI: 1.448, 2.033; 2TT+CT versus 2CC+CT: OR  = 1.330, 95% CI: 1.160, 1.525). Moreover, an increased NTD risk was found after stratification of the MTHFR C677T variant data by ethnicity and source of controls.

Conclusion

The results suggested the maternal MTHFR C677T polymorphism is a genetic risk factor for NTDs. Further functional studies to investigate folate-related gene polymorphisms, periconceptional multivitamin supplements, complex interactions, and the development of NTDs are warranted.     

Analysis of Epigenetic Factors in Mouse Embryonic Neural Stem Cells Exposed to Hyperglycemia

Background

Maternal diabetes alters gene expression leading to neural tube defects (NTDs) in the developing brain. The mechanistic pathways that deregulate the gene expression remain unknown. It is hypothesized that exposure of neural stem cells (NSCs) to high glucose/hyperglycemia results in activation of epigenetic mechanisms which alter gene expression and cell fate during brain development.

Methods and Findings

NSCs were isolated from normal pregnancy and streptozotocin induced-diabetic pregnancy and cultured in physiological glucose. In order to examine hyperglycemia induced epigenetic changes in NSCs, chromatin reorganization, global histone status at lysine 9 residue of histone H3 (acetylation and trimethylation) and global DNA methylation were examined and found to be altered by hyperglycemia. In NSCs, hyperglycemia increased the expression of Dcx (Doublecortin) and Pafah1b1 (Platelet activating factor acetyl hydrolase, isoform 1b, subunit 1) proteins concomitant with decreased expression of four microRNAs (mmu-miR-200a, mmu-miR-200b, mmu-miR-466a-3p and mmu-miR-466 d-3p) predicted to target these genes. Knockdown of specific microRNAs in NSCs resulted in increased expression of Dcx and Pafah1b1 proteins confirming target prediction and altered NSC fate by increasing the expression of neuronal and glial lineage markers.

Conclusion/Interpretation

This study revealed that hyperglycemia alters the epigenetic mechanisms in NSCs, resulting in altered expression of some development control genes which may form the basis for the NTDs. Since epigenetic changes are reversible, they may be valuable therapeutic targets in order to improve fetal outcomes in diabetic pregnancy.