A comparison of the NIRUDAK models and WHO algorithm for dehydration assessment in older children and adults with acute diarrhoea: a prospective, observational study.

BACKGROUND: Despite the importance of accurate and rapid assessment of hydration status in patients with acute diarrhoea, no validated tools exist to help clinicians assess dehydration severity in older children and adults. The aim of this study is to validate a clinical decision support tool (CDST) and a simplified score for dehydration severity in older children and adults with acute diarrhoea (both developed during the NIRUDAK study) and compare their accuracy and reliability with current WHO guidelines. METHODS: A random sample of patients aged 5 years or older presenting with diarrhoea to the icddr,b Dhaka Hospital in Bangladesh between Jan 30 and Dec 13, 2022 were included in this prospective cohort study. Patients with fewer than three loose stools per day, more than 7 days of symptoms, previous enrolment in the study, or a diagnosis other than acute gastroenteritis were excluded. Patients were weighed on arrival and assessed separately by two nurses using both our novel clinical tools and WHO guidelines. Patients were weighed every 4 h to determine their percent weight change with rehydration, our criterion standard for dehydration. Accuracy for the diagnosis of dehydration category (none, some, or severe) was assessed using the ordinal c-index (ORC). Reliability was assessed by comparing the prediction of severe dehydration from each nurse's independent assessment using the intraclass correlation coefficient (ICC). FINDINGS: 1580 patients were included in our primary analysis, of whom 921 (58·3%) were female and 659 (41·7%) male. The ORC was 0·74 (95% CI 0·71-0·77) for the CDST, 0·75 (0·71-0·78) for the simplified score, and 0·64 (0·61-0·67) for the WHO guidelines. The ICC was 0·98 (95% CI 0·97-0·98) for the CDST, 0·94 (0·93-0·95) for the simplified score, and 0·56 (0·52-0·60) for the WHO guidelines. INTERPRETATION: Use of our CDST or simplified score by clinicians could reduce undertreatment and overtreatment of older children and adults with acute diarrhoea, potentially reducing morbidity and mortality for this common disease. FUNDING: US National Institutes of Health. TRANSLATION: For the Bangla translation of the abstract see Supplementary Materials section.

Correction: Derivation of the first clinical diagnostic models for dehydration severity in patients over five years with acute diarrhea.

[This corrects the article DOI: 10.1371/journal.pntd.0009266.].

Impaired Intrauterine Growth in the Context of Maternal Hookworm Infection During Gestation.

Hookworm infection is associated with poor nutritional outcomes, anemia, and impaired cognitive performance. We examined the association between maternal hookworm infection and birth outcomes in a cohort of women in Leyte, Philippines. We observed poor intrauterine growth characteristics associated with maternal hookworm only among male offspring, with lower birth weight, head circumference, and placental surface area. Male neonates also had higher insulin-like growth factor 2 (IGF-2) and lower adiponectin in cord blood. These data intriguingly suggest nutritional impacts of maternal hookworm infection during pregnancy may be divergent based on sex of the offspring.

Continuous diagnostic models for volume deficit in patients with acute diarrhea.

BACKGROUND: Episodes of acute diarrhea lead to dehydration, and existing care algorithms base treatment around categorical estimates for fluid resuscitation. This study aims to develop models for the percentage dehydration (fluid deficit) in individuals with acute diarrhea, to better target treatment and avoid the potential sequelae of over or under resuscitation. METHODS: This study utilizes data from two prospective cohort studies of patients with acute diarrhea in Dhaka, Bangladesh. Data were collected on patient arrival, including weight, clinical signs and symptoms, and demographic information. Consecutive weights were obtained to determine the true volume deficit of each patient. Data were entered into two distinct forward stepwise regression logistic models (DHAKA for under 5 years and NIRUDAK for 5 years and over). RESULTS: A total of 782 patients were included in the final analysis of the DHAKA data set, and 2139 were included in the final analysis of the NIRUDAK data set. The best model for the DHAKA data achieved an R2 of 0.27 and a root mean square error (RMSE) of 3.7 (compared to R2 of 0.06 and RMSE of 5.5 with the World Health Organization child care algorithm) and selected 6 predictors. The best performance model for the NIRUDAK data achieved an R2 of 0.28 and a RMSE of 2.6 (compared to R2 of 0.08 and RMSE of 4.3 with the World Health Organization adolescent/adult care algorithm) and selected 7 predictors with 2 interactions. CONCLUSIONS: These are the first mathematical models for patients with acute diarrhea that allow for the calculation of a patient's percentage dehydration (fluid deficit) and subsequent targeted treatment with fluid resuscitation. These findings are an improvement on existing World Health Organization care algorithms.

Assessing the performance of clinical diagnostic models for dehydration among patients with cholera and undernutrition in Bangladesh.

OBJECTIVE: Accurately assessing dehydration severity is a critical step in reducing mortality from diarrhoea, but is complicated by cholera and undernutrition. This study seeks to assess the accuracy of two clinical diagnostic models for dehydration among patients over five years with cholera and undernutrition and compare their respective performance to the World Health Organization (WHO) algorithm. METHODS: In this secondary analysis of data collected from the NIRUDAK study, accuracy of the full and simplified NIRUDAK models for predicting severe and any dehydration was measured using the area under the Receiver Operator Characteristic curve (AUC) among patients over five with/without cholera and with/without wasting. Bootstrap with 1000 iterations was used to compare the m-index for each NIRUDAK model to that of the WHO algorithm. RESULTS: A total of 2,139 and 2,108 patients were included in the nutrition and cholera subgroups respectively with an overall median age of 35 years (IQR = 42) and 49.6% female. All subgroups had acceptable discrimination in diagnosing severe or any dehydration (AUC > 0.60); though the full NIRUDAK model performed best among patients without cholera, with an AUC of 0.82 (95%CI:0.79, 0.85) and among patients without wasting, with an AUC of 0.79 (95%CI:0.76, 0.81). Compared with the WHO's algorithm, both the full and simplified NIRUDAK models performed significantly better in terms of their m-index (p < 0.001) for all comparisons, except for the simplified NIRUDAK model in the wasting group. CONCLUSIONS: Both the full and simplified NIRUDAK models performed less well in patients over five years with cholera and/or wasting; however, both performed better than the WHO algorithm.

Derivation and Internal Validation of a Score to Predict Dehydration Severity in Patients over 5 Years with Acute Diarrhea.

Diarrheal disease accounts for more than one million deaths annually in patients over 5 years of age. Although most patients can be managed with oral rehydration solution, patients with severe dehydration require resuscitation with intravenous fluids. Scoring systems to assess dehydration have been empirically derived and validated in children under 5 years, but none have been validated for patients over 5 years. In this study, a prospective cohort of 2,172 patients over 5 years presenting with acute diarrhea to International Centre for Diarrhoeal Disease Research, Dhaka Hospital, Bangladesh, were assessed for clinical signs of dehydration. The percent difference between presentation and posthydration stable weight determined severe (≥ 9%), some (3-9%), or no (< 3%) dehydration. An ordinal regression model was derived using clinical signs and demographics and was then converted to a 13-point score to predict none (score of 0-3), some (4-6), or severe (7-13) dehydration. The Novel, Innovative Research for Understanding Dehydration in Adults and Kids (NIRUDAK) Score developed by our team included age, sex, sunken eyes, radial pulse, respiration depth, skin turgor, and vomiting episodes in 24 hours. Accuracy of the NIRUDAK Score for predicting severe dehydration, as measured by the area under the receiver operating characteristic curve, was 0.76 (95% confidence interval = 0.73-0.78), with a sensitivity of 0.78 and a specificity of 0.61. Reliability was also robust, with an Inter-Class Correlation Coefficient of 0.88 (95% confidence interval = 0.84-0.91). This study represents the first empirically derived and internally validated scoring system for assessing dehydration in children ≥ 5 years and adults with acute diarrhea in a resource-limited setting.

Multidrug-resistant enteric pathogens in older children and adults with diarrhea in Bangladesh: epidemiology and risk factors.

BACKGROUND: Antimicrobial resistance (AMR) is a global public health threat and is increasingly prevalent among enteric pathogens in low- and middle-income countries (LMICs). However, the burden of multidrug-resistant organisms (MDROs) in older children, adults, and elderly patients with acute diarrhea in LMICs is poorly understood. This study's aim was to characterize the prevalence of MDR enteric pathogens isolated from patients with acute diarrhea in Dhaka, Bangladesh, and assess a wide range of risk factors associated with MDR. METHODS: This study was a secondary analysis of data collected from children over 5 years, adults, and elderly patients with acute diarrhea at the International Centre for Diarrhoeal Disease Research, Bangladesh Dhaka Hospital between March 2019 and March 2020. Clinical, historical, socio-environmental information, and a stool sample for culture and antimicrobial susceptibility testing were collected from each patient. Univariate statistics and multiple logistic regression were used to assess the prevalence of MDR among enteric pathogens and the association between independent variables and presence of MRDOs among culture-positive patients. RESULTS: A total of 1198 patients had pathogens isolated by stool culture with antimicrobial susceptibility results. Among culture-positive patients, the prevalence of MDR was 54.3%. The prevalence of MDR was highest in Aeromonas spp. (81.5%), followed by Campylobacter spp. (72.1%), Vibrio cholerae (28.1%), Shigella spp. (26.2%), and Salmonella spp. (5.2%). Factors associated with having MDRO in multiple logistic regression included longer transport time to hospital (>90 min), greater stool frequency, prior antibiotic use prior to hospital presentation, and non-flush toilet use. However, pseudo-R2 was low 0.086, indicating that other unmeasured variables need to be considered to build a more robust predictive model of MDR. CONCLUSIONS: MDR enteric pathogens were common in this study population with clinical, historical, and socio-environmental risk factors associated with MDROs. These findings may help guide clinical decision-making regarding antibiotic use and selection in patients at greatest risk of complications due to MDROs. Further prospective research is urgently needed to determine what additional factors place patients at greatest risk of MDRO, and the best strategies to mitigate the spread of MDR in enteric pathogens.

Derivation of the first clinical diagnostic models for dehydration severity in patients over five years with acute diarrhea.

Diarrheal diseases lead to an estimated 1.3 million deaths each year, with the majority of those deaths occurring in patients over five years of age. As the severity of diarrheal disease can vary widely, accurately assessing dehydration status remains the most critical step in acute diarrhea management. The objective of this study is to empirically derive clinical diagnostic models for assessing dehydration severity in patients over five years with acute diarrhea in low resource settings. We enrolled a random sample of patients over five years with acute diarrhea presenting to the icddr,b Dhaka Hospital. Two blinded nurses independently assessed patients for symptoms/signs of dehydration on arrival. Afterward, consecutive weights were obtained to determine the percent weight change with rehydration, our criterion standard for dehydration severity. Full and simplified ordinal logistic regression models were derived to predict the outcome of none (<3%), some (3-9%), or severe (>9%) dehydration. The reliability and accuracy of each model were assessed. Bootstrapping was used to correct for over-optimism and compare each model's performance to the current World Health Organization (WHO) algorithm. 2,172 patients were enrolled, of which 2,139 (98.5%) had complete data for analysis. The Inter-Class Correlation Coefficient (reliability) was 0.90 (95% CI = 0.87, 0.91) for the full model and 0.82 (95% CI = 0.77, 0.86) for the simplified model. The area under the Receiver-Operator Characteristic curve (accuracy) for severe dehydration was 0.79 (95% CI: 0.76-0.82) for the full model and 0.73 (95% CI: 0.70, 0.76) for the simplified model. The accuracy for both the full and simplified models were significantly better than the WHO algorithm (p<0.001). This is the first study to empirically derive clinical diagnostic models for dehydration severity in patients over five years. Once prospectively validated, the models may improve management of patients with acute diarrhea in low resource settings.

A therapeutic vaccine prototype induces protective immunity and reduces cardiac fibrosis in a mouse model of chronic Trypanosoma cruzi infection.

Chagas disease, caused by the parasite Trypanosoma cruzi, develops into chronic Chagas' cardiomyopathy in ~30% of infected individuals, characterized by conduction disorders, arrhythmias, heart failure, and even sudden cardiac death. Current anti-parasitic treatments are plagued by significant side effects and poor efficacy in the chronic phase of disease; thus, there is a pressing need for new treatment options. A therapeutic vaccine could bolster the protective TH1-mediated immune response, thereby slowing or halting the progression of chronic Chagas' cardiomyopathy. Prior work in mice has demonstrated therapeutic efficacy of a Tc24 recombinant protein vaccine in the acute phase of Chagas disease. However, it is anticipated that humans will be vaccinated therapeutically when in the chronic phase of disease. This study investigates the therapeutic efficacy of a vaccine prototype containing recombinant protein Tc24, formulated with an emulsion containing the Toll-like receptor 4 agonist E6020 as an immunomodulatory adjuvant in a mouse model of chronic T. cruzi infection. Among outbred ICR mice vaccinated during chronic T. cruzi infection, there is a significant increase in the number of animals with undetectable systemic parasitemia (60% of vaccinated mice compared to 0% in the sham vaccine control group), and a two-fold reduction in cardiac fibrosis over the control group. The vaccinated mice produce a robust protective TH1-biased immune response to the vaccine, as demonstrated by a significant increase in antigen-specific IFNγ-production, the number of antigen-specific IFNγ-producing cells, and IgG2a antibody titers. Importantly, therapeutic vaccination significantly reduced cardiac fibrosis in chronically infected mice. This is a first study demonstrating therapeutic efficacy of the prototype Tc24 recombinant protein and E6020 stable emulsion vaccine against cardiac fibrosis in a mouse model of chronic T. cruzi infection.

Impact of emergency medicine training implementation on mortality outcomes in Kigali, Rwanda: An interrupted time-series study.

INTRODUCTION: Although emergency medicine (EM) training programmes have begun to be introduced in low- and middle-income countries (LMICs), minimal data exist on their effects on patient-centered outcomes in such settings. This study evaluated the impact of EM training and associated systems implementation on mortality among patients treated at the University Teaching Hospital-Kigali (UTH-K). METHODS: At UTH-K an EM post-graduate diploma programme was initiated in October 2013, followed by a residency-training programme in August 2015. Prior to October 2013, care was provided exclusively by general practice physicians (GPs); subsequently, care has been provided through mutually exclusive shifts allocated between GPs and EM trainees. Patients seeking Emergency Centre (EC) care during November 2012-October 2013 (pre-training) and August 2015-July 2016 (post-training) were eligible for inclusion. Data were abstracted from a random sample of records using a structured protocol. The primary outcomes were EC and overall hospital mortality. Mortality prevalence and risk differences (RD) were compared pre- and post-training. Magnitudes of effects were quantified using regression models to yield adjusted odds ratios (aOR) with 95% confidence intervals (CI). RESULTS: From 43,213 encounters, 3609 cases were assessed. The median age was 32 years with a male predominance (60.7%). Pre-training EC mortality was 6.3% (95% CI 5.3-7.5%), while post-training EC mortality was 1.2% (95% CI 0.7-1.8%), constituting a significant decrease in adjusted analysis (aOR = 0.07, 95% CI 0.03-0.17; p < 0.001). Pre-training overall hospital mortality was 12.2% (95% CI 10.9-13.8%). Post-training overall hospital mortality was 8.2% (95% CI 6.9-9.6%), resulting in a 43% reduction in mortality likelihood (aOR = 0.57, 95% CI 0.36-0.94; p = 0.016). DISCUSSION: In the studied population, EM training and systems implementation was associated with significant mortality reductions demonstrating the potential patient-centered benefits of EM development in resource-limited settings.

3M-052 as an adjuvant for a PLGA microparticle-based Leishmania donovani recombinant protein vaccine.

It is believed that an effective vaccine against leishmaniasis will require a T helper type 1 (TH 1) immune response. In this study, we investigated the adjuvanticity of the Toll-like receptor (TLR) 7/8 agonist 3M-052 in combination with the Leishmania donovani 36-kDa nucleoside hydrolase recombinant protein antigen (NH36). NH36 and 3M-052 were encapsulated in separate batches of poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs). The loading efficiency for NH36 was 83% and for 3M-052 was above 95%. In vitro stimulation of bone marrow-derived dendritic cells, measured by IL-12 secretion, demonstrated that 3M-052 (free or MP-formulated) had a concentration-dependent immunostimulatory effect with an optimum concentration of 2 µg/mL. In immunogenicity studies in BALB/c mice, MP-formulated NH36 and 3M-052 elicited the highest serum titers of TH 1-associated IgG2a and IgG2b antibodies and the highest frequency of IFNγ-producing splenocytes. No dose dependency was observed among MP/NH36/3M-052 groups over a dose range of 4-60 µg 3M-052 per injection. The ability of MP-formulated NH36 and 3M-052 to elicit a TH 1-biased immune response indicates the potential for PLGA MP-formulated 3M-052 to be used as an adjuvant for leishmaniasis vaccines. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1587-1594, 2018.

Global Health and Emergency Care: Defining Clinical Research Priorities.

OBJECTIVES: Despite recent strides in the development of global emergency medicine (EM), the field continues to lag in applying a scientific approach to identifying critical knowledge gaps and advancing evidence-based solutions to clinical and public health problems seen in emergency departments (EDs) worldwide. Here, progress on the global EM research agenda created at the 2013 Academic Emergency Medicine Global Health and Emergency Care Consensus Conference is evaluated and critical areas for future development in emergency care research internationally are identified. METHODS: A retrospective review of all studies compiled in the Global Emergency Medicine Literature Review (GEMLR) database from 2013 through 2015 was conducted. Articles were categorized and analyzed using descriptive quantitative measures and structured data matrices. The Global Emergency Medicine Think Tank Clinical Research Working Group at the Society for Academic Emergency Medicine 2016 Annual Meeting then further conceptualized and defined global EM research priorities utilizing consensus-based decision making. RESULTS: Research trends in global EM research published between 2013 and 2015 show a predominance of observational studies relative to interventional or descriptive studies, with the majority of research conducted in the inpatient setting in comparison to the ED or prehospital setting. Studies on communicable diseases and injury were the most prevalent, with a relative dearth of research on chronic noncommunicable diseases. The Global Emergency Medicine Think Tank Clinical Research Working Group identified conceptual frameworks to define high-impact research priorities, including the traditional approach of using global burden of disease to define priorities and the impact of EM on individual clinical care and public health opportunities. EM research is also described through a population lens approach, including gender, pediatrics, and migrant and refugee health. CONCLUSIONS: Despite recent strides in global EM research and a proliferation of scholarly output in the field, further work is required to advocate for and inform research priorities in global EM. The priorities outlined in this paper aim to guide future research in the field, with the goal of advancing the development of EM worldwide.

Global Health and Emergency Care: Overcoming Clinical Research Barriers.

OBJECTIVES: There are many barriers impeding the conduct of high-quality emergency care research, particularly in low- and middle-income countries. Several of these barriers were originally outlined in 2013 as part of the Academic Emergency Medicine Global Health and Emergency Care Consensus Conference. This paper seeks to establish a broader consensus on the barriers to emergency care research globally and proposes a comprehensive array of new recommendations to overcome these barriers. METHODS: An electronic survey was conducted of a purposive sample of global emergency medicine research experts from around the world to describe the major challenges and solutions to conducting emergency care research in low-resource settings and rank them by importance. The Global Emergency Medicine Think Tank Clinical Research Working Group at the Society for Academic Emergency Medicine 2016 Annual Meeting utilized a modified Delphi technique for consensus-based decision making to categorize and expand upon these barriers and develop a comprehensive array of proposed solutions. RESULTS: The working group identified four broad categories of barriers to conducting emergency care research globally, including 1) the limited availability of research personnel, particularly those with prior research training; 2) logistic barriers and lack of standardization of data collection; 3) ethical barriers to conducting research in resource-limited settings, particularly when no local institutional review board is available; and 4) the relative dearth of funding for global emergency care research. Proposed solutions included building a diverse and interdisciplinary research team structured to promote mentorship of junior researchers, utilizing local research assistants or technologic tools such as telemedicine for language translation, making use of new tools such as mobile health (mHealth) to standardize and streamline data collection, identifying alternatives to local institutional review board approval and the use of community consent when appropriate, and increased advocacy for global emergency care research funding. CONCLUSIONS: Significant barriers to the conduct of high-quality global emergency care research persist, and innovative strategies need to be adopted to promote and grow the field of global emergency care research. This paper provides a global consensus on the most important barriers identified, as well as recommendations for cost-effective strategies for overcoming these barriers with the overall goal of promoting high-quality research and improving emergency care worldwide.

A therapeutic nanoparticle vaccine against Trypanosoma cruzi in a BALB/c mouse model of Chagas disease.

Chagas disease, caused by Trypanosoma cruzi, results in an acute febrile illness that progresses to chronic chagasic cardiomyopathy in 30% of patients. Current treatments have significant side effects and poor efficacy during the chronic phase; therefore, there is an urgent need for new treatment modalities. A robust TH1-mediated immune response correlates with favorable clinical outcomes. A therapeutic vaccine administered to infected individuals could bolster the immune response, thereby slowing or stopping the progression of chagasic cardiomyopathy. Prior work in mice has identified an efficacious T. cruzi DNA vaccine encoding Tc24. To elicit a similar protective cell-mediated immune response to a Tc24 recombinant protein, we utilized a poly(lactic-co-glycolic acid) nanoparticle delivery system in conjunction with CpG motif-containing oligodeoxynucleotides as an immunomodulatory adjuvant. In a BALB/c mouse model, the vaccine produced a TH1-biased immune response, as demonstrated by a significant increase in antigen-specific IFNγ-producing splenocytes, IgG2a titers, and proliferative capacity of CD8(+) T cells. When tested for therapeutic efficacy, significantly reduced systemic parasitemia was seen during peak parasitemia. Additionally, there was a significant reduction in cardiac parasite burden and inflammatory cell infiltrate. This is the first study demonstrating immunogenicity and efficacy of a therapeutic Chagas vaccine using a nanoparticle delivery system.

Impact of vectorborne parasitic neglected tropical diseases on child health.

Chagas disease, leishmaniasis, onchocerciasis and lymphatic filariasis are all vectorborne neglected tropical diseases (NTDs) that are responsible for significant disease burden in impoverished children and adults worldwide. As vectorborne parasitic diseases, they can all be targeted for elimination through vector control strategies. Examples of successful vector control programmes for these diseases over the past two decades have included the Southern Cone Initiative against Chagas disease, the Kala-azar Control Scheme against leishmaniasis, the Onchocerciasis Control Programme and the lymphatic filariasis control programme in The Gambia. A common vector control component in all of these programmes is the use of adulticides including dichlorodiphenyltrichloroethane and newer synthetic pyrethroid insecticides against the insect vectors of disease. Household spraying has been used against Chagas disease and leishmaniasis, and insecticide-treated bed nets have helped prevent leishmaniasis and lymphatic filariasis. Recent trends in vector control focus on collaborations between programmes and sectors to achieve integrated vector management that addresses the holistic vector control needs of a community rather than approaching it on a disease-by-disease basis, with the goals of increased efficacy, sustainability and cost-effectiveness. As evidence of vector resistance to currently used insecticide regimens emerges, research to develop new and improved insecticides and novel control strategies will be critical in reducing disease burden. In the quest to eliminate these vectorborne NTDs, efforts need to be made to continue existing control programmes, further implement integrated vector control strategies and stimulate research into new insecticides and control methods.

Time course study of the antigen-specific immune response to a PLGA microparticle vaccine formulation.

Microparticle-based vaccine delivery systems are known to promote enhanced immune responses to protein antigens and can elicit TH1-biased responses when used in combination with Toll-like receptor (TLR) agonists. It is important to understand the kinetics of the immune responses to microparticle-based protein vaccines in order to predict the duration of protective immunity and to optimize prime-boost vaccination regimens. We carried out a 10-week time course study to investigate the magnitude and kinetics of the antibody and cellular immune responses to poly(lactic-co-glycolic acid) (PLGA) microparticles containing 40 µg ovalbumin (OVA) protein and 16 µg CpG-ODN adjuvant (MP/OVA/CpG) in comparison to OVA-containing microparticles, soluble OVA plus CpG, or OVA formulated with Alhydrogel(®) aluminum adjuvant. Mice vaccinated with MP/OVA/CpG developed the highest TH1-associated IgG2b and IgG2c antibody titers, while also eliciting TH2-associated IgG1 antibody titers on par with Alhydrogel(®)-formulated OVA, with all IgG subtype titers peaking at day 56. The MP/OVA/CpG vaccine also induced the highest antigen-specific splenocyte IFN-γ responses, with high levels of IFN-γ responses persisting until day 42. Thus the MP/OVA/CpG formulation produced a sustained and heightened humoral and cellular immune response, with an overall TH1 bias, while maintaining high levels of IgG1 antibody equivalent to that seen with Alhydrogel(®) adjuvant. The time course kinetics study provides a useful baseline for designing vaccination regimens for microparticle-based protein vaccines.

Cutaneous leishmaniasis in Cuban immigrants to Texas who traveled through the Darién Jungle, Panama.

Cutaneous leishmaniasis is rarely seen in the United States. Four Cuban immigrants traveled along the same route at different times from Cuba to Ecuador, then northward, including through the Darién Jungle in Panama. These patients had chronic ulcerative non-healing skin lesions and were given a diagnosis of leishmaniasis.

Global trends in neglected tropical disease control and elimination: impact on child health.

The neglected tropical diseases (NTDs) are a group of 17 lesser known chronic infections which predominantly affect poor and disenfranchised communities. There are a number of NTDs that cause significant global morbidity in children, including the three major soil transmitted helminth (STH) infections (ascariasis, trichuriasis and hookworm infection), schistosomiasis and trachoma. These NTDs, together with lymphatic filariasis and onchocerciasis, are currently being targeted for global control and elimination through mass drug administration (MDA) campaigns. They represent the most common NTDs and share significant geographical overlap. Additionally, many individuals are polyparasitised with more than a single NTD. Integrated NTD control and elimination MDA programmes offer safe and efficacious treatments for all seven NTDs. However, the current global level of MDA coverage for the leading childhood NTDs, that is, STH infections, schistosomiasis and trachoma, remains well under 50%. Limiting factors for global coverage include insufficient global financial support, drug donation capacity of pharmaceutical companies and targeting school age children to the exclusion of other age groups in need of treatment, such as preschool age children. There is also a need for development of novel prevention and treatment modalities, such as next-generation small molecule drugs and vaccines. Efforts are underway to harness the momentum of a 2012 London Declaration on NTDs and a 2013 World Health Assembly (WHA) resolution as a means to control or in some cases eliminate by 2020 these NTDs that affect children worldwide.

Childhood parasitic infections endemic to the United States.

Endemic parasitic infections in the United States are more frequent than is commonly perceived. Intestinal parasitic infection with Cryptosporidium, Dientamoeba, and Giardia occurs most often in children in northern states during the summer months. Zoonotic Toxocara and Toxoplasma parasitic infections are more frequent in southern states, in African Americans, and in populations with lower socioeconomic status. Approximately 300, 000 people in the United States have Trypanosoma cruzi infection. Local, vector-borne transmission of T cruzi and Leishmania infections has been documented in southern states. Parasitic diseases endemic to the United States are not uncommon but are understudied.