[Tegumentary leishmaniasis and sandflies in Colonia Santa Rosa locality in northern Argentina]. / Leishmaniasis tegumentaria y flebótomos en la localidad de Colonia Santa Rosa del norte de Argentina.

Tegumentary leishmaniasis (TL) is caused by parasites of the genus Leishmania and transmitted by the sandfly species, insects belonging to the order Diptera, family Psychodidae. Historically, the most endemic area of TL in Argentina has been the northern region. The aim of this work was to analyze the presence and temporal variation of TL cases reported between 1985 and 2019 in Colonia Santa Rosa locality, northern Argentina. Furthermore, its clinical forms were characterized and sandflies were captured. Patients were diagnosed by smear and the Montenegro skin test. For sampling, CDC light traps were placed at 14 sites from 7pm to 7am. The correlation between vegetation cover and sandfly abundance was also studied. One hundred and twenty TL cases were diagnosed and the overall prevalence was 0.75% (≈16 000 inhabitants). Patients presented simple and multiple cutaneous leishmaniasis (88.79%) and the mucocutaneous form (10.83%). Skin lesions were more frequent on the lower extremities (46.73%). Of the total number of sandflies, Nyssomyia neivai (95%) was the predominant species followed by Migonemyia migonei (1.9%), cortelezzii complex (1.3%) and Evandromyia sallesi (0.09%). The persistent occurrence of cases and the presence of sandflies in the locality suggest the existence of endemic transmission in the area. This highlights the need to design prevention and control measures for TL in northern Argentina.

Efficacy and Safety of Albendazole and High-Dose Ivermectin Coadministration in School-Aged Children Infected With Trichuris trichiura in Honduras: A Randomized Controlled Trial.

BACKGROUND: The efficacy of currently available anthelminthics against Trichuris trichiura infections is significatively lower than for other soil-transmitted helminths. The combination of ivermectin (IVM) and albendazole (ALB) has shown significant improvements in efficacy. METHODS: Safety and efficacy randomized controlled clinical trial comparing 3 experimental regimens against ALB monotherapy for the treatment of T. trichiura infections in northern Honduras. Infected children were randomized to 4 treatment arms: arm 1, single-dose ALB (400 mg); arm 2, single-dose ALB (400 mg) plus IVM (600 µg/kg); arm 3, ALB (400 mg) for 3 consecutive days; or arm 4, ALB (400 mg) plus IVM (600 µg/kg) for 3 consecutive days. Efficacy was measured based on the egg reduction and cure rates, both assessed 14-21 days after treatment, using the Kato-Katz method. Safety was evaluated by analyzing the frequency and severity of adverse events. RESULTS: Of 176 children randomized to 1 of the 4 treatment arms, 117 completed treatment and follow-up. The egg reduction rates for arms 1, 2, 3, and 4 were 47.7%, 96.7%, 72.1%, and 100%, respectively; with P values <.001 for comparisons between IVM groups and ALB-only arms. The cure rates were 4.2%, 88.6%, 33.3%, and 100%, respectively. A total of 48 adverse events (85.4% mild) were reported in 36 children. CONCLUSIONS: The combined use of ALB and high-dose IVM is a highly effective and well tolerated treatment for the treatment of T. trichiura infections, offering significantly improved treatment for the control of this infection. CLINICAL TRIALS REGISTRATION: NCT04041453.

Quality Improvement Bedside Rounding Audits Enhance Protein Provision for Pediatric Patients Receiving Continuous Renal Replacement Therapy.

OBJECTIVES: Describe quality improvement process improvements in protein delivery of continuous renal replacement therapy initiation. DESIGN: Prospective study. SETTING: PICU and cardiovascular ICU within a quaternary care children's hospital. PATIENTS: PICU and cardiovascular ICU patients receiving continuous renal replacement therapy for greater than 48 hours. Inborn errors of metabolism were excluded. INTERVENTIONS: Plan-Do-Study-Act cycles were initiated. Cycle 1 developed interdisciplinary quality improvement group continuously monitoring nutrition care with thrice weekly bedside safety rounds and protein prescriptions within nephrologist's notes. Cycle 2 included education to intensivists. Cycle 3 initiated monthly quality improvement meetings reviewing nutritional care goals. MEASUREMENTS AND MAIN RESULTS: Primary outcome was percentage of time patients met protein goals in the first 5 days of continuous renal replacement therapy. Secondary outcome was percentage of time patients met protein goals for duration of continuous renal replacement therapy. Cohort (n = 55) mean age was 8.1 years (SD ± 6.8), 62% male, and 31% malnutrition at baseline. Percent of time meeting protein goals by day 5 was 22%, 33%, and 71% and percent of time meeting protein goals throughout was 35%, 39%, and 75% of groups 1, 2, and 3, respectively. Significant improvement occurred after Plan-Do-Study-Act 3 (group 2 vs group 3; p < 0.01) for primary and secondary outcomes. CONCLUSIONS: Implementation of an interprofessional quality improvement team significantly decreased number of continuous renal replacement therapy days with unmet protein goals and improved protein delivery.

Performance of different Trypanosoma cruzi antigens in the diagnosis of Chagas disease in patients with American cutaneous leishmaniasis from a co-endemic region in Argentina.

OBJECTIVE: To determine the ability of recombinant antigens to detect cases of infection with Trypanosoma cruzi among cases of infection with Leishmania spp. by serological methods. METHODS: Sera from 41 patients infected with Leishmania spp. were evaluated with ELISA using single (FRA, CP1 and TSSAVI) or pooled (commercial Rec-ELISA) recombinant proteins or homogenate antigens (commercial H-ELISA). As there is no gold standard antigen to discriminate Chagas disease from leishmaniasis, the correlation of results between defined antigens and the homogenate was made with Kappa Index (KI), the level of correlation considered being used as a criterion of specificity. RESULTS: Single recombinant antigens and Rec-ELISA showed good correlation (KI > 0.8). A low correlation (KI < 0.66) was observed between the results from single recombinant antigens or the commercial recombinant kit and H-ELISA. CONCLUSIONS: The highly correlated results between T. cruzi single or pooled recombinant proteins are indicative of the usefulness of recombinant antigens for Chagas diagnosis. Our results also indicate that in the city of Oran in Argentina, between 12% and 17% of patients with leishmaniasis are also infected with Chagas disease. The high KI values between TSSAVI and the other recombinant proteins suggest that in these patients, the infection may be caused by T. cruzi II and/or V and/or VI lineages.

Clinical Presentation of American Tegumentary Leishmaniasis in a Leishmania (Viannia) braziliensis Endemic Hotspot: A 35-Year History.

American tegumentary leishmaniasis (ATL) is a neglected tropical disease affecting the skin and mucosa. American tegumentary leishmaniasis due to Leishmania (Viannia) braziliensis is endemic in Argentina, where the Department of Oran is a hyperendemic focus. All cases of ATL with laboratory confirmation evaluated at a referral center in Oran city between 1985 and 2019 were analyzed retrospectively. Information from cases included clinical form, lesion size and number, time of evolution, and anatomical location; sex, age, and geographic origin were also studied. The temporal distribution of cases was analyzed. A total of 3,573 cases were included in the analysis. The ratio of males to females was 3:1 and the median age was 33 years old. Eighty-seven percent of cases were from Oran city and its surroundings, highlighting the hyperendemic nature of the area. Regarding clinical forms, 92.5% of cases were cutaneous and 7.5% were mucosal, with a median evolution time until clinical evaluation of 30 days and 7 months, respectively. Single cutaneous lesions were more frequent, localized mainly on the exposed areas in the upper and lower limbs. Secondary events were observed and described in 140 (4%) cases, with a median interval of 3.8 years for the appearance of recurrent mucosal disease in previously cutaneous forms. This is the largest case series of ATL due to L. (V.) braziliensis. The most classic presentation is of adult males with single cutaneous ulcers in exposed body areas, with < 10% of cases with mucosal complications. This comprehensive clinical characterization serves as a basis for future studies of the care and control of this neglected tropical disease.

[Role of three ELISA tests using promastigote homogenates of Leishmania braziliensis, L. amazonensis and L. guyanensis in the diagnosis of tegumentary leishmaniasis]. / El rol de tres pruebas de ELISA con antígenos de promastigotes de Leishmania braziliensis, L. amazonensis y L. guyanensis en el diagnóstico de leishmaniasis tegumentaria.

It is important to know whether the variability of species of Leishmania parasites circulating in a region affects the performance of the ELISA test for the diagnosis of leishmaniasis. Therefore, the aim of this study was to analyze the reactivity of the ELISA using homogenates of promastigotes of Leishmania (V.) braziliensis (ELISAb), Leishmania (L) amazonensis (ELISAa) and Leishmania (V.) guyanensis (ELISAg) against different sera groups. Samples from individuals with cutaneous leishmaniasis (n = 37), mucocutaneous leishmaniasis (n = 8), healthy controls (n = 52), persons infected with Trypanosoma cruzi (n = 11) and mixed infections (n = 14) were included in the study. We calculated sensitivities, specificities, cut offs, and predictive values for the three tests and compared them using ANOVA, kappa index, ROC curves comparison, and confidence intervals calculated by the bootstrap method. Significant differences were found when comparing the OD levels of sera from patients with cutaneous leishmaniasis against healthy controls, but there were no differences when comparing the different ELISAs. The sensitivities calculated for ELISAb and ELISAa were 84.6 and of 88.5% for ELISAg, while the value of specificity for the three tests was 96.2. The kappa index (0.87) and comparison of ROC curves showed similar performance for the three ELISAs (p = 0.225). The high reactivity obtained for these ELISAs in sera of patients with mucocutaneous leishmaniasis indicates this test as an important complement in the diagnosis of the disease.

[Reactivity of GST-SAPA antigen of Trypanosoma cruzi against sera from patients with Chagas disease and leishmaniasis]. / Reactividad del antígeno GST-SAPA de Trypanosoma cruzi frente a sueros de pacientes con enfermedad de Chagas y leishmaniasis.

Serologic diagnosis of Trypanosoma cruzi infection is important due to the limited sensitivity of direct parasitologic methods for diagnosis in the indeterminate and chronic phases of disease. SAPA antigen has been used in several studies and has been shown to be a good marker for use in the diagnosis of T. cruzi infection. Chagas disease and leishmaniasis are endemic in northern Salta with overlapping zones of transmission, which frequently leads to T. cruzi-Leishmania spp. mixed infections. Diagnosis is complicated by the fact that there is significant cross-reactivity when non-specific antigens are used. We evaluated the reactivity of GST-SAPA antigen in the ELISA test (ELISA-SAPA) against sera from persons infected with T. cruzi (n = 154), leishmaniasis (n = 66), mixed infections (29), and healthy controls (n = 28) using commercial ELISA and IHA kits as reference tests. For ELISA-SAPA the sensitivity, specificity and kappa index were calculated for detection of T. cruzi infection. Among sera from patients infected with leishmaniasis, 30.5% of co-infections were detected. ELISA-SAPA sensitivity was 97.1% (confidence interval 95%: 94.5-99.9), specificity was 100% (confidence interval 95%: 99.4-100), and kappa index was 96% (confidence interval 95%: 93-99%), for detection of T. cruzi infection. Sensitivity, specificity and kappa indices have shown a high efficiency of ELISA-SAPA.

Scope and limitations of a multiplex conventional PCR for the diagnosis of S. stercoralis and hookworms.

OBJECTIVES: Describe the diagnostic characteristics of a conventional multiplex PCR for the diagnosis of S. stercoralis, N. americanus and Ancylostomas spp. METHODS: Fecal samples were collected from a cross-sectional study in Orán department, Salta province, Argentina. The stool samples were analyzed using concentration-sedimentation, Harada Mori, McMaster, and Baermann techniques. DNA was extracted from 50 mg fecal sample using the FastPrep® Spin Kit for Soil. Three pairs of primers were used for the amplification of three products of 101, 330, and 577 base pairs (bp) for S. stercoralis, N. americanus and Ancylostoma spp, respectively. The sensitivity and analytical specificity of multiplex PCR were evaluated, as well as the sensitivity and diagnostic specificity, using a composite standard and Bayesian approach. RESULTS AND CONCLUSIONS: Multiplex PCR did not present cross-reaction with other intestinal parasites, and the detection limit for multiplex PCR was between 2 and 20 pg of genomic DNA. In addition it presented a diagnostic sensitivity of 97.4% for S. stercoralis and 90.3% for hookworms with a specificity of 100% and 87.6%, respectively. PCR identified a higher proportion (p <0.01) of coinfections (15.3%) than microscopic techniques (3.5%). Also, multiplex PCR showed that there was a positive association between S. stercoralis and hookworms (odds ratio = 2.12). However, this association was due to N. americanus (odds ratio= 3.22), since no association was observed between S. stercoralis and Ancylostoma spp. Neither was an association observed between the two species of hookworms.

Impact of intestinal parasites on microbiota and cobalamin gene sequences: a pilot study.

BACKGROUND: Approximately 30% of children worldwide are infected with gastrointestinal parasites. Depending on the species, parasites can disrupt intestinal bacterial microbiota affecting essential vitamin biosynthesis. METHODS: Stool samples were collected from 37 asymptomatic children from a previous cross-sectional Argentinian study. A multi-parallel real-time quantitative PCR was implemented for Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Trichuris trichiura, Cryptosporidium spp., Entamoeba histolytica and Giardia duodenalis. In addition, whole-genome sequencing analysis was conducted for bacterial microbiota on all samples and analyzed using Livermore Metagenomic Analysis Toolkit and DIAMOND software. Separate analyses were carried out for uninfected, Giardia-only, Giardia + helminth co-infections, and helminth-only groups. RESULTS: For Giardia-only infected children compared to uninfected children, DNA sequencing data showed a decrease in microbiota biodiversity that correlated with increasing Giardia burden and was statistically significant using Shannon's alpha diversity (Giardia-only > 1 fg/µl 2.346; non-infected group 3.253, P = 0.0317). An increase in diversity was observed for helminth-only infections with a decrease in diversity for Giardia + helminth co-infections (P = 0.00178). In Giardia-only infections, microbiome taxonomy changed from Firmicutes towards increasing proportions of Prevotella, with the degree of change related to the intensity of infection compared to uninfected (P = 0.0317). The abundance of Prevotella bacteria was decreased in the helminths-only group but increased for Giardia + helminth co-infections (P = 0.0262). Metagenomic analysis determined cobalamin synthesis was decreased in the Giardia > 1 fg/µl group compared to both the Giardia < 1 fg/µl and the uninfected group (P = 0.0369). Giardia + helminth group also had a decrease in cobalamin CbiM genes from helminth-only infections (P = 0.000754). CONCLUSION: The study results may provide evidence for an effect of parasitic infections enabling the permissive growth of anaerobic bacteria such as Prevotella, suggesting an altered capacity of vitamin B12 (cobalamin) biosynthesis and potential impact on growth and development in children .

Seroprevalence of the Strongyloides stercoralis Infection in Humans from Yungas Rainforest and Gran Chaco Region from Argentina and Bolivia.

The threadworm, Strongyloides stercoralis, is endemic in tropical and subtropical areas. Data on the prevalence and distribution of infection with this parasite species is scarce in many critical regions. We conducted a seroprevalence study of S. stercoralis infection in 13 locations in the Gran Chaco and Yungas regions of Argentina and Bolivia during the period 2010-2016. A total of 2803 human serum samples were analyzed by ELISA-NIE which has a sensitivity of 75% and specificity of 95%. Results showed that 551 (19.6%) of those samples were positive. The adjusted prevalence was 20.9%, (95% confidence interval (CI) 19.4%-22.4%). The distribution of cases was similar between females and males with an increase of prevalence with age. The prevalence in the different locations ranged from 7.75% in Pampa del Indio to 44.55% in Santa Victoria Este in the triple border between Argentina, Bolivia, and Paraguay in the Chaco region. Our results show that S. stercoralis is highly prevalent in the Chaco and Yungas regions, which should prompt prospective surveys to confirm our findings and the design and deployment of control measures.

High performance of an enzyme linked immunosorbent assay for American tegumentary leishmaniasis diagnosis with Leishmania (Viannia) braziliensis amastigotes membrane crude antigens.

The diagnosis of American tegumentary leishmaniasis (ATL) still requires the design of more effective tools. Leishmania (Viannia) braziliensis is the causal agent of the 90% of Argentinean ATL cases. Considering the current knowledge, an ELISA based crude antigen (CA) for the diagnosis was designed. Ninety-nine subjects diagnosed as ATL, 27 as no-ATL, and 84 donors from non-ATL-endemic areas were included in this study. The current ATL diagnosis was based four techniques, dermal smear microscopic examination (parasitological test), PCR, Leishmanin skin test, and clinical records. We obtained CA extracts from promastigotes and amastigotes from macrophage cultures of different zymodemes of endemic Leishmania species circulating in the study area. Crude antigens from the 'local' main zymodeme of L. (V.) braziliensis showed the highest reactivity against anti-Leishmania antibodies compared to the other included species. The CA of amastigotes of this zymodeme was 3.4 fold more reactive than promastigotes one. Moreover, amastigote-membrane CA (MCA) were 3.6 fold more reactive than the soluble antigens. The MCA-ELISA reached a sensitivity and specificity of 98% (CI = 94.7%-100%) and 63.6% (53.9-73.1), respectively. When anti-Trypanosoma cruzi reactive sera were excluded, the specificity reached 98.4% (94.4-100), while the sensitivity was similar, with a positive predictive value (PV) of 98.6% (94.6-100) and negative PV of 96.3% (91.6-100). The performance of the MCA-ELISA results strongly contribute to the final diagnostic decision, since a non-reactive serological result almost discards the suspected ATL, because of its high negative PV. The developed MCA-ELISA showed a high diagnostic performance, which makes it a good candidate for ATL diagnosis, for seroprevalence studies, or for monitoring treatments efficacy.

Malnutrition Risk in Hospitalized Children: A Descriptive Study of Malnutrition-Related Characteristics and Development of a Pilot Pediatric Risk-Assessment Tool.

BACKGROUND: Underrecognition of pediatric malnutrition may affect nutrition interventions and outcomes. Pediatric malnutrition uses more specific etiology-based criteria but lacks clarity in implementation guidelines. Study goals were to identify malnutrition and risk among hospitalized patients, characterize malnutrition risk factors, and assess reliability of criteria against outcome measures. MATERIALS AND METHODS: All children 44 weeks postmenstrual age-18 years, admitted for 48 hours during a 16-day period, were included (n = 528). Trained dietitians assessed patients in physical assessments (PA), growth, energy intake, increased nutrient losses (IL), altered absorption of nutrients (AA), hypermetabolism and inflammation, laboratory information, micronutrient deficiency, and functional status. Outcome data assessed were length of stay (LOS), intensive care unit (ICU) LOS, ventilation days, nutrition support, and dietitian intervention. RESULTS: Malnutrition prevalence upon admission was 19.7%. Weight/length or BMI/age z-score (ZS) had no effect on LOS. AA and IL upon admission were independently associated with malnutrition (both, P<.01). Wasting and hypermetabolism were independently associated with longer LOS (P<.01). Other factors associated with longer LOS included IL and inflammation (P < .05). Those with hypermetabolism had significant ZS improvements if followed by a dietitian (P < .05). Wasting via PA was the only factor associated with longer ICU LOS (P < .05). CONCLUSIONS: Identification of risk factors (wasting, hypermetabolism, AA, IL) beyond anthropometrics to define malnutrition and risk is important in prioritizing care in a tertiary pediatric facility. Of great significance is the ability of dietitian-based PA to predict LOS and need for intervention.

Tegumentary leishmaniasis and sand flies in a border area between Argentina and Bolivia.

Background: Some sand flies are of medical importance because they are vectors of Leishmania parasites that are responsible for leishmaniasis. The aim of this study was to make a retrospective epidemiological analysis of tegumentary leishmaniasis (TL), to identify Leishmania spp. from patient isolates and to describe the diversity of sand flies from a border area between Bolivia and Argentina. Methods: TL cases included in the study were diagnosed in an endemic area of the north of Argentina from 1985 to 2017. The parasites isolated were characterized by the cytochrome B method. Sand flies were captured with Centers for Disease Control traps in Aguas Blancas and Media Luna-Algarrobito localities. Results: A total of 118 cases of TL were analysed. Eight isolates were characterized as Leishmania (Viannia) braziliensis. A total of 1291 sand flies were captured, including Nyssomyia neivai, Cortelezzii complex, Evandromyia sallesi, Migonemyia migonei and Micropygomyia quinquefer. Within the area, sand flies were found in the backyards of houses. Conclusions: In this region there exists the possibility of peridomestic transmission of TL in the neighbourhoods peripheral to the urban area and in rural environments as well as the risk of transmission to travellers that pass through the customs offices.

Intradialytic Parenteral Nutrition in Pediatrics.

Children with end-stage renal disease (ESRD) on hemodialysis are at increased risk for malnutrition. Aggressive nutrition intervention such as intradialytic parenteral nutrition (IDPN) should be considered to prevent further co-morbidities and mortality associated with malnutrition when other interventions fail. IDPN is a non-invasive method of providing nutrition to malnourished hemodialysis (HD) patients via the HD access throughout the HD treatment. Although the evidence on the long-term benefits of IDPN is scant in pediatrics, there is evidence that it improves metabolic parameters and nutritional status. In this paper, therapy with IDPN including indications, goals of therapy, and elements to monitor will be described. In addition, a practice guideline for prescribing IDPN is provided.

Malnutrition among Hospitalized Children in the United States: Changing Prevalence, Clinical Correlates, and Practice Patterns between 2002 and 2011.

BACKGROUND: Pediatric malnutrition has been associated with adverse clinical outcomes, longer lengths of stay, and higher health care costs. OBJECTIVE: To characterize prevalence, temporal trends, and short-term clinical outcomes of coded diagnoses of pediatric malnutrition (CDM) across sociodemographic, clinical, and hospital characteristics from 2002 to 2011. DESIGN: This study is a retrospective cross-sectional analysis of nationally representative data from the Nationwide Inpatient Sample and the Kids' Inpatient Database. PARTICIPANTS/SETTING: The study sample included pediatric inpatient hospitalizations in the United States. MAIN OUTCOME MEASURES: International Classification of Diseases-9th Revision-Clinical Modification diagnosis codes were used to identify CDM and coded malnutrition subtypes based on an etiology-related definition of pediatric malnutrition. STATISTICAL ANALYSES: The national frequency and prevalence of CDM overall and across patient- and hospital-level characteristics were estimated for children aged 1 month to 17 years. Logistic regression was used to assess the association between CDM and each characteristic. Analyses evaluated conditions associated with the highest burden and risk of CDM, and compared clinical outcomes across malnutrition subtypes. Joinpoint regression was used to describe temporal trends in CDM. RESULTS: Of the 2.1 million pediatric patients hospitalized annually, more than 54,600 had CDM, a national prevalence of 2.6%. Considerable variation was observed based on primary diagnosis, with fluid and electrolyte disorders contributing the most malnutrition cases. Highest CDM rates were among patients with stomach cancer, cystic fibrosis, and human immunodeficiency virus. Patients with CDM experienced worse clinical outcomes, longer lengths of stay, and increased costs of inpatient care. The overall prevalence of CDM increased from 1.9% in 2002 to 3.7% in 2011, an 8% annual increase, and temporal increases were observed in nearly all population subgroups. CONCLUSIONS: Despite improvements, pediatric malnutrition remains underdiagnosed in inpatient settings when relying exclusively on International Classification of Diseases-based codes, which underscores the need for a national benchmarking program to estimate the true prevalence, clinical significance, and cost of pediatric malnutrition.

Assessment of serum pharmacokinetics and urinary excretion of albendazole and its metabolites in human volunteers.

BACKGROUND: Soil Transmitted Helminth (STH) infections negatively impact physical and mental development in human populations. Current WHO guidelines recommend morbidity control of these infections through mass drug administration (MDA) using albendazole (ABZ) or mebendazole. Despite major reductions in STH associated morbidity globally, not all programs have demonstrated the expected impact on prevalence of parasite infections. These therapeutic failures may be related to poor programmatic coverage, suboptimal adherence or the exposure of parasites to sub-therapeutic drug concentrations. As part of the DeWorm3 project, we sought to characterize the serum disposition kinetics and pattern of urinary excretion of ABZ and its main metabolites ABZ sulphoxide (ABZSO) and ABZ sulphone (ABZSO2) in humans, and the assessment of the duration and optimal time point where ABZ and/or its metabolites can be measured in urine as an indirect assessment of an individual's adherence to treatment. METHODOLOGY/PRINCIPAL FINDINGS: Consecutive venous blood and urine samples were collected from eight (8) human volunteers up to 72 h post-ABZ oral administration. ABZ/metabolites were quantified by HPLC. The ABZSO metabolite was the main analyte recovered both in serum and urine. ABZSO Cmax in serum was 1.20 ± 0.44 µg/mL, reached at 4.75 h post-treatment. In urine, ABZSO Cmax was 3.24 ± 1.51 µg/mL reached at 6.50 h post-ABZ administration. CONCLUSION/SIGNIFICANCE: Pharmacokinetic data obtained for ABZ metabolites in serum and urine, including the recovery of the ABZ sulphoxide derivative up to 72 h in both matrixes and the recovery of the amino-ABZ sulphone metabolite in urine samples, are suggesting the possibility of developing a urine based method to assess compliance to ABZ treatment. Such an assay may be useful to optimize ABZ use in human patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03192449.

A randomized clinical trial comparing oral azithromycin and meglumine antimoniate for the treatment of American cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis.

Azithromycin was compared with meglumine antimoniate for treatment of patients with cutaneous leishmaniasis. Patients were randomized to receive oral azithromycin, 500 mg/day (22 patients) or intramuscular meglumine antimoniate, 10 mg Sb/kg/day (23 patients), both for 28 days, with a second cycle of 15 days if necessary, and followed-up for one year after completion of treatment. Efficacy, defined as complete re-epithelization without relapse for 12 months after completing therapy, was 82.6% (95% confidence interval [CI] = 67-98%) for meglumine antimoniate and 45.5% (95% CI = 25-66%) for azithromycin. All patients who failed treatment with azithromycin were treated with meglumine antimoniate and clinically cured. Azithromycin was well tolerated; meglumine antimoniate caused arthralgias and local symptoms in 78% of the patients. In 17 cases, species identification was obtained; Leishmania (Viannia) braziliensis was identified in all of them. For the treatment of American cutaneous leishmaniasis caused by L. (V.) braziliensis, meglumine antimoniate is significatively more efficacious than azithromycin, which was clinically curative in almost half of the patients and well-tolerated.

Reappraisal of Leishmanin Skin Test (LST) in the management of American Cutaneous Leishmaniasis: A retrospective analysis from a reference center in Argentina.

Leishmania (Viannia) braziliensis is the species most frequently implicated with cutaneous and mucosal leishmaniasis in the Americas; its diagnosis is based on the identification of amastigotes in lesions, which is limited by low parasite burden. Leishmanin Skin Test (LST) is a support tool for diagnosis, based on delayed type hypersensitivity responses to Leishmania antigens injected intradermally, used in endemic areas as a complement to diagnosis. A retrospective analysis of individuals evaluated for their first episode of tegumentary leishmaniasis at a reference center in Argentina during the period 2006-2015 was performed, with the goal of assessing its usefulness as a support tool in the diagnosis of leishmaniasis. Demographic, clinical and diagnostic work-up were analyzed in individuals with clinically compatible lesions, lesion`s smear and LST. A total of 733 cases that met the case definition were included in the analysis; 678 (93%) localized cutaneous cases, 50 (7%) with mucosal involvement and 5 (<1%) disseminated. Diagnostic confirmation was reached in 474 (65%) cases through positive smears from skin or mucosal lesions, with only 6 cases among this group having negative LST. Among smear negative cases, 190 were negative also by LST, but in 69 instances LST was positive. Across age groups, similar ratios of sensitivity between smear and LST were calculated. Lesions older than 21 days-old were found to correlate with positive results both for smear and LST significantly more than younger lesions. These findings support the clinical use of LST as a diagnostic complement for American Cutaneous Leishmaniasis across all age groups even in endemic areas. In this analysis, the correlation with smear was high. Standardization of this technique and further research into its most adequate preparation and utilization protocols across different sites will help in the management of suspicious clinical cases.

Serologic Monitoring of Public Health Interventions against Strongyloides stercoralis.

Northwestern Argentina is endemic for soil-transmitted helminths, and annual deworming programs are carried out in prioritized areas. High prevalence of Strongyloides stercoralis was reported in this area; therefore, control programs including ivermectin are being evaluated. The NIE-enzyme linked immunosorbent assay (ELISA) was used for this purpose. In this community trial, two groups of patients, classified according to housing and living conditions were evaluated. Simultaneous with baseline survey, Group 1 was moved to new households with access to improved water and sanitation facilities (W and S), where deworming (MDA, massive drug administration) took place within 1 month; whereas Group 2 received MDA but remained living with unimproved W and S. The mean time interval between baseline and the follow-up was 331 days for Group 1 and 508 for Group 2. Anti-NIE levels were measured for each individual before and after interventions and follow-up optical density (OD) ratios were calculated to quantify the variation. A significant decrease of the anti-NIE levels between baseline and follow-up was observed in both groups. Nonetheless, the number of patients that achieved the cure criteria (OD ratio < 0.6) was higher in Group 1 than Group 2 with values of 72.7% (24/33) and 45.0% (18/40), respectively (P = 0.0197). Our results support the conclusion that a combined intervention including deworming and improvements in life conditions is more effective, in terms of the proportion of subjects cured than deworming alone. Furthermore, we found that NIE-ELISA is a useful test for assessing the response to treatment and to evaluate the outcome of control intervention programs.

Leishmaniasis tegumentaria y flebótomos en la localidad de Colonia Santa Rosa del norte de Argentina / Tegumentary leishmaniasis and sandflies in Colonia Santa Rosa locality in northern Argentina

Resumen La leishmaniasis tegumentaria (LT) es causada por parásitos del género Leishmania y transmitida por especies de flebótomos, insectos pertenecientes al orden Diptera, familia Psychodidae. El objetivo de este trabajo fue analizar la presencia de casos de LT y su variación temporal entre 1985 y 2019, las formas clínicas, la ubicación de las lesiones en los pacientes y la presencia de flebótomos en la localidad de Colonia Santa Rosa, del norte de Argentina. Los pacientes se diagnosticaron mediante frotis e intradermorreacción de Montenegro. Se colocaron trampas CDC en 14 sitios en el horario de 19 a 7. Se diagnosticaron 120 casos de LT y la prevalencia global fue del 0,75% (^16.000 habitantes). Los pacientes presentaron formas cutáneas simples y múltiples (88,79%) y mucocutáneas (10,83%). Las lesiones cutáneas fueron más frecuentes en extremidades inferiores. Del total de flebótomos, Nyssomyia neivai fue la especie predominante (95%), y, en menor proporción, estuvieron presentes Migonemyia migonei (1,9%), complejo cortelezzii (1,3%) y Evandromyia sallesi (0,09%). La persistente ocurrencia de casos y la presencia de flebótomos en la citada localidad nos sugiere la transmisión endémica en la zona. Esto senala la necesidad de planificar medidas preventivas y de control de la LT en el norte de Argentina.

Abstract Tegumentary leishmaniasis (TL) is caused by parasites of the genus Leishmania and transmitted by the sandfly species, insects belonging to the order Diptera, family Psychodidae. Historically, the most endemic area of TL in Argentina has been the northern region. The aim of this work was to analyze the presence and temporal variation of TL cases reported between 1985 and 2019 in Colonia Santa Rosa locality, northern Argentina. Furthermore, its clinical forms were characterized and sandflies were captured. Patients were diagnosed by smear and the Montenegro skin test. For sampling, CDC light traps were placed at 14 sites from 7pm to 7am. The correlation between vegetation cover and sandfly abundance was also studied. One hundred and twenty TL cases were diagnosed and the overall prevalence was 0.75% (M6 000 inhabitants). Patients presented simple and multiple cutaneous leishmaniasis (88.79%) and the mucocutaneous form (10.83%). Skin lesions were more frequent on the lower extremities (46.73%). Of the total number of sandflies, Nyssomyia neivai (95%) was the predominant species followed by Migonemyia migonei (1.9%), cortelezzii complex (1.3%) and Evandromyia sallesi (0.09%). The persistent occurrence of cases and the presence of sandflies in the locality suggest the existence of endemic transmission in the area. This highlights the need to design prevention and control measures for TL in northern Argentina.