Review of Leishmaniasis Treatment: Can We See the Forest through the Trees?

There are three known clinical syndromes of leishmaniasis: cutaneous (CL), mucocutaneous (MCL), and visceral disease (VL). In MCL and VL, treatment must be systemic (either oral or intravenous), while CL treatment options vary and include observation-only localized/topical treatment, oral medications, or parenteral drugs. Leishmaniasis treatment is difficult, with several factors to be considered. First, the efficacy of treatments varies among different species of parasites prevalent in different areas on the globe, with each species having a unique clinical presentation and resistance profile. Furthermore, leishmaniasis is a neglected tropical disease (NTD), resulting in a lack of evidence-based knowledge regarding treatment. Therefore, physicians often rely on case reports or case series studies, in the absence of randomized controlled trials (RCT), to assess treatment efficacy. Second, defining cure, especially in CL and MCL, may be difficult, as death of the parasite can be achieved in most cases, while the aesthetic result (e.g., scars) is hard to predict. This is a result of the biological nature of the disease, often diagnosed late in the course of disease (with possible keloid formation, etc.). Third, physicians must consider treatment ease of use and the safety profile of possible treatments. Thus, topical or oral treatments (for CL) are desirable and promote adherence. Fourth, the cost of the treatment is an important consideration. In this review, we aim to describe the diverse treatment options for different clinical manifestations of leishmaniasis. For each currently available treatment, we will discuss the various considerations mentioned above (efficacy, ease of use, safety, and cost).

Impact of the COVID-19 era on clinical presentation, management and microbiology in paediatric peritonsillar abscess: A case-control study.

OBJECTIVES: Peritonsillar abscess (PTA) is the most common soft-tissue infection of the head and neck. This potential complication of tonsillitis has demonstrated unique microbial trends during the COVID-19 pandemic. This era has resulted in a major shift in the hygiene and social habits of the general population, which has resulted in changes in the presentation, management and microbiology of several infectious diseases. To date, the impact of COVID 19 on PTA microbiology and clinical presentation in the paediatric population has yet to be investigated. DESIGN: Retrospective chart review comparing all cases of paediatric (age 0-18) PTA in an academic tertiary centre during the COVID-19 pandemic (03/2020-02/2022) and compared them to two control groups: pre-COVID (03/2018-02/2020) and post-COVID (03/2022-03/2023). All patients were treated with either needle aspiration, incision and drainage or both means in addition to intravenous antibiotics. SETTING: A large Ear Nose and Throat department in a tertiary referral center. PARTICIPANTS: Consecutive children aged 18 years or under, admitted with a diagnosis of Peritonsillar abscess. MAIN OUTCOME MEASURES: We analyzed the clinical and microbiologcal features of all cases of pediatric peritonsillar abscess during the COVID-19 era (03/2020-02/2022) and compared them to a pre and post control cases. RESULTS: A total of 96 PTA cases were included (35 pre-COVID, 35 COVID and 26 post-COVID). The means of procedural treatment shifted in favour of incision and drainage versus needle aspiration during the COVID era. The length of hospitalisation increased during the COVID era (3.6 days vs. 2.1 and 3.1 pre and post-COVID respectively, p < .001). No other notable differences in the clinical and demographic features were found between the three eras. The COVID-19 era saw an increase in Fusobacterium (37.1% vs. 8.6% and 24% pre and post-COVID, respectively; p = .008) and Streptococcus Anginosus (31.4% vs. 5.7% and 7.7% pre and post-COVID, respectively; p = .007) species isolation. CONCLUSIONS: The COVID-19 pandemic did not seem to impact the clinical presentation of paediatric PTA yet resulted in a change in microbiological pathogens. The choice of I&D as a means to shorten hospital stay during the pandemic may have led to an actual increase in hospital stay, suggesting that NA may be the preferred management approach.

Performance of Echinococcosis Serology is Associated with Disease Endemicity, Hydatid Cyst Location, Eosinophilia, Imaging Finding, and Treatment.

BACKGROUND: We aimed to assess echinococcosis serology performance for diagnosing cystic echinococcosis (CE) in children living in CE-endemic vs. non-endemic populations, and in different clinical settings. METHODS: A retrospective cohort study, assessing children with ELISA test for echinococcosis, 2005-2021. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated comparing CE-endemic vs. non-endemic populations, cases with/without eosinophilia, and cases with/without CE-suggestive imaging findings. Additionally, we examined the association between serology titers/levels (values) and clinical characteristics. RESULTS: Of 273 cases, 66 (24%) were confirmed as CE. Overall, 97% of CE were in Bedouin children, and the pre-test probability was 28% vs. 9% (p < 0.001) in CE-endemic vs. non-endemic population, respectively. Sensitivity was higher in hepatic than extra-hepatic CE (74% vs. 47%). Overall specificity was 86%. PPVs were higher in CE-endemic population compared to non-endemic (66% vs. 22%), while NPVs were higher in non-endemic population (100% vs. 87%). Eosinophilia was associated with lower specificity (73% vs. 94%) and PPV (47% vs. 78%). Typical imaging was associated with higher specificity (94% vs. 82%) and PPV (91% vs. 11%), while NPVs were lower in typical imaging cases (77% vs. 98%). Higher titer levels (above median) were associated with typical imaging (76% vs. 49%), higher PPV (79% vs. 43%), albendazole treatment (100% vs. 56%), surgery (60% vs. 19%), and new imaging finding (75% vs. 0%). CONCLUSIONS: Echinococcosis serology performance was impacted by disease endemicity, and by various clinical characteristics. These findings may assist physicians in the interpretation of echinococcosis serology results.

Effect of the COVID-19 pandemic on the pediatric infectious disease landscape.

This narrative review aims to present an overview of the COVID-19 pandemic's effects on the landscape of pediatric infectious diseases. While COVID-19 generally results in mild symptoms and a favorable prognosis in children, the pandemic brought forth significant consequences. These included persistent symptoms among infected children ("long COVID"), a profound transformation in healthcare utilization (notably through the widespread adoption of telemedicine), and the implementation of optimization strategies within healthcare settings. Furthermore, the pandemic resulted in alterations in the circulation patterns of respiratory pathogens, including influenza, RSV, and Streptococcus pneumoniae. The possible reasons for those changes are discussed in this review. COVID-19 effect was not limited to respiratory infectious diseases, as other diseases, including urinary tract and gastrointestinal infections, have displayed decreased transmission rates, likely attributable to heightened hygiene measures and shifts in care-seeking behaviors. Finally, the disruption of routine childhood vaccination programs has resulted in reduced immunization coverage and an upsurge in vaccine hesitancy. In addition, the pandemic was associated with issues of antibiotic misuse and over-prescription.     Conclusion: In conclusion, the COVID-19 pandemic has left a profound and multifaceted impact on the landscape of pediatric infectious diseases, ranging from the emergence of "long COVID" in children to significant changes in healthcare delivery, altered circulation patterns of various pathogens, and concerning disruptions in vaccination programs and antibiotic usage. What is Known: • COVID-19 usually presents with mild symptoms in children, although severe and late manifestations are possible. • The pandemic resulted in a dramatically increased use of health care services, as well as alterations in the circulation patterns of respiratory pathogens, decreased rates of other, non-respiratory, infections, disruption of routine childhood vaccination programs, and antibiotic misuse. What is New: • Possible strategies to tackle future outbreaks are presented, including changes in health care services utilization, implementation of updated vaccine programs and antibiotic stewardship protocols. • The decline in RSV and influenza circulation during COVID-19 was probably not primarily related to NPI measures, and rather related to other, non-NPI measures implementation, including specific pathogen-host interactions on the level of the biological niche (the nasopharynx).

Dynamics of Pediatric Antibiotic Use Differ between High- and Low-Prescribing Clinics after Pneumococcal Conjugate Vaccines.

OBJECTIVE: To compare dispensed oral antibiotic prescription rates (DAPRs) after implementation of pneumococcal conjugate vaccine (PCV) in high antibiotic-prescribing clinics (HPC) with low antibiotic-prescribing clinics (LPC) in 2 distinct ethnic groups of children (Jewish and Bedouin children) <5 years of age. METHODS: Clinics with ≥50 insured children, active both pre-PCV (2005-2009) and post-PCV (2010-2018) implementation, were included. HPC and LPC were defined by DAPRs above or below the median in each age and ethnic group. Monthly dispensed antibiotic prescription rate (DAPR) trends (adjusted for age and ethnicity) were calculated using interrupted time series. Mean yearly incidence rate-ratios (late PCV13 vs pre-PCV) were calculated. RESULTS: Bedouin HPC had the highest pre-PCV overall-DAPR per 1000 child-years ± SD (2520.4 ± 121.2), followed by Jewish HPC (1885.5 ± 47.6), Bedouin LPC (1314.8 ± 81.6), and Jewish LPC (996.0 ± 19.6). Shortly after PCV implementation, all DAPRs and amoxicillin/amoxicillin-clavulanate DAPRs declined in all groups except Jewish LPC, stabilizing within 4-5 years post-PCV. The rates and magnitudes of declines were directly proportional to the pre-PCV DAPR magnitudes, achieving near-complete closure of the pre-PCV DAPR gaps between the 4 groups (rates during late-PCV13 ranging from 1649.4 ± 23.5 [Bedouin HPC] to 1200.3 ± 72.4 [Jewish LPC]). CONCLUSIONS: PCVs are a powerful tool in reducing outpatient antibiotic consumption among young children, especially in HPC, resulting in partial closure of DAPR gap between HPC and LPC. The higher impact on HPC suggests that PCV-associated declines of respiratory disease may strongly contribute to a judicious antibiotic approach in clinics with high antibiotic consumption.

The impact of pneumococcal conjugate vaccine on ceftriaxone consumption in the community among young children.

OBJECTIVES: Following pneumococcal conjugate vaccine (PCV) introduction, community pediatric dispensed prescription rates (DPR) of oral antibiotics declined, in parallel to respiratory tract infection (RTI). We assessed the dynamics of outpatient parenteral ceftriaxone DPR. METHODS: Computerized data for children <5 years were examined during 13 years (including 4 pre-PCV years). DPR from clinics with ≥50 insured children, active both before and after PCV implementation were included. Interrupted time series with segmented regression stratified by age and ethnicity, and adjusted for seasonality was applied to show monthly DPR trends. RESULTS: A total of 29,226 prescriptions were dispensed. No significant trends in ceftriaxone DPR were seen pre-PCV. Shortly after PCV implementation, DPR abruptly and significantly declined, stabilizing in late-PCV period (5 years postimplementation). The dynamics were compared between the two ethnic groups in the region, Jewish and Bedouin children (the latter with higher crowding and respiratory disease rates). Among Jewish children, ceftriaxone was mainly dispensed during winter vs no seasonality among Bedouin children. CONCLUSIONS: In southern Israel, outpatient ceftriaxone DPR declined post-PCV in young children, similar to the trends of RTIs and oral antibiotic prescriptions, suggesting a causative role of PCVs. The differences between the two ethnic groups suggest possible involvement of additional factors.

Albendazole Monotherapy for Pediatric Cystic Echinococcosis: A Case Series.

BACKGROUND: Data regarding albendazole monotherapy for cystic echinococcosis (CE) are scarce, especially in children. We report our experience treating CE in children with albendazole monotherapy. METHODS: A retrospective case series, 2005-2021, assessing factors leading to albendazole monotherapy, demographic, clinical, duration of treatment and follow-up, and outcome (changes in cyst size and side effects) characteristics. RESULTS: Overall, we identified 18 patients with 31 cysts; liver: 68% (n = 21), lungs: 29% (n = 9), and kidney: 3% (n = 1). Mean cyst size was 4.5 ± 2.6 cm. Reasons for administrating albendazole monotherapy were small (< 4 cm) cyst size (56%), difficulty to operate (33%) and comorbidity (22%). Duration of treatment (range 1-32 months) was 1, 2-3, 4-6 and > 6 months in 28% (n = 5), 39% (n = 7), 17% (n = 3) and 17% (n = 3) of children, respectively. Duration of follow up (range 1-87 months) was 1, 2-3, 4-6 and > 6 months in 11% (n = 2), 11% (n = 2), 17% (n = 3) and 61% (n = 11) of children, respectively. Overall, 83% (n = 15) of patients experienced lack of cyst growth, and 72% (n = 13) experienced reduction in cyst size, while 44% (n = 8) experienced reduction larger than 50%. Full resolution was noted in 22% (n = 4) of patients. In three cases (17%) treatment failure was recorded: one (6%) recurrence, and two cases (11%) of cyst growth. Neutropenia was recorded in two patients (11%), and liver enzymes elevation was recorded in six patients (33%). CONCLUSIONS: Albendazole monotherapy may be an adequate treatment for selected cases of CE disease in children, especially in CE with small, hepatic cysts.

Case Report: Extensive Facial Cutaneous Leishmaniasis in a Neonate.

Cutaneous leishmaniasis (CL) is a skin infection caused by various species of the Leishmania parasite and is spread by the bite of an infected female sandfly. In southern Israel, CL caused by Leishmania major is endemic. Cutaneous leishmaniasis is considered a self-limiting disease, characterized by progressive, long-lasting nodulo-ulcerative skin lesions, which usually resolve in several months to years, and leads to scarring, cosmetic disfigurement, and future stigmatization. Although CL is a common disease among children, reports of CL in children younger than 1 year are rare. We present a case of extensive facial CL in an infant whose initial lesions appeared only 25 days after birth. The patient was treated with intravenous liposomal amphotericin B. Two months later, marked improvement was seen, with complete resolution of the inflammation and atrophic scar formation. To our knowledge, this is the earliest age of CL published to date.

Dynamics of invasive pneumococcal disease in infants < 2 years old following PCV7/13 implementation using two infant and a booster dose schedule: evidence for indirect protection of young infants, Israel, 2004 to 2019.

BackgroundPneumococcal conjugated vaccine (PCV)7 and PCV13 programmes started in Israel from July 2009 and November 2010 respectively, with a 2+1 schedule (one dose at 2 months old, one at 4 months old, and a booster dose at 12 months old). Thereafter, invasive pneumococcal disease (IPD) rates substantially declined in children. Uptake of all three doses in < 2-year-olds since 2012 is > 90%. For still incompletely vaccinated infants (≤ 12 months old), how well the PCV 2+1 programme shields from IPD is not fully resolved.AimTo assess the adequacy of protection conferred by the 2+1 schedule PCV vaccination programme, particularly among incompletely-vaccinated infants.MethodsThis was a population-based, prospective, nationwide active IPD surveillance study in Israel, 2004-2019, in children < 24 months old. We estimated annual incidence rates (IR) of overall IPD, IPD caused by PCV13 serotypes (VT13), and non-PCV13 serotypes (NVT13). Annual IPD IRs were stratified by age: < 4 months (receiving ≤ 1 dose), 4-6 months (immediately post dose 2), 7-12 months (a few months post dose 2), and 13-23 months (post dose 3). Late-PCV (2004-2008) to pre-PCV13 (2016-2019) mean annual IR ratios (IRRs) were calculated.Results2,569 IPD episodes were recorded. VT13 decreased > 90% in all age groups, while NVT13 seemed to increase. All-IPD rates declined in all age groups by 56-70%. The 2+1 schedule impact on 7-12-month-old infants (pre-booster) was similar to that on 13-23-month-old children (post booster), with PCV13 IPD reductions of 97% and 98%, respectively.ConclusionsIndirect (herd) protection of infants, including < 4 month-olds with ≤ 1 PCV dose, was achieved by the 2+1 PCV schedule programme which thus seems adequate.

A Hypothesis-Generating Prospective Longitudinal Study to Assess the Relative Contribution of Common Respiratory Viruses to Severe Lower Respiratory Infections in Young Children.

BACKGROUND: Respiratory viruses such as respiratory syncytial virus (RSV), influenza, parainfluenza and human metapneumovirus are well-established etiologies of acute lower respiratory tract infections (ALRIs; LRI-viruses). In contrast, adenovirus (AdV), rhinovirus/enterovirus (RV/EV) and seasonal human coronaviruses (CoV), collectively termed AdV/RV/CoV, are detected both in healthy children and children with ALRI. METHODS: The methods include a prospective longitudinal case-control study, assessing the prevalence of LRI-viruses versus AdV/RV/CoV in ALRI [community-acquired alveolar pneumonia (CAAP) and bronchiolitis] during hospitalization (visit 1), 7-14 days (visit 2) and 28-35 days (visit 3) in 2-17-month-old children. Controls were 2-27-month-old children hospitalized for elective surgery during the same respiratory seasons. RESULTS: We enrolled 99 infants (37 CAAP, 38 bronchiolitis and 24 controls) and obtained 211 nasopharyngeal swabs. Overall, 163 (77%) had greater than or equal to 1 viruses detected; RV/EV (n = 94; 45%) and RSV (n = 71; 34%) were the most frequently detected viruses. In CAAP, the overall LRI-virus prevalence was 78.4%, 32.4% and 5.4% in visits 1, 2 and 3, respectively; the respective rates in bronchiolitis were 73.7%, 34.5% and 8.0%. In controls, no LRI-viruses were detected. In contrast, the overall AdV/RV/CoV prevalence was high among controls (70.8%) and similar among CAAP (48.6%, 40.5% and 40.5%) and bronchiolitis (47.4, 58.6% and 64.0%) across visits. CONCLUSIONS: Among ALRI cases, LRI-viruses dominated during the acute disease, with prevalence declining within 28-35 days, suggesting their causative role. In contrast, AdV/RV/CoV prevalence was similar during all 3 visits and in controls, suggesting that carriage of these viruses is common during the viral respiratory season. The current study is relatively small and of short duration; however, the findings are supported by other recent studies.

The COVID-19 pandemic as an opportunity for unravelling the causative association between respiratory viruses and pneumococcus-associated disease in young children: a prospective study.

BACKGROUND: In young children, rates of lower respiratory infections (LRI) and invasive pneumococcal disease (IPD) have been associated with respiratory syncytial virus (RSV), human metapneumovirus (hMPV), influenza (flu), and parainfluenza (PIV) (collectively termed here as pneumonia and pneumococcal disease-associated viruses [PDA-viruses]). However, their contribution to the pathogenesis of these disease endpoints has not yet been elucidated. The COVID-19 pandemic provided a unique opportunity to examine the question. METHODS: This prospective study comprised all children <5 years, living in southern Israel, during 2016 through 2021. The data were previously collected in multiple ongoing prospective surveillance programs and include: hospital visits for community-acquired alveolar pneumonia (CAAP), non-CAAP LRI; nasopharyngeal pneumococcal carriage (<3 years of age); respiratory virus activity; and nationwide, all-ages COVID-19 episodes and IPD in children <5 years. A hierarchical statistical model was developed to estimate the proportion of the different clinical endpoints attributable to each virus from monthly time series data, stratified by age and ethnicity. A separate model was fit for each endpoint, with covariates that included a linear time trend, 12-month harmonic variables to capture unexplained seasonal variations, and the proportion of tests positive for each virus in that month. FINDINGS: During 2016 through 2021, 3,204, 26,695, 257, and 619 episodes of CAAP, non-CAAP LRI, pneumococcal bacteremic pneumonia and non-pneumonia IPD, respectively, were reported. Compared to 2016-2019, broad declines in the disease endpoints were observed shortly after the pandemic surge, coincident with a complete disappearance of all PDA-viruses and continued circulation of rhinovirus (RhV) and adenovirus (AdV). From April 2021, off-season and abrupt surges of all disease endpoints occurred, associated with similar dynamics among the PDA-viruses, which re-emerged sequentially. Using our model fit to the entire 2016-2021 period, 82% (95% CI, 75-88%) of CAAP episodes in 2021 were attributable to the common respiratory viruses, as were 22%-31% of the other disease endpoints. Virus-specific contributions to CAAP were: RSV, 49% (95% CI, 43-55%); hMPV, 13% (10-17%); PIV, 11% (7-15%); flu, 7% (1-13%). RhV and AdV did not contribute. RSV was the main contributor in all endpoints, especially in infants. Pneumococcal carriage prevalence remained largely stable throughout the study. INTERPRETATION: RSV and hMPV play a critical role in the burden of CAAP and pneumococcal disease in children. Interventions targeting these viruses could have a secondary effect on the burden of disease typically attributed to bacteria. FUNDING: There was no funding for this study.

Treatment of Cystic Echinococcosis in Children: A Single Center Experience.

BACKGROUND: Cystic echinococcosis (CE) treatment is complicated, relying on cysts characteristics, host factors and possible treatment adverse events. We assessed childhood CE treatment characteristics. METHODS: A retrospective cohort study, 2005-2021, which presents our experience with treating children with CE. We compared therapeutic interventions use in association with the location, size and number of cysts. Additionally, we assessed complications rate following those interventions. RESULTS: Sixty six children had CE; 97% were Bedouins. Overall, 183 cysts were identified in 74 organs: liver (n = 47, 64%), lungs (n = 23, 31%), brain, para-ovarian, kidney and peritoneum (other-grouped, n = 4, 5%). Mean ± Standard deviation largest cyst size (per patient) was 6.6 ± 3.2 cm. Treatment with albendazole was administered to 94% of CE, while albendazole monotherapy was used in 27% (n = 18, including 4 cases with extra-hepatic cysts). Surgical interventions included drainage/puncture, aspiration, injection and reaspiration (PAIR; n = 20), mainly performed in hepatic-CE (40% vs. 4% in pulmonary-CE, and 0% in other-CE), excision and drainage (n = 34) and complete excision (n = 10), mainly done in other-CE (50% vs. 26% and 4% in pulmonary-CE and hepatic-CE, respectively). Larger cyst size was associated with complete excision compared with albendazole monotherapy. The number of cysts was not associated with the chosen intervention. Fever was recorded following 39% of surgical interventions. Local surgical complications were relatively rare. CONCLUSIONS: Cysts location and size affected treatment choice among CE patients. Procedures with drainage had relatively higher rate of complications, including recurrence. Albendazole monotherapy may be a viable therapeutic option in selected CE cases.

Neurologic Manifestations of Influenza in Children.

OBJECTIVE: We assessed the neurologic manifestation of influenza among hospitalized children with influenza (neuro-flu), comparing their demographic and clinical characteristics to hospitalized children without neurologic manifestation (classic-flu). METHODS: A retrospective, cohort study. All children with laboratory confirmed influenza (PCR), admitted to the Soroka University Medical Center (SUMC) between 2016 and 2019 were included. RESULTS: Overall, 951 patients were identified: 201 with neuro-flu, and 750 with classic-flu. Seizures (n = 125) were the most common neurological manifestation of neuro-flu (seizure-flu): 73 simple febrile seizures, 45 atypical febrile seizures, and 7 afebrile seizures. Neurological comorbidities rates were significantly higher in neuro-flu versus classic-flu (13.0% vs. 6.0%), while respiratory and cardiac comorbidities were less common in neuro-flu (4.5% and 0.5% vs. 8.0% and 4.5%, respectively). Neuro-flu (compared with classic-flu) was associated with leukocytosis (21.0% vs. 13.0%, P < 0.001) and lower C-reactive protein (CRP) levels (2.4 ± 4.1 vs. 3.3 ± 5.4, P = 0.03). Notably, patients with classic flu had a more prominent respiratory disease, as they had more chest radiographs (CXR) performed (60.5% vs. 45.0%, P < 0.001), higher rates of pneumonia (27.0% vs. 12.0%, P < 0.001), and antibiotic (antibacterial) treatment (60.0% vs. 42.0%, P < 0.001). CONCLUSIONS: Influenza can appear as a neurologic disease, manifested mainly with febrile seizures. Children with neuro-flu have more neurologic comorbidities, suggesting that neuro-flu is mainly driven by host-factors, rather than by pathogen-factors. The relatively lower rates of pneumonia in neuro-flu suggests that these patients are admitted in the early stage of the influenza infection, which triggers the neurologic response.

Topical liposomal amphotericin B gel treatment for cutaneous leishmaniasis caused by Leishmania major: a double-blind, randomized, placebo-controlled, pilot study.

BACKGROUND: Cutaneous leishmaniasis (CL) topical treatments may have low efficacy, while systemic treatments have adverse effects (AEs) and high cost. Since treatment options for CL nowadays have numerous disadvantages, an alternative topical treatment is vastly needed. We assessed liposomal amphotericin B gel (LAmB gel) treatment efficacy and safety. METHODS: A randomized, double-blind, placebo-controlled trial. Adults with CL (PCR proven, ≤5 lesions) were randomized for 28 days with LAmB gel (cases) versus placebo gel (controls), followed by LAmB gel for 28 days (both groups). Lesion size, ulceration, induration, scarring, swelling, and AEs (pain, itch, erythema, discharge, fever, and urticaria) were assessed at days 1, 28, and 56. PCR was repeated at day 56. RESULTS: Thirteen patients (four cases, nine controls) with 39 lesions (11 cases, 28 controls) caused by Leishmania major (L. major) were randomized. Ulcer, induration, scarring, and swelling were noted in 18%, 91%, 0%, and 27% of cases, respectively, versus 86%, 89%, 7%, and 54% of controls, respectively. At day 28, improvement rates were low in both groups. Induration improved comparing LAmB gel treatment for 56 days versus 28 days. Ulceration, induration, and swelling improved comparing all patients at 56 days versus 28 days. PCR turned negative in three of four cases and eight of nine controls. Mild, only local, AEs were reported in <30% of the patients. CONCLUSIONS: LAmB gel is safe and may be considered as an alternative topical treatment for CL caused by L. major. Further, larger-scale studies are warranted to evaluate the long-term impact of LAmB gel on the management of CL.

Remote Versus In-person Outpatient Clinic Visits and Antibiotic Use Among Children During the COVID-19 Pandemic.

BACKGROUND: The proportion of remote clinic visits was expected to increase among children during the COVID-19 pandemic which might result in antibiotic overuse. METHODS: In southern Israel, 2 ethnic groups, Jewish and Bedouin, live side-by-side. Computerized data on visits for children <18 years were examined from clinics with ≥50 insured children, active both pre-COVID-19 and during the COVID-19 pandemic. Visits were divided into in-person and remote. Monthly infectious diagnoses and dispensed antibiotic prescription rates were calculated by age (<5, 5-17 years) and ethnic groups. Mean monthly rates of 2 parallel seasons (pre-COVID-19 and COVID-19 periods) were compared. RESULTS: Overall 2,120,253 outpatient clinic visits were recorded. Remote clinic visit rates (per 1000 children) increased from 97.04 and 33.86 in the pre-COVID-19 to 179.75 and 50.05 in the COVID-19 period in Jewish and Bedouin children, respectively ( P < 0.01) along with a reduction of in-person visit rates in both populations. Comparing pre-COVID-19 and COVID-19 periods, the rates of overall infectious diagnoses in remote visits increased. Nevertheless, dispensed antibiotic prescription rates in remote visits (per 1000 visits) remained unchanged (9.84 vs. 8.67, P = 0.70, in the Jewish population and 14.32 vs. 14.17, P = 1.00, in the Bedouin population in the pre-COVID-19 and COVID-19 periods, respectively) with a similar distribution of antibiotic categories. CONCLUSIONS: COVID-19 pandemic resulted in an expansion of remote visits of children <18 years with an increase in infectious diagnoses. However, remote dispensed antibiotic prescription rates remained unchanged. These dynamics were more accentuated in Jewish children, characterized by higher socio-economic conditions, compared to Bedouin children.

Disproportionate reduction in respiratory vs. non-respiratory outpatient clinic visits and antibiotic use in children during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic led to improved hygiene and reduced social encounters. Near elimination of the activity of respiratory syncytial virus and influenza viruses were observed, worldwide. Therefore, we assessed the rates of pediatric outpatient clinic visits and medications prescribed at those visits during the coronavirus disease 2019 (COVID-19) pandemic and pre-COVID-19 period (2016-2019). METHODS: Monthly and annual incidence rates for respiratory and non-respiratory diagnoses and dispensed prescription rates were calculated. Acute gastroenteritis (AGE) visits were analyzed separately since the mode of transmission is influenced by hygiene and social distancing. RESULTS: Overall, 5,588,702 visits were recorded. Respiratory and AGE visits declined by 49.9% and 47.3% comparing the COVID-19 and pre-COVID-19 periods. The respective rate reductions for urinary tract infections, trauma, and skin and soft tissue infections were 18.2%, 19.9%, and 21.8%. Epilepsy visits increased by 8.2%. Overall visits rates declined by 21.6%. Dispensed prescription rates of antibiotics and non-antibiotics respiratory medications declined by 49.3% and 44.4%, respectively. The respective declines for non-respiratory antibiotics and non-antibiotics were 15.1% and 0.2%. Clinic visits and prescription rates reductions were highest in April-May, following the first lockdown in Israel. CONCLUSIONS: COVID-19 pandemic resulted in a substantial reduction in respiratory outpatient clinic visits and dispensed respiratory drugs, with only a mild reduction seen for non-respiratory visits. These trends were probably driven by COVID-19 mitigation measures and by the profound disruption to non-SARS COV-2 respiratory virus activity.

Genomic Epidemiology of Clinical Brucella melitensis Isolates from Southern Israel.

Brucellosis, a zoonosis mainly transmitted by consumption of unpasteurized dairy products, is endemic in Southern Israel, mainly among the Bedouin Arab population. However, the genomic epidemiology of B. melitensis in this region has not yet been elucidated. A cohort of brucellosis cases (n = 118) diagnosed between 2017-2019 was studied using whole-genome sequencing (WGS). Phylogenetic analyses utilized core genome MLST (cgMLST) for all local isolates and core genome SNPs for 347 human-associated B. melitensis genomes, including Israeli and publicly available sequences. Israeli isolates formed two main clusters, presenting a notable diversity, with no clear dominance of a specific strain. On a global scale, the Israeli genomes clustered according to their geographical location, in proximity to genomes originating from the Middle East, and formed the largest cluster in the tree, suggesting relatively high conservation. Our study unveils the genomic epidemiology of B. melitensis in Southern Israel, implicating that rather than a common source, the transmission pattern of brucellosis among Bedouin communities is complex, predominantly local, and household-based. Further, genomic surveillance of B. melitensis is expected to inform future public health and veterinary interventions and clinical care.

Human Toxocariasis in Israel: A Nationwide Serology-Based Analysis, 2005-2019.

Toxocariasis is a rare and underdiagnosed disease, and data concerning epidemiological aspects of toxocariasis in Israel are lacking. We describe the epidemiology of toxocariasis in Israel. Epidemiological data of all serology tests between 2005 and 2019 were retrieved and compared with detailed demographics. Overall, 464 positive cases from a total of 10,896 tests conducted were identified, reflecting a mean positivity rate of 4.4% (yearly range, 2-22%). Over the years, a significant increase in yearly tests was noted, without a parallel change in the positivity rate. The greatest positivity was noted among males and children (< 18 years). No differences were noted when comparing urban/rural and Jewish/non-Jewish sub-groups. A significant correlation between toxocariasis incidence and dog ownership rate was observed in major cities (r[8] = 0.82, P < 0.005). Our study shows that, in Israel, toxocariasis is not restricted to specific populations or locations. The risk factor of dog contacts was reiterated by nationwide dog registration data. There is need for a seroprevalence survey to understand the disease situation more fully.

The impact of the pneumococcal conjugate vaccines on the incidence of community-acquired alveolar pneumonia in premature compared with in term-born infants.

BACKGROUND: Preterm-born children are prone to respiratory infections and complications during infancy and early childhood. In Israel, pneumococcal conjugated vaccines (PCVs) were introduced in 2009-2010, with high vaccination coverage. We assessed the impact of PCV implementation on community-acquired alveolar pneumonia (CAAP) in children < 2 years old born prematurely, in comparison with term born infants. METHODS: We conducted a prospective, active, population-based surveillance of children < 2 years old with radiologically-proven CAAP, visiting the only regional medical center. CAAP incidence in the pre-PCV and post-PCV eras were compared in early premature (29-32 weeks gestational age [WGA]), late premature (33-36 WGA) and term-born infants (>36 WGA). RESULTS: Of 214,947 births during the study period, 6'791 CAAP episodes were diagnosed; 211, 653 and 5,806 were in early premature, late premature and term infants, respectively. After PCV implementation, overall CAAP visits were reduced by 44% (95% CI 36-51): 60%, 21% and 45% among those born early preterm, late preterm and at term, respectively (statistically significant for children born early preterm and at term). For outpatients, the respective rate reductions were 79%, 40% and 65% (statistically significant for the children born at term). Importantly, the mean annual rates in the post-PCV period became similar in all 3 groups. The rate reductions among the hospitalized children were lower those that among the non-hospitalized children, with reductions of 56%, 16% and 33% for the three groups, respectively (statistically significant for early preterm and at term children). CONCLUSIONS: CAAP reduction trends after PCV implementation for preterm-born infants were similar to those for term-born infants. Whether this was because of similar direct PCV- protection, because of indirect (herd) protection or both, is unclear. Post-PCV implementation, the gaps in CAAP rates between infants born prematurely and at term were reduced.