Hyperendemic Region Research Articles

Efficacy of Sustained-Release Formulation of Moxidectin (Guardian SR) in Preventing Heartworm Infection over 18 Months in Dogs Living in a Hyperendemic Area.

This study investigates the efficacy of a sustained-release (SR) moxidectin microsphere formulation in preventing canine heartworm infection over 18 months in Canary Hound dogs, a hunting breed common in the Canary Islands, which is a hyperendemic region. These dogs typically do not receive preventive treatments and act as reservoirs for the disease. This field study was conducted across 11 hunting kennels with 109 dogs living outdoors, none of whom were receiving heartworm prophylaxis, with Dirofilaria immitis prevalence ranging from 11.1% to 57.1% (average 36.7%). Among these, 20 clinically healthy, heartworm-negative dogs were randomly selected to receive a single subcutaneous injection of moxidectin SR (0.17 mg/kg body weight). Antigen and Knott's tests were performed at 6, 12, 18, and 24 months. All dogs completed the study without adverse reactions and remained heartworm-negative throughout. By the end of the study, kennel heartworm prevalence ranged from 14.3% to 46.7% (average 35.4%). A single subcutaneous dose of moxidectin SR at the recommended dosage may prevent patent heartworm infection in dogs for up to 18 months in hyperendemic regions. Further studies are required to confirm these findings. Extending the efficacy period of moxidectin could improve owner compliance, particularly among those with lower animal health awareness.

Impact of pre-existing cross-reactive antibodies on cyclic dengue outbreaks in the hyperendemic region of Bali, Indonesia

The four serotypes of the dengue virus (DENV) cause a range of diseases ranging from mild fever to severe conditions. Understanding the immunological interactions among the four serotypes is crucial in comprehending the dynamics of serotype shifting during outbreaks in areas where all four serotypes co-circulate. Hence, we evaluated the neutralizing antibody and antibody-dependent enhancement responses against the four DENV serotypes using acute-phase plasma samples collected from 48 laboratory-confirmed dengue patients during a dengue outbreak in Bali, Indonesia in 2022. Employing single-round infectious particles to exclusively investigate immunogenicity to the structural surface proteins of DENV, which are the targets of antibodies, we found that individuals with a probable prior history of DENV-1 infection exhibited increased susceptibility to secondary DENV-3 infection, attributed to cross-reactive antibodies with limited neutralizing activity against DENV-3 (geometric mean 50 % neutralization titer (GMNT50) = 47.6 ± 11.5). This susceptibility was evident in vitro, with a mean fold enhancement of 28.4 ± 33.9. Neutralization titers against DENV-3 were significantly lower compared to other serotypes (DENV-1 GMNT50 = 678.1 ± 9.0; DENV-2 GMNT50 = 210.5 ± 8.7; DENV-4 GMNT50 = 95.14 ± 7.0). We demonstrate that prior immunity to one serotype provides limited cross-protection against the other serotypes, influencing the dominant serotype in subsequent outbreaks. These findings underscore the complexity of dengue immunity and its implications for vaccine design and transmission dynamics in hyperendemic regions.

Hepatitis E Virus Genotype 3 among Hemodialysis Patients in Mexico: First Identification of Chronic Infection.

The global distribution of hepatitis E virus (HEV) is attributed to its capacity to spread through several routes of transmission; hemodialysis has gained increased amounts of attention in recent years. Although Mexico is considered a hyperendemic region for hepatitis E, no HEV surveillance is performed in the country. The frequency of HEV in hemodialysis (HD) patients has not been determined. Herein, we conducted a cross-sectional single-center analytical study including 67 serum samples from HD patients. Anti-HEV IgG and IgM antibodies and the viral genome were determined; partial regions within the HEV genome were sequenced for further phylogenetic analysis. Globally, 14.9% of the tested patients exhibited reactivity for IgG antibodies against HEV, and none showed reactivity to IgM. A total of 5.9% of the samples showed HEV genome amplification, and sequencing confirmed the identity of genotype 3; subsequent analysis of positive cases revealed two acute cases and chronic hepatitis E infection in one patient. Notably, the chronic patient was negative for anti-HEV IgG antibodies. Our findings highlight the importance of viral genome testing in HD patients and the need to establish guidelines for HEV detection in Mexico.

Unraveling Dengue Virus Diversity in Asia: An Epidemiological Study through Genetic Sequences and Phylogenetic Analysis.

Dengue virus (DENV) is the causative agent of dengue. Although most infected individuals are asymptomatic or present with only mild symptoms, severe manifestations could potentially devastate human populations in tropical and subtropical regions. In hyperendemic regions such as South Asia and Southeast Asia (SEA), all four DENV serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) have been prevalent for several decades. Each DENV serotype is further divided into multiple genotypes, reflecting the extensive diversity of DENV. Historically, specific DENV genotypes were associated with particular geographical distributions within endemic regions. However, this epidemiological pattern has changed due to urbanization, globalization, and climate change. This review comprehensively traces the historical and recent genetic epidemiology of DENV in Asia from the first time DENV was identified in the 1950s to the present. We analyzed envelope sequences from a database covering 16 endemic countries across three distinct geographic regions in Asia. These countries included Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka from South Asia; Cambodia, Laos, Myanmar, Thailand, and Vietnam from Mainland SEA; and Indonesia, the Philippines, Malaysia, and Singapore from Maritime SEA. Additionally, we describe the phylogenetic relationships among DENV genotypes within each serotype, along with their geographic distribution, to enhance the understanding of DENV dynamics.

Repeat controlled human Plasmodium falciparum infections delay bloodstream patency and reduce symptoms

Resistance to clinical malaria takes years to develop even in hyperendemic regions and sterilizing immunity has rarely been observed. To evaluate the maturation of the host response against controlled repeat exposures to P. falciparum (Pf) NF54 strain-infected mosquitoes, we systematically monitored malaria-naïve participants through an initial exposure to uninfected mosquitoes and 4 subsequent homologous exposures to Pf-infected mosquitoes over 21 months (n = 8 males) (ClinicalTrials.gov# NCT03014258). The primary outcome was to determine whether protective immunity against parasite infection develops following repeat CHMI and the secondary outcomes were to track the clinical signs and symptoms of malaria and anti-Pf antibody development following repeat CHMI. After two exposures, time to blood stage patency increases significantly and the number of reported symptoms decreases indicating the development of clinical tolerance. The time to patency correlates positively with both anti-Pf circumsporozoite protein (CSP) IgG and CD8 + CD69+ effector memory T cell levels consistent with partial pre-erythrocytic immunity. IFNγ levels decrease significantly during the participants’ second exposure to high blood stage parasitemia and could contribute to the decrease in symptoms. In contrast, CD4-CD8 + T cells expressing CXCR5 and the inhibitory receptor, PD-1, increase significantly after subsequent Pf exposures, possibly dampening the memory response and interfering with the generation of robust sterilizing immunity.

Isolation of Caribbean Ciguatoxin-5 (C-CTX5) and confirmation of its structure by NMR spectroscopy

Ciguatera poisoning occurs throughout subtropical and tropical regions globally. The Virgin Islands in the Caribbean Sea is a known hyperendemic region for ciguatera and has been associated with Caribbean ciguatoxin (C-CTX) contamination in fish. An algal C-CTX (C-CTX5) was identified in Gambierdiscus silvae and G. caribeaus isolated from benthic algal samples collected in waters south of St. Thomas, US Virgin Islands. The highest CTX-producing isolate, G. silvae 1602 SH-6, was grown at large-scale to isolate sufficient C-CTX5 for structural confirmation by NMR spectroscopy. A series of orthogonal extraction and fractionation procedures resulted in purification of approximately 40 μg of C-CTX5, as estimated by quantitative NMR. A suite of 1D and 2D NMR experiments were acquired that verified the structure originally proposed for C-CTX5. The structural confirmation and successful isolation of C-CTX5 opens the way for work on the stability, toxicology and biotransformation of C-CTXs, as well as for the production of quantitative reference materials for analytical method development and validation. The strategies developed for purification of C-CTX5 may also apply to isolation and purification of CTXs from the Pacific Ocean and other regions.

Hepatitis B Virus Infection: A Mini Review.

Hepatitis B and C viruses (HBV and HCV) are the leading causes of end-stage liver disease worldwide. Although there is a potent vaccine against HBV, many new infections are recorded annually, especially in poorly resourced places which have lax vaccination policies. Again, as HBV has no cure and chronic infection is lifelong, vaccines cannot help those already infected. Studies to thoroughly understand the HBV biology and pathogenesis are limited, leaving much yet to be understood about the genomic features and their role in establishing and maintaining infection. The current knowledge of the impact on disease progression and response to treatment, especially in hyperendemic regions, is inadequate. This calls for in-depth studies on viral biology, mainly for the purposes of coming up with better management strategies for infected people and more effective preventative measures for others. This information could also point us in the direction of a cure. Here, we discuss the progress made in understanding the genomic basis of viral activities leading to the complex interplay of the virus and the host, which determines the outcome of HBV infection as well as the impact of coinfections.

Clinical Manifestations of Dengue in Children and Adults in a Hyperendemic Region of Colombia.

Dengue is the most common arboviral disease in the world. Traditionally, it has affected more adults, but the incidence in children has increased in recent years. Colombia is no stranger to this change; therefore, we aimed to find the differences in signs, symptoms, and clinical, hematological, and hemogram characteristics between children under 12 years old and individuals aged 12 years and older in an endemic region of Colombia in 2020-2022. The analyses were conducted with baseline data, corresponding to a cross-sectional design. Multiple correspondence analysis was used for general, dermatological, and clinical symptom profiles. Discriminant analysis was used for laboratory profiles. Multiple correspondence analysis was applied to nominal categorical data, employing Euclidean distances to analyze age groups. Discriminant analysis was applied to a training sample and validated on a test sample. The overall agreement of the model's discrimination, sensitivity, specificity, and fit indicators was calculated. The results indicated that individuals under 12 years exhibited distinct dermatological and clinical features, including rash, pruritus, hypotension, lymphocyte count, and platelet count, compared with those aged 12 years and older. In contrast, those 12 years and older were profiled for general and clinical symptoms such as pain (back pain, retro-orbital pain, headache), dizziness, chills, hematuria, tachypnea, and elevated/high hematocrit, hemoglobin, and basophil values. These findings are crucial to understanding the high incidence in children; they also facilitate rapid understanding of the disease in clinical care settings and differentiate it from other febrile outbreaks. This will affect disease control, particularly in severe cases, and reduce mortality.

Health-related quality of life of children and adolescents with leprosy in a hyperendemic region, Midwest Brazil

Health-related quality of life of children and adolescents with leprosy in a hyperendemic region, Midwest Brazil

Temporal Analysis of Cutaneous Leishmaniasis Incidence in an Endemic Area of Southeast Iran.

Cutaneous leishmaniasis (CL) is the most common type of leishmaniasis in tropical and subtropical areas. This study investigated the trend of CL changes from 2009 to 2022, and predicted the number of leishmaniasis cases until 2024. This ecological study was performed on new monthly confirmed CL cases from 2009 to 2022 from the leishmaniasis registration system in southeast Iran. The time series method was used to investigate the trend of changes in CL from 2009 to 2022. SARIMA model was run to predict the number of leishmaniasis cases until 2024 by controlling the effect of climatic variables on the disease process. The analysis showed a significant increase in CL cases in 2015 and from 2021 to 2022. The minimum number of registered cases was observed in 2018, with 81 cases. The maximum number was also observed in 2021, with 318 patients. The leishmaniasis cases decreased from January to June and increased from July to December. According to the results of SARIMA (1, 0, 0) (1, 0, 0) multivariate analysis, the temperature in log 12 has a significant negative correlation with the number of leishmaniasis cases. This model predicted a decreasing trend in leishmaniasis cases until 2024. The southeast region of Fars province is one of the hyper-endemic regions of the disease, and it is prone to periodic outbreaks. An active surveillance system must investigate the CL incidence trend and evaluate the effectiveness of interventions to prevent the occurrence of new outbrea.

Genotyping and clonal origin of Sporothrix brasiliensis in human sporotrichosis cases in Argentina

Sporothrix brasiliensis is considered a highly virulent emerging pathogen that causes sporotrichosis in humans, mainly after zoonotic transmission from infected cats. The epidemic of this zoonosis that originated from Brazil has spread in the last decades, generating hyperendemic regions in Latin America. We present two cases of human sporotrichosis causes by S. brasiliensis in Buenos Aires, Argentina, with good clinical response to differing treatments after contact with sick cats. Using Short tandem repeat (STR) genotyping, the two S. brasiliensis cases appear to be introduced from Brazil and likely originate from the same source.

Management of very severe tungiasis cases through repeated community-based treatment with a dimeticone oil formula: A longitudinal study in a hyperendemic region in Uganda.

Tungiasis (sand flea disease) is a neglected tropical disease that is endemic in Sub-Saharan Africa and Latin America. Tungiasis causes pain, mobility restrictions, stigmatisation and reduced quality of life. Very severe cases with hundreds of sand fleas have been described, but treatment of such cases has never been studied systematically. During a larger community-based tungiasis control programme in a hyperendemic region in Karamoja, northeastern Uganda, 96 very severe tungiasis cases were identified and treated with the dimeticone formula NYDA®. They were repeatedly followed-up and treated again when necessary. The present study traces tungiasis frequency, intensity and morbidity among these 96 individuals over 2 years. At baseline, very severe tungiasis occurred in all age groups, including young children. Throughout the intervention, tungiasis frequency decreased from 100% to 25.8% among the 96 individuals. The overall number of embedded sand fleas in this group dropped from 15,648 to 158, and the median number of embedded sand fleas among the tungiasis cases decreased from 141 to four. Walking difficulties were reported in 96.9% at the beginning and in 4.5% at the end of the intervention. Repeated treatment with the dimeticone formula over 2 years was a successful strategy to manage very severe cases in a hyperendemic community. Treatment of very severe cases is essential to control the spread and burden of tungiasis in endemic communities.

Gender differences in trachomatous scarring prevalence in a formerly trachoma hyperendemic district in Tanzania.

Trachoma is a chronic conjunctivitis caused by the bacterium Chlamydia trachomatis. Repeated infections lead to trachomatous conjunctival scarring which can progress to potentially blinding trachomatous trichiasis (TT). In trachoma hyperendemic conditions, women compared to men have an increased risk of scarring and TT, which can progress to blinding corneal opacification. This study determined if there were gender differences in scarring prevalence and severity when trachoma prevalence approaches elimination, in a formerly trachoma hyperendemic region. A cross-sectional prevalence study was conducted amongst adults age 15 years and older in Kongwa district, Tanzania in 2019. 3168 persons over age 15 years agreed to be examined and had at least one eye with a gradable image. Ocular photographs were graded for scarring according to a published four-step severity scale. Overall, about half of all study participants had scarring. However, more females (52.3%) had any scarring compared to males (47.2%), OR = 1.22 (95% CI = 1.05-1.43). For every year increase in age, there was a 6.5% increase in the odds of having more severe scarring (95% CI: 5.8%, 7.2%). Women were more likely than men to have severe scarring, OR 2.36 (95% CI: 1.84-3.02). Residence in a community with TF≥10% was associated with a 1.6-fold increased odds of any scarring. Overall scarring prevalence and more severe scarring prevalence was higher in females compared to males, even adjusting for age and community TF prevalence. The data suggest that processes occur that lead to women preferentially progressing towards more severe scarring compared to men.

Seroreversion to Chlamydia trachomatis Pgp3 Antigen Among Children in a Hyperendemic Region of Amhara, Ethiopia.

Monitoring trachoma transmission with antibody data requires characterization of decay in IgG to Chlamydia trachomatis antigens. In a 3-year longitudinal cohort in a high-transmission setting, we estimated a median IgG half-life of 3 years and a seroreversion rate of 2.5 per 100 person-years (95% confidence interval, 1.6-3.5). Clinical Trials Registration NCT02754583.

Patterns of Mannose-Binding Lectin (MBL) responses to <i>Plasmodium falciparum</i> infections in hyperendemic settings

Background: malaria caused by Plasmodium falciparum remains a significant and major public health concern in Africa, particularly in hyperendemic regions. Recurrent fevers and high quantities of inflammatory mediators in the circulation define the disease's blood stages. By binding to non-self-pathogen oligosaccharide surfaces, Mannose-Binding Lectin (MBL) and lectin complement pathways trigger innate immune processes and contribute to the formation of adaptive immune responses. Methods: in Sudan, we investigated the varied immune response levels of MBL to the different phases of P. falciparum infection in White Nile and Blue Nile states endemic to malaria. And we looked at the interaction of regulatory Interleukin 6 (IL- 6) cytokines on MBL during infection. Our study was based on a total of 108 cases, in which 86 patients (62.0%) were uncomplicated and (17.6%) were severe, all met the diagnostic criteria and were clinically admitted for malaria infections. For the determination of serum MBL and IL-6 levels, a commercial ELISA kit was employed. Results: the analysis of the results revealed significantly elevated levels of MBL and IL-6 in both severe and uncomplicated cases (p<0.001). And MBL average in contrast to residents, Blue Nile patients had high parasitemia (599.9 ng/mL) and this difference was statistically significant (p-value<0.05). The remarkable positive correlation of IL-6 serum levels with MBL among malaria patients and healthy controls (r=0.399, p<0.001) was noted too. Conclusions: according to the findings of this study, patients living in hyperendemic areas exhibit a different MBL response rate and appear to be more homogeneous in proportion to the density of P. falciparum due to parasitemia. In addition, it is also dependent on the regulatory immune mediator IL-6.

Arsenic exposure to mouse visceral leishmaniasis model through their drinking water linked to the disease exacerbation via modulation in host protective immunity: a preclinical study

A large body of evidence has shown a direct link between arsenic exposure and drug resistance to Leishmania parasites against antimonial preparations in visceral leishmaniasis (VL) hyper-endemic regions, especially in India and its sub-continent. However, the implicated roles of arsenic on the VL host, pathophysiological changes, and immune function have not yet been clarified, particularly at the reported concentration of arsenic in the VL hyper-endemic area of Bihar, India. Herein, we exposed the mouse VL model to arsenic (0.5 mg/L to 2 mg/L) through their drinking water and analyzed its effect on T cells proliferation, Th1/Th2-mediators, MAPK signaling cascade, and parasite load in preclinical models. Coherently, the parasite count in Giemsa stained spleen imprint has been investigated and found significant positive associations with levels of arsenic exposure. The liver and kidney function tests (AST, ALT, ALP, BUN, Creatinine, Urea, etc.) are apparent to hepatonephric toxicity in arsenic exposed VL mice compared to unexposed. This observation appears to be consistent with the up-regulated expression of immune regulatory Th2 mediators (IL-4, IL-10, TGF-β) and down-regulated expression of Th1 mediators (IL-12, IFN-γ, TNF-α) with a suppressed leishmanicidal function of macrophage (ROS, NO, iNOS). We also established that arsenic exposure modulated the host ERK-1/2 and p38 MAPK signaling cascade, limited T lymphocyte proliferation, and a lower IgG2a/IgG1 ratio to favor the Leishmania parasite survival inside the host. This study suggests that the contorted Th1-subtype and exacerbated Th2-subtype immune responses are involved in the increased susceptibility and pathogenesis of Leishmania parasite among subjects/individuals regularly exposed to arsenic.

S35 Granulomatous Opportunistic Infections in a Tertiary IBD Center Located in a Tuberculosis Hyperendemic Region in Brazil

S35 Granulomatous Opportunistic Infections in a Tertiary IBD Center Located in a Tuberculosis Hyperendemic Region in Brazil

Amlodipine and lufenuron as repurposing drugs against Sporothrix brasiliensis.

Sporotrichosis caused by Sporothrix brasiliensis is a globally emerging infectious disease with limited therapeutic options. Thus, we aimed to evaluate the in vitro activity of amlodipine (AML) and lufenuron (LUF) alone and their interaction with itraconazole (ITZ), the first-choice drug against S. brasiliensis. Twenty clinical isolates of S. brasiliensis from two hyperendemic regions were tested through a microdilution assay to evaluate the minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) of AML and LUF. Checkerboard assay was performed with 10 isolates for both drug interactions with ITZ. AML showed inhibitory and fungicidal activity against all isolates included, with MIC values ranging from 32 to 256 µg/mL, and MFC from 64 to 256 µg/mL. However, none of the S. brasiliensis isolates were inhibited by the highest soluble concentration of LUF (MIC >64 µg/mL for all strains). Synergic interaction of AML and LUF with ITZ occurred in 50% and 40% of the isolates tested, without any antagonistic effects. Both repurposing drugs evaluated in our study showed a promising in vitro activity, especially in synergy with ITZ against S. brasiliensis, warranting future in vivo investigations regarding its activity.

Seroprevalence of anti-HEV IgG in children: very early exposure in young children in a hyperendemic region.

Hepatitis E virus (HEV) can be considered an emerging zoonotic pathogen and is an important cause of acute viral hepatitis in high-income countries. Corsica has been identified as a hyperendemic region for HEV. We aimed to characterize the prevalence of IgG among children and estimate the annual force of infection of HEV. From April 2020 to June 2021, we collected 856 "residual sera" in 13 medical biology laboratories. Sera were tested using the Wantaï HEV IgG assay. Data were weighted according to the distribution by sex and age of the real Corsican population. Serocatalytic models were applied to assess the annual force of infection of HEV. The weighted seroprevalence was 30.33% [27.15-34.0]. The seroprevalence was only associated with increasing age (7.25-40.52%; p < 0.001). The annual probability of infection was 5.4% for adults and children above 10-year-old and 2.2% for children under 10 yo. Our study demonstrates that in the hyperendemic island of Corsica, (i) exposure of the population to HEV is homogeneous at the spatial level with no difference between genders; (ii) HEV exposure occurs from birth, resulting in 7.4% seropositivity at the age of 4 years; and (iii) super exposure is observed after the age of 9 years. Accordingly, specific studies should be conducted to determine the breadth of the situation identified in our study. The role of the environment and its contamination by domestic or wild swine excreta should be investigated using a One Health approach.

Frequency, Markers and Costs of Secondary Bacterial Infection in Pediatric Dengue.

Secondary bacterial infection (SBI) occurs in a proportion of individuals with dengue and results in longer hospitalization, higher mortality, and increased health-related costs. However, the frequency, risk factors and predictive biomarkers of this comorbidity in pediatric dengue is partially known. We conducted a retrospective multicenter study in a dengue hyperendemic region of Colombia, analyzing 1597 children from two pediatric cohorts. We included children with confirmed dengue (mild to severe disease) and evaluated the rate of SBI, their clinical characteristics, diagnostic predictors and attention costs. We also assessed the diagnostic performance of plasma interleukin (IL)-6 for detecting SBI in pediatric dengue. The frequency of SBI in children with dengue with warning signs in cohorts 1 and 2 was 2.4% and 7.3%, respectively, and this rate reached 30.7% and 38.2% in children with severe disease. Staphylococcus aureus and Escherichia coli were the more frequent infectious agents. Increased total leukocytes and C-reactive protein levels, as well as high IL-6 at hospital admission, in children <48 months of age were early indications of SBI in dengue. Higher rates of organ dysfunction, the requirement of a longer hospitalization and a 2.3-fold increase in attention costs were observed in SBI. An important proportion of children with dengue course with SBI and exhibit higher morbidity. Elevated leukocytes, C-reactive protein and IL-6 in young children are early markers of SBI. Physicians should identify children with dengue and risk factors for SBI, microbiologically confirm the bacterial infection, and rationally and timely provide antimicrobial therapy.