Endemic Disease Research Articles

Results of Epizootiological Survey of the Territories of the Republic of Crimea and Sevastopol in 2015–2022

Introduction: Systematic studies of endemic zoonotic diseases on the Crimean Peninsula resumed in 2015 after a long break. Objective: To specify boundaries and determine epizootiological activity of the natural foci of infectious diseases in the Crimea and to update the list of possible reservoir hosts and vectors based on the results of field studies conducted in 2015–2022. Materials and methods: Counting and trapping of small mammals, ixodid ticks and mosquitoes, collecting of pellets of birds of prey, sampling of water and other zoological and entomological materials were carried out in the Crimea in the years 2015 to 2022. Results and discussion: According to the results of epidemiological and epizootiological monitoring of the Crimean Peninsula, the samples tested positive for tularemia were collected on the territory of 14 administrative entities, leptospirosis – 21, hantaviruses – 12, tick-borne encephalitis – 2, Crimean-Congo hemorrhagic fever – 7, Lyme borreliosis – 21, West Nile fever – 3, Q fever – 2, Marseilles fever – 6, monocytic ehrlichiosis – 1, and granulocytic anaplasmosis – 8 entities. A new hantavirus was identified in the Leninsky district. Positive findings of markers of the Crimean-Congo hemorrhagic fever virus were registered not only in the main vector, but also in other species of ixodid ticks. True boundaries of the natural foci of Lyme borreliosis in the Crimea were much wider and ran through both forest and steppe zones. A stable reproducing population of epidemiologically significant Ae. albopictus mosquitoes was found on the southern coast of Crimea. Conclusions: Based on the findings, we specified the boundaries and confirmed the activity of natural foci of infectious diseases during the study period, updated sources of infections, reservoir hosts and vectors, and compiled the “List of enzootic (endemic) territories of the Crimea, on which circulation of infectious agents common to humans and animals was found based on the results of field material studies in 2015–2022,” all facilitating managerial decisions on prevention of natural focal infections.

A Review of the Leishmanicidal Properties of Lectins.

Lectins are proteins widely distributed among plants, animals and microorganisms that have the ability to recognize and interact with specific carbohydrates. They have varied biological activities, such as the inhibition of the progression of infections caused by fungi, bacteria, viruses and protozoa, which is related to the interaction of these proteins with the carbohydrates present in the cell walls of these microorganisms. Leishmaniasis are a group of endemic infectious diseases caused by protozoa of the genus Leishmania. In vitro and in vivo tests with promastigotes and amastigotes of Leishmania demonstrated that lectins have the ability to interact with glycoconjugates present on the cell surface of the parasite, it prevents their development through various mechanisms of action, such as the production of ROS and alteration of membrane integrity, and can also interact with defense cells present in the human body, thus showing that these molecules can be considered alternative pharmacological targets for the treatment of leishmaniasis. The objective of the present work is to carry out a bibliographic review on lectins with leishmanicidal activity, emphasizing the advances and perspectives of research in this theme. Through the analysis of the selected studies, we were able to conclude that lectins have great potential for inhibiting the development of leishmaniasis. However, there are still few studies on this subject.

Epidemiological evolution of dengue in the pre-pandemic to post-pandemic periods in the Americas and Brazil

Introduction: Dengue is an asymptomatic infection or present symptoms like low fever to disabling high fever, severe headache, retroocular, muscle and joint pain, in addition to skin rashes, and if associated with COVID-19, it can worsen the illness condition. Objective: investigate the epidemiological evolution of dengue in the pre-pandemic, pandemic and post-pandemic periods from an American and Brazilian perspective. Methodology: descriptive study, based on the search for information in epidemiological bulletins, data from DATASUS and the Pan American Health Organization/World Health Organization, in addition to articles available in databases provided by SciELO, ScienceDirect and Pubmed. Results: In the period before the pandemic, the high number of notifications was due to the DENV2 serotype, causing a large epidemic. In the years 2020-2021 there was a drop in the number of notifications due to the introduction of social and public health measures, misdiagnosis between the signs/symptoms of dengue and COVID-19, inaccurate serological tests and underreporting. In 2022 and 2023, the epidemiological scenario again points to increasing notification of dengue cases, mainly due to changes in routine vector control during the pandemic, combined with favorable environmental factors, such as increased rainfall. Conclusion: the neglect of both dengue fever and other diseases has negatively impacted the population today, since in order to mitigate the damage caused by the pandemic, actions to promote and prevent the health of endemic diseases in our territory, when placed in the background, have caused the underreporting of cases, influenced by changes in the political, economic and health spheres of society.

Relationship of Water Media Characteristics (pH, Temperature, TDS) to Density of Aedes sp Mosquito Flars in Karanggeneng Village, Lamongan District

DHF (Dengue hemorrhagic fever) is a tropical endemic disease in Indonesia with a fluctuating trend in Lamongan. The main factor under control is the larval breeding habitat. This study aimed to determine the relationship between the characteristics of the water medium and the density of Aedes sp. mosquito larvae in Karanggeneng Village, Lamongan Regency. We conducted this quantitative study using a cross-sectional observational method on a sample of 80 houses in Karanggeneng Village, employing a straightforward random sampling technique. We recorded the data collection in the observation sheet and analyzed it with a chi-square test. The results showed that 37 houses were positive for Aedes sp. larvae based on HI (DF = 6), CI (DF = 6), and BI (DF = 7), so Karanggeneng Village has a high mosquito larval density. There is a significant relationship between water media and the presence of Aedes sp. mosquito larvae. The relationship between pH (p-value = 0.000), temperature (p-value = 0.000), and TDS (p-value = 0.000) is significant. We recommend regularly draining the water container weekly to prevent mosquito larvae from using it as a habitat.

Incidence of cutaneous Leishmaniasis in humans during the COVID-19 pandemic in Baluchistan Province, Pakistan.

Cutaneous leishmaniasis (CL) is one of the neglected tropical diseases that affects impoverished communities throughout the world. In Pakistan CL is an endemic disease. This study aimed to determine the incidence of CL infection in the Baluchistan province of Pakistan from January 2020 to March 2022 during the COVID-19 pandemic. A total of 1047 clinically suspected cases of CL from Bolan Medical College Hospital, Quetta, were followed up in the study. The data regarding the epidemiological characterstics, pathological information, and treatment of patients was collected. Out of 1047 probable cases of CL, 594 (56.73%) cases were found to be positive for CL. Females had the highest infection rate, with the majority of reported cases being in the 0-9-year age group. Most CL cases were reported in April in the year 2020, with a few cases reported in June. But in the year 2021, the highest number of cases were reported in December. The number of overall cases has gradually increased in the year 2022, most likely because of the reduction in COVID-19 pandemic restrictions. The p value for the positive as compared to suspected cases in the years 2020, 2021, and 2022 was calculated as 0.8925, 0.8763, and 0.8535 respectively. Further epidemiological studies and health education campaigns are recommended to increase public awareness. It is strongly advised that local, provincial, and national health authorities establish and maintain effective leishmaniasis surveillance systems to promptly identify disease outbreaks and implement timely control measures.

Prognostic factors for the development of obstetric and perinatal pathology in pregnant women under conditions of iodine deficiency

According to the World Health Organization (WHO), iodine deficiency is the main cause of mental retardation in children, and at the same time, it significantly affects the pathological course of pregnancy and childbirth. The problem is complicated by the fact that more than 100.000 children with cretinism are born annually in the world. In recent years, there has been a significant increase in endemic thyroid diseases in Ukraine, the main cause of which is insufficient iodine consumption. Iodine deficiency conditions are aggravated by socio‑economic, ecological and radiological factors, while at the same time mass and group iodine prophylaxis is carried out improperly on the state level. Objective. To determine prognostic factors for the development of obstetric and perinatal pathology in pregnant women under conditions of iodine deficiency. Materials and methods. To compile a diagnostic table of prognostic factors of the threat of miscarriage, the analysis has been performed of 185 cases of threatened abortion (111 in the first trimester, 56 in the second, 18 in the third) and 223 control observations (without the threat of miscarriage). A diagnosis was considered as confirmed if it was established using all applicable methods of examination of pregnant women. Results. The risk factors of the occurrence of perinatal pathology include hypothyroxinemia (DC=–2.5) and ioduria in pregnant women less than 100 mg/l (DC=–1.9). In the intranatal period, a negative impact is exerted by the lack of coordination and weakness of labor activity (DC=–8.1). Levels of thyroid‑stimulating hormone (TSH) in umbilical cord blood >10 mIU/ml (DC=–4.6) are the prognostically favorable factors for the postnatal adaptation of the newborn, especially TSH levels >20 mIU/ml (DC=–8.3). Conduction of iodine prophylaxis (DC=7.7) and ioduria in pregnant women 200—400 mg/l (DC=5.1) contribute to the improvement of perinatal outcomes. Conclusions. A retrospective review of the prognostic significance of the diagnostic table in 188 patients with diffuse nontoxic goiter revealed its sensitivity (76%) and specificity (68%). On the basis of the conducted research, we established risk factors for the development of obstetric and perinatal complications, and assessed their informativeness. The developed algorithm is represented by a diagnostic table for the prediction of complications of pregnancy, childbirth and adverse perinatal outcomes in women with endemic thyropathies.

What is the state of the art on traditional medicine interventions for zoonotic diseases in the Indian subcontinent? A scoping review of the peer-reviewed evidence base

BackgroundTraditional medicine (TM) interventions are plausible therapeutic alternatives to conventional medical interventions against emerging and endemic zoonotic diseases, particularly in low-and middle-income countries that may lack resources and infrastructure. Despite the growing popularity in the usage of TM interventions, their clinical safety and effectiveness are still contested within conventional healthcare in many countries.MethodsWe conducted a scoping review of the peer-reviewed literature that synthesises and maps the evidence on TM interventions for the treatment and prevention of zoonoses on the Indian subcontinent. The region, a global hotspot of biodiversity and emerging infections, is characterised by high prevalence of TM use. Based on the scientific literature (mostly case study research, n=l06 studies), our review (1) maps the scope of the literature, (2) synthesises the evidence on the application of TM interventions for zoonoses, and (3) critically reflects on the state of TM and identifies areas for future research focus.ResultsThe evidence synthesis confirmed widespread usage of TM interventions for zoonoses on the subcontinent, with the majority of research reported from India (n=99 studies, 93.4%), followed by Pakistan (n=3 studies, 2.8%), Bangladesh (n=2 studies, 1.9%), and Sri Lanka (n=1, 0.9%). Most of the reviewed studies reported on ethno-medicinal uses of plant species, primarily for treating dengue (n=20 studies), tuberculosis (n=18 studies), Escherichia coli infection (n=16 studies), lymphatic filariasis and cholera (n=9 apiece). However, the evidence on the safety and effectiveness of these reported TM interventions is limited, indicating that these data are rarely collected and/or shared within the peer-reviewed literature.ConclusionThis review thus highlights that, whilst TMs are already being used and could offer more widely accessible interventions against emerging and endemic zoonoses and ectoparasites, there is an urgent need for rigorous clinical testing and validation of the safety and effectiveness of these interventions.

A Comparative Study on Soil-Crop Selenium Characteristics in High-Incidence Areas of Keshan Disease in Chinese Loess and Black Soil

With the gradual emphasis on health by people, the research on the pathogenesis of endemic diseases has become increasingly in-depth. Through analyzing the environmental selenium characteristics and conducting a comparative study in typical areas of Chinese loess and black soil in this paper, it is concluded that the environmental selenium in the two regions has different characteristics. The soil in the loess area has the characteristics of high alkalinity, low selenium, and relatively high selenium availability, and the crops are selenium-deficient, while the soil in the black soil area has the characteristics of high organic matter, low selenium availability, and relatively high selenium in crops. The research concluded that the environmental occurrence mechanism of Keshan disease in the loess area and the black soil area is different. Keshan disease can be induced in both low-selenium and sufficient-selenium environments, and environmental selenium should be one of the inducing factors of Keshan disease. This research provides a reference for predicting the areas where Keshan disease occurs and for disease prevention, and it can also serve in the prevention and control of endemic diseases.

Vascular catheter-related infections: an endemic disease in healthcare institutions. An opinion paper of the Spanish Society of Cardiovascular Infections (SEICAV).

Catheter-related infections (CRI) are a serious healthcare problem due to their potential to cause serious complications, including bacteraemia or infective endocarditis, and to increase patient morbidity and mortality. In addition, these in fections significantly prolong hospital stay and cost. Preventing CRI is crucial and is considered a criterion for quality and safety in healthcare. For these reasons, the Spanish Society of Cardiovascular Infections (SEICAV) has considered it pertinent to review this topic, with experts in different areas including clinical microbiologists, infectious disease specialists, surgeons and nurses. The data were presented at a session held at the Ramón Areces Foundation, which was organised in the form of specific questions grouped into three round tables. The first panel analysed the scale of the problem including epidemiological, clinical and diagnostic aspects; the second panel addressed advances in the treatment of CRI; and the third panel reviewed developments in the prevention of CRI. The recorded session is available on the Areces Foundation website and we believe it maybe of interest not only to health professionals, but also to any non-expert citizen interested in the subject.

Vaccination for communicable endemic diseases: optimal allocation of initial and booster vaccine doses.

For some communicable endemic diseases (e.g., influenza, COVID-19), vaccination is an effective means of preventing the spread of infection and reducing mortality, but must be augmented over time with vaccine booster doses. We consider the problem of optimally allocating a limited supply of vaccines over time between different subgroups of a population and between initial versus booster vaccine doses, allowing for multiple booster doses. We first consider an SIS model with interacting population groups and four different objectives: those of minimizing cumulative infections, deaths, life years lost, or quality-adjusted life years lost due to death. We solve the problem sequentially: for each time period, we approximate the system dynamics using Taylor series expansions, and reduce the problem to a piecewise linear convex optimization problem for which we derive intuitive closed-form solutions. We then extend the analysis to the case of an SEIS model. In both cases vaccines are allocated to groups based on their priority order until the vaccine supply is exhausted. Numerical simulations show that our analytical solutions achieve results that are close to optimal with objective function values significantly better than would be obtained using simple allocation rules such as allocation proportional to population group size. In addition to being accurate and interpretable, the solutions are easy to implement in practice. Interpretable models are particularly important in public health decision making.

Parallel multi-criteria decision analysis for sub-national prioritization of zoonoses and animal diseases in Africa: The case of Cameroon.

The use of multi-criteria decision analysis (MCDA) for disease prioritization at the sub-national level in sub-Sahara Africa (SSA) is rare. In this research, we contextualized MCDA for parallel prioritization of endemic zoonoses and animal diseases in The Adamawa and North regions of Cameroon. MCDA was associated to categorical principal component analysis (CATPCA), and two-step cluster analysis. Six and seven domains made of 17 and 19 criteria (out of 70) respectively were selected by CATPCA for the prioritization of zoonoses and animal diseases, respectively. The most influencing domains were "public health" for zoonoses and "control and prevention" for animal diseases. Twenty-seven zoonoses and 40 animal diseases were ranked and grouped in three clusters. Sensitivity analysis resulted in high correlation between complete models and reduced models showing the robustness of the simplification processes. The tool used in this study can be applied to prioritize endemic zoonoses and transboundary animal diseases in SSA at the sub-national level and upscaled at the national and regional levels. The relevance of MCDA is high because of its contextualization process and participatory nature enabling better operationalization of disease prioritization outcomes in the context of African countries or other low and middle-income countries.

Evaluation of the current situation of sheep production characteristics in Nkasi District, Tanzania

Abstract. Kapongo RY, Mbaga SH. 2024. Evaluation of the current situation of sheep production characteristics in Nkasi District, Tanzania. Intl J Trop Drylands 8: 44-57. This study was conducted in two divisions, Namanyere and Mkwamba of Nkasi District in the Rukwa Region, Tanzania, to assess the sheep production status of smallholder farmers. Eight wards, namely Namanyere, Mtenga, Chala, Swaila, Kipande, Sintali, Kate, and Isale, were surveyed from November 2010 to April 2011. The random sampling technique was adopted to get 20 respondents from each selected ward. Two villages from each ward were chosen randomly, whereby ten respondents were interviewed in each village. A structured questionnaire was used to collect data from smallholder farmers keeping sheep and was complimented by secondary data from the district council offices. The results showed that sheep strains kept mainly by smallholder farmers were variant crosses of local strains and Red Maasai. The strains were deemed tolerant to diseases/parasites, heat, and drought and had better carcasses. Most smallholder farmers adopted an extensive grazing system during both dry and wet seasons. Breeding was uncontrolled; however, rams were selected based on their body sizes, conformation, and performance (e.g., number of lambs per ewe's lifetime, age at first lambing, and lambing intervals). Traits such as disease tolerance, drought, and heat tolerance scored higher for most strains. The average age at first lambing was 6.5 months, the lambing interval was three months, and the average number of lambs per ewe's lifetime was 14. The constraints to sheep production mostly were poor market availability, endemic diseases, and mortality of lambs. On marketing, fewer sheep were sold in the market compared to goats, and the price was 22% lower than that of goats.

Schistosomal appendicitis: a case report

BackgroundSchistosomiasis is one of the endemic parasitic diseases in many developing countries. Despite this, appendicitis secondary to schistosomiasis is an uncommon condition even in some endemic areas. Schistosomal appendicitis, an incidentally discovered appendicitis associated with schistosomiasis histological findings, affects young males predominantly. Timely diagnosis and treatment, including appendectomy and anti-helminthic therapy, are crucial.Case reportA 24-year-old Sudanese male patient presented with abdominal pain. Diagnosed with acute appendicitis, he underwent appendectomy, revealing appendix inflammation with Schistosoma ova in histopathology. Abdominal ultrasound detected no complications. Weakly positive Schistosoma serology was noted, but stool and urine analysis showed no infection evidence. Prescribed praziquantel, patient had 3-year post-op follow-up without complications.ConclusionsThis case report underscores the significance of including schistosomiasis in the differential diagnosis of appendicitis, particularly in regions where the disease is endemic. It underscores the necessity of histopathological evaluations for accurate diagnosis, emphasizing the potential implications for clinical practice in similar settings.

Are phlebotomine sand flies (Diptera: Psychodidae) really attracted to UV-light sources?

Phlebotomine sand flies are the sole confirmed vector of leishmaniosis, a group of endemic and re-emerging diseases in southern European countries such as Spain. Light traps are the major surveillance method currently being employed. Nevertheless, color light attraction by sand flies remains mostly unknown. Following prior research, the effect of UV-LED light sources, and its synergic effect with different color lights has been evaluated employing a modified Flebocollect (FC) light trap model. Results suggest that female Phlebotomus perniciosus sand flies are more attracted to a FC trap lured with the combination of blue and UV LED light sources than commercial CDC (Center for Disease Control and prevention) traps (Bonferroni post-hoc test; p < 0.08; blue/UV mean = 0.50; CDC mean = 0.13), while the combination of red and UV modified-traps excel in capturing Sergentomyia minuta sand flies (Bonferroni post-hoc test; p < 0.04; blue/UV mean = 1.19; CDC mean = 0.66). However, based on our prior studies, incorporating UV light sources into sand fly traps does not seem to enhance their attractiveness, as it has not resulted in higher capture rates. These findings contribute to understanding how sand flies’ vision and light color detection is. Further research is recommended to standardize trap construction procedures and explore variations in different endemic regions according to different sand fly species.

A simple modification to the classical SIR model to estimate the proportion of under-reported infections using case studies in flu and COVID-19

BackgroundUnder-reporting and, thus, uncertainty around the true incidence of health events is common in all public health reporting systems. While the problem of under-reporting is acknowledged in epidemiology, the guidance and methods available for assessing and correcting the resulting bias are obscure. ObjectiveWe aim to design a simple modification to the Susceptible – Infected – Removed (SIR) model for estimating the fraction or proportion of reported infection cases. MethodsThe suggested modification involves rescaling of the classical SIR model producing its mathematically equivalent version with explicit dependence on the reporting parameter (true proportion of cases reported). We justify the rescaling using the phase plane analysis of the SIR model system and show how this rescaling parameter can be estimated from the data along with the other model parameters. ResultsWe demonstrate how the proposed method is cross-validated using simulated data with known disease cases and then apply it to two empirical reported data sets to estimate the fraction of reported cases in Missoula County, Montana, USA, using: (1) flu data for 2016–2017 and (2) COVID-19 data for fall of 2020. ConclusionsWe establish with the simulated and COVID-19 data that when most of the disease cases are presumed reported, the value of the additional reporting parameter in the modified SIR model is close or equal to one, so that the original SIR model is appropriate for data analysis. Conversely, the flu example shows that when the reporting parameter is close to zero, the original SIR model is not accurately estimating the usual rate parameters, and the re-scaled SIR model should be used. This research demonstrates the role of under-reporting of disease data and the importance of accounting for under-reporting when modeling simulated, endemic, and pandemic disease data. Correctly reporting the “true” number of disease cases will have downstream impacts on predictions of disease dynamics. A simple parameter adjustment to the SIR modeling framework can help alleviate bias and uncertainty around crucial epidemiological metrics (e.g.: basic disease reproduction number) and public health decision making.

No evidence of mpox virus circulation in putative animal reservoirs in Gabon wildlife

ObjectivesMpox is a neglected viral endemic tropical disease in Central and Western African countries transmitted to humans by an animal. However, the natural reservoir of the virus remains elusive. In this study, we looked for potential reservoirs of the mpox virus (MPXV) in Gabonese wildlife to prevent future outbreaks and enrich the literature with additional data on animal reservoirs. MethodsDNA was extracted from the livers and spleens from 2549 animals (bats [859], bushmeats [356], rodents [1309], and shrews [25]) collected between 2012 and 2021. DNA was analyzed by real-time and conventional polymerase chain reaction, targeting the 14 kD protein and the rpo subunit RNA polymerase of orthopoxviruses. ResultsNo MPXV DNA was detected despite the presence of potential host reservoirs such as Critcetomys, Crocidura, Praomys, and Atherurus africanus. This absence could be due to (i) the low number of animals collected for some species, (ii) the acute nature of mpox infection but also (iii) the lack of the potential reservoir Funisciurus anerythrus among collected animals, and (iv) the fact that the samplings are not included in the probable ecological niche of MPXV. ConclusionLongitudinal studies including potential ecological niches of F. anerythrus and MPXV in Gabon may be useful to get more information on MPXV circulation.

Prevalence Study and Overview of Rabies in the Province of Ouarzazate-Morocco

Background: Rabies is a cosmopolitan anthropozoonosis for which humans are accidental victims. In Morocco, rabies is an endemic disease, with new cases of human rabies reported every year. The aim of our study is to analyze the epidemiological aspects of rabies in the province of Ouarzazate. Materials and Methods: This is a retrospective study using records available at the Ouarzazate Municipal Hygiene Office. It includes 1,759 cases of exposure to animal bites between 2016 and 2019. Results: We identified 1,759 cases of animal bites during the period of 4 years of study, representing an average annual exposure rate of 190/100,000 inhabitants. Most cases were rural (65%). The median age of bitten cases was 28 years, with people under 15 years of age exposed in 32% of cases. Males predominate, with 61.3% of cases. Dogs are the main animal aggressors at 47.8%, followed by cats at 33%. The upper limbs are the preferred sites of aggression (89.2%). Exposure was grade III in 76.8% of cases. Lesions were multiple in 52.1% and superficial in 62.6%. No cases of human rabies have been recorded since 2001, despite 20 cases being exposed to a biologically confirmed rabid animal during our study. Conclusion: Rabies remains a public health concern in the province of Ouarzazate, despite the presence of a national rabies control program. Effective control of this zoonosis requires strengthening education and community engagement, as well as close collaboration between animal health and human health sectors for integrated management of bite cases.

A comprehensive analysis of non-pharmaceutical interventions and vaccination on Ebolavirus disease outbreak: Stochastic modeling approach.

Ebolavirus disease (EVD) outbreaks have intermittently occurred since the first documented case in the 1970s. Due to its transmission characteristics, large outbreaks have not been observed outside Africa. However, within the continent, significant outbreaks have been attributed to factors such as endemic diseases with similar symptoms and inadequate medical infrastructure, which complicate timely diagnosis. In this study, we employed a stochastic modeling approach to analyze the spread of EVD during the early stages of an outbreak, with an emphasis on inherent risks. We developed a model that considers healthcare workers and unreported cases, and assessed the effect of non-pharmaceutical interventions (NPIs) using actual data. Our results indicate that the implementation of NPIs led to a decrease in the transmission rate and infectious period by 30% and 40% respectively, following the declaration of the outbreak. We also investigated the risks associated with delayed outbreak recognition. Our simulations suggest that, when accounting for NPIs and recognition delays, prompt detection could have resulted in a similar outbreak scale, with approximately 50% of the baseline NPIs effect. Finally, we discussed the potential effects of a vaccination strategy as a follow-up measure after the outbreak declaration. Our findings suggest that a vaccination strategy can reduce both the burden of NPIs and the scale of the outbreak.

A feasibility study of controlled human infection with intradermal Bacillus Calmette-Guérin (BCG) injection: Pilot BCG controlled human infection model.

Tuberculosis (TB) caused 1.5 million deaths in 2020, making it the leading infectious killer after COVID-19. Bacille Calmette-Guerin (BCG) is the only licensed vaccine against TB but has sub-optimal efficacy against pulmonary TB and reduced effectiveness in regions close to the equator with high burden. Efforts to find novel vaccines are hampered due to the need for large-scale, prolonged, and costly clinical trials. Controlled human infection models (CHIMs) for TB may be used to accelerate vaccine development by ensuring only the most promising vaccine candidates are selected for phase 3 trials, but it is not currently possible to give participants Mycobacterium tuberculosis as a challenge agent. This study aims to replicate and refine an established BCG CHIM at the Liverpool School of Tropical Medicine. Participants will receive an intradermal injection with licensed BCG vaccine (Statens Serum Institut strain). In phase A, participants will undergo punch biopsy two weeks after administration, paired with minimally invasive methods of skin sampling (skin swab, microbiopsy, skin scrape). BCG detection by classical culture and molecular methods will be compared between these techniques and gold standard punch biopsy. Techniques meeting our pre-defined sensitivity and specificity criteria will be applied in Phase B to longitudinally assess intradermal BCG growth two, seven and fourteen days after administration. We will also measure compartmental immune responses in skin, blood and respiratory mucosa in Phase B. This feasibility study will transfer and refine an existing and safe model of BCG controlled human infection. Longitudinal BCG quantification has the potential to increase model sensitivity to detect vaccine and therapeutic responses. If successful, we aim to transfer the model to Malawi in future studies, a setting with endemic TB disease, to accelerate development of vaccines and therapeutics relevant for underserved populations who stand to benefit the most. Registration: ISRCTN: ISRCTN94098600 and ClinicalTrials.gov: NCT05820594.

Endemic La Crosse Virus Neuroinvasive Disease in North Carolina Residents: 2000-2020.

La Crosse virus neuroinvasive disease (LACVND) is the most common cause of arboviral encephalitis in children within the United States; in North Carolina, it is the most prevalent endemic mosquito-borne disease in humans. Here we report a surveillance summary of confirmed and probable LACVND during 2000-2020 using North Carolina Electronic Disease Surveillance System data, and we describe associated demographic characteristics, spatiotemporal distribution, clinical features, and mortality rates. A total of 355 cases (74.9% confirmed) were reported from 41 North Carolina counties; most cases (92%) occurred in 19 Western North Carolina counties. An average of 17 cases were reported annually with the majority (94%) of cases occurring between mid-June and early October (epiweeks 25-41). The median case age was nine years (range: 1-95 years), 79% were aged ≤ 18 years, and 56.6% were male. Cases commonly presented with headache (95.4%), fever (95.1%), and altered mental status (80.8%); encephalitis (82.0%) and meningitis (45.9%) were frequently diagnosed. Encephalitis was more common in children (87%) than adults (62%) (P < .001). Similarly, seizures were more common in children (54%) than adults (27%) (P < .01). The case fatality rate was 1.4%; however, differences in age-specific rates were observed. Changes in case definitions and reporting requirements, missing data, different reporting sources, and the retrospective nature of this study are all important limitations of our study. Given the persistent endemicity of La Crosse virus in Western North Carolina, clinicians and public health providers should consider La Crosse virus disease in all individuals, especially children, with compatible symptoms and a travel history to endemic counties. Prevention measures and educational outreach/public health messaging should focus on caregivers and children in Western North Carolina counties and during times when transmission risk is higher (i.e., summer and early fall).