Endemic Areas Research Articles

High-resolution early warning system for human Puumala hantavirus infection risk in Germany

The fluctuation of human infections by the Puumala orthohantavirus (PUUV) in Germany has been linked to weather and phenology parameters that drive the population growth of its host species. We quantified the annual PUUV-outbreaks at the district level by binarizing the reported infections in the period 2006–2021. With these labels we trained a model based on a support vector machine classifier for predicting local outbreaks and incidence well in advance. The feature selection for the optimal model was performed by a heuristic method and identified five monthly weather variables from the previous two years plus the beech flowering intensity of the previous year. The predictive power of the optimal model was assessed by a leave-one-out cross-validation in 16 years that led to an 82.8% accuracy for the outbreak and a 0.457 coefficient of determination for the incidence. Prediction risk maps for the entire endemic area in Germany will be annually available on a freely-accessible permanent online platform of the German Environment Agency. The model correctly identified 2022 as a year with low outbreak risk, whereas its prediction for large-scale high outbreak risk in 2023 was not confirmed.

Clinical usefulness of urinary symptoms and urinalysis in diagnosis of Schistosoma haematobium infection in an endemic area in Southern Nigeria: descriptive study

Background: Schistosoma haematobium infection occurs worldwide with the largest number of cases seen in sub-Saharan Africa. Most of the infections are acquired during childhood and are linked to urogenital diseases which contributes significantly to morbidity and mortality. A study on the use of urinary symptoms, signs and urinalysis in the diagnosis of S. haematobium infection might aid in providing early, prompt and rapid intervention that will limit associated complications. Methods: The study was a descriptive cross-sectional of 421 children aged 6-12 years in Ohaukwu LGA, Ebonyi State, recruited from four public primary schools using multistage sampling method. Urinary symptoms and signs were obtained using a questionnaire; urine samples were collected for urinalysis and urine microscopy. Simple proportions and odds ratio (CI) were used to analyze the data. Sensitivity, specificity, positive predictive value and negative predictive value were calculated for various symptoms and signs. The data was analyzed with IBM-SPSS 20. Significance was set at p<0.05. Results: The prevalence of S. haematobium infection among school children in Ohaukwu LGA was 30.17%. Visible blood in urine 71.77% and dysuria 70.16% were the predominant symptoms while liver tenderness 8.87% was the most common sign. The sensitivity vs specificity of visible blood in urine and microscopic haematuria were 71.77% vs 94.43% and 100.00% vs 97.21% respectively. Conclusions: Microscopic haematuria alone was highly sensitive and specific and can be a reliable alternative to the gold standard in making diagnosis of S. haematobium infection in children living in this endemic region.

Survey of Rickettsia species in hematophagous arthropods from endemic areas for Japanese spotted fever in China.

Japanese spotted fever (JSF) is caused by Rickettsia japonica, mainly vectored by hard ticks. However, whether R. japonica can be transmitted by other arthropods remains unknown. Moreover, it is of interest to investigate whether other Rickettsia species cause spotted fever in endemic areas. In this study, a survey of Rickettsia species was performed in hematophagous arthropods (mosquitoes, tabanids, and ticks) from endemic areas for JSF in Hubei Province, central China. The results showed that the diversity and prevalence of Rickettsia species in mosquitoes are low, suggesting that mosquitoes may not be the vector of zoonotic Rickettsia species. A novel Rickettsia species showed a high prevalence (16.31%, 23/141) in tabanids and was named "Candidatus Rickettsia tabanidii." It is closely related to Rickettsia from fleas and mosquitoes; however, its pathogenicity in humans needs further investigation. Five Rickettsia species were identified in ticks. Rickettsia japonica, the agent of JSF, was detected only in Haemaphysalis longicornis and Haemaphysalis hystricis, suggesting that they may be the major vectors of R. japonica. Notably, two novel species were identified in H. hystricis ticks, one belonging to the spotted fever group and the other potentially belonging to the ancestral group. The latter one named "Candidatus Rickettsia hubeiensis" may provide valuable insight into the evolutionary history of Rickettsia.

An Updated Economic Assessment of Moxidectin Treatment Strategies for Onchocerciasis Elimination.

Concerns that annual mass administration of ivermectin, the predominant strategy for onchocerciasis control and elimination, may not lead to elimination of parasite transmission (EoT) in all endemic areas have increased interest in alternative treatment strategies. One such strategy is moxidectin. We performed an updated economic assessment of moxidectin- relative to ivermectin-based strategies. We investigated annual and biannual community-directed treatment with ivermectin (aCDTI, bCDTI) and moxidectin (aCDTM, bCDTM) with minimal or enhanced coverage (65% or 80% of total population taking the drug, respectively) in intervention-naive areas with 30%, 50%, or 70% microfilarial baseline prevalence (representative of hypo-, meso-, and hyperendemic areas). We compared programmatic delivery costs for the number of treatments achieving 90% probability of EoT (EoT90), calculated with the individual-based stochastic transmission model EPIONCHO-IBM. We used the costs for 40 years of program delivery when EoT90 was not reached earlier. The delivery costs do not include drug costs. aCDTM and bCDTM achieved EoT90 with lower programmatic delivery costs than aCDTI with 1 exception: aCDTM with minimal coverage did not achieve EoT90 in hyperendemic areas within 40 years. With minimal coverage, bCDTI delivery costs as much or more than aCDTM and bCDTM. With enhanced coverage, programmatic delivery costs for aCDTM and bCDTM were lower than for aCDTI and bCDTI. Moxidectin-based strategies could accelerate progress toward EoT and reduce programmatic delivery costs compared with ivermectin-based strategies. The costs of moxidectin to national programs are needed to quantify whether delivery cost reductions will translate into overall program cost reduction.

Validation of a New Duplex Real-Time Polymerase Chain Reaction for Chlamydia trachomatis DNA Detection in Ocular Swab Samples.

Trachoma is the world-leading infectious cause of preventable blindness and is caused by the bacteria Chlamydia trachomatis. In developing countries, diagnosis is usually based on clinical evaluation. Serological-based tests are cheaper than molecular-based ones, but the latter are more sensitive and specific. The present study developed a new duplex qPCR which concomitantly detects the C. trachomatis cryptic plasmid and the human 18S rRNA gene, with an LOD95% for C. trachomatis DNA of 13.04 genome equivalents per reaction. The new qPCR was tested using 50 samples from an endemic area and 12 from a non-endemic area that were previously characterized using direct immunofluorescence assay (DFA) and clinical evaluation. Among the 50 endemic samples, 3 were found to be positive by clinical evaluation (6%), 18 were found to be positive by DFA (36%), and 48 were found to be positive by qPCR (96%). Next, the new duplex qPCR was validated using 50 samples previously characterized by qPCR. Validation was carried out on a benchtop instrument (ABI7500) or on a portable point-of-care instrument (Q3-Plus), showing 95% specificity and 100% sensitivity. The ubiquitous presence of C. trachomatis DNA in samples from the endemic region confirms that constant monitoring is of paramount importance for the effective measurement of the elimination of trachoma. The newly developed duplex qPCR presented in this study, along with its validation in a portable qPCR system, constitutes important tools toward achieving this goal.

Echinococcus granulosus Sensu Stricto and Echinococcus multilocularis in a Gray Wolf (Canis lupus) in Turkey: Further Evidence for Increased Risk of Alveolar Echinococcosis in Urban Areas.

The aim of this study was to identify Echinococcus species by morphological and molecular means. A dead gray wolf (Canis lupus) was found near Erzurum province and brought to the parasitology laboratory. Sedimentation and counting technique (SCT) and polymerase chain reaction (PCR) analysis were conducted. The SCT implications indicated that the wolf had a substantial worm burden (62,720 and 49,280 parasites) due to a co-infection of E. granulosus s.l. and E. multilocularis. Genus/species-specific PCR was used to analyze DNA extracted from adult worms and confirmed as E. granulosus s.s. and E. multilocularis, utilizing COI and 12S rRNA gene sequence analysis, respectively. This report presents the first co-detection of E. granulosus s.s. and E. multilocularis in a gray wolf found in an urban area in a highly endemic area for human echinococcosis in northeastern Turkey. The results emphasize that AE is not only a problem of rural areas, but also occurs in urban areas, which may pose a threat to public health. Therefore, surveillance in urban areas is crucial. The need to develop new control strategies for domestic and wildlife in the study area is also highlighted.

Masqueraders Around Disaster: Clinical Features of Scrub Typhus in Fukushima, Japan.

Scrub typhus (ST) is endemic in Fukushima, with the largest number of cases reported in Japan from 2009 to 2010. Although ST is highly treatable, its atypical clinical presentation impedes diagnosis, causing delays in treatment. We review the clinical features of ST in adults from 2008 to 2017 at Ohta Nishinouchi General Hospital in Fukushima, Japan. Fifty-five cases (serotype Karp 24, Irie/Kawasaki 21, Hirano/Kuroki 10) of ST were confirmed via serology based on elevated immunoglobulin (Ig)M and IgG and polymerase chain reaction positivity of eschar samples. The mean age was 69 years, and 64% were female. The case fatality rate was 1.8% (1/55). Approximately 70% of cases (38/55) were not diagnosed as ST upon the initial clinic visit. Inappropriate use of antibiotics was identified in 22% of cases (12/55). In terms of atypical clinical features, 1 or more of the manifestations, fever, rash, and eschar, was absent in 31% of cases (17/55). Approximately 11% of cases presented without eschar (6/55; Karp 1, Irie/Kawasaki 1, Hirano/Kuroki 4). Moreover, severe complications were observed with shock and disseminated intravascular coagulation in 7% of cases (4/55), Thus, while 53% of cases presented with the typical triad (29/55), unusual complications and atypical features occurred in 40% (22/55). Diagnosis of ST becomes clinically challenging in the absence of typical features. In Fukushima, an endemic area of ST, an atypical presentation involving multisystem disease is common.

Geospatial analysis and prevalence of Schistosoma mansoni and soil-transmitted helminth infections in an endemic area in Eastern Brazilian Amazon.

This study evaluated the occurrence of Schistosoma mansoni and soil-transmitted helminths in an endemic area in the Eastern Brazilian Amazon, analysing prevalence and spatial distribution. The study was conducted in four localities of Primavera Municipality, in Pará state. Data was obtained from the Decit 40/2012 project and the participants were divided into five age range categories for evaluation: children, adolescents, young adults, adults and elderly individuals. For the diagnostic tests, Kato-Katz slides were prepared to detect S. mansoni and soil-transmitted helminths eggs. The spatial distribution map and the Kernel Density Estimation were performed to assess the presence and location of infections. Stool samples revealed the presence of hookworms, S. mansoni, Ascaris lumbricoides and Trichuris trichiura eggs. Mono-, bi- and poly-parasitic infections were observed, with a significant prevalence of hookworm monoparasitism. The high frequency of children infected with soil-transmitted helminths confirms their significance as an ongoing public health problem in the poorest municipalities of Brazil. The Geographic Information System plays a crucial role in environmental surveillance and in the control of epidemics and endemic diseases, enabling accurate assessment and informed decision-making for their control.

Nanopore adaptive sampling of a metagenomic sample derived from a human monkeypox case.

In 2022, a series of human monkeypox cases in multiple countries led to the largest and most widespread outbreak outside the known endemic areas. Setup of proper genomic surveillance is of utmost importance to control such outbreaks. To this end, we performed Nanopore (PromethION P24) and Illumina (NextSeq. 2000) Whole Genome Sequencing (WGS) of a monkeypox sample. Adaptive sampling was applied for in silico depletion of the human host genome, allowing for the enrichment of low abundance viral DNA without a priori knowledge of sample composition. Nanopore sequencing allowed for high viral genome coverage, tracking of sample composition during sequencing, strain determination, and preliminary assessment of mutational pattern. In addition to that, only Nanopore data allowed us to resolve the entire monkeypox virus genome, with respect to two structural variants belonging to the genes OPG015 and OPG208. These SVs in important host range genes seem stable throughout the outbreak and are frequently misassembled and/or misannotated due to the prevalence of short read sequencing or short read first assembly. Ideally, standalone standard Illumina sequencing should not be used for Monkeypox WGS and de novo assembly, since it will obfuscate the structure of the genome, which has an impact on the quality and completeness of the genomes deposited in public databases and thus possibly on the ability to evaluate the complete genetic reason for the host range change of monkeypox in the current pandemic.

Magnetic resonance imaging features and classification of intraspinal echinococcosis

ObjectiveThis study aimed to investigate the magnetic resonance imaging (MRI) features and classification of echinococcosis of the spinal canal. MethodsThe clinical manifestations and MRI findings and classification of 19 patients diagnosed with intraspinal echinococcosis over 10 years (2011–2020) were retrospectively analyzed. ResultsThe mean age of the nine males and 10 females was 39 years (range 28–65 years). Among these, the number of cases with thoracic, lumbar, sacral, thoracolumbar, and lumbosacral, cervical, and lumbar segments was nine (47 %), five (26 %), one (5 %), one (5 %), two (11 %), and one (5 %) cases, respectively. Furthermore, 13 cases (69 %) involved adjacent vertebral bodies, accessories, and surrounding soft tissues. The lesion was confined to the intramedullary, extramedullary subdural, extramedullary epidural, and multiple spaces in one (Type I) (5 %), four (Type II) (21 %), one (Type III) (5 %), and thirteen (69 %) cases, respectively. Moreover, nine cases (47 %) had a history of hydatid disease in the spine or other tissues. The clinical manifestations were chest and lumbosacral pain in 18 cases (95 %) and chest and lumbosacral pain accompanied by lower limb dysfunction in four cases (21 %). The MRI revealed different sizes of T1WI low-signal and T2WI high-signal vesicles with a “grape-like” appearance, with 16 cases (84 %) showing low signals on the edge of the cyst wall. ConclusionIntraspinal echinococcosis is rare, even in endemic areas. However, intraspinal echinococcosis should be considered when there is a history of echinococcosis in other sites or when there are clear MRI characteristics for the disease.

Field sensitivity and specificity of the SD BIOLINE onchocerciasis IgG4 Rapid Diagnostic Test in children

Skin biopsies (Skin snips) have historically been the gold standard for the diagnosis of onchocerciasis. However, in low prevalence areas and in areas with successful ivermectin mass drug administration (MDA) programs, skin snips are not sensitive enough to decide when to stop MDA; thus, serological diagnostic tools have been recommended for this purpose. This study assessed the sensitivity and specificity of the Ov16 Rapid Diagnostic Test (SD BIOLINE Onchocerciasis RDT) compared to skin snip in endemic areas undergoing ivermectin mass distribution using Community Directed Treatment with Ivermectin (CDTI) strategy. A cross-sectional study was conducted between September and November 2016 in five endemic villages in the Cascades region in Burkina Faso. Children aged 2 to 9-years were examined during the impact epidemiological survey using both the skin snip and Ov16 Rapid Diagnostic Test. The Ov16 Rapid Diagnostic Test sensitivity and specificity were determined with reference to the skin biopsy. Skin snip positivity was 1.25% in this population, while seroprevalence was 6.5%. When compared to the skin snip as the gold standard, the sensitivity of the Ov16 Rapid Diagnostic Test was 60% and the specificity 94%. When the Ov16 Rapid Diagnostic Test was considered as the gold standard, the skin snip exhibited a sensitivity of 11.5% and a specificity of 99.5%. These results are similar to other studies comparing the performance of the Ov16 ELISA to skin snips, suggesting that the Ov16 RDT may be a useful tool for ivermectin STOP MDA and post transmission surveys, assuming that the prevalence of infection is low or close to zero, and the Ov16 RDT detected also pre patent infections.

Recurrent Chagas' disease meningomyelitis in an HIV-infected patient.

Chagas' disease reactivation leading to monophasic acute or subacute meningoencephalitis or space-occupying lesions is a well-described AIDS-defining condition in Latin America. We report a 59-year-old man native from the Northeast region of Brazil, with a second episode of subacute chagasic meningomyelitis. He had long-term multidrug-resistant HIV and had abandoned combined antiretroviral therapy (CD4+ lymphocyte count, 16 cells/mm³, and HIV viral load 169 403 copies/mL). He initially received benznidazole but switched to nifurtimox after developing myelotoxicity. He was discharged home having made a partial neurological improvement. Chagas' disease should be included in the differential diagnosis of meningomyelitis in people living with HIV/AIDS who are from endemic areas of this parasitic disease.

Unveiling the threat: Balochistan's path to congo virus endemicity

Dear Madam, The detection of 16 cases of Crimean Congo Haemorrhagic Fever Virus (CCHFV) in the Balochistan province this year (1) and a 2020 study indicating a seroprevalence of 2.7% in humans and 36.2% in livestock in Pakistan, with Balochistan showing a significantly higher prevalence in the collected samples (2), has raised concerns about the region's susceptibility to becoming an endemic area for this tick-borne zoonotic disease. Balochistan's arid climate creates an ideal environment for Hyalomma Marginatum ticks to thrive, thereby increasing the risk of transmission. Rural areas, which constitute a significant proportion of Balochistan, are generally more affected due to livestock farming, which plays a significant role in Pakistan’s economy. However, urban areas in Pakistan experience higher infection rates during Eid-Ul-Adha when there is a large-scale animal trade, with increased incidence in high-risk groups, like butchers, veterinarians, and healthcare professionals. The region also encounters challenges due to the cross-border movement of livestock and infected individuals with neighbouring countries, like Afghanistan and Iran, where the virus is endemic (3). Another contributing factor to the endemicity of the virus is the perception of neglect, resulting in limited resources, inadequate vector control and healthcare infrastructure, and insufficient awareness and preventive measures (3), which create significant obstacles in the early detection and management of virus-borne diseases. A Bulgarian vaccine introduced in 1974 led to a decline in cases from 1974 to 1996, but there is insufficient statistical evidence to attribute this decline solely to the vaccine. Thus, there is no universally recognised vaccination available for the virus currently. However, researchers are working to create an effective vaccine (4). Currently, treatment for CCHFV involves supportive care and antivirals, like ribavirin. Although treatments-FDA-approved treatments in use, including steroids, convalescent serum, and specific immunoglobulins, it’s important to note that these treatments are experimental and require further evaluation of their efficacy and safety profile (5). The most effective approach to reducing the prevalence of CCHFV in Balochistan is through prevention methods, including raising awareness among high-risk groups, especially butchers who should wear appropriate protection, handle slaughter in designated areas, and ensure proper waste disposal (4). It is also crucial to discourage tourists from visiting areas where ticks are prevalent, and local law enforcement should limit the unrestricted movement of livestock. Additionally, programmes should be introduced to vaccinate animals against the virus, and suspected animals should be quarantined.

The Vicious Worm education tool improves the knowledge of community health workers on Taenia solium cysticercosis in Rwanda.

The pork tapeworm Taenia solium causes human taeniasis and cysticercosis when ingested as viable cysts and eggs, respectively. Despite its high health burden in low-income countries, knowledge of the parasite in endemic areas such as Rwanda is often limited. Here, we assess whether The Vicious Worm education software can increase knowledge in endemic areas of Rwanda. A cross-sectional mixed-methods study was conducted to evaluate knowledge about T. solium among community health workers trained using the Vicious Worm education software. Knowledge was assessed before, immediately after, and four weeks after the training. The health workers perceptions of the software were analysed thematically. A total of 207 community health workers were recruited from Nyamagabe district in Southern Province, Rwanda. Participants were composed of males (33.5%) and females (66.5%), aged between 22 and 68 years, and most (71%) had only completed primary education. Knowledge of cysticercosis at baseline was low, particularly knowledge of human cysticercosis and neurocysticercosis. The overall knowledge score increased significantly after training and was maintained four weeks after the training. Overall, insufficient knowledge was associated with neurocysticercosis-related questions, which after the training, remained relatively lower compared to questions of other categories. Participants reported the software to be user-friendly and educational. Digital illiteracy and the lack of smartphones were among the critical challenges highlighted in responses. This study has shown gaps in knowledge regarding T. solium infections within rural Rwanda, particularly neurocysticercosis. Health education using the Vicious Worm education software should be considered in integrated control programs.

Screening of voluntary blood donors for beta-thalassemia trait in an endemic area in Northwest India for 15 years: Results and future directions after screening more than 300 thousand donors

Abstract: BACKGROUND: North-West India has a high prevalence of the Thalassemia, and the Beta Thalassemia Trait often remains undetected in the population. Recognizing the need to address this public health issue, we initiated “Blood the Lifeline” project in 2006 with the aim to eradicate Thalassemia through proactive measures, including screening of voluntary blood donors. AIM: The primary aim of this study was to screen voluntary blood donors in an endemic area in northwestern India for Thalassemia trait. The study aimed to determine its prevalence, identify gender and ethnic group-wise distributions, and assess the implications for future interventions. METHODS: The screening program was conducted from January 2006 till December 2022. Voluntary blood donors were recruited from the target area and underwent Thalassemia trait screening. The screening process involved High Performance Liquid Chromatography using VARIANT II fully automated HPLC system to identify Thalassemia trait. Data regarding the total number of cases screened, gender distribution, ethnic group-wise distribution, and positive and negative cases were collected and analyzed. Screening Process: EDTA Pilot tube from each donor was collected and analyzed within 24 hrs of collection. RBC Counts, Hb Concentration, MCV, MCH, RDW-SD were noted to differentiate between Iron Deficiency Anaemia & thalassemia trait & following Criteria’s were taken into account: Total RBC Count: > 5.0 x 106 / micro-liter, Hb: < 11.7 g/dl, MCV: < 77 fl, MCH: < 28 pg & RDW-SD: < 45 fl. A combination of Formulas like Mentzer’s index= MCV/RBC <13; Shine and Lal Index (S&L) = MCV × (MCH/100) < 1530; Green & King (MCV2) × RDW]/ (Hb × 100) < 65 were used for screening. All the above formulas were introduced into the Blood Bank Software to exclude out the blood units requiring screening & confirmation. If any of the samples were positive on initial screening, then confirmatory test was done by demonstrating the elevation of concentration of HbA2 by HPLC VARIANT II fully automated analyser. RESULTS: A total of 377,503 voluntary blood donors for a 16 year period were screened and data was analysed .The Mean Hemoglobin of positive donors was 12.1 gm/dl; Mean RBC Count was 6.24 m/cu mm, MCV 67.79 fl, MCH 21.04 pg, RDW-SD 42.11fl & HbA2 was 7.48%. The majority of positive cases were found in the Sindhi (16.68%), Punjabi (10.32%), and Muslim (9.81%) ethnic groups. The Rajasthani population accounted for 6.01% of positive cases. CONCLUSION: This comprehensive screening program revealed a relatively high prevalence of Thalassemia trait in 2.29% of the screened population. The communities with higher prevalence (Sindhi, Punjabi, and Muslim) were educated about the disease and a targeted screening program will be further carried out in these ethnic groups. The data helped in planning genetic counseling, carrier screening, and pre-marital screening programs to reduce the transmission of Thalassemia in these populations. By focusing efforts on specific groups and locations with higher prevalence, a community based approach to prevent the birth of children with Thalassemia major is being implemented. It is also being used for analyzing the implications of different local policies pertaining to Thalassemia trait in the region. Collaborative efforts between healthcare organizations, community leaders, and governmental agencies are crucial to address the burden of Thalassemia and work towards its eradication. The results of this study serve as a foundation for future initiatives aimed at minimizing the impact of Thalassemia at a community level.

A Theileria annulata parasite with a single mutation, methionine 128 to isoleucine (M128I), in cytochrome B is resistant to buparvaquone.

Tropical theileriosis is a fatal leukemic-like disease of cattle caused by the tick-transmitted protozoan parasite Theileria annulata. The economics of cattle meat and milk production is severely affected by theileriosis in endemic areas. The hydroxynaphtoquinone buparvaquone (BPQ) is the only available drug currently used to treat clinical theileriosis, whilst BPQ resistance is emerging and spreading in endemic areas. Here, we chronically exposed T. annulata-transformed macrophages in vitro to BPQ and monitored the emergence of drug-resistant parasites. Surviving parasites revealed a significant increase in BPQ IC50 compared to the wild type parasites. Drug resistant parasites from two independent cloned lines had an identical single mutation, M128I, in the gene coding for T. annulata cytochrome B (Tacytb). This in vitro generated mutation has not been reported in resistant field isolates previously, but is reminiscent of the methionine to isoleucine mutation in atovaquone-resistant Plasmodium and Babesia. The M128I mutation did not appear to exert any deleterious effect on parasite fitness (proliferation and differentiation to merozoites). To gain insight into whether drug-resistance could have resulted from altered drug binding to TaCytB we generated in silico a 3D-model of wild type TaCytB and docked BPQ to the predicted 3D-structure. Potential binding sites cluster in four areas of the protein structure including the Q01 site. The bound drug in the Q01 site is expected to pack against an alpha helix, which included M128, suggesting that the change in amino acid in this position may alter drug-binding. The in vitro generated BPQ resistant T. annulata is a useful tool to determine the contribution of the various predicted docking sites to BPQ resistance and will also allow testing novel drugs against theileriosis for their potential to overcome BPQ resistance.

M. tuberculosis Infection Attributable to Exposure in Social Networks of Tuberculosis Cases in an Urban African Community.

The persistence of tuberculosis today and its global disparity send a powerful message that effective tuberculosis control must respond to its regional epidemiology. Active case finding through contact investigation is a standard protocol used for tuberculosis control, but its effectiveness has not been established, especially in endemic areas. To quantify the potential effectiveness of contact investigation in Kampala, Uganda, we used a cross-sectional design to evaluate the social networks of 123 tuberculosis index cases and 124 controls without tuberculosis. Tuberculous infection was present in 515 of 989 tuberculosis case contacts (52.1%) and 396 of 1026 control contacts (38.6%; adjusted prevalence ratio, 1.4; 95% CI, 1.3-1.6). The proportion of infected participants with known exposure within the social network of the tuberculosis case was 35%. The population-attributable fraction was 11.1% for any known exposure, with 7.3% attributable to household exposure and 3.4% attributable to extrahousehold exposure. This low population-attributable fraction indicates that contact tracing in the social networks of index cases will have only a modest effect in reducing tuberculous infection in a community. New approaches to community-level active case finding are needed.

Post-kala-azar dermal leishmaniasis (PKDL) drug efficacy study landscape: A systematic scoping review of clinical trials and observational studies to assess the feasibility of establishing an individual participant-level data (IPD) platform.

Post-kala-azar dermal leishmaniasis (PKDL) is a dermatosis which can occur after successful treatment of visceral leishmaniasis (VL) and is a public health problem in VL endemic areas. We conducted a systematic scoping review to assess the characteristics of published PKDL clinical studies, understand the scope of research and explore the feasibility and value of developing a PKDL individual patient data (IPD) platform. A systematic review of published literature was conducted to identify PKDL clinical studies by searching the following databases: PubMed, Scopus, Ovid Embase, Web of Science Core Collection, WHO Global Index Medicus, PASCAL, Clinicaltrials.gov, Ovid Global Health, Cochrane Database and CENTRAL, and the WHO International Clinical Trials Registry Platform. Only prospective studies in humans with PKDL diagnosis, treatment, and follow-up measurements between January 1973 and March 2023 were included. Extracted data includes variables on patient characteristics, treatment regimens, diagnostic methods, geographical locations, efficacy endpoints, adverse events and statistical methodology. A total of 3,418 records were screened, of which 56 unique studies (n = 2,486 patients) were included in this review. Out of the 56 studies, 36 (64.3%) were from India (1983-2022), 12 (21.4%) from Sudan (1992-2021), 6 (10.7%) were from Bangladesh (1991-2019), and 2 (3.6%) from Nepal (2001-2007). Five (8.9%) studies were published between 1981-1990 (n = 193 patients), 10 (17.9%) between 1991-2000 (n = 230 patients), 10 (17.9%) between 2001-2010 (n = 198 patients), and 31 (55.4%) from 2011 onwards (n = 1,865 patients). Eight (14.3%) were randomised clinical trials, and 48 (85.7%) were non-randomised studies. The median post-treatment follow-up duration was 365 days (range: 90-540 days) in 8 RCTs and 360 days (range: 28-2,373 days) in 48 non-randomised studies. Disease diagnosis was based on clinical criterion in 3 (5.4%) studies, a mixture of clinical and parasitological methods in 47 (83.9%) and was unclear in 6 (10.7%) studies. Major drugs used for treatment were miltefosine (n = 636 patients), liposomal amphotericin B (L-AmB) (n = 508 patients), and antinomy regimens (n = 454 patients). Ten other drug regimens were tested in 270 patients with less than 60 patients per regimen. Our review identified studies with very limited sample size for the three major drugs (miltefosine, L-AmB, and pentavalent antimony), while the number of patients combined across studies suggest that the IPD platform would be valuable. With the support of relevant stakeholders, the global PKDL community and sufficient financing, a PKDL IPD platform can be realised. This will allow for exploration of different aspects of treatment safety and efficacy, which can potentially guide future healthcare decisions and clinical practices.

Effect of PCV-2 Vaccination on Cytokines Gene Expression Profile in Wild Boar Peripheral Blood Mononuclear Cells after Stimulation with Mycobacteria Antigens

Wild boar (Sus scrofa) is a common wild ungulate known as the most important reservoir of tuberculosis (TB) in Spain. The severity of TB lesions in this species and the high prevalence of porcine circovirus type 2 (PCV-2) have been related. PCV-2 is ubiquitous in swine populations, being usual for the free-living ones the contact with this agent. Recent studies found a correlation between a decrease of generalised TB prevalence in wild boar populations and the PCV-2-vaccination. The aim of this study was to find out if PCV-2 vaccination modulates the gene expression of cytokines from immune cells after its exposition with mycobacterial antigens using an in vitro methodology. A total of 46 wild boars from a PCV-2 infection endemic area were blood-sampled before and after the PCV-2 vaccination of 22 of them. Peripheral blood mononuclear cells (PBMC) were obtained and isolated from these samples. Aliquots of the cells were in vitro cultured and respectively stimulated with PPDa, PPDb, and a mitogen. A complete analysis of the gene expression of cytokines from the cultured PBMC was carried out. Also, Mycobacterium bovis and PCV-2 contacts were revealed by ELISA and/or qPCR. The results demonstrated that the animals which have had contact with PCV-2 and had been vaccinated, manifested a significant decrease in gene expression of proinflammatory cytokines, like interleukin 1 beta, interleukin 6, and tumour necrosis factor-alpha, possibly related with the severity of TB lesions, and also a significant decrease of interleukin 10, a key cytokine. In conclusion, in case of possible infection or contact events with the virus, PCV-2 vaccination could be an effective measure to reduce the TB severity in wild boar populations, which could decrease the intra and interspecies transmission of TB.

Bilateral multifocal chorioretinitis as the only presentation of acute West Nile virus infection: a case report.

To describe a case of bilateral multifocal chorioretinitis as the only presentation of acute West Nile virus (WNV) infection in the absence of neurological involvement. A 78-year-old Italian woman was admitted to our emergency department because she noticed blurry vision in both eyes. She did not report fever, fatigue, or neurological symptoms in the last few days. Multimodal imaging showed the presence of bilateral hyperfluorescent lesions with a linear distribution, that corresponded to hypocyanescent spots on indocyanine green angiography. Antibody serology showed the presence of IgM antibodies, IgG antibodies, and ribonucleic acid (RNA) for WNV. Magnetic resonance imaging (MRI) of the brain ruled out central nervous system involvement. Three months later, the patient reported spontaneous resolution of her symptoms and remission of the chorioretinal infiltrates. In endemic areas, it is important to think of acute WNV infection as an explanatory etiology in cases of multifocal chorioretinitis, even without neurological involvement.