Introduction of New Dengue Virus Lineages of Multiple Serotypes after COVID-19 Pandemic, Nicaragua, 2022.

Major dengue epidemics throughout Nicaragua's history have been dominated by 1 of 4 dengue virus serotypes (DENV-1-4). To examine serotypes during the dengue epidemic in Nicaragua in 2022, we performed real-time genomic surveillance in-country and documented cocirculation of all 4 serotypes. We observed a shift toward co-dominance of DENV-1 and DENV-4 over previously dominant DENV-2. By analyzing 135 new full-length DENV sequences, we found that introductions underlay the resurgence: DENV-1 clustered with viruses from Ecuador in 2014 rather than those previously seen in Nicaragua; DENV-3, which last circulated locally in 2014, grouped instead with Southeast Asia strains expanding into Florida and Cuba in 2022; and new DENV-4 strains clustered within a South America lineage spreading to Florida in 2022. In contrast, DENV-2 persisted from the formerly dominant Nicaragua clade. We posit that the resurgence emerged from travel after the COVID-19 pandemic and that the resultant intensifying hyperendemicity could affect future dengue immunity and severity.

The epidemiology and clinical features of the neglected myiasis: A pilot surveillance study from Oman.

BACKGROUND: Myiasis is a neglected disease, characterized by ill-defined diagnostics and management protocols. Published epidemiological and clinical studies of myiasis are still scarce, although several countries, such as Oman, have reported a few cases over the past 30 years. This study explores the epidemiological profile and clinical characteristics of myiasis in South Batinah Governorate (SBG), Oman. METHODOLOGY: A prospective surveillance study was conducted in SBG from 1st November 2018 to 31st October 2019. Clinical and epidemiological data were collected using a pre-designed reporting form for suspected and confirmed cases. RESULTS: A total of 188 cases were reported, of which 81.4% were male. One-third of cases were 11-20 years old, and a quarter reported exposure inside house. The rate of exposure was 16 per 10000 in Nakhal and Wadi Mawel. About 57% patients reported multiple re-exposure. Almost 60% of patients developed nasal or oral myiasis, 25% developed myiasis in the eye, and 4% in the ear. The most common respiratory symptoms were cough (83%), runny nose (48%), and foreign body sensation (35%). Over 50% of patients with eye exposures had redness, pain, and itchiness. Most patients (89.3%) kept animals at homes. Many cases occurred between December 2018 and April 2019, with almost one-third of exposures occurring at 5 p.m. Re-exposure likelihood for patients residing in Nakhal and Wadi Mawel was high; OR = 2.49 (95% CI 1.14-5.45), with OR = 3.59 (95% CI 1.37-9.39) for 11-20-year-olds and, OR = 3.01 (95% CI 1.07-8.42) for patients ≥ 31 years. CONCLUSION: The myiasis exposure rate is high in certain areas and age groups, which is most likely associated with animal-related activities. The disease has a significant impact upon people's health in SBG. Therefore, urgent active-surveillance and clinical studies are warranted to explore possible preventive measures and treatment options. Adopting one health approach could offer an effective strategy for preventing myiasis in human and animal populations.

Phylogenetic and immunological investigations of complete TSA56 ORF of Orientia tsutsugamushi present in acute encephalitis syndrome cases from eastern Uttar Pradesh, India.

Scrub typhus (ST) caused by Orientia tsutsugamushi (OT), has long been known to cause acute encephalitis syndrome (AES) and acute febrile illness (AFI). The immunodominant 56 kDa protein of OT, which is encoded by the 56 kDa gene (1600 bp encoding 516-541 amino acids) is a commonly studied antigen for genotype and serotype assignment. Previous studies from India have utilized partial type specific antigen (TSA) 56 kDa sequences for OT strain characterisation. On the other hand, understanding the antigenic diversity of current OT strains, is critical for developing specific diagnostic tests and vaccines against ST. As a result, the current study analyses antigenic variants using the entire TSA56 ORF of OT from AES cases. Phylogenetic investigation using complete TSA56 ORF sequences revealed Karp and Gilliam were the circulating predominant strains of OT. Furthermore, Immuno-informatical analysis demonstrated that the majority of high-binding affinity CD4 TCEs against the most prevalent Indian human leukocyte antigen alleles were present in the S-VDIII/IV and S-VDIV spacer regions of TSA56 ORF. TSA56 conserved spacer is crucial for OT immunological response investigations. Further, the pathophysiological effects of spacer domains in ST require further investigation. Furthermore, the characterization of the TSA56 spacer region of the OT from different parts of India is critical for developing region-specific ST diagnostic assays and vaccines.

Cranial vault reduction cranioplasty for severe macrocephaly due to holoprosencephaly and subdural hygroma: a case report.

BACKGROUND: Severe macrocephaly can still be found in developing countries. This condition is usually caused by neglected hydrocephalus and can cause a lot of morbidities. Cranial vault reconstruction cranioplasty is the main treatment option for severe macrocephaly. Holoprosencephaly is often seen with features of microcephaly. Hydrocephalus should be considered as the main cause in HPE patients with features of macrocephaly. In this report, we present a rare case of cranial vault reduction cranioplasty procedure in patient with severe macrocephaly due to holoprosencephaly and subdural hygroma. CASE DESCRIPTION: A 4-year-10-month-old Indonesian boy was admitted with head enlargement since birth. He had a history of VP shunt placement when he was 3 months old. But the condition was neglected. Preoperative head CT showed massive bilateral subdural hygroma that compressed brain parenchyma caudally. From the craniometric calculation, the occipital frontal circumference was 70.5 cm with prominent vertex expansion, the distance between nasion to inion was 11.91 cm and the vertical height was 25.59 cm. The preoperative cranial volume was 24.611 cc. The patient underwent subdural hygroma evacuation and cranial vault reduction cranioplasty. The postoperative cranial volume was 10.468 cc. CONCLUSION: Subdural hygroma can be a rare cause of severe macrocephaly in holoprosencephaly patients. Cranial vault reduction cranioplasty and subdural hygroma evacuation is still the main treatment option. Our procedure successfully reduces significant cranial volume (57.46% volume reduction).

Epidemiology and complications of snakebite in rural area of Badin and Thar Sind, Pakistan.

OBJECTIVE: To identify the population at risk of snakebite, the peak season and the site of bite. METHODS: The retrospective study was conducted at the Indus Hospital, Badin, Pakistan, and comprised data of patients bitten by snake between January 2017 and December 2020 in the rural area of the Sindh province who presented to the emergency room and were treated according to the institutional protocol. Data was collected on a structured proforma. Data was analysed using SPSS 21. RESULTS: Of the 695 patients, 517(74.4%) were males and 178(25.6%) were females. The overall mean age was 29.9±15.7 years. Majority of the patients were farmers 294(42.3%), followed by labourers 195(28.1%). The most common site of snakebite was foot 556(80%). In 476(68.5%) cases, the snake type was not identified. Viper bite was noted in 193(28.2%) cases. Proteinuria, haematuria and renal dysfunction were observed in 302(43.5%), 302(43.5%) and 112(16.1%) patients, while leucocytosis, raised prothrombin time and low platelets were found in 305(43.5%), 268 (38.6%) and 100(14.4%) patients, respectively. Maximum number of cases took place in the peak summer month of July 112(16.1%). There were 8(1.2%) mortalities. CONCLUSIONS: Morbidity and mortality by snakebite was found to be prevalent in the study site, calling for preventing strategies.

Neurological disease caused by Oropouche virus in northern Brazil: should it be included in the scope of clinical neurological diseases?

We describe two neurological cases of Oropouche virus infection in northern Brazil, where the virus is endemic but neglected as a pathogen. This study reiterates the necessity of developing protocols for diagnosing infections and training medical personnel to recognize the pathogenicity of Oropouche virus in neurological infections.

Whipworm Infection Promotes Bacterial Invasion, Intestinal Microbiota Imbalance, and Cellular Immunomodulation.

Infections with Trichuris trichiura are among the most common causes of intestinal parasitism in children worldwide, and the diagnosis is based on microscopic egg identification in the chronic phase of the infection. During parasitism, the adult worm of the trichurid nematode maintains its anterior region inserted in the intestinal mucosa, which causes serious damage and which may open access for gut microorganisms through the intestinal tissue. The immune-regulatory processes taking place during the evolution of the chronic infection are still not completely understood. By use of the Swiss Webster outbred mouse model, mice were infected with 200 eggs, and tolerance to the establishment of a chronic Trichuris muris infection was induced by the administration of a short pulse of dexamethasone during nematode early larval development. The infected mice presented weight loss, anemia, an imbalance of the microbiota, and intense immunological cell infiltration in the large intestine. It was found that mice have a mixed Th1/Th2/Th17 response, with differences being found among the different anatomical locations. After 45 days of infection, the parasitism induced changes in the microbiota composition and bacterial invasion of the large intestine epithelium. In addition, we describe that the excretory-secretory products from the nematode have anti-inflammatory effects on mouse macrophages cultured in vitro, suggesting that T. muris may modulate the immune response at the site of insertion of the worm inside mouse tissue. The data presented in this study suggest that the host immune state at 45 days postinfection with T. muris during the chronic phase of infection is the result of factors derived from the worm as well as alterations to the microbiota and bacterial invasion. Taken together, these results provide new information about the parasite-host-microbiota relationship and open new treatment possibilities.

Synthesis and antifungal activity of new hybrids pyrimido[4,5-d]pyridazinone-N-acylhydrazones.

Paracoccidioidomycosis is an endemic mycosis in Latin America for which there is a high mortality rate and limited treatment options. There are no specific drugs to treat the systemic disease. Thus, there is a need for further studies focused on the development of specific drugs. In this work we synthesized new hybrids pyrimido[4,5-d]pyridazinone-N-acylhydrazone (5a-p) by simple methodologies with good yields. The antifungal activity of compounds was evaluated against P. brasiliensis (Pb18) and Candida spp. Compounds 5a, 5f, 5i, 5 k, 5m and 5n showed significant inhibition against Pb18 with MIC of 0.125 to 64 µg mL-1. Compound 5a is the most promising, showing potent fungicidal profile with MFC of 0.5 µg mL-1, synergic effect with amphotericin B, besides showing no toxicity against HeLa and Vero cells.

Madurella mycetomatis infection of the foot: a case report of a neglected tropical disease in a non-endemic region.

BACKGROUND: Mycetoma is an uncommon chronic granulomatous infection of cutaneous and subcutaneous tissues that can be caused by filamentous bacteria (actinomycetoma) or fungi (eumycetoma). It is the prerogative of young men between the third and fourth decade and is transmitted through any trauma causing an inoculating point. The classic clinical triad associates a painless hard and swelling subcutaneous mass, multiple fistulas, and the pathognomonic discharge of grains. Although endemic in many tropical and subtropical countries, mycetoma can also be found in non-endemic areas as in Morocco, and causes then diagnosis problems leading to long lasting complications. Therefore, we should raise awareness of this neglected disease for an earlier management. Under medical treatment however, mycetoma has a slow healing and surgery is often needed, and relapses are possible. CASE PRESENTATION: Herein we report a case of a 64 years old patient, with a history of eumycetoma occurring ten years ago treated with oral terbinafine coupled with surgery. A complete remission was seen after 2 years. He presented a relapse on the previous scar 6 months ago. There wasn't any bone involvement in the magnetic resonance imaging (MRI). The patient was put under oral terbinafine with a slow but positive outcome. CONCLUSION: Through this case report, we perform a literature review and highlight the importance of increase awareness of mycetoma in clinical practice especially in non-endemic regions.

Complete genome sequence and in silico analysis of L. interrogans Canicola strain DU114: A virulent Brazilian isolate phylogenetically related to serovar Linhai.

Canine leptospirosis is often caused by Leptospira interrogans serovar Canicola. Infected dogs may become asymptomatic carriers of the pathogen, which leads to many public health concerns. In this work, we present the complete genome sequencing and in silico analysis from a virulent Brazilian strain of L. interrogans serovar Canicola, previously isolated from a stray dog in Sao Paulo City. Comparative genomic analysis with a reference genome allowed identification of 1031 INDELs and several arrangement variations. Out of 35,361 SNPs identified, 6780 were missense mutations and 16,114 were synonymous mutations. The Gene Ontology terms more affected by mutations were described. Interestingly, phylogenetic analyses indicated a genetic relatedness of the isolate with serovar Linhai strain 56,609. In addition, we found several virulence-related genes and main outer membrane proteins associated with pathogenesis. This genomic information about canine isolates may help to elucidate the molecular diversity and mechanisms of Leptospira spp. pathogenicity.

Design, synthesis, and in vitro biological evaluation of novel thiazolopyrimidine derivatives as antileishmanial compounds.

A series of thiazolopyrimidine derivatives was designed and synthesized as a Leishmania major pteridine reductase 1 (LmPTR1) enzyme inhibitor. Their LmPTR1 inhibitor activities were evaluated using the enzyme produced by Escherichia coli in a recombinant way. The antileishmanial activity of the selected compounds was tested in vitro against Leishmania sp. Additionally, the compounds were evaluated for cytotoxic activity against the murine macrophage cell line RAW 264.7. According to the results, four compounds displayed not only a potent in vitro antileishmanial activity against promastigote forms but also low cytotoxicity. Among them, compound L16 exhibited an antileishmanial activity for both the promastigote and amastigote forms of L. tropica, with IC50 values of 7.5 and 2.69 µM, respectively. In addition, molecular docking studies and molecular dynamics simulations were also carried out in this study. In light of these findings, the compounds provide a new potential scaffold for antileishmanial drug discovery.

Trypanocidal Essential Oils: A Review.

Trypanosomiases are diseases caused by parasitic protozoan trypanosomes of the genus Trypanosoma. In humans, this includes Chagas disease and African trypanosomiasis. There are few therapeutic options, and there is low efficacy to clinical treatment. Therefore, the search for new drugs for the trypanosomiasis is urgent. This review describes studies of the trypanocidal properties of essential oils, an important group of natural products widely found in several tropical countries. Seventy-seven plants were selected from literature for the trypanocidal activity of their essential oils. The main chemical constituents and mechanisms of action are also discussed. In vitro and in vivo experimental data show the therapeutic potential of these natural products for the treatment of infections caused by species of Trypanosoma.

Building an innovative Chagas disease program for primary care units, in an urban non- endemic city.

BACKGROUND: On an absolute basis, Argentina is the country with the largest affected population with Chagas Disease (ChD). This constitutes a significant public health issue. As a consequence of Argentina's migratory patterns, there has been a significant increase of affected population in urban centers. An innovative project for early diagnosis and timely treatment of ChD was designed for Municipal Primary Care Facilities of La Plata City, a non- endemic area, in line with a proposal from the Pan-American Health Organization. The project was a public -private intervention. The objectives of this study were to demonstrate the feasibility of the primary healthcare level for early diagnosis and timely treatment of ChD; to design and implement a tailor made program and to innovate in a public-private association. METHODS: The healthcare barriers for early diagnosis and timely treatment for the population with ChD of La Plata were analyzed. The four dimensions described by Peters et al. (Ann N Y Acad Sci 1136:161-71, 2008) were used. The baseline was measured during a previous pilot project and the same items were evaluated at the end of 2017. The model from Damschroder et al. (Implement Sci 4:50, 2009) was used during the implementation process. RESULTS: With all the information gathered during this investigation, a "patient-centered" model was designed. During the program, 17,894 people were serologically tested for ChD, 1,394 were positive and 1,035 were treated. Additionally, 3,750 children from 46 public schools were evaluated for risk factors of ChD. CONCLUSIONS: This project showed the feasibility of the primary healthcare level for early diagnosis and timely treatment of ChD. Tailor made programs and public-private associations should be considered for vulnerable populations in emerging economies in order to enhance efforts and obtain better results. This program may be replicated in other countries of Latin America were Chagas is a main public health issue and, with the corresponding adaptations, for other neglected diseases as well.

Biological evaluation of mimetic peptides as active molecules for a new and simple skin test in an animal model.

A skin test is a widely used tool in diagnostic evaluations to investigate cutaneous leishmaniases (CL). The actual antigen (Montenegro skin test [MST] antigen) presents some difficulties that pertain to its manufacturing and validation. To contribute to overcoming this problem, we propose the application of new-generation molecules that are based on skin antigen tests. These antigens were obtained through biotechnology pathways by manufacturing synthetic mimetic peptides. Three peptides, which were selected by phage display, were tested as skin test antigens in an animal model (Cavia porcellus) that was immunized with Leishmania amazonensis or Leishmania braziliensis. The peptide antigens, individually (PA1, PA2, PA3) or in a mix (PAMix), promoted induration reactions at 48 and 72 h after the test was performed. The indurations varied from 0.5 to 0.7 cm. In the animals immunized with L. amazonensis, the PA3 antigen showed better results than the standard MST antigen. In animals immunized with L. braziliensis, two peptide antigens (PA2 and PAMix) promoted induration reactions for a longer period of time than the standard MST antigen. These results validate our hypothesis that peptides could be used as antigens in skin tests and may replace the current antigen for CL diagnosis.

Chromoblastomycosis.

Chromoblastomycosis (CBM), also known as chromomycosis, is one of the most prevalent implantation fungal infections, being the most common of the gamut of mycoses caused by melanized or brown-pigmented fungi. CBM is mainly a tropical or subtropical disease that may affect individuals with certain risk factors around the world. The following characteristics are associated with this disease: (i) traumatic inoculation by implantation from an environmental source, leading to an initial cutaneous lesion at the inoculation site; (ii) chronic and progressive cutaneous and subcutaneous tissular involvement associated with fibrotic and granulomatous reactions associated with microabscesses and often with tissue proliferation; (iii) a nonprotective T helper type 2 (Th2) immune response with ineffective humoral involvement; and (iv) the presence of muriform (sclerotic) cells embedded in the affected tissue. CBM lesions are clinically polymorphic and are commonly misdiagnosed as various other infectious and noninfectious diseases. In its more severe clinical forms, CBM may cause an incapacity for labor due to fibrotic sequelae and also due to a series of clinical complications, and if not recognized at an early stage, this disease can be refractory to antifungal therapy.

Buruli Ulcer: Review of a Neglected Skin Mycobacterial Disease.

Buruli ulcer is caused by Mycobacterium ulcerans This neglected disease occurs in scattered foci around the world, with a higher concentration of cases in West Africa. The mycobacteria produce mycolactones that cause tissue necrosis. The disease presents as a painless skin nodule that ulcerates as necrosis expands. Finding acid-fast bacilli in smears or histopathology, culturing the mycobacteria, and performing M. ulcerans PCR in presumptive cases confirm the diagnosis. Medical treatment with oral rifampin and intramuscular streptomycin or oral treatment with rifampin plus clarithromycin for 8 weeks is supported by the World Health Organization. This review summarizes the epidemiology, pathogenesis, clinical presentation, diagnostic tests, and advances in treatment.

Historical, current and expected future occurrence of rabies in enzootic regions.

Rabies is one of the oldest recorded pathogens, with the broadest distribution of any known viral zoonosis. Antarctica is believed to be free of all lyssaviruses, but no laboratory-based surveillance has taken place to support this supposition. Re-introduction of the disease is possible in Pacific Oceania, as evidenced by a historical outbreak in Guam and the translocation of rabid bats to Hawaii. Australia is the only inhabited continent with enzootic rabies, without the presence of rabies virus. Europe and North America have broken the cycle of dog-mediated rabies, with a few remaining focal points in Latin America and the Caribbean, but wildlife rabies predominates. The greatest burden resides in the 'Old World'. The elimination of human rabies mediated via dogs by 2030 in Africa, Asia and the Middle East will not be simple, rapid or inexpensive, but it may be achievable through the use of widely available tools and the application of lessons learned during the course of the 20th century.

La rage est l'une des plus anciennes maladies infectieuses enregistrées et la zoonose virale la plus largement représentée dans le monde. On présume que l'Antarctique est indemne de tout lyssavirus mais cette hypothèse n'est étayée par aucune surveillance basée sur des analyses de laboratoire. Il existe une menace de réintroduction de la maladie en Océanie, comme l'ont révélé le foyer historique survenu à Guam ainsi que l'arrivée de chauves-souris enragées à Hawaï. L'Australie est le seul continent habité où la rage ne sévit pas à l'état enzootique, le virus de la rage y étant absent. L'Europe et l'Amérique du Nord ont mis fin au cycle de la rage transmise par les chiens, dont il ne subsiste que quelques rares foyers de propagation en Amérique latine ; en revanche, la rage sylvatique reste prépondérante dans ces régions. Le fardeau le plus lourd est supporté par l'Ancien Monde. L'élimination de la rage humaine transmise par les chiens à l'horizon 2030 en Afrique, en Asie et au Moyen-Orient ne sera pas une tâche facile, rapide ni exempte de coûts mais elle peut réussir grâce aux outils disponibles partout dans le monde et aux enseignements tirés de l'expérience acquise tout au long du xxe siècle.

La rabia, causada por uno de los patógenos más antiguos de los que hay constancia, presenta la distribución más amplia de cuantas zoonosis víricas se conocen. Se piensa que la Antártida está libre de todo tipo de lisavirus, pero no ha habido labores de vigilancia en laboratorio que prueben tal suposición. Oceanía está bajo la amenaza de reintroducción de la enfermedad, como demuestran el histórico brote registrado en Guam o el desplazamiento de murciélagos rabiosos a Hawái. Australia es el único continente habitado en el que no hay rabia enzoótica, esto es, en que el virus rábico no está presente. Europa y América del Norte han interrumpido el ciclo de la rabia transmitida por perros, de la que aún quedan contados focos en América Latina y el Caribe, aunque sigue prevaleciendo la rabia de la fauna silvestre. La carga más importante recae en el «Viejo Mundo¼. La eliminación de la rabia humana transmitida por perros para 2030 en África, Asia y el Oriente Medio no será sencilla, rápida ni barata, pero es factible si se emplean herramientas que ya están extendidas y se aplican las lecciones que hemos aprendido a lo largo del siglo XX.

[Paracoccidioidomycosis: chronicle of a neglected disease]. / Paracoccidioidomicosis: crónica de una enfermedad olvidada.

Paracoccidioidomycosis (PCM) is among the systemic mycoses which are endemic only in Latin America. In Argentina, the vast majority of the cases are reported at north of latitude 34.5° S. The disease is produced by thermodimorphic fungi of the genus Paracoccidoides: P. brasiliensis (S1), P. americana (PS2), P. restrepiensis (PS3), P. venezuelensis (PS4) y P. lutzii. The natural habitat of members of this genus is the soil, where they produce infectious conidia. Little is known, however, about their specific ecologic niche(s), and this knowledge gap hampers the design of measures to control the infection. Rural male workers are the group most at risk of developing PCM. Infection occurs by inhalation of aerosolized conidia and may either be asymptomatic or cause mild respiratory symptoms. In turn, this primary infection may be self-limited or progress to severe pulmonary or disseminated disease. The disease has two clinical presentations: (i) acute or subacute (juvenile), frequent in children, adolescents and people with immunodeficiencies; and (ii) chronic progressive, in adults. Active lesions often resolve into fibrotic scars which can cause dysphagia, dysphonia, adrenal insufficiency, and intestinal obstruction. Although efficient tools are available for diagnosis and treatment, the nonspecific nature of PCM clinical manifestations frequently delay the diagnosis. In addition, the poor adherence to long antifungal treatments allows the advance of the disease and the development of extensive fibrosis compromising severely and permanently respiratory and adrenal functions, thus altering the patient"s quality of life and even causing his/her death.

Paracoccidioidomycosis after Highway Construction, Rio de Janeiro, Brazil.

Transmission of Paracoccidioides spp. fungi to humans is usually related to manipulation of soil. Rural workers are the most affected group. We report an outbreak of paracoccidioidomycosis after deforestation and massive earth removal during construction of a highway in Rio de Janeiro, Brazil. Extensive environmental disturbances might be involved in fungal transmission.

The future of academic haematology.

Recent advances in the basic medical sciences, particularly cell biology and genomics, have great promise for the future development of all aspects of haematological practice. They will also impinge on the hitherto neglected fields of haematology, including haematology involving the care of the rapidly increasing number of elderly patients and the complex problems of haematological practice in the developing countries. To obtain the maximum benefit from these new developments it will be necessary to review the patterns of training of haematologists of the future at every level. In short, it will be important to try to design and develop various career pathways for training haematologists including those who wish to work full time in basic research, combine research with clinical practice, or commit all their time to clinical work and teaching.