Molecular Docking Analysis of Adhatoda vasica with Thromboxane A2 Receptor (TXA2R) (6IIU) and Antiviral Molecules for Possible Dengue Complications.

OBJECTIVE: The present study is an in silico model of platelet amplification potential of Adhatoda vasica, which can be used to treat thrombocytopenia in dengue complications. METHODS: Docking studies have proved to be an essential tool that facilitates the structural diversity of natural products to be harnessed in an organized manner. In the present study, vasicine containing natural anti-dengue potential was subjected to docking studies using Schrodinger glides software (ver.11.1). The docking study was carried out to find out the potential molecular targets for selected protein. The docking was carried out on different ligands, like vasicine, ramatroban, chloroquine, celgosivir, and standard eltrombopag downloaded from PubChem and retrieved to glide software and ligands prepared using lig prep wizard. Docking was performed using the ligand docking wizard of Glide-maestro 2018. RESULTS: The docking score of vasicine (-5.27) is nearly identical to the standard eltrombopag (-6.08), and both ligands bind with one hydrogen bond. The validation score of ramatroban is -12.39, binding with five hydrogen bonds, Celgosivir exhibited a docking score of -7.3 with three hydrogen bonds, and chloroquine displayed no hydrogen bond but had a docking score of -4.6. CONCLUSION: Vasicine was found to be the most suitable target of platelet amplification potential from Adhatoda vasica. However, the molecular docking results are preliminary, and it has been indicated that vasicine could be one of the potential ligands to treat the thrombocytopenia of dengue; experimental evaluation will be carried out in the near future.

Micronutrient Supplementation and Clinical Outcomes in Patients with Dengue Fever.

Dengue fever (DF) is a viral infection that is common in tropical countries and represents a significant cause of global morbidity and mortality. Despite its prevalence and severity, treatment options for DF remain limited and consist primarily of supportive measures. Several recent studies have concluded that micronutrient supplementation may improve clinical outcomes in patients with DF, but no review has summarized and synthesized these findings. We conducted a literature review to identify articles investigating the effect of micronutrient supplementation on clinical outcomes among patients with DF. We found several studies which indicated that supplemental vitamin C, vitamin D, vitamin E, and zinc may be useful adjuncts in DF treatment. Folic acid supplementation did not appear to affect clinical outcomes. The reviewed studies have significant limitations including small sample sizes and limited data about the baseline nutritional status of study subjects. We identify a need for additional high-quality randomized trials to elucidate the role of micronutrient supplementation in DF treatment.

Efficacy & safety of Carica papaya leaf extract (CPLE) in severe thrombocytopenia (≤30,000/µl) in adult dengue - Results of a pilot study.

Severe thrombocytopenia in dengue often prompts platelet transfusion primarily to reduce bleeding risk. In India, about 11-43% of dengue patients report receiving platelet transfusions which is considered scarce and expensive especially in resource limited settings. Herein, we evaluated the efficacy and safety of Carica papaya leaf extract (CPLE) in the management of severe thrombocytopenia (≤30,000/µL) in dengue infection. 51 laboratory confirmed adult dengue patients with platelet counts ≤30,000/µL were randomly assigned to either treatment (n = 26) or placebo (n = 24) group. By day 3, CPLE treated patients reported significantly (p = 0.007) increased platelet counts (482%± 284) compared to placebo (331%±370) group. In the treatment group, fewer patients received platelet transfusions (1/26 v/s 2/24) and their median time for platelets to recover to ≥ 50,000/µL was 2 days (IQR 2-3) compared to 3 days (IQR 2-4) in placebo. Overall, CPLE was safe and well tolerated with no significant decrease in mean hospitalization days. Plasma cytokine profiling revealed that by day 3, mean percent increase in TNFα and IFNγ levels in treatment group was less compared to that observed in placebos; (TNFα: 58.6% v/s 127.5%; p = 0.25 and IFNγ: 1.93% v/s 62.6% for; p = 0.12). While a mean percent increase in IL-6 levels occurred in placebos (15.92%±29.93%) by day 3, a decrease was noted in CPLE group (12.95%±21.75%; p = 0.0232). Inversely, CPLE treated patients reported a mean percent increase compared to placebo by day 3 (143% ±115.7% v/s 12.03%± 48.4%; p = 0.006). Further, by day 3, a faster clearance kinetics of viral NS1 antigenemia occurred-mean NS1 titers in treatment group decreased to 97.3% compared to 88% in placebos (p = 0.023). This study demonstrates safety and efficacy of CPLE in increasing platelet counts in severe thrombocytopenia in dengue infections. A possible immunomodulatory and antiviral activity may be attributed to CPLE treatment. These findings merit validation in larger prospective studies. Trial registration Name of the registry: Clinical Trials Registry-India (CTRI) Registration No.: CTRI-REF/2017/02/013314.

Encefalomielitis diseminada aguda posinfecciosa en un paciente con sospecha de infección por virus dengue / Postinfectious acute disseminated encephalomyelitis in a patient with suspected dengue virus infection

Introducción: La infección por virus dengue es considerada una de las arbovirosis de mayor prevalencia en los países tropicales. La encefalomielitis diseminada aguda es un trastorno inflamatorio desmielinizante y multifocal que afecta al sistema nervioso central, de inicio agudo y curso clínico monofásico. El proceso inflamatorio se encuentra mediado por mecanismos inmunológicos y su relación con infecciones por el virus dengue aún no se establece con claridad. Objetivo: Describir un caso clínico con manifestaciones del sistema nervioso central después de una probable infección por el virus dengue. Presentación del caso: Paciente femenina de 50 años, con antecedentes de hipertensión arterial controlada. Quince días después de un cuadro de fiebre de 4 días de duración, que posiblemente fue por una infección por el virus dengue, comienza con síntomas y signos de afectación neurológica caracterizadas por ligera irritabilidad, dificultad para la concentración en una actividad específica de la vida cotidiana. Progresivamente se nota dificultad motora en el hemicuerpo izquierdo además de encontrarse agitada y distraída, motivo por el cual se decide su ingreso hospitalario. Se realiza el diagnóstico a través de los hallazgos en el examen físico, los estudios positivos de resonancia magnética nuclear y el resultado positivo de la IgM de dengue en sangre. Tanto la evolución clínica como la respuesta al tratamiento con esteroides fueron favorables. Conclusiones: El evento ocurrido en este caso sugiere que los facultativos deben tener presente el diagnóstico de encefalomielitis diseminada aguda en pacientes que han tenido infección previa o alta sospecha de esta por el virus dengue(AU)

Introduction: Dengue virus infection is one of the most prevalent arboviruses in tropical countries. Acute disseminated encephalomyelitis is an inflammatory demyelinating multifocal disorder affecting the central nervous system. Its onset is acute and its clinical course monophasic. The inflammatory process is mediated by immunological mechanisms, and its relationship to dengue virus infections is still not clear. Objective: Describe a clinical case of central nervous system manifestations after probable dengue virus infection. Case presentation: Female 50-year-old patient with a history of controlled hypertension. Fifteen days after a 4-day fever episode, possibly due to dengue virus infection, the patient starts presenting neurological signs and symptoms, such as slight irritability and difficulty to concentrate on a specific activity of daily living. The patient notices progressive motor difficulty in her left hemibody and she feels agitated and distracted. It is therefore decided for her to be hospitalized. A diagnosis is made based on physical examination findings, positive nuclear magnetic resonance studies, and the positive result of the dengue IgM blood test. Both the patient's clinical evolution and her response to treatment with steroids were favorable. Conclusions: The event herein described suggests that physicians should consider the diagnosis of acute disseminated encephalomyelitis in patients with previous infection or high suspicion of infection with dengue virus(AU)

Effect of Adjuvant Homeopathy with Usual Care in Management of Thrombocytopenia Due to Dengue: A Comparative Cohort Study.

BACKGROUND: Dengue is an emerging threat to public health. At present, no clear modalities are available for the prevention and management of thrombocytopenia due to dengue. This article reports the clinical outcomes of integrative homeopathic care in a hospital setting during a severe outbreak of dengue in New Delhi, India, during the period September to December 2015. METHODS: Based on preference, 138 patients received a homeopathic medicine along with usual care (H+UC), and 145 patients received usual care (UC) alone. Assessment of thrombocytopenia (platelet count < 100,000/mm3) was the main outcome measure. Kaplan-Meier analysis enabled comparison of the time taken to reach a platelet count of 100,000/mm3. RESULTS: There was a statistically significantly greater rise in platelet count on day 1 of follow-up in the H+UC group compared with UC alone (mean difference = 12,337; 95% confidence interval [CI], 5,421 to 19,252; p = 0.001). This trend persisted until day 5 (mean difference = 14,809; 95% CI, 1,615 to 28,004; p = 0.02). The time taken to reach a platelet count of 100,000/mm3 was nearly 2 days earlier in the H+UC group compared with UC alone (H+UC: 3.44 days ± standard error of the mean [SEM] 0.18; 95% CI, 3.08 to 3.80; UC: 5.28 days ± SEM 0.29; 95% CI, 4.71 to 5.86; p < 0.001). CONCLUSION: These results suggest a positive role of adjuvant homeopathy in thrombocytopenia due to dengue. Randomized controlled trials may be conducted to obtain more insight into the comparative effectiveness of this integrative approach.

Bloodstream infections in hospitalized adults with dengue fever: Clinical characteristics and recommended empirical therapy.

BACKGROUND: Dengue is an important mosquito-borne tropical viral disease and dual infection, though rare, has been regarded as a risk factor for severe disease and mortality. However, few studies focused on bloodstream infections (BSIs) and empirical antibiotic therapy rarely addressed. METHODS: Dengue patients with concurrent or subsequent BSIs between July 1 and December 31, 2015 were included. Clinical information, laboratory data, and drug susceptibility data were collected. RESULTS: Totally 80 patients, with an in-hospital mortality rate of 32.5%, were included and categorized into three groups. 32 patients in Group I (BSI onset within 48 h after admission), 32 in Group II (between 48 h and one week), and 16 in Group III (more than one week). Patients in Group I were older (mean age: 75.6 vs. 72.6 or 69.6 years; P = 0.01) and had a higher Charlson comorbidity index (3.1 vs. 1.8 or 1.9; P = 0.02) than those in Group II or III. Streptococcus species (28.9%, 11/38) and Escherichia coli (23.7%, 9/38) were major pathogens in Group I. Enterobacteriaceae (38.2%, 13/34) isolates predominated in Group II. Fatal patients more often received inappropriate empirical antibiotic than the survivors (61.5% vs. 35.2%; P = 0.03). According to susceptibility data, pathogens in Group I and II shared similar susceptibility profiles, and levofloxacin, cefepime, or piperacillin/tazobactam, can be empirically prescribed for those hospitalized within one week. CONCLUSIONS: BSI pathogens vary among dengue patients. For adults with dengue and suspected BSI hospitalized within one week, empirical antimicrobial agents are recommended.

Dengue fever manifesting with tetany as the first presentation of primary hypoparathyroidism: a case report.

BACKGROUND: Primary hypoparathyroidism is associated with diverse variety of symptomatology of hypocalcemia including seizures and tetany. We report a case of previously undiagnosed asymptomatic primary hypoparathyroidism with extensive basal ganglia calcifications presenting for the first time with hypocalcemic tetany during acute dengue infection. Although hypocalcemia is known to occur in dengue infection symptomatic hypocalcemia is very infrequent. CASE PRESENTATION: A 32 year old male with short stature who has undergone bilateral cataract surgery 2 years ago but who was otherwise healthy, presented with fever and generalized body aches of 3 days duration and carpal spasms/tetany occurring on the third day of the illness. He was diagnosed to have acute dengue fever along with severe hypocalcemia. Subsequent workup confirmed that the patient had primary hypoparathyroidism with extensive basal ganglia and cerebellar calcifications which was previously undiagnosed. His acute illness and hypocalcemia was managed successfully and was commenced on regular calcium supplementations to alleviate the hypocalcemic effects of his chronic illness. CONCLUSION: Clinical features of hypocalcemia may not commonly manifest up to the same degree of severity of hypocalcemia in primary hypoparathyroidism even till late adulthood but potential early clues such as short stature and premature cataract should be actively investigated. Worsening of already existing hypocalcemia during acute dengue fever led to the ultimate diagnosis of primary hypoparathyroidism in this patient which was lifesaving.

Dengue-associated hypokalemic paralysis: causal or incidental?

Dengue-associated hypokalemic paralysis is considered an important but under-emphasized neuromuscular complication of dengue virus infection. Review of the published literature reveals that 35 instances of hypokalemic paralysis associated with dengue have been recorded from the Indian subcontinent and all but two, were males. The median age of presentation is 29 years and moderate to severe grade pure motor quadriparesis is precipitated during the phase of defervescence of moderate to high-grade fever. Recovery starts within 12h of potassium supplementation and is usually complete in a couple of days. Redistribution or increased loss of potassium from the body is speculated as the pathophysiological mechanism involved in the causation of hypokalemia. It is not possible to derive the exact etiopathological correlation from the published literature either due to a lack of comprehensive reporting or inadequate work-up of the patients. Curious is the fact that only 35 patients had manifest-paralysis when more than two-thirds affected with the dengue virus exhibit hypokalemia; whether this indicates a genetically mediated channel disorder or an incidental association remains to be seen.

Dengue y paludismo en un mismo paciente / Dengue and malaria in the same patient

Fundamento: la epidemia de dengue es un problema de la actualidad en muchos países, que obliga a los sistemas de asistencia sanitaria a estar en constante vigilancia. Presentación de caso: se presenta una paciente de 11 años de edad que presenta fiebre alta, molestar general y dolor de cabeza. En su evolución llamó la atención la no mejoría clínica de su estado físico, un discreto tinte ictérico con orinas colúricas así como punta de bazo palpable. Conclusiones: es importante realizar el diagnóstico diferencial en un síndrome febril agudo aunque se tenga un diagnóstico clínico epidemiológico de dengue, especialmente con el paludismo, incorporando la gota gruesa a los exámenes complementarios de urgencia(AU)

Background: The epidemic of dengue is currently a problem in many countries which compels the systems of sanitary attendance to be in constant surveillance. Case presentation: An 11 year old female white patient came to the casualty department complaining of high fever, headache and general malaise. Her follow up called the attention for she did not improve her physical state, there was a discrete icteric dye with colored urines and the tip of the spleen was palpable. Conclusion: It is important to make a differential diagnosis, it is an acute febrile syndrome though it has a clinical epidemiological diagnosis of dengue, especially with malaria embodying thick blood smear when ordering urgent laboratory tests(AU)

Management of thrombocytopenia and flu-like symptoms in dengue patients with herbal water of Euphorbia hirta.

BACKGROUND: Incidence of dengue increased 30 fold between 1960 and 2010. This increase is believed to be due to a combination of urbanisation, population growth, increased international travel, and global warming. We tried to find out the effect of herbal water of Tawa-tawa, also called Euphorbia hirta, on the flu like symptoms and blood parameters especially on thrombocytopenia. METHODS: Total 125 patients with confirmed dengue fever admitted in medical ward of Sir Ganga Ram Hospital Lahore were included in this experimental study. Duration of study was 3 months. Patients were divided into 2 groups, i.e., group A (ages between 30 to 55 years) and group B (ages between 14 to 25 years). A blood sample was obtained on the day of enrolment and after 24 hours of using Tawa-tawa. The variables used were platelet count, haematocrit (HCT), WBC count, serum AST, ALT, IgM/IgG. RESULTS: In men, platelet count was < 25,000 and in women, it was > 50,000. Haematocrit were >40% in men and 30-40% in women. TLC in a range of 4,000-11,000/mm3 was observed in both males and females. IgM 'haemagglutination' antibody titres (> 1:160) was observed in 71.3% females and 50% males. Serum AST was > 40 IU/L in 38% females and 36% males. Serum ALT was > 40 IU/L in 9.5% females and 12% males. In both group A and B platelet count and TLC were increased nonsignificantly after herbal water of Euphorbia hirta (E. Hirta). Haematocrit value decreased nonsignificantly after using the herbal water. Over 70% of patients showed moderate increase in their platelet count. However leucopoenia improved significantly after the use of aqueous extract of E. hirta. A marked recovery in fever and flu like symptoms was observed. CONCLUSION: In over 70% patients there was improvement in platelet count, TLC, fever, and flue-like symptoms.

Caracterización de los pacientes con dengue en el Centro Diagnóstico Integral de Tucupita, Estado Delta Amacuro, Julio - diciembre de 2009 / Characterization of the patients suffering from dengue at the Comprehensive Center of Diagnostic in Tucupita, Delta Amacuro State, July-December 2009

Se revisaron las 31 historias clínicas de los pacientes ingresados en el Centro Diagnóstico Integral Raúl Maza Mérida del estado Delta Amacuro, municipio Tucupita con el diagnóstico positivo de dengue, confirmado de forma clínica e inmunológica (IgM positiva). Se analizaron las variables: sexo, edad, procedencia, incidencia por meses, síntomas, complicaciones, resultados analíticos e imagenológicos y evolución. El método estadístico utilizado fue el test Ji cuadrado de Pearson, considerando valores de p < 0,05 estadísticamente significativos y además valores porcentuales. La enfermedad predominó en el sexo masculino con un (58.1 por ciento), entre el grupo de edades de 15 y 29 años (48.4 por ciento). Julio (35.5 por ciento) resultó ser el mes de mayor incidencia, no reportándose en los meses de noviembre ni diciembre. El malestar general y la fiebre en el 100 por ciento de los pacientes fueron los síntomas más frecuentes al inicio de la enfermedad, y la cefalea el signo que más perduró en la evolución. Hubo una disminución de los ingresos al segundo día de haber comenzado los síntomas...(AU)

Thirty one clinical charts of the patients admitted at Raul Maza Merida Comprehensive Center of Diagnostic in Delta Amacuro State, Tucupita municipality were analyzed, these patients suffered from dengue which was verified immunological (IgM) and clinically. Sex, age, origin, incidence per months, symptoms, complications, analytical and imaging results together with the follow up of evolution were the variables considered. The statistical method used was Pearson's chi square test, taking into consideration the values of p< 0, 05 statistically significant along with other percentage values. Male sex (58,1 per cent), 15 and 29 years old (48, 4 per cent) prevailed, and July (35,5 per cent) was the month showing the highest incidence, no cases were reported in November or December. General malaise and fever were present in 100 per cent of the patients' most frequent symptoms in the onset period, and headache the most lasting sign during the disease progress, observing a reduction of admissions on the second day of the onset of symptoms. The 62,5 per cent of the cases of hemorrhagic dengue presented complications, only 4,3 per cent of fevers due to dengue resulted in statistical significance. Megacaryopoietic series was the last to be recovered. Echo-sonographic alterations were detected in 25,8 per cent of the cases and only 9,6 per cent presented radiological alterations. The presence of ascitic fluids resulted the most frequent finding, 100 per cent of the patients underwent parenteral hydration, and paracetamol was the most used antipyretic solution. At fifth day 96,7 per cent of patients were asymptomatic...(AU)

Acute hypokalaemic quadriparesis in dengue fever.

The authors report acute hypokalaemic quadriparesis in two young patients that occurred during dengue epidemic in 2010 in India. Both patients developed flexic type of pure motor weakness in all four limbs without bladder bowel involvement, following 2 to 3 days of fever and malaise. Higher mental functions were normal. Serum potassium level was very low; 2-2.5 m mol/l. Non-structural protein (NS(1))-antigen and immunoglobulin M-antibody for dengue were positive in both patients. Both patients improved with potassium supplementation. In follow-up, they are doing well.

Dengue fever with ischemic stroke: a case report.

BACKGROUND: Dengue fever, especially dengue hemorrhagic fever, often presents with thrombocytopenia and hemorrhagic phenomenon. Neurologic manifestations are uncommon. REVIEW SUMMARY: We report a case of dengue fever with thrombocytopenia and ischemic stroke. Only supportive treatment was instituted. The neurologic deficits of the patient were initially progressive and then improved. The platelet count correlated well with the disease severity and the neurologic deficits. The time course was compatible with the critical stage in dengue hemorrhagic fever. Some studies show that immunomodulators or immunosuppressants may reverse thrombocytopenia such that the bleeding episodes improve rapidly. CONCLUSION: Dengue fever may present as ischemic stroke.

Oral calcium administration attenuates thrombocytopenia in patients with dengue fever. Report of a pilot study.

Global climate change is one of the instigating and contributing factors for epidemic outbreaks of infectious diseases in human populations. In the years 2003 to 2005 the city of Tampico, in the northern state of Tamaulipas, Mexico, experienced recurrent outbreaks of dengue virus infections (DV) and the resulting dengue fever (DF). One of the hallmark symptoms of DF, which appears to worsen as the environmental temperature increases, is thrombocytopenia. In as much as it is a hallmark for hemorrhagic manifestations, thrombocytopenia is a useful sign to monitor the course of infected patients. Extracellular calcium (Ca2+ o) plays a key role in blood clotting; its chelation in vitro with ethylenediaminetetracetic acid (EDTA) or citrate prevents clotting, while exogenous recalcification of plasma leads to shortening of clotting time. In vivo, Ca2+ o is essential for platelet function and for the regulation of the immune response. In this work we report a significant increase (p<0.05) in the number of blood platelets of patients with clinical signs and symptoms of DF following oral administration of calcium carbonate (CAL, 1.2 to 1.8 g/day; n=10) when compared with a control group (CTL, n=10): 89 (46-132) versus 206 (155-257). Data expressed as mean value (95% confidence interval, C.I.) for x1000 cells/mm3. CAL also improved overall clinical condition and reduced by 36 % the duration of signs and symptoms of DF: 6.7-11.3 days, versus 11.5-16.6 days (95 % C.I., p<0.05) when compared with CTL patients. The possible mechanism of calcium attenuated thrombocytopenia and clinical improvement is discussed.

Dengue in Nicaragua, 1994: reintroduction of serotype 3 in the Americas

The principal aim of the report presented here is to describe the reappearance of dengue serotype 3 in the Americas, following a 17-year absence, throughthe recent experience of Nicaragua. In all, 356 serum samples obtained through Nicaragua's dengue monitoring system in October 1994 during an epidemic were examined. Anti-dengue IgM antibodies were detected in 43 percent of these, with sera from 12 of the 18 areas covered by Nicaragua's local integrated health care systems yielding positive results. In addition, dengue virus was isolated from 5 of 24 sera obtained from patients with hemorrhagic sympthoms, dengue 3 being isolated from 3 of these samples and dengue 1 from the other 2. A diagnosis of dengue with hemorrhagic manifestations or of hemorrhagic dengue was supported or confirmed by laboratory findings obtained from 26 of 39 patients hospitalized in Leon or Managua. The most frequent sympthoms of 18 patients diagnosed as having dengue with hemorrhagic manifestations were fever, headache, vomiting, myalgia, arthralgia, and epistaxis. The remaining eight patients, diagnosed as having probable hemorragic dengue, exhibited fever, general malaise, hemorrhaging, thromboctytopenia, hemoconcentration, and hemagglutination-inhibition antibody titers ranging from 640 to 20 480. Overall, the reappearance of dengue serotype 3 in the Region was confirmed, together with its ability to produce cases of hemorrhagic dengue. At least in Nicaragua, it is apparent that the introduction of dengue serotype 3 has prompted an increase in the number of classical dengue and the hemorrhagic dengue cases, a scenario that might constitute the grim prelude to future developments in the Americas if urgent attention is not given to controlling the disease's mosquito vector (AU)