Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 42
Filtrar
1.
J Prev Med Hyg ; 62(3): E628-E634, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34909490

RESUMO

The number of outbreaks have progressively increased since many years in India. In this era of globalization and rapid international travel, any infectious disease in one country can become a potential threat to the entire globe. Outbreaks of Nipah, Zika, Crimean-Congo Haemorrhagic Fever and Kyasanur Forest Disease have been reported since a decade and now we are facing COVID-19 pandemic. One of the challenges in the prevention of these outbreaks is that as the cases decrease, the felt need declines, the public demand decreases and the mitigation responses get overshadowed by the need of emergency responses elsewhere. The One Health approach is a movement to promote alliance between medicine field, veterinary medicine and environmental sciences to upgrade the health of humans, animals, and ecosystem. The data in this article is compiled from different websites and publications of World Health Organization (WHO), Centre for Disease Control and Prevention (CDC), Integrated Disease Surveillance Programme (IDSP), grey literature and media. There is an urgent need for better surveillance and disease burden assessments in the country and to gain detailed insights into vector biology, factors of environment influencing the diseases, mapping of endemic areas, strengthen intersectoral coordination, infection control practices, and ensure use of Personal Protective Equipment's (PPE) and availability of drugs and vaccines to handle the outbreaks in a better way.


Assuntos
COVID-19 , Febre Hemorrágica da Crimeia , Infecção por Zika virus , Zika virus , Animais , Surtos de Doenças/prevenção & controle , Ecossistema , Febre Hemorrágica da Crimeia/epidemiologia , Humanos , Índia/epidemiologia , Pandemias , SARS-CoV-2
2.
Cureus ; 13(9): e18400, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34729277

RESUMO

Introduction In the coronavirus disease 2019 (COVID-19) pandemic, healthcare workers (HCWs) are at the frontline around the world and categorized as a priority group for COVID-19 vaccines. Our study aimed to find out the COVID-19 vaccine awareness, attitude, and acceptance in HCWs in western India. Methods A cross-sectional study was carried out between January 14 and January 28, 2021, at a tertiary care hospital located in western India. Data were collected anonymously using Google Forms. Descriptive statistics were used to determine the sociodemographic variables. The knowledge and attitude of HCWs were analyzed using mean and SD. Multivariate analysis was done to find out the association between participants' attitudes with demographic characteristics. Results Of the total health care workers, 498 answered the survey. The mean age of participants was 29.8 years (SD 6.4), and 354 (71.1%) were male. Among the respondents, 445 (89.4%) would accept a COVID-19 vaccine when available. Four-hundred seventy-six (476) HCWs (95.6%) had excellent knowledge regarding COVID-19 and COVID-19-appropriate behavior. The majority of the subjects (399) had a neutral attitude toward COVID-19 vaccination. Health care professionals (doctors and nurses) had higher acceptance for vaccination against COVID-19 than non-professionals. Conclusions The higher rates of COVID-19 vaccine acceptability and the excellent knowledge among HCWs will directly enhance the level and acceptability of vaccine among the general population and will definitely help in reducing the mortality and morbidity related to COVID-19.

3.
Disaster Med Public Health Prep ; : 1-5, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34384516

RESUMO

Modeling studies indicate that the closure of schools during the coronavirus disease (COVID-19) pandemic may not be well grounded for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as evidences indicate that children are less affected by this virus, and the clinical attack rates in the 0-19 age group are low. Experts also opine that school closures might have negative effects on the scholastic abilities of children and also an adverse impact on the economy and health care system, considering the responsibilities conferred upon the parents. Also, in a developing country like India, it is difficult for the rural population to afford distance online learning, which brings into importance the reopening of schools in a safe environment to avoid adversities such as increased drop-outs in the upcoming academic year, loss of in-person benefits such as mid-day meal scheme. This study highlights a field experience in relation to readiness assessment of a rural school in the Jodhpur district of Rajasthan, India, for a safe reopening to accept students in a safe and conducive atmosphere, which shall help prevent transmission of the virus in the schools among the children. In this regard, an indigenous readiness checklist has been developed to achieve the purpose, which assesses the readiness in 3 domains: (1) procedural readiness; (2) supplies, sanitation, and infrastructure-related; and (3) education and training.

4.
J Family Med Prim Care ; 10(6): 2400-2404, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34322445

RESUMO

Aims: The indigenously developed Indian Council of Medical Research (ICMR)-NIV COVID Kavach IgG enzyme linked immunosorbent assay (ELISA) has been recommended for seroprevalence among vulnerable populations in India, which provided essential services throughout the lockdown. The staff working in the High Court was one such group. We compared anti-SARS-CoV-2 IgG seropositivity among the staff of Jodhpur and Jaipur High Courts, Rajasthan, India. Methods: Asymptomatic judiciary staff of Jodhpur and Jaipur benches of High Courts were enrolled after informed written consent. A questionnaire was filled and 3-5 ml venous blood was collected from participants. The ICMR-NIV COVID Kavach IgG ELISA and EUROIMMUN IgG ELISA were used for detection of Anti-SARS-CoV-2 IgG antibodies. Results: A total of 63 samples (41 from Jodhpur and 22 from Jaipur) were collected between 28th July to 4th August 2020. The overall anti-SARS-CoV-2 IgG seroprevalence was found to be 6.35%. Seropositivity was higher among the staff from Jaipur (13.64%) as compared to Jodhpur (2.44%). The Kavach ELISA results were in complete agreement with EUROIMMUN ELISA. The infection control measures were deemed effective. Conclusion: Seroprevalence among the staff of Jodhpur High Court was found to be lower than Jaipur, reflecting higher susceptibility to COVID-19 in the former. Many offices worldwide are closed till mid 2020 but need to come up with pre-emptive policies eventually. This study may help to anticipate the possible challenges when other government/private offices start functioning. The infection control practices of one workplace may help formulate guidelines for other offices.

5.
Infect Drug Resist ; 14: 2233-2239, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34163188

RESUMO

Purpose: Jodhpur administration directed its efforts to control and mitigate COVID 19 infection by implementing and monitoring facility isolation (FI) and home isolation (HI) measures. This study is conducted with a hypothesis that there is no difference in the quality of life and cost-effectiveness of mildly symptomatic or asymptomatic patients in HI and FI. Patients and Methods: A mixed-method study was conducted in Jodhpur in September 2020. The purposive sampling technique was used and data from 120 individuals admitted in HI and FI were collected. The information about the status and functioning of isolation facilities was collected from various sources. Multi-stakeholder interactions with 15 personnel engaged in managing isolation facilities were done. EQ-5D version (EQ-5D-5L) which consists of the EQ-5D descriptive system and the EQ visual analog scale (EQ-VAS) was used to assess health-related quality of life. Results: The strength of HI strategy is demonstrated by its ability to provide psychological and social support with minimal logistic requirements but the issue of sufficient household infrastructure, adequate family and societal support for implementing this strategy is of concern. The strength of FI strategy includes its ability to provide support to patients who have issues of sufficient household infrastructure, adequate family and societal support, but this strategy poses a threat of increasing human resource constraints and financial load on the health system. The respondents from HI obtained a mean EQ-5D index score of 0.90 and a mean VAS score of 85, whereas it was 0.80 and 78.5, respectively, for FI. The cost estimated for home isolation was Rs 549 (7.43 US $) per person, whereas it was Rs 2440 (33.02 US $) for facility Isolation. Conclusion: Though HI seems advantageous in terms of a better quality of life and cost-saving over FI, both the strategies are context-specific having their own trade-offs.

6.
J Infect Dev Ctries ; 15(5): 618-624, 2021 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-34106883

RESUMO

INTRODUCTION: This study was planned to assess the trends of epidemiological indicators and demographic determinants related to the COVID-19 in India. METHODOLOGY: This was a descriptive analysis of the COVID-19 cases and their outcomes between 1st March to 31st May 2020 in India. Unpaired t-test and ANOVA were used to determine the statistical differences. Linear regression models were prepared to estimate the effect of testing on the fatalities. The Infection Fatality Rate (IFR)/Case Fatality Rate (CFR), doubling time, and Basic Reproduction Number (R0) per week were calculated. RESULTS: Two-thirds of the cases were between 21-50 years of age, while three-fourth of deaths were among people above 50-years of age. The mean age of people infected with COVID-19 was declining throughout the study period. The mean age of infected males and females was significantly different. The male-female ratio of both infection and deaths due to COVID-19 was near about 2:1. IFR/CFR was 3.31 (95% CI = 3.13-3.50) in April, which reduced to 2.84 (95% CI = 2.77-2.92) in May. An incremental trend was observed in the recovery rates (9.42% to 48.18%), tests conducted / million population (12 / million to 2708 / million) and doubling time (3.59 to 17.71 days). The number of tests was significantly influencing the fatalities (ß = 0.016, 95% CI = 0.012-0.020). The overall R0 was found to be 1.72. CONCLUSIONS: Public health interventions were likely effective in containing the spread of COVID-19. There is a need to further improve the testing capacity. The high-risk category of individuals being prioritized for hospital admission should be redefined to include individuals older than 50 years.


Assuntos
Teste para COVID-19/estatística & dados numéricos , COVID-19/mortalidade , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , COVID-19/diagnóstico , Criança , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Fatores de Risco , SARS-CoV-2 , Distribuição por Sexo , Adulto Jovem
7.
Epidemiol Infect ; 149: e132, 2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-34011421

RESUMO

The coronavirus disease 2019 (COVID-19) vaccine was launched in India on 16 January 2021, prioritising health care workers which included medical students. We aimed to assess vaccine hesitancy and factors related to it among medical students in India. An online questionnaire was filled by 1068 medical students across 22 states and union territories of India from 2 February to 7 March 2021. Vaccine hesitancy was found among 10.6%. Concern regarding vaccine safety and efficacy, lack of awareness regarding their eligibility for vaccination and lack of trust in government agencies predicted COVID-19 vaccine hesitancy among medical students. On the other hand, the presence of risk perception regarding themselves being affected with COVID-19 reduced vaccine hesitancy as well as hesitancy in participating in COVID-19 vaccine trials. Vaccine-hesitant students were more likely to derive information from social media and less likely from teachers at their medical colleges. Choosing between the two available vaccines (Covishield and Covaxin) was considered important by medical students both for themselves and for their future patients. Covishield was preferred to Covaxin by students. Majority of those willing to take the COVID-19 vaccine felt that it was important for them to resume their clinical posting, face-to-face classes and get their personal life back on track. Around three-fourths medical students viewed that COVID-19 vaccine should be made mandatory for both health care workers and international travellers. Prior adult vaccination did not have an effect on COVID-19 vaccine hesitancy. Targeted awareness campaigns, regulatory oversight of vaccine trials and public release of safety and efficacy data and trust building activities could further reduce COVID-19 vaccine hesitancy among medical students.


Assuntos
Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Tomada de Decisões , Estudantes de Medicina/psicologia , COVID-19/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Índia/epidemiologia , Fatores de Risco , SARS-CoV-2/imunologia , Inquéritos e Questionários , Vacinação/psicologia , Vacinação/estatística & dados numéricos
8.
J Phys Chem B ; 125(12): 3032-3044, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33754735

RESUMO

Protamine, an arginine-rich basic protein, compacts DNAs in sperm nuclei to densities higher than those in somatic cells. The mechanism of this compaction in sperm cells is even less clear than in somatic cells. Even the preferred binding site, if any, of protamine on DNA is not clearly identified. In this work, we carry out fully atomistic (or all-atom) molecular dynamics simulations to estimate the relative stabilities of protamine binding sites on DNA. Free energy calculated with umbrella sampling on a short arginine stretch bound to the major and minor grooves suggests that a short arginine stretch would prefer the DNA major groove as its binding site. Complementary umbrella sampling simulations where an arginine stretch or a whole protamine is transferred from the major to the minor groove also lead to the same conclusion. We find that the protamine located in the major groove better utilizes the DNA backbone as the binding site and represents the best compromise between enthalpy and entropy gain.


Assuntos
Simulação de Dinâmica Molecular , Protaminas , Sítios de Ligação , DNA , Entropia , Masculino
9.
J Infect Public Health ; 14(2): 260-262, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33493923

RESUMO

This is a case study of a positive COVID-19 case who was diagnosed and isolated early on in the infection. However, her seventeen close contacts who were quarantined and under observation remained negative indicating no viable chain of transmission despite high-risk contact. We further discuss the importance of effective contact tracing coupled with strict isolation or quarantine in breaking the chain of transmission.


Assuntos
COVID-19/diagnóstico , COVID-19/prevenção & controle , Busca de Comunicante , Adulto , Feminino , Humanos , Índia , RNA Viral/isolamento & purificação
10.
Open Forum Infect Dis ; 8(1): ofaa599, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33506066

RESUMO

We studied the pattern and duration of viral ribonucleic acid (RNA) shedding in 32 asymptomatic and 11 paucisymptomatic coronavirus disease 2019 cases. Viral RNA shedding in exhaled breath progressively diminished and became negative after 6 days of a positive reverse-transcription polymerase chain reaction test. Therefore, the duration of isolation can be minimized to 6 days.

11.
Trans R Soc Trop Med Hyg ; 115(7): 820-831, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33444432

RESUMO

BACKGROUND: Understanding risk factors of symptomatic coronavirus disease 2019 (COVID-19) vis-à-vis asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, severe disease and death is important. METHODS: An unmatched case-control study was conducted through telephonic interviews among individuals who tested positive for SARS-CoV-2 in Jodhpur, India from 23 March to 20 July 2020. Contact history, comorbidities and tobacco and alcohol use were elicited using standard tools. RESULTS: Among 911 SARS-CoV-2-infected individuals, 47.5% were symptomatic, 14.1% had severe COVID-19 and 41 (4.5%) died. Older age, working outside the home, cardiac and respiratory comorbidity and alcohol use were found to increase the risk of symptomatic disease as compared with asymptomatic infection. Current tobacco smoking (odds ratio [OR] 0.46 [95% confidence interval {CI} 0.26 to 0.78]) but not smokeless tobacco use (OR 0.81 [95% CI 0.55 to 1.19]) appeared to reduce the risk of symptomatic disease. Age ≥60 y and renal comorbidity were significantly associated with severe COVID-19. Age ≥60 y and respiratory and cardiac comorbidity were found to predispose to mortality. CONCLUSIONS: The apparent reduced risk of symptomatic COVID-19 among tobacco smokers could be due to residual confounding owing to unknown factors, while acknowledging the limitation of recall bias. Cross-protection afforded by frequent upper respiratory tract infection among tobacco smokers could explain why a similar association was not found for smokeless tobacco use, thereby being more plausible than the 'nicotinic hypothesis'. Those with comorbidities and age ≥60 y should be prioritized for hospital admission.


Assuntos
COVID-19 , SARS-CoV-2 , Idoso , Estudos de Casos e Controles , Humanos , Índia/epidemiologia , Fatores de Risco , Tabaco
12.
Trop Doct ; 51(1): 84-91, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32903147

RESUMO

Cases of kala-azar reported during 2013-2018 in Bihar, India were retrospectively analysed. Of 2187 villages reporting cases of kala-azar in 2018, 573 (26.2%) had reported no case in the previous five years but contributed to 20% of disease burden in 2018. On applying potential thresholds of kala-azar outbreaks, 805, 519 and 103 villages reported more than twice, thrice and five times their previous five-year annual average in 2018, respectively. Indoor residual spraying (IRS) in villages reporting any case of kala-azar in the past three years as per current guidelines could cover 72% of incident cases in 2018 vis-a-vis 80% if villages reporting cases in the past five years were considered. Therefore, IRS may be expanded to villages reporting cases in the past five years. Village case trends can be utilised to configure potential outbreak alarms (early warning and response system) on a pre-organised dashboard. A data-driven strategy for villages newly reporting cases and those in potential outbreak situations could prove effective in achieving and sustaining the elimination of kala-azar.


Assuntos
Erradicação de Doenças/métodos , Surtos de Doenças/prevenção & controle , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/prevenção & controle , Notificação de Doenças/estatística & dados numéricos , Surtos de Doenças/estatística & dados numéricos , Humanos , Incidência , Índia/epidemiologia , Estudos Retrospectivos
13.
JMIR Public Health Surveill ; 6(4): e22678, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33001839

RESUMO

BACKGROUND: On March 9, 2020, the first COVID-19 case was reported in Jodhpur, Rajasthan, in the northwestern part of India. Understanding the epidemiology of COVID-19 at a local level is becoming increasingly important to guide measures to control the pandemic. OBJECTIVE: The aim of this study was to estimate the serial interval and basic reproduction number (R0) to understand the transmission dynamics of the COVID-19 outbreak at a district level. We used standard mathematical modeling approaches to assess the utility of these factors in determining the effectiveness of COVID-19 responses and projecting the size of the epidemic. METHODS: Contact tracing of individuals infected with SARS-CoV-2 was performed to obtain the serial intervals. The median and 95th percentile values of the SARS-CoV-2 serial interval were obtained from the best fits with the weibull, log-normal, log-logistic, gamma, and generalized gamma distributions. Aggregate and instantaneous R0 values were derived with different methods using the EarlyR and EpiEstim packages in R software. RESULTS: The median and 95th percentile values of the serial interval were 5.23 days (95% CI 4.72-5.79) and 13.20 days (95% CI 10.90-18.18), respectively. R0 during the first 30 days of the outbreak was 1.62 (95% CI 1.07-2.17), which subsequently decreased to 1.15 (95% CI 1.09-1.21). The peak instantaneous R0 values obtained using a Poisson process developed by Jombert et al were 6.53 (95% CI 2.12-13.38) and 3.43 (95% CI 1.71-5.74) for sliding time windows of 7 and 14 days, respectively. The peak R0 values obtained using the method by Wallinga and Teunis were 2.96 (95% CI 2.52-3.36) and 2.92 (95% CI 2.65-3.22) for sliding time windows of 7 and 14 days, respectively. R0 values of 1.21 (95% CI 1.09-1.34) and 1.12 (95% CI 1.03-1.21) for the 7- and 14-day sliding time windows, respectively, were obtained on July 6, 2020, using method by Jombert et al. Using the method by Wallinga and Teunis, values of 0.32 (95% CI 0.27-0.36) and 0.61 (95% CI 0.58-0.63) were obtained for the 7- and 14-day sliding time windows, respectively. The projection of cases over the next month was 2131 (95% CI 1799-2462). Reductions of transmission by 25% and 50% corresponding to reasonable and aggressive control measures could lead to 58.7% and 84.0% reductions in epidemic size, respectively. CONCLUSIONS: The projected transmission reductions indicate that strengthening control measures could lead to proportionate reductions of the size of the COVID-19 epidemic. Time-dependent instantaneous R0 estimation based on the process by Jombart et al was found to be better suited for guiding COVID-19 response at the district level than overall R0 or instantaneous R0 estimation by the Wallinga and Teunis method. A data-driven approach at the local level is proposed to be useful in guiding public health strategy and surge capacity planning.


Assuntos
Infecções por Coronavirus/transmissão , Epidemias , Pneumonia Viral/transmissão , COVID-19 , Infecções por Coronavirus/epidemiologia , Humanos , Índia/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Estudos Prospectivos
14.
Disaster Med Public Health Prep ; : 1-7, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33087205

RESUMO

OBJECTIVE: During the coronavirus disease (COVID-19) pandemic, Indian nationals evacuated from Iran were quarantined at Jaisalmer, Rajasthan. We wished to study the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in this closed population. METHODS: A basic susceptible, exposed, infected, and removed (SEIR) compartmental model was developed using the daily stepwise approach in Microsoft Excel. An advanced model using standard differential equations in Python software version 3.6 was used to estimate R0 based on model fit to actual data. RESULTS: Forty-eight SARS-CoV-2 infections were found among the 474 quarantined individuals. Out of these, 44 (92%) were asymptomatic. R0 for the overall duration was found to be 2.29 (95% CI: 1.84-2.78). Male gender and age ≥ 60 years were associated with SARS-CoV-2 infection (RR = 4.33, 95% CI: 2.07-9.05 and 5.32, 95% CI: 3.13-9.04, respectively). Isolation of infected individuals and stricter quarantine of remaining individuals reduced the R0 from 2.41 initially to 1.17 subsequently. CONCLUSION: R0 value was found comparable to the earlier studies indicating similar transmission dynamics among quarantined individuals in India. Universal testing and prompt isolation of infected individuals reduced the transmission of SARS-CoV-2. Smaller group sizes should be preferred to large groups during facility-based quarantine in evacuation situations. The role of asymptomatic individuals appears to be strong in SARS-CoV-2 transmission within closed populations.

15.
Trans R Soc Trop Med Hyg ; 114(7): 549-552, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32478835

RESUMO

BACKGROUND: The visceral leishmaniasis (kala-azar) elimination programme in India relies on indoor residual spraying (IRS) for sand-fly vector control. Insecticide supplied by a new manufacturer was introduced for IRS in 2019. We aimed to explore whether this led to a change in insecticide quantity being used in the field. METHODS: We compared measurements of weights of 250 mL of insecticide powder of two different manufacturers using a certified and calibrated weighing instrument. RESULTS: The density of insecticide supplied in 2019 was 43.4% lower than that in 2018, thereby leading to underdosing during current IRS activity. CONCLUSIONS: Insecticide-measuring containers should be recalibrated prior to every IRS round and also when an insecticide manufacturer changes, so that the insecticide dose is maintained within the recommended range.


Assuntos
Inseticidas , Leishmaniose Visceral , Phlebotomus , Psychodidae , Animais , Índia , Leishmaniose Visceral/prevenção & controle
16.
Sci Rep ; 10(1): 7992, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409687

RESUMO

The last decade has witnessed a swiftly increasing interest in the design and production of novel multivalent molecules as powerful alternatives for conventional antibodies in the fight against cancer and infectious diseases. However, while it is widely accepted that large-scale flexibility (10-100 nm) and free/constrained dynamics (100 ns -µs) control the activity of such novel molecules, computational strategies at the mesoscale still lag behind experiments in optimizing the design of crucial features, such as the binding cooperativity (a.k.a. avidity). In this study, we introduced different coarse-grained models of a polymer-linked, two-nanobody composite molecule, with the aim of laying down the physical bases of a thorough computational drug design protocol at the mesoscale. We show that the calculation of suitable potentials of mean force allows one to apprehend the nature, range and strength of the thermodynamic forces that govern the motion of free and wall-tethered molecules. Furthermore, we develop a simple computational strategy to quantify the encounter/dissociation dynamics between the free end of a wall-tethered molecule and the surface, at the roots of binding cooperativity. This procedure allows one to pinpoint the role of internal flexibility and weak non-specific interactions on the kinetic constants of the nanobody-wall encounter and dissociation. Finally, we quantify the role and weight of rare events, which are expected to play a major role in real-life situations, such as in the immune synapse, where the binding kinetics is likely dominated by fluctuations.

17.
J Phys Chem B ; 124(5): 727-734, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-31917571

RESUMO

The cell is an extremely complex environment, notably highly crowded, segmented, and confining. Overall, there is overwhelming and ever-growing evidence that to understand how biochemical reactions proceed in vivo, one cannot separate the biochemical actors from their environment. Effects such as excluded volume, obstructed diffusion, weak nonspecific interactions, and fluctuations all team up to steer biochemical reactions often very far from what is observed in ideal conditions. In this paper, we use Ficoll PM70 and PEG 6000 to build an artificial crowded milieu of controlled composition and density in order to assess how such environments influence the biocatalytic activity of lactate dehydrogenase (LDH). Our measurements show that the normalized apparent affinity and maximum velocity decrease in the same fashion, a behavior reminiscent of uncompetitive inhibition, with PEG resulting in the largest reduction. In line with previous studies on other enzymes of the same family, and in agreement with the known role of a surface loop involved in enzyme isomerization and regulation of access to the active site, we suggest that the crowding matrix interferes with the conformational ensemble of the enzyme. This likely results in both impaired enzyme-complex isomerization and thwarted product release. Molecular dynamics simulations confirm that excluded-volume effects lead to an entropic force that effectively tends to push the loop closed, thereby effectively shifting the conformational ensemble of the enzyme in favor of a more stable complex isoform. Overall, our study substantiates the idea that most biochemical kinetics cannot be fully explained without including the subtle action of the environment where they take place naturally, in particular accounting for important factors such as excluded-volume effects and also weak nonspecific interactions when present, confinement, and fluctuations.


Assuntos
Ficoll/química , L-Lactato Desidrogenase/antagonistas & inibidores , L-Lactato Desidrogenase/química , Biocatálise , Domínio Catalítico , Difusão , Entropia , Humanos , Cinética , Simulação de Dinâmica Molecular , NAD/química , Polietilenoglicóis/química , Ácido Pirúvico/química
18.
BMC Infect Dis ; 20(1): 10, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906924

RESUMO

BACKGROUND: A visceral leishmaniasis outbreak was reported from a village in a low-endemic district of Bihar, India. METHODS: Outbreak investigation with house-to-house search and rapid test of kala-azar suspects and contacts was carried out. Sandfly collection and cone bio-assay was done as part of entomological study. RESULTS: A spatially and temporally clustered kala-azar outbreak was found at Kosra village in Sheikhpura district with 70 cases reported till December 2018. Delay of more than a year was found between diagnosis and treatment of the index case. The southern hamlet with socio-economically disadvantaged migrant population was several times more affected than rest of the village (attack rate of 19.0% vs 0.5% respectively, ORMH = 39.2, 95% CI 18.2-84.4). The median durations between onset of fever to first contact with any health services, onset to kala-azar diagnosis, diagnosis to treatment were 10 days (IQR 4-18), 30 days (IQR 17-73) and 1 day (IQR 0.5 to 3), respectively, for 50 kala-azar cases assessed till June 2017. Three-fourths of these kala-azar cases had out-of-pocket medical expenditure for their condition. Known risk factors for kala-azar such as illiteracy, poverty, belonging to socially disadvantaged community, migration, residing in kutcha houses, sleeping in rooms with unplastered walls and non-use of mosquito nets were present in majority of these cases. Only half the dwellings of the kala-azar cases were fully sprayed. Fully gravid female P. argentipes collected post indoor residual spraying (IRS) and low sandfly mortality on cone-bioassay indicated poor effectiveness of vector control. CONCLUSIONS: There is need to focus on low-endemic areas of kala-azar. The elimination programme should implement a routine framework for kala-azar outbreak response. Complete case-finding, use of quality-compliant insecticide and coverage of all sprayable surfaces in IRS could help interrupt transmission during outbreaks.


Assuntos
Surtos de Doenças , Leishmaniose Visceral/epidemiologia , Migrantes , Animais , Surtos de Doenças/prevenção & controle , Feminino , Humanos , Incidência , Índia/epidemiologia , Controle de Insetos/estatística & dados numéricos , Inseticidas/administração & dosagem , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/terapia , Leishmaniose Visceral/transmissão , Psychodidae/fisiologia , Fatores de Risco
19.
J Vector Borne Dis ; 57(3): 240-248, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-34472508

RESUMO

BACKGROUND & OBJECTIVES: Indoor residual spraying (IRS) is part of a key strategy for elimination of visceral leishmaniasis (kala-azar). IRS for kala-azar elimination in India uses 125 g 5% alpha-Cypermethrin wettable powder which is mixed with 7.5 litres of water and sprayed on walls using hand compression sprayers. Insecticide quantity is measured volumetrically through a container. METHODS: A cross-sectional study design with cluster random sampling was adopted to select 272 IRS squads of 46 blocks across 12 districts in Bihar, India. The quantity of insecticide measured by the container used by each IRS squad was recorded. RESULTS: Mean weight of insecticide measured was found to be 147 g (SD 33.9). One-thirds of squads were measuring less than the nationally recommended quantity of 125 g. Two-fifths of squads were overdosing with use of more than 150 g insecticide powder. Shoving the containers into a heap of insecticide powder resulted in heavier and less consistent measurements as compared to filling the containers from the top. Different types of measuring containers and different manufacturers of insecticide were shown to significantly account for the variation in the quantity of insecticide being measured. INTERPRETATION AND CONCLUSION: Standardization of insecticide measurement by IRS squads is needed, both to prevent under-dosing and overdosing of insecticide residue on walls. Standard operating procedures for calibrating and using uniform measuring containers should be implemented. Further, use of measuring containers may be replaced altogether with manufacturer-packaged amounts of insecticide formulation which could be directly used to prepare one-tank load of insecticide suspension.

20.
J Vector Borne Dis ; 57(2): 161-169, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-34290161

RESUMO

BACKGROUND & OBJECTIVES: Detection and treatment of post-kala-azar dermal leishmaniasis (PKDL) cases is considered important for kala-azar elimination. The objective of our study was to find out the proportion of different forms of lesions, interruption of treatment and rate of treatment completion, cure rates of PKDL, risk factors for developing severe forms of PKDL and utilization of services offered by the kala-azar elimination program. METHODS: A cross-sectional survey of PKDL patients registered for treatment at all levels of care during 2015 and 2016 was done. RESULTS: 576 PKDL patients who had started treatment in 2015 and 2016 were studied. Three-fourths of all patients were found to be clinically cured after a year of follow-up. Around 90% lesions were of macular type. Interruption of treatment was observed in one-fourth of PKDL patients. Median duration between kala-azar treatment and development of PKDL was 4.5 years. Around 79% patients had past history of kala-azar treatment. Discontinuation of treatment during earlier kala-azar episode was significantly associated with the development of papular and nodular forms of lesion. 43% of patients had received the incentive of INR 2000 after completion of treatment. Around three-fourths women in the reproductive age group were found not to use any contraceptive method during PKDL treatment. INTERPRETATION & CONCLUSION: PKDL treatment interruption should be reduced through ensuring drug supply and timely retrieval of patients. Directly observed treatment should be implemented and combination regimen should be explored to improve final cure rate. Delivery of financial incentive to PKDL patients and counselling and contraception to women of reproductive age group should be improved.


Assuntos
Antiprotozoários/uso terapêutico , Leishmaniose Cutânea/epidemiologia , Leishmaniose Visceral/complicações , Fosforilcolina/análogos & derivados , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Doenças Endêmicas , Feminino , Humanos , Índia/epidemiologia , Lactente , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/etiologia , Leishmaniose Cutânea/parasitologia , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/parasitologia , Masculino , Pessoa de Meia-Idade , Fosforilcolina/uso terapêutico , Fatores de Risco , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...