Serosurveillance of dengue infection and correlation with mosquito pools for dengue virus positivity during the COVID-19 pandemic in Tamil Nadu, India - A state-wide cross-sectional cluster randomized community-based study.

Background: Dengue is a vector-borne viral disease impacting millions across the globe. Nevertheless, akin to many other diseases, reports indicated a decline in dengue incidence and seroprevalence during the COVID-19 pandemic (2020-22). This presumably could be attributed to reduced treatment-seeking rates, under-reporting, misdiagnosis, disrupted health services and reduced exposure to vectors due to lockdowns. Scientific evidence on dengue virus (DENV) disease during the COVID-19 pandemic is limited globally. Methods: A cross-sectional, randomized cluster sampling community-based survey was carried out to assess anti-dengue IgM and IgG and SARS-CoV-2 IgG seroprevalence across all 38 districts of Tamil Nadu, India. The prevalence of DENV in the Aedes mosquito pools during 2021 was analyzed and compared with previous and following years of vector surveillance for DENV by real-time PCR. Findings: Results implicate that both DENV-IgM and IgG seroprevalence and mosquito viral positivity were reduced across all the districts. A total of 13464 mosquito pools and 5577 human serum samples from 186 clusters were collected. Of these, 3·76% of mosquito pools were positive for DENV. In the human sera, 4·12% were positive for DENV IgM and 6·4% were positive for DENV IgG. The anti-SARS-CoV-2 antibody titres correlated with dengue seropositivity with a significant association whereas vaccination status significantly correlated with dengue IgM levels. Interpretation: Continuous monitoring of DENV seroprevalence, especially with the evolving variants of the SARS-CoV-2 virus and surge in COVID-19 cases will shed light on the transmission and therapeutic attributes of dengue infection.

Spatiotemporal Epidemiology of Malaria in India from 2007 to 2022.

India is a major contributor to the global burden of malaria, especially Plasmodium vivax infection. Understanding the spatiotemporal trends of malaria across India over the last two decades may assist in targeted intervention. The population-normalized spatiotemporal trends of malaria epidemiology in India from 2007 to 2022 were analyzed using a geographic information system with the publicly available "malaria situation" report of the National Vector Borne Disease Control Program (NVBDCP). The NVBDCP data showed malaria cases to have steeply declined from 1.17 million in 2015 to 0.18 million cases in 2022; this is 10.1 and 18.7 fold lower than the WHO's estimate of 11.93 million and 3.38 million cases in 2015 and 2022, respectively. From 2007 to 2022, Mizoram, Meghalaya, Tripura, Odisha, Chhattisgarh, and Jharkhand consistently reported high caseloads of Plasmodium falciparum. In the same period, the P. vivax caseload was high in Arunachal Pradesh, Mizoram, Nagaland, Jharkhand, Odisha, Chhattisgarh, Goa, Daman and Diu, Dadra and Nagar Haveli, and Andaman and Nicobar Islands. The distribution of forest cover, annual rainfall, and proportion of the Scheduled Tribe population (the most underprivileged in Indian society) spatially correlated with malaria cases and deaths. Mizoram is the only state where cases were higher in 2022 than in 2007. Overall, India has made tremendous progress in controlling malaria and malaria-related deaths in the last decade. The decline could be attributed to the effective vector and parasite control strategies implemented across the country.

Spatio-temporal epidemiology and associated indicators of COVID-19 (wave-I and II) in India.

The spatio-temporal distribution of COVID-19 across India's states and union territories is not uniform, and the reasons for the heterogeneous spread are unclear. Identifying the space-time trends and underlying indicators influencing COVID-19 epidemiology at micro-administrative units (districts) will help guide public health strategies. The district-wise daily COVID-19 data of cases and deaths from February 2020 to August 2021 (COVID-19 waves-I and II) for the entire country were downloaded and curated from public databases. The COVID-19 data normalized with the projected population (2020) and used for space-time trend analysis shows the states/districts in southern India are the worst hit. Coastal districts and districts adjoining large urban regions of Mumbai, Chennai, Bengaluru, Goa, and New Delhi experienced > 50,001 cases per million population. Negative binomial regression analysis with 21 independent variables (identified through multicollinearity analysis, with VIF < 10) covering demography, socio-economic status, environment, and health was carried out for wave-I, wave-II, and total (wave-I and wave-II) cases and deaths. It shows wealth index, derived from household amenities datasets, has a high positive risk ratio (RR) with COVID-19 cases (RR: 3.577; 95% CI: 2.062-6.205) and deaths (RR: 2.477; 95% CI: 1.361-4.506) across the districts. Furthermore, socio-economic factors such as literacy rate, health services, other workers' rate, alcohol use in men, tobacco use in women, overweight/obese women, and rainfall have a positive RR and are significantly associated with COVID-19 cases/deaths at the district level. These positively associated variables are highly interconnected in COVID-19 hotspot districts. Among these, the wealth index, literacy rate, and health services, the key indices of socio-economic development within a state, are some of the significant indicators associated with COVID-19 epidemiology in India. The identification of district-level space-time trends and indicators associated with COVID-19 would help policymakers devise strategies and guidelines during public health emergencies.

Spontaneous Modulation Doping in Semi-Crystalline Conjugated Polymers Leads to High Conductivity at Low Doping Concentration.

The possibility to control the charge carrier density through doping is one of the defining properties of semiconductors. For organic semiconductors, the doping process is known to come with several problems associated with the dopant compromising the charge carrier mobility by deteriorating the host morphology and/or introducing Coulomb traps. While for inorganic semiconductors these factors can be mitigated through (top-down) modulation doping, this concept has not been employed in organics. Here, this work shows that properly chosen host/dopant combinations can give rise to spontaneous, bottom-up modulation doping, in which the dopants preferentially sit in an amorphous phase, while the actual charge transport occurs predominantly in a crystalline phase with an unaltered microstructure, spatially separating dopants and mobile charges. Combining experiments and numerical simulations, this work shows that this leads to exceptionally high conductivities at relatively low dopant concentrations.

Switching global correlations on and off in a many-body quantum state by tuning local entanglement.

A quantum many-body state built on a classical 1D Ising model with locally entangled qubits is considered. This setup can model an infinite player quantum Prisoner's dilemma game with each site representing two entangled players (or qubits). The local entanglement γ between two qubits placed on a site in the 1D Ising model and classical coupling between adjacent sites of the Ising model have an apposite influence on qubits. It points to a counter-intuitive situation wherein local entanglement at a site can exactly cancel global correlations, signaling an artificial quantum many-body state wherein, by locally tuning the entanglement at a particular site, one can transition from a strongly correlated quantum state to an uncorrelated quantum state and then to a correlated classical state. In other words, we can simulate a state similar to a type II superconducting state via local tuning of entanglement in a 1D Ising chain with entangled qubits.

The Impact, Emerging Needs, and New Research Questions Arising from 12 Years of the Center for the Study of Complex Malaria in India.

The Center for the Study of Complex Malaria in India (CSCMi) was launched in 2010 with the overall goal of addressing major gaps in our understanding of "complex malaria" in India through projects on the epidemiology, transmission, and pathogenesis of the disease. The Center was mandated to adopt an integrated approach to malaria research, including building capacity, developing infrastructure, and nurturing future malaria leaders while conducting relevant and impactful studies to assist India as it moves from control to elimination. Here, we will outline some of the interactions and impacts the Center has had with malaria policy and control counterparts in India, as well as describe emerging needs and new research questions that have become apparent over the past 12 years.

Learnings from two independent malaria elimination demonstration projects in India.

PROBLEM: India and sub-Saharan Africa contributes about 85% of the global malaria burden, and India is committed to eliminating malaria by 2030. APPROACH: Two novel initiatives-the Malaria Elimination Demonstration Project (MEDP) in Madhya Pradesh and Durgama Anchalare Malaria Nirakaran (DAMaN) in Odisha-were initiated independently to demonstrate that indigenous malaria can be eliminated in a short period of time. LOCAL SETTING: These initiatives focused on rural, tribal areas where there is a high malaria burden and complex epidemiology. RELEVANT CHANGES: The case management and vector control strategies used in these programmes were based on the national guidelines, with context-specific changes and introduction of accountability at management, operational, technical and financial levels. The MEDP achieved a 91% reduction in malaria cases and recorded zero transmission for 6 consecutive and a total of 9 mo. The DAMaN project brought about an 88% reduction in malaria cases. LESSONS LEARNED: Malaria elimination will require robust surveillance and case management, monitoring of vector control interventions, community-centric information education communication and behaviour change communication initiatives and management controls, as well as regular internal and external reviews.

A model for malaria elimination based on learnings from the Malaria Elimination Demonstration Project, Mandla district, Madhya Pradesh.

BACKGROUND: Malaria Elimination Demonstration Project (MEDP) was started as a Public-Private-Partnership between the Indian Council of Medical Research through National Institute of Research in Tribal Health, Govt. of Madhya Pradesh and Foundation of Disease Elimination and Control of India, which is a Corporate Social Responsibility (CSR) initiative of the Sun Pharmaceutical Industries Limited. The project's goal was to demonstrate that malaria can be eliminated from a high malaria endemic district along with prevention of re-establishment of malaria and to develop a model for malaria elimination using the lessons learned and knowledge acquired from the demonstration project. METHODS: The project employed tested protocols of robust surveillance, case management, vector control, and capacity building through continuous evaluation and training.  The model was developed using the learnings from the operational plan, surveillance and case management, monitoring and feedback, entomological investigations and vector control, IEC and capacity building, supply chain management, mobile application (SOCH), and independent reviews of MEDP. RESULTS: The MEDP has been operational since April 2017 with field operations from August 2017, and has observed: (1) reduction in indigenous cases of malaria by about 91 %; (2) need for training and capacity building of field staff for diagnosis and treatment of malaria; (3) need for improvement insecticide spraying and for distribution and usage of bed-nets; (4) need for robust surveillance system that captures and documents information on febrile cases, RDT positive individuals, and treatments provided; (5) need for effective supervision of field staff based on advance tour plan; (6) accountability and controls from the highest level to field workers; and (7) need for context-specific IEC. CONCLUSIONS: Malaria elimination is a high-priority public health goal of the Indian Government with a committed deadline of 2030. In order to achieve this goal, built-in systems of accountability, ownership, effective management, operational, technical, and financial controls will be crucial components for malaria elimination in India. This manuscript presents a model for malaria elimination with district as an operational unit, which may be considered for malaria elimination in India and other countries with similar geography, topography, climate, endemicity, health infrastructure, and socio-economic characteristics.

Thermodynamic susceptibility as a measure of cooperative behavior in social dilemmas.

The emergence of cooperation in the thermodynamic limit of social dilemmas is an emerging field of research. While numerical approaches (using replicator dynamics) are dime a dozen, analytical approaches are rare. A particularly useful analytical approach is to utilize a mapping between the spin-1/2 Ising model in 1D and the social dilemma game and calculate the magnetization, which is the net difference between the fraction of cooperators and defectors in a social dilemma. In this paper, we look at the susceptibility, which probes the net change in the fraction of players adopting a certain strategy, for both classical and quantum social dilemmas. The reason being, in statistical mechanics problems, the thermodynamic susceptibility as compared to magnetization is a more sensitive probe for microscopic behavior, e.g., observing small changes in a population adopting a certain strategy. In this paper, we find the thermodynamic susceptibility for reward, sucker's payoff, and temptation in classical Prisoner's Dilemma to be positive, implying that the turnover from defect to cooperate is greater than vice versa, although the Nash equilibrium for the two-player game is to defect. In the classical hawk-dove game, the thermodynamic susceptibility for resource suggests that the number of players switching to hawk from dove strategy is dominant. Entanglement in Quantum Prisoner's Dilemma has a non-trivial role in determining the behavior of thermodynamic susceptibility. At maximal entanglement, we find that sucker's payoff and temptation increase the number of players switching to defect. In the zero-temperature limit, we find that there are two second-order phase transitions in the game, marked by a divergence in the susceptibility. This behavior is similar to that seen in type-II superconductors wherein also two second-order phase transitions are seen.

Hydroxychloroquine as prophylaxis or treatment for COVID-19: What does the evidence say?

Hydroxychloroquine (HCQ), an antimalarial has been proposed as possible treatment for coronavirus disease-2019 (COVID-19). India has approved the use of HCQ for prophylaxis of asymptomatic health workers treating suspected or confirmed COVID-19 cases, and asymptomatic household contacts of confirmed patients. The U.S. Food and Drug Administration has issued Emergency Use Authorization for the use of HCQ to treat COVID-19 in adolescents and adults. In this review, we go over the available evidence for and against HCQ's use as prophylaxis or treatment for COVID-19, especially in the Indian context.

Increase of Plasma TNF-α Is Associated with Decreased Levels of Blood Platelets in Clinical Dengue Infection.

Dengue virus (DENV) infection has become an increasingly common concern in tropical and subtropical regions. It has protean manifestations ranging from febrile phase to severe life-threatening illness. In this study, we estimated Th1 and Th2 cytokines and correlated the levels with dengue severity along with certain hematological and biochemical parameters. We also studied the seroprevalence of dengue between October and December 2017 at the Government Theni Medical College, India. Individuals with dengue fever (DF) were positive for either IgM or IgG, or both. The biochemical and hematological parameters along with plasma tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), granulocyte monocyte-colony stimulating factor (GM-CSF), interleukin (IL)-13, IL-12p70, IL-10, IL-5, IL-4, and IL-2 cytokines were estimated. The prevalence of DF was 42.9% during the study period. IL-2, TNF-α, IL-4, and IL-10 levels were significantly elevated (p < 0.005) in patients with secondary DENV infection, whereas the level of IL-13 remained unaltered during both primary and secondary infections. No statistically significant difference was noticed with IL-12p70, IL-5, IFN-γ, and GM-CSF between the healthy controls and the primary and secondary DENV-infected groups. Increase of 1 unit of TNF-α was associated with a decrease of 160 units of blood platelets. Together, the study suggests that TNF-α could play a key role in the pathogenesis of dengue, and despite the decrease in platelet levels, it remains to be seen whether any other inflammatory cells regulate the levels of TNF-α in DENV infection.

Adsorptive removal of surfactant using dolochar: A kinetic and statistical modeling approach.

Disturbingly high rates of consumption of surfactants in household and industries have led to mark them as emerging contaminants in the environment. In the present work, removal of sodium dodecyl sulfate (SDS), an anionic surfactant, using an industrial waste (dolochar) was explored. The adsorbent material was characterized with the help of Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Kinetic evaluation was performed using first, pseudo-first, second, and pseudo-second order models. Adsorption of SDS over dolochar was expressed best by pseudo-second order kinetic model with regression coefficient (R2 ) of .99. Three input parameters including adsorbent dose (20-10 g/L), initial concentration (30-100 mg/L) of the surfactant, and contact time (2-60 min) were chosen for optimization using response surface methodology based on Box-Behnken design (BBD) approach. A total of 15 experiments were run to examine the effect of these variables on removal of SDS by dolochar in a multivariate system. A regression analysis indicated the experimental data fitted well to a quadratic polynomial model with coefficient of regression (R2 ) as .99. ANOVA and lack-of-fit test depicted the precision and efficiency of the model. The optimized conditions for SDS removal were found to be adsorbent dose 16.62 g/L, contact time 40 min, and initial concentration 47 mg/L with removal efficiency as 98.91%. PRACTITIONER POINTS: Daily ablutions and use of personal care products introduce a number of surfactants and recalcitrant compounds into the environment. Adsorption is a handy and easy to operate treatment technique to remove graywater pollutants. Kinetic and statistical modeling may be recommended as one of the most prominent tools to understand the removal mechanism. Decentralized treatment of graywater using industrial wastes is recommended as sustainable solution in the developing nations.

Malaria in North-East India: Importance and Implications in the Era of Elimination.

Worldwide and in India, malaria elimination efforts are being ramped up to eradicate the disease by 2030. Malaria elimination efforts in North-East (NE) India will have a great bearing on the overall efforts to eradicate malaria in the rest of India. The first cases of chloroquine and sulfadoxine-pyrimethamine resistance were reported in NE India, and the source of these drug resistant parasites are most likely from South East Asia (SEA). NE India is the only land route through which the parasites from SEA can enter the Indian mainland. India's malaria drug policy had to be constantly updated due to the emergence of drug resistant parasites in NE India. Malaria is highly endemic in many parts of NE India, and Plasmodium falciparum is responsible for the majority of the cases. Highly efficient primary vectors and emerging secondary vectors complicate malaria elimination efforts in NE India. Many of the high transmission zones in NE India are tribal belts, and are difficult to access. The review details the malaria epidemiology in seven NE Indian states from 2008 to 2018. In addition, the origin and evolution of resistance to major anti-malarials are discussed. Furthermore, the bionomics of primary vectors and emergence of secondary malaria vectors, and possible strategies to prevent and control malaria in NE are outlined.

Effect of insecticide-treated bed nets on visceral leishmaniasis incidence in Bangladesh. A retrospective cohort analysis.

BACKGROUND: Visceral leishmaniasis (VL) is a parasitic disease, transmitted by the sand fly species Phlebotomus argentipes in the Indian sub-continent. Effective vector control is highly desirable to reduce vector density and human and vector contact in the endemic communities with the aim to curtail disease transmission. We evaluated the effect of long lasting insecticide treated bed nets (LLIN) and bed nets impregnated with slow-release insecticide tablet K-O TAB 1-2-3 (jointly insecticide-treated nets or ITN) on VL incidence in a highly endemic sub-district (upazila) in Bangladesh. METHODS: Several distributions of LLIN or K-O TAB 1-2-3 for self-impregnation of bed nets at home took place in Fulbaria upazila, Mymensigh district from 2004 to 2008 under three research projects, respectively funded by CDC, Atlanta, USA (2004) and WHO-TDR, Geneva, Switzerland (2006 & 2008). We included all households (n = 8142) in the 20 villages that had benefited in the past from one of these interventions (1295 donated LLIN and 11,918 local bed nets impregnated with K-O TAB 1-2-3) in the "exposed cohort". We recruited a "non-exposed cohort" in villages with contemporaneously similar incidence rates who had not received such vector control interventions (7729 HHs from nine villages). In both cohorts, we visited all families house to house and ascertained any VL cases for the 3 year period before and after the intervention. We evaluated the incidence rate (IR) of VL in both cohorts as primary endpoint, applying the difference-in-differences method. RESULTS: The study identified 1011 VL cases (IR 140.47/10,000 per year [py]) before the intervention, of which 534 and 477 cases in the intervention and control areas respectively. The IR was 144.13/10,000 py (534/37050) and 136.59/10,000 py (477/34923) in the intervention and control areas respectively, with no significant difference (p = 0.3901) before the intervention. After the intervention, a total of 555 cases (IR 77.11/10,000 py) were identified of which 178 (IR 48.04/10,000 py) in the intervention and 377 (107.95/10,000 py) in the control area. The intervention area had a significant lower IR than the control area during follow up, rate difference = -59.91, p<0.0001. The IR during follow up was significantly reduced by 96.09/10,000 py in the intervention area (p<0.0001) and 28.63/10,000 py in control area (p<0.0001) compared to baseline. There was a strong and significant overall effect of the ITN intervention, δ = -67.45, p <0.0001. Sex (OR = 1.36, p<0.0001) and age (OR = 0.99, p<0.0001) also had a significant effect on VL incidence. Male had a higher risk of VL than female and one year increase in age decreased the likelihood of VL by about 0.92%. Two third of the VL incidence occurred in the age range 2 to 30 years (median age of VL patients was 17 years). CONCLUSION: VL incidence rate was significantly lower in the ITN intervention cohort compared to control in Bangladesh. Some bias due to more intense screen-and-treat activities or other interventions in the intervention area cannot be ruled out. Nonetheless, given their feasibility and sustainability, ITNs should be considered for integrated vector control during the maintenance phase of the VL elimination programme.

Perspective of mitigating atmospheric heavy metal pollution: using mosses as biomonitoring and indicator organism.

Mosses were proved as an ideal and reliable biomonitor as well as an indicator of atmospheric trace metal pollution. They are used as model indicator species of air pollution since long back due to their simple structure, genetic diversity, totipotency, rapid colony-forming ability, and high metal resistance behavior. Bryomonitoring technique is gradually being popularized as an economically viable procedure for estimating the degrees of environmental health and evaluating the toxic pollutants in biosphere. Thus, in the present scenario, many parts of the world use these organisms for monitoring the air pollution. This article describes an overview of the relationship of terrestrial mosses with trace metals with respect to their uptake, accumulation, and toxification as well as detoxification and tolerance mechanisms. The review article explicitly expresses the caliber of the cryptogamic mosses in establishing the pristine environment around the world. It also highlights the underpinning mechanisms and potential for future research directions. We have referred more than 250 articles, which deals with the assessment and impact of different heavy metals on 52 numbers of different moss species belongs to different climatic zones. The present review covers the research work in this area carried out worldwide since 1965.

Recent Updates on Mouse Models for Human Immunodeficiency, Influenza, and Dengue Viral Infections.

Well-developed mouse models are important for understanding the pathogenesis and progression of immunological response to viral infections in humans. Moreover, to test vaccines, anti-viral drugs and therapeutic agents, mouse models are fundamental for preclinical investigations. Human viruses, however, seldom infect mice due to differences in the cellular receptors used by the viruses for entry, as well as in the innate immune responses in mice and humans. In other words, a species barrier exists when using mouse models for investigating human viral infections. Developing transgenic (Tg) mice models expressing the human genes coding for viral entry receptors and knock-out (KO) mice models devoid of components involved in the innate immune response have, to some extent, overcome this barrier. Humanized mouse models are a third approach, developed by engrafting functional human cells and tissues into immunodeficient mice. They are becoming indispensable for analyzing human viral diseases since they nearly recapitulate the human disease. These mouse models also serve to test the efficacy of vaccines and antiviral agents. This review provides an update on the Tg, KO, and humanized mouse models that are used in studies investigating the pathogenesis of three important human-specific viruses, namely human immunodeficiency (HIV) virus 1, influenza, and dengue.

Indoor residual spraying for kala-azar vector control in Bangladesh: A continuing challenge.

BACKGROUND: Visceral leishmaniasis (VL) in the Indian subcontinent is a fatal disease if left untreated. Between 1994 to 2013, the Ministry of Health of Bangladesh reported 1,09,266 cases of VL and 329 VL related deaths in 37 endemic districts. Indoor residual spraying (IRS) using dichlorodiphenyltrichloroethane (DDT) was used by the national programme in the 1960s to control malaria. Despite findings of research trials demonstrating that the synthetic pyrethroid deltamethrin 5 WP was very effective at reducing vector densities, no national VL vector control operations took place in Bangladesh between 1999 to early 2012. In 2012, IRS using deltamethrin 5 WP was re-introduced by the national programme, which consisted of pre-monsoon spraying in eight highly endemic sub-districts (upazilas). The present study aims to evaluate the effectiveness of IRS on VL vectors, as well as the process and performance of the spraying activities by national programme staff. METHODS: Five highly endemic upazilas of Mymensingh district were purposively selected (Fulbaria, Trishal, Mukthagacha, Gaforgaon and Bhaluka) to conduct the present study using the WHO/TDR monitoring and evaluation tool kit. IRS operations, conducted by 136 squads/teams, and 544 spraymen, were observed using check lists and questionnaires included in the WHO/TDR monitoring and evaluation tool kit. A household (HH) acceptability survey of IRS was conducted in all study areas using a structured questionnaire in 600 HHs. To measure the efficacy of IRS, pre-IRS (two weeks prior) and post-IRS (at one and five months after), vector density was measured using CDC light traps for two consecutive nights. Bioassays, using the WHO cone-method, were carried out in 80 HHs (40 sprayed and 40 unsprayed) to measure the effectiveness of the insecticide on sprayed surfaces. RESULTS: Of the 544 spraymen interviewed pre-IRS, 60%, 3% and 37% had received training for one, two and three days respectively. During spraying activities, 64% of the spraying squads had a supervisor in 4 upazilas but only one upazila (Mukthagacha) achieved 100% supervision of squads. Overall, 72.8% of the spraying squads in the study upazilas had informed HHs members to prepare their houses prior to spraying. The required personal protective equipment was not provided by the national programme during our observations and the spraying techniques used by all sprayers were sub-standard compared to the standard procedure mentioned in the M&E toolkit. In the HH interviews, 94.8% of the 600 respondents said that all their living rooms and cattle sheds had been sprayed. Regarding the effectiveness measurements (i.e. reduction of vector densities), a total of 4132 sand flies were trapped in three intervals, of which 3310 (80.1%) were P. argentipes; 46.5% (1540) males and 53.5% (1770) females. At one month post-IRS, P. argentipes densities were reduced by 22.5% but the 5 months post-IRS reduction was only 6.4% for both male and female. The bioassay tests showed a mean corrected mortality of P. argentipes sand flies at one month post-IRS of 87.3% which dropped to 74.5% at 4 months post-IRS in three upazilas, which is below the WHO threshold level (80%). CONCLUSION: The national programme should conduct monitoring and evaluation activities to ensure high quality of IRS operations as a pre-condition for achieving a fast and sustained reduction in vector densities. This will continue to be important during the maintenance phase of VL elimination on the Indian subcontinent. Further research is needed to determine other suitable vector control option(s) when the case numbers are very low.

Control of Phlebotomus argentipes (Diptera: Psychodidae) sand fly in Bangladesh: A cluster randomized controlled trial.

BACKGROUND: A number of studies on visceral leishmaniasis (VL) vector control have been conducted during the past decade, sometimes came to very different conclusion. The present study on a large sample investigated different options which are partially unexplored including: (1) indoor residual spraying (IRS) with alpha cypermethrin 5WP; (2) long lasting insecticide impregnated bed-net (LLIN); (3) impregnation of local bed-nets with slow release insecticide K-O TAB 1-2-3 (KOTAB); (4) insecticide spraying in potential breeding sites outside of house using chlorpyrifos 20EC (OUT) and different combinations of the above. METHODS: The study was a cluster randomized controlled trial where 3089 houses from 11 villages were divided into 10 sections, each section with 6 clusters and each cluster having approximately 50 houses. Based on vector density (males plus females) during baseline survey, the 60 clusters were categorized into 3 groups: (1) high, (2) medium and (3) low. Each group had 20 clusters. From these three groups, 6 clusters (about 300 households) were randomly selected for each type of intervention and control arms. Vector density was measured before and 2, 4, 5, 7, 11, 14, 15, 18 and 22 months after intervention using CDC light traps. The impact of interventions was measured by using the difference-in-differences regression model. RESULTS: A total of 17,434 sand flies were collected at baseline and during the surveys conducted over 9 months following the baseline measurements. At baseline, the average P. argentipes density per household was 10.6 (SD = 11.5) in the control arm and 7.3 (SD = 8.46) to 11.5 (SD = 20.2) in intervention arms. The intervention results presented as the range of percent reductions of sand flies (males plus females) and rate ratios in 9 measurements over 22 months. Among single type interventions, the effect of IRS with 2 rounds of spraying (applied by the research team) ranged from 13% to 75% reduction of P. argentipes density compared to the control arm (rate-ratio [RR] ranged from 0.25 to 0.87). LLINs caused a vector reduction of 9% to 78% (RR, 0.22 to 0.91). KOTAB reduced vectors by 4% to 73% (RR, 0.27 to 0.96). The combination of LLIN and OUT led to a vector reduction of 26% to 86% (RR, 0.14 to 0.74). The reduction for the combination of IRS and OUT was 8% to 88% (RR, 0.12 to 0.92). IRS and LLIN combined resulted in a vector reduction of 13% to 85% (RR, 0.15 to 0.77). The IRS and KOTAB combination reduced vector densities by 16% to 86% (RR, 0.14 to 0.84). Some intermediate measurements for KOTAB alone and for IRS plus LLIN; and IRS plus KOTAB were not statistically significant. The bioassays on sprayed surfaces or netting materials showed favourable results (>80% mortality) for 22 months (IRS tested for 12 months). In the KOTAB, a gradual decline was observed after 6 months. CONCLUSIONS: LLIN and OUT was the best combination to reduce VL vector densities for 22 months or longer. Operationally, this is much easier to apply than IRS. A cost analysis of the preferred tools will follow. The relationship between vector density (males plus females) and leishmaniasis incidence should be investigated, and this will require estimates of the Entomological Inoculation Rate.

Temporo-spatial distribution of insecticide-resistance in Indian malaria vectors in the last quarter-century: Need for regular resistance monitoring and management.

The Indian vector control programme similar to other programmes in the world is still reliant on chemical insecticides. Anopheles culicifacies is the major vector out of six primary malaria vectors in India and alone contributes about 2/3 malaria cases annually; and per se its control is actually control of malaria in India. For effective management of vectors, current information on their susceptibility status to different insecticides is essential. In this review, an attempt was made to compile and present the available data on the susceptibility status of different malaria vector species in India from the last 2.5 decades. Literature search was conducted by different means mainly web and library search; susceptibility data was collated from 62 sources for the nine malaria vector species from 145 districts in 21 states and two union territories between 1991 and 2016. Interpretation of the susceptibility/resistance status was made on basis of the recent WHO criteria. Comprehensive analysis of the data indicated that An. culicifacies, a major vector species was resistant to at least one insecticide in 70% (101/145) of the districts. It was reported mostly resistant to DDT and malathion whereas, its resistant status against deltamethrin varied across the districts. The major threat for the malaria control programmes is multiple-insecticide-resistance in An. culicifacies which needs immediate attention for resistance management in order to sustain the gains achieved so far, as the programmes have targeted malaria elimination by 2030.

Elimination of Kala-Azar from the Southeast Asia Region.

AbstractVisceral leishmaniasis (VL), popularly known as kala-azar, is essentially a disease of poverty. Kala-azar is caused by a parasite, Leishmania donovani. Recent review indicates that worldwide 98 countries are endemic for kala-azar. Approximately 0.2-0.4 million new VL cases occur each year worldwide. More than 90% of global VL cases occur in Bangladesh, Brazil, Ethiopia, India, South Sudan, and Sudan. This trend is slowly changing due to the progress in kala-azar elimination in southeast Asia, where Bangladesh has reported an average of some 600 new cases in 2014-2015. With the advancement in our knowledge about the disease and development of tools to diagnose and treat VL, it was considered that elimination of kala-azar was possible from India, Nepal, and Bangladesh. The three countries signed a memorandum of understanding in 2005 for collaboration. Miltefosine is the first ever oral drug developed to treat VL, which was later replaced by lipid amphotericin B. The main components of the strategy are early diagnosis using rK39 strip test and complete treatment utilizing miltefosine for 28 days. Dichlorodiphenyltrichloroethane or pyrethroids were deployed for vector control. There was much to be desired for better performance of the vector control activity. Pharmacovigilance and monitoring of drug resistance were the weakest part of the program. In the post-elimination phase, surveillance reinforced by active case finding will of a crucial factor for sustainability of the elimination. A strong political will is required to ensure elimination of kala-azar from the Indian subcontinent and its sustainability in the post-elimination phase.