Characterization of the anopheline vector breeding habitats: Implications for elimination of malaria in tribal inhabited Car Nicobar Island.

Background & objectives: Malaria is an important public health problem in Andaman & Nicobar archipelago. Among the three districts, Nicobar is the most endemic district where API is >2. In this district, the malaria incidence in Car Nicobar Tehsil has declined steadily over the past 10 years. A renewed initiative to consolidate this gain is being made with the ultimate objective of achieving zero indigenous transmission of malaria in Car Nicobar. So, the present study undertook a close environmental monitoring of water bodies for assessing changes in the risk potential of mosquito vector breeding habitats which can augment the elimination programme. Methods: The breeding habitats of anopheline mosquitoes were sampled in 16 areas of Car Nicobar Island for eight time periods during 2017-2020. Along with anophelines, various associated water parameters (n=60) were estimated, viz. physicochemical (n=13), and biological, which included culicine mosquito immatures, insect predators (n=5), phytoplanktons (n=31) and zooplanktons (n=10). Results: In the 16 study sites, overall 1126 surface water stagnating bodies constituting 21 different habitat types were surveyed. Of these, 17 were positive for anopheline breeding. Water bodies from three villages were consistently found to be positive for anopheline breeding. However, early instars of anopheline larvae were more abundant compared to the late instars. Four anopheline species were recorded, including Anopheles sundaicus, A. barbirostris, A. insulaeflorum and A. subpictus, in which 48 per cent were A. sundaicus. Multivariable analysis indicated that anopheline density was significantly higher in permanent water bodies than in temporary habitats (P<0.05) (high risk of anophelines). The highest pH (≥8.2), dissolved solids (≥0.39) levels showed significantly (P<0.05) decreased larval densities (lower risk of breeding), adjusted with breeding sites and season. Nitrite levels increased (P=0.022) larval densities. Interpretation & conclusions: The present study facilitated estimating the productive period of a larval habitat enabling target larval sources to reduce adult populations. Implementing larviciding strategy before monsoon season is presumably the most cost-effective strategy. The output can be utilized for environmental monitoring of mosquito breeding risk in other malaria endemic areas, particularly where medium/large water bodies are the predominant breeding sites for malaria vectors.

Non-communicable diseases as a major contributor to deaths in 12 tribal districts in India.

Background & objectives: Non-communicable diseases (NCDs) are the leading cause of death in India. Although studies have reported a high prevalence of NCD in tribal populations, there are limited data pertaining mortality due to NCDs. Therefore, in this study we estimated the proportion of deaths due to NCDs among 15 yr and older age group in tribal districts in India. Methods: We conducted a community-based survey in 12 districts (one per State) with more than 50 per cent tribal population. Data were collected using a verbal autopsy tool from the family member of the deceased. The estimated sample size was 452 deaths per district. We obtained the list of deaths for the reference period of one year and updated it during the survey. The cause of death was assigned using the International Classification of Diseases-10 classification and analyzed the proportions of causes of death. The age-standardized death rate (ASRD) was also estimated. Results: We surveyed 5292 deaths among those above 15 years of age. Overall, NCDs accounted for 66 per cent of the deaths, followed by infectious diseases (15%) and injuries (11%). Cardiovascular diseases were the leading cause of death in 10 of the 12 sites. In East Garo Hills (18%) and Lunglei (26%), neoplasms were the leading cause of death. ASRD due to NCD ranged from 426 in Kinnaur to 756 per 100,000 in East Garo Hills. Interpretation & conclusions: The findings of this community-based survey suggested that NCDs were the leading cause of death among the tribal populations in India. It is hence suggested that control of NCDs should be one of the public health priorities for tribal districts in India.

Preparedness of primary & secondary care health facilities for the management of non-communicable diseases in tribal population across 12 districts in India.

Background and objectives: Non-communicable diseases (NCDs) are highly prevalent in the tribal populations; however, there are limited data regarding health system preparedness to tackle NCDs among these populations. We estimated the availability of human resources, equipment, drugs, services and knowledge of doctors for NCD management in the selected tribal districts in India. Methods: A cross-sectional survey was conducted in 12 districts (one from each State) with at least 50 per cent tribal population in Andaman and Nicobar Islands, Himachal Pradesh, Madhya Pradesh, Odisha and eight northeastern States. Primary health centres (PHCs), community health centres (CHCs) and district/sub-district hospitals (DHs) were surveyed and data on screening and treatment services, human resources, equipment, drugs and information systems indicators were collected and analysed. The data were presented as proportions. Results: In the present study 177 facilities were surveyed, including 156 PHCs/CHCs and 21 DHs. DHs and the majority (82-96%) of the PHCs/CHCs provided outpatient treatment for diabetes and hypertension. Overall, 97 per cent of PHCs/CHCs had doctors, and 78 per cent had staff nurses. The availability of digital blood pressure monitors ranged from 35 to 43 per cent, and drugs were either not available or inadequate. Among 213 doctors, three-fourths knew the correct criteria for hypertension diagnosis, and a few correctly reported diabetes diagnosis criteria. Interpretation & conclusions: The results of this study suggest that the health system of the studied tribal districts was not adequately prepared to manage NCDs. The key challenges included inadequately trained workforce and a lack of equipment and drugs. It is suggested that capacity building and, procurement and distribution of equipment, drugs and information systems to track NCD patients should be the key focus areas of national programmes.

TruenatTM - micro real-time-polymerase chain reaction for rapid diagnosis of leptospirosis at minimal resource settings.

Background & objectives: The biological spectrum of leptospirosis ranges from acute undifferentiated febrile illness to severe fatal syndrome or a combination of syndromes. Diagnosis on clinical grounds alone is difficult and depends on laboratory support. However, no confirmatory tests are available, which is rapid and can be performed with minimum facilities available. The objectives of this study were to evaluate the diagnostic utility, accuracy and reproducibility of a rapid real time-PCR based method (TruenatTM) for early diagnosis of leptospirosis, and its usage in low resource settings. Methods: The Truenat™ test was performed using plasma sample collected from confirmed patients and controls. DNA was extracted from plasma samples and the reaction was performed as per the manufacturer's instructions. Leptospiral isolates were also used to assess the performance using different serovars. Results: Evaluation of the Truenat™ test with RT-PCR as the gold standard showed that Truenat™ had a sensitivity of 97.4 per cent and a specificity of 98.6 per cent. The overall agreement with RT-PCR was 98.2 per cent. Interpretation & conclusions: Our results showed that the test would be a useful tool for early diagnosis of leptospirosis in settings with minimal facilities and the test results could be obtained within an hour. This indicates that a specific therapy can be instituted during the early phase of the disease even at peripheral healthcare facilities as well during the outbreaks.

Elimination of diurnally sub-periodic Wuchereria bancrofti in Andaman and Nicobar Islands, India, using mass DEC-fortified salt as a supplementary intervention to MDA.

Feasibility of implementing a DEC-fortified (DEC at 0.2% w/w and iodine) salt strategy to hasten elimination of diurnally sub-periodic Wuchereria bancrofti (DspWB) from the lone foci in Nancowry islands, Nicobar district, India, was assessed. This is a two-arm community-based study: one arm (12 villages, population 2936) received double fortified salt along with annual mass drug administration (MDA) of DEC plus albendazole (DEC-salt+MDA-arm), and another (14 villages; population 4840) received MDA under the National Filaria Elimination Programme. DEC salt was distributed on camp mode supplemented by door delivery. Monthly survey was carried out in fixed and random households to assess the coverage, usage of DEC salt and DEC content. The impact on prevalence of mf at community level and antigenaemia among children was assessed. A total of 21 metric tonnes of free-flow DEC salt manufactured by Tamil Nadu Salt Corporation, India, was distributed for 1 year. In the DEC-salt+MDA-arm, > 90% of the households received and used the DEC salt. DEC was within therapeutic range (0.2-0.32% w/w) in the samples collected from kitchens. Community mf prevalence reduced from 2.27 to 0.14% in the DEC-salt-arm (< 1% in all the villages) and 1.26 to 0.74% (> 1% in 4 out of 14 villages) in the MDA-arm. Ag prevalence reduced to zero from 1.0 (DEC-salt+MDA-arm) and 6.3% (MDA-arm) in 2-3 years old, 1.2 and 3.6% from 2.9 in the DEC-salt-arm and 4.5% in the MDA-arm among 6-7 years old. It was feasible to deliver DEC-fortified salt covering > 90% of the households with compliance reaching the elimination target in the islands.

Geographical distribution of primary & secondary dengue cases in India - 2017: A cross-sectional multicentric study.

Background & objectives: Dengue virus infection is endemic in India with all the four serotypes of dengue virus in circulation. This study was aimed to determine the geographic distribution of the primary and secondary dengue cases in India. Methods: A multicentre cross-sectional study was conducted at Department of Health Research / Indian Council of Medical Research (DHR)/(ICMR) viral research and diagnostic laboratories (VRDLs) and selected ICMR institutes located in India. Only laboratory-confirmed dengue cases with date of onset of illness less than or equal to seven days were included between September and October 2017. Dengue NS1 antigen ELISA and anti-dengue IgM capture ELISA were used to diagnose dengue cases while anti-dengue IgG capture ELISA was used for identifying the secondary dengue cases. Results: Of the 1372 dengue cases, 897 (65%) were classified as primary dengue and 475 (35%) as secondary dengue cases. However, the proportion varied widely geographically, with Theni, Tamil Nadu; Tirupati, Andhra Pradesh and Udupi-Manipal, Karnataka reporting more than 65 per cent secondary dengue cases while Srinagar, Jammu and Kashmir reporting as low as 10 per cent of the same. The median age of primary dengue cases was 25 yr [interquartile range (IQR 17-35] while that of secondary dengue cases was 23 yr (IQR 13.5-34). Secondary dengue was around 50 per cent among the children belonging to the age group 6-10 yr while it ranged between 20-43 per cent among other age groups. Interpretation & conclusions: Our findings showed a wide geographical variation in the distribution of primary and secondary dengue cases in India. It would prove beneficial to include primary and secondary dengue differentiation protocol in the national dengue surveillance programme.

Overexpression of heat shock GroEL stress protein in leptospiral biofilm.

Leptospira is the causative agent of leptospirosis, which is an emerging zoonotic disease. Recent studies on Leptospira have demonstrated biofilm formation on abiotic surfaces. The protein expressed in the biofilm was investigated by using SDS-PAGE and immunoblotting in combination with MALDI-TOF mass spectrometry. The proteins expressed in Leptospira biofilm and planktonic cells was analyzed and compared. Among these proteins, one (60 kDa) was found to overexpress in biofilm as compared to the planktonic cells. MALDI-TOF analysis identified this protein as stress and heat shock chaperone GroEL. Our findings demonstrate that GroEL is associated with Leptospira biofilm. GroEL is conserved, highly immunogenic and a prominent stress response protein in pathogenic Leptospira spp., which may have clinical relevance.

Outbreak investigation of fever mimicking dengue in Havelock Island, an important tourist destination in the Andaman & Nicobar Archipelago, 2014.

An upsurge of fever cases of unknown origin, but resembling dengue and leptospirosis was reported in Havelock, Andaman & Nicobar Islands, an important tourism spot, during May 2014. Investigations were carried out to determine the aetiology, and to describe the epidemiology of the outbreak. The data on fever cases attending Primary Health Centre (PHC), Havelock showed that the average number of cases reporting per week over the last 2 years was 46·1 (95% confidence interval 19·4-72·9). A total of 27 (43·5%) patients out of the 62 suspected cases were diagnosed as having DENV infection based on a positive enzyme immunoassay or reverse transcriptase-polymerase chain reaction. The overall attack rate was 9·4 cases/1000 population and it ranged between 2·8 and 18·8/1000 in different villages. The nucleotide sequencing showed that the virus responsible was DENV-3. DENV-3 was first detected in the Andaman & Nicobar Islands in 2013 among wharf workers in Port Blair and within a year it has spread to Havelock Island which is separated from South Andaman by 36 nautical miles.

Prevalence of female genital tuberculosis, its risk factors and associated clinical features among the women of Andaman Islands, India: a community-based study.

OBJECTIVE: There is scarcity of information on the prevalence of female genital tuberculosis (FGTB) in the community. The present study was carried out to estimate the prevalence of FGTB, its risk factors and associated clinical features. STUDY DESIGN: Community-based cross-sectional survey. METHODS: This study was carried during October 2011 and May 2014 in the Andaman Islands. A total of 13,300 women aged 20-59 years were primarily screened using a structured questionnaire. About 721 (5.4%) were found initially eligible for screening for genital tuberculosis by clinical examination and specimen collection for laboratory tests but only 460 (63.8%) expressed their willingness. Endometrial specimens were collected from 405 (88%) subjects. The association of the potential risk factors with genital tuberculosis was tested by Chi-squared test. A similar analysis was performed to identify clinical features associated with genital tuberculosis. RESULTS: The estimated prevalence of FGTB was 45.1 cases per 100,000 women (95% confidence interval [CI]: 16.6-98.1). Infertility and oligomenorrhoea were identified as clinical features associated with FGTB. Past history of tuberculosis and history of close contact with tuberculosis cases were identified as risk factors. CONCLUSIONS: This study shows the prevalence of FGTB among the female population of the Andaman Islands. Though the estimated prevalence was close to the expected prevalence, but as only 63.8% of the eligible women could be adequately screened, a much higher prevalence of FGTB could not be ruled out. Infertility, oligomenorrhoea, past history of tuberculosis and contact with tuberculosis case were identified as factors associated with genital tuberculosis.

Antimicrobial and antimalarial properties of medicinal plants used by the indigenous tribes of Andaman and Nicobar Islands, India.

In this study, methanol extracts of six medicinal plants (Alstonia macrophylla, Claoxylon indicum, Dillenia andamanica, Jasminum syringifolium, Miliusia andamanica and Pedilanthus tithymaloides) traditionally used by Nicobarese tribes of Andaman and Nicobar Islands were studied for antimicrobial and antimalarial activities as well as preliminary photochemical analysis. Plants were collected from Car Nicobar of Andaman and Nicobar Islands and the ethnobotanical data were gathered from traditional healers who inhabit the study area. The methanol extracts were obtained by cold percolation method and the antimicrobial activity was found using agar well diffusion method. Among the plants tested, J. syringifolium, D. andamanica, C. indicum were most active. The antimalarial activity was evaluated against Plasmodium falciparum chloroquine-sensitive MRC-2 isolate. The crude extract of M. andamanica showed excellent antimalarial activity followed by extracts of P. tithymaloides, J. syringifolium and D. andamanica. The chemical injury to erythrocytes was also carried out and it showed that, there were no morphological changes in erythrocytes by the methanol crude extracts. The in vitro antimicrobial and antimalarial activity might be due to the presence of alkaloids, flavonoids, triterpenes, sterols, tannins and saponins in the methanol extracts of tested plants.

Molecular detection of pathogenic leptospiral protein encoding gene (lipL32) in environmental aquatic biofilms.

UNLABELLED: Leptospirosis is a zoonotic disease often encountered during post-monsoon season due to exposure with contaminated water. Leptospires have long been regarded as solitary organisms that persist in soil and aquatic environments. Here, the presence of leptospires in the aquatic biofilm exposed in the paddy field, sewers and stagnant rain water was demonstrated. Biofilm samples from paddy field water, submerged paddy leaves, sewers and stagnant rain waters from urban and rural areas were collected. Total genomic DNA was extracted and pathogenic leptospiral specific gene amplification was carried out to determine the spatial distribution of the bacteria. The degree of pathogenic Leptospira in biofilms from paddy field surface water, submerged leaf, were 33·3% and 27·2% respectively, whereas in rural and urban area, the sampling sites such as stagnant rain water, domestic sewer and collective sewers showed 11·1%, 13% and 16·6% with leptospires respectively. Higher proportion of pathogenic Leptospira in aquatic ecosystems, such as paddy field, could be one of the main factors for the occurrence of disease, more among the agricultural workers. This study would help to identify various survival strategies of leptospires in the environment and thus disease transmission. SIGNIFICANCE AND IMPACT OF THE STUDY: Little is known regarding the mechanisms by which pathogenic leptospires persist in aqueous environment, outside the mammalian host. In this view this is the first report of the distribution of Leptospira in environmental biofilm such as sewers and paddy leaf surfaces. This ability of pathogenic Leptospira to survive in aquatic ecosystems especially in biofilms could be one of the main factors which facilitate its survival in the environment, and thus disease transmission among the risk groups, such as sewage and agriculture worker. This study will encourage researchers in the field to consider biofilm as an important factor, when detecting leptospires in environment.

Diurnally subperiodic filariasis among the Nicobarese of Nicobar district - epidemiology, vector dynamics & prospects of elimination.

In India diurnally subperiodic filariasis (DspWB) is prevalent only in the Nicobar district of Andaman and Nicobar Islands. Studies undertaken at different points of time indicate that this form of filariasis is restricted to a small region in Nancowry group of islands where it is transmitted by mosquito Downsiomyia nivea, a day biting mosquito. Studies on prevalence, distribution, and assessment of endemicity status, vector incrimination, bioecology, host seeking behaviour, population dynamics of the vector, transmission dynamics and clinical epidemiology indicate the prevalence and persistence of this infection in the Nancowry group of islands with perennial transmission. There was no control programme in these islands, until the National programme to eliminate filariasis was launched in 2004. Eight rounds of annual mass drug administration (MDA) with diethyl carbamazine (DEC) + albendazole have been completed. Despite this, microfilaria prevalence remains at above one per cent, the level identified for initiating transmission assessment survey to decide on continuation of MDA further. This necessitates adjunct measures to the ongoing MDA programme in these islands. The vector control options could be an adjunct measure, but the vector is a forest dweller with a unique bio-ecology, therefore, not a technically feasible option. Use of DEC fortified salt for six months to one year could hasten the process of elimination. Although administration of DEC-fortified salt is simple, rapid, safe, and cost-effective, challenges are to be tackled for evolving operationally realistic strategy. Such a strategy requires commitment of all sections of the society, a distribution mechanism that ensures the use of DEC-fortified salt in the Nancowry islands. Here we discuss the plan of action to serve the indigenous communities and operationalizing DEC fortified salt strategy through an inter-sectoral approach involving multiple stakeholders.

Herbal medicine & healthcare practices among Nicobarese of Nancowry group of Islands - an indigenous tribe of Andaman & Nicobar Islands.

BACKGROUND & OBJECTIVES: Tribal people often depend on herbal medicines and the traditional knowledge practitioners (TKPs) serve as their healthcare service providers. This study was an attempt to document the use of medicinal plants by the Nicobarese of Nancowry group of Islands. METHODS: Field survey was conducted in all the five inhabited Islands of the Nancowry group of Islands. All the TKPs were interviewed with a questionnaire-guided ethnomedicinal survey protocol. Voucher specimens of all the cited plants (botanic species) were collected and a Community Biodiversity Register of Nicobarese of Nancowry was prepared. RESULTS: A total of 77 TKPs were identified, who together were using 132 medicinal plant species belonging to 113 genera and 62 families. The TKPs were treating a total of 43 ailments. Seven endemic and three rare plant species were recorded. The most common plant part used was leaves. Remedies were usually prepared using water as the excipient. Routes for administration of medicinal plant preparations were oral, topical and others. The information collected from the TKPs were collated in the form of Community Biodiversity Registers. INTERPRETATION & CONCLUSIONS: The present survey shows that the medicinal plants play a pivotal role in the healthcare of the Nicobarese tribe of Nancowry group of Islands. Efforts to document the medicinal plant species and the formulations used by them are necessary to prevent the loss of this precious knowledge.

Leptospirosis among the self-supporting convicts of Andaman Island during the 1920s--the first report on pulmonary haemorrhage in leptospirosis?

Several researchers had carried out investigations on the possibility of existence of Weil's disease in Andaman Islands during early 20 th century. The first report of a series of confirmed cases of leptospirosis that occurred during 1929 was published in 1931.There were several reports during 1995 to 2009 that described detailed account of leptospirosis including various clinical syndromes. The possibility of pulmonary involvement in leptospirosis being a manifestation historically overlooked rather than newly emerged during the past two decades is examined in this review in the context of Andaman Islands. Two case series of leptospirosis, one occurred in 1929 and the other in 1996-1997 were reviewed with special emphasis on pulmonary involvement and haemorrhagic manifestations. The similarities and differences in the clinical profile of patients of the two case series were analysed. The review shows that respiratory system involvement and pulmonary haemorrhage as evidenced by presence of haemoptysis as a complication of leptospirosis was occurring during 1920s in Andaman Islands. The incidence of pulmonary involvement, however, rose from 9.4 per cent during 1929 to 52 per cent in 1996-1997. The case fatality ratio in patients with pulmonary involvement, which was 50 per cent during 1929 and 42.9 per cent during 1996-1997, was higher than that in cases without pulmonary involvement.Fever, conjunctival congestion, jaundice, vomiting, diarrhoea, hepatomagaly, haemoptysis, haematemesis and subconjunctival haemorrhage were common in both series. The case series in Andaman Islands in 1929 was probably the first report of pulmonary haemorrhage as a manifestation of leptospirosis. The increase in the incidence of pulmonary involvement in leptospirosis in the recent past is probably due to the increase in the density and diversity of its animal vectors,the broadening of the range of circulating serovars and the interactions between the vector and the agent. An increased virulence of Leptospira through gene acquisition and loss on an evolutionary time scale and the resulting change in the gene content, gene order and gene expression cannot be ruled out.

Emergence of an unusual genotype of rotavirus in andaman and nicobar islands, India.

Rotavirus is the most common cause of severe diarrhoea worldwide, affecting over 125 million young children every year in developing countries. The present study is a part of ongoing childhood diarrhoeal surveillance to determine the strain diversity of rotaviruses prevalent in Andaman and Nicobar Islands. From October 2010 to February 2012, 296 stool samples from children (age group 6-60 months) with gastroenteritis were obtained from different referral hospitals/primary health centres and community health centres in Andaman and Nicobar Islands. A total of 47 samples were found positive for GARV. Among these, 21 (44.7%) samples belong to G2P[4], 12 (25.5%) samples were G1P[8], 10 (21.2%) samples belong to G9P[4], 2 (4.3%) samples belong to G1P[4] and 2 (4.3%) samples had a mixed genotype. Rotavirus G2 genotype remains the most common genotype in these islands. The prevalence of G9 rotavirus reported in the present study is higher than that reported from mainland India. The results emphasize the role of the unusual serotype G9 as an epidemiologically important genotype and the need to include G9 specificity in a rotavirus vaccine.

Pan-India influenza-like illness (ILI) and Severe acute respiratory infection (SARI) surveillance: epidemiological, clinical and genomic analysis.

Background: Over time, COVID-19 testing has significantly declined across the world. However, it is critical to monitor the virus through surveillance. In late 2020, WHO released interim guidance advising the use of the existing Global Influenza Surveillance and Response System (GISRS) for the integrated surveillance of influenza and SARS-CoV-2. Methods: In July 2021, we initiated a pan-India integrated surveillance for influenza and SARS-CoV-2 through the geographically representative network of Virus Research and Diagnostic Laboratories (VRDLs) across 26 hospital and laboratory sites and 70 community sites. A total of 34,260 cases of influenza-like illness (ILI) and Severe acute respiratory infection (SARI) were enrolled from 4 July 2021 to 31 October 2022. Findings: Influenza A(H3) and B/Victoria dominated during 2021 monsoon season while A(H1N1)pdm09 dominated during 2022 monsoon season. The SARS-CoV-2 "variants of concern" (VoC) Delta and Omicron predominated in 2021 and 2022, respectively. Increased proportion of SARI was seen in extremes of age: 90% cases in < 1 year; 68% in 1 to 5 years and 61% in ≥ 8 years age group. Approximately 40.7% of enrolled cases only partially fulfilled WHO ILI and SARI case definitions. Influenza- and SARS-CoV-2-infected comorbid patients had higher risks of hospitalization, ICU admission, and oxygen requirement. Interpretation: The results depicted the varying strains and transmission dynamics of influenza and SARS-CoV-2 viruses over time, thus emphasizing the need to continue and expand surveillance across countries for improved decision making. The study also describes important information related to clinical outcomes of ILI and SARI patients and highlights the need to review existing WHO ILI and SARI case definitions.

Dengue: a newly emerging viral infection in Andaman and Nicobar Islands, India.

Prior to 2009 dengue fever had not been reported in the Andaman and Nicobar archipelago. In 2009, a few patients with dengue fever-like illness were reported, some of whom tested positive for dengue antibodies. In 2010, 516 suspected cases were reported, including some with dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS); 80 (15·5%) were positive for dengue antibodies. DENV RNA was detected in five patients and PCR-based typing showed that three of these belonged to serotype 1 and two to serotype 2. This was confirmed by sequence typing. Two clones of dengue virus, one belonging to serotype 1 and the other to serotype 2 appeared to be circulating in Andaman. Emergence of severe diseases such as DHF and DSS might be due to recent introduction of a more virulent strain or because of the enhancing effect of sub-neutralizing levels of antibodies developed due to prior infections. There is a need to revise the vector-borne disease surveillance system in the islands.

Synthesis of ring-A modified lupeol derivatives and their anti-proliferative activity: identification of potent lead active against MCF-7 breast cancer cells.

In continuation of our research program aimed at the development of new natural product-based anticancer agents, a series of lupeol derivatives (5a-5k and 6a-6i) were prepared with the introduction of aryl functionalities and amino acids at C-3 position. All the synthesised derivatives were assessed for in vitro anticancer activity against four human cancer cell lines using MTT assay. Interestingly, the compounds 5j, 5k, and 6 g showed potent activity against MCF7 cells as compared with the parent compound. Further, the flowcytometry analysis revealed that the 5j,5k, and 6 g arrest the cells at the G2/M phase and induce the early apoptosis in MCF7 cells. In addition, the selected compounds inhibit the BcL2 expression and increase the Bax protein expression in MCF7 cells. Overall, these results indicated that the lupeol derivatives could serve as a promising launch point for the development of anticancer agents.