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Among six dominant mosquito vector species involved in malaria transmission in India, Anopheles minimus is a major species in northeast India and held responsible for focal disease outbreaks characterized by high-rise of Plasmodium falciparum infections and attributable death cases. It has been now genetically characterized that among the three-member species of the Minimus Complex spread in Asia, An. minimus (former species A) is prevalent in India including northeastern states and east-central state of Odisha. It is recorded in all seasons and accounts for perennial transmission evidenced by records of sporozoite infections. This species is highly anthropophilic, and largely endophilic and endophagic, recorded breeding throughout the year in slow flowing seepage water streams. The populations of An. minimus in India are reported to be highly diverse indicating population expansion with obvious implications for judicious application of vector control interventions. Given the rapid ecological changes due to deforestation, population migration and expansion and developmental activities, there is scope for further research on the existence of potential additional sibling species within the An. minimus complex and bionomics studies on a large geographical scale for species sanitation. For control of vector populations, DDT continues to be applied on account of retaining susceptibility status even after decades of residual spraying. Anopheles minimus is a highly adaptive species and requires continuous and sustained efforts for its effective control to check transmission and spread of drug-resistant malaria. Anopheles minimus populations are reportedly diminishing in northeastern India whereas it has staged comeback in east-central State of Odisha after decades of disappearance with its eco-biological characteristics intact. It is the high time to siege the opportunity for strengthening interventions against this species for its population diminution to sub-optimal levels for reducing transmission in achieving malaria elimination by target date of 2030.

The malaria situation in India is complex as a result of diverse socio-environmental conditions. India contributes a substantial burden of malaria outside sub-Saharan Africa, with the third highest Plasmodium vivax prevalence in the world. Successful malaria control in India is likely to enhance malaria elimination efforts in the region. Despite modest gains, there are many challenges for malaria elimination in India, including: varied patterns of malaria transmission in different parts of the country demanding area-specific control measures; intense malaria transmission fuelled by favourable climatic and environment factors; varying degrees of insecticide resistance of vectors; antimalarial drug resistance; a weak surveillance system; and poor national coordination of state programmes. Prevention and protection against malaria are low as a result of a weak health-care system, as well as financial and socioeconomic constraints. Additionally, the open borders of India provide a potential route of entry for artesunate-resistant parasites from southeast Asia. This situation calls for urgent dialogue around tackling malaria across borders—between India's states and neighbouring countries—through sharing of information and coordinated control and preventive measures, if we are to achieve the aim of malaria elimination in the region.

The northeastern States of India are co-endemic for Plasmodium falciparum and P. vivax malaria. The transmission intensity is low-to-moderate resulting in intermediate to stable malaria. Malaria control prioritized P. falciparum being the predominant and life threatening infection (>70%). P. vivax malaria remained somewhat neglected. The present study provides a status report of P. vivax malaria in the northeastern States of India. Data on spatial distribution of P. vivax from seven northeastern States (Arunachal Pradesh, Assam, Manipur, Meghalaya, Mizoram, Nagaland and Tripura) were analysed retrospectively from 2008-2013. In addition, cross-sectional malarial surveys were conducted during 1991-2012 in malaria endemic pockets across the States of Assam, Meghalaya, Mizoram and Tripura to ascertain the prevalence of P. vivax in different age groups. Vivax malaria was encountered in all northeastern States but there existed a clear division of two malaria ecotypes supporting ≤30 and >30 per cent of total malaria cases. High proportions of P. vivax cases (60-80%) were seen in Arunachal Pradesh and Nagaland in the north with alpine environment, 42-67 per cent in Manipur, whereas in Assam it varied from 23-31 per cent with subtropical and tropical climate. Meghalaya, Tripura and Mizoram had the lowest proportion of P. vivax cases. Malaria cases were recorded in all age groups but a higher proportion of P. vivax consistently occurred among <5 yr age group compared to P. falciparum (P<0.05). P. vivax cases were recorded throughout the year with peak coinciding with rainy season although transmission intensity and duration varied. In northeast India, P. vivax is a neglected infection. Estimating the relapsing pattern and transmission dynamics of P. vivax in various ecological settings is an important pre-requisite for planning malaria elimination in the northeastern States.

Background Sulphadoxine and pyrimethamine are anti-folate drugs that show synergistic anti-malarial effect. Point mutations in dihydrofolate reductase ( dhfr ) and dihydropteorate synthatase ( dhps ) cause anti-folate drug resistance phenotype in human malaria parasites. This study presents pattern of point mutations in dhfr/dhps genes among Indian sub-continent. Methods Microscopically diagnosed one hundred Plasmodium vivax field isolates were collected from five widely separated geographical regions of India. Dhfr and dhps genes were PCR amplified and sequenced. Previously published mutations data were collected and analyzed using Chi square test to identify geographical cluster of mutant/wild type genotypes. Results Sequence analysis revealed single (S58R), double (S58R/S117N) and quadruple (F57L/S58R/T61M/S117T/) point mutations at dhfr and single (A383G) to double (A383G/A553G) mutations at dhps in P. vivax field isolates. In addition, three new mutations were also observed at dhfr . Both, dhfr and dhps genes revealed tandem repeat variations in field isolates. Dhps revealed very low mutation frequency (14.0%) compared to dhfr (50.70%). Comparative analysis revealed a progressive increase in frequency of quadruple mutant dhfr genotype (p < 0.001) within five years in north-eastern state (Kamrup, Assam). Frequency of dhfr genotypes revealed three distinct geographical clusters of wild (northern India), double mutant (southern India), and quadruple mutant (north-eastern and island regions of India) on the Indian sub-continent. Conclusion Study suggests that SP may be susceptible to P. vivax in India, except Andaman and north-eastern state. The distinction of geographical regions with sensitive and resistant parasite phenotypes would be highly useful for designing and administering national anti-malarial drug policy.

Malaria is a major public health problem in Tripura and focal disease outbreaks are of frequent occurrence. The state is co-endemic for both Plasmodium falciparum and P. vivax and transmission is perennial and persistent. The present study was aimed to review data on disease distribution to prioritize high-risk districts, and to study seasonal prevalence of disease vectors and their bionomical characteristics to help formulate vector species-specific interventions for malaria control. Data on malaria morbidity in the State were reviewed retrospectively (2008-2012) for understanding disease distribution and transmission dynamics. Cross-sectional mass blood surveys were conducted in malaria endemic villages of South Tripura district to ascertain the prevalence of malaria and proportions of parasite species. Mosquito collections were made in human dwellings of malaria endemic villages aiming at vector incrimination and to study relative abundance, resting and feeding preferences, and their present susceptibility status to DDT. The study showed that malaria was widely prevalent and P. falciparum was the predominant infection (>90%), the remaining were P. vivax cases. The disease distribution, however, was uneven with large concentration of cases in districts of South Tripura and Dhalai coinciding with vast forest cover and tribal populations. Both Anopheles minimus s.s. and An. baimaii were recorded to be prevalent and observed to be highly anthropophagic and susceptible to DDT. Of these, An. minimus was incriminated (sporozoite infection rate 4.92%), and its bionomical characteristics revealed this species to be largely indoor resting and endophagic. For effective control of malaria in the state, it is recommended that diseases surveillance should be robust, and vector control interventions including DDT spray coverage, mass distribution of insecticide-treated nets/ long-lasting insecticidal nets should be intensified prioritizing population groups most at risk to avert impending disease outbreaks and spread of drug-resistant malaria.

Background Malaria is endemic in Garo hills of Meghalaya, and death cases are reported annually. Plasmodium falciparum is the major parasite, and is solely responsible for each malaria-attributable death case. Garo hills are categorized high-risk for drug-resistant malaria; however, there exists no data on malaria transmitting mosquitoes prevalent in the region. Included in this report are entomological observations with particular reference to vector biology characteristics for devising situation specific intervention strategies for disease transmission reduction. Methods The epidemiological data of the West Garo hills have been reviewed retrospectively for 2001-2009 to ascertain the disease transmission profile given the existing interventions. Point prevalence study was conducted in Dalu Community Health Centre that lies in close proximity to international border with Bangladesh to ascertain the true prevalence of malaria, and parasite species. Mosquito collections were made in human dwellings of malaria endemic villages aiming at vector incrimination, and to study relative abundance, resting and feeding preferences, and their present susceptibility status to DDT. Results Investigations revealed that the West Garo hill district is co-endemic for Plasmodium falciparum and Plasmodium vivax , but P. falciparum was the predominant infection (> 82%). Malaria transmission was perennial and persistent with seasonal peak during May-July corresponding to months of high rainfall. Entomological collections revealed that Anopheles minimus was the predominant species that was incriminated by detection of sporozoites in salivary glands (infection rate 2.27%), and was ascertained to be fully susceptible to DDT. Conclusion For the control of malaria, improved diagnosis and sustained supply of drugs for artemisinin-based combination therapy are strongly advocated, which should be enforced for treatment of every single case of P. falciparum . Greater political commitment is called for organized vector control operations along border/high-risk areas to contain the spread of drug-resistant malaria, and averting impending disease outbreaks.

The artemisinin-based combination treatment (ACT) of dihydroartemisinin (DHA) and piperaquine (PQP) is a promising novel anti-malarial drug effective against multi-drug resistant falciparum malaria. The aim of this study was to show non-inferiority of DHA/PQP vs. artesunate-mefloquine (AS+MQ) in Asia. This was an open-label, randomised, non-inferiority, 63-day follow-up study conducted in Thailand, Laos and India. Patients aged 3 months to 65 years with Plasmodium falciparum mono-infection or mixed infection were randomised with an allocation ratio of 2:1 to a fixed-dose DHA/PQP combination tablet (adults: 40 mg/320 mg; children: 20 mg/160 [DOSAGE ERROR CORRECTED] mg; n = 769) or loose combination of AS+MQ (AS: 50 mg, MQ: 250 mg; n = 381). The cumulative doses of study treatment over the 3 days were of about 6.75 mg/kg of DHA and 54 mg/kg of PQP and about 12 mg/kg of AS and 25 mg/kg of MQ. Doses were rounded up to the nearest half tablet. The primary endpoint was day-63 polymerase chain reaction (PCR) genotype-corrected cure rate. Results were 87.9% for DHA/PQP and 86.6% for AS+MQ in the intention-to-treat (ITT; 97.5% one-sided confidence interval, CI: >-2.87%), and 98.7% and 97.0%, respectively, in the per protocol population (97.5% CI: >-0.39%). No country effect was observed. Kaplan-Meier estimates of proportions of patients with new infections on day 63 (secondary endpoint) were significantly lower for DHA/PQP than AS+MQ: 22.7% versus 30.3% (p = 0.0042; ITT). Overall gametocyte prevalence (days 7 to 63; secondary endpoint), measured as person-gametocyte-weeks, was significantly higher for DHA/PQP than AS+MQ (10.15% versus 4.88%; p = 0.003; ITT). Fifteen serious adverse events were reported, 12 (1.6%) in DHA/PQP and three (0.8%) in AS+MQ, among which six (0.8%) were considered related to DHA/PQP and three (0.8%) to AS+MQ. DHA/PQP was a highly efficacious drug for P. falciparum malaria in areas where multidrug parasites are prevalent. The DHA/PQP combination can play an important role in the first-line treatment of uncomplicated falciparum malaria. Controlled-Trials.com ISRCTN81306618.

Background Bhutan has achieved a major reduction in malaria incidence amid multiple challenges. This case study seeks to characterize the Bhutan malaria control programme over the last 10 years. Methods A review of the malaria epidemiology, control strategies, and elimination strategies employed in Bhutan was carried out through a literature review of peer-reviewed and grey national and international literature with the addition of reviewing the surveillance and vector control records of the Bhutan Vector-Borne Disease Control Programme (VDCP). Data triangulation was used to identify trends in epidemiology and key strategies and interventions through analysis of the VDCP surveillance and programme records and the literature review. Enabling and challenging factors were identified through analysis of socio-economic and health indicators, corroborated through a review of national and international reports and peer-review articles. Findings Confirmed malaria cases in Bhutan declined by 98.7% from 1994 to 2010. The majority of indigenous cases were due to Plasmodium vivax (59.9%) and adult males are most at-risk of malaria. Imported cases, or those in foreign nationals, varied over the years, reaching 21.8% of all confirmed cases in 2006. Strategies implemented by the VDCP are likely to be related to the decline in cases over the last 10 years. Access to malaria diagnosis in treatment was expanded throughout the country and evidence-based case management, including the introduction of artemisinin-based combination therapy (ACT) for P. falciparum , increasing coverage of high risk areas with Indoor Residual Spraying, insecticide-treated bed nets, and long-lasting insecticidal nets are likely to have contributed to the decline alongside enabling factors such as economic development and increasing access to health services. Conclusion Bhutan has made significant strides towards elimination and has adopted a goal of national elimination. A major challenge in the future will be prevention and management of imported malaria infections from neighbouring Indian states. Bhutan plans to implement screening at border points to prevent importation of malaria and to targeted prevention and surveillance efforts towards at-risk Bhutanese and migrant workers in construction sites.

The effect of an external magnetic field on the isotopic selectivity in a two-color three-step polarization-based isotope-selective photoionization of atomic samarium has been studied. Isotope-selective photoionization of samarium is realized through a level scheme having total angular momentum (J) sequence 0-1-1-continuum by using two lasers linearly polarized in the same direction and the isotopic selectivity is measured by varying the magnetic field strength perpendicular to the laser polarization axis while keeping the delay between the laser pulses fixed and vice versa. The experimental data have been analyzed and compared with the results of the numerical calculations. The magnetic field perpendicular to the laser polarization axis present in the laser-atom interaction region has been found to degrade the isotopic selectivity. Further, the Lande factor ( g J ) of the excited energy level 16 690.76 cm−1 (J = 1) of samarium has been determined from the observed oscillation in the isotopic selectivity. The value of g J , thus obtained, is in good agreement with that reported in the literature.

Dengue is one of the major public health problems worldwide, transmitted mainly by Aedes aegypti and Ae. albopictus mosquitoes. Rapid urbanisation and industrialisation have led to an increase in vector population in Northeastern states of India. In 2013, Guwahati, the capital city of Assam, India experienced an outbreak of dengue. This study was undertaken with an objective to determine infection rates of dengue viruses (DENV) in both the established vectors present in this region. During the outbreak (2013), adults and larvae of both the vector species were collected from different container habitats found in case reporting areas and container index was also recorded. The mosquitoes were first pooled, homogenised and processed for NS1-ELISA. This was followed by RT-PCR of the mosquito pools. Both Ae. aegypti and Ae. albopictus were found breeding in containers with container index in the range of 29.41 to 80%. Six pools of Ae. aegypti were found to be positive for NS1 antigen. RT-PCR assay revealed positivity in only the NS1-ELISA positive pools, exhibiting circulation of serotype DENV-2. Minimum infection rate of female and male Ae. aegypti was recorded as 10.87 and 11.03 respectively. This is the maiden report of detection of DENV in wild caught Ae. aegypti mosquitoes from Northeastern Region of India. The study also demonstrates the presence of transovarial transmission of dengue virus in this part of country. This information is useful in respect of both entomological as well as epidemiological point of view for taking appropriate vector control measures.