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.

Field testing & evaluation of the efficacy & duration of effectiveness of a biolarvicide, Bactivec® SC (Bacillus thuringiensis var. israelensis SH-14) in Bengaluru, India

Background & objectives: Different formulations of Bacillus thuringiensis var. israelensis (Bti) have been tested against different mosquito vectors and other insects for their residual activity. In the present study, the efficacy and residual activity of a new formulation of Bti (Bactivec Suspension Concentrate) were evaluated against immature stages of Anopheles stephensi Liston (Diptera: Culicidae), Aedes aegypti Linnaeus (Diptera: Culicidae) and Culex quinquefasciatus Say (Diptera: Culicidae), in natural habitats in Phase II and Phase III in Bengaluru, India. Methods: Preferential breeding habitats of the mosquito species were selected and four dosages (0.25, 0.5, 1 and 2 ml/50 l) were tested in Phase II trial. Two most effective dosages, 0.5 and 1 ml/50 l were selected for Phase III trial. The evaluation was carried out essentially following the guidelines of the World Health Organization Pesticide Evaluation Scheme. Pre-treatment and post-treatment densities were recorded at regular intervals, and >80 per cent reduction in pupae was taken as the duration of effectiveness. Results: Bactivec SC treated at the dosage of 1 ml/50 l could produce 10-17 days efficacy (>80% reduction in pupae) in clean water habitats tested, whereas 0.5 ml/50 l dosage showed residual activity from 7 to 14 days against Ae. aegypti and An. stephensi in Phase III studies. In polluted water habitats, 4-7 days efficacy could be recorded against Cx. quinquefasciatus in Phase III. Interpretation & conclusions: The Bactivec SC formulation was operationally feasible and easy to handle. For the control of Anopheles and Aedes mosquitoes in freshwater habitats, 1 ml/50 l dosage was found effective, whereas in polluted water habitats against Cx. quinquefasciatus 5 ml/m2 was found effective.

A multicentric study with arteether in patients of uncomplicated falciparum malaria.

Two hundred and sixty seven patients of uncomplicated P. falciparum malaria completed study in a multicentric phase III clinical trial of Arteether. Arteether was given intramuscularly in a dose of 150 mg daily for three consecutive days. Each patient was followed upto 28 days of alpha, beta arteether therapy. The cure rate was 97% with fever clearance time between 1-7 days (24-168 hours) and parasite clearance time between 1-3 days (24-72 hours). Parasite reappearance rate was found to be 3% and reported at only three of the centres. Following the treatment no adverse effect was observed on haematological, biochemical and vital clinical parameters.

Studies on malaria during pregnancy in a tribal area of central India (Madhya Pradesh).

In tribal villages of central India where malaria is highly prevalent (mesoendemic), this preliminary study was undertaken to determine the effects of malaria infection in a group of 456 pregnant women with or without fever. Only 96 women were found infected with malaria, of which Plasmodium falciparum accounted for 64% of the detected parasites, while P. vivax for the remaining 36%. There were no instances of cerebral malaria or death however, one abortion and four still births were recorded among 38 primigravid women. Only one neonate was found infected with P. falciparum on day 21 though parasitemia was not high. Anemia was commonly present in most of the women (80%). Failure to clear P. falciparum parasitemia after a chloroquine regimen (25 mg/kg of body weight) was commonly observed. Persistent P. falciparum parasitemia was recorded in 8% cases. Poor response to chloroquine suggests the need to change the drug policy.

Bromo-deoxyuridine based assay for detection of parasite and drug sensitivity in Plasmodium falciparum in vitro.

A non-radioactive, thymidine analogue-bromodeoxyuridine (Brdu), derivative of uridine has been used for incorporation in DNA in culture of P. falciparum at various dosages and at different time period. Parasite growth rate and effect of chloroquine in culture were monitored by microscopic observation of stained smears and incorporation of Brdu molecules were visualized by immunofluorescence and measured by enzyme immuno assay using anti-Brdu. Uptaking of Brdu in parasite is slower unlike tumour cells. A positive correlation between parasite growth and Brdu uptake measurement by ELISA has been observed.

In vitro antimalarial activity of monoterpenic fragment analogues of aplasmomycin.

Synthetic analogues of a monoterpenic fragment of aplasmomycin were tested for their antimalarial activity in Plasmodium falciparum culture in vitro. The antimalarial activities of these agents were evaluated in chloroquine sensitive strains. Parasite growth was inhibited in a dose dependent manner in the presence of the synthetic compounds (3-9).

Curative efficacy of norfloxacin in falciparum malaria.

Fifteen patients of uncomplicated falciparum malaria from Delhi were treated with norfloxacin (10 with 400 mg, 5 with 800 mg, both twice daily) for 3 days and the response was measured according to the WHO extended in vivo test criteria. The lower dose produced S response in two, RII response in five and RIII response in three patients, while the higher dose produced S response in four and RI response in one patient. In patients with S or RI response, the parasite clearance time was 68.6 +/- 9.1 h the defervescence time being 48 h. Thus, norfloxacin did reveal in vivo activity in falciparum malaria, but a dose of 400 mg twice daily proved to be curative only in a small percentage of cases and not consistently. Nausea and bitter taste were the only side effects noted in two patients.

Single dose pharmacokinetics of lithium & prediction of maintenance dose in manic depressive patients.

Pharmacokinetics of lithium was studied in 60 manic-depressive patients after an initial dose of 900 mg, in serial blood samples for 24 h. The values (mean +/- SD) obtained were peak serum Li concentration 0.81 +/- 0.18 mEq/l; time to peak 2.57 +/- 0.87 h; total Li clearance 33.2 +/- 15.5 ml/min; volume of distribution 0.62 +/- 0.26 l/kg; elimination rate constant 0.0514 +/- 0.02 h; area under serum concentration-time curve 16.41 +/- 11.41 mEq/1 h; serum half life 15.34 +/- 6.06 h. Thereafter, the applicability of various dose prediction methods was evaluated vis-a-vis the actual doses needed to attain steady state serum lithium concentration of 0.6-1.2 mEq/l in 46 patients. The method based on body weight was not found suitable. A nomographic method predicted higher doses in 27 patients, while Zetin's mathematical model predicted dose was in the range of +/- 150 mg of the actual dose in 21 patients. A method for predicting maintenance dose based on 24 h serum lithium level and body weight is suggested.

Influence of clonidine, methyldopa and propranolol on acute toxicity of fenitrothion in mice.

The effect of pretreatment with clonidine, methyldopa and propranolol, and of atropine was studied in mice on acute toxicity of fenitrothion, the active ingredient of TIK-20. Atropine significantly decreased and propranolol somewhat decreased the fenitrothion induced death in mice. Clonidine and methyldopa somewhat increased the percentage mortality due to fenitrothion.