Mass drug administration against lymphatic filariasis: experiences from Kozhikode district of Kerala State

The mass DEC drug administration to eliminate lymphatic filariasis in Kozhikode district was monitored from 2001 to 2003 to assess the drug distribution coverage, compliance, reasons for non-compliance, side reactions, mf prevalence and intensity, infection and infectivity rates in the vector. The drug distribution coverage and compliance were much below the required level. "No disease so not necessary" (42.5%) and "fear of side reactions" (25.2%) were the two major reasons for non-compliance. The adverse reactions were minimal. No appreciable changes were found in the mf prevalence and intensity. For the successful implementation of the MDA programme, proper planning, intense and timely efforts to motivate the community and innovative drug delivery strategies are required.     

HCO(3)(-) secretion in the rat colonic crypt is closely linked to Cl(-) secretion

BACKGROUND & AIMS: The mechanism of colonic HCO(3)(-) secretion has not been established largely because of a lack of experimental methods for its detailed study. The present studies were designed to establish whether the isolated, perfused crypt of the rat distal colon is an excellent model to study HCO(3)(-) movement and the mechanism of colonic HCO(3)(-) secretion. METHODS: HCO(3)(-) secretion was determined in isolated, microperfused crypts by measuring [HCO(3)(-)] by microcalorimetry on nanoliter samples. RESULTS: Net HCO(3)(-) absorption was observed during lumen and bath perfusion with an HCO(3)(-)-Ringer solution. Vasoactive intestinal polypeptide (60 nmol/L), acetylcholine (100 nmol/L), or dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP, 0.5 mmol/L) induced active HCO(3)(-) secretion that required bath but not lumen HCO(3)(-)/CO(2). DBcAMP-stimulated HCO(3)(-) secretion was not affected by acetazolamide, an inhibitor of carbonic anhydrase. Removal of lumen Cl(-) did not alter DBcAMP-stimulated HCO(3)(-) secretion but reduced fluid secretion. DBcAMP-stimulated HCO(3)(-) secretion was closely linked to active Cl(-) secretion because HCO(3)(-) secretion was substantially reduced by removal of bath Cl(-), by addition of bath bumetanide, an inhibitor of Na-K-2Cl cotransport and Cl(-) secretion, and by addition of lumen NPPB, a Cl(-) channel inhibitor. CONCLUSIONS: These studies establish that colonic crypt HCO(3)(-) secretion (1) is not a result of an apical membrane Cl(-)-HCO(3)(-) exchange, (2) is tightly associated with Cl(-) secretion, and (3) primarily occurs via an apical membrane Cl(-) channel.     

Longitudinal studies in South Indian villages on Japanese encephalitis virus infection in mosquitoes and seroconversion in goats

Japanese encephalitis (JE) is endemic in Cuddalore district, Tamil Nadu, where Culex tritaeniorhynchus Giles was the major vector. We screened 45 100 adult female Cx. tritaeniorhynchus (902 pools) by enzyme-linked immunosorbent assay and isolated and confirmed JE virus (JEV) by using an insect bioassay system. We had 69 isolates of which 62 (90%) were identified as JEV. The average vector abundance per man hour for Cx. tritaeniorhynchus was 324.5 per month for the period June 1998-May 2000. The average minimum infection rate (MIR) per month in Cx. tritaeniorhynchus was 1.4 (range 0.0-5.6). Every year, a new batch of goats, 20 in the first year and 31 in the second year, born during the non-JE transmission period (January-June), aged <6 months and negative for haemagglutination inhibition (HI) antibodies were procured and placed in the villages as sentinels. Fortnightly, blood specimens were collected from these goats and tested for JE antibodies by HI test. Seroconversions (SCs) were recorded in 14 goats (70%) in the first year and 23 goats (74%) in the second year. JE HI antibody titres in goats were low (1:10-1:80) and these levels declined to undetectable levels in about 4 weeks following SCs. The time sequence of events indicated that four of five peaks of MIR in mosquitoes were followed 1-3 months later by peaks in the proportion of seroconverted goats. We suggest the screening of goats and cattle as a more feasible tool to stratify areas according to JE infection risk to the human population through the regular health system rather than screening mosquitoes using monoclonal antibodies, which is possible only in specialized laboratories.     

High-dose radioimmunotherapy versus conventional high-dose therapy and autologous hematopoietic stem cell transplantation for relapsed follicular non-Hodgkin lymphoma: a multivariable cohort analysis

We performed a multivariable comparison of 125 consecutive patients with follicular lymphoma (FL) treated at our centers with either high-dose radioimmunotherapy (HD-RIT) using 131I-anti-CD20 (n = 27) or conventional high-dose therapy (C-HDT) (n = 98) and autologous hematopoietic stem cell transplantation. The groups were similar, although more patients treated with HD-RIT had an elevated pretransplantation level of lactate dehydrogenase (41% versus 20%, P =.03) and elevated international prognostic score (41% versus 19%, P =.02). Patients treated with HD-RIT received individualized therapeutic doses of 131I-tositumomab (median, 19.7 GBq [531 mCi]) to deliver 17 to 31 Gy (median, 27 Gy) to critical organs. Patients treated with C-HDT received total body irradiation plus chemotherapy (70%) or chemotherapy alone (30%). Patients treated with HD-RIT experienced improved overall survival (OS) (unadjusted hazard ratio [HR] for death = 0.4 [95% confidence interval (95% CI), 0.2-0.9], P =.02; adjusted HR, 0.3, P =.004) and progression-free survival (PFS) (unadjusted HR =.6 [95% C.I., 0.3-1.0], P =.06; adjusted HR, 0.5, P =.03) versus patients treated with C-HDT. The estimated 5-year OS and PFS were 67% and 48%, respectively, for HD-RIT and 53% and 29%, respectively, for C-HDT. One hundred-day treatment-related mortality was 3.7% in the HD-RIT group and 11% in the C-HDT group. The probability of secondary myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) was estimated to be.076 at 8 years in the HD-RIT group and.086 at 7 years in the C-HDT group. HD-RIT may improve outcomes versus C-HDT in patients with relapsed FL.     

Study on the factors affecting the MDA programme in Kerala state

The Mass Annual Single dose DEC administration (MDA) was initiated in India from 1997. In Kerala MDA was studied as a pilot project in Alappuzha and Kozhikode District from 2000-04 and the first round of MDA was launched in Kerala covering eleven endemic districts, in March 2005. On evaluation, the drug distribution coverage, compliance, etc. were found to be not satisfactory and a need to elicit the factors for poor performance of MDA is felt essential. The main reasons for poor performance of MDA in Kerala state were the lack of adequate prior information to the target population regarding the importance LF elimination programme and inadequate awareness. The fear of side reactions, antipropagonda, poor IEC activities repeated postponement of programme, insufficient time for mobilisation etc. were the other reasons for poor compliance. The purpose of the present study was to bring the observations to the notice of the authorities so that appropriate remedial measures are incorporated.     

Leptospira autumnalis isolated from a human case from Avadi, India, and the serovar's predominance in local rat and bandicoot populations

Leptospira were successfully isolated from the urine of an Indian patient who had been clinically diagnosed as having leptospirosis. In an attempt to determine the source of this infection, 28 rats (Rattus rattus) and 58 bandicoots (Bandicota bengalensis) living in the vicinity of the patient's home in Avadi, a suburban area of the city of Chennai (Madras), India, were then investigated. Each animal was checked for infection by microscopical examination of fresh and stained urine, serological analysis of serum, and the culture of urine and kidney samples. Direct, dark-field, observation of fresh urine samples and examination of urine samples after Fontana's silver staining were found to be the least sensitive of the tests used. The results of the serological microscopic agglutination test (MAT) indicated that four (14.3%) of the rats and nine (16.1%) of the bandicoots had significant agglutinins, predominantly for the serogroups icterohaemorrhagiae and autumnalis. Leptospira were isolated from at least one culture of samples from one rat and each of four bandicoots. Each of these rodent isolates and the human isolate were typed as Leptospira interrogans serovar autumnalis.     

The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies.     

Toxicity effect of Delonix elata (Yellow Gulmohr) and predatory efficiency of Copepod,Mesocyclops aspericornis for the control of dengue vector,Aedes aegypti

Objective

To evaluate the toxicity, predatory efficiency of Delonix elata (D. elata) and Mesocyclops aspericornis (M. aspericornis) against dengue vector, Aedes aegypti (Ae. aegypti).

Methods

A mosquitocidal bioassay was conducted at different concentration of plant extract followed by WHO standard method. The probit analysis of each tested concentration and control were observed by using software SPSS 11 version package. The each tested concentration variable was assessed by DMRT method. The predatory efficiency of copepod was followed by Deo et al., 1988. The predator, M. aspericornis was observed for mortality, abnormalities, survival and swimming activity after 24 h treatment of plant and also predation on the mosquito larvae were observed.

Results

D. elata were tested for biological activity against the larvae, and pupae of Ae. aegypti. Significant mortality effects were observed in each life stage. The percentage of mortality was 100% in first and second instars whereas 96%, 92% in third and fourth instars. Fitted probit-mortality curves for larvae indicated the median and 90% lethal concentrations of D. elata for instars 1-4 to be 4.91 (8.13), 5.16 (8.44), 5.95 (7.76) and 6.87 (11.23), respectively. The results indicate that leaf extract exhibits significant biological activity against life stages. The present study revealed that D. elata is potentially important in the control of Ae. aegypti. Similar studies were conducted for predatory efficiency of Copepod, M. aspericornis against mosquito vector Ae. Aegypti. This study reported that the predatory copepod fed on 39% and 25% in I and III instar larvae of mosquito and in combined treatment of D. elata and copepod maximum control of mosquito larval states and at 83%, 80%, 75% and 53% in I, II, III and IV instars, respectively.

Conclusions

The combined action of plant extract and predatory copepod to effectively control mosquito population and reduce the dengue transmitting diseases.     

Chemical activation of a high-affinity glutamate transporter in human erythrocytes and its implications for malaria-parasite-induced glutamate uptake

Human erythrocytes have a low basal permeability to L-glutamate and are not known to have a functional glutamate transporter. Here, treatment of human erythrocytes with arsenite was shown to induce the uptake of L-glutamate and D-aspartate, but not that of D-glutamate or L-alanine. The majority of the arsenite-induced L-glutamate influx was via a high-affinity, Na(+)-dependent system showing characteristics of members of the "excitatory amino acid transporter" (EAAT) family. Western blots and immunofluorescence assays revealed the presence of a member of this family, EAAT3, on the erythrocyte membrane. Erythrocytes infected with the malaria parasite Plasmodium falciparum take up glutamate from the extracellular environment. Although the majority of uptake is via a low-affinity Na(+)-independent pathway there is, in addition, a high-affinity uptake component, raising the possibility that the parasite activates the host cell glutamate transporter.