SummaryThis paper reports on DEC distribution and compliance with treatment in a large-scale annual single-dose mass treatment programme to eliminate lymphatic filariasis in the south Indian state of Tamil Nadu. 76.9% of households (82.5% in rural areas and 58.0% in urban areas) were aware of drug distribution for control of filariasis. DEC was given to 70% (= distribution rate) (range 0-92%) of the population and 53.5% (range 12-89%) complied with treatment. The distribution rate was more than 75% in 74% of the villages and compliance was in the range of 51-75% in 76% of the villages. About 5% of the treated population reported side-effects. Distribution and compliance were higher in rural than urban areas and similar between males and females. Qualitative data showed that some socio-economic factors, logistic and drug-related problems and people's poor knowledge and perceived benefits of treatment played a role in a proportion of the population not receiving or taking the drug. The Tamil Nadu programme showed that large-scale repeated annual DEC mass treatment is feasible and that existing health services are capable of delivering the drug to all communities. While even poor to moderate compliance rates can reduce the vector transmission of infection to some extent, improved drug distribution and compliance with treatment are necessary to consolidate the gains of earlier rounds of treatment and achieve the goal of filariasis elimination within a reasonable time frame.

Background: The recommended strategy for elimination of Lymphatic filariasis is single-dose, once-yearly mass treatment with anti-filarial drugs and the program is in operation on a national level in India. Rate of coverage and consumption is the most crucial factor in the success of Mass Drug Administration (MDA) program. In spite of massive efforts, the program demonstrated suboptimal coverage and consumption in urban areas than rural. The involvement of Anganwadi workers (AWWs) of the Integrated Child Development Scheme (ICDS) as communicators and drug distributors was attempted to enhance the coverage and consumption in urban areas and the results presented here.

In the mass drug administrations (MDA) that form the principal strategy of the Global Programme to Eliminate Lymphatic Filariasis, treatment coverages of at least 65%-80% will be needed if the programme is to be successful. In the Indian state of Tamil Nadu, where treatment coverages were typically <65%, a comprehensive strategy of advocacy and communication, called the "communication for behavioural impact" (COMBI) campaign, has been developed and implemented, in an attempt to improve treatment coverage. This strategy combined advocacy, aimed at state-, district- and village-level administrations, with communication activities targeted at individual communities. The main aim was to alter the behaviour of many of those included in the rounds of MDA, so that they would be more likely to accept and consume the diethylcarbamazine tablets offered to them. The COMBI campaign had two variants, COMBI(+) and the more intensive COMBI(+ +), each of which has been implemented in six districts. Both the variants included the "personal selling" of treatment, via door-to-door visiting by a total of 113,500 filaria-prevention assistants. These assistants were able to visit 34%-49% of the households in each target community. In the COMBI(+ +) districts, up to 44% and 38% of households received information on lymphatic filariasis and its elimination via television commercials and posters, respectively. Overall, 78% of the villages in the COMBI(+ +) districts and 33% of those in the COMBI(+) districts were considered to have had good exposure to the communication campaign. At the end of this campaign about 30% more people (than pre-campaign) believed that lymphatic filariasis could be eliminated and many of those targeted considered lymphatic filariasis to be a dreadful disease, knew that a particular day had been designated "Filaria Day", and thought that the tablets offered in MDA should be consumed to prevent or eliminate the disease. Apparently as the result of the COMBI campaign, drug consumption increased, from 33% of those living in endemic communities, to 37% in the COMBI(+) districts and to 49% in the COMBI(+ +). Coverages as high as 65%-73% were recorded among those who had had the maximum exposure to the communication campaign. These results indicate that the COMBI campaign favourably changed the perception and behaviour of the people towards the elimination of lymphatic filariasis. The costs of the COMBI(+) and COMBI(+ +) strategies were only U.S.$0.002 and U.S.$0.009 per capita, respectively.

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The potential of repeated mass administration of diethylcarbamazine (DEC) and ivermectin to eliminate lymphatic filariasis has been examined in a study implemented in 10 villages with a population of 18415 in south India. During ten rounds of mass drug administration, 49-84% of the eligible population received treatment in different villages. Ten rounds of mass administration of DEC alone reduced the microfilaria (mf) prevalence and intensity by 93% and 97%, respectively, and the vector infection and infectivity rates by 91% and 89%, respectively. The corresponding figures with nine rounds of administration of ivermectin alone were 83%, 90%, 89% and 79%. Out of five villages in each treatment arm, the mf rate declined to

Background. The endothelial cell marker PAL‐E is not reactive to vessels in the normal brain. The present study concerns the PAL‐E reactivity in brain tumors in contrast to normal brain and nonneoplastic brain disease. Methods. A total of 122 specimens were examined: brain tumors (n = 94), nonneoplastic brain disease (n = 19), normal brain (n = 8), and fetal brain (n = 1). Standard immunohistochemical procedures using a panel of endothelial cell markers were applied to detect vessels reactive to PAL‐E. Results. PAL‐E reactivity to endothelial cells was found in all cases of glioblastoma multiforme, in 75% of the cases of anaplastic astrocytoma, and in 46% of the cases of astrocytoma. Furthermore, PAL‐E reactivity was present in diseases with a developmental etiology, such as primitive tumors and congenital vascular malformations. The developing human brain (6‐weeks' gestation age) and special sites of the mature brain, sites without blood‐brain barrier, showed a strong reactivity, which indicates a relation with the status of blood‐brain barrier development. Conclusions. PAL‐E is the only marker out of a panel of endothelial cell markers that shows no reactivity to endothelial cells in the normal brain with an intact blood‐brain barrier. In primary and metastatic brain tumors, PAL‐E is reactive to endothelial cells, except for 25% of anaplastic astrocytoma and 54% of astrocytoma. PAL‐E reactivity in brain tumors most likely is related to angiogenesis and to blood‐tumor barrier properties not present in the normal blood‐brain barrier.

SummaryLymphatic filariasis (LF) is targeted for global elimination. Transmission interruption through repeated annual single-dose mass administration of anti-filarial drugs is the mainstay of the LF elimination strategy. This study examined the ability of six rounds of mass administration of diethylcarbamazine (DEC) or ivermectin (IVM) to interrupt transmission of Wuchereria bancrofti by Culex quinquefasciatus, the predominant parasite and vector species, respectively. After six rounds of mass drug administration (MDA), received by 54-75% of the eligible population ( ‡15 kg body weight), the resting vector infection and infectivity rates fell by 83% and 79% in the DEC arm, 85% and 84% in the IVM arm and 31% and 45% in the placebo arm, respectively. The landing vector infection and infectivity rates fell by 83% and 94% in the DEC arm, 63% and 75% in the IVM arm and 1% each in the placebo arm, respectively. The filarial larval load per resting mosquito declined by 92% and 93% and per landing mosquito by 83% and 69% in the DEC and IVM arms, respectively. The annual infective biting rate (AIBR) fell from 735 to 93 (87%) in the DEC arm, 422 to 102 (76%) in the IVM arm and 472 to 398 (16%) in the placebo arm. The annual transmission potential (ATP) declined from 2514 to 125 (95%), 1212 to 241 (80%) and 1547 to 1402 (9%) in the DEC, IVM and placebo arms, respectively. However, mosquitoes with infection [microfilaria/larva 1/larva 2 (Mf/L1/L2)] were found in all study villages. Three of five villages in the IVM arm and two of five in the DEC arm recorded no resting mosquitoes with infective-stage (L3) larva. Although the ATP, after six rounds of MDA, fell substantially and remained at 125 and 241 in the DEC and IVM arms, respectively, the cumulative exposure to infective stage larvae (ATP) during the treatment period of 6 years was as high as 2995 in the DEC arm and 1522 in the IVM arm, because of considerable level of transmission during the initial (1-3) rounds of MDA. We conclude that (i) six rounds of MDA, even with 54-75% treatment coverage, can reduce LF transmission very appreciably; (ii) better treatment coverage and a few more rounds of MDA may achieve total interruption of transmission; (iii) high vector densities may partly nullify the reductions achieved in vector infection and infectivity rates by MDA and (iv) achievement of 'true zero' Mf prevalence in communities and 0% infection rate (mosquitoes with Mf/L1/L2) in mosquitoes may be necessary to totally interrupt Culex-transmitted LF.

Annual mass drug administration (MDA) is the recommended strategy for lymphatic filariasis (LF) elimination. We assessed the effect of six rounds of mass administration of diethylcarbamazine (DEC) and albendazole (ALB) on microfilaria (Mf) prevalence and intensity and vector infection and infectivity rates and circulating filarial antigenaemia (CFA) in a group of five villages in south India, endemic for Culex-transmitted bancroftian filariasis. During different rounds of MDA, 60-70% of the eligible population (>15 kg body weight) was treated. The MDA reduced the Mf prevalence from 8.10% (CI 6.18-10.01) to 1.01% (CI 0.31-1.71) (P<0.05) and geometric mean intensity of Mf from 0.31 (CI 0.22-0.40) to 0.02 (CI 0.00-0.04) (P<0.05), equivalent to a fall of 86% and 94% respectively. The vector infection and infectivity rates declined from 13.11% (CI 11.52-14.70) to 0.78% (CI 0.16-1.40) (P<0.05) and 1.04% (CI 0.56-1.52) to 0.13% (CI 0.00-0.39) (P<0.05), respectively. Four out of the five villages recorded <0.5% Mf prevalence and 0% vector infection rate. Circulating filarial antigenaemia (CFA) fell by 86% in the total population and 100% in 1-10 year old children. One of the five villages, which showed the highest baseline vector infection rate, showed >1.0% Mf rate. The results suggest that six rounds of mass administration of DEC and ALB, with 60-70% treatment coverage, is likely to achieve total interruption of transmission and elimination of LF in the majority of villages.