Enhanced efficacy of sequential administration of Albendazole for the clearance of Wuchereria bancrofti infection: Double blind RCT.

Till today, there is no effective treatment protocol for the complete clearance of Wuchereria bancrofti (W.b) infection that causes secondary lymphoedema. In a double blind randomized control trial (RCT), 146 asymptomatic W. b infected individuals were randomly assigned to one of the four regimens for 12 days, DEC 300 mg + Doxycycline 100 mg coadministration or DEC 300 mg + Albendazole 400 mg co-administration or DEC 300 mg + Albendazole 400 mg sequential administration or control regimen DEC 300 mg and were followed up at 13, 26 and 52 weeks post-treatment for the clearance of infection. At intake, there was no significant variation in mf counts (F(3,137)=0.044; P=0.988) and antigen levels (F(3,137)=1.433; P=0.236) between the regimens. Primary outcome analysis showed that DEC + Albendazole sequential administration has an enhanced efficacy over DEC + Albendazole co-administration (80.6 Vs 64.7%), and this regimen is significantly different when compared to DEC + doxycycline co-administration and control (P<0.05), in clearing microfilaria in 13 weeks. Secondary outcome analysis showed that, all the trial regimens were comparable to control regimen in clearing antigen (F(3, 109)=0.405; P=0.750). Therefore, DEC + Albendazole sequential administration appears to be a better option for rapid clearance of W. b microfilariae in 13 weeks time. (Clinical trials.gov identifier - NCT02005653).

Enhanced efficacy of sequential administration of Albendazole for the clearance of Wuchereria bancrofti infection: Double blind RCT

Till today, there is no effective treatment protocol for the complete clearance of Wuchereria bancrofti (W.b) infection that causes secondary lymphoedema. In a double blind randomized control trial (RCT), 146 asymptomatic W. b infected individuals were randomly assigned to one of the four regimens for 12 days, DEC 300 mg + Doxycycline 100 mg coadministration or DEC 300 mg + Albendazole 400 mg co-administration or DEC 300 mg + Albendazole 400 mg sequential administration or control regimen DEC 300 mg and were followed up at 13, 26 and 52 weeks post-treatment for the clearance of infection. At intake, there was no significant variation in mf counts (F(3,137)=0.044; P=0.988) and antigen levels (F(3,137)=1.433; P=0.236) between the regimens. Primary outcome analysis showed that DEC + Albendazole sequential administration has an enhanced efficacy over DEC + Albendazole co-administration (80.6 Vs 64.7%), and this regimen is significantly different when compared to DEC + doxycycline co-administration and control (P<0.05), in clearing microfilaria in 13 weeks. Secondary outcome analysis showed that, all the trial regimens were comparable to control regimen in clearing antigen (F(3, 109)=0.405; P=0.750). Therefore, DEC + Albendazole sequential administration appears to be a better option for rapid clearance of W. b microfilariae in 13 weeks time. (Clinical trials.gov identifier – NCT02005653)

Cost-effective antigen testing for delimitation, monitoring and evaluation in bancroftian filariasis.

This study was focussed on identifying a cost-effective method for delimitation, monitoring and evaluation in bancroftian filariasis. Finger prick blood samples were collected between 20.00 and 23.00 hours for the detection of microfilariae (mf) from the available population in a village which was endemic for lymphatic filariasis. Simultaneously, from each individual, four spots of 25-µl blood samples were collected on Whatman number 3 filter paper and air dried. Dried filter paper spots were pooled in quantities of 1, 5, 10, 15, 20 and 25 on unknown and simulated mf and antigen prevalence. Pooled samples were assayed for circulating filarial antigen (CFA) using TropBIO Og4C3 ELISA kits. The community mf and CFA rates were 3.4% and 25.9%, respectively. The pool sizes of 20 and 25 showed CFA positivity in all the above categories tested. The results of the pooled blood spot samples suggest that, in areas with mf and CFA prevalence rates between 1 and 10%, pools of 20 or 25 could be considered as the ideal pool size for the detection of filarial infection in the community. CFA prevalence at the level of 5-6% following desirable rounds of mass drug administration (MDA) indicates that the community mf prevalence is likely to be at the 1% level.

A comparison of genotype and markers of disease severity of chronic hepatitis C in patients with and without end-stage renal disease.

INTRODUCTION: This study was conducted to compare the genotype and markers of disease severity of chronic hepatitis C (CHC), namely viral load, alanine transaminase (ALT) levels and histopathological findings on liver biopsy, in patients with and without end-stage renal disease (ESRD). METHODS: This was a cross-sectional retrospective comparative study that included ESRD patients on haemodialysis and non-ESRD patients with CHC who underwent liver biopsy between January 2004 and December 2006. Blood tests for viral load (VL) (hepatitis C virus, ribonucleic acid, polymerase chain reaction), genotyping and ALT were administered. VL was grouped into low (less than 5 log10) and high (more than or equal to 5 log10) VL, genotype into G1 and 2, 3, 4, and ALT into normal and elevated ALT. Necroinflammatory activity was grouped into mild (G0-6) and moderate/severe (G7-18) activity, and fibrosis into mild (S0-2) and moderate/severe (S3-6) fibrosis. These variables were compared between the two groups. RESULTS: Genotype 1 was significantly higher in ESRD patients than in non-ESRD patients, in whom genotypes 2, 3 and 4 were higher. Although the proportion of patients with high VL was greater and the duration of CHC was longer in the ESRD group, the ALT levels were lower and the histopathological grading of necroinflammatory activity and stages of fibrosis were less severe in ESRD compared to non-ESRD patients. CONCLUSION: The lower levels of ALT observed in CHC patients with ESRD translate to histopathological benefits.

Effect of a single dose of diethylcarbamazine, albendazole or both on the clearance of Wuchereria bancrofti microfilariae and antigenaemia among microfilaria carriers: a randomized trial.

BACKGROUND: Lymphatic filariasis is a major vector-borne parasitic disease. The global programme to eliminate lymphatic filariasis was launched in 1997 and currently over 570 million people are covered under it in 48 countries. Mass annual single-dose drug administration of diethylcarbamazine (DEC), co-administrated with albendazole for 5-6 years and mass distribution of diethylcarbamazine-fortified salt are the two strategies for elimination of filariasis. METHODS: Asymptomatic volunteers residing in Puducherry, India were screened for microfilaria (mf) by examining nocturnal thick blood smears. Those testing positive were randomly assigned to receive a single dose of DEC (6 mg/kg body weight) or albendazole 400 mg or both. Participants were hospitalized for 5 days. Membrane filtration count was used to assess microfilaraemia and ELISA (Og4C3) assay to measure circulating filarial antigens (CFA). Measurements were done before treatment and at 1, 2 and 3 years post-treatment. Viability of the adult worms was assessed by looking for the filarial dance sign (FDS) using ultrasound examination of the scrotum in men with hydrocele. RESULTS: Fifty-four microfilaraemic Individuals were studied. The mf prevalence started decreasing only by day 180 posttreatment in the DEC group but much earlier in the other two groups (day 30 in the albendazole and day 90 in the DEC with albendazole group). The decrease in mfwas marginal (17.6%, 26.3% and 27.8%, respectively) by the end of year 1 posttreatment, but significant (96.7%, 78.6% and 93.3%, respectively) by the end of year 2 post-treatment (p < 0.05). By the end of year 3, the level decreased to 80% in the DEC, 90% in the albendazole and to 100% in the DEC and albendazole groups. However, the mf intensity decreased significantly (by 39%; p < 0.05) by day 7 post-treatment in both the DEC and DEC with albendazole groups, but only by day 30 in the albendazole group. In all the drug groups, the prevalence as well as intensity of CFA returned to pretreatment levels by the end of year 3 post-treatment. CONCLUSION: Annual single-dose administration of all the 3 drug regimens significantly reduced antigenaemia levels. There were no significant differences in the efficacy and overall pattern of CFA clearance between the 3 drug regimens.

Impact of seven rounds of mass administration of diethylcarbamazine and ivermectin on prevalence of chronic lymphatic filariasis in south India.

OBJECTIVE: To evaluate the impact of seven rounds of mass administration of diethylcarbamazine (DEC) and ivermectin on the prevalence of chronic lymphatic filariasis and to compare it with that observed in a placebo arm in a community-level trial. METHODS: Cross-sectional clinical surveys were carried out before and after seven rounds of mass drug administration (MDA). About 54-75% of the target population were treated at each round of MDA. RESULTS: After seven rounds, the hydrocele prevalence had declined from the pre-intervention level of 20.5-5.1% (P < 0.05) in the DEC arm, from 23.9% to 10.4% (P < 0.05) in the ivermectin arm and from 20.4% to 10.9% (P < 0.05) in the placebo arm, equivalent to reductions of 75.3%, 56.6% and 46.6%, respectively. The lymphoedema/elephantiasis prevalence declined only marginally and without statistical significance from 3.7% to 3.2%, 4.6% to 3.9% and 2.9% to 2.3% in the DEC, ivermectin and placebo arm. After the seventh MDA, none of the sampled people in the 0-20 age group was found with hydrocele and there was a statistically significant decline in hydrocele prevalence in all other age groups in the communities treated with DEC, the drug known to have macrofilaricidal effect. The impact was relatively less in ivermectin arm. CONCLUSION: Repeated DEC administration has the potential to prevent incidence of new hydrocele cases and may resolve the manifestation at least in a proportion of affected people. Apart from reducing the microfilaraemia prevalence and transmission of infection, MDA also results in significant public health benefits by reducing the burden of hydrocele in treated communities.

The plight of chronic filarial lymphoedema patients in choice of health care and health care providers in Pondicherry, India.

Lymphatic filariasis has a wide spectrum of clinical manifestations with asymptomatic parasite carriers at one end and irreversible lymphoedema of extremities at the other. Irreversible lymphoedema of extremities is one of the disabling conditions that drive the affected patients to seek treatment from various systems of medicines and health care providers. This study attempts to map the care seeking pattern and behaviour of patients with chronic filarial lymphoedema of lower limbs in an urban area. Consecutive filarial lymphoedema patients from the VCRC filariasis clinic were recruited for the study. A pre-tested semi-structured questionnaire was used for interrogation of the patients. A total of 56 lymphoedema patients participated in the study. Majority (94.6%) of the patients sought medical management only. There was no difference (P>0.05) between the proportion of patients attending government (37.5%) and private (44.3%) medical care facilities There was also no difference in the proportion of patients' first consultations in private or government health care facilities. About 57.1% patients approaching governmental institutions opted for primary/secondary health care system. No particular sequential pattern of seeking health care was observed and the 56 study subjects followed 40 treatment-seeking routes by switching from one care provider to the other. The causes of not coming to the clinic for further check-up were 'no acute attacks' (30.4%), 'reduction in oedema volume' (21.7%), 'advised treatment being taken at home' (26.1%) and 'loss of daily wages' (21.7%). The study highlights the need to involve the private medical sector in morbidity management of filarial lymphoedema and to make governmental health facilities more accessible and user-friendly.

Locomotor disability in bancroftian filarial lymphoedema patients.

Disability prevention in cases with lymphatic filarial disease has been a research priority in view of the current programme on global elimination of lymphatic filariasis. This is also important for estimation of disease burden, impact evaluation, developing strategy for morbidity management and rehabilitation for lymphoedema patients in the endemic countries. In this communication, we are presenting the results of quantification of functional limitations of lower extremities with lymphoedema caused due to bancroftian filariasis by objective assessment of movement of joints and power of muscles in the affected legs. A total of 81 consecutive lymphoedema patients attending a filariasis clinic in Pondicherry urban locality were recruited for the study. Assessment for restriction of movement of joints and loss of power of muscles was carried out as in Manual for doctors to evaluate permanent physical impairment, prescribed by an expert group of WHO and Ministry of Health, Govt. of India on evaluation for permanent disability. Of the cases assessed, 40% in grade-I, 55% in grade-II, 77.3% in grade-III and 94.7% in grade-IV lymphoedema cases had functional limitations either in joint movements or power of muscles or both. The effective loss of locomotor/function (combined loss of joint movement and power of muscles in %) increased with stage of lymphoedema (grade-I-4.3+7.4, grade-II-7.0+8.4, grade-III-15.4+14.8 and grade IV- 33.2+22.8). The degree of loss varied significantly between the grades (P< 0.0001). The methodology used in this study can be adapted to evaluate the impact of the morbidity management component of strategy for Elimination of Lymphatic Flariasis (ELF) programme. This study will also enable researchers for fine-tuning the method for estimating disease burden and, to develop and evaluate strategies for morbidity management/rehabilitation of filarial lymphoedema patients.

Impact of 10 years of diethylcarbamazine and ivermectin mass administration on infection and transmission of lymphatic filariasis.

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

Kinetics of microfilaraemia & antigenaemia status by Og(4)C(3) ELISA in bancroftian filariasis.

BACKGROUND & OBJECTIVE: Bancroftian filariasis caused by Wuchereria bancrofti is endemic in many parts of India. In recent years diagnosis of W. bancrofti infection has been revolutionized with the availability of filarial antigen tests, which is important in monitoring success of chemotherapy. We carried out this study to measure microfilariaemia and antigenemia levels in bancroftian microfilariae (mf) carriers at 1 yr follow up after chemotherapy, in lymphoedema patients and in endemic controls from a filariasis endemic area in Tamil Nadu State using Og(4)C(3) ELISA to identify the best marker to assess success of chemotherapy. METHODS: Serum samples were collected from 30 bancroftian microfilaremic (Mf) carriers pre-treatment and at sequential intervals (7,30,60,90,180 and 365 days) following treatment with diethylcarbamazine (DEC:6mg/kg body weight, single dose), 30 lymphoedema patients (without treatment) at periodic intervals, and 68 control subjects (24 endemic normal subjects in filariasis endemic area in Tamil Nadu State, 24 non-endemic normal subjects residing in Chandigarh, India; 5 brugian filariasis, 5 endemic control subject in brugian filariasis endemic area and 10 other disease controls). The circulating antigen of W. bancrofti was measured quantitatively using Og(4)C(3) ELISA kit. RESULTS: In Mf carriers, there was no significant difference in microfilariae count in pre- and post-treatment (PT) samples till day 30 while significant differences were observed in pre- and sequentially collected post-treatment (PT) samples day 60 to 180 (P<0.001), day 365 (P<0.005). However, there was no significant difference in antigenaemia levels between pre-treatment (day 0) and PT samples collected on day 7 onwards till day 365. Though of the 19 patients who could be followed up till 365 days PT, 4 (21%) were amicrofilaraemic, none became antigen negative. No significant difference was found in antigenaemia levels in sequentially collected samples from lymphoedema patients. Significant differences were observed in antigenaemia levels in samples collected at the start of study in mf carriers as compared to lymphoedema patients and endemic normal subjects (P<0.001). Subjects (non-endemic control) residing in filariasis free area (24), brugian endemic area (5), B.malayi infected patients (5) and patients with other parasitic diseases (10) were found antigen negative. INTERPRETATION & CONCLUSION: Annual single dose of DEC therapy alone may not result in complete clearance of infection and detection of antigenaemia rather than microfilaraemia may be taken into consideration as an indicator of successful chemotherapy. The study supports the earlier view that filarial antigenaemia is relatively common in amicrofilaraemic and asymptomatic subjects in endemic areas and further studies are needed to determine the clinical significance, prognosis and effective management of such infections in endemic areas.

Effects of ivermectin and diethylcarbamazine on microfilariae and overall microfilaria production in bancroftian filariasis.

Ivermectin and diethylcarbamazine (DEC) are used in mass treatment programs for the elimination of lymphatic filariasis because of their strong effects on microfilaremia. However, the effects of treatment on adult worms and the degree of individual variation in efficacy are unclear. We analyzed series of microfilaria (Mf) counts from individuals treated with a single dose of 400 microg/kg ivermectin or 6 mg/kg DEC (N = 23 in each group; 1 year follow-up). For each individual, we estimated the microfilaricidal effect and the reduction in overall Mf production (e.g., caused by death or sterilization of worms, or inhibited Mf release from the female worm uterus). Ivermectin on average killed 96% of Mf and reduced Mf production by 82%. DEC killed 57% of Mf and reduced Mf production by 67%, with some individuals responding very poorly. The strong reduction in overall Mf production is good news for control of lymphatic filariasis, but the prospects of elimination will be diminished if part of the population systematically responds poorly to treatment.

Pattern of community compliance with spaced, single-dose, mass administrations of diethylcarbamazine or ivermectin, for the elimination of lymphatic filariasis from rural areas of southern India.

Current programmes to eliminate lymphatic filariasis (LF) are largely based on annual mass administrations of single doses of antifilarial drugs. The level and pattern of compliance by the target population are important determinants of the success of such mass drug administrations (MDA). Community compliance was therefore investigated during a study in southern India of the effects, on Wuchereria bancrofti microfilaraemia and transmission, of spaced MDA based on diethylcarbamazine (DEC) or ivermectin (IVM). During six rounds of MDA, the frequency of compliance in the target populations, in the five study villages given DEC and the five given IVM, ranged from 55%-77%. Analysis of the relevant cohort data indicated that about 30% of the villagers had complied with treatment during all six rounds, but 3.5% of those in the DEC arm and 4.0% of those in the IVM arm had never complied with treatment. Most of the villagers (>90%) had received treatment at least once, however, and >60% had each received treatment in at least four of the six rounds. Overall, there was a significant negative correlation (r=-0.78; P=0.008) between the size of the village, in terms of the number of villagers, and the mean frequency of compliance over the six rounds of MDA. The pattern of community compliance was found to be 'semi-systematic', laying between random and systematic. In terms of the elimination of LF, a semi-systematic pattern of compliance is worse than random compliance but better than systematic. The relevance of the levels and patterns of compliance to LF control or elimination is discussed.

Tolerability and efficacy of a three-age class dosage schedule of Diethylcarbamazine citrate (DEC) in the treatment of microfilaria carriers of Wuchereria bancrofti and its implications in mass drug administration (MDA) strategy for elimination of lymphatic filariasis (LF).

A six-age class dosage schedule of Diethylcarbamazine (DEC) of 50mg (1-2 years), 100mg (3-4 years), 150mg (5-8 years), 200mg (9-11 years), 250mg (12-14 years) and 300mg for above 14 years is being adopted for annual single dose MDA for LF elimination treat Wuchereria bancrofti microfilaria carriers. In order to increase the community compliance as well as to make the distribution easier during MDA, a revised 3 age class dosage schedule of 100mg (2-4 years), 200mg (5-14 years) and 300mg for above 14 years was evaluated for its tolerability and efficacy. By this change, it was observed that the 4-8 years age class is receiving 50 mg higher and 11-14 years age class is receiving 50mg lesser dose compared to the earlier class schedule. Therefore, the safety aspect in the age class of 4-8 years and efficacy component in the age class of 11-14 years were assessed. Apparently "healthy" asymptomatic microfilaraemic volunteers between the age class of 4-8 and 11-14 years were recruited for the study. The incidence of side reaction in the 4-8 years age class was 50.0% with 150mg dose and 66.7% with 200mg (P>0.05). No life threatening adverse reactions was observed in any dosage schedule. Fever, headache and myalgia, the predominant adverse reactions were mild and similar in both schedules. The mean intensity of the three major specific adverse reactions (fever, headache and myalgia) also did not differ significantly (P>0.05). For the purpose of LF elimination, efficacy in terms of reduction in mean microfilaria load is important. In the 11-14 year age class considerable reduction in the geometric mean density (GMD) was observed by day 90 and 180 post-therapy in both groups (250mg group and 200mg group) compared to pre-therapy level. By day 360 post-therapy, the difference was statistically not significant (P>0.05) (reduction of 72.2% in 250mg and 69.6% reduction in 200mg). The reductions in GMD were statistically significant when compared to pre-therapy levels in both the old (250mg) and new (200mg) doses. Thus, three- age class dosage schedule is as safe and efficacious as the six- age class schedule.

The preferential site of adult Wuchereria bancrofti: an ultrasound study of male asymptomatic microfilaria carriers in Pondicherry, India.

BACKGROUND: The traditional method of detection of microfilaria in night blood specimens for the diagnosis of Wuchereria bancrofti infection is being replaced with circulating filarial antigen in day blood specimens, which has a high sensitivity. However, both methods are indirect tests to detect the presence of adult worms in vivo. Localization of adult worms in vivo in their natural habitat may help in understanding better the end-point of drug treatment, the adulticidal action of antifilarial drugs, and in locating the site of lymphatic pathology. We used ultrasound examination to assess the preferential location of adult worms in an area endemic for lymphatic filariasis. METHODS: Ultrasound examination was done in 36 asymptomatic male carriers of Wuchereria bancrofti microfilaria to detect the location of adult worms. Both sides of the scrotum (root of the scrotum, epididymis, spermatic cord, testis and the adjoining area), lymphatic vessels and inguinal, popliteal, axillary and epitrochlear lymph nodes were examined using a 7.5 MHz probe in real-time B mode. RESULTS: The 'filaria dance sign (FDS)' suggesting the presence of adult worms was observed in 22 carriers (61%). The preferential site of location of the adult worms was the intrascrotal juxtatesticular lymphatic vessels in 'nests' along the lymphatic vessels of the epididymis, spermatic cord and paratesticular region. The number of nests varied between 1 and 4 with a mean size of 0.3 cm2. In 95% of cases, localization of the worms was unilateral. The mean microfilaria (SD) count-positive cases for those with the filarial dance sign (264 [199]) was significantly higher (p<0.05) than for the negative cases (171 [196]). CONCLUSION: Ultrasound visualization of adult worms of Wuchereria bancrofti in vivo is possible and confirms the concept that the worms have their own territory and reside in 'nests'. The preferential site of localization of the adult worms in men is the intrascrotal juxtatesticular lymphatic vessels.

Comparison of an immunochromatographic card test with night blood smear examination for detection of Wuchereria bancrofti microfilaria carriers.

BACKGROUND: At present, two diagnostic tests--Og4C3 ELISA and an immunochromatographic card test (ICT)--are available to detect circulating filarial antigens of Wuchereria bancrofti in serum/whole blood samples collected during the day. We aimed to assess the sensitivity of the new format card test 'NOW ICT Filariasis' in detecting microfilaria carriers of W. bancrofti in comparison with conventional microscopic techniques and Og4C3 ELISA. METHODS: A total of 200 persons were selected from two villages following a quota sampling design (100 in each village). The required number of houses was selected using a systematic sampling procedure with a random start of the first household. Blood samples were taken from all the available persons in each selected house until the quota of 100 was reached. The new format ICT test, Og4C3 ELISA and night blood smear examination for microfilaria were carried out following standard procedures. RESULTS: The sensitivity of the new format ICT test was 100% among microfilaria carriers (detected by both early and late readings). The kappa statistic measure of agreement between the two readings of all the samples (n =200) tested was 0.811 (p<0.05). The new format test also reported 25% of microfilaria-negative individuals as being positive for circulating filarial antigens. However, the diagnostic lines were not stable beyond 10 minutes (particularly in the case of amicrofilaraemic persons). Though there was an overall agreement between the results of ICT and Og4C3 tests (kappa =0.612; p< 0.05), the sensitivity of the Og4C3 test was lower than that of ICT. CONCLUSION: The new format ICT test is highly sensitive in detecting microfilaria carriers in endemic communities. Improvement in the format to provide stable diagnostic lines, specificity of the format and cost of the test kit are to be considered before its large-scale use.

Tolerability and efficacy of single dose diethylcarbamazine (DEC) alone or co-administration with Ivermectin in the clearance of Wuchereria bancrofti microfilaraemia in Pondicherry, South India.

The tolerability and efficacy of single dose DEC (12mg/kg body weight) or co-administration of DEC (6mg/kg body weight) with Ivermectin (200 or 400 mcg/kg of body weight) was studied in 60 asymptomatic W. bancrofti microfilariae (Mf) carriers following a double blind randomized design. The drugs were tolerated well. The incidence of adverse reactions of DEC (85.0%), DEC + Ivermectin 200mcg (95.0%) and DEC + Ivermectin 400mcg (100%) did not vary significantly (P>0.05). The mean score of adverse reaction intensity due to DEC + Ivermectin 200mcg (1.41) was significantly higher compared to DEC (0.61) (P<0.05). However, there was no significant difference between and DEC +Ivermectin 400mcg (0.89) and DEC + Ivermectin 200mcg (1.41) and DEC + Ivermectin 400mcg and DEC. The major adverse reactions were fever, headache and myalgia in all groups. The incidence and intensity of the adverse reactions were maximum between 24 to 48 hours of post therapy. The haematological and biochemical parameters did not vary significantly between pre and 7-day post therapy values in any of the study groups (P>0.05). Efficacy was measured in terms of proportion of cases clearing microfilaraemia completely and reduction in geometric mean parasite density in comparison to pre therapy levels. At the end of one year, DEC with Ivermectin 400mcg group showed significantly higher efficacy in complete clearance of Mf (94.4%) than that of DEC with Ivermectin 200mcg (60.0%) or DEC alone (52.6%) (P<0.05). However, no significant difference was observed in reduction of geometric mean Mf density (99.9%, 99.7%, 99.5% respectively). In all the groups, the tolerability and efficacy of the drugs were independent of host age and gender.

The impact of six rounds of single-dose mass administration of diethylcarbamazine or ivermectin on the transmission of Wuchereria bancrofti by Culex quinquefasciatus and its implications for lymphatic filariasis elimination programmes.

Lymphatic 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 (> or =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.

The prevalences of Wuchereria bancrofti antigenaemia in communities given six rounds of treatment with diethylcarbamazine, ivermectin or placebo tablets.

The ICT filariasis card test was used to determine the prevalences of Wuchereria bancrofti antigenaemia among villagers in India. Prior to the tests, those living in the 15 study villages had been treated six times, in six rounds of mass treatment (with 54%-75% coverage) spread over 6 years, with single doses of diethylcarbamazine (five villages), ivermectin (five villages) or placebo (five villages). The corresponding overall prevalences (and ranges) of filarial antigenaemia were 20.2% (13.7%-28.6%), 22.6% (15.3%-34.3%) and 25.9% (22.6%-29.3%), respectively. The overall prevalence of antigenaemia in the villages where diethylcarbamazine (DEC) had been distributed (but not that in the 'ivermectin' villages) was significantly lower than that recorded in the 'placebo' villages (z =2.56; P <0.05). The prevalences of antigenaemia among the villagers aged 1-5 years (18.9%, 15.6% and 22.4% in the DEC, ivermectin and placebo villages, respectively) did not differ significantly with treatment (P >0.05). The results indicate that annual mass treatments based on DEC or ivermectin, with 54%-75% treatment coverage, may have only a limited effect on the prevalence of infection with adult W. bancrofti. The possible reasons for the antigenaemias observed are discussed.

Detection of day blood filarial antigens by Og4C3 ELISA test using filter paper samples.

BACKGROUND: The launching of the global filariasis elimination programme has necessitated the use of highly sensitive and specific diagnostic tests. The Og4C3 monoclonal antibody-based ELISA test has been found to be highly specific and sensitive for the diagnosis of filariasis using night blood samples. However, it requires a serum sample which poses problems of transport and storage. Collection of blood samples on filter paper the will greatly circumvent these problems. Therefore, we evaluated the utility of the Og4C3 assay on filter paper samples collected during daytime. METHODS: Blood samples were collected from 63 microfilariae (mf) carriers during different time periods in a day on filter paper discs as well as venous blood for sera. The mf carriers and chronic (hydrocele n = 20; lymphoedema n = 120) and acute filariasis (adenolymphangitis n = 39) patients were from the endemic areas and the non-endemic normals were from Uthagamandalam district of Tamil Nadu, India. The filarial antigens in the samples were determined using the Og4C3 filarial antigen assay as per the manufacturer's instructions (JCU TrapBio, Australia). The sensitivity of the assay on sera and filter paper samples collected during night and also on filter paper samples collected during different time intervals of the day were compared with those of the membrane filtration technique, which was used as a gold standard. RESULTS: The geometric mean titre of the sera samples collected during night was 11 units/ml for non-endemic normals and 601.2 units/ml for mf carriers. The specificity of the assay on sera samples collected during night was 100% and the sensitivity 96.8% and the positive and negative values were 100% and 95.2%, respectively. The antigen positivity of the filter paper samples collected during morning hours was 93.3% while it was 76.6% and 86.7% for afternoon and evening hours. A significant association was observed between antigenaemia levels and mf density in the blood samples collected during the night. CONCLUSION: The samples collected on filter paper during the day can be used as an alternative to sera samples for detection of filarial antigens employing Og4C3 ELISA. Also, samples collected during morning hours yield a higher positivity. The assay when applied to serum samples will be useful especially when quantitative results are required.