Clinical manifestations of severe forms of P. falciparum malaria in koraput district of Orissa State, India.
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
S P Pani
Publications and source records attributed to S P Pani.
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.
Animals↗
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.
Adult↗
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.
Adolescent↗
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.
Adolescent↗
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.
Animals↗
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.
Animals↗
The effect of six rounds of single dose mass treatment with diethylcarbamazine or ivermectin on Wuchereria bancrofti infection and its implications for lymphatic filariasis elimination.
Annual mass treatment with single-dose diethylcarbamazine (DEC) or ivermectin (IVM) in combination with albendazole (ALB) for 4-6 years is the principal tool of lymphatic filariasis (LF) elimination strategy. This placebo-controlled study examined the potential of six rounds of mass treatment with DEC or IVM to eliminate Wuchereria bancrofti infection in humans in rural areas in south India. A percentage of 54-75 of the eligible population (> or =15 kg body weight) received treatment during different rounds of treatment - 27.4% in the DEC arm and 30.7% in the IVM arm received all six treatments, 4.8% and 5.6% received none, and the remainder received one to five treatments. After six cycles of treatment, the microfilaria (Mf) prevalence in treated communities dropped by 86% in the DEC arm (P < 0.01) (n = 5 villages) and by 72% in the IVM arm (P < 0.01) (n = 5 villages), compared with 37% in the placebo arm (P < 0.05) (n = 5 villages). The geometric mean intensity of Mf fell by 91% (t = 8.11, P < 0.05), 84% (t = 6.91, P < 0.05) and 46% (t = 2.98, P < 0.05) in the DEC, IVM and placebo arms, respectively. The proportion of high-count Mf (>50 Mf per 60 mm(3) of blood) carriers was reduced by 94% (P < 0.01) in the DEC arm and by 90% (P < 0.01) in the IVM arm. Among those who received all six treatments, 1.4% in the DEC arm and 2.4% in the IVM arm remained positive for Mf. Two of five villages in the DEC arm and one of five in the IVM arm showed zero Mf prevalence, but continued to have low levels of transmission of infection. The results also indicate that DEC is as effective as or slightly better than IVM against microfilaraemia. Results from this and other recent operational studies proved that single-dose treatment with antifilarials is very effective at community level, feasible, logistically easier and cheap and hence a highly appropriate strategy to control or eliminate LF. Higher treatment coverage than that observed in this study and a few more than six cycles of treatment and more effective treatment tools/strategies may be necessary to reduce microfilaraemia to zero level in all communities, which may lead to elimination of LF.
Animals↗
A geostatistical analysis of the geographic distribution of lymphatic filariasis prevalence in southern India.
Gaining a better understanding of the spatial population structure of infectious agents is increasingly recognized as being key to their more effective mapping and to improving knowledge of their overall population dynamics and control. Here, we investigate the spatial structure of bancroftian filariasis distribution using geostatistical methods in an endemic region in Southern India. Analysis of a parasite antigenemia prevalence dataset assembled by sampling 79 villages selected using a World Health Organization (WHO) proposed 25 x 25 km grid sampling procedure in a 225 x 225 km area within this region was compared with that of a corresponding microfilaraemia prevalence dataset assembled by sampling 119 randomly selected villages from a smaller subregion located within the main study area. A major finding from the analysis was that once large-scale spatial trends were removed, the antigenemia data did not show evidence for the existence of any small-scale dependency at the study sampling interval of 25 km. By contrast, analysis of the randomly sampled microfilaraemia data indicated strong spatial contagion in prevalence up to a distance of approximately 6.6 kms, suggesting the likely existence of small spatial patches or foci of transmission in the study area occurring below the sampling scale used for sampling the antigenemia data. While this could indicate differences in parasite spatial population dynamics based on antigenemia versus microfilaraemia data, the result may also suggest that the WHO recommended 25 x 25 km sampling grid for rapid filariasis mapping could have been too coarse a scale to capture and describe the likely local variation in filariasis infection in this endemic location and highlights the need for caution when applying uniform sampling schemes in diverse endemic regions for investigating the spatial pattern of this parasitic infection. The present results, on the other hand, imply that both small-scale spatial processes and large-scale factors may characterize the observed distribution of filariasis in the study region. Our preliminary analysis of a mountain range associated large-scale trend in the antigenemia data suggested that a nonlinear relationship of infection prevalence with elevation might be a factor behind such observed global spatial patterns. We conclude that geostatistic methods can provide a powerful framework for carrying out the empirical investigation and analysis of parasite spatial population structure. This study shows that their successful application, however, will crucially depend on our gaining a more thorough understanding of the appropriate geographic scales at which spatial studies should be carried out.
Adult↗
A comprehensive study of morbidity in school age children.
Explore the source record for details and available documents.
Adolescent↗
EPIFIL: the development of an age-structured model for describing the transmission dynamics and control of lymphatic filariasis.
Mathematical models of transmission dynamics of infectious diseases provide a useful tool for investigating the impact of community based control measures. Previously, we used a dynamic (constant force-of-infection) model for lymphatic filariasis to describe observed patterns of infection and disease in endemic communities. In this paper, we expand the model to examine the effects of control options against filariasis by incorporating the impact of age structure of the human community and by addressing explicitly the dynamics of parasite transmission from and to the vector population. This model is tested using data for Wuchereria bancrofti transmitted by Culex quinquefasciatus in Pondicherry, South India. The results show that chemotherapy has a larger short-term impact than vector control but that the effects of vector control can last beyond the treatment period. In addition we compare rates of recrudescence for drugs with different macrofilaricidal effects.
Adolescent↗
Development of rapid assessment procedures for the delimitation of lymphatic filariasis-endemic areas.
Lymphatic filariasis caused by Wuchereria bancrofti is a major public health problem in 73 tropical and subtropical countries including India. Delimitation of endemic areas is essential to plan control operations. The current method of night blood survey (NBS) for delimitation is cumbersome, time-consuming and expensive. Therefore, there is a need to develop assessment procedures which can rapidly delimit endemic areas. For this purpose we evaluated three procedures: direct interviewing of key informants using structured questionnaires, an indirect method of a self-administered questionnaires to key informants and physical examination by health workers for the presence of chronic filarial disease. Thirty rural communities in a filariasis-endemic region in Cuddalore district in Tamil Nadu State in southern India constituted the study population. The determination of filariasis endemicity in the village communities assessed by the above procedures was compared in terms of rapidity, specificity, sensitivity and cost with the microfilaria rate and disease rate obtained by night blood sample survey and clinical examination by physicians. Prevalence score, control preference score and weighted mean number of cases with filarial disease per village were calculated using the key informant questionnaire techniques. While the prevalence and control preference score showed low sensitivity and moderate specificity, weighted mean number of cases showed high sensitivity and moderate specificity in identifying endemic villages. The prevalence of disease as determined by the physical examination of a sample population by health workers was highly sensitive in identifying communities endemic for filariasis. The degree of association between the disease rates estimated by physician and trained health workers was significant (r = 0.56; P < 0.05). These observations suggest that the weighted mean number of cases per village obtained through key informant techniques may be considered at a primary level to crudely identify endemic areas, followed by physical examination by health workers for filariasis, since it is relatively cheap and rapid.
Adolescent↗
Evaluation of the ICT whole blood antigen card test to detect infection due to nocturnally periodic Wuchereria bancrofti in South India.
The commercially available ICT Card Test for bancroftian filariasis was evaluated for its sensitivity and specificity in detecting microfilaria carriers among 189 individuals each in filariasis-endemic and nonendemic areas in South India, and compared to both conventional night blood finger prick thick blood smear examination and venous blood membrane filtration. Though the specificity of the test was 100% in comparison to both, the sensitivity was 98.5% against the finger prick thick blood smear and 71.9 compared to the membrane filtration technique. Similarly, the positive predictive value was 100% against both techniques, but the negative predictive values were 99.5% against the finger prick thick blood smear and 88.3% compared to the membrane filtration technique. The test's lower sensitivity compared to the filtration technique requires further investigation.
Animals↗
Tolerability and efficacy of single-dose diethyl carbamazine (DEC) or ivermectin in the clearance of Wuchereria bancrofti microfilaraemia in Pondicherry, south India.
In a double blind design the tolerability and efficacy of single-dose DEC (6 mg/kg/body weight) or ivermectin (400 microg/kg/body weight) was studied in 30 asymptomatic W. bancrofti parasite carriers each. Although both drugs were tolerated well, the adverse reaction score (DEC 0.5; ivermectin 1.5) and overall incidence (DEC 65.0%; ivermectin 93.3%) were significantly higher in the ivermectin group. Major adverse reactions were fever, headache and myalgia, all of which peaked on the second day post-therapy. Efficacy was measured in terms of proportion of cases clearing parasitaemia and reduction in mean parasite density compared to pre-therapy levels. Although at the end of one year the ivermectin group showed a significantly higher efficacy (34.8%, 97.0%) compared to DEC (8.3%, 83.8%), at the end of the second year there was no significant difference in efficacy between the drugs (73.7%, 99.5% for ivermectin; 47.8%, 98.9% for DEC). The tolerability and efficacy of the two drugs were not significantly different between gender, age and weight classes of patients.
Adult↗
Treatment costs and loss of work time to individuals with chronic lymphatic filariasis in rural communities in south India.
This year-round case-control study investigated treatment costs and work time loss to people affected by chronic lymphatic filariasis in two rural communities in south India. About three-quarters of the patients sought treatment for filariasis at least once and 52% of them paid for treatment, incurring a mean annual expenditure of Rs. 72 (US $2.1; range Rs. 0-1360 (US $39.0)). Doctor's fees and medicines constituted 57% and 23% of treatment costs. The proportion of people seeking treatment was smaller and treatment costs constituted a higher proportion of household income in lower income groups. Most patients did not leave work, but spent only 4.36+/-3.41 h per day on economic activity compared to 5.25+/-3.52 h worked by controls; the mean difference of 0.89+/-4.20 h per day was highly significant (P<0.01). This loss of work time is perpetual, as chronic disease manifestations are mostly irreversible. An estimated 8% of potential male labour input is lost due to the disease. Regression analyses revealed that lymphatic filariasis has a significant effect on work time allotted to economic activity (P<0.05) but not on absenteeism from work (P>0.05). Female patients spent 0.31+/-1.42 h less on domestic activity compared to their matched controls (P<0.05). The results clearly show that the chronic form of lymphatic filariasis inflicts a considerable economic burden on affected individuals.
Absenteeism↗
Direct and indirect costs of the acute form of lymphatic filariasis to households in rural areas of Tamil Nadu, south India.
This study examined the direct and indirect costs due to acute form of lymphatic filariasis caused by Wuchereria bancrofti to the households in rural communities in Tamil Nadu state in south India. For nearly one-third of the acute adenolymphangitis (ADL) episodes the affected did not seek treatment and for 27% of the episodes they consulted health personnel, underwent treatment and paid for it. On average, the ADL patients spent Rupees (Rs.) 2.35 (US $ 0.07) per episode on treatment, but expenditure was as high as Rs. 32.11 (US $ 0.92) among those who paid. Doctor's fees and medicines constituted 83% of the total treatment costs. Patients with multiple and longer duration episodes and with better living conditions spent relatively more on treatment. The proportion of patients who spent money on treatment was smaller in poorer households, but their treatment costs formed a relatively higher proportion of their income than those of middle and high-income households. The ADL episodes curtailed economic and domestic activities. In 87% of the episodes, the affected were not able to attend any economic activity compared to 37% of the episodes in the case of controls. Patients spent only 0.68 +/- 1.91 hours on economic activity compared to 4.40 +/- 3.74 hours by the control individuals during the ADL episodes. The sign rank test showed that the mean difference of 3.73 +/- 3.81 and 2.14 +/- 1.83 hours in the time spent on economic and domestic activity respectively between cases and controls was highly significant (P < 0.01). Regression analysis demonstrated that the difference in the time spent on activities is only due to ADL and no socio-economic variable had any effect on it. The cost of treatment and loss in economic activities combined with high incidence in the study communities indicate the extent of the economic burden imposed by the hitherto neglected acute form of lymphatic filariasis and the necessity to control it.
Acute Disease↗
Epifil: a dynamic model of infection and disease in lymphatic filariasis.
The lack of a quantitative framework that describes the dynamic relationships between infection and morbidity has constrained efforts aimed at the community-level control of lymphatic filariasis. In this paper, we describe the development and validation of EPIFIL, a dynamic model of filariasis infection intensity and chronic disease. Infection dynamics are modeled using the well established immigration-death formulation, incorporating the acquisition of immunity to infective larvae over time. The dynamics of disease (lymphodema and hydrocele) are modeled as a catalytic function of a variety of factors, including worm load and the impact of immunopathological responses. The model was parameterized using age-stratified data collected from a Bancroftian filariasis endemic area in Pondicherry in southern India. The fitted parameters suggest that a relatively simple model including only acquired immunity to infection and irreversible progression to disease can satisfactorily explain the observed infection and disease patterns. Disease progression is assumed to be a consequence of worm induced damage and to occur at a high rate for hydrocele and a low rate for lymphodema. This suggests that immunopathology involvement may not be a necessary component of observed age-disease profiles. These findings support a central role for worm burden in the initiation and progression of chronic filarial disease.
Adolescent↗
Functional impairment caused by lymphatic filariasis in rural areas of south India.
The functional impairment caused by lymphatic filariasis was assessed through qualitative and quantitative methods in rural areas of Tamil Nadu, South India. About 66% of the patients said that their occupational activities were hampered by the disease. They either work fewer hours or alter their activity. Some had completely given up their job. Domestic chores of most of the female patients were also impeded. Most of those affected try to avoid travel. The disability was worse in patients with acute disease. In view of the results of our and other similar studies, the disability-adjusted life years lost due to lymphatic filariasis must be revised and the public health importance of the disease reassessed. Considerable functional impairment coupled with recent information on economic burden and productivity loss caused by lymphatic filariasis necessitates paying more attention to the control of the disease.
Adult↗