P. Vanamail

Episodic adenolymphangitis and lymphoedema in patients with bancroftian filariasis

In order to explore the relationship between acute and chronic disease, age-specific data on the frequency and duration of episodic adenolymphangitis (ADL) in patients with 3 defined grades of lymphoedema in bancroftian filariasis were examined. The age distribution of grades I and II exhibited a convex age profile, but that of grade III showed a monotonic increase. The mean duration of oedema increased with its grade (grade I, 0.3 years; grade III, 9.9 years). The mean number of ADL episodes in the previous year for all cases was 4.2 and it increased with grade (grade I, 2.4 and grade III, 6.2). The mean duration of each ADL episode for all cases was 4.1 d and it was independent of grade and age. The mean period lost to ADL episodes in the previous year was 17.5 d; it increased from 9.4 d with grade I to 28.5 d with grade III. The results imply that there is a dynamic progression through the grades of lymphoedema and that the frequency of ADL episodes is positively associated with this progression. However, the study design could not separate cause from effect.

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.

Estimation of age-specific rates of acquisition and loss of Wuchereria bancrofti infection

This study uses a reversible catalytic model to estimate the age-specific rates of gain and loss of Wuchereria bancrofti infection from data collected during a control programme in Pondicherry, South India. The data describe the infection status in 1981 and 1986 of two cohorts of individuals, one living in an area where vector reduction had been achieved, and the other in a comparable endemic area. The rate of loss of infection in the absence of reinfection is estimated for the cohort in the control area, and the rate of gain of infection by the cohort in the endemic area estimated by substitution in the model. The mean expected life span of patent infection is estimated to be 5.4 years. The instantaneous rate of loss of infection is independent of age, while the rate of gain of infection exhibits a convex age-profile, peaking in the 16-20 year age-class. The reduced rate of gain in adults is largely attributable to the increasing proportion of potentially resistant individuals with clinical disease. The results suggest that the age-distribution of bancroftian filariasis is primarily determined by age-dependency in the rate of acquisition of infection.

Estimation of the fecund life span of Wuchereria bancrofti in an endemic area

A stochastic approach appropriate for general use in endemic communities was applied to estimate the average yearly instantaneous rate of loss of Wuchereria bancrofti microfilaraemia from infected individuals, and gain by uninfected individuals, from longitudinal data. This method was shown to give similar results (i.e., the rate of loss was independent of age, while the rate of gain differed significantly between age classes) to a previously used method based on transmision interruption, provided that the intersurvey interval was > 5 years. The method was used to estimate the fecund life span of W. bancrofti in an endemic area at 5 years. The results suggest that the life span is at the lower end of previous estimates.

Placebo-controlled community trial of four cycles of single-dose diethylcarbamazine or ivermectin against Wuchereria bancrofti infection and transmission in India

A double-blind placebo-controlled trial was carried out in 1994-98 to compare the effects of 4 cycles of single-dose diethylcarbamazine (DEC) or ivermectin on prevalence and geometric mean intensity (GMI) of microfilaraemia in the human population, infection rates in the vector population, and transmission intensity of Culex-transmitted Wuchereria bancrofti in rural areas in Tamil Nadu state, south India. Fifteen villages (population approximately 26,800) were included in the study: 5 villages each were randomly assigned to community-wide treatment with DEC or ivermectin or placebo. People over 14 kg bodyweight received DEC 6 mg/kg, ivermectin 400 micrograms/kg or a placebo, all identically packaged. After 2 cycles of treatment at a 6-month interval, the code was broken and the study continued as an open trial, with third and fourth cycles of treatment at a 12-month interval; 54-77% of eligible people (20,872) received treatment during the 4 cycles. Microfilaraemia prevalence and GMI fell by 48% and 65% with DEC and 60% and 80% with ivermectin respectively after 4 cycles of treatment. There was no change in the incidence of acute adenolymphangitis. Infection in resting mosquitoes fell significantly in all arms: 82%, 78% and 42% in the ivermectin, DEC and placebo arm, respectively. Landing mosquitoes also showed the same trend. The decline in infectivity was significant for resting (P < 0.05) and landing mosquitoes (P < 0.05) with ivermectin and DEC (P < 0.05), and for neither in the placebo group (P > 0.05). Transmission intensity was reduced by 68% with ivermectin and 63% with DEC. Transmission was apparently interrupted in 1 village with ivermectin, but infected resting mosquitoes were consistently found in this village. Single-dose community-level treatment with DEC or ivermectin is effective in reducing W. bancrofti infection in humans and mosquitoes, and may result in total interruption of transmission after several years of control. There is an immediate need to define the role of vector, parasite and community factors that influence the elimination of lymphatic filariasis, particularly the duration of treatment vis-à-vis efficacy of drugs, treatment compliance and efficiency of vectors.

Bancroftian filariasis in Pondicherry, south India: 1. Pre-control epidemiological observations.

A 5-year Integrated Vector Management (IVM) project was implemented in Pondicherry, South India, for the control of Bancroftian filariasis. The efficacy of the IVM strategy was compared with routine control strategy under the national programme. The present paper describes the pre-control epidemiological features of filariasis as determined by a mass blood survey in 1981. Of 24946 persons examined 8.41% were microfilaraemic. Microfilaraemia prevalence was homogeneous throughout the study area. The prevalence and intensity of microfilaraemia were age dependent, and increased monotonically until about 20 years, following which there was a decline until about 40 years to become relatively stable in older age classes. The gender profiles of both prevalence and intensity of microfilaraemia showed no difference between the sexes until about 15 years of age, following which both were higher in males compared to females. The distribution of microfilarial counts was overdispersed, indicating aggregation of adult worms.

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. Apercentage of 54–75 of the eligible population (≥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 mm3 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.

Frequency distribution of Wuchereria bancrofti microfilariae in human populations and its relationships with age and sex

This paper examines the effects of host age and sex on the frequency distribution of Wuchereria bancrofti infections in the human host. Microfilarial counts from a large data base on the epidemiology of bancroftian filariasis in Pondicherry, South India are analysed. Frequency distributions of microfilarial counts divided by age are successfully described by zero-truncated negative binomial distributions, fitted by maximum likelihood. Parameter estimates from the fits indicate a significant trend of decreasing overdispersion with age in the distributions above age 10; this pattern provides indirect evidence for the operation of density-dependent constraints on microfilarial intensity. The analysis also provides estimates of the proportion of mf-positive individuals who are identified as negative due to sampling errors (around 5% of the total negatives). This allows the construction of corrected mf age-prevalence curves, which indicate that the observed prevalence may underestimate the true figures by between 25% and 100%. The age distribution of mf-negative individuals in the population is discussed in terms of current hypotheses about the interaction between disease and infection.

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 (≥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.

Wuchereria bancrofti microfilaraemia in children in relation to parental infection status.

A total of 946 families with 2302 children was surveyed for microfilaraemia due to Wuchereria bancrofti. The prevalence of microfilaraemia among offspring born to microfilaraemic parents was significantly higher than in those born to amicrofilaraemic parents (P = 0.0049; relative risk = 3.40). However, there was no statistically significant difference between the prevalence of microfilaraemia in children born to microfilaraemic mothers or microfilaraemic fathers, suggesting that parental (not only maternal) infection is the important risk factor, and it may be exposure within the household which is important. Logistic regression analyses also confirmed that the risk of infection for offspring born to either microfilaraemic mothers or microfilaraemic fathers was higher than that for offspring born to amicrofilaraemic parents and indicated that infection in children < or = 20 years old was primarily dependent on parental infection status and minimally influenced by factors other than household exposure.