Integrating mass drug administration with vector control for the elimination of lymphatic filariasis.
The occurrence of filarial disease depends on high rates of disease transmission and continued endemicity. It has been calculated that statistically an average of several thousands of bites by infective vector (range 2700 to > 100,000) take place before a new human case of infection is established (6). For Culex quinquefasciatus transmission of W. bancrofti (7), it was estimated that about 2,765 infective bites would be the average exposure leading to patent microfilaraemia where the mean annual biting rate (ABR) exceeded 80,000 bites/person/year and the mricrofilaraemia rate among adults of different ethnic groups reached 4-11%. Realization that a high proportion of LF cases are contracted during childhood, years before microfilaraemia develops (8), indicates that LF incidence can be caused by far fewer infective mosquito bites than was previously believed necessary. Hence targeting of young children in the mass drug administration (MDA) programme should be emphasized (9).
In many tropical situations, with various vectors it has been observed that, below a critical number of infective bites, LF is not sustained as an endemic disease. For example in cities with good environmental management (e.g., Singapore and Mumbai) and islands such as Cuba, Trinidad, Guam and Mauritius, LF disappeared--apparently as a result of improved sanitation limiting the vector density. Moreover, in the Solomon Islands, parts of Togo and Papua New Guinea, interruption of filariasis transmission resulted from insecticide house-spraying operations by the anti-malaria programme (10,11). Generally, by application of standard methods of mosquito control, it is possible to greatly reduce the risks of transmission, if not to prevent it altogether.
Culex Vectors of Wuchereria bancrofti
About half of the world's burden of LF is transmitted by Culex species and in India 98% of LF parasite is transmitted by Cx. quinquefasciatus, which bites only in darkness and transmits only nocturnally periodic Wi bancrofti in most endemic urban areas. Culex quinquefasciatus typically breeds in stagnant, organically polluted water. In many urban areas, the majority of Culex breeding sites are in flooded pit latrines and soakage pits, which can be targeted for specific control measures (12,13). In low-lying areas, especially where monsoon climate causes prolonged extensive flooding of ditches and gulley, source-reduction of Culex is virtually unmanageable. Where possible, keeping open drains flowing has been demonstrated to effectively suppress the adult Cx. quinquefasciatus biting populations (e.g. in Pondicherry, India, and Tanga, Tanzania), but this needs sustained effort and expenditure (14). Upgraded sanitation and drainage is undoubtedly the long-term solution to the urban Culex problem. Although expensive, the broader benefits to social progress and health (against other enteric diseases and helminth infections) make sanitation systems more cost-effective in the long-run. In economically advanced situations (e.g. Singapore, Costa Rica, Trinidad), Culex has been readily reduced to levels where LF transmission breaks down. In developing countries more cost-effective methodology needs to be implemented to reduce the burden of cost on government funding agencies to tackle Culex problem.
Intervention Strategies for Culex quinquefasciatus
Various methods are available to control the breeding of Cx. quinquefasciatusi At least 2/3 of this vector production is from flooded pits and application of expanded polystyrene beads (EPBs) to the pits is recommended for prolonged suppression of vector potential. This approach would be inadequate in situations (areas with monsoon climate) where the majority of vector Culex breeding-sites are in flooded ditches, surface pools and water storage containers. Habitual use of insecticide treated nets is essential wherever LF remains endemic (being popular against nuisance mosquitoes as well giving substantial protection against malaria and other mosquito-borne diseases), particularly where Culex and other mosquitoes are left uncontrolled. Improved sanitation and drainage systems, where affordable, greatly reduce transmission risks of LF as well as other helminth and enteric diseases. Various options available for vector control are outlined in the present write-up.
Use of chemical insecticides
For larval control, extensive use of organophosphate insecticides (e.g. fenthion, temephos) has been made, but the widespread development of resistance reduces their effectiveness against Culex populations. Oiling is seldom suitable because the lighter 'mosquito larvicidal oils' (MLOs) are readily emulsified by detergents often present in polluted waters preferred by Cx. quinquefasciatus, while heavier oils tend to clog soakage pits. To avoid selection pressure on immature stages of mosquitoes (larvae and pupae), pyrethroid insecticides should never be used for larviciding--since pyrethroids are invaluable adulticides. Even so, adult Culex mosquitoes are relatively more tolerant than other types of mosquitoes against most insecticide applications, making adulticidal control of Culex rather ineffectivei Generally larviciding programmes, with high costs of chemicals, equipment and labour, are uneconomical and unsustainable against Culex vectors of W. bancrofti. In situations where Culex breeds prolifically in flooded drains and sites that cannot be readily treated, larviciding cannot be expected to have sufficient impact to reduce filariasis prevalence, particularly where monsoon climate and periodic flooding cause extensive breeding sites to be unmanageable except by major drainage improvements (15).
Use of expanded polystyrene beads
An excellent method of Culex control employs floating layers of expanded polystyrene beads which create a physical barrier to egg-laying adult Culex while suffocating larvae and pupae. Floating EPBs are extremely durable, giving prolonged suppression of Culex populations (16). EPBs can only be used effectively in habitats where stagnant water is confined within walls, e.g. pit latrines, soakage pits, cess pits, flooded cellars, etc. Sustainable control of Cx. quinquefasciatus has been demonstrated over several years among communities in Zanzibar, Tanzania (17-18), and Tamil Nadu, India (19,20), where the application of EPBs in all pits found to be breeding-sites of Cx. quinquefasciatus virtually eliminated the Culex nuisance mosquito problem. In these situations the vector control (VC) operations were transferred to the community, and the youth volunteers were involved in monitoring the breeding of filariasis vectors in cess pits. One application of EPBs to each pit resulted in few years of control in East African towns. Most importantly, this simple method for sustained control of Culex greatly enhanced the impact of time-limited MDA, by preventing resurgence after MDA ceased (21). In St. Vincent and the Grenadines, West Indies, this method was applied using shredded waste polystyrene (SWAP) to give long-lasting control of Cx. quinquefasciatus in pit latrines (22). Floating carpets of EPBs or SWAP are not suitable for flood-prone areas and exposed breeding-sites from where they may be flushed away. In places where at least 2/3 of Culex breeding is attributed to breeding-sites in pits suitable for polystyrene treatment, this method should be applied to control the filariasis vector population in situations where improving the sanitation system (e.g., water closet with mains drainage or well maintained mosquito proof septic tanks and cess pits) is not feasible to prevent breeding of mosquitoes and flies.
Bacillus sphaericus (Bs) can kill Culex larvae in polluted water, and may have some recycling potential, whereas Bacillus thuringiensis israelensis (Bti) is not effective in such habitats. These biopesticides are commercially available, mainly for use against pest mosquitoes in wetlands of prosperous countries. In practice, for LF vector control, B. sphaericus in open breeding sites did not contribute usefully to adult Culex suppression beyond what was achieved with EPBs applied to pits in the same areas (of Zanzibar and Tamil Nadu). There have been problems with B. sphaericus quality control and rapid development of resistance against it by Cx. quinquefasciatusi. Field resistance to Bi sphaericus was observed in a population of Cx. quinquefasciatus in Kochi, south India, exposed to 35 rounds of spraying with a formulation of Bi sphaericus 1593M over a 2 year period (23). Enthusiasm for these bioproducts seems to be inappropriate for LF vector control in poor economic situations in developing countries. Among the insect growth regulators (IGRs), pyriprroxyfen is most potent (24) and could be used to suppress immature Culex populations.
Insecticide impregnated materials
Measures that restrict access of Cx. cuinquefasciatus into houses, such as the installation of ceilings, or the use of eaves curtains impregnated with insecticides, have been shown to reduce Culex biting. Insecticide treated bed nets divert Culex to bite birds and hence reduce the transmission potential of W. bancrofti to humans. It was demonstrated that pyrethroid impregnated bed nets killed very few Cx. quinquefasciatus but reduced significantly their feeding rate success (25). In the Kenyan coast a shift from human to animal feeding was observed after the use of pyrethroid impregnated bednets (26). Statistically significant reductions of indoor-resting and man-biting densities of the mosquitoes An. subpictus and Cx. quinquefasciatus were observed for 14 weeks, in two field trials using hessian curtains impregnated with deltamethrin in south India (27). In filaria endemic areas where stagnant polluted drains are the potential breeding grounds for Cx. quinquefasciatus, implementation of pyrethroid impregnated materials will greatly reduce the man-vector contact.
Mass drug administration and vector control
Vector control (with EPS beads in soakage pits and larvivorous fishes in unused wells) in Tirukoilur, south India, when used as an adjunct to MDA given annually, brought about reduction in filariometric indices, and provided a strong evidence of the benefit of integrating vector control with MDA (19-20). Vector density greatly decreased in villages where vector control was used as an adjunct to MDA and almost no infective moscuitoes were found in the small numbers still remaining in Tirukoiluri During the first year, the reduction in transmission potential (estimated from mosquito landing catches) was more rapid when MDA was combined with VC, which was equalized in the second year. In the absence of M DA in the third year, the transmission reduction was sustained in MDA+VC villages, while in MDA alone villages a resurgence in filarial infection variables was noticed (21) (Fig. 1).
[FIGURE 1 OMITTED]
[FIGURE 2 OMITTED]
Filarial antigenaemia was low and continued to decrease significantly in the age group 15-25 years in villages receiving MDA+VC in contrast to villages receiving only MA. A definite impact of vector control was observed in the age group 15-25 years among villages receiving MDA with vector control. In the youngest age group of 2-5 years, the regression equations for MDA alone and MDA+VC demonstrated significant differences (Fig. 2). In MDA+VC the line demonstrated a steep slope downwards with b=-0.81.
Considerable numbers of filarial larvae (including L3 stages) were found in the mosquitoes caught in the villages receiving M DA alone. Very few or no filarial larvae were found in villages receiving MDA with vector control but very few mosquitoes were available for dissection here. This indicates that the children in MDA+VC villages are receiving low/nil infective bites.
Annual MDAs alone decreased the filarial infection load in the community if there were no lapses. However, residual microfilaraemia of 0.4% and antigenaemia positivity of 4.6% were observed even after 36 years of filariasis control in French Polynesia (28). MDA with DEC drug combination was found to be more effective than DEC alone in decreasing filarial infection variables (29). Vector control was found to be important during any lapse in the MDA programme (21). The importance of vector control methods has been emphasized, as they play a key role in the prevention of disease transmission. In China, the campaign against LF turned successful when vector control was integrate with other intervention measures, such as DEC administration (selective and mass treatment, and as fortified salt), resulting in the interruption of filarial transmission without any resurgence.
It seems unlikely that MDA would be sufficient for sustained interruption of transmission in areas of Culex transmission of lymphatic filariasis, due to their high vectorial efficiency (30). Therefore, vector control would be an important supplement to sustain the interruption of transmission in some epidemiological settings (31). In Makunduchi, Zanzibar, tie Culex mosquito population decreased by about 98% after applying EPS beads to all the wet pit latrines, without any change in a nearby untreated community (17). One round of MDA with DEC resulted in decreasing the proportion of mosquitoes with third-stage larvaeCL3) causing an overall 99.7% decrease in the number of infective bites per year in the treated area and microfilaremia remained low for 10 years. Integration of vector control with MDA can decrease the time required for filariasis elimination by complementing the benefits brought about by MDA. Achievement of <100 ATP and <0.5 HI, are considered as levels necessary for preventing the occurrence of new infections (32). This low transmission level should be maintained for a sufficiently long period to interrupt transmission and it is a more affordable and sustainable way to eliminate filariasis, especially when communities can be empowered to carry out simple vector control operations along with MDA.
Integrated vector control
In Pondicherry, India, in a five year integrated vector control (IVC) programme, various measures were taken to prevent vector breeding included closing of wells, application of expanded polystyrene beads in overhead tanks and sanitation structures. Biological control methods by the release of larvivorous fishes in suitable habitats were also included. In the few areas were chemical larvicides were required, fenthion was chosen in addition to juvenile hormone analoguesi After 5 years of IVC, the indoor resting density of Cx. quinquefasciatus was reduced by 90% and the prevalence of microfilaraemia decreased by 60% (14). An analysis of the costs showed that the integrated control methods compared favourably with control using conventional insecticides. But the withdrawals of the strategy lead to the resurgence of the vector species.
Involvement of Community
Involvement of the community for the success of vector control programmes assumes greater significance as the problem revolves mostly around human and his environment. The individuals, families and the community have to be progressively informed, involved and educated. All vector control programmes should begin with formation of a core or co-ordination committee, comprising of various heads of government agencies and leaders of local society. Public health officials will be concerned with transmitting technical subjects of the programme to these functionaries, who can inspire individuals, families and local leaders to participate actively in the task of elimination of vector breeding in and around their houses, which will ultimately lead to disease (vector-borne) free society. The government should provide the resources to the community leaders, who can arrange for volunteers to accomplish the tasks when individual families cannot. In motivation of community involvement in a local vector control programme, a prime question to be answered is the reason for their involvement in spite of the little time they can spare due to other pressing priorities locally. For community to participate in any programme, their expected role should be spelt out. A continued dialogue is a pre-requisite between the health personnel and the people, aimed at motivation of the attitudes of the community so that people may accept the control programme as the people's programme.
Effective vector control would be important supplementary approach to expedite interruption of transmission and also can sustain the gains of MDAs. It is the most cost-effective option when unit costs of individual case detection and treatment become progressively greater as case numbers decline. Vector control can achieve twin goals of reducing vectorial capacity and minimizing the opportunities for human-vector contact. In India the vector control towards Cx. quinquefasciatus should be appropriately implemented depending on the prevailing local conditions, so as to sustain the control methods employed. Vector control can be made cost-effective by spatial and temporal targeting of the vectors. Community should be empowered to participate from the planning stage itself and education should form the integral part of the vector control strategy. There are a number of challenges for MDA-based LF elimination programmes and these challenges can be met by integrating vector control with MDA. The potential benefits of VC has been spelled out as (i) suppressing LF transmission without identifying individual foci of infection; (ii) minimizing risk of resurgence; (iii) reducing risk of drug resistance; and (iv) enhancing community support by reduced mosquito nuisance (31).
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This write-up has been contribute by Dr. I. P. Sunish, Research Officer, Dr. R. Rajendran, Scientist D, Mr. A. Munirathinam, Technical Officer and Dr. B.K.Tyagi, Scientist F and Officer-in-Charge, Centre for Resarch in Medical Entomology, Maduraii