The authors have declared that no competing interests exist.
Conceived and designed the experiments: GJW WAS QAtB SJdV PUF ASG. Performed the experiments: QAtB WAS ASG. Analyzed the data: QAtB WAS ASG GJW PUF SJdV. Wrote the paper: WAS QAtB SJdV PUF GJW ASG.
Current address: Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, United States of America
The Global Program to Eliminate Lymphatic Filariasis (LF) has a target date of 2020. This program is progressing well in many countries. However, progress has been slow in some countries, and others have not yet started their mass drug administration (MDA) programs. Acceleration is needed. We studied how increasing MDA frequency from once to twice per year would affect program duration and costs by using computer simulation modeling and cost projections. We used the LYMFASIM simulation model to estimate how many annual or semiannual MDA rounds would be required to eliminate LF for Indian and West African scenarios with varied pre-control endemicity and coverage levels.
The Global Program to Eliminate Lymphatic Filariasis (LF) employs annual mass drug administration (MDA) of antifilarial drugs to reduce infection rates in populations and interrupt transmission. While this program is working well in many countries, progress has been slow in others, and some countries have not yet started MDA programs. We used computer simulation modeling and cost projections to study how increasing MDA frequency from once to twice per year would affect program duration and costs. Our results suggest that semiannual MDA is likely to reduce the time required to eliminate LF by 50% and reduce total program costs (excluding the cost of donated drugs) in most situations. For these and other reasons, we expect semiannual MDA to be superior to annual MDA in most endemic settings. Semiannual MDA should be considered as a means of accelerating LF elimination in areas where it can be implemented, because this may improve prospects for global elimination of LF by the target year 2020.
The Global Program to Eliminate Lymphatic Filariasis (GPELF) was launched in 2000 with the aim of eliminating lymphatic filariasis (LF) as a public health problem by 2020
As indicated in the GPELF 2010 progress report, progress toward LF elimination varies widely between countries
With the goal of LF elimination by 2020 in mind, it is now important and timely to study whether elimination programs can be accelerated. A straightforward option would be to increase the frequency of MDA from once per year (annual) to twice per year (semiannual). While increasing MDA frequency might be expected to shorten the time required for elimination, the magnitude of this effect is uncertain. Only one study directly compared the impact of annual and semiannual MDA and this was for brugian filariasis: semiannual MDA with DEC alone caused a more rapid decline in mf prevalence than annual treatment. However, the duration of this study was too short to support conclusions regarding elimination
For decision-making, it is also important to consider how costs per year and overall costs for LF elimination programs are likely to change if MDA frequency is increased. Of course, costs per year will increase, but they will not necessarily double, and the cumulative cost for the entire program may even decline. The costs of twice yearly MDA have not been formally studied for LF or other neglected tropical diseases. However, they can be projected from detailed cost data by activity and cost item that are available for yearly MDA for LF and soil-transmitted helminthiasis
We have used the well-established simulation model LYMFASIM to estimate the number of treatment rounds and duration of MDA programs that would be needed to eliminate LF with annual and semiannual MDA in different settings. Simulations were performed for typical endemic areas in West Africa (with IVM+ALB treatment and
The LYMFASIM model describes the transmission of
The model simulates a closed population, consisting of a discrete number of individuals. The population composition changes over time due to birth and death of individuals. The history of infection and disease is simulated at the level of the individual human, taking account of individual variation in exposure to mosquito bites (age-related or random), life span, immune responsiveness to infection, compliance with MDA programs, and responsiveness to treatment. Worms in humans are also simulated individually, allowances made for separate sexes and variable life spans. Mature female worms produce mf during their reproductive lifespan at certain rates when there are male worms present in the human body. Because of all these factors, worm loads and mf intensity vary between human individuals, as well as their contribution to the average force of infection working on the population. In calculating the latter, the model considers the vector species-specific non-linear relationship between mf intensity in human blood and the average number of mf engorged by biting mosquitoes.
The primary outcomes of the model are predicted trends in the mf prevalence rate and mean mf intensity in the population. These outcomes are based on mf counts for all individuals in the population, while taking account of test characteristics that determine sampling variation and the possibility of false-negative test results. This makes simulation outcomes directly comparable to field data. For the present study, we assumed that mf counts were done by microscopic examination of a 20-µl or 60-µl thick smear of night finger-prick blood.
We used previously developed LYMFASIM model variants for India and West Africa. The India model describes the epidemiology of bancroftian filariasis in India which is transmitted by
Parameter value | ||
Description | India | West Africa |
Average number of mosquito bites/adult person/month, for areas with low, intermediate and high pre-control Mf prevalence | 1600,1950,2700 | 430, 485, 650 |
Exposure at birth, fraction of maximum exposure |
0.26 | 0 |
Age at which exposure reaches maximum |
19.1 years | 20.0 years |
Shape parameter for γ distribution describing individual variation in exposure (mean = 1; a higher value indicates less variability) | 1.13 | 0.26 |
Function that specifies the number of L3-larvae developing in mosquitoes after a single blood meal as a function of human mf density in 20 µl of blood ( |
(0.089 |
1.67(1-exp(-(0.027 |
Success ratio: the fraction of incoming L3 larvae that survive and develop into mature adult worms. | 1.03×10−3 | 8.8×10−3 |
Fraction of L3 larvae, from 1 blood meal, released by a mosquito when it bites | 0.1 | 0.1 |
Mean life span of parasites in human host | 10.2 years | 10.0 years |
Shape parameter for the Weibull distribution that describes variation in parasite life span | 2.0 | 2.0 |
Duration of immature stage of parasite in human host | 8 months | 8 months |
Fraction of microfilariae surviving per month | 0.9 | 0.9 |
Number of Mf produced/female parasite/month/20 µl of peripheral blood | 0.61 | 0.58 |
Scale parameter for sigmoid function relating strength of anti-L3 immunity to experience of infection by L3 | 5.89×10−5 | n.a. |
Shape parameter for γ distribution describing individual variation in ability to develop anti-L3 immunity | 1.07 | n.a. |
Duration of immunological memory for anti-L3 immunity | 9.6 months | n.a. |
Clumping factor for the negative binomial distribution describing variation in mf-counts in 20 µL blood smears from an individual with given mf density. Between brackets: idem, for 60 µL blood smears | 0.345 (1.035) | 0.33 (0.99) |
The table lists parameters related to transmission and parasite development, for which the values may vary between the models. See original publications for a full justification of the parameter values
n.a. = not applicable.
Exposure increases with age until a maximum is achieved at a certain age; exposure remains at its maximum level thereafter.
The relationship between human blood mf density and mosquito parasite uptake also differs between the two models, reflecting known differences between the vector species. The India model for
The West Africa model assumes relatively strong inter-individual variation in exposure to mosquito bites (indicated by the low value for the shape parameter of the gamma distribution in the West Africa model), to capture the variation between people in mf density in the human blood. The India model assumes less variability in exposure, because the variability in human mf density is partly attributed to acquired immunity and the associated individual differences in immune responsiveness. Further, the monthly biting rate (mbr, defined as average number of mosquito bites per adult person per month) is known to vary between communities, and we considered different values as explained below.
We performed simulation experiments to estimate the duration of MDA required to achieve LF elimination using different values for key parameters in the Indian and West African models. Mbr values were chosen to simulate communities with low, intermediate or high pre-control mf prevalence levels that are encountered in these regions. The simulated pre-treatment mf prevalence levels (based on 60 µL blood smears) were 7.7%, 11.5% and 15% for India and 12.5%, 20% and 27.5% for West Africa. Corresponding values for 20 µL blood smears would be approximately 5%, 7.5% and 10% for India and 9%, 14% and 20% for West Africa.
For each setting, we simulated a range of treatment scenarios that varied with respect to simulated treatment regimens (DEC+ALB or IVM+ALB), frequency of treatment (annual or 6-monthly), treatment coverage (55%, 70% or 85% of the total population; constant over time), and the number of treatment rounds (1, 2, …, 20 rounds). Compliance with offered treatment was simulated as a partially systematic process. That is to say, it is neither completely random (where each person has the same chance to get treated in each round) nor completely systematic (where all individuals either take all or none of the treatments), but somewhere in between. The simulated proportion of systematic non-compliers (i.e. those who never take treatment) for a given number of treatment rounds is not fixed; it depends on overall treatment coverage levels; the proportion of systematic non-compliers in the total population increases when the overall coverage declines, and vice versa. This mechanism fairly represented the attendance pattern of a mass treatment program for onchocerciasis in Asubende, Ghana
Baseline treatment efficacy assumptions were based on expert opinion and ultrasound studies
To calculate the probability of LF elimination for a certain setting and treatment scenario, we performed repeated simulations (n = 1000), all with the exact same assumptions. We recorded for each run whether elimination was reached (defined as mf prevalence <0.1%, measured 60 years after the first MDA to allow for slow extinction of the parasite population when mf prevalence was brought below its breakpoint level). The elimination probability was defined as the percentage of runs that reached this outcome. The required number of MDA rounds for elimination was estimated as the lowest number of MDA rounds that resulted in a ≥99% probability of elimination. For annual MDA programs, the estimated required number of MDA rounds equals the duration of MDA in years. For semiannual MDA programs, the duration of MDA in years equals the number of MDA rounds divided by 2.
We estimated the costs of MDA for LF programs with annual and semiannual treatment from the perspective of the endemic country government. The cost analysis covers financial and economic costs. The financial costs are the costs of all inputs purchased in cash for MDA, including purchased MDA drugs, materials and supplies, ministry of health personnel salaries, and per diem payments for community drug distributors
For India, we based our calculations on published data on the total cost per treatment round as estimated by Ramaiah and Das
For West Africa we used recently published data from Burkina Faso on total costs of MDA (measured in 2002) excluding the cost of donated drugs
We used a series of calculation steps to estimate the relative cost in 2009 for treating a population with 100,000 eligible persons in both India and West Africa, while correcting for salary or per diem changes, inflation since the original cost study, and potential programmatic changes (see
India | Burkina Faso | Reference | |
1. Total cost of MDA as reported, including the cost of drugs (US$, base year |
70,412 |
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2. Total cost of MDA as reported, excluding costs of drugs (US$, base year value) | 110,000 |
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3. Population at risk | 2,269,477 | 2,613,000 | |
4. Percentage of the population at risk that is eligible for treatment (%) | 90 | 85 | |
5. Cost per 100,000 eligibles, incl. the cost of drugs (US$, base year value) | 3,447 |
n.a. | |
6. Cost per 100,000 eligibles, excl. the cost of drugs (US$, base year value) | 808 |
4,953 | |
7. As 6), (US$, comparative value in 2009) | 1,139 |
9,299 |
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8. As 7) after correction for recent programmatic and salary changes, excl. cost of drugs | 2,710 |
12,378 |
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9. as 8), incl. the cost of any purchased drugs | 3,634 |
n.a. | |
10. as 9), incl. the cost of purchased and donated drugs | 5,834 |
434,578 |
The table displays the source data and describes all steps that were taken to estimate the cost of a single MDA round per 100,000 eligibles.
n.a. = not applicable.
The term base year refers to the year in which cost were originally measured (1996 for India, 2002 for West Africa).
Calculated from 1), 3) and 4), assuming that drugs (50 mg DEC tablets) were purchased for all eligible persons.
For India: cost of DEC (50-mg tablets; 5.2 tablets p.p. on average; 0.026 US$ p.p. on average) were subtracted.
Correction for inflation, using the annual deflators as published by the World Bank
We assume that sensitization efforts in India are intensified to achieve higher coverage, as studied elsewhere
Volunteer remuneration has changed. In 2002, volunteers were paid for 2 days of training only, not distribution. By 2010 Burkina volunteers were remunerated for about 2.5 days training and 7 days distribution; the daily rate remained the same. [sources:
In India, DEC has to be purchased by the government, at 0.00924 US% p.p. on average (for 100 mg tablets, 2.75 tablets p.p. on average).
Donated drug: albendazole (0.022 US$ p.p.).
Donated drugs: albendazole (0.022 US$ p.p.) and ivermectin (4.2 US$ p.p. on average).
Firstly, the cost of treating a population with 100,000 eligibles once (the result of step 1 above) was split up by program activity (sensitization, drug distribution, etc.) and cost item (personnel, supplies, transportation, equipment and facilities). Information about this for India was available from Krishnamoorthy et al
Secondly, we made assumptions on the relative increase in cost
Overall program and economic costs were calculated, taking account of the total required program duration as predicted by LYMFASIM. The overall costs were discounted at a rate of 3% to adjust for a preference to delay cost to the future (some further explanation about discounting can be found in the supporting information text S1). Separate calculations were made including and excluding the cost of donated drugs. We assumed that drugs would be purchased or provided for all people eligible for MDA and that any unused drugs are wasted: i.e. they are not used in later MDA rounds, because they were either distributed and not consumed or they were lost, damaged, or expired
We studied the extent to which key assumptions affect conclusions regarding the relative cost of the two MDA schedules (once or twice yearly MDA) in a univariate sensitivity analysis. On the cost side, we assessed the effect of changing the discount rate to 0% or 6% instead of 3%, the effect of including the cost of donated drugs, and we considered the scenario where drugs are only bought for people who are actually treated instead of for all eligibles (with the idea that any remaining drugs would be stored and used in a later round). These factors do not influence the number of rounds required, but they may affect the total costs of annual and semiannual treatment programs and influence policy decisions.
With respect to the simulations, we examined the impact of changing assumptions regarding the efficacy of drugs on adult worms. This may affect the total number of treatment rounds (and total costs) required for LF elimination programs with annual or semiannual MDA. The fraction of worms assumed to be killed or permanently sterilized after each treatment was varied with low, medium (baseline) and high values (50%, 65%, and 80% for DEC+ALB, and 20%, 35% and 50% for IVM+ALB). Further, we studied the impact of including variability in this parameter, so that the fraction of worms killed or sterilized varies randomly between individuals in each treatment cycle and within individuals in different treatment cycles. The variation is described by a beta distribution with the mean equal to the baseline fraction of worms killed/sterilized and standard deviation equal to 0.3.
The presented trends are for an African setting with pre-control mf prevalence around 20%, where 6 rounds of annual mass drug administration with IVM+ALB were provided starting at time 0. Coverage was 70% and drug efficacy was quantified according to our baseline assumptions. The figure displays the trend of 25 runs, simulated by LYMFASIM, all with the same input assumptions. Variation in the outcomes is due to stochasticity.
Panel A shows the results for an Indian setting with a pre-control mf prevalence of about 11.5%, for annual and semiannual mass drug administration and for different coverage levels (percentage of the total population that is treated per round). Similarly, panel B shows the results for an African setting with a pre-control mf prevalence of about 20%. The indicated mf prevalence levels are for diagnosis with 60 µL night blood smears.
India | West Africa | ||||||
Annual | Semiannual | Annual | Semiannual | ||||
Cost per round ( = cost per year) | Cost per year | Average cost per round | Cost per round ( = cost per year) | Cost per year | Average cost per round | ||
Planning |
Personnel | 43 | 43 | 22 | 1,903 | 1,903 | 952 |
Supplies | 0 | 0 | 0 | 41 | 41 | 21 | |
Transportation | 8 | 8 | 4 | 360 | 360 | 180 | |
Equipment/facilities | 9 | 9 | 5 | 237 | 237 | 118 | |
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Training | Personnel | 991 | 991 | 495 | |||
Supplies | 107 | 107 | 53 | ||||
Transportation | 143 | 143 | 71 | ||||
Equipment/facilities | 2 | 2 | 1 | ||||
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Sensitization |
Personnel | 684 | 923 | 462 | 262 | 354 | 177 |
Supplies | 823 | 1,646 | 823 | 52 | 103 | 52 | |
Transportation | 318 | 430 | 215 | 64 | 86 | 43 | |
Equipment/facilities | 18 | 18 | 9 | 103 | 103 | 52 | |
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Enumeration | Personnel | 227 | 453 | 227 | |||
Supplies | 60 | 121 | 60 | ||||
Transportation | 0 | 0 | 0 | ||||
Equipment/facilities | 0 | 0 | 0 | ||||
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Drug distribution |
Personnel | 318 | 636 | 318 | 4,770 | 9,540 | 4,770 |
Supplies (excl. drug) | 0 | 0 | 0 | 2,777 | 5,554 | 2,777 | |
DEC (purchased) | 924 | 1,848 | 924 | - | - | - | |
ALB (donated) | 2,200 | 4,400 | 2,200 | 2,200 | 4,400 | 2,200 | |
IVM (donated) | 0 | 0 | 0 | 420,000 | 840,000 | 420,000 | |
Transportation | 49 | 98 | 49 | 71 | 142 | 71 | |
Equipment/facilities | 57 | 57 | 29 | 82 | 82 | 41 | |
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Supervision | Personnel | 40 | 79 | 40 | |||
Supplies | 0 | 0 | 0 | ||||
Transportation | 26 | 51 | 26 | ||||
Equipment/facilities | 29 | 29 | 15 | ||||
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Surveillance/laboratory | Personnel | 305 | 305 | 153 | |||
Supplies | 1 | 1 | 1 | ||||
Transportation | 34 | 34 | 17 | ||||
Equipment/facilities | 0 | 0 | 0 | ||||
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Adverse reaction monitoring | Personnel | 73 | 147 | 73 | |||
Supplies | 0 | 1 | 0 | ||||
Transportation | 0 | 0 | 0 | ||||
Equipment/facilities | 0 | 0 | 0 | ||||
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Costs per year and per treatment round for annual and semiannual mass drug administration programs, per 100,000 eligible persons, in 2009 US$. Cost for West Africa were based on detailed data from Burkina Faso. See
Abbrevations: DEC = diethylcarbamazine, ALB = albendazole, IVM = ivermectin.
including administration for West Africa.
including training of personnel for India.
including supervision and enumeration for West Africa.
It is assumed that drugs were purchased for all persons eligible for MDA.
# rounds required | Program costs (USD ×1000) | |||||
Setting | Pre-treatment mf prevalence | Coverage (%) | Annual | Semiannual | Annual | Semiannual |
India | 7.7% | 55 | 3 | 3 | 10.6 | 9.6 |
70 | 2 | 2 | 7.2 | 6.5 | ||
85 | 2 | 2 | 7.2 | 6.5 | ||
11.5% | 55 | 5 | 5 | 17.1 | 15.8 | |
70 | 3 | 3 | 10.6 | 9.6 | ||
85 | 2 | 2 | 7.2 | 6.5 | ||
15% | 55 | 9 | 10 | 29.1 | 30.4 | |
70 | 5 | 5 | 17.1 | 15.8 | ||
85 | 3 | 3 | 10.6 | 9.6 | ||
West Africa | 12.5% | 55 | 7 | 7 | 79.4 | 68.2 |
70 | 5 | 5 | 58.4 | 49.4 | ||
85 | 4 | 4 | 47.4 | 39.9 | ||
20% | 55 | 11 | 12 | 118.0 | 112.9 | |
70 | 7 | 7 | 79.4 | 68.2 | ||
85 | 6 | 6 | 69.1 | 59.0 | ||
27.5% | 55 | >20 |
>20 |
n.a. | n.a. | |
70 | 13 | 14 | 135.6 | 129.9 | ||
85 | 9 | 9 | 99.3 | 86.5 |
Abbrevations: n.a. = not available.
Situation unfavorable for elimination.
The total costs of MDA programs depend on the cost per round, the required number of MDA rounds, and thereby also on local circumstances and coverage rates.
Ratio of total program costs, with between brackets the estimated total program costs for semiannual over annual MDA (in US$ * 1000) | ||||||||
Region | India | West Africa | ||||||
Pre-control mf prevalence | 7.7% | 11.5% | 15% | 12.5% | 20% | 27.5% | ||
No of MDA rounds required for elimination, semiannual/annual | 2/2 | 3/3 | 5/5 | 5/5 | 7/7 | 14/13 | ||
Assumptions in cost calculations | ||||||||
Discount rate (fraction) | Donated drugs cost | Purchasing drugs | ||||||
0.03 |
excl |
all eligibles |
0.90 (6.5/7.2) | 0.91 (9.6/10.6) | 0.92 (15.8/17.1) | 0.85 (49/58) | 0.86 (68/79) | 0.96 (130/136) |
0 | excl | all eligibles | 0.89 (6.5/7.3) | 0.89 (9.7/10.9) | 0.88 (16.1/18.2) | 0.82 (51/62) | 0.82 (71/87) | 0.88 (142/161) |
0.06 | excl | all eligibles | 0.92 (6.5/7.1) | 0.92 (9.5/10.3) | 0.95 (15.4/16.2) | 0.87 (48/55) | 0.90 (66/73) | 1.03 (120/116) |
0.03 | incl | all eligibles | 0.95 (10.9/11.5) | 0.95 (16.1/17.0) | 0.96 (26.5/27.5) | 1.03 (2112/2050) | 1.05 (2915/2789) | 1.17 (5549/4760) |
0.03 | excl | treated individuals only | 0.88 (6.0/6.8) | 0.90 (9.0/10.0) | 0.91 (14.8/16.2) | n.r. | n.r. | n.r. |
0.03 | incl | treated individuals only | 0.93 (9.5/10.1) | 0.94 (14.1/15.0) | 0.95 (23.1/24.2) | 1.03 (1748/1698) | 1.04 (2412/2311) | 1.16 (4592/3944) |
The values in the table are the ratio of total program costs, for semiannual MDA/annual MDA. This ratio shows which approach is less expensive (with values <1 indicating that semiannual MDA is less expensive and vice versa), and it provides an indication of the relative differences in cost. Between brackets, the total program costs estimates are given for semiannual/annual MDA programs, in 2009 US$ ×1000.
n.r.: not relevant, because costs of drugs, which are all donated, are not included in the cost projections.
baseline assumptions.
Ratio of total program costs, with between brackets the number of MDA rounds required for elimination, semiannual/annual | ||||||||
Region | India | West Africa | ||||||
Pre-control mf prevalence | 7.7% | 11.5% | 15% | 12.5% | 20% | 27.5% | ||
Assumptions in simulations | ||||||||
% of AW killed or permanently sterilized by | ||||||||
DEC+ALB (India) | IVM+ALB (West Africa) | Random variation in % of AW killed | ||||||
65% | 35% | No | 0.90 (2/2) | 0.91 (3/3) | 0.92 (5/5) | 0.85 (5/5) | 0.86 (7/7) | 0.96 (14/13) |
50% | 20% | No | 0.91 (3/3) | 0.91 (4/4) | 1.07 (7/6) | 0.98 (8/7) | 0.89 (12/12) | n.a. |
80% | 50% | No | 0.90 (2/2) | 0.91 (3/3) | 0.91 (4/4) | 0.83 (3/3) | 0.85 (5/5) | 0.88 (10/10) |
65% | 35% | Yes, beta distribution with mean as specified and sd 0.30 | 0.90 (2/2) | 0.69 (3/4) | 0.92 (5/5) | 0.85 (5/5) | 0.98 (8/7) | 0.96 (14/13) |
The values in the table are the ratio of total program costs, for semiannual MDA/annual MDA. This ratio shows which approach is less expensive (with values <1 indicating that semiannual MDA is less expensive and vice versa), and it provides an indication of the relative differences in cost. The ratio is based on the estimated cost per round (under our baseline assumptions,
n.a. estimate not available: conditions unfavorable for elimination.
Including the costs of donated drugs changed the outcome of the cost analysis significantly. The costs per treatment round increased by a large amount (by an amount that was the same for annual and semiannual treatment), and the relative difference was reduced. While semiannual MDA remained cheaper in most Indian scenarios, it became slightly more expensive in the West African scenarios. The highest increase (17%) was seen in the West African scenario with the highest endemicity (pre-control mf prevalence of 27%), because here semiannual MDA would require one more round than annual MDA. Whether drugs are purchased for all eligibles in every round or for the percentage of people treated only (assuming that previously unused drugs were not wasted/expired), hardly affected the ratio of total program cost of semiannual over annual MDA.
Model assumptions about the percentages of adult worms killed (or permanently sterilized) by a single treatment affected the total number of treatment rounds needed to achieve elimination and therefore the estimated total program costs. However, this did not have a major impact on ratios of total program cost for semiannual vs. annual MDA programs (
Our simulations and cost calculations suggest that semiannual MDA will achieve LF elimination in about half of the time that would be required with annual MDA. Estimated total program costs were strongly driven by the required number of treatment rounds, and this in turn depended on pre-treatment endemicity levels and MDA coverage rates. However, total program costs for endemic countries (i.e. excluding the cost of donated drugs) were always lower for the semiannual MDA program or comparable.
Cost calculations were based on observed data from 1996 and 2002
Estimates of the required duration of MDA in different settings were obtained by computer simulation, because empirical evidence from LF elimination programs is still limited. Many countries have made great strides, and some have stopped MDA, but no country that had ongoing transmission of LF in 2000 has been verified to have interrupted transmission of the infection using MDA
Field studies are needed to confirm projected cost reductions that can be achieved with semiannual MDA in both regions and to assess any indirect effects that might affect the relative efficiency of annual vs. semiannual MDA. For example, the likelihood that unused medication is stored and used in subsequent rounds may be higher in semiannual than in annual MDA programs. Also, it is possible that increased treatment frequency will increase coverage rates (e.g. due to higher population awareness) and reduce systematic non-compliance (e.g. due to the fact that MDA does not always take place in the same season). Such changes could reduce the number of MDA rounds needed for elimination and further increase the efficiency of semiannual vs. annual MDA programs. But the opposite could also occur if insufficient effort is made to maintain high coverage rates.
The efficiency gain in cost per treatment round achieved by shifting from annual to semiannual MDA was somewhat different for India and West Africa. This reflects differences in program organization and costing structure in the two regions
The duration of MDA varies between regions because of differences in exposure patterns to mosquitoes, characteristics of the vector, timing of MDA, immigration of people, etc. Simulation results are therefore not directly generalizable to other areas, but this is not pertinent to the comparison of annual and semiannual MDA durations. This becomes clear when one compares results projected in this study for LF elimination programs in India and West Africa; although there are important differences between these models that result in very different estimates for the number of MDA rounds needed for elimination (generally higher in Africa), the basic conclusion that doubling MDA frequency halves the required duration of LF elimination programs and reduces total program costs is valid for both of these regions and it should also apply to other regions.
Besides the total program costs, there are other important factors to consider in deciding whether MDA frequency should be increased. Increasing treatment frequency leads to a faster decline in the incidence of LF infection. This should increase the likelihood of achieving LF elimination by the target year of 2020, which is very relevant for countries that have not yet started their MDA programs. Incidence of clinical manifestations will also decline faster, which results in larger population health gain in terms of the total number of DALYs averted and results in increased productivity. Quantification of these extra benefits was beyond the purpose of this study. Increasing the treatment frequency and reducing program duration may also be beneficial for other reasons. E.g., shorter programs may be more politically attractive to health officials, and they would also be expected to have reduced risks of interruption due to natural disasters, political instability, or wars. Shorter programs may also reduce the risk of emergence of resistance to anthelmintics during LF elimination programs. Since albendazole and ivermectin also affect other diseases than LF, increasing the treatment frequency would increase their impact on diseases like soil-transmitted helminths and other NTD's – albeit for a shorter period.
Potential barriers for increasing the frequency of MDA are the increased cost per year and practical difficulties that may be associated with semiannual MDA. Increased annual drug requirements may exceed supplies of donated drugs. Also, more frequent MDA might overwhelm countries' capacities for delivering MDA to endemic populations, in view of already heavily burdened health systems and many competing health priorities
Poor-performing programs, with very low treatment coverage, require relatively many treatment rounds. Increasing the treatment frequency from annually to semiannually would reduce the total program duration by about half, but not the number of treatment rounds. However, investments or strategies that increase coverage rates will improve results of annual or semiannual MDA, thereby reducing the number of treatment rounds required and the total costs (see
In summary, computer simulations suggest that the frequency of MDA – annual vs semiannual – does not strongly influence the total number of treatment rounds required to achieve LF elimination. The costs per year are higher with semiannual MDA, but total program costs (excluding donated drugs) are projected to be lower or about the same when semiannual MDA is used. The few situations where the total program costs of semiannual MDA are slightly higher are also challenging situations for LF elimination where semiannual MDA may improve the odds of success. Therefore, we expect semiannual MDA to be superior to annual MDA in most endemic settings. Considering the GPELF goal of LF elimination by 2020, semiannual MDA should be considered as a means of accelerating LF elimination in areas where it can be implemented.
(PDF)
We thank Anne Haddix and James Crittle for their valuable advice on cost projection methods and Luc Coffeng for his technical assistance in analyzing the simulation results.