# The Impact of Mass Drug Administration on Lymphatic Filariasis

Authors: Isaac Frimpong Aboagye; Yvonne Abena Afadua Addison
Journal: Journal of Tropical Medicine
 (2022)

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## Abstract

Mass drug administration (MDA) has made a significant impact on the control of lymphatic filariasis (LF) since the establishment of the Global Programme to Eliminate Lymphatic Filariasis. However, its implementation is associated with several challenges, hampering interruption of parasite transmission and LF elimination in endemic areas. This study assessed the impact of MDA by comparing baseline microfilaria and antigen prevalence with those after three years (mid-term) and ≥5 years of MDA implementation and their respective prevalence reductions and identified specific challenges that may hinder its effective implementation. Three years of MDA implementation were observed to have microfilaria prevalence reductions (88.54% to 98.66%) comparable to those of studies that implemented MDA for five to 10 years (≥5 years, 79.23% to 98.26%). Inadequate community understanding of and participation in the LF MDA programme are major drawbacks to its effective implementation. The implementation of MDA that incorporates community participation, incentivisation, education, and training strategies has the potential of increasing MDA coverage and compliance, thereby interrupting parasite transmission and reducing microfilarial prevalence to levels that warrant LF elimination.


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## Body

## 1. Introduction

Lymphatic filariasis (LF) is a debilitating, neglected tropical disease caused by three species of parasitic worms:Wuchereria bancrofti, Brugia malayi, and B. timori. These arthropod-borne nematodes are transmitted to humans by the bite of infected mosquitoes in the genera Culex, Anopheles, Mansonia, and Aedes. Globally, 51.4 million people are estimated to be infected with LF [1], and the disease can compromise the health of victims and have an enormous socioeconomic burden [2, 3].In 1997, following major advances in diagnosing and testing for LF infection and improved understanding of the epidemiology and treatment of chronic LF-related disease, the 50th World Health Assembly resolved to eliminate LF as a public health problem [4]. Subsequently, the World Health Organization (WHO) in the year 2000 established the Global Programme to Eliminate Lymphatic Filariasis (GPELF) to assist member states in achieving this goal by 2020 through morbidity management and preventive annual mass drug administration (MDA) [5].Mass drug administration involving the two principal regimens of albendazole plus either ivermectin or diethylcarbamazine [DEC] for 4–6 years [6] or the exclusive use of table salt or cooking salt fortified with DEC for 1-2 years [7] has been implemented in various settings with varying degrees of successes and challenges. This study assessed the impact of MDA implementation on the control of LF in endemic areas and identifies specific challenges that may hinder effective implementation of MDA and reduction in microfilarial prevalence to levels below target thresholds [8] to warrant LF elimination.


## 2. Materials and Methods

### 2.1. Search Strategy

The search for relevant literature published in English language was carried out in the PubMed Central data-base from 19 December 2021 to 4 January 2022 using the search terms: “lymphatic filariasis, mass drug administration, effect, prevalence” with no limit to years. Details of the review protocol (Text S1) are registered with the OSF Registries (Registration DOI: 10.17605/OSF.IO/YQSPT) and can be accessed (osf.io/ct6rb). This review and the selection of relevant literature were undertaken using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) guidelines [9].


### 2.2. Eligibility Criteria

The review employed stringent eligibility criteria. Based on the recommendation of WHO’s Technical Advisory Group on the Global Elimination of LF on the assessment of the impact of MDA [10], studies from the baseline that have carried out a series of mass drug administration (MDA) using the two principal regimens [6, 7] but not reported on transmission assessment surveys (TASs) and verification of LF elimination were included in the review. Studies which reported on prevalence of LF, an indicator in the operational definition of LF elimination [11], and the primary outcome of interest in this review were included. Studies which did not meet these criteria, including those reporting on LF prevalence without MDA, missed rounds of MDA, mono- and triple-therapies against LF, control of LF using mosquito nets and MDA, LF mapping, systematic reviews, and coinfections were excluded from the review.


### 2.3. Method of Study Selection, Data Collection, and Analysis

The studies for the review were selected using a similar relevant article identification approach described previously [12]. The articles were screened independently by reading the titles to exclude nonlymphatic filariasis studies. The abstracts of lymphatic filariasis studies were read to assess their relevance based on the inclusion criteria. Full text articles deemed to be relevant were downloaded and used for the review.Each relevant full text article was read to document its characteristics: country, setting, population, drugs administered in MDA programme, MDA coverage, and compliance. Data on microfilaria (Mf) and Mf antigenic cases reported at baseline, three years (mid-term), and ≥5 years (pretransmission assessment survey, pre-TAS) of MDA implementation were extracted and used to calculate their respective prevalence using the following equation:(1)P=ncN×100%,where P = prevalence, nc = number of cases, and N = sample size. The percentage reductions for mid-term and pre-TAS microfilaria and Mf antigen prevalence compared to baseline prevalence were calculated using the following equations:(2)MPR=BP−MPBP×100%,(3)PPR=BP−PPBP×100%,where MPR = mid-term prevalence reduction, BP = baseline prevalence, MP = mid-term prevalence, PPR = pre-TAS prevalence reduction, and PP = pre-TAS prevalence.


### 2.4. Definition of Variables

Prevalence in this review is the proportion of persons diagnosed as having microfilaria (Mf) of any of the LF parasites or Mf antigen in their blood and was calculated before (baseline), three years (mid-term), and ≥5 years (pre-TAS) of MDA implementation. MDA coverage is the percentage of the population at risk of LF covered by MDA, and compliance with MDA is the percentage of persons who ingested the prescribed drugs during MDA implementation in an LF endemic area.


### 2.5. Risk of Study Bias Assessment

The risk of bias in individual studies was assessed independently by reviewers using the quality assessment tool developed for prevalence studies [13]. It was based on the assignment of numbers to a yes (0, low risk) and no (1, high risk) answers for ten parameters (Supplemental Table S1) on the external and internal validity of the studies. The overall study quality assessment was determined by summing up the assigned numbers based on the levels of risk of bias categorized as low (≤2), moderate (3-4) or high (≥5).


## 2.1. Search Strategy

The search for relevant literature published in English language was carried out in the PubMed Central data-base from 19 December 2021 to 4 January 2022 using the search terms: “lymphatic filariasis, mass drug administration, effect, prevalence” with no limit to years. Details of the review protocol (Text S1) are registered with the OSF Registries (Registration DOI: 10.17605/OSF.IO/YQSPT) and can be accessed (osf.io/ct6rb). This review and the selection of relevant literature were undertaken using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) guidelines [9].


## 2.2. Eligibility Criteria

The review employed stringent eligibility criteria. Based on the recommendation of WHO’s Technical Advisory Group on the Global Elimination of LF on the assessment of the impact of MDA [10], studies from the baseline that have carried out a series of mass drug administration (MDA) using the two principal regimens [6, 7] but not reported on transmission assessment surveys (TASs) and verification of LF elimination were included in the review. Studies which reported on prevalence of LF, an indicator in the operational definition of LF elimination [11], and the primary outcome of interest in this review were included. Studies which did not meet these criteria, including those reporting on LF prevalence without MDA, missed rounds of MDA, mono- and triple-therapies against LF, control of LF using mosquito nets and MDA, LF mapping, systematic reviews, and coinfections were excluded from the review.


## 2.3. Method of Study Selection, Data Collection, and Analysis

The studies for the review were selected using a similar relevant article identification approach described previously [12]. The articles were screened independently by reading the titles to exclude nonlymphatic filariasis studies. The abstracts of lymphatic filariasis studies were read to assess their relevance based on the inclusion criteria. Full text articles deemed to be relevant were downloaded and used for the review.Each relevant full text article was read to document its characteristics: country, setting, population, drugs administered in MDA programme, MDA coverage, and compliance. Data on microfilaria (Mf) and Mf antigenic cases reported at baseline, three years (mid-term), and ≥5 years (pretransmission assessment survey, pre-TAS) of MDA implementation were extracted and used to calculate their respective prevalence using the following equation:(1)P=ncN×100%,where P = prevalence, nc = number of cases, and N = sample size. The percentage reductions for mid-term and pre-TAS microfilaria and Mf antigen prevalence compared to baseline prevalence were calculated using the following equations:(2)MPR=BP−MPBP×100%,(3)PPR=BP−PPBP×100%,where MPR = mid-term prevalence reduction, BP = baseline prevalence, MP = mid-term prevalence, PPR = pre-TAS prevalence reduction, and PP = pre-TAS prevalence.


## 2.4. Definition of Variables

Prevalence in this review is the proportion of persons diagnosed as having microfilaria (Mf) of any of the LF parasites or Mf antigen in their blood and was calculated before (baseline), three years (mid-term), and ≥5 years (pre-TAS) of MDA implementation. MDA coverage is the percentage of the population at risk of LF covered by MDA, and compliance with MDA is the percentage of persons who ingested the prescribed drugs during MDA implementation in an LF endemic area.


## 2.5. Risk of Study Bias Assessment

The risk of bias in individual studies was assessed independently by reviewers using the quality assessment tool developed for prevalence studies [13]. It was based on the assignment of numbers to a yes (0, low risk) and no (1, high risk) answers for ten parameters (Supplemental Table S1) on the external and internal validity of the studies. The overall study quality assessment was determined by summing up the assigned numbers based on the levels of risk of bias categorized as low (≤2), moderate (3-4) or high (≥5).


## 3. Results

### 3.1. Study Selection and Risk of Bias Assessment

A total of 1,678 results were obtained from the PubMed Central literature search out of which 14 were deemed to be relevant to the research question. Figure1 shows the study selection process.Figure 1
Flow chart of study selection process (PRISMA guide).Based on the risk of bias assessment of the 14 studies included, 9 (64.3%) and five (35.7%) were observed to have low and moderate risks of publication bias, respectively (Supplemental TableS1).


### 3.2. Data Extraction

Characteristics of the relevant lymphatic filariasis studies extracted are presented in Table1. Based on the assessment of the impact of mass drug administration (MDA) on lymphatic filariasis (LF) control, data on microfilaria (Mf) and Mf antigenic cases reported at baseline, three years (mid-term), and ≥5 years (pretransmission assessment survey, pre-TAS) of MDA implementation were extracted and presented in Table 2. Baseline, mid-term and pre-TAS microfilaria (Table 3) and Mf antigen (Table 4) prevalence were calculated. The percentage reductions for mid-term and pre-TAS microfilaria (Table 3) and Mf antigen (Table 4) prevalence compared to baseline prevalence were also calculated.Table 1
Mass drug administration coverage and compliance in lymphatic filariasis studies included in this review.
Reference, countrySetting and population (age group, years)Drug administered in MDA programmeMDA coverage or compliance (%)[14], MaliInhabitants of villages (≥2)Albendazole and ivermectin>67[15], American SamoaHousehold members in villages (≥2)Diethylcarbamazine and albendazole(∗56, 19–71)[16], EgyptCommunity members (>5)Diethylcarbamazine and albendazole>85[17], Sierra LeoneCommunity members (>5)Albendazole and ivermectin82.5–88.5[18], Sierra LeoneCommunity members (>5)Albendazole and ivermectin75.9–79.6[19], NigeriaCommunity members (>5)Albendazole and ivermectin72.2–96[20], EgyptVillage surveys (≥2)Diethylcarbamazine and albendazole>†80[21], IndiaCommunity members, —Diethylcarbamazine-medicated salt100[22], TanzaniaStudents (≥1)Albendazole and ivermectin62.1–94.8[23], TanzaniaStandard 1 pupils (7.5–8.1)Albendazole and ivermectin87.7–94.5[24], TanzaniaStudents and community members (≥1 and ≥10)Albendazole and ivermectin75–98.7[25], TanzaniaStudents and community members (≥10)Albendazole and ivermectin46–56[26], IndonesiaResidents in villages (≥5)Diethylcarbamazine and albendazole†70.1–89.8[27], Papua New GuineaResidents of rural villages (≥2)Diethylcarbamazine and albendazole†72.9†Compliance; MDA, mass drug administration; —: data not available; ∗mean MDA coverage.Table 2
Microfilaria and antigenic cases at baseline and after MDA implementation reported by lymphatic filariasis (LF) studies.
Reference, countryDiagnostic methodBaseline LF cases (N)LF cases (N); years of MDAIMf∗AntigenMf∗Antigen[14], MaliThick blood film & ICT—244 (1139)—0 (760); 6[15], American SamoaThick blood smear & ICT—483 (3018)5 (1881); 643 (1881); 6[16], EgyptThick blood smear, ICT & RACT115 (1000)190 (1000)2 (1000); 527 (1000); 5[17], Sierra LeoneThick blood film214 (8233)—18 (6023); 3—[18], Sierra LeoneThick blood film214 (8233)—23 (4230); 5—[20], EgyptThick blood film & ICT274 (1877)612 (1877)22 (1828); 5144 (1828); 5[21], IndiaThick blood film678 (14963)—4 (6649); 3—[19], NigeriaThick blood smear & ICT206 (4198)527 (2439)15 (1720); 7–10127 (1720); 7–10[22], TanzaniaCounting chamber225 (919)—68 (674); 3—[23], TanzaniaFinger-prick blood & ICT counting chamber & ICT—210 (888)—101 (953); 349 (855); 4[24], TanzaniaCounting chamber & ICT225 (919)—11 (393); 677 (393); 6[25], TanzaniaCounting chamber & ICT225 (919)—20 (60); 869 (422); 8[26], IndonesiaThick blood smear & ICT193 (2165)47 (722)5 (1776); 310 (871); 3[27], Papua New GuineaMembrane filtration & RACT106 (757)265 (558)7 (529); 393 (543); 3∗Cases based on Mf antigen using the immunochromatographic test (ICT) or rapid-format antigen card test (RACT); Mf, microfilaria; N, sample size; MDAI, mass drug administration implementation; —: data not available.Table 3
Percentage microfilaria prevalence reduction at mid-term and pretransmission assessment survey (pre-TAS) compared to baseline prevalence in LF mass drug administration.
Reference, countryBaseline Mf prevalence (N)LF prevalence (N); ∗% PRMid-term MfPre-TAS Mf[16], Egypt11.50 (1000)—0.20 (1000); 98.26[17], Sierra Leone2.60 (8233)0.30 (6023); 88.54—[18], Sierra Leone2.60 (8233)—0.54 (4230); 79.23[20], Egypt14.60 (1877)—1.20 (1828); 91.78[21], India4.53 (14963)0.06 (6649); 98.66—[19], Nigeria4.91 (4198)—0.87 (1720); 82.28[22], Tanzania24.48 (919)10.10 (674); 58.74—[24], Tanzania24.48 (919)—2.80 (393); 88.56[25], Tanzania24.48 (919)—33.33 (60);†36.15[26], Indonesia8.91 (2165)0.28 (1776); 96.86—[27], Papua New Guinea14 (757)1.32 (529); 90.57—Mf: microfilaria; LF: lymphatic filariasis;N, sample size; pre-TAS: pretransmission assessment survey; ∗% PR, percentage prevalence reduction compared to baseline prevalence; —: no data available; †increase in prevalence.Table 4
Percentage antigenic prevalence reduction at mid-term and pre-TAS compared to baseline prevalence in LF mass drug administration.
Reference, countryBaseline antigen prevalence (N)LF antigen prevalence (N); ∗% antigen PRMid-termPre-TAS[14], Mali21.42 (1139)—0 (760); 100.00[15], American Samoa16.00 (3018)—2.29 (1881); 85.69[16], Egypt19.00 (1000)—2.70 (1000); 85.79[20], Egypt32.61 (1877)—7.88 (1828); 75.84[19], Nigeria21.61 (2439)—7.38 (1720); 65.85[23], Tanzania23.65 (888)10.60 (953); 51.18—[26], Indonesia6.51 (722)1.15 (871); 82.33—[27], Papua New Guinea47.49 (558)17.13 (543); 63.93—LF: lymphatic filariasis;N: sample size; pre-TAS, pretransmission assessment survey; ∗% antigen PR, percentage antigen prevalence reduction compared to baseline antigen prevalence; —: no data available.


## 3.1. Study Selection and Risk of Bias Assessment

A total of 1,678 results were obtained from the PubMed Central literature search out of which 14 were deemed to be relevant to the research question. Figure1 shows the study selection process.Figure 1
Flow chart of study selection process (PRISMA guide).Based on the risk of bias assessment of the 14 studies included, 9 (64.3%) and five (35.7%) were observed to have low and moderate risks of publication bias, respectively (Supplemental TableS1).


## 3.2. Data Extraction

Characteristics of the relevant lymphatic filariasis studies extracted are presented in Table1. Based on the assessment of the impact of mass drug administration (MDA) on lymphatic filariasis (LF) control, data on microfilaria (Mf) and Mf antigenic cases reported at baseline, three years (mid-term), and ≥5 years (pretransmission assessment survey, pre-TAS) of MDA implementation were extracted and presented in Table 2. Baseline, mid-term and pre-TAS microfilaria (Table 3) and Mf antigen (Table 4) prevalence were calculated. The percentage reductions for mid-term and pre-TAS microfilaria (Table 3) and Mf antigen (Table 4) prevalence compared to baseline prevalence were also calculated.Table 1
Mass drug administration coverage and compliance in lymphatic filariasis studies included in this review.
Reference, countrySetting and population (age group, years)Drug administered in MDA programmeMDA coverage or compliance (%)[14], MaliInhabitants of villages (≥2)Albendazole and ivermectin>67[15], American SamoaHousehold members in villages (≥2)Diethylcarbamazine and albendazole(∗56, 19–71)[16], EgyptCommunity members (>5)Diethylcarbamazine and albendazole>85[17], Sierra LeoneCommunity members (>5)Albendazole and ivermectin82.5–88.5[18], Sierra LeoneCommunity members (>5)Albendazole and ivermectin75.9–79.6[19], NigeriaCommunity members (>5)Albendazole and ivermectin72.2–96[20], EgyptVillage surveys (≥2)Diethylcarbamazine and albendazole>†80[21], IndiaCommunity members, —Diethylcarbamazine-medicated salt100[22], TanzaniaStudents (≥1)Albendazole and ivermectin62.1–94.8[23], TanzaniaStandard 1 pupils (7.5–8.1)Albendazole and ivermectin87.7–94.5[24], TanzaniaStudents and community members (≥1 and ≥10)Albendazole and ivermectin75–98.7[25], TanzaniaStudents and community members (≥10)Albendazole and ivermectin46–56[26], IndonesiaResidents in villages (≥5)Diethylcarbamazine and albendazole†70.1–89.8[27], Papua New GuineaResidents of rural villages (≥2)Diethylcarbamazine and albendazole†72.9†Compliance; MDA, mass drug administration; —: data not available; ∗mean MDA coverage.Table 2
Microfilaria and antigenic cases at baseline and after MDA implementation reported by lymphatic filariasis (LF) studies.
Reference, countryDiagnostic methodBaseline LF cases (N)LF cases (N); years of MDAIMf∗AntigenMf∗Antigen[14], MaliThick blood film & ICT—244 (1139)—0 (760); 6[15], American SamoaThick blood smear & ICT—483 (3018)5 (1881); 643 (1881); 6[16], EgyptThick blood smear, ICT & RACT115 (1000)190 (1000)2 (1000); 527 (1000); 5[17], Sierra LeoneThick blood film214 (8233)—18 (6023); 3—[18], Sierra LeoneThick blood film214 (8233)—23 (4230); 5—[20], EgyptThick blood film & ICT274 (1877)612 (1877)22 (1828); 5144 (1828); 5[21], IndiaThick blood film678 (14963)—4 (6649); 3—[19], NigeriaThick blood smear & ICT206 (4198)527 (2439)15 (1720); 7–10127 (1720); 7–10[22], TanzaniaCounting chamber225 (919)—68 (674); 3—[23], TanzaniaFinger-prick blood & ICT counting chamber & ICT—210 (888)—101 (953); 349 (855); 4[24], TanzaniaCounting chamber & ICT225 (919)—11 (393); 677 (393); 6[25], TanzaniaCounting chamber & ICT225 (919)—20 (60); 869 (422); 8[26], IndonesiaThick blood smear & ICT193 (2165)47 (722)5 (1776); 310 (871); 3[27], Papua New GuineaMembrane filtration & RACT106 (757)265 (558)7 (529); 393 (543); 3∗Cases based on Mf antigen using the immunochromatographic test (ICT) or rapid-format antigen card test (RACT); Mf, microfilaria; N, sample size; MDAI, mass drug administration implementation; —: data not available.Table 3
Percentage microfilaria prevalence reduction at mid-term and pretransmission assessment survey (pre-TAS) compared to baseline prevalence in LF mass drug administration.
Reference, countryBaseline Mf prevalence (N)LF prevalence (N); ∗% PRMid-term MfPre-TAS Mf[16], Egypt11.50 (1000)—0.20 (1000); 98.26[17], Sierra Leone2.60 (8233)0.30 (6023); 88.54—[18], Sierra Leone2.60 (8233)—0.54 (4230); 79.23[20], Egypt14.60 (1877)—1.20 (1828); 91.78[21], India4.53 (14963)0.06 (6649); 98.66—[19], Nigeria4.91 (4198)—0.87 (1720); 82.28[22], Tanzania24.48 (919)10.10 (674); 58.74—[24], Tanzania24.48 (919)—2.80 (393); 88.56[25], Tanzania24.48 (919)—33.33 (60);†36.15[26], Indonesia8.91 (2165)0.28 (1776); 96.86—[27], Papua New Guinea14 (757)1.32 (529); 90.57—Mf: microfilaria; LF: lymphatic filariasis;N, sample size; pre-TAS: pretransmission assessment survey; ∗% PR, percentage prevalence reduction compared to baseline prevalence; —: no data available; †increase in prevalence.Table 4
Percentage antigenic prevalence reduction at mid-term and pre-TAS compared to baseline prevalence in LF mass drug administration.
Reference, countryBaseline antigen prevalence (N)LF antigen prevalence (N); ∗% antigen PRMid-termPre-TAS[14], Mali21.42 (1139)—0 (760); 100.00[15], American Samoa16.00 (3018)—2.29 (1881); 85.69[16], Egypt19.00 (1000)—2.70 (1000); 85.79[20], Egypt32.61 (1877)—7.88 (1828); 75.84[19], Nigeria21.61 (2439)—7.38 (1720); 65.85[23], Tanzania23.65 (888)10.60 (953); 51.18—[26], Indonesia6.51 (722)1.15 (871); 82.33—[27], Papua New Guinea47.49 (558)17.13 (543); 63.93—LF: lymphatic filariasis;N: sample size; pre-TAS, pretransmission assessment survey; ∗% antigen PR, percentage antigen prevalence reduction compared to baseline antigen prevalence; —: no data available.


## 4. Discussion

### 4.1. Impact of MDA on Lymphatic Filariasis Control

One of the two strategies to achieve the goal of lymphatic filariasis (LF) elimination is preventive chemotherapy [28] delivered through mass drug administration (MDA), aimed at interrupting LF transmission. MDA involving albendazole plus either ivermectin or diethylcarbamazine [DEC] for 4–6 years [6] or the exclusive use of table salt or cooking salt fortified with DEC for 1-2 years [7] is recommended for effective control of LF [29]. Albendazole and ivermectin are administered in areas where LF is co-endemic with onchocerciasis, as observed in sub-Saharan Africa [30]. However, treatment with DEC is contraindicated in areas where onchocerciasis or loiasis might coexist [29], accounting for its use in onchocerciasis-free regions. This is due to the potential for severe adverse events such as the induction of strong local inflammation in patients with ocular microfilariae attributable to microfilariae death [31]. These regimens, at adequate levels of coverage, safely and effectively reduce the number of microfilariae circulating in the blood and, therefore, the prevalence of infection in the entire LF endemic community [11].This review assessed the impact of MDA implementation by comparing baseline microfilaria and antigen prevalence with those of three years (mid-term) and ≥5 years (pre-TAS) and their respective percentage reductions. Although the stringent eligibility criteria limited the number of articles, this review provides useful information for stakeholders in the control of LF. In this review, 11 (78.57%) and three (21.43%) studies reported variable MDA coverage (19% to 100%) and compliance (70.10% to 80%), respectively (Table1), highlighting the challenge of attaining and maintaining high treatment coverage. To achieve interruption of parasite transmission, MDA coverage of at least 80% [32] and compliance exceeding 65–75% [33] are required.The percentage microfilaria (Mf) prevalence reduction three years after MDA implementation was high, ranging from 88.54% to 98.66% in the majority of the mid-term studies (4 [80%], Table3), with one reporting a low prevalence reduction of 58.74%. Interestingly, these reductions are comparable to those of studies that implemented MDA for five to 10 years (≥5 years) with a majority of them (5, 83.33%) having prevalence reductions ranging from 79.23% to 98.26% (Table 3) with one unusually increasing in Mf prevalence by 36.15% attributable to very low MDA coverage of 46–56% [25]. The percentage antigen prevalence reductions at three years and five to 10 years of MDA implementation compared to baseline antigen prevalence appeared to be comparable (Table 4). Various studies have reported that two [16, 34] or three [18] years of MDA implementation with high coverage (≥80%) have a similar impact on the reduction of LF prevalence compared with ≥5 years of MDA recommended for interruption of parasite transmission [32]. They suggest that effectively addressing the challenges of MDA implementation has the potential to cause an early interruption of parasite transmission, thereby reducing the years of MDA implementation. These findings highlight the importance of effective implementation of MDA in LF control.


### 4.2. Challenges of MDA Implementation

The implementation of MDA in LF control is associated with several challenges such as low compliance [35] and the difficulty attaining and maintaining of high treatment coverage [36, 37]. Widespread noncompliance may increase the number of individuals serving as reservoirs of infection in the population, thereby increasing the chance of LF transmission [16, 32]. Inadequate community understanding of and participation in LF MDA programme is, therefore, a major drawback to its effective implementation. Moreover, the difficulty in retaining community health volunteers, involved in training and drug distribution, on account of low financial incentives [38], inaccurate [39, 40], and late data reporting on LF treatment coverage [41] has also been documented. These challenges create the opportunity for LF parasites to remain in circulation in endemic areas, making interruption of their transmission difficult.


### 4.3. Implications for Lymphatic Filariasis Elimination

Mass drug administration (MDA) for LF control is aimed at reducing the density of parasites circulating in the blood of LF victims and the prevalence of infection in communities to levels where transmission is no longer sustainable by the mosquito vector [6]. In this regard, community participation in MDA programmes is highly recommended. The involvement of opinion, traditional, and religious leaders in MDA implementation campaigns will generate interest in and acceptance of the programme and, thus, enhance cooperation and programme participation.Educating community members on the importance of the programme, the safety of the drug, and its side effects will allay their fears and should be an integral part of MDA programmes. Provision of incentives in the form of bed nets to community members [42] and adequate allowances to community health volunteers for training and drug distribution [43, 44] has the desired effects of increasing drug uptake and community participation. The use of convenient period for drug distribution may also increase drug uptake, as absence from home during drug distribution is an important reason for not taking the drugs [36]. These strategies are likely to increase compliance with MDA and MDA coverage to the required levels [32, 33] to interrupt parasite transmission and reduce microfilarial prevalence to levels that warrant LF elimination.


## 4.1. Impact of MDA on Lymphatic Filariasis Control

One of the two strategies to achieve the goal of lymphatic filariasis (LF) elimination is preventive chemotherapy [28] delivered through mass drug administration (MDA), aimed at interrupting LF transmission. MDA involving albendazole plus either ivermectin or diethylcarbamazine [DEC] for 4–6 years [6] or the exclusive use of table salt or cooking salt fortified with DEC for 1-2 years [7] is recommended for effective control of LF [29]. Albendazole and ivermectin are administered in areas where LF is co-endemic with onchocerciasis, as observed in sub-Saharan Africa [30]. However, treatment with DEC is contraindicated in areas where onchocerciasis or loiasis might coexist [29], accounting for its use in onchocerciasis-free regions. This is due to the potential for severe adverse events such as the induction of strong local inflammation in patients with ocular microfilariae attributable to microfilariae death [31]. These regimens, at adequate levels of coverage, safely and effectively reduce the number of microfilariae circulating in the blood and, therefore, the prevalence of infection in the entire LF endemic community [11].This review assessed the impact of MDA implementation by comparing baseline microfilaria and antigen prevalence with those of three years (mid-term) and ≥5 years (pre-TAS) and their respective percentage reductions. Although the stringent eligibility criteria limited the number of articles, this review provides useful information for stakeholders in the control of LF. In this review, 11 (78.57%) and three (21.43%) studies reported variable MDA coverage (19% to 100%) and compliance (70.10% to 80%), respectively (Table1), highlighting the challenge of attaining and maintaining high treatment coverage. To achieve interruption of parasite transmission, MDA coverage of at least 80% [32] and compliance exceeding 65–75% [33] are required.The percentage microfilaria (Mf) prevalence reduction three years after MDA implementation was high, ranging from 88.54% to 98.66% in the majority of the mid-term studies (4 [80%], Table3), with one reporting a low prevalence reduction of 58.74%. Interestingly, these reductions are comparable to those of studies that implemented MDA for five to 10 years (≥5 years) with a majority of them (5, 83.33%) having prevalence reductions ranging from 79.23% to 98.26% (Table 3) with one unusually increasing in Mf prevalence by 36.15% attributable to very low MDA coverage of 46–56% [25]. The percentage antigen prevalence reductions at three years and five to 10 years of MDA implementation compared to baseline antigen prevalence appeared to be comparable (Table 4). Various studies have reported that two [16, 34] or three [18] years of MDA implementation with high coverage (≥80%) have a similar impact on the reduction of LF prevalence compared with ≥5 years of MDA recommended for interruption of parasite transmission [32]. They suggest that effectively addressing the challenges of MDA implementation has the potential to cause an early interruption of parasite transmission, thereby reducing the years of MDA implementation. These findings highlight the importance of effective implementation of MDA in LF control.


## 4.2. Challenges of MDA Implementation

The implementation of MDA in LF control is associated with several challenges such as low compliance [35] and the difficulty attaining and maintaining of high treatment coverage [36, 37]. Widespread noncompliance may increase the number of individuals serving as reservoirs of infection in the population, thereby increasing the chance of LF transmission [16, 32]. Inadequate community understanding of and participation in LF MDA programme is, therefore, a major drawback to its effective implementation. Moreover, the difficulty in retaining community health volunteers, involved in training and drug distribution, on account of low financial incentives [38], inaccurate [39, 40], and late data reporting on LF treatment coverage [41] has also been documented. These challenges create the opportunity for LF parasites to remain in circulation in endemic areas, making interruption of their transmission difficult.


## 4.3. Implications for Lymphatic Filariasis Elimination

Mass drug administration (MDA) for LF control is aimed at reducing the density of parasites circulating in the blood of LF victims and the prevalence of infection in communities to levels where transmission is no longer sustainable by the mosquito vector [6]. In this regard, community participation in MDA programmes is highly recommended. The involvement of opinion, traditional, and religious leaders in MDA implementation campaigns will generate interest in and acceptance of the programme and, thus, enhance cooperation and programme participation.Educating community members on the importance of the programme, the safety of the drug, and its side effects will allay their fears and should be an integral part of MDA programmes. Provision of incentives in the form of bed nets to community members [42] and adequate allowances to community health volunteers for training and drug distribution [43, 44] has the desired effects of increasing drug uptake and community participation. The use of convenient period for drug distribution may also increase drug uptake, as absence from home during drug distribution is an important reason for not taking the drugs [36]. These strategies are likely to increase compliance with MDA and MDA coverage to the required levels [32, 33] to interrupt parasite transmission and reduce microfilarial prevalence to levels that warrant LF elimination.


## 5. Conclusion

This study revealed high microfilaria (Mf) prevalence reductions for studies that implemented MDA for LF control for three years, comparable to those of studies that implemented MDA for five to 10 years. However, variable MDA coverage ranging from 19% to 100% was reported, highlighting the challenge of attaining and maintaining the high LF treatment coverage (≥80%) required to achieve interruption of parasite transmission. Mass drug administration (MDA) for LF control should aim at drawing attention to the importance of the programme and improving its understanding as well as community participation. This approach is fundamental to increasing compliance with MDA and MDA coverage, thereby interrupting parasite transmission.



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