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Meta-Analysis
. 2019 Jan 8;1(1):CD003753.
doi: 10.1002/14651858.CD003753.pub4.

Albendazole alone or in combination with microfilaricidal drugs for lymphatic filariasis

Cara L Macfarlane  1 , Shyam S Budhathoki, Samuel Johnson, Marty Richardson, Paul Garner
Affiliations
Meta-Analysis

Albendazole alone or in combination with microfilaricidal drugs for lymphatic filariasis

Cara L Macfarlane et al. Cochrane Database Syst Rev. .

Abstract

Background: The Global Programme to Eliminate Lymphatic Filariasis recommends mass treatment of albendazole co-administered with the microfilaricidal (antifilarial) drugs diethylcarbamazine (DEC) or ivermectin; and recommends albendazole alone in areas where loiasis is endemic.

Objectives: To assess the effects of albendazole alone, and the effects of adding albendazole to DEC or ivermectin, in people and communities with lymphatic filariasis.

Search methods: We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials, MEDLINE (PubMed), Embase (OVID), LILACS (BIREME), and reference lists of included trials. We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform and ClinicalTrials.gov to identify ongoing trials. We performed all searches up to 15 January 2018.

Selection criteria: We included randomized controlled trials (RCTs) and cluster-RCTs that compared albendazole to placebo or no placebo, or compared albendazole combined with a microfilaricidal drug to a microfilaricidal drug alone, given to people known to have lymphatic filariasis or communities where lymphatic filariasis was known to be endemic. We sought data on measures of transmission potential (microfilariae (mf) prevalence and density); markers of adult worm infection (antigenaemia prevalence and density, and adult worm prevalence detected by ultrasound); and data on clinical disease and adverse events.

Data collection and analysis: At least two review authors independently assessed the trials, evaluated the risks of bias, and extracted data. The main analysis examined albendazole overall, whether given alone or added to a microfilaricidal drug. We used data collected from all randomized individuals at time of longest follow-up (up to 12 months) for meta-analysis of outcomes. We evaluated mf density data up to six months and at 12 months follow-up to ensure that we did not miss any subtle temporal effects. We conducted additional analyses for different follow-up periods and whether trials reported on individuals known to be infected or both infected and uninfected. We analysed dichotomous data using the risk ratio (RR) with a 95% confidence interval (CI). We could not meta-analyse data on parasite density outcomes and we summarized them in tables. Where data were missing, we contacted trial authors. We used GRADE to assess the certainty of evidence.

Main results: We included 13 trials (12 individually-randomized and one small cluster-randomized trial) with 8713 participants in total. No trials evaluated population-level effects of albendazole in mass drug administration programmes. Seven trials enrolled people with a variety of inclusion criteria related to filarial infection, and six trials enrolled individuals from endemic areas. Outcomes were reported as end or change values. Mf and antigen density data were reported using the geometric mean, log mean and arithmetic mean, and reductions in density were variously calculated. Two trials discounted any increases in mf density in individuals at follow-up by setting any density increase to zero.For mf prevalence over two weeks to 12 months, albendazole alone or added to another microfilaricidal drug makes little or no difference (RR 0.95, 95% CI 0.85 to 1.07; 5027 participants, 12 trials, high-certainty evidence). For mf density there is no trend, with some trials reporting a greater reduction in mf density with albendazole and others a greater reduction with the control group. For mf density up to six months and at 12 months, we do not know if albendazole has an effect (one to six months: 1216 participants, 10 trials, very low-certainty evidence; at 12 months: 1052 participants, 9 trials, very low-certainty evidence).For antigenaemia prevalence between six to 12 months, albendazole alone or added to another microfilaricidal drug makes little or no difference (RR 1.04, 95% CI 0.97 to 1.12; 3774 participants, 7 trials, high-certainty evidence). For antigen density over six to 12 months, the trend shows little or no effect of albendazole; but we do not know if albendazole has an effect on antigen density (1374 participants, 5 trials, very low-certainty evidence). For adult worm prevalence detected by ultrasound at 12 months, albendazole added to a microfilaricidal drug may make little or no difference (RR 1.16, 95% CI 0.72 to 1.86; 165 participants, 3 trials, low-certainty evidence).For people reporting adverse events, albendazole makes little or no difference (RR 0.97, 95% CI 0.84 to 1.13; 2894 participants, 6 trials, high-certainty evidence).We also provide meta-analyses and GRADE tables by drug, as operationally this may be of interest: for albendazole versus placebo (4 trials, 1870 participants); for albendazole with DEC compared to DEC alone (8 trials, 3405 participants); and albendazole with ivermectin compared to ivermectin alone (4 trials, 3438 participants).

Authors' conclusions: There is good evidence that albendazole makes little difference to clearing microfilaraemia or adult filarial worms in the 12 months post-treatment. This finding is consistent in trials evaluating albendazole alone, or added to DEC or ivermectin. Trials reporting mf density included small numbers of participants, calculated density data variously, and gave inconsistent results.The review raises questions over whether albendazole has any important contribution to the elimination of lymphatic filariasis. To inform policy for areas with loiasis where only albendazole can be used, it may be worth conducting placebo-controlled trials of albendazole alone.

PubMed Disclaimer

Conflict of interest statement

CM received salary support from the COUNTDOWN Research Consortium.

SB has no known conflict of interest.

SJ has no known conflict of interest.

MR has no known conflict of interest.

Paul Garner is the Director of READ‐It, a UK AID development programme to help ensure evidence synthesis contributes to decision making, particularly relevant to low‐ and middle‐income countries for the benefit of the poor in these countries. The Department for International Development (DFID) had no part in preparing this review. Paul Garner is also a named investigator on COUNTDOWN, which is funded by a grant from DFID to promote community mass drug distribution to control neglected tropical diseases in endemic areas.

Figures

1
1
Study flow diagram.
2
2
‘Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
3
3
‘Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1 Albendazole alone or added to a microfilaricidal drug, Outcome 1 Microfilaraemia (mf) prevalence: longest follow‐up (up to 12 months).
1.2
1.2. Analysis
Comparison 1 Albendazole alone or added to a microfilaricidal drug, Outcome 2 Antigenaemia prevalence: longest follow‐up (up to 12 months).
1.3
1.3. Analysis
Comparison 1 Albendazole alone or added to a microfilaricidal drug, Outcome 3 Adult worm prevalence by ultrasound: longest follow‐up (up to 12 months).
1.4
1.4. Analysis
Comparison 1 Albendazole alone or added to a microfilaricidal drug, Outcome 4 New clinical disease (new cases hydrocoele).
1.5
1.5. Analysis
Comparison 1 Albendazole alone or added to a microfilaricidal drug, Outcome 5 Pre‐existing clinical disease (net improvement).
1.6
1.6. Analysis
Comparison 1 Albendazole alone or added to a microfilaricidal drug, Outcome 6 Adverse events.
2.1
2.1. Analysis
Comparison 2 Albendazole versus placebo, Outcome 1 Microfilaraemia (mf) prevalence: longest follow‐up (up to 12 months).
2.2
2.2. Analysis
Comparison 2 Albendazole versus placebo, Outcome 2 Microfilaraemia (mf) prevalence: stratified by baseline infection (up to 6 months follow‐up).
2.3
2.3. Analysis
Comparison 2 Albendazole versus placebo, Outcome 3 Microfilaraemia (mf) prevalence: stratified by baseline infection (12 months follow‐up).
2.4
2.4. Analysis
Comparison 2 Albendazole versus placebo, Outcome 4 Antigenaemia prevalence: longest follow‐up (up to 12 months).
2.5
2.5. Analysis
Comparison 2 Albendazole versus placebo, Outcome 5 Antigenaemia prevalence: stratified by baseline infection (6 months follow‐up).
2.6
2.6. Analysis
Comparison 2 Albendazole versus placebo, Outcome 6 Antigenaemia prevalence: stratified by baseline infection (12 months follow‐up).
2.7
2.7. Analysis
Comparison 2 Albendazole versus placebo, Outcome 7 Clinical disease.
2.8
2.8. Analysis
Comparison 2 Albendazole versus placebo, Outcome 8 Adverse events.
3.1
3.1. Analysis
Comparison 3 Albendazole plus DEC versus DEC, Outcome 1 Microfilaraemia (mf) prevalence: longest follow‐up (up to 12 months).
3.2
3.2. Analysis
Comparison 3 Albendazole plus DEC versus DEC, Outcome 2 Microfilaraemia (mf) prevalence: stratified by baseline infection (up to 6 months follow‐up).
3.3
3.3. Analysis
Comparison 3 Albendazole plus DEC versus DEC, Outcome 3 Microfilaraemia (mf) prevalence: stratified by baseline infection (12 months follow‐up).
3.4
3.4. Analysis
Comparison 3 Albendazole plus DEC versus DEC, Outcome 4 Microfilaraemia (mf) prevalence: stratified by baseline infection (24 months follow‐up).
3.5
3.5. Analysis
Comparison 3 Albendazole plus DEC versus DEC, Outcome 5 Microfilaraemia (mf) prevalence: stratified by baseline infection (36 months follow‐up).
3.6
3.6. Analysis
Comparison 3 Albendazole plus DEC versus DEC, Outcome 6 Antigenaemia prevalence: longest follow‐up (up to 12 months).
3.7
3.7. Analysis
Comparison 3 Albendazole plus DEC versus DEC, Outcome 7 Antigenaemia prevalence: stratified by baseline infection (6 months follow‐up).
3.8
3.8. Analysis
Comparison 3 Albendazole plus DEC versus DEC, Outcome 8 Antigenaemia prevalence: stratified by baseline infection (12 months follow‐up).
3.9
3.9. Analysis
Comparison 3 Albendazole plus DEC versus DEC, Outcome 9 Antigenaemia prevalence: stratified by baseline infection (24 months follow‐up).
3.10
3.10. Analysis
Comparison 3 Albendazole plus DEC versus DEC, Outcome 10 Antigenaemia prevalence: stratified by baseline infection (36 months follow‐up).
3.11
3.11. Analysis
Comparison 3 Albendazole plus DEC versus DEC, Outcome 11 Adult worm prevalence by ultrasound: longest follow‐up (up to 12 months).
3.12
3.12. Analysis
Comparison 3 Albendazole plus DEC versus DEC, Outcome 12 Adult worm prevalence by ultrasound: stratified by baseline infection (6 month follow‐up).
3.13
3.13. Analysis
Comparison 3 Albendazole plus DEC versus DEC, Outcome 13 Adult worm prevalence by ultrasound: stratified by baseline infection (12 month follow‐up).
3.14
3.14. Analysis
Comparison 3 Albendazole plus DEC versus DEC, Outcome 14 Adult worm prevalence by ultrasound: stratified by baseline infection (24 month follow‐up).
3.15
3.15. Analysis
Comparison 3 Albendazole plus DEC versus DEC, Outcome 15 Adverse events.
3.16
3.16. Analysis
Comparison 3 Albendazole plus DEC versus DEC, Outcome 16 Adverse events: stratified by type.
4.1
4.1. Analysis
Comparison 4 Albendazole plus ivermectin versus ivermectin, Outcome 1 Microfilaraemia (mf) prevalence: longest follow‐up (up to 12 months).
4.2
4.2. Analysis
Comparison 4 Albendazole plus ivermectin versus ivermectin, Outcome 2 Microfilaraemia (mf) prevalence: stratified by baseline infection (up to 6 months follow‐up).
4.3
4.3. Analysis
Comparison 4 Albendazole plus ivermectin versus ivermectin, Outcome 3 Microfilaraemia (mf) prevalence: stratified by baseline infection (12 months follow‐up).
4.4
4.4. Analysis
Comparison 4 Albendazole plus ivermectin versus ivermectin, Outcome 4 Antigenaemia prevalence: longest follow‐up (up to 12 months).
4.5
4.5. Analysis
Comparison 4 Albendazole plus ivermectin versus ivermectin, Outcome 5 Antigenaemia prevalence: stratified by baseline infection (6 months follow‐up).
4.6
4.6. Analysis
Comparison 4 Albendazole plus ivermectin versus ivermectin, Outcome 6 Antigenaemia prevalence: stratified by baseline infection (12 months follow‐up).
4.7
4.7. Analysis
Comparison 4 Albendazole plus ivermectin versus ivermectin, Outcome 7 Clinical disease.
4.8
4.8. Analysis
Comparison 4 Albendazole plus ivermectin versus ivermectin, Outcome 8 Adverse events.
See this image and copyright information in PMC

Update of

Comment in

References

References to studies included in this review

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Debrah 2006 {published data only}
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