Intervention Review

You have free access to this content

Albendazole for lymphatic filariasis

  1. David Addiss2,
  2. Carrol L Gamble3,
  3. Paul Garner4,
  4. Hellen Gelband5,
  5. Henry OD Ejere6,
  6. Julia A Critchley1,*,
  7. International Filariasis Review Group4

Editorial Group: Cochrane Infectious Diseases Group

Published Online: 21 JAN 2009

Assessed as up-to-date: 13 AUG 2005

DOI: 10.1002/14651858.CD003753.pub3

Database Title

Additional Information

How to Cite

Addiss D, Gamble CL, Garner P, Gelband H, Ejere HOD, Critchley JA, International Filariasis Review Group. Albendazole for lymphatic filariasis. Cochrane Database of Systematic Reviews 2005, Issue 4. Art. No.: CD003753. DOI: 10.1002/14651858.CD003753.pub3.

Author Information

  1. 1

    Newcastle University, Institute of Health and Society, Newcastle, Tyne and Wear, UK

  2. 2

    Centers for Disease Control and Prevention, Division of Parasitic Diseases, Atlanta, Georgia, USA

  3. 3

    University of Liverpool, Centre for Medical Statistics and Health Evaluation, Liverpool, UK

  4. 4

    Liverpool School of Tropical Medicine, International Health Group, Liverpool, Merseyside, UK

  5. 5

    Resources for the Future, Washington, DC, USA

  6. 6

    Metropolitan Hospital, Department of Medicine, New York, USA

*Julia A Critchley, Institute of Health and Society, Newcastle University, William Leech Building, The Medical School, Newcastle, Tyne and Wear, NE2 4HH, UK. J.A.Critchley@newcastle.ac.uk.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 21 JAN 2009

SEARCH

ARTICLE TOOLS

View Full Article (HTML) Summary (60K)Standard (391K)Full (696K)
 
Characteristics of included studies [ordered by study ID]
Beach 1999
MethodsIndividually randomized controlled trial

Generation of allocation sequence: random-number table

Allocation concealment: concealed by third party

Blinding: "Double blind" stated, although drugs were not identical, patients had no way of identifying them; outcome assessors blinded

Inclusion of all randomized participants in the analysis: 585 analysed of 965 randomized (61%)

Length of follow up: 4 months

Method of microfilariae (mf) assessment/volume of blood: thick smear; 20 µL of finger-prick blood
ParticipantsNumber randomized: 965, of whom 113 were mf positive

Children (male and female) aged 5 to 11 years with Wuchereria bancrofti filariasis
Interventions1. Albendazole: 400 mg, 244 participants
2. Ivermectin: 200 to 400 µg/kg, 240 participants
3. Albendazole plus ivermectin: doses as above, 245 participants
4. Placebo: 229 participants
Outcomes1. Post-treatment reduction in % mf prevalence
2. % reduction in geometric mean mf density (Note: standard deviation not reported; no values reported for the albendazole group)
3. Prevalence of W. bancrofti among all children in each treatment group
4. Frequency of the occurrence of specific systemic adverse events, such as fever, headache, weakness, muscle/joint pain, itching, rash, abdominal pain, and diarrhoea
NotesLocation: Leogane, Haiti

Endemicity level: not stated




Dunyo 2000
MethodsIndividually randomized controlled trial

Generation of allocation sequence: computer generated

Allocation concealment: concealed by third party

Blinding: identical placebos used for each group

Inclusion of all randomized participants in the analysis: 273 analysed of 340 microfilariae (mf) positive randomized (80%)

Length of follow up: 12 months

Method of mf assessment/volume of blood: mf in 100µL of finger-prick blood using the counting chamber technique, daytime collection

Antigen testing: ELISA from finger-prick blood specimens
ParticipantsNumber randomized: 1425, of whom 340 mf positive were followed up

Individuals (male and female) aged 6 to 87 years with or without Wuchereria bancrofti
Interventions1. Albendazole: 400 mg, 88 participants
2. Ivermectin: 150 to 200 µg/kg, 79 participants
3. Albendazole plus ivermectin: doses as above, 90 participants
4. Placebo: 83 participants
Outcomes1. Number of individuals mf positive at 12 months post-treatment
2. Geometric mean mf density (Note: standard deviation not reported)
3. % of pretreatment mf concentration
4. Geometric mean circulating filarial antigen (CFA) density
5. Geometric mean CFA density as % of pretreatment value
6. New infections (appearance of antigenaemia)
7. New disease events (lymphoedema or hydrocoele)
8. Mortality during follow up
9. Frequency of specific systemic adverse events as well as the number of individuals presenting with any adverse event post-treatment; reactions graded as 0 = none, 1 = mild (noticeable to patient but not interfering with daily activities), 2 = moderate (some interference with daily activities), 3 = severe (complete interruption of daily activities)

(Note: Adjusted and unadjusted mf geometric mean mf intensities given)
NotesLocation: southern Ghana (Butre, Achowa, Adjan, and Miamia villages)

Endemicity level: 18% to 25%




Fox 2005
MethodsIndividually randomized controlled trial

Generation of allocation sequence: random number table

Allocation concealment: unclear

Blinding: "Double blind" stated, although no dummy procedure; in reality, only outcome assessors likely to be 'blind'

Inclusion of all randomized participants in the analysis: 990 of 1292 (76%) analysed

Length of follow up: 6 months

Method of microfilariae (mf) assessment/volume of blood: 20 µL thick smear between 7:30 and 9:30 pm

Antigen testing: Og4C3 assay for circulating filarial antigen (CFA)
ParticipantsNumber randomized: 990

Children aged 5 to 11 years attending any of 12 selected primary schools
Interventions1. Albendazole alone: 400 mg, 256 participants
2. Diethylcarbamazine (DEC) alone: 6 mg/kg body weight, 246 participants
3. Placebo: 243 participants
4. DEC and albendazole: doses as above, 245 participants
Outcomes1. % of children in each group who had no mf detected in blood 3 and 6 months post-treatment
2. Mean % reduction in mf density 3 and 6 months post-treatment
3. Geometric mean % reduction in mf density 3 and 6 months post-treatment
4. CFA: % of children with negative CFA 6 months post-treatment
5. Mean % reduction in CFA density, geometric mean
6. % reduction in CFA density 6 months after treatment
7. Adverse events: assessed every day for 7 d after treatment by blinded clinicians who questioned and examined children at school; adverse events recorded were self-reported or documented fever, headache, myalgias, and cough; also reported a mean treatment impact score by day for the first seven days (1 = symptoms noticed, but did not interfere with daily activities, 2 = symptoms caused some interference with daily activities, 3 = symptoms prevented usual daily activities)

(Note: standard deviations for geometric mean density changes reported on request)
NotesLocation: Leogane commune, Haiti

Endemicity level: 14.7% of children had mf and 31.4% were positive CFA at baseline




Jayakody 1993
MethodsIndividually randomized controlled trial

Generation of allocation sequence: pre-determined randomization list

Allocation concealment: states randomization list 'restricted'

Blinding: unclear

Inclusion of all randomized participants in the analysis: 20 analysed of 29 randomized (74%)

Length of follow up: 19 months

Method of microfilariae (mf) assessment/volume of blood: membrane filtration for using a Nucleopore filter (3 µm pore size)
ParticipantsNumber randomized: 29

Asymptomatic men aged 18 to 65 with Wuchereria bancrofti mf

Patients with mf density in night blood films > 100 mf/mL at least once during previous week included
Interventions1. Albendazole: 400 mg given twice daily for 21 d, 16 participants
2. Diethylcarbamazine (DEC): 6 mg/kg daily for 21 d, 13 participants
Outcomes1. Post-treatment % prevalence reduction
2. % reduction in geometric mean mf density
3. Adverse events: the prevalence and severity of "scrotal syndrome" (pain in the scrotum, enlargement of epididymis, and some systemic features, such as fever, thought to be caused by death of adult worms) during the treatment period
NotesLocation: Colombo, Sri Lanka

Endemicity level: not stated




Kshirsagar 2004
MethodsIndividually randomized controlled trial

Generation of allocation sequence: states randomized, exact details unclear

Allocation concealment: unclear

Blinding: used identical placebos and double dummy procedure

Inclusion of all randomized participants in the analysis: 1395/1403 (99%) analysed in safety study; 103 microfilariae (mf)-positive men were selected for the efficacy study, but follow up of these was adequate at some time points but inadequate at others

Length of follow up: 12 months

Method of mf assessment/volume of blood: thick smear, 60 µL of finger-prick blood or venepuncture between 9 and 11pm

Antigen testing: immunochromatographic card

Detection of adult filarial worm by USG machine; all regions of scrotum and spermatic cord systematically studied, and "filaria dance sign" identified
ParticipantsNumber: 1403 randomized for safety study; 103 for efficacy assessment

Safety study: males and females over 5 years old with and without Wuchereria bancrofti

Efficacy assessment: males aged 18 to 50
Interventions1. Diethylcarbamazine (DEC): 6 mg/kg body weight and albendazole 400 mg
2. DEC plus albendazole-placebo
Outcomes1. Number mf positive at 3, 6, and 12 months (and % of pretreatment levels)
2. Number immunochromatographic card test (ICT) positive at 3, 6, and 12 months (and % pretreatment levels)
3. Number ultrasonography USG positive at 3, 6, and 12 months (and % pretreatment levels); results stratified for those mf positive at baseline (43 participants), with clinical disease (30 participants), and mf negative and asymptomatic (30 participants)
4. Adverse events: total incidence and number of participants with adverse drug reactions on days 2 or 5, number of early terminations, number of participants where adverse events interfered with daily activities, and global assessment of tolerability (very good or good, satisfactory, poor or insufficient, not assessable). Also categorized the severity of adverse reactions according to the National Cancer Institute Common Toxicity Criteria (NCI 1999)
NotesLocation: 2 endemic villages in Wardha, Maharashtra (Western India)

Endemicity level: 7.27% in 1995

Efficacy data: at many time points there were no men with clinical disease or mf negative at baseline surveyed




Pani 2002
MethodsIndividually randomized controlled trial

Generation of allocation sequence: unclear

Allocation concealment: adequate - coding of drugs performed by independent monitor

Blinding: comparable placebo and outcome assessors 'blind'

Inclusion of all randomized participants in the analysis: implies no losses to follow up (54 analysed out of 54 randomized)

Length of follow up: 24 months

Method of microfilariae (mf) assessment/volume of blood: not clear, 1 mL venous blood collected between 7:30 to 8:30 pm

Antigen testing: immunochromatographic card test and by Og4C3 ELISA test kit on 50 µL serum
ParticipantsNumber randomized: 54

Asymptomatic volunteers (male and female) between 10 and 57 years old who were mf positive
Interventions1. Albendazole: 400 mg, 19 participants
2. Diethylcarbamazine (DEC): 6 mg/kg, 17 participants
3. Albendazole plus DEC: doses as above, 18 participants
Outcomes1. % of individuals mf positive post-treatment
2. % reduction in geometric mean mf
3. % reduction in filarial antigen prevalence
4. Adverse events: monitored all participants in hospital for adverse reactions at 8-h intervals for the first 24 h, then every 24 h for a further 3 d; proportion of individuals reporting any systemic adverse event and intensity (using a simple scoring system) of adverse events were noted

(Note: no standard deviation reported for geometric mean mf density)
NotesLocation: Pondicherry, India

Endemicity level: not given in report




Simonsen 2004
MethodsIndividually randomized controlled trial

Generation of allocation sequence: computer generated

Allocation concealment: concealed by third party

Blinding: used identical placebos and double dummy procedure

Inclusion of all randomized participants in the analysis: 1221 of 1829 (67%) analysed

Length of follow up: 12 months

Method of microfilariae (mf) assessment/volume of blood: 100 µL finger-prick blood, counting chamber technique

Antigen testing: circulating filarial antigen (CFA) on TropBio filter paper collection discs; blood sampling for mf and CFA started at 9 pm
ParticipantsNumber randomized: 1829, of which 1221 (67%) followed up; 103 had mf

School children aged 6 to 18 years with or without Wuchereria bancrofti
Interventions1. Albendazole plus ivermectin: 400 mg albendazole, 150 to 200 µg/kg ivermectin, 586 participants
2. Ivermectin alone: dose as above, 635 participants
OutcomesResults reported only in 103 mf-positive participants at baseline

1. Number of individuals mf positive at 6 and 12 months post-treatment
2. Geometric mean mf concentration and % of pretreatment geometric means at 6 and 12 months
3. Number of children CFA positive at 6 and 12 months and % of pretreatment CFA
4. Geometric mean density CFA and % of pretreatment CFA geometric mean density
5. New cases of mf positivity amongst those mf negative at baseline
6. New cases of CFA positivity amongst those CFA negative at baseline
7. Adverse reactions: children followed for 5 d after treatment by passive observation; specific adverse reactions, such as headache, fever, joint pain, diarrhoea, dizziness, vomiting and itching noted, but number of events in each treatment group not clearly reported

(Note: standard deviation not reported for geometric mean mf density)
NotesLocation: 6 primary schools in coastal Tanzania

Endemicity level: known to be high; school mf prevalence was 17.3% overall for the 6 schools


 
Characteristics of excluded studies [ordered by study ID]
StudyReason for exclusion
Dunyo 2002Update of Dunyo 2000 following retreatment of each treatment group; retreatment carried out only with the combination (ALB plus IV), hence no comparison group given IV alone
Ismail 1998The comparison groups – ALB versus ALB plus IV versus ALB plus DEC versus DEC plus IV – do not match those in the review; these comparisons do not provide answers to the question as to whether adding ALB to IV or DEC improves outcomes compared to IV or DEC alone; the comparisons would have to include IV alone or DEC alone as comparators to be relevant to the review
Makunde 2003Comparison groups do not match those in review; for single infections with Wuchereria bancrofti these were ALB plus IV versus ALB alone; for co-infections of W. bancrofti and Onchocerca volvulus these were IV plus ALB versus placebo
Shenoy 1999The comparison groups – ALB versus ALB plus IV versus ALB plus DEC versus DEC plus IV – do not match those in the review; excluded for reasons stated above for Ismail 1998
Shenoy 2002Study of safety and tolerability of adding ALB to DEC; carried out only in patients without microfilariaemia (ie presumably uninfected)
 ALB: albendazole; DEC: diethylcarbamazine; IV: ivermectin.


 
Characteristics of ongoing studies [ordered by study ID]
Dahoma (ongoing)
Trial name or titleAssessment of safety and efficacy of ivermectin and albendazole co-administration
Methods—
Participants1000 participants living in an area endemic for lymphatic filariasis and soil transmitted helminths in Zanzibar, Tanzania
Interventions1. Ivermectin
2. Albendazole plus ivermectin
Outcomes1. Reappearance of microfilariae at 12 months
2. Microfilariae at 3 and 6 months
3. Adverse drug reactions
Starting date—
Contact informationMark Bradley
SmithKline Beecham
GlaxoWellcome House West
Berkeley Avenue
Greenford
Middlesex UB6 0NN
UK
Phone: +44 208 966 8543
Fax: +44 208 966 8827
Email: mhb38319@GlaxoWellcome.co.uk
Notes—
 The names of principal investigator is used as the study ID.


 
Comparison 1. Albendazole versus placebo
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
 1 Microfilariae (mf) prevalence: all participants (both mf positive or negative at baseline)2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only
    1.1 At 3 to 4 months
2783Risk Ratio (M-H, Fixed, 95% CI)0.95 [0.66, 1.37]
    1.2 At 6 months
1499Risk Ratio (M-H, Fixed, 95% CI)1.00 [0.66, 1.53]
 2 Microfilariae (mf) prevalence: only participants mf positive at baseline2195Risk Ratio (M-H, Fixed, 95% CI)0.97 [0.87, 1.09]
 3 Antigen prevalence: all participants (both mf positive or negative at baseline)21090Risk Ratio (M-H, Fixed, 95% CI)0.95 [0.81, 1.12]
 4 New clinical disease1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
    4.1 Hydrocoele
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
 5 Pre-existing clinical disease1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
    5.1 Improvement in lymphoedema
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
    5.2 Improvement in hydrocoele
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
 6 Adverse events1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
    6.1 Systemic
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
 
Comparison 2. Albendazole versus ivermectin
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
 1 Microfilariae (mf) prevalence: all participants (both mf positive or negative at baseline)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
 2 Microfilariae (mf) prevalence: only participants mf positive at baseline2198Risk Ratio (M-H, Fixed, 95% CI)0.84 [0.72, 0.98]
 3 Antigen prevalence: all participants (antigen positive or negative at baseline)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
 4 New clinical disease1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
    4.1 Hydrocoele
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
 5 Pre-existing clinical disease1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
    5.1 Improvement in lymphoedema
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
    5.2 Improvement in hydrocoele
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
 6 Adverse events1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
    6.1 Systemic
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
 
Comparison 3. Albendazole plus ivermectin versus ivermectin
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
 1 Microfilariae (mf) prevalence: all participants (both mf positive or negative at baseline)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
 2 Microfilariae (mf) prevalence: only participants mf positive at baseline3Risk Ratio (M-H, Random, 95% CI)Subtotals only
    2.1 At 4 to 6 months
2255Risk Ratio (M-H, Random, 95% CI)0.49 [0.18, 1.39]
    2.2 At 12 months
2348Risk Ratio (M-H, Random, 95% CI)1.00 [0.88, 1.13]
 3 Antigen prevalence: all participants (antigen positive or negative) at baseline1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
 4 Antigen prevalence: only participants antigen positive at baseline2Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
    4.1 Data at 6 months
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
    4.2 Data at 12 months
2Risk Ratio (M-H, Fixed, 95% CI)Not estimable
 5 New clinical disease1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
    5.1 Hydrocoele
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
 6 Pre-existing clinical disease1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
    6.1 Improvement in lymphoedema
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
    6.2 Improvement in hydrocoele
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
 7 Adverse events2Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
    7.1 Total
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
    7.2 Systemic
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
 
Comparison 4. Albendazole versus diethylcarbamazine (DEC)
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
 1 Microfiliariae (mf) prevalence: all participants (both mf positive or negative at baseline)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
    1.1 At 3 months
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
    1.2 At 6 months
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
 2 Microfilariae (mf) prevalence: only participants mf positive at baseline2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only
    2.1 After 3 months
136Risk Ratio (M-H, Fixed, 95% CI)0.95 [0.82, 1.10]
    2.2 After 1 year
256Risk Ratio (M-H, Fixed, 95% CI)1.19 [0.57, 2.49]
    2.3 After 2 years
136Risk Ratio (M-H, Fixed, 95% CI)3.58 [0.44, 28.97]
 3 Antigen prevalence: all participants (both antigen positive or negative at baseline)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
 4 Antigen prevalence: only participants antigen positive at baseline1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
    4.1 ICT test
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
 5 Adverse events1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
 6 Adverse events: scrotal syndrome1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
 
Comparison 5. Albendazole plus diethylcarbamazine (DEC) versus DEC
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
 1 Microfilariae (mf) prevalence: all participants (both mf positive or negative at baseline)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
    1.1 At 3 months
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
    1.2 At 6 months
1Risk Ratio (M-H, Fixed, 95% CI)Not estimable
 2 Microfilariae (mf) prevalence: only participants mf positive at baseline2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only
    2.1 At 3 months
273Risk Ratio (M-H, Fixed, 95% CI)1.06 [0.83, 1.36]
    2.2 At 6 months
142Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.62, 1.61]
    2.3 At 12 months
278Risk Ratio (M-H, Fixed, 95% CI)0.99 [0.69, 1.44]
    2.4 At 2 years
135Risk Ratio (M-H, Fixed, 95% CI)0.94 [0.06, 13.93]
 3 Antigen prevalence: all participants (both antigen positive and negative at baseline)2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only
    3.1 Data at 6 months
2592Risk Ratio (M-H, Fixed, 95% CI)1.00 [0.82, 1.24]
    3.2 Data at 12 months
1103Risk Ratio (M-H, Fixed, 95% CI)0.95 [0.69, 1.31]
 4 Antigen prevalence: only participants antigen positive at baseline1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
 5 Adverse events2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only
    5.1 Any
21430Risk Ratio (M-H, Fixed, 95% CI)0.88 [0.71, 1.08]
    5.2 Interfered with daily activities
11395Risk Ratio (M-H, Fixed, 95% CI)1.06 [0.64, 1.73]
View Full Article (HTML) Summary (60K)Standard (391K)Full (696K)