Correspondence

Mass Treatment of Filariasis in New Guinea

N Engl J Med 2003; 348:1179-1181March 20, 2003

Article

To the Editor:

Bockarie et al. (Dec. 5 issue)1 provide encouraging new evidence that mass treatment with antifilarial drugs can interrupt transmission of Wuchereria bancrofti. However, their conclusion that this strategy can eliminate filarial lymphedema may be overly optimistic. Bockarie et al. credit mass treatment with an impressive 69 percent cure rate among a subgroup of persons who entered the study with lymphedema. However, the overall prevalence of lymphedema decreased only from 5 percent to 4 percent, suggesting that the incidence of new-onset lymphedema, presumably also filarial in origin, was substantial. Furthermore, this reduction in prevalence just reached statistical significance, and the denominator changed (from 1273 to 998), making it difficult to interpret the results.

Decreases in the prevalence of lymphedema have been observed previously after mass treatment with antifilarial drugs,2,3 but these earlier studies focused primarily on interrupting filarial transmission. Few details are provided on how lymphedema and coexisting conditions were assessed. Others have noted no such reduction in the prevalence of lymphedema after mass treatment.4,5 In a recent clinical trial, diethylcarbamazine had no effect on chronic lymphedema.6

David G. Addiss, M.D., M.P.H.
Centers for Disease Control and Prevention, Atlanta, GA 30341
daddiss@cdc.gov

6 References

1. 1

   Bockarie MJ, Tisch DJ, Kastens W, et al. Mass treatment to eliminate filariasis in Papua New Guinea. N Engl J Med 2002;347:1841-1848
   Full Text | Web of Science | Medline

2. 2

   Partono F, Purnomo, Oemijati S, Soewarta A. The long term effects of repeated diethylcarbamazine administration with special reference to microfilaraemia and elephantiasis. Acta Trop 1981;38:217-225
   Web of Science | Medline

3. 3

   Meyrowitsch DW, Simonsen PE, Makunde WH. Mass diethylcarbamazine chemotherapy for control of bancroftian filariasis through community participation: comparative efficacy of a low monthly dose and medicated salt. Trans R Soc Trop Med Hyg 1996;90:74-79
   CrossRef | Web of Science | Medline

4. 4

   Ciferri F, Siliga N, Long G, Kessel JF. A filariasis-control program in American Samoa. Am J Trop Med Hyg 1969;18:369-378
   Web of Science | Medline

5. 5

   Fan PC, Peng HW, Chen CC. Follow-up investigations on clinical manifestations after filariasis eradication by diethylcarbamazine medicated common salt on Kinmen (Quemoy) Islands, Republic of China. J Trop Med Hyg 1995;98:461-464
   Medline

6. 6

   Das LK, Subramanyam Reddy G, Pani SP. Some observations on the effect of Dalfon 500 (micronized purified flavinoid fraction of Rutaceae aurantiae) in bancroftian filarial lymphoedema. Filaria J (in press).
   

To the Editor:

Although the results reported by Bockarie et al. represent a proof of principle for the potential success of an elimination strategy,1 we cannot ignore the presence of adult worms, since most subjects tested (>75 percent) still had antigenemia, although there were no new infections. According to an evaluation of the effects in India of the current strategy for the elimination of filariasis involving the mass administration of diethylcarbamazine alone or with albendazole, there was a significant reduction in antigenemia among young children but not in older age groups.2 A quarter of the adults continued to have antigenemia. Greater efforts must be made to operationalize innovative advocacy for better compliance with treatment2 and to identify better antifilarial drugs. We need to prevent a resurgence of transmission by the remaining nonsusceptible adult worms that can reproduce microfilariae with the assistance of persistent contact between vectors and humans.

R. Rajendran, Ph.D.
I.P. Sunish, Ph.D.
T.R. Mani, M.Sc.
Centre for Research in Medical Entomology, Madurai, TN 625002, India
crmeicmr@satyam.net.in

2 References

1. 1

   Ottesen EA. Major progress toward eliminating lymphatic filariasis. N Engl J Med 2002;347:1885-1886
   Full Text | Web of Science | Medline

2. 2

   Rajendran R, Sunish IP, Mani TR, et al. Influence of mass administration of diethylcarbamazine, alone or with albendazole, on the prevalence of filarial antigenaemia. Ann Trop Med Parasitol 2002;96:595-602
   CrossRef | Web of Science | Medline

Author/Editor Response

Addiss correctly notes that the decrease in the overall prevalence of lymphedema in the study population over the five-year study period was small (from 5 percent to 4 percent) relative to the 69 percent rate of reversal of disease in a subgroup examined at both the beginning and the end of the study. As he comments, the sample size used to calculate the change in the overall prevalence of lymphedema decreased from 1273 to 998. Persons with and persons without lymphatic disease migrated into and out of study villages over the five-year period. The change in the denominator between the first and fifth years thus reflects this phenomenon and the inherent difficulty of maintaining follow-up in a rural setting. For this reason, we reported data for the subgroup of adults with preexisting lymphedema for whom follow-up data were available during subsequent years.

To address the issue of new-onset lymphedema raised by Addiss, we identified 695 adults without lymphedema who were examined in both 1993 and 1998. Two of them had new-onset lymphedema, resulting in a five-year cumulative incidence of 0.003. We cannot comment on data in the cited article by Das et al. suggesting that diethylcarbamazine has no effect on chronic lymphedema, since this work is in press and unavailable to us.

With regard to the comments by Rajendran et al., our observation that more than 75 percent of the subsample tested for filarial antigenemia remained positive after three rounds of treatment does not indicate that we ignored the importance to filariasis control programs of eliminating lymphatic-dwelling adult worms. We reported a 76 percent decrease in the mean antigen level, suggesting that mass drug administration was effective in reducing the burden of adult worms but that few persons were cured of infection as indicated by conversion from antigen-positive to antigen-negative status. We had anticipated that only a small proportion of persons would become antigen-negative, because the worm burdens were expected to be high in this area, where filariasis is endemic, and because of existing estimates of diethylcarbamazine activity against adult W. bancrofti worms.1-3 Cure of infection would presumably require additional years of mass treatment with currently available antifilarial drugs or the development of new drugs with greater activity against adult worms.

Daniel J. Tisch, M.P.H.
James W. Kazura, M.D.
Case Western Reserve University, Cleveland, OH 44106-4983
jxk14@po.cwru.edu

3 References

1. 1

   Tisch DJ, Hazlett FE, Kastens W, Alpers MP, Bockarie MJ, Kazura JW. Ecologic and biologic determinants of filarial antigenemia in bancroftian filariasis in Papua New Guinea. J Infect Dis 2001;184:898-904
   CrossRef | Web of Science | Medline

2. 2

   Noroes J, Dreyer G, Santos A, Mendes VG, Medeiros Z, Addiss D. Assessment of the efficacy of diethylcarbamazine on adult Wuchereria bancrofti in vivo. Trans R Soc Trop Med Hyg 1997;91:78-81
   CrossRef | Web of Science | Medline

3. 3

   Dreyer G, Addiss D, Santos A, Figueredo-Silva J, Noroes J. Direct assessment in vivo of the efficacy of combined single-dose ivermectin and diethylcarbamazine against adult Wuchereria bancrofti. Trans R Soc Trop Med Hyg 1998;92:219-222
   CrossRef | Web of Science | Medline