Oral drug therapy for multiple neglected tropical diseases: a systematic review

Methodological quality of the review: Low confidence

Author: Reddy M, Gill SS, Kalkar SR, Wu W, Anderson PJ, Rochon PA

Geographical coverage: Zanzibar, Kenya, Malaysia, Sri Lanka, New Guinea, Thailand, Bolivia, France, United States, Zaire, Iran, Nigeria and Ethiopia

Sector: Neglected tropical diseases

Sub-sector: Drug treatments, elephantiasis, hookworm, river blindness, roundworm, schistosomiasis, trachoma and whipworm

Equity focus: None specified

Review type: Effectiveness review

Quantitative synthesis method: Narrative synthesis

Qualitative synthesis method: Not applicable

Background:

Neglected tropical diseases (NTDs) include 13 conditions that occur in areas of extreme poverty, and which are poverty promoting. NTDs produce a disease burden almost as great as that associated with human immunodeficiency virus/AIDS, tuberculosis or malaria, yet are virtually unknown by healthcare workers in North America, because they occur almost exclusively in the poorest regions of the world. Seven of the most prevalent diseases have existing oral drug treatments. Identifying treatments that are effective against more than one disease could facilitate efficient and inexpensive treatment.

Objectives:

To systematically review the evidence for drug treatments and to increase awareness that NTDs exist and that treatments are available.

Main findings:

29 randomised controlled trials (RCTs) were identified, of which three targeted four diseases simultaneously, 20 targeted three diseases, and six targeted two diseases. Trials were published between 1972 and 2005, and baseline prevalence of individual diseases varied among RCTs.

Albendazole plus diethylcarbamazine significantly reduced the prevalence of elephantiasis (16.7% to 5.3%), hookworm (10.3% to 1.9%), roundworm (34.5% to 2.3%) and whipworm (55.5% to 40.3%). Albendazole plus ivermectin significantly reduced the prevalence of elephantiasis (12.6% to 4.6%), hookworm (7.8% to 0%), roundworm (33.5% to 6.1%) and whipworm (42.7% to 8.9%). Levamisole plus mebendazole significantly reduced the prevalence of hookworm (94.0% to 71.8%), roundworm (62.0% to 1.4%) and whipworm (93.1% to 74.5%). Pyrantel-oxantel significantly reduced hookworm (93.4% to 85.2%), roundworm (22.8% to 1.4%) and whipworm (86.8% to 59.5%), while albendazole alone significantly reduced the prevalence of hookworm (8.1% to 1.3%), roundworm (28.4% to 0.9%) and whipworm (51.9% to 31.9%).

No RCT examined the treatment of river blindness or trachoma as part of an intervention to target two or more NTDs. Adverse events were generally inadequately reported.

Authors concluded that at least two of the most prevalent NTDs can be treated simultaneously with existing oral drug treatments, facilitating effective and efficient treatment. In addition, they noted that increasing awareness about NTDs, their global impact and the availability of oral drug treatments is an essential step in controlling these diseases.

Methodology:

Authors conducted a search on MEDLINE for RCTs studying oral drug treatments for NTDs. Although the authors did not restrict the search to studies written in English, these were excluded because there were few non-English language trials identified. Also, the total number of participants in these trials was small relative to the total number in the sample.

Authors included only the most prevalent NTDs for which the World Health Organisation (WHO) has identified the existence of effective oral drug therapy. Based on 2007 WHO data, the seven most prevalent NTDs are elephantiasis, hookworm, river blindness, roundworm, schistosomiasis, trachoma and whipworm.

It is not clear from the review if the two authors independently screened studies for inclusion and extracted data of included studies. Authors used a narrative synthesis approach which seemed appropriate due to the heterogeneity of included studies.

Applicability/external validity:

Authors did not discuss the generalizability of the results.

Geographic focus:

Authors focused on several settings including low- and middle-income settings. However, authors did not discuss how findings are applicable to these settings.

Summary of quality assessment:

Overall, there is low confidence in the conclusions about the effects of this study as important limitations were identified. Authors clearly stated the methods used to analyse the findings of the review, however methods used to screen studies for inclusion and to extract data of included studies were not clear. It is not clear from the review if the two authors independently screened studies and extracted data of studies, avoiding bias within the review. In addition, authors did not conduct a thorough search of the literature; as such publication bias was not avoided within the review. These limitations may have an impact on the overall conclusions in the review.