Test-and-not-treat: importance for mass drug administration
Authors: Jesica Herrick
Journal: The Lancet Infectious Diseases (2019)

The helminth Loa loa is endemic in much of west and central Africa. Symptoms of loiasis include transient localised angioedema and subconjunctival migration of adult worms; however, most residents of endemic areas have an asymptomatic infection and a high microfilarial count.1Herrick JA Metenou S Makiya MA et al.Eosinophil-associated processes underlie differences in clinical presentation of loiasis between temporary residents and those indigenous to loa-endemic areas.Clin Infect Dis. 2015; 60: 55-63Crossref PubMed Scopus (28) Google Scholar Despite the high proportion of infected individuals who are asymptomatic, loiasis is clinically important because serious adverse events can occur when some patients with loiasis receive medication for other filarial helminth infections during mass drug administration (MDA) programmes.2Twum-Danso NA Loa loa encephalopathy temporally related to ivermectin administration reported from onchocerciasis mass treatment programs from 1989 to 2001: implications for the future.Filaria J. 2003; 2: S7Crossref PubMed Google Scholar The principal risk factor for these adverse events is a high microfilarial count (odds ratio >1000 for serious adverse events in those with a microfilarial count >50 000 microfilariae per mL).3Gardon J Gardon-Wendel N Demanga N Kamgno J Chippaux JP Boussinesq M Serious reactions after mass treatment of onchocerciasis with ivermectin in an area endemic for Loa loa infection.Lancet. 1997; 350: 18-22Summary Full Text Full Text PDF PubMed Scopus (433) Google Scholar Although these reactions are believed to be immune-mediated, steroids have not been shown to prevent adverse events after treatment.4Herrick JA Legrand F Gounoue R et al.Posttreatment reactions after single-dose diethylcarbamazine or ivermectin in subjects with Loa loa infection.Clin Infect Dis. 2017; 64: 1017-1025Crossref PubMed Scopus (20) Google Scholar Because of the risk of these adverse events, MDA programmes have been impeded in the large geographical areas where loiasis is endemic, leaving many patients at risk of blindness or other disabling symptoms of filarial infections.1Herrick JA Metenou S Makiya MA et al.Eosinophil-associated processes underlie differences in clinical presentation of loiasis between temporary residents and those indigenous to loa-endemic areas.Clin Infect Dis. 2015; 60: 55-63Crossref PubMed Scopus (28) Google Scholar, 5Boussinesq M Loiasis.Ann Trop Med Parasitol. 2006; 100: 715-731Crossref PubMed Scopus (125) Google Scholar The test-and-not-treat strategy is a novel approach in which a L loa microfilarial count is measured in all individuals participating in MDA, allowing those with high microfilarial loads (ie, those at risk of serious adverse events) to be excluded from MDA. This strategy has only become practicable with the development of the LoaScope, a mobile telephone-based field-friendly test that provides highly accurate measures of microfilarial counts.6D'Ambrosio MV Bakalar M Bennuru S et al.Point-of-care quantification of blood-borne filarial parasites with a mobile phone microscope.Sci Transl Med. 2015; 7: 286re4Crossref PubMed Scopus (152) Google Scholar Feasibility testing has shown that the test-and-not-treat strategy can prevent serious adverse events associated with MDA in areas where loiasis is endemic.7Kamgno J Pion SD Chesnais CB et al.A test-and-not-treat strategy for onchocerciasis in Loa loa-endemic areas.N Engl J Med. 2017; 377: 2044-2052Crossref PubMed Scopus (93) Google Scholar However, a key limitation of this strategy is the increased cost associated with testing of microfilarial counts. In The Lancet Infectious Diseases, Sébastian Pion and colleagues8Pion SDS Nana-Djeunga H Niamsi-Emalio Y et al.Implications for annual retesting after a test-and-not-treat strategy for onchocerciasis elimination in areas co-endemic with Loa loa infection: an observational cohort study.Lancet Infect Dis. 2019; (published online Oct 29,)https://doi.org/10.1016/S1473-3099(19)30554-7Date: 2019Summary Full Text Full Text PDF PubMed Scopus (9) Google Scholar compared microfilarial counts between two MDA campaigns that were run 18 months apart, to evaluate the necessity of obtaining microfilarial counts from the same patient before each MDA. Their results showed that, of the 6983 individuals for whom complete data were available, more than 99·9% of those with a safe L loa microfilarial count who were treated with ivermectin in 2015 had a L loa microfilarial density below the threshold associated with serious adverse events on repeat testing 18 months later. The authors therefore conclude that individuals who have microfilarial counts below the exclusion threshold during the first round of MDA do not need to be retested before a second round. This adapted approach would substantially decrease the costs of the test-and-not-treat strategy. An important issue highlighted by these findings is that a relatively low number of individuals could be accurately matched between the two MDA campaigns. Retention of participants in long-term programmes can be a crucial challenge in low-income and middle-income countries. Several factors impact retention, such as rurality of residence, lower socioeconomic status, lower health literacy, and poor health at the time of treatment initiation.9Bockarie MJ Kelly-Hope LA Rebollo M Molyneux DH Preventive chemotherapy as a strategy for elimination of neglected tropical parasitic diseases: endgame challenges.Philos Trans R Soc Lond B Biol Sci. 2013; 368: 20120144Crossref PubMed Scopus (95) Google Scholar Pion and colleagues also noted that the main problem in their study was uncertainty in identifying participants, which stemmed partly from an absence of standardised spelling of names, confusion over the dates of birth of elderly individuals, and a highly mobile population that made it difficult to match participants by their village of residence. Misidentification of patients has been acknowledged to be an important cause of adverse events in health care, although very few published data have examined the importance of this issue in developing countries. Several strategies have been suggested to overcome this problem, including the use of biometrics (fingerprint or iris scan), use of two methods of identification, and additional training of clinical or study staff on patient identification.10Latham T Malomboza O Nyirenda L et al.Quality in practice: implementation of hospital guidelines for patient identification in Malawi.Int J Qual Health Care. 2012; 24: 626-633Crossref PubMed Scopus (10) Google Scholar Despite these problems with patient identification, a large subset of patients (43·2%) could be definitively matched between the two MDA campaigns. Pion and colleagues found that, within this group, individuals could be safely retreated with ivermectin without repeating a microfilarial count. These findings could have an important impact on the potential costs associated with the test-and-not-treat strategy, since substantially fewer individuals would have to be tested during follow-up rounds of MDA. Overall, these results show promise that MDA programmes could possibly be safely restarted in loa-endemic areas using the test-and-not-treat strategy. Implications for annual retesting after a test-and-not-treat strategy for onchocerciasis elimination in areas co-endemic with Loa loa infection: an observational cohort studyIndividuals treated with ivermectin do not need to be retested for L loa microfilaraemia before the next treatment, provided that they can be re-identified. This adjusted approach will enable substantial cost savings and facilitate reaching programmatic goals for elimination of onchocerciasis in areas that are co-endemic for loiasis. Full-Text PDF Open Access