Dataset Information

Geostatistical modelling enables efficient safety assessment for mass drug administration with ivermectin in Loa loa endemic areas through a combined antibody and LoaScope testing strategy for elimination of onchocerciasis.

ABSTRACT: The elimination of onchocerciasis through community-based Mass Drug Administration (MDA) of ivermectin (Mectizan) is hampered by co-endemicity of Loa loa, as individuals who are highly co-infected with Loa loa parasites can suffer serious and occasionally fatal neurological reactions from the drug. The test-and-not-treat strategy of testing all individuals participating in MDA has some operational constraints including the cost and limited availability of LoaScope diagnostic tools. As a result, a Loa loa Antibody (Ab) Rapid Test was developed to offer a complementary way of determining the prevalence of loiasis. We develop a joint geostatistical modelling framework for the analysis of Ab and Loascope data to delineate whether an area is safe for MDA. Our results support the use of a two-stage strategy, in which Ab testing is used to identify areas that, with acceptably high probability, are safe or unsafe for MDA, followed by Loascope testing in areas whose safety status is uncertain. This work therefore contributes to the global effort towards the elimination of onchocerciasis as a public health problem by potentially reducing the time and cost required to establish whether an area is safe for MDA.

SUBMITTER: Johnson O

PROVIDER: S-EPMC8863288 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Geostatistical modelling enables efficient safety assessment for mass drug administration with ivermectin in Loa loa endemic areas through a combined antibody and LoaScope testing strategy for elimination of onchocerciasis.

Johnson Olatunji O Giorgi Emanuele E Fronterrè Claudio C Amoah Benjamin B Atsame Julienne J Ella Sylvie Ntsame SN Biamonte Marco M Ogoussan Kisito K Hundley Lee L Gass Katherine K Diggle Peter J PJ

PLoS neglected tropical diseases 20220209 2

The elimination of onchocerciasis through community-based Mass Drug Administration (MDA) of ivermectin (Mectizan) is hampered by co-endemicity of Loa loa, as individuals who are highly co-infected with Loa loa parasites can suffer serious and occasionally fatal neurological reactions from the drug. The test-and-not-treat strategy of testing all individuals participating in MDA has some operational constraints including the cost and limited availability of LoaScope diagnostic tools. As a result, ...[more]

PMID: 35139080

Similar Datasets

Project description:BackgroundImplementation of an ivermectin-based community treatment strategy for the elimination of onchocerciasis or lymphatic filariasis has been delayed in Central Africa because of the occurrence of serious adverse events, including death, in persons with high levels of circulating Loa loa microfilariae. The LoaScope, a field-friendly diagnostic tool to quantify L. loa microfilariae in peripheral blood, enables rapid, point-of-care identification of persons at risk for serious adverse events.MethodsA test-and-not-treat strategy was used in the approach to ivermectin treatment in the Okola health district in Cameroon, where the distribution of ivermectin was halted in 1999 after the occurrence of fatal events related to L. loa infection. The LoaScope was used to identify persons with an L. loa microfilarial density greater than 20,000 microfilariae per milliliter of blood, who were considered to be at risk for serious adverse events, and exclude them from ivermectin distribution. Active surveillance for posttreatment adverse events was performed daily for 6 days.ResultsFrom August through October 2015, a total of 16,259 of 22,842 persons 5 years of age or older (71.2% of the target population) were tested for L. loa microfilaremia. Among the participants who underwent testing, a total of 15,522 (95.5%) received ivermectin, 340 (2.1%) were excluded from ivermectin distribution because of an L. loa microfilarial density above the risk threshold, and 397 (2.4%) were excluded because of pregnancy or illness. No serious adverse events were observed. Nonserious adverse events were recorded in 934 participants, most of whom (67.5%) had no detectable L. loa microfilariae.ConclusionsThe LoaScope-based test-and-not-treat strategy enabled the reimplementation of community-wide ivermectin distribution in a heretofore "off limits" health district in Cameroon and is a potentially practical approach to larger-scale ivermectin treatment for lymphatic filariasis and onchocerciasis in areas where L. loa infection is endemic. (Funded by the Bill and Melinda Gates Foundation and others.).

Project description:BACKGROUND:Loiasis is a filarial infection endemic in the rainforest zone of west and central Africa particularly in Cameroon, Gabon, Republic of Congo, and Democratic Republic of the Congo. Repeated treatments with ivermectin have been delivered using the annual community directed treatment with ivermectin (CDTI) approach for several years to control onchocerciasis in some Loa loa-Onchocerca volvulus co-endemic areas. The impact of CDTI on loiasis parasitological indicators is not known. We, therefore, designed this cross sectional study to explore the effects of several rounds of CDTI on parasitological indicators of loiasis. METHODOLOGY/PRINCIPAL FINDINGS:The study was conducted in the East, Northwest and Southwest 2 CDTI projects of Cameroon. Individuals who consented to participate were interviewed for ivermectin treatment history and enrolled for parasitological screening using thick smears. Ivermectin treatment history was correlated with loiasis prevalence/intensity. A total of 3,684 individuals were recruited from 36 communities of the 3 CDTI projects and 900 individuals from 9 villages in a non-CDTI district. In the East, loiasis prevalence was 29.3% (range = 24.2%-34.6%) in the non-CDTI district but 16.0% (3.3%-26.6%) in the CDTI district with 10 ivermectin rounds (there were no baseline data for the latter). In the Northwest and Southwest 2 districts, reductions from 30.5% to 17.9% (after 9 ivermectin rounds) but from 8.1% to 7.8% (not significantly different after 14 rounds) were registered post CDTI, respectively. Similar trends in infection intensity were observed in all sites. There was a negative relationship between adherence to ivermectin treatment and prevalence/intensity of infection in all sites. None of the children (aged 10-14 years) examined in the East CDTI project harboured high (8,000-30,000 mf/ml) or very high (>30,000 mf/ml) microfilarial loads. Individuals who had taken >5 ivermectin treatments were 2.1 times more likely to present with no microfilaraemia than those with less treatments. CONCLUSION:In areas where onchocerciasis and loiasis are co-endemic, CDTI reduces the number of, and microfilaraemia in L. loa-infected individuals, and this, in turn, will help to prevent non-neurological and neurological complications post-ivermectin treatment among CDTI adherents.

Project description:BackgroundA test-and-not-treat (TaNT) strategy has been developed to prevent people with high concentrations of circulating Loa loa microfilariae (>20 000 microfilariae per mL) developing serious adverse events after ivermectin treatment during mass drug administration to eliminate onchocerciasis. An important question related to cost and programmatic issues is whether annual retesting is required for everyone. We therefore aimed to investigate changes in L loa microfilarial densities during TaNT campaigns run 18 months apart.MethodsIn this observational cohort study, we assessed the participants of two TaNT campaigns for onchocerciasis. These campaigns, which were run by a research team, together with personnel from the Ministry of Health and community health workers, were done in six health areas (in 89 communities) in Okola health district (Cameroon); the first campaign was run between Aug 10, and Oct 29, 2015, and the second was run between March 7, and May 26, 2017. All individuals aged 5 years and older were invited to be screened for Loa loa microfilaraemia before being offered ivermectin (unless contraindicated). L loa microfilarial density was measured at the point of care using the LoaScope. All those with a L loa microfilarial density of 20 000 microfilariae per mL or less were offered treatment; in the first 2 weeks of the 2015 campaign, a higher exclusion threshold of 26 000 microfilariae per mL or less was used. At both rounds of the intervention, participants were registered with a paper form, in which personal information were collected. In 2017, we also recorded whether each individual reported participation in the 2015 campaign. The primary outcome, assessed in all participants, was whether L loa microfilarial density was above or below the exclusion threshold (ie, the criteria that guided the decision to treat).FindingsIn the 2015 TaNT campaign, 26 415 people were censused versus 29 587 people in the 2017 TaNT campaign. All individuals aged 5 years and older without other contraindications to treatment (22 842 people in 2015 and 25 421 people in 2017) were invited to be screened for L loa microfilaraemia before being offered ivermectin. In 2015, 16 182 individuals were examined with the LoaScope, versus 18 697 individuals in the same communities in 2017. 344 (2·1%) individuals were excluded from ivermectin treatment because of a high L loa microfilarial density in 2015, versus 283 (1·5%) individuals in 2017 (p<0·0001). Records from 2017 could be matched to those from 2015 for 6983 individuals (43·2% of the 2015 participants). In this cohort, in 2017, 6981 (>99·9%) of 6983 individuals treated with ivermectin in 2015 had L loa microfilariae density below the level associated with neurological serious adverse events.InterpretationIndividuals 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.FundingBill & Melinda Gates Foundation, Division of Intramural Research (National Institute of Allergy and Infectious Diseases, US National Institutes of Health).

Project description:Currently, national governments of onchocerciasis endemic African countries are working towards the elimination of the disease using mass drug administration (MDA) with ivermectin as a primary strategy. Attainment of this goal requires implementation of prolonged high MDA coverage in all endemic areas, and vigilant monitoring and evaluation of the program. This study was thus conducted with the purpose of i) providing estimate of ivermectin coverage, ii) validating the MDA coverage reported through community drug distributors (CDDs), iii) determining the factors associated with MDA coverage, and iv) estimating the difference between MDA program reach and survey coverage rates following MDA campaign carried out in May 2017 in Asosa and Yeki districts in Ethiopia. A community-based cross-sectional study was conducted among 2,824 study participants in Asosa and Yeki districts. A total of 50 kebeles (smallest administrative units) were randomly selected from the two districts. A systematic sampling was employed to select study households from the 50 kebeles. Then, a household member was randomly selected for the interview. Univariate and multivariate logistic regression analysis were used to determine the odds ratio and to observe the associations between the MDA survey coverage and the variables used. Eighty-seven percent (2458/2824) of the respondents from both districts responded that they were offered ivermectin during the May 2017 MDA campaign. At the district level, 1182 individuals from Yeki and 1276 from Asosa, received the drug, that indicate 88.5% and 85.8% MDA program reach in Yeki and Assosa districts, respectively. Whereas, a total of 366 individuals were not offered ivermectin in both study districts. Of these, 47(12.8%), 143(39.1%), and 176(48.1%) did not receive the drug because of program implementation-related reasons, ineligibility criteria, and personal issues, respectively. Of the 1488 and 1336 respondents in Asosa and Yeki, 1272 and 1182 participants took the drug, resulting in survey coverage rate of 85.5% (95% CI: 83.6-87.2%) and 88.5% (95% CI: 86.7-90.1%), respectively. Multivariable logistic regression analysis revealed significantly low survey coverage rate in females (AOR = 0.5, 95%CI: 0.3-0.6; p<0.001) and in those whose age ranges between 15-24 years (AOR = 0.5, 95%CI: 0.3-0.8; p = 0.007) and 25-34 years (AOR = 0.5, 95%CI: 0.3-0.9; p = 0.021) in Asosa. The researchers believe that the current study generated operational evidence on MDA program reach and coverage rates in two study districts in Ethiopia. The survey coverages were lower than the recommended 90% minimum threshold for success. Only Yeki district reached the 90% threshold survey coverage. Both districts had reported higher coverages than the survey estimates (even outside the 95% CI), thus, were not validated. The majority (60.9%) of the reasons for not receiving the drug were related to program implementation and recipients`personal issues. Efforts must therefore be directed to enhance MDA coverage in future rounds via proper MDA planning and implementation, such as allocating adequate time to the MDA activities, health education, and mobilizing of all segments of the population, including adolescents and the youth. The researchers also recommend such studies to be extended to other MDA programs for other neglected tropical diseases (NTDs).

Project description:The occurrence of Serious Adverse Experiences (SAEs) following Mectizan(R) treatment of onchocerciasis in Loa loa endemic areas has been increasingly reported over the past decade. These SAEs include a severely disabling, and potentially fatal, encephalopathy, which appears to correlate with a high load of L. loa microfilariae (> 30,000 mf/ml).Previous consultations organized by the Mectizan(R) Donation Program (MDP) in 1995 and 1999 have developed useful "case" definitions of encephalopathic SAEs following Mectizan(R) treatment and have summarized available evidence on its pathogenesis and optimal clinical management. At both meetings, the need for better understanding of the pathogenesis of the encephalopathy was emphasized, including the need for biological and autopsy specimens from the affected cases.Following a recommendation at the Joint Action Forum of the African Programme for Onchocerciasis Control in December 2001, the MDP, on behalf of the Mectizan(R) Expert Committee, organized a Scientific Working Group on L. loa associated SAEs following Mectizan(R) treatment in May 2002. The present report includes the background, new evidence, conclusions and recommendations from that Scientific Working Group. The following points represent a summary of the present status:1. Although there are more and better quality clinical and epidemiological data on L. loa, the pathogenesis of the Mectizan(R)-related L. loa encephalopathy remains obscure.2. Very limited progress has been made in research on the pathogenesis of encephalopathy, because of the lack of specimens from cases, and the lack of animal models.3. There has been no particular breakthrough in terms of the medical management of patients with L. loa encephalopathy; however, a favorable outcome usually results from prompt general nursing and nutritional care which remain the major interventions.The main recommendations for future actions are as follows:1. Validate and update the mapping of L. loa with a combination of remote sensing and RAPLOA techniques.2. Conduct an expert analysis of the apparent clustering of encephalopathic SAEs reported so far.3. Investigate a possible "pre-treatment" scheme with high-dose albendazole in L. loa endemic communities at high risk of encephalopathic SAEs if treated with Mectizan(R); this study will be conducted in collaboration with WHO/TDR.4. Establish a post of Loiasis Technical Advisor for research and operational support in Cameroon, to conduct population surveys and to facilitate better data collection from SAE cases, including postmortem studies as appropriate.5. Investigate the possibility of developing an animal model of L. loa encephalopathy; this activity would be linked to the above-mentioned research agenda in Cameroon.6. Investigate the best care model for encephalopathic SAEs, including identification of early warning signs and therapeutic interventions.7. Develop further models for health education messages needed for community compliance with Mectizan(R) treatment, and family support for SAE cases.8. Conduct research studies on the safety of combination therapy of Mectizan(R) and albendazole in areas co-endemic for L. loa and lymphatic filariasis (LF) with coordination from the relevant technical bodies that oversee these issues.The above recommendations will be implemented through a continuing collaboration between the interested parties represented at the Scientific Working Group, involved in onchocerciasis control and/or the Global Programme to Eliminate Lymphatic Filariasis.

Dataset Information

Geostatistical modelling enables efficient safety assessment for mass drug administration with ivermectin in Loa loa endemic areas through a combined antibody and LoaScope testing strategy for elimination of onchocerciasis.

Publications

Geostatistical modelling enables efficient safety assessment for mass drug administration with ivermectin in Loa loa endemic areas through a combined antibody and LoaScope testing strategy for elimination of onchocerciasis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets