Feasibility of Onchocerciasis Elimination Using a "Test-and-not-treat" Strategy in Loa loa Co-endemic Areas.
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ABSTRACT: Background
Mass drug administration (MDA) with ivermectin is the main strategy for onchocerciasis elimination. Ivermectin is generally safe, but is associated with serious adverse events in individuals with high Loa loa microfilarial densities (MFD). Therefore, ivermectin MDA is not recommended in areas where onchocerciasis is hypo-endemic and L loa is co-endemic. To eliminate onchocerciasis in those areas, a test-and-not-treat (TaNT) strategy has been proposed. We investigated whether onchocerciasis elimination can be achieved using TaNT and the required duration.Methods
We used the individual-based model ONCHOSIM to predict the impact of TaNT on onchocerciasis microfilarial (mf) prevalence. We simulated precontrol mf prevalence levels from 2% to 40%. The impact of TaNT was simulated under varying levels of participation, systematic nonparticipation, and exclusion from ivermectin resulting from high L loa MFD. For each scenario, we assessed the time to elimination, defined as bringing onchocerciasis mf prevalence below 1.4%.Results
In areas with 30% to 40% precontrol mf prevalence, the model predicted that it would take between 14 and 16 years to bring the mf prevalence below 1.4% using conventional MDA, assuming 65% participation. TaNT would increase the time to elimination by up to 1.5 years, depending on the level of systematic nonparticipation and the exclusion rate. At lower exclusion rates (≤2.5%), the delay would be less than 6 months.Conclusions
Our model predicts that onchocerciasis can be eliminated using TaNT in L loa co-endemic areas. The required treatment duration using TaNT would be only slightly longer than in areas with conventional MDA, provided that participation is good.
SUBMITTER: Blok DJ
PROVIDER: S-EPMC8204788 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.).
| S-EPMC5629452 | biostudies-literature
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).
| S-EPMC8150319 | biostudies-literature
Project description:BackgroundSevere adverse events after treatment with ivermectin in individuals with high levels of Loa loa microfilariae in the blood preclude onchocerciasis elimination through community-directed treatment with ivermectin (CDTI) in Central Africa. We measured the cost of a community-based pilot using a test-and-not-treat (TaNT) strategy in the Soa health district in Cameroon.MethodsBased on actual expenditures, we empirically estimated the economic cost of the Soa TaNT campaign, including financial costs and opportunity costs that will likely be borne by control programs and stakeholders in the future. In addition to the empirical analyses, we estimated base-case, less intensive, and more intensive resource use scenarios to explore how costs might differ if TaNT were implemented programmatically.ResultsThe total costs of US$283 938 divided by total population, people tested, and people treated with 42% coverage were US$4.0, US$9.2, and US$9.5, respectively. In programmatic implementation, these costs (base-case estimates with less and more intensive scenarios) could be US$2.2 ($1.9-$3.6), US$5.2 ($4.5-$8.3), and US$5.4 ($4.6-$8.6), respectively.ConclusionsTaNT clearly provides a safe strategy for large-scale ivermectin treatment and overcomes a major obstacle to the elimination of onchocerciasis in areas coendemic for Loa loa. Although it is more expensive than standard CDTI, costs vary depending on the setting, the implementation choices made by the institutions involved, and the community participation rate. Research on the required duration of TaNT is needed to improve the affordability assessment, and more experience is needed to understand how to implement TaNT optimally.
| S-EPMC7146010 | biostudies-literature
Project description:The specificity of skin snips for onchocerciasis diagnoses is considered to be almost 100%. Our molecular methods revealed that microfilariae emerging from skin snips collected from highly microfilaremic Loa loa-infected individuals were largely misidentified as Onchocerca volvulus. This has important implications for onchocerciasis diagnostic testing in Loa-endemic areas.
| S-EPMC6792118 | biostudies-literature
Project description: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.
| S-EPMC8863288 | biostudies-literature
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.
| S-EPMC6161907 | biostudies-literature
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.
| S-EPMC2147660 | biostudies-literature
Project description:Recently, there has been much debate about the prospects of eliminating HIV from high endemic countries by a test-and-treat strategy. This strategy entails regular HIV testing in the entire population and starting antiretroviral treatment immediately in all who are found to be HIV infected. We present the concept of the elimination threshold and investigate under what conditions of treatment uptake and dropout elimination of HIV is feasible. We used a deterministic model incorporating an accurate description of disease progression and variable infectivity. We derived explicit expressions for the basic reproduction number and the elimination threshold. Using estimates of exponential growth rates of HIV during the initial phase of epidemics, we investigated for which populations elimination is within reach. The concept of the elimination threshold allows an assessment of the prospects of elimination of HIV from information in the early phase of the epidemic. The relative elimination threshold quantifies prospects of elimination independently of the details of the transmission dynamics. Elimination of HIV by test-and-treat is only feasible for populations with very low reproduction numbers or if the reproduction number is lowered significantly as a result of additional interventions. Allowing low infectiousness during primary infection, the likelihood of elimination becomes somewhat higher. The elimination threshold is a powerful tool for assessing prospects of elimination from available data on epidemic growth rates of HIV. Empirical estimates of the epidemic growth rate from phylogenetic studies were used to assess the potential for elimination in specific populations.
| S-EPMC3785722 | biostudies-literature
Project description:BackgroundLoiasis is a filarial disease caused Loa loa. The main vectors are Chrysops silacea and C. dimidiata which are confined to the tropical rainforests of Central and West Africa. Loiasis is a mild disease, but individuals with high microfilaria loads may suffer from severe adverse events if treated with ivermectin during mass drug administration campaigns for the elimination of lymphatic filariasis and onchocerciasis. This poses significant challenges for elimination programmes and alternative interventions are required in L. loa co-endemic areas. The control of Chrysops has not been considered as a viable cost-effective intervention; we reviewed the current knowledge of Chrysops vectors to assess the potential for control as well as identified areas for future research.ResultsWe identified 89 primary published documents on the two main L. loa vectors C. silacea and C dimidiata. These were collated into a database summarising the publication, field and laboratory procedures, species distributions, ecology, habitats and methods of vector control. The majority of articles were from the 1950-1960s. Field studies conducted in Cameroon, Democratic Republic of Congo, Equatorial Guinea, Nigeria and Sudan highlighted that C. silacea is the most important and widespread vector. This species breeds in muddy streams or swampy areas of forests or plantations, descends from forest canopies to feed on humans during the day, is more readily adapted to human dwellings and attracted to wood fires. Main vector targeted measures proposed to impact on L. loa transmission included personal repellents, household screening, indoor residual spraying, community-based environmental management, adulticiding and larviciding.ConclusionsThis is the first comprehensive review of the major L. loa vectors for several decades. It highlights key vector transmission characteristics that may be targeted for vector control providing insights into the potential for integrated vector management, with multiple diseases being targeted simultaneously, with shared human and financial resources and multiple impact. Integrated vector management programmes for filarial infections, especially in low transmission areas of onchocerciasis, require innovative approaches and alternative strategies if the elimination targets established by the World Health Organization are to be achieved.
| S-EPMC5382514 | biostudies-literature
Project description:BACKGROUND: The occurrence of Loa loa encephalopathy following mass treatment of onchocerciasis with Mectizan(R) has adversely affected onchocerciasis control efforts in central Africa. Persons with very high densities of L. loa microfilaremia are at increased risk of encephalopathy, but little is known about the geographic distribution of these persons within central Africa. RAPLOA, a new technique that correlates the proportion of community members reporting a history of eyeworm with the prevalence of high-intensity L. loa microfilaremia in that community, may be useful for rapid assessment of areas at potential risk of treatment-related L. loa encephalopathy. Validation of RAPLOA is ongoing. The operational and risk-reduction advantages of RAPLOA over the current technique of village-by-village rapid epidemiologic assessment for onchocerciasis (REA) are unknown. METHODS: We developed a decision model to compare four strategies for minimizing sequelae of L. loa encephalopathy following mass treatment with Mectizan(R) in areas co-endemic for onchocerciasis and loiasis: REA; RAPLOA with threshold eyeworm prevalences of 40% and 20% (RAPLOA-40 and RAPLOA-20, respectively); and combined REA/RAPLOA-40. RESULTS: In the model, all four strategies significantly reduced risk of death and neurologic complications from L. loa encephalopathy, but RAPLOA-20 and REA resulted in half as many such cases as did RAPLOA-40 or combined REA/RAPLOA-40. CONCLUSION: RAPLOA is likely to be useful programmatically in reducing risk of L. loa encephalopathy following mass treatment with Mectizan(R). It also may be cost-saving. Before full-scale implementation, additional data are needed on geographic clustering of high-density L. loa microfilaremia and on RAPLOA's reliability and cost.
| S-EPMC2147661 | biostudies-literature