Community-based door to door census of suspected people living with epilepsy: empowering community drug distributors to improve the provision of care to rural communities in Cameroon

Background Epilepsy is a severe neurological disorder with huge psychological, social, and economic consequences, including premature deaths and loss of productivity. Sub-Saharan Africa carries the highest burden of epilepsy. The management of epilepsy in Cameroon remains unsatisfactory due to poor identification of cases and a limited knowledge of the distribution of the disease. The objective of this study was to determine whether community drug distributors (CDDs) - volunteers selected by their communities to distribute ivermectin against onchocerciasis and who have been proven efficient to deliver other health interventions such as insecticide-treated bed nets to prevent malaria, vitamin A tablets, and albendazole to treat soil transmitted helminthiasis - can be used to reliably identify people living with epilepsy to promote better management of cases. Methods This study was carried out in three health Districts in Cameroon. An exhaustive house to house census was carried out by trained CDDs under the supervision of local nurses. In each household, all suspected cases of epilepsy were identified. In each health district, five communities were randomly selected for a second census by trained health personnel (research team). The results of the two censuses were compared for verification purposes. Results A total of 53,005 people was registered in the 190 communities surveyed with 794 (1.4%) individuals identified as suspected cases of epilepsy (SCE) by the CDDs. In the 15 communities where the SCE census was verified, the average ratio between the number of suspected cases of epilepsy reported in a community by the research team and that reported by the CDDs was 1.1; this ratio was  1.2 in 6 communities. Conclusions The results of this study suggest that CDDs, who are present in about 200,000 communities in 31 Sub Saharan African countries where onchocerciasis is endemic, can be successfully used to assess epilepsy prevalence, and therefore map epilepsy in many African countries

The geographic distribution of onchocerciasis in the 20 participating countries of the African Programme for Onchocerciasis Control:(2) pre-control endemicity levels and estimated number infected

BACKGROUND: The original aim of the African Programme for Onchocerciasis Control (APOC) was to control onchocerciasis as a public health problem in 20 African countries. In order to identify all high risk areas where ivermectin treatment was needed to achieve control, APOC used Rapid Epidemiological Mapping of Onchocerciasis (REMO). REMO involved spatial sampling of villages to be surveyed, and examination of 30 to 50 adults per village for palpable onchocercal nodules. REMO has now been virtually completed and we report the results in two articles. A companion article reports the delineation of high risk areas based on expert analysis. The present article reports the results of a geostatistical analysis of the REMO data to map endemicity levels and estimate the number infected. METHODS: A model-based geostatistical analysis of the REMO data was undertaken to generate high-resolution maps of the predicted prevalence of nodules and of the probability that the true nodule prevalence exceeds the high risk threshold of 20%. The number infected was estimated by converting nodule prevalence to microfilaria prevalence, and multiplying the predicted prevalence for each location with local data on population density. The geostatistical analysis included the nodule palpation data for 14,473 surveyed villages. RESULTS: The generated map of onchocerciasis endemicity levels, as reflected in the prevalence of nodules, is a significant advance with many new endemic areas identified. The prevalence of nodules was > 20% over an area of 2.5 million km2 with an estimated population of 62 million people. The results were consistent with the delineation of high risk areas of the expert analysis except for borderline areas where the prevalence fluctuated around 20%. It is estimated that 36 million people would have been infected in the APOC countries by 2011 if there had been no ivermectin treatment. CONCLUSIONS: The map of onchocerciasis endemicity levels has proven very valuable for onchocerciasis control in the APOC countries. Following the recent shift to onchocerciasis elimination, the map continues to play an important role in planning treatment, evaluating impact and predicting treatment end dates in relation to local endemicity levels

How can onchocerciasis elimination in Africa be accelerated? Modelling the impact of increased ivermectin treatment frequency and complementary vector control

Background: Great strides have been made toward onchocerciasis elimination by mass drug administration (MDA) of ivermectin. Focusing on MDA-eligible areas, we investigated where the elimination goal can be achieved by 2025 by continuation of current practice (annual MDA with ivermectin) and where intensification or additional vector control is required. We did not consider areas hypoendemic for onchocerciasis with loiasis coendemicity where MDA is contraindicated. Methods: We used 2 previously published mathematical models, ONCHOSIM and EPIONCHO, to simulate future trends in microfilarial prevalence for 80 different settings (defined by precontrol endemicity and past MDA frequency and coverage) under different future treatment scenarios (annual, biannual, or quarterly MDA with different treatment coverage through 2025, with or without vector control strategies), assessing for each strategy whether it eventually leads to elimination. Results: Areas with 40%–50% precontrol microfilarial prevalence and ≥10 years of annual MDA may achieve elimination with a further 7 years of annual MDA, if not achieved already, according to both models. For most areas with 70%–80% precontrol prevalence, ONCHOSIM predicts that either annual or biannual MDA is sufficient to achieve elimination by 2025, whereas EPIONCHO predicts that elimination will not be achieved even with complementary vector control. Conclusions: Whether elimination will be reached by 2025 depends on precontrol endemicity, control history, and strategies chosen from now until 2025. Biannual or quarterly MDA will accelerate progress toward elimination but cannot guarantee it by 2025 in high-endemicity areas. Long-term concomitant MDA and vector control for high-endemicity areas might be useful

Comparative evaluation of automated KingFisher Flex Purification System 96 (ThermoFisher Scientific) and manual QIAamp Viral RNA Mini Kit (Qiagen) extraction methods for SARS-CoV-2

Background: The extraction step of the viral material of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) influences the quality of reverse transcriptase-polymerase chain reaction (RT-PCR) results in diagnosis of coronavirus disease 2019 (COVID-19). The purpose of this cross-sectional study was to evaluate the diagnostic performance of the automated extraction system "KingFisher Flex Purification System 96 (ThermoFisher)" compared to the manual method with the "QIAamp Viral RNA Mini Kit (Qiagen)". Methodology: From October to December 2020, comparative diagnostic evaluation of two methods of SARSCoV-2 RNA extraction methods was conducted on 159 fresh and 120 frozen nasopharyngeal and oropharyngeal specimens collected from travellers and suspected cases or contacts of COVID-19 patients in Burkina Faso. The FastPlexTM Triplex 1-Step COVID 19 Detection Kit (RT-PCR, RNA extraction free) (Precigenome LLC) was used to amplify on the same PCR plate, RNA extracts from manual QIAamp Viral RNA Mini Kit and automated KingFisher Flex Purification System 96 (ThermoFisher) using the QuantStudio5 thermal cycler (Applied Biosystems). Analysis of the diagnostic performance of the SARS-CoV-2 RT-PCR assay following RNA extraction by the two methods was done using an online OpenEpi software. Results: For fresh samples, the study found a slightly higher RT-PCR positivity rate following manual extraction (12.6%) than automated extraction (9.4%). For frozen samples, the positivity rate was far higher for manual (38.33%) than automated extraction method (20.83%). The results show that the performance of the automated extraction was inferior when compared to the manual extraction for both fresh samples (sensitivity 35%, specificity 94.2%) and frozen samples (sensitivity 43.5%, specificity 93.2%). However, using McNemar Chi-square with Yates correction, there was no significant difference in positivity rate of RT-PCR (x2=0.76, p=0.38) between the two extraction methods for the fresh samples, but there was a significant difference (x2=12.9, p= 0.0003) in the extraction of the frozen samples. Conclusion: The results of this study showed that KingFisher Flex Purification System 96 (ThermoFisher) automatic extraction method was less sensitive and specific than QIAamp Viral RNA Mini Kit (Qiagen) manual extraction method. This information can serve as guide to laboratories in the choice of RNA extraction methods to use for RT-PCR detection of SARS-CoV-2

Progress towards onchocerciasis elimination in the participating countries of the African Programme for Onchocerciasis Control: Epidemiological evaluation results

Background: The African Programme for Onchocerciasis Control (APOC) was created in 1995 to establish community-directed treatment with ivermectin (CDTi) in order to control onchocerciasis as a public health problem in 20 African countries that had 80 % of the global disease burden. When research showed that CDTi may ultimately eliminate onchocerciasis infection, APOC was given in 2008 the additional objective to determine when and where treatment can be safely stopped. We report the results of epidemiological evaluations undertaken from 2008 to 2014 to assess progress towards elimination in CDTi areas with ≥6 years treatment. Methods: Skin snip surveys were undertaken in samples of first-line villages to determine the prevalence of O. volvulus microfilariae. There were two evaluation phases. The decline in prevalence was evaluated in phase 1A. Observed and model-predicted prevalences were compared after correcting for endemicity level and treatment coverage. Bayesian statistics and Monte Carlo simulation were used to classify the decline in prevalence as faster than predicted, on track or delayed. Where the prevalence approached elimination levels, phase 1B was launched to determine if treatment could be safely stopped. Village sampling was extended to the whole CDTi area. Survey data were analysed within a Bayesian framework to determine if stopping criteria (overall prevalence <1.4 % and maximum stratum prevalence <5 %) were met. Results: In phase 1A 127 665 people from 639 villages in 54 areas were examined. The prevalence had fallen dramatically. The decline in prevalence was faster than predicted in 23 areas, on track in another 23 and delayed in eight areas. In phase 1B 108 636 people in 392 villages were examined in 22 areas of which 13 met the epidemiological criteria for stopping treatment. Overall, 32 areas (25.4 million people) had reached or were close to elimination, 18 areas (17.4 million) were on track but required more years treatment, and in eight areas (10.4 million) progress was unsatisfactory. Conclusions: Onchocerciasis has been largely controlled as a public health problem. Great progress has been made towards elimination which already appears to have been achieved for millions of people. For most APOC countries, nationwide onchocerciasis elimination is within reach

African Program for Onchocerciasis Control 1995–2010: Impact of Annual Ivermectin Mass Treatment on Off-Target Infectious Diseases

Since its initiation in 1995, the African Program for Onchocerciasis Control (APOC) has had a substantial impact on the prevalence and burden of onchocerciasis through annual ivermectin mass treatment. Ivermectin is a broad-spectrum anti-parasitic agent that also has an impact on other co-endemic parasitic infections. In this study, we roughly assessed the additional impact of APOC activities on the burden of the most important off-target infections: soil-transmitted helminthiases (STH; ascariasis, trichuriasis, hookworm, and strongyloidiasis), lymphatic filariasis (LF), and scabies. Based on a literature review, we formulated assumptions about the impact of ivermectin treatment on the disease burden of these off-target infections. Using data on the number of ivermectin treatments in APOC regions and the latest estimates of the burden of disease, we then calculated the impact of APOC activities on off-target infections in terms of disability-adjusted life years (DALYs) averted. We conservatively estimated that between 1995 and 2010, annual ivermectin mass treatment has cumulatively averted about 500 thousand DALYs from co-endemic STH infections, LF, and scabies. This impact comprised approximately an additional 5.5% relative to the total burden averted from onchocerciasis (8.9 million DALYs) and indicates that the overall cost-effectiveness of APOC is even higher than previously reported

Mapping the global distribution of Buruli ulcer through a systematic review with an evidence consensus approach

Background Buruli ulcer can cause disfigurement and long-term loss of function. It is underdiagnosed and under-reported, and its current distribution is unclear. We aimed to synthesise and evaluate data on Buruli ulcer prevalence and distribution. Methods We did a systematic review of Buruli ulcer prevalence and used an evidence consensus framework to describe and evaluate evidence for Buruli ulcer distribution worldwide. We searched PubMed and Web of Science databases from inception to Aug 6, 2018, for records of Buruli ulcer and Mycobacterium ulcerans detection, with no limits on study type, publication date, participant population, or location. English, French, and Spanish language publications were included. We included population-based surveys presenting Buruli ulcer prevalence estimates, or data that allowed prevalence to be estimated, in the systematic review. We extracted geographical data on the occurrence of Buruli ulcer cases and M ulcerans detection from studies of any type for the evidence consensus framework; articles that did not report original data were excluded. For the main analysis, we extracted prevalence estimates from included surveys and calculated 95% CIs using Byar's method. We included occurrence records, reports to WHO and the Global Infectious Diseases and Epidemiology Network, and surveillance data from Buruli ulcer control programmes in the evidence consensus framework to grade the strength of evidence for Buruli ulcer endemicity. This study is registered with PROSPERO, number CRD42018116260. Findings 2763 titles met the search criteria. We extracted prevalence estimates from ten studies and occurrence data from 208 studies and five unpublished surveillance datasets. Prevalence estimates within study areas ranged from 3·2 (95% CI 3·1–3·3) cases per 10 000 population in Côte d'Ivoire to 26·9 (23·5–30·7) cases per 10 000 population in Benin. There was evidence of Buruli ulcer in 32 countries and consensus on presence in 12. Interpretation The global distribution of Buruli ulcer is uncertain and potentially wider than currently recognised. Our findings represent the strongest available evidence on Buruli ulcer distribution so far and have many potential applications, from directing surveillance activities to informing burden estimates

Projected Number of People With Onchocerciasis-Loiasis Coinfection in Africa, 1995 to 2025

BACKGROUND: Onchocerciasis elimination through mass drug administration (MDA) is hampered by coendemicity of Loa loa, as people with high L. loa microfilariae (mf) density can develop serious adverse events (SAEs) after ivermectin treatment. We assessed the geographical overlap of onchocerciasis and loiasis prevalence and estimated the number of coinfected individuals at risk of post-ivermectin SAEs in West and Central Africa from 1995 to 2025. METHODS: Focusing on regions with suspected loiasis transmission in 14 countries, we overlaid precontrol maps of loiasis and onchocerciasis prevalence to calculate precontrol prevalence of coinfection by 5 km2 × 5 km2 pixel, distinguishing different categories of L. loa mf intensity. Using statistical and mathematical models, we predicted prevalence of both infections and coinfection for 2015 and 2025, accounting for the impact of MDA with ivermectin. RESULTS: The number of people infected with onchocerciasis was predicted to decline from almost 19 million in 1995 to 4 million in 2025. Of these, 137 000 people were estimated to also have L. loa hypermicrofilaremia (≥20 000 L. loa mf/mL) in 1995, declining to 31 000 in 2025. In 2025, 92.8% of coinfecte

Identifying co-endemic areas for major filarial infections in sub-Saharan Africa: seeking synergies and preventing severe adverse events during mass drug administration campaigns

BACKGROUND: Onchocerciasis and lymphatic filariasis (LF) are major filarial infections targeted for elimination in most endemic sub-Saharan Africa (SSA) countries by 2020/2025. The current control strategies are built upon community-directed mass administration of ivermectin (CDTI) for onchocerciasis, and ivermectin plus albendazole for LF, with evidence pointing towards the potential for novel drug regimens. When distributing microfilaricides however, considerable care is needed to minimise the risk of severe adverse events (SAEs) in areas that are co-endemic for onchocerciasis or LF and loiasis. This work aims to combine previously published predictive risk maps for onchocerciasis, LF and loiasis to (i) explore the scale of spatial heterogeneity in co-distributions, (ii) delineate target populations for different treatment strategies, and (iii) quantify populations at risk of SAEs across the continent. METHODS: Geographical co-endemicity of filarial infections prior to the implementation of large-scale mass treatment interventions was analysed by combining a contemporary LF endemicity map with predictive prevalence maps of onchocerciasis and loiasis. Potential treatment strategies were geographically delineated according to the level of co-endemicity and estimated transmission intensity. RESULTS: In total, an estimated 251 million people live in areas of LF and/or onchocerciasis transmission in SSA, based on 2015 population estimates. Of these, 96 million live in areas co-endemic for both LF and onchocerciasis, providing opportunities for integrated control programmes, and 83 million live in LF-monoendemic areas potentially targetable for the novel ivermectin-diethylcarbamazine-albendazole (IDA) triple therapy. Only 4% of the at-risk population live in areas co-endemic with high loiasis transmission, representing up to 1.2 million individuals at high risk of experiencing SAEs if treated with ivermectin. In these areas, alternative treatment strategies should be explored, including biannual albendazole monotherapy for LF (1.4 million individuals) and 'test-and-treat' strategies (8.7 million individuals) for onchocerciasis. CONCLUSIONS: These maps are intended to initiate discussion around the potential for tailored treatment strategies, and highlight populations at risk of SAEs. Further work is required to test and refine strategies in programmatic settings, providing the empirical evidence needed to guide efforts towards the 2020/2025 goals and beyond

Atypical Clinical Manifestations of Loiasis and Their Relevance for Endemic Populations

Background: Loiasis is mostly considered a relatively benign infection when compared with other filarial and parasitic diseases, with Calabar swellings and eyeworm being the most common signs. Yet, there are numerous reports in the literature of more serious sequelae. Establishing the relationship between infection and disease is a crucial first step toward estimating the burden of loiasis. Methods: We conducted a systematic review of case reports containing 329 individuals and detailing clinical manifestations of loiasis with a focus on nonclassical, atypical presentations. Results: Results indicate a high proportion (47%) of atypical presentations in the case reports identified, encompassing a wide range of cardiac, respiratory, gastrointestinal, renal, neurological, ophthalmological, and dermatological pathologies. Individuals with high microfilarial densities and residing in an endemic country were at greater risk of suffering from atypical manifestations. Conclusions: Our findings have important implications for understanding the clinical spectrum of conditions associated with Loa loa infection, which extends well beyond the classical eyeworm and Calabar swellings. As case reports may overestimate the true rate of atypical manifestations in endemic populations, large-scale, longitudinal clinico-epidemiological studies will be required to refine our estimates and demonstrate causality between loiasis and the breadth of clinical manifestations reported. Even if the rates of atypical presentations were found to be lower, given that residents of loiasis-endemic areas are both numerous and the group most at risk of severe atypical manifestations, our conclusions support the recognition of loiasis as a significant public health burden across Central Africa