Can mass drug administration of moxidectin accelerate onchocerciasis elimination in Africa?

Epidemiological and modelling studies suggest that elimination of Onchocerca volvulus transmission (EoT) throughout Africa may not be achievable with annual mass drug administration (MDA) of ivermectin alone, particularly in areas of high endemicity and vector density. Single-dose Phase II and III clinical trials demonstrated moxidectin's superiority over ivermectin for prolonged clearance of O. volvulus microfilariae. We used the stochastic, individual-based EPIONCHO-IBM model to compare the probabilities of reaching EoT between ivermectin and moxidectin MDA for a range of endemicity levels (30 to 70% baseline microfilarial prevalence), treatment frequencies (annual and biannual) and therapeutic coverage/adherence values (65 and 80% of total population, with, respectively, 5 and 1% of systematic non-adherence). EPIONCHO-IBM's projections indicate that biannual (six-monthly) moxidectin MDA can reduce by half the number of years necessary to achieve EoT in mesoendemic areas and might be the only strategy that can achieve EoT in hyperendemic areas. Data needed to improve modelling projections include (i) the effect of repeated annual and biannual moxidectin treatment; (ii) inter- and intra-individual variation in response to successive treatments with moxidectin or ivermectin; (iii) the effect of moxidectin and ivermectin treatment on L3 development into adult worms; and (iv) patterns of adherence to moxidectin and ivermectin MDA. This article is part of the theme issue 'Challenges in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.

Effect of onchocerciasis elimination measures on the incidence of epilepsy in Maridi, South Sudan: a 3-year longitudinal, prospective, population-based study.

BACKGROUND: High onchocerciasis transmission predisposes endemic communities to a high epilepsy burden. The 4·4% epilepsy prevalence documented in 2018 in Maridi, South Sudan, prompted the strengthening of onchocerciasis elimination measures. Community-directed treatment with ivermectin was implemented annually in 2017, 2018, and 2019, interrupted in 2020, and re-implemented biannually in 2021. We aimed to assess the effect of these interventions, along with slash and clear vector control on the incidence of epilepsy, including nodding syndrome. METHODS: In this longitudinal, prospective, population-based study, we did a two-stage house-to-house epilepsy survey before (May 10-30, 2018) and after (March 9-19, 2022) the strengthening of onchocerciasis elimination interventions in South Sudan. Strengthening also included the implementation of a community-based slash and clear vector control method that we initiated in 2019 at the Maridi dam (the main blackfly breeding site). Eight sites were surveyed near the Maridi dam and inclusion required residence in one of these sites. All household residents were first screened by community workers, followed by confirmation of the epilepsy diagnosis by trained clinicians. The primary outcome was epilepsy incidence, including nodding syndrome, which was assessed via self-reported new-onset epilepsy in the previous 4 years of each survey, confirmed by clinician assessment. FINDINGS: The preintervention survey included 17 652 people of whom 736 had epilepsy (315 female and 421 male), and the post-intervention survey included 14 402 people of whom 586 had epilepsy (275 female and 311 male). When biannual community-directed treatment with ivermectin was initiated in 2021, the intervention's coverage rose by 15·7% (95% CI 14·6-16·8); although only 56·6% of the population took ivermectin in 2021. Between 2018 and 2022, epilepsy incidence decreased from 348·8 (307·2-395·8) to 41·7 (22·6-75·0) per 100 000 person-years. Similarly, the incidence of nodding syndrome decreased from 154·7 (127·6-187·3) to 10·4 (2·7-33·2) per 100 000 person-years. The identified risk factors for epilepsy were: living closer to the Maridi dam, being aged between 6 and 40 years, not taking ivermectin, and being male. INTERPRETATION: In onchocerciasis-endemic areas with high epilepsy prevalence, strengthening onchocerciasis elimination interventions can decrease the incidence of epilepsy, including nodding syndrome. Additional efforts are needed to increase community-directed treatment with ivermectin coverage and sustain blackfly control in Maridi. FUNDING: Research for Health in Humanitarian Crisis, European Research Council, Research Foundation-Flanders, Research Foundation-Flanders, the Italian Agency for Development Cooperation, and La Caixa Foundation.

Preliminary assessment of Onchocerca-induced visual impairment using clinical fundus camera in Gashaka local government area of Taraba state, north eastern Nigeria.

Introduction: Onchocerciasis is the world's second leading cause of infectious blindness and remains a major problem in parts of Africa. In light of the efforts targeted towards improving ongoing elimination program, this study assessed onchocerca-induced visual impairments in Gashaka local government areas (LGA) in Taraba State, north-eastern Nigeria. Methods: In 2019, we recruited 158 consenting visually impaired persons across three communities in Garbabi ward of Gashaka LGA. To avoid confusion with co-endemic trachoma, the integrity of the tarsal conjunctiva, eyelashes were assessed using direct light. The anterior segment of the eye was also examined using a torchlight with oblique illumination. However, the posterior segment of the eye was assessed using a fundus camera. Two photographic images for the left and right eye of each participant were captured using the clinical fundus camera. The photographic eye images that were too dark were discarded, and only clear images were analyzed by two ophthalmologists. An ocular manifestation report was recorded for each participant following consensus between the ophthalmologists. Results: Of the 316 photographic eye images, almost half 146 (46.2%) from 73 participants were just too destroyed for light to penetrate and was not included in the analysis. Only 170 from 85 participants were clear and examinable. A total of 33 (39%) participants had chorioretinitis suggestive of onchocerciasis, including 22(25.9%) with chorio-retinal atrophy, 7(8.2%) and 4(4.7%) had chorioretinal atrophy in combination with early cataract and signs of trachoma respectively. In addition, 3(3.5%) of the participant had eye images which showed lens opacities, 1(1.2%) showed signs of keratoconus and 1(1.2%) showed a scared and pigmented cornea, possibly due to onchocerciasis. Furthermore, 28 (32.9%) had some ill-defined changes and 19 (22.4%) showed poorly defined chorio-retinal atrophy. Conclusion: In a bid to sustain MDA gains towards elimination of onchocerciasis, this work highlights the need for continuous assessment of onchocerciasis induced visual impairment, strengthening of ivermectin delivery and optimizing compliance and patient care among affected populations. These would require resource acquisition and local capacity building. Our preliminary findings call for further operational research on ocular morbidity as well as future stakeholders' consultations in this important and understudied area.

Social, Educational and Medical Aspects after Cataract Surgery of Bilaterally Blind Children in Kinshasa-Perception of Parents and Children.

The study investigated the influence of bilateral cataract surgery on the social and educational development of previously bilaterally blind children in Sub-Saharan Africa (SSA), where the prevalence of blindness due to cataract is higher than in high-income countries. The views of both, parents and children, were evaluated with structured interviews based on a newly developed questionnaire related to surgery, follow-up, and family life after surgery. The mean age of the children at interview was 14.4 ± 8.1 years, with 27 females and 26 males. Satisfaction with the outcome of the surgery was reported by 91% of parents. Parents would recommend surgery, because of the children being happy and able to act more independently, with personal, educational and familial factors essentially contributing to the reported satisfaction. The results also showed that 85.0% of children did not wear eyeglasses. Reasons given were mainly cost-related, but also included limited communication between families and health institutions. Providing and maintaining a high-quality and accessible pediatric cataract surgery and healthcare service for follow-up is a major requisite to reduce childhood blindness in SSA. Our study proved the necessity and effectiveness of a community-based rehabilitation program that cares about each individual child, whatever his or her social background.

Ophthalmic Ultrasonography in Sub-Saharan Africa-A Kinshasa Experience.

The aim of this study was to analyze the use of the diagnostic B-scan ultrasound. Should it be made accessible to all surgical centers in Sub-Saharan Africa in order to (i) avoid unnecessary cataract surgery and (ii) evaluate extraocular pathology? This study was conducted in Kinshasa from 2006 to 2019. Three hundred and twenty-three patients were included and separated into two groups. Group 1 included 262 patients with dense cataract. Group 2 consisted of 61 patients with pathologies of the ocular adnexa, and all were examined with a B-scan ultrasound. In group 1, there were 437 systematically screened eyes. Three hundred and ninety-eight eyes (91.08%) showed no abnormalities, 13 (2.97%) retinal detachments were identified, and 15 (3.43%) demonstrated a detached posterior hyaloid membrane. In the second group, 61 patients were examined (group 2). In 20 of them, surgery was performed for biopsy, tumor excision, mucoceles drainage, and palliative treatment. The need for routine B-scan examinations in dense cataract patients seems to be limited and can most likely be replaced by a thorough application of locally available examination techniques. B-scan application is recommended to manage orbital patients in the most cost-effective way.

Predictive value of retinal function by the Purkinje test in patients scheduled for cataract surgery in Kinshasa, DR Congo.

AIM: To assess the retinal function in patients with dense cataracts in resource poor settings in Kinshasa, DR Congo. METHODS: In a tertiary eye care center, the Purkinje entoptic test was performed as part of the ophthalmological examination in 98 eyes in patients with cataract, using a penlight. Totally 92 cataract patients including 86 patients suffered from unilateral and 6 from bilateral cataracts were included in the study. The investigator asked the patients about their perception of the vascular pattern most commonly described as a leafless or dead tree. Visual acuity≥6/60 was considered an indication of good visual function and visual acuity<6/60 of poor function. Following small incision cataract surgery, best corrected visual acuity (BCVA) was determined and compared with the preoperative findings. RESULTS: Out of 98 eyes, there were 80 (81.6%) where the Purkinje entoptic phenomenon was reported by the patients. After cataract surgery, out of the 80 eyes, there were 75 (93.8%) with a BCVA of better than 6/60, whereas in 5 eyes (6.2%), BCVA was 6/60 or less. Out of the 18 eyes (18.4%) where no Purkinje tree was recognized, there were 14 (77.8%) with BCVA of better than 6/60, whereas in 4 (22.2%) BCVA was 6/60 or less. CONCLUSION: The Purkinje entoptic test is successfully used for preoperative assessment of retinal function in patients with dense cataract. However, further investigation and refinement of the test is necessary to validate the method for use in sub-Saharan conditions.

Ocular Morbidity-A Critical Analysis to Improve Outpatient Services in an Eye Department in a Sub-Saharan Megacity.

The aim of this study was to analyse outpatient services in an ophthalmic clinic of a church-run hospital providing secondary level care in an African megacity, paying special attention to the poorest users of the services. The range of examination was reviewed from 500 patient records of all ages consecutively chosen on random days attending the outpatient department for the first time in order to optimize workflow and to analyse the offered treatment modalities. Mean age was 41.9 ± 21.9 years, and 53.6% of the patients were female. Of the patients, 74.8% presented with visual impairment. The most frequent findings were refractive errors (35.8%), presbyopia (21.2%), allergic conjunctivitis (14.0%), cataract (13.2%) and glaucoma (6.4%). Patient management consisted of optical treatment (49.6%), surgery (11.4%) and medical treatment (39.0%). These results show the importance of the demand in refractive services and the need to train specific service providers. Knowing the frequencies of common conditions enables more appropriate diagnostic and treatment strategies, e.g., the importance of refractive errors, and should lead to improvements in training, staffing, therapeutics and patient outcomes. This approach can be applied to many other outpatient services and should be evaluated in light of the city's impoverished health outreach and educational situation.

A framework for scabies control.

Scabies is a neglected tropical disease (NTD) that causes a significant health burden, particularly in disadvantaged communities and where there is overcrowding. There is emerging evidence that ivermectin-based mass drug administration (MDA) can reduce the prevalence of scabies in some settings, but evidence remains limited, and there are no formal guidelines to inform control efforts. An informal World Health Organization (WHO) consultation was organized to find agreement on strategies for global control. The consultation resulted in a framework for scabies control and recommendations for mapping of disease burden, delivery of interventions, and establishing monitoring and evaluation. Key operational research priorities were identified. This framework will allow countries to set control targets for scabies as part of national NTD strategic plans and develop control strategies using MDA for high-prevalence regions and outbreak situations. As further evidence and experience are collected and strategies are refined over time, formal guidelines can be developed. The control of scabies and the reduction of the health burden of scabies and associated conditions will be vital to achieving the targets set in WHO Roadmap for NTDs for 2021 to 2030 and the Sustainable Development Goals.

Medicine donation programmes supporting the global drive to end the burden of neglected tropical diseases.

Neglected tropical diseases (NTDs) are targeted for global control or elimination. Recognising that the populations most in need of medicines to target NTDs are those least able to support and sustain them financially, the pharmaceutical industry created mechanisms for donating medicines and expertise to affected countries through partnerships with the WHO, development agencies, non-governmental organisations and philanthropic donors. In the last 30 y, companies have established programmes to donate 17 different medicines to overcome the burden of NTDs. Billions of tablets, capsules, intravenous and oral solutions have been donated, along with the manufacturing, supply chains and research necessary to support these efforts. Industry engagement has stimulated other donors to support NTDs with funds and oversight so that the 'heath benefit' return on investment in these programmes is truly a 'best value in public health'. Many current donations are 'open-ended', promising support as long as necessary to achieve defined health targets. Extraordinary global health advances have been made in filariasis, onchocerciasis, trachoma, trypanosomiasis, leishmaniasis, schistosomiasis, intestinal parasites and others; and these advances are taking place in the context of strengthening health systems and meeting the global development goals espoused by the WHO. The pharmaceutical manufacturers, already strong collaborators in initiating or supporting these disease-targeted programmes, have committed to continuing their partnership roles in striving to meet the targets of the WHO's new NTD roadmap to 2030.

Onchocerca volvulus and epilepsy: A comprehensive review using the Bradford Hill criteria for causation.

BACKGROUND: The possibility that onchocerciasis may cause epilepsy has been suggested for a long time, but thus far, an etiological link has not been universally accepted. The objective of this review is to critically appraise the relationship between Onchocerca volvulus and epilepsy and subsequently apply the Bradford Hill criteria to further evaluate the likelihood of a causal association. METHODS: PubMed and gray literature published until September 15, 2020, were searched and findings from original research were synthesized. Adherence to the 9 Bradford Hill criteria in the context of onchocerciasis and epilepsy was determined to assess whether the criteria are met to strengthen the evidence base for a causal link between infection with O. volvulus and epilepsy, including the nodding syndrome. RESULTS: Onchocerciasis as a risk factor for epilepsy meets the following Bradford Hill criteria for causality: strength of the association, consistency, temporality, and biological gradient. There is weaker evidence supporting causality based on the specificity, plausibility, coherence, and analogy criteria. There is little experimental evidence. Considering the Bradford Hill criteria, available data suggest that under certain conditions (high microfilarial load, timing of infection, and perhaps genetic predisposition), onchocerciasis is likely to cause epilepsy including nodding and Nakalanga syndromes. CONCLUSION: Applying the Bradford Hill criteria suggests consistent epidemiological evidence that O. volvulus infection is a trigger of epilepsy. However, the pathophysiological mechanisms responsible for seizure induction still need to be elucidated.

What does the COVID-19 pandemic mean for the next decade of onchocerciasis control and elimination?

BACKGROUND: Mass drug administration (MDA) of ivermectin for onchocerciasis has been disrupted by the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modelling can help predict how missed/delayed MDA will affect short-term epidemiological trends and elimination prospects by 2030. METHODS: Two onchocerciasis transmission models (EPIONCHO-IBM and ONCHOSIM) are used to simulate microfilarial prevalence trends, elimination probabilities and age profiles of Onchocerca volvulus microfilarial prevalence and intensity for different treatment histories and transmission settings, assuming no interruption, a 1-y (2020) interruption or a 2-y (2020-2021) interruption. Biannual MDA or increased coverage upon MDA resumption are investigated as remedial strategies. RESULTS: Programmes with shorter MDA histories and settings with high pre-intervention endemicity will be the most affected. Biannual MDA is more effective than increasing coverage for mitigating COVID-19's impact on MDA. Programmes that had already switched to biannual MDA should be minimally affected. In high-transmission settings with short treatment history, a 2-y interruption could lead to increased microfilarial load in children (EPIONCHO-IBM) and adults (ONCHOSIM). CONCLUSIONS: Programmes with shorter (annual MDA) treatment histories should be prioritised for remedial biannual MDA. Increases in microfilarial load could have short- and long-term morbidity and mortality repercussions. These results can guide decision-making to mitigate the impact of COVID-19 on onchocerciasis elimination.

Cataract surgery in Kinshasa-Is there a place for "Monovision"?

OBJECTIVES: Monovision is a method of correcting presbyopia where one eye is focused for far and the other for near vision. It is a simple, cost-effective approach to overcome the loss of accommodation with age and to become spectacles independent. METHODOLOGY: About 50 patients, where bilateral cataract extraction was indicated, were included in this study performed at the St. Joseph's Eye Hospital in Kinshasa (DR Congo). Small incision cataract surgery technique (SICS) was applied with the implantation of 6 mm PMMA lenses in the capsular bag. IOL refractive power choice was made to achieve a post-operative refraction of -0.5 dpt for the eye selected for far vision. The second eye received an implant heading for a post-operative myopia of -1.5 dpt suitable for intermediated and near vision. According to the literature, monovision criteria have been regarded as fulfilled when (a) far vision was 0.5 (logMAR) or better and (b) near vision was P3 (0.40, Decimal 32 cm) or better. Spectacle dependence after bilateral cataract surgery heading for monovision was analysed using a dedicated questionnaire. RESULTS: Out of all 50 patients 22 (44%) fulfilled the above defined criteria of monovision in terms of post-operative refraction and visual acuity. About 19 out of these 22 (86.3%) patients were happy without glasses. Two of them used bifocal spectacles, whereas the remaining patient refused spectacles. About 28 patients did not fulfill monovision criteria. Out of these 28 patients, however, 9 (32.1%) of them are happy without glasses. CONCLUSION: In view of the described local circumstances aiming for monovision after bilateral cataract surgery is a suitable approach to optimise cataract surgical outcomes with no extra costs for surgery but considerable improvement of patient's visual performance in daily life.

Bilateral paediatric cataract surgery - outcomes of 298 children from Kinshasa, the Democratic Republic of the Congo.

INTRODUCTION: The leading cause of childhood blindness globally is paediatric cataract. Bilateral cataract surgery can help to improve visual performance and to diminish the burden of childhood blindness. OBJECTIVE: To report in a retrospective observational cohort study the long-term outcomes of 298 children who had bilateral cataract surgery with IOL implantation from 2001-2016 in Kinshasa. METHODS: A standardized surgical treatment of paediatric cataract was practiced on 298 children. Patient's follow-up, complications, and visual outcomes were recorded and analysed. RESULTS: The mean age was 5.7 ± 4.3 years and males were predominant (64.9%). Most of children were living mainly in urban poorest areas (96.3%). Strabismus, nystagmus and microcornea were encountered in 20.1%, 25.1% and 8.7% of children, respectively. Using WHO criteria most of patients were classified as blind preoperatively and 81.9% of them had improved visual outcomes after surgery. Main reasons for reduced vision during follow-up were secondary cataract (5.7%), IOL decentration (1.2%), retinal detachment (1.2%), and secondary glaucoma (1.5%). CONCLUSION: In spite of the post conflict challenges, elimination of cataract blindness in children remains a priority. Children present at a late age for surgery and long term follow-up is poor. There is need for program strengthening in these areas.

Elimination of onchocerciasis in Africa by 2025: an ambitious target requires ambitious interventions.

To achieve the elimination of onchocerciasis transmission in all African countries will entail enormous challenges, as has been highlighted by the active discussion around onchocerciasis intervention strategies and evaluation procedures in this journal.Serological thresholds for onchocerciasis elimination, adapted for the African setting, need to be established. The Onchocerciasis Technical Advisory Subgroup of the World Health Organization is currently developing improved guidelines to allow country elimination committees to make evidence-based decisions. Importantly, onchocerciasis-related morbidity should not be forgotten when debating elimination prospects. A morbidity management and disease prevention (MMDP) strategy similar to that for lymphatic filariasis will need to be developed. This will require collaboration between the onchocerciasis elimination program, the community and other partners including primary health and mental health programs.In order to reach the goal of onchocerciasis elimination in most African countries by 2025, we should prioritize community participation and advocate for tailored interventions which are scientifically proven to be effective, but currently considered to be too expensive.

Role of a Community-based Program for Identification and Referral of Pediatric Cataract Patients in Kinshasa, Democratic Republic of the Congo.

PURPOSE: The purpose of this study is to describe the methodology and to assess the effectiveness of a community-based rehabilitation (CBR) program to identify and refer children with blinding cataract for the management and surgery to reduce the burden of childhood blindness due to cataract in Kinshasa. METHODS: Church-based volunteers were trained to identify children with presumed eye disorders in their localities and households and to refer them for cataract identification by an ophthalmic nurse during parishes' visits. Volunteers were parishioners living in the quartiers where identification took place and worked as community workers with the CBR program. Nurses used a lamp-torch to rule out cataract. Selected children were referred to the tertiary eye health facility at St Joseph Hospital for diagnosis and management. RESULTS: Identification took place in 31 out of 165 parishes in the Archdioceses of Kinshasa from 2000 to 2016 and 11,106 children aged <16 years were screened. Among them, 1277 children (11.5%) were presumed to have cataract. Ninety-two children among them died before surgery; 107 children were lost to further follow-up and did not report to the CBR center for referral. Reasons given were change of home address, moving in their lieu of origin, death, and refusal of treatment by the parents. Finally, only 1078 children were referred to the pediatric ophthalmologist and 705 children (65.4%) were definitively diagnosed to have treatable cataract, while in 373 children (34.6%), cataract surgery was not indicated for several reasons. There was a positive history of familial cataract in 36 children (2.8%). CONCLUSION: Using church-based volunteers and ophthalmic nurses during community screening proved efficient in the identification and referral of pediatric cataract. Keeping regular identification activities in the community and maintaining high-quality and accessible pediatric cataract surgery services can help to clear up the backlog of cataract blind children.

Valuing the Unpaid Contribution of Community Health Volunteers to Mass Drug Administration Programs.

Community health volunteers (CHVs) are being used within a growing number of healthcare interventions, and they have become a cornerstone for the delivery of mass drug administration within many neglected tropical disease control programs. However, a greater understanding of the methods used to value the unpaid time CHVs contribute to healthcare programs is needed. We outline the two main approaches used to value CHVs' unpaid time (the opportunity cost and the replacement cost approaches). We found that for mass drug administration programs the estimates of the economic costs relating to the CHVs' unpaid time can be significant, with the averages of the different studies varying between US$0.05 and $0.16 per treatment. We estimated that the time donated by CHVs' to the African Programme for Onchocerciasis Control alone would be valued between US$60 and $90 million. There is a need for greater transparency and consistency in the methods used to value CHVs' unpaid time.

A Serological Survey of Human Onchocerciasis in Yemen.

Yemen is a country that has been treating severe cases of oncho-dermatitis since 1992 and is now moving to a program aimed at the elimination of the transmission of Onchocerca volvulus. It is important to ensure that the currently acceptable tools used in epidemiological assessment of onchocerciasis in Africa and Latin America also apply to Yemen. Five hundred and ten blood samples from three known O. volvulus-endemic areas, locations that have never been under a mass treatment program, were tested for the presence of antibodies against a panel of O. volvulus-specific antigens using enzyme-linked immunosorbent assay (Ov16) and luciferase immunoprecipitation system (Ov-FAR-1 and Ov-MSA-1) assays. Overall, 31.4% of the samples tested were positive, with positivity increasing with age. Positivity was seen in 76.5% of those presenting with clinical onchocerciasis but importantly also in more than 28.5% of those defined as free of oncho-dermatitis; these latter individuals are likely to be serving as a source for persistent reinfection. This study supports the use of the current O. volvulus-specific serologic methodology in Yemen.