A global call for action to tackle skin-related neglected tropical diseases (skin NTDs) through integration: An ambitious step change.

On 8 June 2022, the World Health Organization (WHO) released pivotal guidance, "Ending the neglect to attain the Sustainable Development Goals: A strategic framework for integrated control and management of skin-related neglected tropical diseases." Skin-related neglected tropical diseases, or skin NTDs, comprise a group of NTDs that produce signs and symptoms on the skin and include at least 9 diseases or disease groups. Moving away from disease-specific approaches, it is anticipated that synergies will be identified and integrated building on this shared feature, where possible, to achieve a greater health impact. This paper intends to draw attention to the prospects created by this scheme. The framework is a key basis for a proposal produced by WHO dedicated to skin NTD integration and describes the practical opportunities for this evolving strategy. It underlines the wider health benefits that will follow, thus working towards Universal Health Coverage and skin health for all.

The burden of skin disease and eye disease due to onchocerciasis in countries formerly under the African Programme for Onchocerciasis Control mandate for 1990, 2020, and 2030.

BACKGROUND: Onchocerciasis ("river blindness") can cause severe morbidity, including vision loss and various skin manifestations, and is targeted for elimination using ivermectin mass drug administration (MDA). We calculated the number of people with Onchocerca volvulus infection and onchocercal skin and eye disease as well as disability-adjusted life years (DALYs) lost from 1990 through to 2030 in areas formerly covered by the African Programme for Onchocerciasis Control. METHODS: Per MDA implementation unit, we collated data on the pre-control distribution of microfilariae (mf) prevalence and the history of control. Next, we predicted trends in infection and morbidity over time using the ONCHOSIM simulation model. DALY estimates were calculated using disability weights from the Global Burden of Disease Study. RESULTS: In 1990, prior to MDA implementation, the total population at risk was 79.8 million with 26.0 million (32.5%) mf-positive individuals, of whom 17.5 million (21.9%) had some form of onchocercal skin or eye disease (2.5 million DALYs lost). By 2030, the total population was predicted to increase to 236.1 million, while the number of mf-positive cases (about 6.8 million, 2.9%), people with skin or eye morbidity (4.2 million, 1.8%), and DALYs lost (0.7 million) were predicted to decline. CONCLUSIONS: MDA has had a remarkable impact on the onchocerciasis burden in countries previously under the APOC mandate. In the few countries where we predict continued transmission between now and 2030, intensified MDA could be combined with local vector control efforts, or the introduction of new drugs for mopping up residual cases of infection and morbidity.

How does onchocerciasis-related skin and eye disease in Africa depend on cumulative exposure to infection and mass treatment?

BACKGROUND: Onchocerciasis (river-blindness) in Africa is targeted for elimination through mass drug administration (MDA) with ivermectin. Onchocerciasis may cause various types of skin and eye disease. Predicting the impact of MDA on onchocercal morbidity is useful for future policy development. Here, we introduce a new disease module within the established ONCHOSIM model to predict trends over time in prevalence of onchocercal morbidity. METHODS: We developed novel generic model concepts for development of symptoms due to cumulative exposure to dead microfilariae, accommodating both reversible (acute) and irreversible (chronic) symptoms. The model was calibrated to reproduce pre-control age patterns and associations between prevalences of infection, eye disease, and various types of skin disease as observed in a large set of population-based studies. We then used the new disease module to predict the impact of MDA on morbidity prevalence over a 30-year time frame for various scenarios. RESULTS: ONCHOSIM reproduced observed age-patterns in disease and community-level associations between infection and disease reasonably well. For highly endemic settings with 30 years of annual MDA at 60% coverage, the model predicted a 70% to 89% reduction in prevalence of chronic morbidity. This relative decline was similar with higher MDA coverage and only somewhat higher for settings with lower pre-control endemicity. The decline in prevalence was lowest for mild depigmentation and visual impairment. The prevalence of acute clinical manifestations (severe itch, reactive skin disease) declined by 95% to 100% after 30 years of annual MDA, regardless of pre-control endemicity. CONCLUSION: We present generic model concepts for predicting trends in acute and chronic symptoms due to history of exposure to parasitic worm infections, and apply this to onchocerciasis. Our predictions suggest that onchocercal morbidity, in particular chronic manifestations, will remain a public health concern in many epidemiological settings in Africa, even after 30 years of MDA.

Implementation of test-and-treat with doxycycline and temephos ground larviciding as alternative strategies for accelerating onchocerciasis elimination in an area of loiasis co-endemicity: the COUNTDOWN consortium multi-disciplinary study protocol.

BACKGROUND: Onchocerciasis is a priority neglected tropical disease targeted for elimination by 2025. The standard strategy to combat onchocerciasis is annual Community-Directed Treatment with ivermectin (CDTi). Yet, high prevalence rates and transmission persist following > 12 rounds in South-West Cameroon. Challenges include programme coverage, adherence to, and acceptability of ivermectin in an area of Loa loa co-endemicity. Loiasis patients harbouring heavy infections are at risk of potentially fatal serious adverse events following CDTi. Alternative strategies are therefore needed to achieve onchocerciasis elimination where CDTi effectiveness is suboptimal. METHODS/DESIGN: We designed an implementation study to evaluate integrating World Health Organisation-endorsed alternative strategies for the elimination of onchocerciasis, namely test-and-treat with the macrofilaricide, doxycycline (TTd), and ground larviciding for suppression of blackfly vectors with the organophosphate temephos. A community-based controlled before-after intervention study will be conducted among > 2000 participants in 20 intervention (Meme River Basin) and 10 control (Indian River Basin) communities. The primary outcome measure is O. volvulus prevalence at follow-up 18-months post-treatment. The study involves four inter-disciplinary components: parasitology, entomology, applied social sciences and health economics. Onchocerciasis skin infection will be diagnosed by skin biopsy and Loa loa infection will be diagnosed by parasitological examination of finger-prick blood samples. A simultaneous clinical skin disease assessment will be made. Eligible skin-snip-positive individuals will be offered directly-observed treatment for 5 weeks with 100 mg/day doxycycline. Transmission assessments of onchocerciasis in the communities will be collected post-human landing catch of the local biting blackfly vector prior to ground larviciding with temephos every week (0.3 l/m3) until biting rate falls below 5/person/day. Qualitative research, including in-depth interviews and focus-group discussions will be used to assess acceptability and feasibility of the implemented alternative strategies among intervention recipients and providers. Health economics will assess the cost-effectiveness of the implemented interventions. CONCLUSIONS: Using a multidisciplinary approach, we aim to assess the effectiveness of TTd, alone or in combination with ground larviciding, following a single intervention round and scrutinise the acceptability and feasibility of implementing at scale in similar hotspots of onchocerciasis infection, to accelerate onchocerciasis elimination.

Onchodermatitis: Where Are We Now?

Onchocerciasis causes debilitating pruritus and rashes as well as visual impairment and blindness. Prior to control measures, eye disease was particularly prominent in savanna areas of sub-Saharan Africa whilst skin disease was more common across rainforest regions of tropical Africa. Mass drug distribution with ivermectin is changing the global scene of onchocerciasis. There has been successful progressive elimination in Central and Southern American countries and the World Health Organization has set a target for elimination in Africa of 2025. This literature review was conducted to examine progress regarding onchocercal skin disease. PubMed searches were performed using keywords 'onchocerciasis', 'onchodermatitis' and 'onchocercal skin disease' over the past eight years. Articles in English, or with an English abstract, were assessed for relevance, including any pertinent references within the articles. Recent progress in awareness of, understanding and treatment of onchocercal skin disease is reviewed with particular emphasis on publications within the past five years. The global burden of onchodermatitis is progressively reducing and is no longer seen in children in many formerly endemic foci.

Pre-control relationship of onchocercal skin disease with onchocercal infection in Guinea Savanna, Northern Nigeria.

BACKGROUND: Onchocerca volvulus infection can result in blindness, itching and skin lesions. Previous research concentrated on blindness. METHODS: A clinical classification system of the cutaneous changes in onchocerciasis was used for the first time in this study within the context of an early ivermectin drug trial in the savanna region of Kaduna State, northern Nigeria. Skin examinations were performed in 6,790 individuals aged 5+ years in endemic communities and 1,343 individuals in nonendemic communities. RESULTS / DISCUSSION: There was increased risk for all forms of onchocercal skin disease in endemic communities with the most common finding being the presence of nodules (1,438 individuals, 21.2%), followed by atrophy (367, 6.1% of those < 50 years), acute papular onchodermatitis, APOD (233, 3.4%), depigmentation (216, 3.2%) and chronic papular onchodermatitis, CPOD (155, 2.3%). A further 645 individuals (9.5%) complained of pruritus but had completely normal skin. APOD was more common in males whereas atrophy, hanging groin and nodules were more common in females. After controlling for age and sex, microfilarial positivity was a risk factor for CPOD, depigmentation, hanging groin and nodules (OR 1.54, p = 0.046; OR 2.29, p = 0.002; OR 2.18, p = 0.002 and OR 3.80, p <0.001 respectively). Comparable results were found using presence of nodules as the marker for infection. Microfilarial load showed similar, though weaker, results. A total of 2621(38.6%) endemic residents had itching with normal skin, or had one or more types of onchocercal skin disease including nodules, which may be considered as a composite index of the overall prevalence of onchocercal skin disease. CONCLUSION: Significant levels of onchocercal skin disease were documented in this savanna area, which subsequently resulted in a reassessment of the true burden of skin disease in onchocerciasis. This paper represents the first detailed report of the association of onchocercal skin disease with markers for onchocercal infection.

Onchocerciasis in the Democratic Republic of Congo: Survey of knowledge, attitude and perception in Bandundu province.

A community-directed treatment with ivermectin (CDTI) for fighting onchocerciasis was started in 2003 in the hyperendemic province of Bandundu, Democratic Republic of Congo (DRC); such initiative was supported by the African Programme for Onchocerciasis Control (APOC). As the APOC stopped at the end of 2015, there was an urgent need to assess the sustainability of an ivermectin treatment. A cross-sectional survey of knowledge, attitude and perception was conducted to determine the awareness level of local population regarding the disease. A multi-stage random sampling technique allowed the selection of 450 heads of households. Most respondents (96.9%) knew about onchocerciasis as a disease. The black-fly was viewed as the causing agent of onchocerciasis by 49.9% of respondents. The most commonly cited clinical manifestations were nodules (34.4%) and pruritus (31.1%), while blindness was the most frequently reported complication (90.7%). Approximately 55.1% of respondents had a good knowledge of onchocerciasis and CDTI. Overall, only 37% of participants had a favourable attitude and 46% a positive perception. Good knowledge was associated with school attendance (adjusted OR=1.9, 95%CI: 1.3-2.8, p=0.001), while education and continuation of treatment were related with good attitude (adjusted OR=9.7, 95%CI:4.8-19.5 and adjusted OR=19.8, 95%CI: 9.7-40.6, respectively, both with p<0.001). Good perception was associated with being at least 46 years old, non-Catholic and continuing the treatment (adjusted OR=3.2, 95%CI:1.2-9.1; adjusted OR=29.6, 95%CI:14.1-62.2 and adjusted OR=5.1, 95%CI:1.6-16.0 respectively, all with p<0.001). A good level of knowledge, attitude and perception is needed for a massive adherence of population to onchocerciasis control programmes. In the area of study (Moanza, DRC), good attitude and perception motivated the continuation of treatment in the population. In the future, different plans should focus on educational strategies to maintain a massive adherence and reduce onchocerciasis prevalence.

Onchocerciasis: the pre-control association between prevalence of palpable nodules and skin microfilariae.

BACKGROUND: The prospect of eliminating onchocerciasis from Africa by mass treatment with ivermectin has been rejuvenated following recent successes in foci in Mali, Nigeria and Senegal. Elimination prospects depend strongly on local transmission conditions and therefore on pre-control infection levels. Pre-control infection levels in Africa have been mapped largely by means of nodule palpation of adult males, a relatively crude method for detecting infection. We investigated how informative pre-control nodule prevalence data are for estimating the pre-control prevalence of microfilariae (mf) in the skin and discuss implications for assessing elimination prospects. METHODS AND FINDINGS: We analyzed published data on pre-control nodule prevalence in males aged ≥ 20 years and mf prevalence in the population aged ≥ 5 years from 148 African villages. A meta-analysis was performed by means of Bayesian hierarchical multivariate logistic regression, accounting for measurement error in mf and nodule prevalence, bioclimatic zones, and other geographical variation. There was a strong positive correlation between nodule prevalence in adult males and mf prevalence in the general population. In the forest-savanna mosaic area, the pattern in nodule and mf prevalence differed significantly from that in the savanna or forest areas. SIGNIFICANCE: We provide a tool to convert pre-control nodule prevalence in adult males to mf prevalence in the general population, allowing historical data to be interpreted in terms of elimination prospects and disease burden of onchocerciasis. Furthermore, we identified significant geographical variation in mf prevalence and nodule prevalence patterns warranting further investigation of geographical differences in transmission patterns of onchocerciasis.

African Programme For Onchocerciasis Control 1995-2015: model-estimated health impact and cost.

BACKGROUND: Onchocerciasis causes a considerable disease burden in Africa, mainly through skin and eye disease. Since 1995, the African Programme for Onchocerciasis Control (APOC) has coordinated annual mass treatment with ivermectin in 16 countries. In this study, we estimate the health impact of APOC and the associated costs from a program perspective up to 2010 and provide expected trends up to 2015. METHODS AND FINDINGS: With data on pre-control prevalence of infection and population coverage of mass treatment, we simulated trends in infection, blindness, visual impairment, and severe itch using the micro-simulation model ONCHOSIM, and estimated disability-adjusted life years (DALYs) lost due to onchocerciasis. We assessed financial costs for APOC, beneficiary governments, and non-governmental development organizations, excluding cost of donated drugs. We estimated that between 1995 and 2010, mass treatment with ivermectin averted 8.2 million DALYs due to onchocerciasis in APOC areas, at a nominal cost of about US$257 million. We expect that APOC will avert another 9.2 million DALYs between 2011 and 2015, at a nominal cost of US$221 million. CONCLUSIONS: Our simulations suggest that APOC has had a remarkable impact on population health in Africa between 1995 and 2010. This health impact is predicted to double during the subsequent five years of the program, through to 2015. APOC is a highly cost-effective public health program. Given the anticipated elimination of onchocerciasis from some APOC areas, we expect even more health gains and a more favorable cost-effectiveness of mass treatment with ivermectin in the near future.

Onchodermatitis.

PURPOSE OF REVIEW: This review is timely because awareness of the burden of disease from onchodermatitis has increased significantly over recent years. Recent progress in the field is reviewed with emphasis on publications within the past 2 years. RECENT FINDINGS: Advances have been made in understanding immunopathogenesis and in diagnosis and treatment. The World Bank/WHO African Programme for Onchocerciasis Control (APOC), which uses annual community-directed treatment with ivermectin (CDTI) via the Mectizan Donation Programme, now covers 19 African countries. Development of ivermectin resistance is a concern. Unlike ivermectin, which is a microfilaricide, doxycycline, which targets Wolbachia endosymbiotic bacteria, sterilizes adult female worms and has a macrofilaricidal effect. Moxidectin, which sterilizes or kills adult worms has started a phase III trial with ivermectin. Additional primary healthcare interventions have been successfully integrated with CTDI. In Latin America, transmission has been interrupted in half of the original endemic foci and Colombia is the first nation to have achieved countrywide interruption of transmission. The first report of elimination using ivermectin in an African setting is a milestone. Two African foci using vector control plus CDTI have reported vector elimination. SUMMARY: Results of the longer-term impact of large-scale ivermectin distribution by the APOC are awaited. Research is needed into new drug targets within Wolbachia's metabolic pathways. Elimination of transmission of disease is on the horizon but more research is needed on when and where ivermectin treatment can be stopped.