Impact of ivermectin and vector control on onchocerciasis transmission in Togo: Assessing the empirical evidence on trends in infection and entomological indicators.

BACKGROUND: The World Health Organization's 2021-2030 Road Map for Neglected Tropical Diseases boosted global commitment towards the elimination of onchocerciasis, but the timeline to elimination will vary strongly between countries in Africa. To assess progress towards elimination in the Republic of Togo, we reviewed the history of control and time trends in infection. METHODOLOGY/PRINCIPAL FINDINGS: We collated all available programmatic, entomological, and epidemiological data since the initiation of the Onchocerciasis Control Programme (OCP) in Togo through different data sources. We then visualised data trends over time, to assess the impact of interventions on infection and transmission levels. Vector control was initiated by OCP from 1977 (northern and central parts of Togo) or 1988 (southern regions) up to 2002 (most areas) or 2007 ("special intervention zones" [SIZ], parts of Northern and Central Togo). Between 1988 and 1991, Togo initiated ivermectin mass drug administration (MDA) in eligible communities. The impact of vector control was high in most river basins, resulting in low annual biting rates and annual transmission potential declining to very low levels; the impact was lower in river basins designated as SIZ. Repeated, longitudinal ivermectin mass treatments have overall strongly reduced onchocerciasis transmission in Togo. Epidemiological surveys performed between 2014 and 2017 showed that the prevalence of skin microfilariae (mf) and anti-OV16 IgG4 antibodies had declined to low levels in several districts of the Centrale, Plateaux, and Maritime region. Yet, relatively high mf prevalences (between 5.0% and 32.7%) were still found in other districts during the same period, particularly along the Kéran, Mô and Ôti river basins (SIZ areas). CONCLUSIONS/SIGNIFICANCE: Trends in infection prevalence and intensity show that onchocerciasis levels have dropped greatly over time in most areas. This demonstrates the large impact of long-term and wide-scale interventions, and suggest that several districts of Togo are approaching elimination.

Onchocerciasis-associated epilepsy in Maridi, South Sudan: Modelling and exploring the impact of control measures against river blindness.

BACKGROUND: Onchocerciasis, also known as "river blindness", is caused by the bite of infected female blackflies (genus Simuliidae) that transmit the parasite Onchocerca volvulus. A high onchocerciasis microfarial load increases the risk to develop epilepsy in children between the ages of 3 and 18 years. In resource-limited settings in Africa where onchocerciasis has been poorly controlled, high numbers of onchocerciasis-associated epilepsy (OAE) are reported. We use mathematical modeling to predict the impact of onchocerciasis control strategies on the incidence and prevalence of OAE. METHODOLOGY: We developed an OAE model within the well-established mathematical modelling framework ONCHOSIM. Using Latin-Hypercube Sampling (LHS), and grid search technique, we quantified transmission and disease parameters using OAE data from Maridi County, an onchocerciasis endemic area, in southern Republic of South Sudan. Using ONCHOSIM, we predicted the impact of ivermectin mass drug administration (MDA) and vector control on the epidemiology of OAE in Maridi. PRINCIPAL FINDINGS: The model estimated an OAE prevalence of 4.1% in Maridi County, close to the 3.7% OAE prevalence reported in field studies. The OAE incidence is expected to rapidly decrease by >50% within the first five years of implementing annual MDA with good coverage (≥70%). With vector control at a high efficacy level (around 80% reduction of blackfly biting rates) as the sole strategy, the reduction is slower, requiring about 10 years to halve the OAE incidence. Increasing the efficacy levels of vector control, and implementing vector control simultaneously with MDA, yielded better results in preventing new cases of OAE. CONCLUSIONS/SIGNIFICANCES: Our modeling study demonstrates that intensifying onchocerciasis eradication efforts could substantially reduce OAE incidence and prevalence in endemic foci. Our model may be useful for optimizing OAE control strategies.

[Invasive group A streptococcal infections in the Netherlands]. / Invasieve groep A-streptokokkeninfecties in Nederland.

Group A streptococcal (GAS) infections are caused by the Gram-positive bacterium Streptococcus pyogenes. Infection can occur via droplet infection from the throat and via (in)direct contact with infected people. GAS can cause a wide variety of diseases, ranging from superficial skin infections, pharyngitis and scarlet fever, to serious invasive diseases such as puerperal sepsis, pneumonia, necrotising soft tissue infections (NSTI) (also known as necrotising fasciitis/myositis), meningitis and streptococcal toxic shock syndrome (STSS). In invasive GAS infections, the bacteria has penetrated into a sterile body compartment (such as the bloodstream, deep tissues, or the central nervous system). Invasive GAS infections are rare but serious, with high morbidity and mortality. Since March 2022, the National Institute for Public Health and the Environment (RIVM) reported a national increase in notifiable invasive GAS infections (NSTI, STSS and puerperal fever). Particularly NSTI has increased compared to the years before the SARS-CoV-2 pandemic. Remarkably, the proportion of children aged 0 to 5 years with invasive GAS-infections is higher in 2022 than in the previous years (12% compared to 4%). While seasonal peaks occur, the current elevation exceeds this variation. To promote early recognition and diagnosis of invasive GAS infections different clinical cases are presented.

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.

Standardisation of lymphatic filariasis microfilaraemia prevalence estimates based on different diagnostic methods: a systematic review and meta-analysis.

BACKGROUND: Lymphatic filariasis (LF) infection is generally diagnosed through parasitological identification of microfilariae (mf) in the blood. Although historically the most commonly used technique for counting mf is the thick blood smear based on 20 µl blood (TBS20), various other techniques and blood volumes have been applied. It is therefore a challenge to compare mf prevalence estimates from different LF-survey data. Our objective was to standardise microfilaraemia (mf) prevalence estimates to TBS20 as the reference diagnostic technique. METHODS: We first performed a systematic review to identify studies reporting on comparative mf prevalence data as measured by more than one diagnostic test, including TBS20, on the same study population. Associations between mf prevalences based on different diagnostic techniques were quantified in terms of odds ratios (OR, with TBS20 blood as reference), using a meta-regression model. RESULTS: We identified 606 articles matching our search strategy and included 14 in our analyses. The OR of the mf prevalences as measured by the more sensitive counting chamber technique (≥ 50 µl blood) was 2.90 (95% confidence interval (CI): 1.60-5.28). For membrane filtration (1 ml blood) the OR was 2.39 (95% CI: 1.62-3.53), Knott's technique it was 1.54 (95% CI: 0.72-3.29), and for TBS in ≥ 40 µl blood it was 1.37 (95% CI: 0.81-2.30). CONCLUSIONS: We provided transformation factors to standardise mf prevalence estimates as detected by different diagnostic techniques to mf prevalence estimates as measured by TBS20. This will facilitate the use and comparison of more datasets in meta-analyses and geographic mapping initiatives across countries and over time.

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 coinfected cases with loiasis hypermicrofilaremia are predicted to live in hypoendemic areas currently not targeted for MDA. CONCLUSIONS: Loiasis coinfection is a major concern for onchocerciasis elimination in Africa. We predict that under current strategies, at least 31 000 coinfected people still require treatment for onchocerciasis in 2025 while being at risk of SAEs, justifying continued efforts in research and development for safer drugs and control strategies.

Burden of onchocerciasis-associated epilepsy: first estimates and research priorities.

BACKGROUND: Since the 1990s, evidence has accumulated of an increased prevalence of epilepsy in onchocerciasis-endemic areas in Africa as compared to onchocerciasis-free areas. Although the causal relationship between onchocerciasis and epilepsy has yet to be proven, there is likely an association. Here we discuss the need for disease burden estimates of onchocerciasis-associated epilepsy (OAE), provide them, detail how such estimates should be refined, and discuss the socioeconomic impact of OAE, including a cost-estimate for anti-epileptic drugs. MAIN BODY: Providing OAE burden estimates may aid prevention of epilepsy in onchocerciasis- endemic areas by inciting and informing collaboration between onchocerciasis control programmes and mental health services. Epilepsy not only massively impacts the health of those affected, but it also carries a high socioeconomic burden for the households and communities involved. We used previously published geospatial estimates of onchocerciasis in Africa and a separately published logistic regression model quantifying the association between onchocerciasis and epilepsy to estimate the number of OAE cases. We then applied disability weights for epilepsy to quantify the burden in terms of years of life lived with disability (YLD) and estimate the cost of treatment. We estimate that in 2015 roughly 117 000 people were affected by OAE across onchocerciasis-endemic areas previously under the African Programme for Onchocerciases control (APOC) mandate where OAE has ever been reported or suspected, and another 264 000 persons in onchocerciasis-endemic areas where OAE has never been investigated before. The total number of YLDs due to OAE was 39 300 and 88 700 in these areas respectively, based on a weighted mean disability weight of 0.336. The burden of OAE is approximately 13% of the total YLDs attributable to onchocerciasis and 10% of total YLDs attributable to epilepsy. We estimated that by 2015 the total costs of treatment with anti-epileptic drug for OAE cases would have been a minimum of 12.4 million US$. CONCLUSIONS: These estimates suggest a considerable health, social and economic burden of OAE in Africa. The treatment and care for people with epilepsy, especially in hyperendemic onchocerciasis areas with high epilepsy prevalence thus requires more financial and human resources.

Diagnosing Polyparasitism in a High-Prevalence Setting in Beira, Mozambique: Detection of Intestinal Parasites in Fecal Samples by Microscopy and Real-Time PCR.

BACKGROUND: Many different intestinal parasite species can co-occur in the same population. However, classic diagnostic tools can only frame a particular group of intestinal parasite species. Hence, one or two tests do not suffice to provide a complete picture of infecting parasite species in a given population. The present study investigated intestinal parasitic infections in Beira, Mozambique, i.e. in the informal settlement of Inhamudima. Diagnostic accuracy of five classical microscopy techniques and real-time PCR for the detection of a broad spectrum of parasites was compared. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional population-based survey was performed. One stool sample per participant (n = 303) was examined by direct smear, formal-ether concentration (FEC), Kato smear, Baermann method, coproculture and real-time PCR. We found that virtually all people (96%) harbored at least one helminth, and that almost half (49%) harbored three helminths or more. Remarkably, Strongyloides stercoralis infections were widespread with a prevalence of 48%, and Ancylostoma spp. prevalence was higher than that of Necator americanus (25% versus 15%), the hookworm species that is often assumed to prevail in East-Africa. Among the microscopic techniques, FEC was able to detect the broadest spectrum of parasite species. However, FEC also missed a considerable number of infections, notably S. stercoralis, Schistosoma mansoni and G. intestinalis. PCR outperformed microscopy in terms of sensitivity and range of parasite species detected. CONCLUSIONS/SIGNIFICANCE: We showed intestinal parasites-especially helminths-to be omnipresent in Inhamudima, Beira. However, it is a challenge to achieve high diagnostic sensitivity for all species. Classical techniques such as FEC are useful for the detection of some intestinal helminth species, but they lack sensitivity for other parasite species. PCR can detect intestinal parasites more accurately but is generally not feasible in resource-poor settings, at least not in peripheral labs. Hence, there is a need for a more field-friendly, sensitive approach for on-the-spot diagnosis of parasitic infections.

Diagnostic performance of Schistosoma real-time PCR in urine samples from Kenyan children infected with Schistosoma haematobium: day-to-day variation and follow-up after praziquantel treatment.

BACKGROUND: In an effort to enhance accuracy of diagnosis of Schistosoma haematobium, this study explores day-to-day variability and diagnostic performance of real-time PCR for detection and quantification of Schistosoma DNA compared to other diagnostic tools in an endemic area before and after treatment. METHODOLOGY: Previously collected urine samples (N = 390) from 114 preselected proven parasitological and/or clinical S. haematobium positive Kenyan schoolchildren were analyzed by a Schistosoma internal transcribed spacer-based real-time PCR after 14 years of storage. Pre-treatment day-to-day fluctuations of PCR and microscopy over three consecutive days were measured for 24 children using intra-class correlation coefficient. A combined 'gold standard' (PCR and/or microscopy positive) was used to measure sensitivity and negative predictive value (NPV) of several diagnostic tools at baseline, two and 18 months post-treatment with praziquantel. PRINCIPAL FINDINGS: All 24 repeatedly tested children were PCR-positive over three days with little daily variation in median Ct-values, while 83.3% were found to be egg-positive for S. haematobium at day 1 and 75.0% at day 2 and 3 pre-treatment, signifying daily fluctuations in microscopy diagnosis. Of all 114 preselected schoolchildren, repeated microscopic measurements were required to detect 96.5% versus 100% of positive pre-treatment cases by single PCR. At two months post-treatment, microscopy and PCR detected 22.8% versus 69.3% positive children, respectively. Based on the 'gold standard', PCR showed high sensitivity (>92%) as compared to >31% sensitivity for microscopy, both pre- and post-treatment. CONCLUSIONS/SIGNIFICANCE: Detection and quantification of Schistosoma DNA in urine by real-time PCR was shown to be a powerful and specific diagnostic tool for detection of S. haematobium infections, with less day-to-day variation and higher sensitivity compared to microscopy. The superior performance of PCR before, and two and 18 months post-treatment provides a compelling argument for PCR as an accurate and reproducible tool for monitoring treatment efficacy.

State of affairs of tuberculosis in prison facilities: a systematic review of screening practices and recommendations for best TB control.

BACKGROUND: Prisoners are at high risk of developing tuberculosis (TB), causing morbidity and mortality. Prison facilities encounter many challenges in TB screening procedures and TB control. This review explores screening practices for detection of TB and describes limitations of TB control in prison facilities worldwide. METHODS: A systematic search of online databases (e.g., PubMed and Embase) and conference abstracts was carried out. Research papers describing screening and diagnostic practices among prisoners were included. A total of 52 articles met the inclusion criteria. A meta-analysis of TB prevalence in prison facilities by screening and diagnostic tools was performed. RESULTS: The most common screening tool was symptom questionnaires (63·5%), mostly reporting presence of cough. Microscopy of sputum with Ziehl-Neelsen staining and solid culture were the most frequently combined diagnostic methods (21·2%). Chest X-ray and tuberculin skin tests were used by 73·1% and 50%, respectively, as either a screening and/or diagnostic tool. Median TB prevalence among prisoners of all included studies was 1,913 cases of TB per 100,000 prisoners (interquartile range [IQR]: 332-3,517). The overall annual median TB incidence was 7·0 cases per 1000 person-years (IQR: 2·7-30·0). Major limitations for successful TB control were inaccuracy of diagnostic algorithms and the lack of adequate laboratory facilities reported by 61·5% of studies. The most frequent recommendation for improving TB control and case detection was to increase screening frequency (73·1%). DISCUSSION: TB screening algorithms differ by income area and should be adapted to local contexts. In order to control TB, prison facilities must improve laboratory capacity and frequent use of effective screening and diagnostic tools. Sustainable political will and funding are critical to achieve this.

Do socio-economic factors influence supermarket content and shoppers' purchases?

ISSUE ADDRESSED: Obesity is at crisis proportions. Individuals of low socio-economic status (SES) are more likely to consume higher energy dense diets than their high socio-economic status counterparts. The contribution of supermarket purchases of energy dense, nutrient poor foods has not been well-researched and has largely depended on unverified self-report. METHODS: We estimated the proportion of supermarket shelf space dedicated to non-core foods in nine supermarkets (in five high and four low SES areas) in metropolitan Sydney. We analysed 204 shoppers' dockets (102 from high and 102 from low SES areas) for purchases of confectionery; sugar sweetened, carbonated beverages and cordials, sweet biscuits and cakes, and crisps and popcorn. RESULTS: After adjusting for the number of people shopped for, low SES shoppers purchased significantly more non-core foods than high SES shoppers (p=0.039), especially chips and sugar sweetened, carbonated beverages and cordials. There was no difference in the shelf space dedicated to non-core foods, or between non-core foods purchased and the proportion of shelf space occupied by them in either low or high SES areas. CONCLUSIONS: Increased purchase of non-core foods by low SES shoppers who are already at higher risk of obesity than high SES shoppers is cause for concern. Further research is required to explore underlying reasons for this association.