Correction: Onchocerciasis: Target product profiles of in vitro diagnostics to support onchocerciasis elimination mapping and mass drug administration stopping decisions.

[This corrects the article DOI: 10.1371/journal.pntd.0010682.].

Onchocerciasis: Target product profiles of in vitro diagnostics to support onchocerciasis elimination mapping and mass drug administration stopping decisions.

In June 2021, the World Health Organization (WHO), recognizing the need for new diagnostics to support the control and elimination of onchocerciasis, published the target product profiles (TPPs) of new tests that would support the two most immediate needs: (a) mapping onchocerciasis in areas of low prevalence and (b) deciding when to stop mass drug administration programs. In both instances, the test should ideally detect an antigen specific for live, adult O. volvulus female worms. The preferred format is a field-deployable rapid test. For mapping, the test needs to be ≥ 60% sensitive and ≥ 99.8% specific, while to support stopping decisions, the test must be ≥ 89% sensitive and ≥ 99.8% specific. The requirement for extremely high specificity is dictated by the need to detect with sufficient statistical confidence the low seroprevalence threshold set by WHO. Surveys designed to detect a 1-2% prevalence of a given biomarker, as is the case here, cannot tolerate more than 0.2% of false-positives. Otherwise, the background noise would drown out the signal. It is recognized that reaching and demonstrating such a stringent specificity criterion will be challenging, but test developers can expect to be assisted by national governments and implementing partners for adequately powered field validation.

Hepatoprotective Activity of Leptadenia hastata (Asclepiadaceae) on Acetaminophen-Induced Toxicity in Mice: In Vivo Study and Characterization of Bioactive Compounds through Molecular Docking Approaches.

MATERIALS AND METHODS: Various aqueous extracts were prepared from this plant and preadministered per os to albino mice 3 h before APAP administration, once daily for one week. Animals from the normal group were given only distilled water while those from negative control received only APAP 250 mg/kg. After treatment, mice were sacrificed, the liver was collected for histopathology analysis, and different biochemical markers (alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNFα)) were measured. The content of the active extract was analyzed by HPLC/UV. Molecular docking was conducted using iGEMDOCK software, and the drug-likeness and pharmacokinetic profiles were evaluated using Swiss ADME. RESULTS: APAP administration significantly increased (p < 0.001) ALT in liver homogenates when compared to normal controls whereas the stem decoction at 250 mg/kg significantly (p < 0.001) reduced this activity to a normal value comparable to silymarin 50 mg/kg which is better than leaf and root extracts. Moreover, the stem decoction also significantly reduced the MDA levels (p < 0.05) and increased those of GSH, SOD, and CAT (p < 0.001) at doses of 250 and 500 mg/kg compared to the negative control. A significant (p < 0.001) decrease of TNFα levels and leukocyte infiltration was observed following treatment with this extract. The HPLC/UV analysis of the decoction revealed the presence of dihydroxycoumarin, quinine, and scopoletin with the following retention times: 2.6, 5.1, and 7.01 min, respectively. In silico studies showed that quinine and dihydroxycoumarin had great potentials to be orally administered drugs and possessed strong binding affinities with TNFα, TNF receptor, cyclooxygenase-2, iNOS, cytochrome P450 2E1, and GSH reductase. CONCLUSION: Based on these results, L. hastata could be considered a source of promising hepatoprotective compounds with antioxidant and anti-inflammatory properties.

Slaying little dragons: the impact of the Guinea Worm Eradication Program on dracunculiasis disability averted from 1990 to 2016.

Background: The objective of this study was to document the worldwide decline of dracunculiasis (Guinea worm disease, GWD) burden, expressed as disability-adjusted life years (DALYs), from 1990 to 2016, as estimated in the Global Burden of Disease study 2016 (GBD 2016). While the annual number of cases of GWD have been consistently reported by WHO since the 1990s, the burden of disability due to GWD has not previously been quantified in GBD. Methods: The incidence of GWD was modeled for each endemic country using annual national case reports. A literature search was conducted to characterize the presentation of GWD, translate the clinical symptoms into health sequelae, and then assign an average duration to the infection. Prevalence measures by sequelae were multiplied by disability weights to estimate DALYs. Results: The total DALYs attributed to GWD across all endemic countries (n=21) in 1990 was 50,725 (95% UI: 35,265-69,197) and decreased to 0.9 (95% UI: 0.5-1.4) in 2016. A cumulative total of 12,900 DALYs were attributable to GWD from 1990 to 2016. Conclusions: Using 1990 estimates of burden propagated forward, this analysis suggests that between 990,000 to 1.9 million DALYs have been averted as a result of the eradication program over the past 27 years.

The cost-effectiveness of an eradication programme in the end game: Evidence from guinea worm disease.

BACKGROUND: Of the three diseases targeted for eradication by WHO, two are so-called Neglected Tropical Diseases (NTDs)-guinea worm disease (GWD) and yaws. The Guinea Worm Eradication Programme (GWEP) is in its final stages, with only 25 reported in 2016. However, global eradication still requires certification by WHO of the absence of transmission in all countries. We analyze the cost-effectiveness of the GWEP in the end game, when the number of cases is lower and the cost per case is higher than at any other time. Ours is the first economic evaluation of the GWEP since a World Bank study in 1997. METHODS: Using data from the GWEP, we estimate the cost of the implementation, pre-certification and certification stages. We model cost-effectiveness in the period 1986-2030. We compare the GWEP to two alternative scenarios: doing nothing (no intervention since 1986) and control (only surveillance and outbreak response during 2016-2030). We report the cost per case averted, cost per disability adjusted life year (DALY) averted and cost per at-risk life year averted. We assess cost-effectiveness against a threshold of about one half GDP per capita (less than US$ 500 in low income countries). All costs are expressed in US$ of 2015. RESULTS: The GWEP cost an estimated US$ 11 (95% uncertainty interval, 4.70-12.49) per case averted in the period 1986-2030. The pre-certification and certification phases can cost as much as US$ 0.0041 and US$ 0.0015 per capita per year. The cost per DALY averted by the GWEP relative to doing nothing is estimated at US$ 222 (118-372) in 1986-2030. The GWEP is probably more cost-effective than control by the year 2030. The GWEP is certainly more cost-effective than control if willingness to pay for one year of life lived without the risk of GWD exceeds US$ 0.10. DISCUSSION: Even if economic costs are two times as high as the financial costs estimated for the period to 2020, the GWEP will still be cost-effective relative to doing nothing. Whether the GWEP turns out to be the most cost-effective alternative in the period beyond 2015 depends on the time horizon. When framed in terms of the number of years of life lived without the risk of GWD, a case can be made more easily for finishing the end game, including certification of the absence of transmission.

Measuring treatment coverage for neglected tropical disease control programs: analysis of a survey design.

Monitoring of treatment coverage following mass drug administration is essential to ensure program success. Coverage results reported by drug administrators are often validated by using population surveys. This study evaluates the design of a multistage cluster sample survey conducted in 2007-2008 and implemented at the district level to assess drug coverage in the 4 African countries of Burkina Faso, Ghana, Niger, and Uganda. Estimates of precision of coverage were calculated, and factors contributing to the observed variance were analyzed. Precision of ±5 percentage points was obtained in 39% (n = 12) of cases, and precision of ±10 percentage points was obtained in 77% (n = 24) of cases. The factor having the largest impact on the actual precision obtained in these surveys was the high level of clustering, the impact of which is incorporated in the design effect. Key recommendations are made for the design and analysis of future surveys; guidelines are presented for thinking through the number of clusters that should be selected and how a cluster should be designed.

Dracunculiasis (guinea worm disease): eradication without a drug or a vaccine.

Dracunculiasis, commonly known as guinea worm disease, is a nematode infection transmitted to humans exclusively via contaminated drinking water. The disease prevails in the most deprived areas of the world. No vaccine or medicine is available against the disease: eradication is being achieved by implementing preventive measures. These include behavioural change in patients and communities--such as self-reporting suspected cases to health workers or volunteers, filtering drinking water and accessing water from improved sources and preventing infected individuals from wading or swimming in drinking-water sources--supplemented by active surveillance and case containment, vector control and provision of improved water sources. Efforts to eradicate dracunculiasis began in the early 1980s. By the end of 2012, the disease had reached its lowest levels ever. This paper reviews the progress made in eradicating dracunculiasis since the eradication campaign began, the factors influencing progress and the difficulties in controlling the pathogen that requires behavioural change, especially when the threat becomes rare. The challenges of intensifying surveillance are discussed, particularly in insecure areas containing the last foci of the disease. It also summarizes the broader benefits uniquely linked to interventions against dracunculiasis.

The epidemiology of trachoma in the five northern districts of Sierra Leone.

PURPOSE: In 2008, a trachoma prevalence survey was conducted in the five northern districts of Sierra Leone to determine if and where specific components of the SAFE strategy (Surgery, Antibiotics, Face washing, Environmental change) should be initiated. METHODS: A cross-sectional survey at district level was implemented using two-stage random cluster sampling: probability proportionate sampling was used to select villages in the first stage and compact segment sampling of households in the second stage. Both eyes of 16,780 individuals were examined using the World Health Organization simplified trachoma grading system. Data were also collected on village- and household-level behavior and environmental factors related to trachoma. RESULTS: Prevalence of trachomatous inflammation-follicular (TF) in children aged 1-9 years was highest in Kambia at 3.52% (95% Confidence Interval (CI): 2.28-4.75%), while the prevalence of trachomatous trichiasis (TT) in persons over 15 years of age was highest in Port Loko at 0.27% (95% CI: 0.03-0.50%). Across all districts, the percentage of households reporting washing children's faces less than once per day was very low, while latrine coverage and accessible and safe water sources were not highly prevalent. CONCLUSIONS: In all districts but Koinadugu, TT prevalence was greater than the WHO elimination threshold, indicating the need for 1,016 TT surgeries to prevent blindness. District TF prevalence rates did not warrant mass antibiotic distribution. Although not required given the low prevalence of TF, we recommend the construction of 35,941 household latrines and provision of water sources within a 30-minute walk roundtrip for 17,551 households to bring Sierra Leone closer to reaching Millennium Development Goal 7.

Raman investigation of stable and metastable states of 4-octyl-4'-cyanobiphenyl confined in porous silica matrices.

We study the polymorphism of solid phases of 4-octyl-4(')-cyanobiphenyl (8CB) by Raman spectroscopy. For bulk 8CB, the Raman spectrum of the CN stretch is featured by a single peak, which shifts abruptly at the smectic-A-crystal transition. In confinement, the CN peak splits both at high and low temperatures. In the isotropic and liquid crystal phases, the signature of the liquid crystal bulk (LC) coexists with another peak that is assigned to LC molecules interacting with the matrice interface. We find correlations between the volumic fractions of interfacial liquid and the texture of the matrices. At low temperatures, we assign the splitting of the CN peak to the coexistence of different metastable solid phases. For strong confinements, the temperature dependence of the CN stretching frequency extends to that of the liquid, which suggests the existence of frozen-in smecticlike solid phases. We discuss the structure of these metastable solid phases in the light of neutron diffraction measurements. We also report on the peculiar analogy between the effect of quenched disorder due to the porous matrices and the effect of thermal quenching.

Active infection with Helicobacter pylori in healthy couples.

The mode of spread of Helicobacter pylori infection is subject to ongoing debate. Recent studies among patients with gastrointestinal disorders suggest a potential role of conjugal transmission. In this study, the clustering of H. pylori infection was assessed among 110 employees of a health insurance company and their partners. Active infection with H. pylori was measured by the 13C-urea breath test. Information on potential confounders was collected by a standardized questionnaire. Overall, 16 employees (14.5%) and 24 partners (21.8%) were infected. While only 7% (6/86) of employees with an uninfected partner were infected, this applied to 42% (10/24) of employees with an infected partner. A very strong relation between partners' infection status persisted after control for age and other potential confounders (adjusted odds ratio, 7.0; 95% confidence interval, 1.8-26.7). Furthermore, the risk of infection increased with the number of years lived with an infected partner. These results support the hypothesis of a major role of spouse-to-spouse transmission of H. pylori infection.

Role of genetic factors in bronchial cancer. Based upon a case of anaplastic lung carcinoma in identical twins.

Having observed homozygotic identical twin brothers suffering simultaneously from anaplastic bronchial cancer leading rapidly to death in both cases, the authors assessed the frequency of such cases. The available literature failed to reveal any identical observations, although four cases of twins suffering from bronchial cancer featuring different histologies (three epidermoidal and one bronchiolar-alveolar) were noted. Statistics show that, in the area where the observed twins were living, anaplastic cancer occurs each year in 0.39% of 53-year-old men. The case of these twins therefore supports the idea of the role of genetic factors in the determination of bronchial cancer.

[Reversible cardiogenic shock due to 5FU. Apropos of a case report]. / Choc cardiogénique reversible dû au 5 FU. A propos d'une observation.

The authors report the case of a man with a laryngeal neoplasm treated by chemotherapy including 5 FU who presented a severe cardiogenic shock responding to medical therapy with a favourable outcome. This classical clinical presentation is commented by the authors. Based on the electrocardiogram, the echocardiography and a review of literature, they favour as first underlying hypothesis the secondary metabolic pathway linked to ribonucleic acid (RNA), rather than a possible coronary spasm.

Concurrent anaplastic bronchial cancer in identical twin brothers.

After having observed homozygotic identical twin brothers who simultaneously suffered from anaplastic bronchial cancer which rapidly led to death in both cases, the authors assess the frequency of such cases. Review of the available literature failed to produce identical observations, although 4 cases of twins suffering from bronchial cancer with differing histologies (3 epidermoidal and 1 bronchiolar-alveolar) were noted. Statistics show that in the area where the observed twins were living, anaplastic cancer occurs each year in 0.39 of 53-year-old men. The cases of these twins therefore support the notion of the role of genetic factors in the determination of bronchial cancer.

[Continuous emission Doppler study with spectrum analysis in the evaluation of aortic stenosis in adults. Apropos of 30 cases]. / Le Doppler à émission continue avec analyse spectrale dans l'évaluation des sténoses aortiques de l'adulte. A propos de 30 cas.

The value of continuous wave doppler with spectral analysis for the evaluation of aortic stenosis in adults being controverted, we analyzed prospectively the results obtained in 30 consecutive elderly patients (mean age 63 years) investigated by invasive and non-invasive methods. In 24 patients who underwent both ultrasonic and catheter examinations, the correlation between mean gradients measured by catheterization and calculated separately by doppler was 0.80. For a semi-quantitative evaluation of the aortic valve area, we suggest to use an additional severity index R calculated from doppler data (R = mean gradient/maximal instantaneous gradient) which correlated well (r = -0.68) with the aortic valve area. In our experience, this index makes it possible to separate patients with a less than 0.75 cm2 aortic valve area, as calculated from Gorlin's formula (R greater than 0.65) from patients with a more than 0.75 cm2 aortic valve area (R less than 0.65), irrespective of the associated cardiac index. It is concluded that the doppler ultrasound method provides a highly satisfactory evaluation of transaortic gradient, as well as a semi-quantitative evaluation of the stenotic aortic ostium in the majority of elderly patients with aortic stenosis.

[Genetic factors in the development of bronchial cancer. Apropos of a pair of identical twins]. / Facteurs génétiques dans le déterminisme du cancer bronchique. A propos d'une paire de jumeaux univitellins.

An anaplastic bronchial cancer was observed to occur simultaneously in identical twin brothers, with a rapidly fatal outcome. This led to authors to appraise the prevalence of such cases and to study the role of genetic factors in the determining bronchial cancer. A review of the literature has not revealed an identical case, on the other hand 4 twin pairs suffered from a bronchial cancer with a different histology (3 epidermoid and 1 bronchoalveolar) were reported. Familial cases of bronchial cancer were also recorded. The authors go on to allude to the intervention of genetic factors in the defense mechanisms of the lung: mucociliary clearance, immunological defense and the role of aryl hydrocarbon hydroxylase. The precise identification of these factors remains difficult on account of their interaction with environmental factors.