Tau-crystallin/alpha-enolase: one gene encodes both an enzyme and a lens structural protein.

tau-Crystallin has been a major component of the cellular lenses of species throughout vertebrate evolution, from lamprey to birds. Immunofluorescence analysis of the embryonic turtle lens, using antiserum to lamprey tau-crystallin showed that the protein is expressed throughout embryogenesis and is present at high concentrations in all parts of the lens. Partial peptide sequence for the isolated turtle protein and deduced sequences for several lamprey peptides all revealed a close similarity to the glycolytic enzyme enolase (E.C. 4.2.1.11). A full-sized cDNA for putative duck tau-crystallin was obtained and sequenced, confirming the close relationship with alpha-enolase. Southern blot analysis showed that the duck genome contains a single alpha-enolase gene, while Northern blot analysis showed that the message for tau-crystallin/alpha-enolase is present in embryonic duck lens at 25 times the abundance found in liver. tau-Crystallin possesses enolase activity, but the activity is greatly reduced, probably because of age-related posttranslational modification. It thus appears that a highly conserved, important glycolytic enzyme has been used as a structural component of lens since the start of vertebrate evolution. Apparently the enzyme has not been recruited for its catalytic activity but for some distinct structural property. tau-Crystallin/alpha-enolase is an example of a multifunctional protein playing two very different roles in evolution but encoded by a single gene

Projections of Ebola outbreak size and duration with and without vaccine use in Équateur, Democratic Republic of Congo, as of May 27, 2018.

As of May 27, 2018, 6 suspected, 13 probable and 35 confirmed cases of Ebola virus disease (EVD) had been reported in Équateur Province, Democratic Republic of Congo. We used reported case counts and time series from prior outbreaks to estimate the total outbreak size and duration with and without vaccine use. We modeled Ebola virus transmission using a stochastic branching process model that included reproduction numbers from past Ebola outbreaks and a particle filtering method to generate a probabilistic projection of the outbreak size and duration conditioned on its reported trajectory to date; modeled using high (62%), low (44%), and zero (0%) estimates of vaccination coverage (after deployment). Additionally, we used the time series for 18 prior Ebola outbreaks from 1976 to 2016 to parameterize the Thiel-Sen regression model predicting the outbreak size from the number of observed cases from April 4 to May 27. We used these techniques on probable and confirmed case counts with and without inclusion of suspected cases. Probabilistic projections were scored against the actual outbreak size of 54 EVD cases, using a log-likelihood score. With the stochastic model, using high, low, and zero estimates of vaccination coverage, the median outbreak sizes for probable and confirmed cases were 82 cases (95% prediction interval [PI]: 55, 156), 104 cases (95% PI: 58, 271), and 213 cases (95% PI: 64, 1450), respectively. With the Thiel-Sen regression model, the median outbreak size was estimated to be 65.0 probable and confirmed cases (95% PI: 48.8, 119.7). Among our three mathematical models, the stochastic model with suspected cases and high vaccine coverage predicted total outbreak sizes closest to the true outcome. Relatively simple mathematical models updated in real time may inform outbreak response teams with projections of total outbreak size and duration

Importance of Coverage and Endemicity on the Return of Infectious Trachoma after a Single Mass Antibiotic Distribution

Trachoma, caused by ocular chlamydia infection, is the most common infectious cause of blindness in the world. The World Health Organization (WHO) recommends the SAFE strategy (eyelid surgery, antibiotics, facial hygiene, environmental improvements) for trachoma control. Oral antibiotics reduce the transmission of ocular chlamydia, but re-infection of treated individuals is common. Therefore, the WHO recommends annual mass antibiotic treatments to the entire village. The success of treatment is likely based on many factors, including the antibiotic coverage, or percentage of villagers who receive antibiotics. However, no studies have analyzed the importance of antibiotic coverage for the reduction of ocular chlamydia. Here, we performed multivariate regression analyses on data from a clinical trial of mass oral antibiotics for trachoma in a severely affected area of Ethiopia. At the relatively high levels of antibiotic coverage in our study, coverage was associated with post-treatment infection at two months, but not at six months. The amount of infection at baseline was strongly correlated with post-treatment infection at both two and six months. These results suggest that in areas with severe trachoma treated with relatively high antibiotic coverage, increasing coverage even further may have only a short-term benefit

Case report: Rare skeletal manifestations in a child with primary hyperparathyroidism

Background: Primary hyperparathyroidism (PHPT) is uncommon among children with an incidence of 1:300,000. This diagnosis is often missed in children in contrast to adults where it is detected at a pre symptomatic stage due to routine blood investigations. Etiology of PHPT can be due to adenoma, hyperplasia or rarely carcinoma. Case presentation: A 12year old Sri Lankan girl presented with progressive difficulty in walking since 1year. On examination she had bilateral genu valgum. Skeletal survey revealed valgus deformity of knee joints, bilateral subluxation of upper femoral epiphysis(SUFE), epiphyseal displacement of bilateral humeri, rugger jersey spine and subperiosteal bone resorptions in lateral aspects of 2nd and 3rd middle phalanges. There were no radiological manifestations of rickets. Metabolic profile revealed hypercalcemia with hypophosphatemia. Intact parathyroid hormone levels were elevated at 790pg/ml. Vitamin D levels were deficient. She had low bone mineral density with Z score of -3.4. Vitamin D supplementation resulted in worsening of hypercalcemia without reduction in PTH levels. Tc 99 Sestamibi uptake scan showed abnormal tracer retention in left inferior pole of thyroid. A large parathyroid gland was removed with histology favoring parathyroid adenoma. Post operatively she developed hypocalcemia. Bilateral osteotomy was done for SUFE and further surgeries for correction of limb deformities planned. Conclusion: PHPT in children is usually diagnosed late when irreversible organ damage has occurred. Children can present with non specific symptoms involving gastrointestinal, musculoskeletal, renal and neurological systems. PHPT can cause disarray in bone and epiphysis in children during pubertal growth spurt. Genu valgum and SUFE are rare skeletal manifestations in PHPT and only 10 cases of genu valgum and 9 cases of SUFE have been reported up to now. So far no cases have been reported on epiphyseal displacement of humeri. Awareness regarding the occurrence of these rare skeletal manifestations especially during puberty is important for early diagnosis to prevent irreversible outcomes

Predicting the emergence of drug-resistant HSV-2: new predictions

BACKGROUND: Mathematical models can be used to predict the emergence and transmission of antiviral resistance. Previously it has been predicted that high usage of antivirals (in immunocompetent populations) to treat Herpes Simplex Virus type 2 (HSV-2) would only lead to fairly low levels of antiviral resistance. The HSV-2 predictions were based upon the assumption that drug-resistant strains of HSV-2 would be less infectious than drug-sensitive strains but that the drug-resistant strains would not be impaired in their ability to reactivate. Recent data suggest that some drug-resistant strains of HSV-2 are likely to be impaired in their ability to reactivate. Objectives: (1) To predict the effect of a high usage of antivirals on the prevalence of drug-resistant HSV-2 under the assumption that drug-resistant strains will be less infectious than drug-sensitive strains of HSV-2 and also have an impaired ability to reactivate. (2) To compare predictions with previous published predictions. METHODS: We generated theoretical drug-resistant HSV-2 strains that were attenuated (in comparison with drug-sensitive strains) in both infectivity and ability to reactivate. We then used a transmission model to predict the emergence and transmission of drug-resistant HSV-2 in the immunocompetent population assuming a high usage of antivirals. RESULTS: Our predictions are an order of magnitude lower than previous predictions; we predict that even after 25 years of high antiviral usage only 5 out of 10,000 immunocompetent individuals will be shedding drug-resistant virus. Furthermore, after 25 years, 52 cases of HSV-2 would have been prevented for each prevalent case of drug-resistant HSV-2. CONCLUSIONS: The predicted levels of drug-resistant HSV-2 for the immunocompetent population are so low that it seems unlikely that cases of drug-resistant HSV-2 will be detected

Reduction and Return of Infectious Trachoma in Severely Affected Communities in Ethiopia

Trachoma is one of the leading causes of blindness in the developing world. The World Health Organization has a multi-pronged approach to controlling the ocular chlamydial infection that causes the disease, including distributing antibiotics to entire communities. Even a single community treatment dramatically reduces the prevalence of the infection. Unfortunately, infection returns back into communities after treatment, at least in severely affected areas such as rural Ethiopia. Here, we assess whether additional scheduled treatments in 16 communities in the Gurage area of Ethiopia further reduce infection, and whether the disease returns after distributions are stopped. In communities with the highest levels of trachoma ever studied, we find that repeated mass oral azithromycin distributions gradually reduce the prevalence of trachoma infection in a community, as long as these treatments are given frequently enough and to enough people in the community. Unfortunately, infection returns into the communities after the last treatment. Sustainable changes or complete local elimination of infection will be necessary to stop the return of ocular chlamydial in communities with very high prevalence of the disease

A rationale for continuing mass antibiotic distributions for trachoma

BACKGROUND: The World Health Organization recommends periodic mass antibiotic distributions to reduce the ocular strains of chlamydia that cause trachoma, the world's leading cause of infectious blindness. Their stated goal is to control infection, not to completely eliminate it. A single mass distribution can dramatically reduce the prevalence of infection. However, if infection is not eliminated in every individual in the community, it may gradually return back into the community, so often repeated treatments are necessary. Since public health groups are reluctant to distribute antibiotics indefinitely, we are still in need of a proven long-term rationale. Here we use mathematical models to demonstrate that repeated antibiotic distributions can eliminate infection in a reasonable time period. METHODS: We fit parameters of a stochastic epidemiological transmission model to data collected before and 6 months after a mass antibiotic distribution in a region of Ethiopia that is one of the most severely affected areas in the world. We validate the model by comparing our predicted results to Ethiopian data which was collected biannually for two years past the initial mass antibiotic distribution. We use the model to simulate the effect of different treatment programs in terms of local elimination of infection. RESULTS: Simulations show that the average prevalence of infection across all villages progressively decreases after each treatment, as long as the frequency and coverage of antibiotics are high enough. Infection can be eliminated in more villages with each round of treatment. However, in the communities where infection is not eliminated, it returns to the same average level, forming the same stationary distribution. This phenomenon is also seen in subsequent epidemiological data from Ethiopia. Simulations suggest that a biannual treatment plan implemented for 5 years will lead to elimination in 95% of all villages. CONCLUSION: Local elimination from a community is theoretically possible, even in the most severely infected communities. However, elimination from larger areas may require repeated biannual treatments and prevention of re-introduction from outside to treated areas