Epidemiological,clinical, and public health response characteristics of a large outbreak of diphtheria among the Rohingya population in Cox’s Bazar,Bangladesh, 2017 to 2019: A retrospective study

BackgroundUnrest in Myanmar in August 2017 resulted in the movement of over 700,000 Rohingya refugees to overcrowded camps in Cox’s Bazar, Bangladesh. A large outbreak of diphtheria subsequently began in this population.Methods and findingsData were collected during mass vaccination campaigns (MVCs), contact tracing activities, and from 9 Diphtheria Treatment Centers (DTCs) operated by national and international organizations. These data were used to describe the epidemiological and clinical features and the control measures to prevent transmission, during the first 2 years of the outbreak. Between November 10, 2017 and November 9, 2019, 7,064 cases were reported: 285 (4.0%) laboratory-confirmed, 3,610 (51.1%) probable, and 3,169 (44.9%) suspected cases. The crude attack rate was 51.5 cases per 10,000 person-years, and epidemic doubling time was 4.4 days (95% confidence interval [CI] 4.2–4.7) during the exponential growth phase. The median age was 10 years (range 0–85), and 3,126 (44.3%) were male. The typical symptoms were sore throat (93.5%), fever (86.0%), pseudomembrane (34.7%), and gross cervical lymphadenopathy (GCL; 30.6%). Diphtheria antitoxin (DAT) was administered to 1,062 (89.0%) out of 1,193 eligible patients, with adverse reactions following among 229 (21.6%). There were 45 deaths (case fatality ratio [CFR] 0.6%). Household contacts for 5,702 (80.7%) of 7,064 cases were successfully traced. A total of 41,452 contacts were identified, of whom 40,364 (97.4%) consented to begin chemoprophylaxis; adherence was 55.0% (N = 22,218) at 3-day follow-up. Unvaccinated household contacts were vaccinated with 3 doses (with 4-week interval), while a booster dose was administered if the primary vaccination schedule had been completed. The proportion of contacts vaccinated was 64.7% overall. Three MVC rounds were conducted, with administrative coverage varying between 88.5% and 110.4%. Pentavalent vaccine was administered to those aged 6 weeks to 6 years, while tetanus and diphtheria (Td) vaccine was administered to those aged 7 years and older. Lack of adequate diagnostic capacity to confirm cases was the main limitation, with a majority of cases unconfirmed and the proportion of true diphtheria cases unknown.ConclusionsTo our knowledge, this is the largest reported diphtheria outbreak in refugee settings. We observed that high population density, poor living conditions, and fast growth rate were associated with explosive expansion of the outbreak during the initial exponential growth phase. Three rounds of mass vaccinations targeting those aged 6 weeks to 14 years were associated with only modestly reduced transmission, and additional public health measures were necessary to end the outbreak. This outbreak has a long-lasting tail, with Rt oscillating at around 1 for an extended period. An adequate global DAT stockpile needs to be maintained. All populations must have access to health services and routine vaccination, and this access must be maintained during humanitarian crises.

Jonathan Polonsky and colleagues report on a diphtheria outbreak among Rohingya people in Cox’s Bazar, Bangladesh during 2017-19.     

Tri-block co-polymer nanocarriers for enhancement of oral delivery of felodipine: preparation,in vitro characterization and ex vivo permeation

This study aimed to prepare, optimize and characterize novel felodipine-loaded polymeric nanomicelles, using a pluronic mixture of F127 and P123. Thin-film hydration method was adopted for the preparation of different polymeric nanomicelles (T1–T12) according to a 4¹.3¹ full factorial design. Factors studied were: Pluronic®:drug ratio (P:D ratio) (10, 20, 30 and 40?w/w) and percent of hydrophilic polymer (F127%) (33.33%, 50% and 66.67% w/w). Optimization criteria were to maximize transmittance percent (T%) and entrapment efficiency percent (EE%) and to minimize particle size (PS) and polydispersity index (PDI). The optimized formulation was further characterized by DSC, FTIR and ¹H NMR studies. It was also subjected to stability testing and ex vivo permeation using rabbit intestines. Spherical nanomicelles of particle size ranging from 26.18 to 87.54?nm were successfully obtained. The optimized formulation was found to be the already prepared formulation T12 (P:D ratio of 40 and 66.67% F127) with suitable T% and EE% of 95.12% and 91.75%, respectively. DSC, FTIR and ¹H NMR studies revealed felodipine (FLD) incorporation within T12 nanomicelles. T12 enhanced the ex vivo intestinal permeation of FLD when compared to a drug suspension and showed good stability. Therefore, pluronic nanomicelles could be promising for improved oral delivery of FLD.     

Immune function differences between two color morphs of the red palm weevil Rhynchophorus ferrugineus (Coleoptera: Curculionidae) at different life stages

Several studies demonstrated that in insects cuticle melanism is interrelated with pathogen resistance, as melanin‐based coloration and innate immunity possess similar physiological pathways. For some insects, higher pathogen resistance was observed in darker individuals than in individuals with lighter cuticular coloration. Here, we investigated the difference in immune response between two color morphs (black and red) and between the life stages (pupa and adult) of the red palm weevil Rhynchophorus ferrugineus (Coleoptera: Curculionidae). Here in this study, cuticle thickness, microbial test (antimicrobial activity, phenoloxidase activity, and hemocyte density), and immune‐related gene expression were evaluated at different stages of RPW. Study results revealed that cuticle thickness of black phenotype was thicker than red phenotype at old‐pupa stage, while no significant difference found at adult stage. These results may relate to the development processes of epidermis in different stages of RPW. The results of antimicrobial activity, phenoloxidase (PO) activity, and hemocyte density analyses showed that adults with a red phenotype had stronger pathogen resistance than those with a black phenotype. In addition to antimicrobial activity and PO activity, we tested relative gene expression in the fat body of old pupae. The results of hemolymph antimicrobial analysis showed that old pupae with a red phenotype were significantly different from those with a black phenotype at 12 hr after Staphylococcus aureus injection, suggesting that red phenotype pupae were more sensitive to S. aureus. Examination of gene expression in the fat body also revealed that the red phenotype had a higher immune response than the black phenotype. Our results were inconsistent with the previous conclusion that dark insects had increased immune function, suggesting that the relationship between cuticle pigmentation and immune function in insects was not a direct link. Additional possible factors that are associated with the immune response, such as life‐history, developmental, physiological factors also need to be considered.     

A kinetic analysis of the inhibition of human prostatic 5 alpha-reductase by 4-hydroxyandrostenedione and related steroids

The inhibition of human prostatic 5 alpha-reductase by androstenedione (A), 4-hydroxyandrostenedione (4-OH-A), and 4-methoxyandrostenedione (4-MeO-A) was studied. All three steroids inhibited 5 alpha-reductase in a concentration-dependent manner. The inhibition was competitive with respect to testosterone and non-competitive with respect to NADPH, indicating that these compounds inhibit 5 alpha-reductase by acting as alternative substrates. Ki values obtained were in the range 0.21-0.3 microM (A), 1.01-2.04 microM (4-OH-A), and 10.2-28.3 microM (4-MeO-A). Thus the two derivatives of androstenedione are poor inhibitors of 5 alpha-reductase and appear to have limited clinical potential.