Epidemiology of nodding syndrome in the Greater Mundri area,South Sudan: Prevalence,spatial pattern and environmental risk factors

BackgroundNodding syndrome (NS) is a progressive neurological disease that has been described in several sub-Saharan African counties, but South Sudan is considered the most affected. However, knowledge about the exact burden and the epidemiological risk factors of NS in South Sudan is lacking.ObjectiveTo determine the prevalence, distribution and epidemiological risk factors of NS in the Greater Mundri area, the epicenter of NS in South Sudan.MethodsA NS prevalence house-to-house survey was conducted in multiple villages between February 2018 and November 2019. Geographical distribution and clustering of NS cases was identified using spatial and binomial regression analysis. Epidemiological risk factors of NS were identified using univariate and multivariate models.ResultsOf the 22,411 persons surveyed in 92 villages, 607 (2.7%) persons with NS were identified, of which 114 (19%) were new-onset cases. The highest prevalence was found in Diko village with a prevalence of 13.7%. NS showed a significant spatial pattern with clustering of cases between adjacent households and along rivers. Risks factors for NS include all behaviors around rivers (drinking, cooking, handwashing and bathing) and exposure to poultry. On the other hand, ownership of mobile phone decreased the risk of NS. Many other factors, including prior ivermectin treatment and internal displacement were not associated with NS.ConclusionOur study demonstrates a very high burden of the NS disease in the Greater Mundri area, strengthens the association with rivers, and identified possible new clues for an underlying cause.     

Contact‐dependent growth inhibition induces high levels of antibiotic‐tolerant persister cells in clonal bacterial populations

Bacterial populations can use bet‐hedging strategies to cope with rapidly changing environments. One example is non‐growing cells in clonal bacterial populations that are able to persist antibiotic treatment. Previous studies suggest that persisters arise in bacterial populations either stochastically through variation in levels of global signalling molecules between individual cells, or in response to various stresses. Here, we show that toxins used in contact‐dependent growth inhibition (CDI) create persisters upon direct contact with cells lacking sufficient levels of CdiI immunity protein, which would otherwise bind to and neutralize toxin activity. CDI‐mediated persisters form through a feedforward cycle where the toxic activity of the CdiA toxin increases cellular (p)ppGpp levels, which results in Lon‐mediated degradation of the immunity protein and more free toxin. Thus, CDI systems mediate a population density‐dependent bet‐hedging strategy, where the fraction of non‐growing cells is increased only when there are many cells of the same genotype. This may be one of the mechanisms of how CDI systems increase the fitness of their hosts.     

Incidence of childhood cancer in Canada during the COVID-19 pandemic

Background:The COVID-19 pandemic has had a major impact on access to health care resources. Our objective was to estimate the impact of the COVID-19 pandemic on the incidence of childhood cancer in Canada. We also aimed to compare the proportion of patients who enrolled in clinical trials at diagnosis, presented with metastatic disease or had an early death during the first 9 months of the COVID-19 pandemic compared with previous years.Methods:We conducted an observational study that included children younger than 15 years with a new diagnosis of cancer between March 2016 and November 2020 at 1 of 17 Canadian pediatric oncology centres. Our primary outcome was the monthly age-standardized incidence rates (ASIRs) of cancers. We evaluated level and trend changes using interventional autoregressive integrated moving average models. Secondary outcomes were the proportion of patients who were enrolled in a clinical trial, who had metastatic or advanced disease and who died within 30 days. We compared the baseline and pandemic periods using rate ratios (RRs) and 95% confidence intervals (CIs).Results:Age-standardized incidence rates during COVID-19 quarters were 157.7, 164.6, and 148.0 per million, respectively, whereas quarterly baseline ASIRs ranged between 150.3 and 175.1 per million (incidence RR 0.93 [95% CI 0.78 to 1.12] to incidence RR 1.04 [95% CI 0.87 to 1.24]). We found no statistically significant level or slope changes between the projected and observed ASIRs for all new cancers (parameter estimate [β], level 4.98, 95% CI −15.1 to 25.04, p = 0.25), or when stratified by cancer type or by geographic area. Clinical trial enrolment rate was stable or increased during the pandemic compared with baseline (RR 1.22 [95% CI 0.70 to 2.13] to RR 1.71 [95% CI 1.01 to 2.89]). There was no difference in the proportion of patients with metastatic disease (RR 0.84 [95% CI 0.55 to 1.29] to RR 1.22 [0.84 to 1.79]), or who died within 30 days (RR 0.16 [95% CI 0.01 to 3.04] to RR 1.73 [95% CI 0.38 to 15.2]).Interpretation:We did not observe a statistically significant change in the incidence of childhood cancer, or in the proportion of children enrolling in a clinical trial, presenting with metastatic disease or who died early during the first 9 months of the COVID-19 pandemic, which suggests that access to health care in pediatric oncology was not reduced substantially in Canada.

Concerns have been raised that the COVID-19 pandemic disrupted health care–seeking behaviours and access to health care, affecting the diagnosis and management of other conditions such as cancer. Studies conducted in the Netherlands and United Kingdom using administrative data have shown as much as a 50% reduction in cancer incidence in adults after March 2020.^1,2 Other studies in adult populations thus far have shown a decrease in the number of new cancer diagnoses, and cancer-related medical visits, therapies and surgeries, ^1,3–5 raising concerns about potential excess cancer mortality in the upcoming years.⁶ This may be explained partly by the suspension or reduction of cancer-screening procedures, such as mammography, colonoscopy and cervical cytology by up to 90%,^3,5,7 because these screening initiatives play a critical role in the detection of cancers in adults. A 2020 retrospective single-centre cohort study in Japan that involved 123 patients with colorectal cancer reported that significantly more of these patients presented with complete intestinal obstruction, which suggests that detection delays might have contributed to diagnosis at later stages of the disease.⁸ It is unclear whether these findings apply to childhood cancer because cancer screening is not part of routine pediatric care, and early detection may not be as important in childhood cancer than in its adult counterpart.⁹In children, case series and single-centre retrospective cohort studies, notably from Italy and the United States, suggested a marked reduction in incident cancers, along with high acuity of care at presentation.^10–13 Similar concerns of delayed clinical presentation were raised in other pediatric patient populations, with reports of children presenting at late stages of sepsis or diabetic ketoacidosis, which suggests a delay in seeking care.^14,15It is possible that fear of COVID-19 dissuaded families with children from seeking care for nonspecific symptoms such as pain, headache or fatigue, which are typical triggers leading to a pediatric cancer diagnosis. Understanding the indirect effects of health policies during the COVID-19 pandemic is important to guide policy-making and mitigate barriers to essential health care in future public health crises.Our objective was to measure the impact of the COVID-19 pandemic and associated restrictions on the incidence of childhood cancer in Canada. We also aimed to compare the proportion of patients who enrolled in clinical trials at diagnosis, presented with metastatic disease or died during the first 9 months of the COVID-19 pandemic compared with previous years.