No abstract

Nodding syndrome is an epileptic disorder of unknown etiology that occurs in children in East Africa. There is an epidemiological association with Onchocerca volvulus, the parasitic worm that causes onchocerciasis (river blindness), but there is limited evidence that the parasite itself is neuroinvasive. We hypothesized that nodding syndrome may be an autoimmune-mediated disease. Using protein chip methodology, we detected autoantibodies to leiomodin-1 more abundantly in patients with nodding syndrome compared to unaffected controls from the same village. Leiomodin-1 autoantibodies were found in both the sera and cerebrospinal fluid of patients with nodding syndrome. Leiomodin-1 was found to be expressed in mature and developing human neurons in vitro and was localized in mouse brain to the CA3 region of the hippocampus, Purkinje cells in the cerebellum, and cortical neurons, structures that also appear to be affected in patients with nodding syndrome. Antibodies targeting leiomodin-1 were neurotoxic in vitro, and leiomodin-1 antibodies purified from patients with nodding syndrome were cross-reactive with O. volvulus antigens. This study provides initial evidence supporting the hypothesis that nodding syndrome is an autoimmune epileptic disorder caused by molecular mimicry with O. volvulus antigens and suggests that patients may benefit from immunomodulatory therapies.

Single short-term exposures to ozone are known to cause acute changes in pulmonary function and neutrophilic airway inflammation. The respiratory health effects of repeated exposures are not as well studied. Pulmonary function decrements are known to attenuate, but it is less clear how injury and inflammation are affected. Using sputum induction (SI) to sample respiratory tract lining fluid after single- and multiday exposures, we designed a study to test the hypothesis that neutrophils would increase after multiday exposure compared with single-day exposure. In a randomized, crossover design, 15 normal healthy subjects were exposed to O3 (0.2 ppm) under two conditions: for 4 hr for 1 day (1D) and for 4 hr for 4 consecutive days (4D). Pulmonary function testing was performed immediately before and after each 4-hr exposure. The SI was performed 18 hr after the end of the 1D and 4D conditions. The symptom and pulmonary function data followed a pattern seen in other multiday O3 exposure studies, with the greatest changes occurring on the second day. In contrast to previous studies using bronchoalveolar lavage, however, there was a significant increase in the percentage of neutrophils and a significant decrease in the percentage of macrophages after the 4D condition compared with the 1D condition. Given that SI likely samples proximal airways better than distal lung, these results add to the body of evidence that differential airway compartmental responses to O3 occur in humans and other species.

Abstract.Integrated community case management (iCCM) aims to reduce child mortality in areas with poor access to health care. iCCM was implemented in 2009 in Kono district, Sierra Leone, a postconflict area with high under-five mortality rates (U5MRs). We evaluated iCCM’s impact and effects on child health using cluster surveys in 2010 (midterm) and 2013 (endline) to compare indicators on child mortality, coverage of appropriate treatment, timely access to care, quality of care, and recognition of community health workers (CHWs). The sample size was powered to detect a 28% decline in U5MR. Clusters were selected proportional to population size. All households were sampled to measure mortality and systematic random sampling was used to measure coverage in a subset of households. We used program data to evaluate utilization and access; 5,257 (2010) and 3,649 (2013) households were surveyed. U5MR did not change significantly (4.54 [95% confidence interval [CI]: 3.47–5.60] to 3.95 [95% CI: 3.06–4.83] deaths per 1,000 per month (P = 0.4)) though a relative change smaller than 28% could not be detected. CHWs were the first source of care for 52% (2010) and 50.9% (2013) of children. Coverage of appropriate treatment of fever by CHWs or peripheral health units increased from 45.5% [95% CI: 39.2–52.0] to 58.2% [95% CI: 50.5–65.5] (P = 0.01); changes for diarrhea and pneumonia were not significant. The continued reliance on the CHW as the first source of care and improved coverage for the appropriate treatment of fever support iCCM’s role in Kono district.