After onset of a cholera epidemic in Haiti in mid-October 2010, a team of researchers from France and Haiti implemented field investigations and built a database of daily cases to facilitate identification of communes most affected. Several models were used to identify spatiotemporal clusters, assess relative risk associated with the epidemic’s spread, and investigate causes of its rapid expansion in Artibonite Department. Spatiotemporal analyses highlighted 5 significant clusters (p<0.001): 1 near Mirebalais (October 16–19) next to a United Nations camp with deficient sanitation, 1 along the Artibonite River (October 20–28), and 3 caused by the centrifugal epidemic spread during November. The regression model indicated that cholera more severely affected communes in the coastal plain (risk ratio 4.91) along the Artibonite River downstream of Mirebalais (risk ratio 4.60). Our findings strongly suggest that contamination of the Artibonite and 1 of its tributaries downstream from a military camp triggered the epidemic.

Effective response to infectious disease epidemics requires focused control measures in areas predicted to be at high risk of new outbreaks. We aimed to test whether mobile operator data could predict the early spatial evolution of the 2010 Haiti cholera epidemic. Daily case data were analysed for 78 study areas from October 16 to December 16, 2010. Movements of 2.9 million anonymous mobile phone SIM cards were used to create a national mobility network. Two gravity models of population mobility were implemented for comparison. Both were optimized based on the complete retrospective epidemic data, available only after the end of the epidemic spread. Risk of an area experiencing an outbreak within seven days showed strong dose-response relationship with the mobile phone-based infectious pressure estimates. The mobile phone-based model performed better (AUC 0.79) than the retrospectively optimized gravity models (AUC 0.66 and 0.74, respectively). Infectious pressure at outbreak onset was significantly correlated with reported cholera cases during the first ten days of the epidemic (p < 0.05). Mobile operator data is a highly promising data source for improving preparedness and response efforts during cholera outbreaks. Findings may be particularly important for containment efforts of emerging infectious diseases, including high-mortality influenza strains.

Importance Because inadvertent damage of parathyroid glands can lead to postoperative hypocalcemia, their identification and preservation, which can be challenging, are pivotal during total thyroidectomy. Objective To determine if intraoperative imaging systems using near-infrared autofluorescence (NIRAF) light to identify parathyroid glands could improve parathyroid preservation and reduce postoperative hypocalcemia. Design, Setting, and Participants This randomized clinical trial was conducted from September 2016 to October 2018, with a 6-month follow-up at 3 referral hospitals in France. Adult patients who met eligibility criteria and underwent total thyroidectomy were randomized. The exclusion criteria were preexisting parathyroid diseases. Interventions Use of intraoperative NIRAF imaging system during total thyroidectomy. Main Outcomes and Measures The primary outcome was the rate of postoperative hypocalcemia (a corrected calcium <8.0 mg/dL [to convert to mmol/L, multiply by 0.25] at postoperative day 1 or 2). The main secondary outcomes were the rates of parathyroid gland autotransplantation and inadvertent parathyroid gland resection. Results A total of 245 of 529 eligible patients underwent randomization. Overall, 241 patients were analyzed for the primary outcome (mean [SD] age, 53.6 [13.6] years; 191 women [79.3%]): 121 who underwent NIRAF-assisted thyroidectomy and 120 who underwent conventional thyroidectomy (control group). The temporary postoperative hypocalcemia rate was 9.1% (11 of 121 patients) in the NIRAF group and 21.7% (26 of 120 patients) in the control group (between-group difference, 12.6% [95% CI, 5.0%-20.1%];P = .007). There was no significant difference in permanent hypocalcemia rates (0% in the NIRAF group and 1.6% [2 of 120 patients] in the control group). Multivariate analyses accounting for center and surgeon heterogeneity and adjusting for confounders, found that use of NIRAF reduced the risk of hypocalcemia with an odds ratio of 0.35 (95% CI, 0.15-0.83;P = .02). Analysis of secondary outcomes showed that fewer patients experienced parathyroid autotransplantation in the NIRAF group than in the control group: respectively, 4 patients (3.3% [95% CI, 0.1%-6.6%) vs 16 patients (13.3% [95% CI, 7.3%-19.4%];P = .009). The number of inadvertently resected parathyroid glands was significantly lower in the NIRAF group than in the control group: 3 patients (2.5% [95% CI, 0.0%-5.2%]) vs 14 patients (11.7% [95% CI, 5.9%-17.4%], respectively;P = .006). Conclusions and Relevance The use of NIRAF for the identification of the parathyroid glands may help improve the early postoperative hypocalcemia rate significantly and increase parathyroid preservation after total thyroidectomy. Trial Registration ClinicalTrials.gov identifier:NCT02892253

Chikungunya virus (CHIKV) is responsible for acute febrile polyarthralgia and, in a proportion of cases, severe complications including chronic arthritis. CHIKV has spread recently in East Africa, South-West Indian Ocean, South-Asia and autochthonous cases have been reported in Europe. Although almost all patients are outpatients, medical investigations mainly focused on hospitalised patients. Here, we detail clinico-biological characteristics of Chikungunya (CHIK) outpatients in Reunion Island (2006). 76 outpatients with febrile arthralgia diagnosed within less than 48 hours were included by general practitioners during the CuraChik clinical trial. CHIK was confirmed in 54 patients and excluded in 22. A detailed clinical and biological follow-up was organised, that included analysis of viral intrahost diversity and telephone survey until day 300. The evolution of acute CHIK included 2 stages: the ‘viral stage’ (day 1–day 4) was associated with rapid decrease of viraemia and improvement of clinical presentation; the ‘convalescent stage’ (day 5–day 14) was associated with no detectable viraemia but a slower clinical improvement. Women and elderly had a significantly higher number of arthralgia at inclusion and at day 300. Based on the study clinico-biological dataset, scores for CHIK diagnosis in patients with recent febrile acute polyarthralgia were elaborated using arthralgia on hands and wrists, a minor or absent myalgia and the presence of lymphopenia (<1G/L) as major orientation criteria. Finally, we observed that CHIKV intra-host genetic diversity increased over time and that a higher viral amino-acid complexity at the acute stage was associated with increased number of arthralgia and intensity of sequelae at day 300. This study provided a detailed picture of clinico-biological CHIK evolution at the acute phase of the disease, allowed the elaboration of scores to assist CHIK diagnosis and investigated for the first time the impact of viral intra-host genetic diversity on the disease course. The mosquito-transmitted chikungunya virus is responsible for acute febrile polyarthralgia and, in a proportion of cases, complications including chronic arthritis. Since 2005, it has massively re-emerged in the Old World. Although the large majority of patients are outpatients, the most detailed studies have focused previously on hospitalised patients (i.e., severe cases). Here, we report the detailed clinico-biological characteristics of ‘standard’ clinical presentations in patients followed-up by general practitioners in Reunion Island (2006) during the CuraChik clinical trial. At the onset of the disease, two stages were observed: (i) a ‘viral stage’ during the first 4 days, associated with an acute febrile polyarthralgic syndrome and a subsequent rapid clinical improvement; the main clinico-biological characteristics during that period were used to elaborate supportive chikungunya diagnostic scores, (ii) a ‘convalescent stage’ (days 5–14) with no detectable viraemia but a slower clinical improvement. Woman and elderly patients were found at risk for more symptomatic forms of the disease at both the acute and late stages (day 300) and we observed that the viral intra-host genetic diversity increased over time and that a higher viral amino-acid complexity at the acute stage was associated with more symptomatic illness at the late stage of the disease.

OBJECT: Gamma Knife surgery (GKS) is one of the surgical alternatives for the treatment of drug-resistant trigeminal neuralgia (TN). This study aims to evaluate the safety and efficacy of GKS in a large population of patients with TN with very long-term clinical follow-up. METHODS: Between July 1992 and November 2010, 737 patients presenting with TN were treated using GKS. Data were collected prospectively and were further retrospectively evaluated at Timone University Hospital. The frequency and severity of pain, as well as trigeminal nerve function, were evaluated before GKS and regularly thereafter. Radiosurgery using the Gamma Knife (model B, C, 4C, or Perfexion) was performed with the help of both MR and CT targeting. A single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.6 mm (range 4–14 mm) anterior to the emergence of the nerve (retrogasserian target). A median maximum dose of 85 Gy (range 70–90 Gy) was prescribed. RESULTS: The safety and efficacy are reported for 497 patients with medically refractory classical TN who were never previously treated by GKS and had a follow-up of at least 1 year. The median age in this series was 68.3 years (range 28.1–93.2 years). The median follow-up period was 43.8 months (range 12–174.4 months). Overall, 456 patients (91.75%) were initially pain free in a median time of 10 days (range 1–180 days). Their actuarial probabilities of remaining pain free without medication at 3, 5, 7, and 10 years were 71.8%, 64.9%, 59.7%, and 45.3%, respectively. One hundred fifty-seven patients (34.4%) who were initially pain free experienced at least 1 recurrence, with a median delay of onset of 24 months (range 0.6–150.1 months). However, the actuarial rate of maintaining pain relief without further surgery was 67.8% at 10 years. The hypesthesia actuarial rate at 5 years was 20.4% and at 7 years reached 21.1%, but remained stable until 14 years with a median delay of onset of 12 months (range 1–65 months). Very bothersome facial hypesthesia was reported in only 3 patients (0.6%). CONCLUSIONS: Retrogasserian GKS proved to be safe and effective in the long term and in a very large number of patients. Even if the probability of long-lasting effects may be modest compared with microvascular decompression, the rarity of complications prompts discussion of using GKS as the pragmatic surgical first- or second-intention alternative for classical TN. However, a randomized trial, or at least a case-matched control study, would be required to compare with microvascular decompression.

Hepatic periportal fibrosis, which affects 5–10% of subjects infected by Schistosoma mansoni, is caused by the T cell-dependent granuloma that develop around schistosome eggs. Experimental models of infection have shown that granuloma and fibrosis are tightly regulated by cytokines. However, it is unknown why advanced periportal fibrosis occurs only in certain subjects. The goal of the present study was to evaluate the cytokine response of S. mansoni-infected subjects with advanced liver disease in an attempt to relate susceptibility to periportal fibrosis with an abnormal production of cytokines that regulate granuloma and fibrosis. Fibrosis was evaluated by ultrasound on 795 inhabitants of a Sudanese village in which S. mansoni is endemic: advanced periportal fibrosis was observed in 12% of the population; 35% of the affected subjects exhibited signs of portal hypertension. Age (odds ratio (OR), 11.5), gender (OR, 4.2), and infection levels (OR, 2.2) were significantly (p ≤ 0.01) associated with hepatic fibrosis. Cytokines produced by egg-stimulated blood mononuclear cells from 99 subjects were measured (75 with no or mild fibrosis; 24 subjects with advanced fibrosis). Multivariate analysis of cytokine levels showed that high IFN-γ levels were associated with a marked reduction of the risk of fibrosis (p = 0.01; OR, 0.1); in contrast, high TNF-α levels were associated with an increased risk (p = 0.05; OR, 4.6) of periportal fibrosis. Moreover, infection levels were negatively associated with IFN-γ production. These results with observations in experimental models strongly suggest that IFN-γ plays a key role in the protection of S. mansoni-infected patients against periportal fibrosis, whereas TNF-α may aggravate the disease.