Quantifying climatic and socioeconomic drivers of urban malaria in Surat, India: a statistical spatiotemporal modelling study.

BACKGROUND: Cities are becoming increasingly important habitats for mosquito vectors of disease. The pronounced heterogeneity of urban landscapes challenges our understanding of the effects of climate and socioeconomic factors on mosquito-borne disease dynamics at different spatiotemporal scales. Here, we quantify the impact of climatic and socioeconomic factors on urban malaria risk, using an extensive dataset in both space and time for reported Plasmodium falciparum cases in the city of Surat, northwest India. METHODS: We analysed 10 years of monthly P falciparum cases resolved at three nested spatial resolutions (seven zones, 32 units, and 478 worker units) with a Bayesian hierarchical mixed model that incorporates the effects of population density, poverty, relative humidity, and temperature, in addition to random effects (structured and unstructured). To reduce dimensionality and avoid correlation of covariates, socioeconomic variables from survey data were summarised into main axes of variation using principal component analysis. With model selection, we identified the main drivers of spatiotemporal variation in malaria incidence rates at each of the three spatial resolutions. We also compared observations to model-fitted cases by quantifying the percentage of predictions within five discrete levels of malaria risk. FINDINGS: The spatial variation of urban malaria cases was stationary over time, whereby locations with high and low yearly cases remained largely consistent across years. Local socioeconomic variation could be summarised with three principal components accounting for approximately 80% of the variance. The model that incorporated local temperature and relative humidity together with two of these principal components, largely representing population density and poverty, best explained monthly malaria patterns in models formulated at the three different spatial scales. As model resolution increased, the effect size of humidity decreased, whereas those of temperature and the principal component associated with population density increased. Model predictions accurately captured aggregated total monthly cases for the city; in space-time, they more closely matched observations at the intermediate scale, with around 57% of units estimated to fall in the observed category on average across years. The mean absolute error was lower at the intermediate level, showing that this is the best aggregation level to predict the space-time dynamics of malaria incidence rates across the city with the selected model. INTERPRETATION: This statistical modelling framework provides a basis for development of a climate-driven early warning system for urban malaria for the units of Surat, including spatially explicit prediction of malaria risk several weeks to months in advance. Results indicate environmental and socioeconomic covariates for which further measurement at high resolution should lead to model improvement. Advanced warning combined with local surveillance and knowledge of disease hotspots within the city could inform targeted intervention as part of urban malaria elimination efforts. FUNDING: US National Institutes of Health.

Lymphatic filariasis elimination endgame in an urban Indian setting: the roles of surveillance and residual microfilaremia after mass drug administration.

BACKGROUND: To secure the gains of lymphatic filariasis (LF) elimination programs, attention is needed to the 'residual microfilaremia phase', in which high-risk populations may be crucial. The present study documents the impact of mass drug administration (MDA) in the urban Indian setting of Surat City, with high rates of in-migration. METHODS: Epidemiological assessment included National Filaria Control Program (NFCP) and World Health Organization recommended routine and pre-MDA microfilaremia surveys respectively. Routine filaria surveys were conducted around the year in approximately 2000-4000 people per month, while pre-MDA surveys were carried out annually among approximately 4000 people from four fixed and four random sites. In 2016, Transmission Assessment Survey (TAS) was done in primary school children. The outcomes were microfilaremia (Mf) and antigen prevalence; more specifically, microfilaremia according to place of birth, in pre-MDA and routine night blood smears (NBS) collected from 2008 to 2015. Prevalence ratios and confidence intervals were calculated. RESULTS: A total of 25 480 pre-MDA and 306 198 routine NBS were examined during the study. In 2008, the Mf prevalence in the routine survey was 63/18 814 (0.33%), declining to 23/39 717 (0.06%) in 2016. Pre-MDA surveys showed a similar decrease from 47/4184 (1.1%) in 2008 to 12/4042 (0.3%) in 2015. In those born outside Surat, microfilaremia decreased below transmission thresholds, but remained more than treble that of the remainder of the population, in both the pre-MDA surveys [prevalence ratio: 3.17, 95% confidence interval (CI): 1.15-8.72], and the routine surveys (3.31, 95% CI: 1.47-7.48). Though the TAS results indicated that MDA endpoints had been reached, sub-group analysis identified that 90% of antigenemic children were from families of high-risk groups. CONCLUSIONS: Extensive long-term epidemiological monitoring suggests that all the urban population, including high-risk groups, have benefitted from the ELF program. To prevent re-establishment of infection in large urban areas with unsanitary conditions conducive to filarial vector breeding, there is need to identify residual microfilaremia by customized surveys in addition to pre-MDA monitoring and TAS. The present findings can be used to develop strategies to prioritize screening, surveillance and plan treatment of high-risk groups after achieving MDA endpoints.

Far-lateral Transcondylar Approach to Anterior Foramen Magnum Lesions - Our Experience.

BACKGROUND: Initial surgical management of the anterior foramen magnum lesions through the posterior approaches was fraught with unacceptable morbidity, mortality, and incomplete removal. The far-lateral approach provides excellent exposure and access to these lesions resulting in complete excision of these lesions with reduced frequency of unwanted complications. MATERIALS AND METHODS: Eight patients with lesions anterior to the brainstem and upper cervical cord were surgically treated using the far-lateral transcondylar approach. Two of these patients had a meningioma while three patients had "white epidermoid." One patient had a vertebral artery (VA) aneurysm while another was a rare case of lower brainstem compression by the VA and the last was a clival chordoma. The technical aspects of this surgical procedure are briefly illustrated in this article. RESULTS: Total excision was achieved in five neoplastic cases while subtotal excision was done in one case. The VA aneurysm was satisfactorily clipped while in the brainstem compression patient, microvascular decompression was done. The VA aneurysm patient developed postoperative lower cranial nerve palsies. There were no fresh postoperative deficits in any of the other patients. One patient had an unexplained sudden cardiorespiratory arrest 18 h after the surgery and succumbed. One patient had cerebrospinal fluid (CSF) otorrhea which was satisfactorily managed by intrathecal CSF drainage. CONCLUSION: The far-lateral transcondylar approach provides excellent approach to lesions located anterior to the brainstem and upper cervical cord. Total excision of these benign lesions is safely possible through this approach.

Suppression of parathyroid hormone secretion in hemodialysis patients by a novel vitamin D analogue: 19-nor-1,25-dihydroxyvitamin D2.

In this double-blind, placebo-controlled, randomized, multicenter study, 35 patients with end-stage renal disease undergoing maintenance hemodialysis were treated three times weekly for 4 weeks with either 19-nor-1,25-dihydroxyvitamin D2 (paricalcitol) intravenously at doses ranging from 0.04 to 0.24 microg/kg or placebo. Eligible patients with secondary hyperparathyroidism (HPT; intact parathyroid hormone [iPTH] level > 300 pg/mL) were initially withdrawn from any existing vitamin D therapy over a 4-week washout period and then randomized to treatment for 4 weeks with either paricalcitol or placebo. Overall, there was a clinically and statistically significant reduction in iPTH level for patients receiving paricalcitol compared with placebo (P = 0.006). The study end point for efficacy was at least a 30% reduction from maximum baseline in iPTH level for 75% of the patients receiving paricalcitol per dosing group. The study end point for efficacy was at least a 30% reduction from maximum baseline in iPTH for 75% of patients receiving paricalcitol per dosing group. Sixty-eight percent (15 of 22) of patients receiving paricalcitol attained this efficacy end point regardless of dosage received (0.04, 0.08, 0.16, and 0.24 microg/kg). Eighty-three percent (5 of 6) of the patients in each of the paricalcitol groups receiving 0.16- and 0.24-microg/kg dosages attained the efficacy end point. Only two patients receiving placebo attained the iPTH end point. There were no clinically relevant differences in serum calcium (Ca) or phosphorus (P) levels between the group treated with paricalcitol and that treated with placebo. Although there was a statistically significant difference between the change from baseline to final-visit Ca levels in the paricalcitol group and the placebo group (P < 0.001), the final-visit mean Ca level in the paricalcitol group was within the normal range (9.44 mg/dL). There was no statistically significant difference between groups for the change from baseline in P level (P = 0.625). Only one patient treated with paricalcitol developed hypercalcemia before or coincident with the iPTH end point. Three other patients receiving paricalcitol experienced elevated serum Ca levels subsequent to reaching the iPTH end point, with iPTH reductions of 83% to 98%. There were no significant differences between patients treated with paricalcitol and patients treated with placebo in adverse reactions. These results show that paricalcitol safely and effectively reduces iPTH levels in hemodialysis patients with secondary HPT.