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Background: Tuberculosis is still one of the most infectious diseases in China. This study aimed to explore the spatio-temporal distribution of TB and the associated factors in mainland China from 2009 to 2015., Methods: A Bayesian spatio-temporal model was utilized to analyse the correlation of socio-economic, healthcare, demographic and meteorological factors with the population level number of TB., Results: The Bayesian spatio-temporal analysis showed that for the population level number of TB, the estimated parameters of the ratio of males to females, the number of beds in medical institutions, the population density, the proportion of the population that is rural, the amount of precipitation, the largest wind speed and the sunshine duration were 0.556, 0.197, 0.199, 29.03,0.1958, 0.0854 and 0.2117, respectively, demonstrating positive associations. However, health personnel, per capita annual gross domestic product, minimum temperature and humidity indicated negative associations, and the corresponding parameters were -0.050, -0.095, -0.0022 and -0.0070, respectively., Conclusions: Socio-economic, number of health personnel, demographic and meteorological factors could affect the case notification number of TB to different degrees and in different directions., (Copyright © 2019. Published by Elsevier B.V.)

Human Trypanosomiasis is a rare occurrence in India. In the cases reported so far the disease causative species have been the species infective to animals viz., Trypanosoma lewisi and Trypanosoma evansi. These animal species usually non pathogenic in humans can acquire the desired virulence and emerge as human pathogens causing serious disease, in the right combination of environmental, host related and organism related factors. We report here a case of trypanosomiasis caused by the rodent parasite T. lewisi in a two months old infant in urban Mumbai. Under the fastly changing environmental scenario there is an urgent need to be prepared for the emerging zoonoses. Any unusual disease occurrence in a given geographical area acquires a special significance in this context and should be reported to assess its public health importance and be prepared to deal with the consequent challenges posed, if any.

Trypanosoma lewisi is an obligatory, flagellated parasite of the rat. Despite the fact that naturally the rats overcome the disease, a lethal infection can be induced by the administration of an immunosuppressive agent, i.e. cyclophosphamide (Cy). In the Cy treated infected rats (CyI) the severity of the trypanosome infection was demonstrated in the internal organs, in the following order: lungs>liver>heart>spleen>kidney. The parasites were not detected in the brain. The accumulation of the parasites in the lungs led to the development of hemorrhagic inflammatory foci. The rupture of blood vessels was accompanied by lymphocyte infiltrations into the damaged tissues and multiple foci of edema around the blood vessels. In most cases the lungs were dark brown in color due to intra-alveolar hemorrhages. The spleen of the CyI rats showed general deformation of the tissue's architecture, migration of macrophages and cell depletion due to the Cy action. The liver showed inflammatory hemorrhagic foci associated with massive destruction of the parenchyma. In spite of the heavy parasitemia (>50%) developed in the CyI rats the brain remained free of parasites, which might explain the non-virulent character of this parasite compared to the African trypanosomes.

The development of Trypanosoma musculi and Trypanosoma lewisi were studied in vitro in the presence of adherent splenic cells. Both parasites developed only when attached by their flagellar tips to adherent splenic cells. During the proliferation of T. musculi, the kinetoplast migrated towards the nucleus, and once in the vicinity of the nucleus, the nuclear division was triggered. The kinetoplast of T. lewisi did not migrate towards the nucleus, but remained at its original location. The nucleus and kinetoplast divided at the same time in both parasites, and parasites started dividing from their flagellar ends and T. musculi and T. lewisi daughter cells were formed within 48 h. The unavailability of the adherent splenic cells in vitro led the parasites to transform into round/oval nonviable forms.

The culture technique used proved to be more simple and economical than the different culture methods described in literature. This process permits the in vitro growth of parasites for a period long enough (10 days) to determine the possible activity of drugs. On the 10th day the cultures are infectious.

Four species of trypanosome were examined for phospholipase activities using 1-[3H]palmitoyl-2-acyl-sn-glycero-3-phosphocholine and 1-acyl-2[14C]linoleoyl-sn-glycero-3-phosphocholine as substrates. The major activity in each species is a phospholipase A1 (EC 3.1.1.32) which does not require calcium. The most effective of the detergents tested for activation of the enzyme from each species, and the Ph optima, are as follows: Trypanosoma brucei, 0.125% Triton X-100 at pH 6.0-8.5; T. congolense, 0.5 mM linoleate at pH 6.0; T. theileri, 0.1% Triton X-100 at pH 6.75; T. lewisi, 0.2 mM sodium dodecyl sulfate at pH 5.2. The specific activity of the enzyme from a pathogenic species, T. brucei, is very high (145 nmol/min/mg/protein) and could contribute to the tissue damage characteristically caused by this parasite. The level in T. lewisi, a non-pathogenic species, is relatively low (1 nmol/min/mg). The levels in T. theileri (31 nmol/min/mg) and T. congolense (10 nmol/min/mg are intermediate. These results are compatible with the hypothesis that phospholipases contribute to the pathogenicity of trypanosomes.

Transketolase and pyruvate changes were studied in rats infected with Trypanosoma lewisi and fed complete, thiamine-deficient and pair-fed control diets. Regardless of the dietary group, marked increases in pyruvate levels were observed in the infected animals. There were no significant differences in erythrocyte transketolase activity of rats given a full complement diet. Significant decreases, however, were observed in the transketolase activity of pair-fed and thiamine deficient rats. The greater decreases occurred in the infected animals.

The phenomenon of natural (innate) resistance is exemplified by the solid resistance of mice to infection with the rat-specific Trypanosoma lewisi. We provide more information about the mechanism of resistance in this model system. Resistance was not diminished in aged mice or reduced by ionizing radiation or splenectomy. There was no difference in resistance of C5-deficient mice (B10.D2/oSn and AKR) compared with their normocomplementemic counterparts (B10.D2/nSn and C57BL/6). Treatment of mice with cobra venom factor resulted in greatly prolonged survival of T. lewisi in mice. Combined treatment of mice with cobra venom factor and silica dust resulted in not only prolonged survival but also considerable intravascular growth of the parasite and resultant death of the mice. T. lewisi cells from irradiated donor rats, or after surface coat removal with trypsin, were eliminated by inoculated mice more efficiently than were parasites acquired from normal rats. Incubation of trypanosomes obtained from irradiated rats in normal rat serum restored their resistance to rapid elimination. From the results of these studies and other recent investigations, we have concluded that murine resistance to T. lewisi involves activation and binding of C3b by uncoated trypanosomes and concomitant participation of radiation-resistant, silica dust-sensitive effector cells (probably macrophages and neutrophils), and rat plasma proteins, integrated into the trypanosome surface coat, stabilize the coat, make it less susceptible to removal when the trypanosome is present in the mouse bloodstream, and thus delay exposure of underlying molecules (receptors?) that activate murine C3.