Abstract. A prospective study was carried out in a cohort of 355 persons in a leishmaniasis-endemic village of the Patna District in Bihar, India, to determine the prevalence of asymptomatic persons and rate of progression to symptomatic visceral leishmaniasis (VL) cases. At baseline screening, 50 persons were positive for leishmaniasis by any of the three tests (rK39 strip test, direct agglutination test, and polymerase chain reaction) used. Point prevalence of asymptomatic VL was 110 per 1,000 persons and the rate of progression to symptomatic cases was 17.85 per 1,000 person-months. The incidence rate ratio of progression to symptomatic case was 3.36 (95% confidence interval [CI] = 0.75-15.01, P = 0.09) among case-contacts of VL compared with neighbors. High prevalence of asymptomatic persons and clinical VL cases and high density of Phlebotomus argentipes sand flies can lead to transmission of VL in VL-endemic areas.

Good long-term survival and retention rates were obtained for VL-HIV-coinfected patients treated with liposomal amphotericin B and cART. Although the initial VL treatment response was excellent, VL relapse within 2 years remained frequent.

Out of 938 parasitologically confirmed patients with visceral leishmaniasis treated with amphotericin B (1 mg/kg bodyweight daily infused in 2 h for 20 days), 935 were cured clinically, 933 parasitologically and 931 ultimately (no relapse within 6 months). Two parasitologically 'not cured' and 4 relapsed patients were cured with 25 infusions, and 1 with double relapse with 30 infusions. The treatment was started only when serum haemoglobin reached 5 g/dL, serum electrolyte imbalance was corrected and sodium stibogluconate-induced myocardial damage stabilized after 10 days' rest. Bronchopneumonia, cardiac failure and acute renal failure caused the death of 1 patient each. Nightblindness, angular stomatitis, neuritis, and petechial haemorrhages improved with appropriate treatment; 2 patients were given blood transfusion for post-treatment anaemia. Nausea and anorexia, and changes in serum creatinine and potassium, became normal in 2 weeks. Immediate withdrawal of the drug and restart after 10 days cured 2 patients who developed acute renal failure. Infusion-related toxicities--shivering, rigor and fever--were minimized but not eliminated by prior administration of hydrocortisone. Tuberculosis and visceral leishmaniasis were treated concurrently. Four pregnant patients were successfully treated without harmful effects on mother and child. It was concluded that the dosage of amphotericin B used was an effective and well-tolerated regimen and achieved 99% cure. Toxicity could be minimized with some precautions. All unresponsive and relapsed patients responded to more amphotericin and no resistance to the drug was seen.

The ribosomal stalk in bacteria is composed of four or six copies of L12 proteins arranged in dimers that bind to the adjacent sites on protein L10, spanning 10 amino acids each from the L10 C-terminus. To study why multiple L12 dimers are required on the ribosome, we created a chromosomally engineered Escherichia coli strain, JE105, in which the peripheral L12 dimer binding site was deleted. Thus JE105 harbors ribosomes with only a single L12 dimer. Compared to MG1655, the parental strain with two L12 dimers, JE105 showed significant growth defect suggesting suboptimal function of the ribosomes with one L12 dimer. When tested in a cell-free reconstituted transcription–translation assay the synthesis of a full-length protein, firefly luciferase, was notably slower with JE105 70S ribosomes and 50S subunits. Further, in vitro analysis by fast kinetics revealed that single L12 dimer ribosomes from JE105 are defective in two major steps of translation, namely initiation and elongation involving translational GTPases IF2 and EF-G. Varying number of L12 dimers on the ribosome can be a mechanism in bacteria for modulating the rate of translation in response to growth condition.