Epidemiological screening and xenomonitoring for human lymphatic filariasis infection in select districts in the states of Maharashtra and Karnataka, India.

Lymphatic filariasis (LF) is a mosquito-transmitted tropical neglected parasitic infection that currently affects over 120 million people around the world and another 856 million people are at risk of acquiring the infection. Mass Drug Administration (MDA) spearheaded by the World Health Organization is the only current strategy to control this infection in endemic areas. In this study, we performed an epidemiological survey in select regions in the southern parts of India to determine the current status of LF infection in subjects. Night blood samples were collected from 916 subjects after proper consent and were screened for the presence of circulating microfilariae of Wuchereria bancrofti in their peripheral blood. Our results showed the presence of 51 (5.56%) cases of human LF infection in the surveyed areas including new cases for LF, which were not recorded previously. Given the presence of new cases of LF infections, we trapped mosquitoes from these regions and screened for the presence of W. bancrofti L3 specific Ssp1 DNA repeat sequences by PCR. Our results confirmed the presence of LF infection in the mosquitoes collected from six out of nine districts that we surveyed. These findings confirm active transmission of LF infection in all of the areas that we surveyed, despite several years of MDA treatment. The findings in this study suggest potential reemergence of LF infection in most of the areas we surveyed and warrants for a more stringent strategy for controlling LF in these endemic areas.

Early quadriceps tendon rupture after primary total knee arthroplasty.

BACKGROUND: Extensor mechanism disruption following total knee arthroplasty (TKA) is a rare complication and results in significant morbidity and severe functional limitations. Quadriceps tendon rupture in the early postoperative period after TKA is one limitation about which there is a significant paucity of available information. METHODS: In this retrospective study of 2404 patients who underwent primary TKA between June 2015 to May 2016, there were 10 quadriceps tendon ruptures in seven patients (three bilateral, four unilateral) presented within 3 months after surgery. The rupture was due to a sudden fall while walking or getting up from a chair. All seven patients presented with haematoma formation around the knee, inability to get up and inability to walk. Diagnosis was confirmed by ultrasonography and managed by exploration and end-to-end tendon repair by suturing. RESULTS: In our study, incidence of quadriceps tendon tear in the early postoperative period (within 3 months) after TKA is 0.29% (seven of 2404). All patients had rupture within 90days of primary TKA; early primary repair was performed in all cases. All patients achieved preoperative range of motion without extension lag or restriction in range of movement within 6 months of repair of the quadriceps tendon. CONCLUSION: Early identification and prompt treatment of quadriceps tendon injury followed by controlled postoperative rehabilitation results in excellent short-term and mid-term outcomes.

Cloning and characterization of high mobility group box protein 1 (HMGB1) of Wuchereria bancrofti and Brugia malayi.

A human homologue of high mobility group box 1 (HMGB1) protein was cloned and characterized from the human filarial parasites Wuchereria bancrofti and Brugia malayi. Sequence analysis showed that W. bancrofti HMGB1 (WbHMGB1) and B. malayi HMGB1 (BmHMGB1) proteins share 99 % sequence identity. Filarial HMGB1 showed typical architectural sequence characteristics of HMGB family of proteins and consisted of only a single HMG box domain that had significant sequence similarity to the pro-inflammatory B box domain of human HMGB1. When incubated with mouse peritoneal macrophages and human promyelocytic leukemia cells, rBmHMGB1 induced secretion of significant levels of pro-inflammatory cytokines such as TNF-α, GM-CSF, and IL-6. Functional analysis also showed that the filarial HMGB1 proteins can bind to supercoiled DNA similar to other HMG family of proteins. BmHMGB1 protein is expressed in the adult and microfilarial stages of the parasite and is found in the excretory secretions of the live parasites. These findings suggest that filarial HMGB1 may have a significant role in lymphatic pathology associated with lymphatic filariasis.

Novel microfilaricidal activity of nanosilver.

PURPOSE: The currently available drug repertoire against lymphatic filariasis, a major health hazard in the developing world, is inadequate and is fraught with serious limitations. Thus, the development of an effective antifilarial strategy has become a global research thrust mandated by the World Health Organization. Nanoparticles of silver endowed with antibacterial potency are known to induce apoptosis in eukaryotic cells. The present study was designed to investigate the possible microfilaricidal efficacy of silver nanoparticles and to establish the validity of apoptotic rationale in antifilarial drug designing. METHODS: This report analyzed the effect of nanoparticles of silver as well as gold (size range: 10-15 nm) on the microfilariae of Brugia malayi obtained from the lavage of peritoneal cavities of infected jirds (Meriones unguiculatus). The study included a microfilarial motility assay, a trypan blue exclusion test, a poly(adenosine diphosphate-ribose) polymerase activity study, ethidium bromide/acridine orange differential staining, and transmission, as well as scanning electron microscopic evaluation of ultrastructural changes in microfilariae. RESULTS: The study demonstrates that nanoparticles of silver, but not of gold, elicited significant loss in microfilarial motility. Differential staining of parasites with ethidium bromide and acridine orange, poly(adenosine diphosphate-ribose) polymerase activity in microfilarial lysate, and electron microscopic findings underscored apoptotic death of parasites attributable to nanosilver. In a trypan blue exclusion test, the 50% lethal dose of nanosilver was measured to be 101.2 µM, which was higher than the recorded complete inhibitory concentration value (50.6 µM), thus supporting nanosilver as a potential drug candidate against lymphatic filariasis. CONCLUSION: The present report provides the first ever conclusive proof in support of apoptosis as a novel stratagem in antifilarial drug designing and nanoscale silver as a valid lead in research on antifilarial therapeutics. The main embargo about the current drug diethylcarbamazine citrate is its empirical use without rationale. Effective microfilaricidal activity of nanosilver at relatively low concentrations as reported in this study, with evidence of the induction of apoptosis in microfilariae, projects nanosilver as a potential drug adjuvant against lymphatic filariasis. The much higher 50% lethal dose value of nanosilver compared to the complete inhibitory concentration value reported in this study argues in favor of a safe therapeutic window of this agent in its antifilarial efficacy.