Long-term persistence of cellular hyporesponsiveness to filarial antigens after clearance microfilaraemia

The persistence of parasite-specific cellular hyporesponsiveness after clearance of blood microfilariae (mf) was studied in 18 individuals who had been treated with a single dose of ivermectin, diethylcarbamazine, or a combination 2-3 years previously and who had initially cleared their parasitemia. At recruitment into the present study, 50% were again mf+ and 50% remained mf-. There were no significant differences between the mf+ and mf- groups in the amount of interferon- g (IFN- g) produced by peripheral blood mononuclear cells in response to adult or microfilarial antigens, although IFN- g production in response to purified protein derivative was greater in the mf+ group (geometric mean [gm] = 3,791 pg/ml; P = 0.02) than in the mf- group (gm = 600 pg/ml). These data suggest that although microfilaremic individuals may temporarily regain the ability to produce IFN- g to parasite antigens post-treatment, they subsequently revert to a state of hyporesponsiveness to mf-containing antigens that appears to be independent of the recurrence of microfilaremia and the response to nonparasite antigens

Australian Aboriginal children with otitis media have reduced antibody titers to specific nontypeable Haemophilus influenzae vaccine antigens

Indigenous populations experience high rates of otitis media (OM), with increased chronicity and severity, compared to those experienced by their nonindigenous counterparts. Data on immune responses to otopathogenic bacteria in these high-risk populations are lacking. Nontypeable Haemophilus influenzae (NTHi) is the predominant otopathogen in Australia. No vaccines are currently licensed to target NTHi; however, protein D (PD) from NTHi is included as a carrier protein in the 10-valent pneumococcal polysaccharide conjugate vaccine (PHiD10-CV), and other promising protein vaccine candidates exist, including outer membrane protein 4 (P4) and protein 6 (P6). We measured the levels of serum and salivary IgA and IgG against PD, P4, and P6 in Aboriginal and non-Aboriginal children with chronic OM who were undergoing surgery and compared the levels with those in healthy non-Aboriginal children (controls). We found that Aboriginal cases had lower serum IgG titers to all NTHi proteins assessed, particularly PD. In contrast, serum IgA and salivary IgA and IgG titers to each of these 3 proteins were equivalent to or higher than those in both non-Aboriginal cases and healthy controls. While serum antibody levels increased with age in healthy controls, no changes in titers were observed with age in non-Aboriginal cases, and a trend toward decreasing titers with age was observed in Aboriginal cases. This suggests that decreased serum IgG responses to NTHi outer membrane proteins may contribute to the development of chronic and severe OM in Australian Aboriginal children and other indigenous populations. These data are important for understanding the potential benefits of PHiD10-CV implementation and the development of NTHi protein-based vaccines for indigenous populations

A controlled trial of ivermectin and diethylcarbamazine in lymphatic filariasis

Ivermectin is a new antifilarial drug that can be given in a single oral dose. To compare the efficacy and side effects of ivermectin with those of diethylcarbamazine, the standard antifilarial treatment, we conducted a randomized, double-blind trial in 40 south Indian men with lymphatic filariasis caused by Wuchereria bancrofti. Patients were randomly assigned to one of three treatments: a single low dose of ivermectin (mean [+ SE], 21.3+0.7 g per kilogram of body weight; n = 13) followed by placebo for 12 days; a single high dose of ivermectin (mean, 126.2+3.7 g per kilogram; n = 13) followed by placebo for 12 days; or diethylcarbamazine for 13 days (6 mg per kilogram per day for 12 days preceded by 3 mg per kilogram for 1 day; n = 14). Eleven patients were initially assigned to receive placebo and after five days were re-assigned to one of the three treatment groups. At day 12 there was complete clearance of microfilariae from the blood in all 26 men who took ivermectin and in 11 of the 14 men who took diethylcarbamazine. At six months the numbers of detectable microfilariae (as a percentage of the pretreatment values) were 18.3 percent after low-dose ivermectin and 19.5 percent after high-dose ivermectin, as compared with 6.0 percent after diethylcarbamazine (P<0.05). The side effects were confined to the first five days and were similar in the three treatment groups. We conclude that in lymphatic filariasis, the clinical response to a single dose of ivermectin compares favourably with that after the standard 12-day course of diethylcarbamazine. Given the practical advantages of single-dose administration, ivermectin should become a useful medication for the control of bancroftian filariasis

Synthetic Hydrogel as an Artificial Vitreous Body. A One-Year Animal Study of Its Effects on the Retina

A hydrogel with a high water content was assessed in vitro and in vivo as a possible vitreous substitute. From a large series of polymers produced by the aqueous polymerization of methyl acrylamidoglycolate methyl ether (MAGME), a gel synthesized in 80% water was selected for an animal study. The gel was injected intravitreally into rabbit eyes and followed clinically by ophthalmoscopy, tonometry, and fundus photography. The gel was clinically well tolerated, but after 6 months ophthalmoscopy revealed progressive pallor of the optic nerve head. The eyes were enucleated one year after injection of polymer. Histopathological examination by light microscopy of retinal and vitreal sections revealed significant retinal disorganization, degeneration of the optic nerve and retinal neural elements, retinal detachment, and inflammatory changes. Analysis of immunohistochemically labeled retinal sections revealed loss of ganglion cells and extensive pathological reaction of the Muller cells and astrocytes. All these findings were consistent with a toxic effect of the polymer itself or some residual contaminants. The cytotoxicity of the hydrogel was assessed in vitro using cultured mouse (Balb/c-3T3) fibroblasts. The bioassay showed both cytostatic and cytocidal effects of the polymer. Our results indicate that hydrogels produced from MAGME monomer cannot function as vitreous substitutes because of severe toxic reaction elicited to the posterior segment of the eye

Hypothyroidism with scholastic excellence

A 9-year-old boy had presented with not gaining adequate height with complaints of constipation from 5 years, lethargy and loss of appetite from past 6 months. He was diagnosed to have hypothyroidism with high thyroid antibody levels. Though he was stunted his neurocognition and scholastic performance was excellent as evidenced by his school rank cards. His physical symptoms had improved after thyroxin supplemen