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

Antibiotics versus topical antiseptics for chronic suppurative otitis media

Background Chronic suppurative otitis media (CSOM), sometimes referred to as chronic otitis media (COM), is a chronic inflammation and infection of the middle ear and mastoid cavity, characterised by ear discharge (otorrhoea) through a perforated tympanic membrane. The predominant symptoms of CSOM are ear discharge and hearing loss. Antibiotics and antiseptics kill or inhibit the micro‐organisms that may be responsible for the infection. Antibiotics can be applied topically or administered systemically via the oral or injection route. Antiseptics are always directly applied to the ear (topically). Objectives To assess the effectiveness of antibiotics versus antiseptics for people with chronic suppurative otitis media (CSOM). Search methods The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL; 2019, Issue 4, via the Cochrane Register of Studies); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 1 April 2019. Selection criteria We included randomised controlled trials (RCTs) with at least a one‐week follow‐up involving patients (adults and children) who had chronic ear discharge of unknown cause or CSOM, where ear discharge had continued for more than two weeks. The intervention was any single, or combination of, antibiotic agent, whether applied topically (without steroids) or systemically. The comparison was any single, or combination of, topical antiseptic agent, applied as ear drops, powders or irrigations, or as part of an aural toileting procedure. Two comparisons were topical antiseptics compared to: a) topical antibiotics or b) systemic antibiotics. Within each comparison we separated where both groups of patients had received topical antibiotic a) alone or with aural toilet and b) on top of background treatment (such as systemic antibiotics). Data collection and analysis We used the standard Cochrane methodological procedures. We used GRADE to assess the certainty of the evidence for each outcome. Our primary outcomes were: resolution of ear discharge or 'dry ear' (whether otoscopically confirmed or not), measured at between one week and up to two weeks, two weeks to up to four weeks, and after four weeks; health‐related quality of life using a validated instrument; and ear pain (otalgia) or discomfort or local irritation. Secondary outcomes included hearing, serious complications and ototoxicity measured in several ways. Main results We identified seven studies (935 participants) across four comparisons with antibiotics compared against acetic acid, aluminium acetate, boric acid and povidone‐iodine. None of the included studies reported the outcomes of quality of life or serious complications. A. Topical antiseptic (acetic acid) versus topical antibiotics (quinolones or aminoglycosides) It is very uncertain if there is a difference in resolution of ear discharge with acetic acid compared with aminoglycosides at one to two weeks (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.72 to 1.08; 1 study; 100 participants; very low‐certainty evidence). No study reported results for ear discharge after four weeks. It was very uncertain if there was more ear pain, discomfort or local irritation with acetic acid or topical antibiotics due to the low numbers of participants reporting events (RR 0.16, 95% CI 0.02 to 1.34; 2 RCTs; 189 participants; very low‐certainty evidence). No differences between groups were reported narratively for hearing (quinolones) or suspected ototoxicity (aminoglycosides) (very low‐certainty evidence). B. Topical antiseptic (aluminium acetate) versus topical antibiotics No results for the one study comparing topical antibiotics with aluminium acetate could be used in the review. C. Topical antiseptic (boric acid) versus topical antibiotics (quinolones) One study reported more participants with resolution of ear discharge when using topical antibiotics (quinolones) compared with boric acid ear drops at between one to two weeks (risk ratio (RR) 1.86, 95% confidence interval (CI) 1.48 to 2.35; 1 study; 411 participants; moderate‐certainty evidence). This means that one additional person will have resolution of ear discharge for every four people receiving topical antibiotics (compared with boric acid) at two weeks. No study reported results for ear discharge after four weeks. There was a bigger improvement in hearing in the topical antibiotic group compared to the topical antiseptic group (mean difference (MD) 2.79 decibels (dB), 95% CI 0.48 to 5.10; 1 study; 390 participants; low‐certainty evidence) but this difference may not be clinically significant. There may be more ear pain, discomfort or irritation with boric acid compared with quinolones (RR 0.56, 95% CI 0.32 to 0.98; 2 studies; 510 participants; low‐certainty evidence). Suspected ototoxicity was not reported. D. Topical antiseptic (povidone‐iodine) versus topical antibiotics (quinolones) It is uncertain if there is a difference between quinolones and povidone‐iodine with respect to resolution of ear discharge at one to two weeks (RR 1.02, 95% CI 0.82 to 1.26; 1 RCT, 39 participants; very low‐certainty evidence). The study reported qualitatively that there were no differences between the groups for hearing and no patients developed ototoxic effects (very low‐certainty evidence). No results for resolution of ear discharge beyond four weeks, or ear pain, discomfort or irritation, were reported. E. Topical antiseptic (acetic acid) + aural toileting versus topical + systemic antibiotics (quinolones) One study reported that participants receiving topical and oral antibiotics had less resolution of ear discharge compared with acetic acid ear drops and aural toileting (suction clearance every two days) at one month (RR 0.69, 95% CI 0.53 to 0.90; 100 participants). The study did not report results for resolution of ear discharge at between one to two weeks, ear pain, discomfort or irritation, hearing or suspected ototoxicity. Authors' conclusions Treatment of CSOM with topical antibiotics (quinolones) probably results in an increase in resolution of ear discharge compared with boric acid at up to two weeks. There was limited evidence for the efficacy of other topical antibiotics or topical antiseptics and so we are unable to draw conclusions. Adverse events were not well reported

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