• Avidity of serogroup A meningococcal IgG antibodies after immunization with different doses of a tetravalent A/C/Y/W135 polysaccharide vaccine

      Bårnes, G K; Naess, L M; Rosenqvist, E; Guerin, P J; Caugant, D A; Department of Bacteriology and Immunology, Norwegian Institute of Public Health, Oslo, Norway; Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; Department of Infectious Disease Epidemiology, Norwegian Institute of Public Health, Oslo, Norway; Epicentre, Paris, France; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, CCVTM, Oxford, UK; Department of International Health, University of Oslo, Oslo, Norway (Blackwell, 2011-06-08)
      In the absence of an affordable conjugate meningococcal vaccine, mass vaccination campaigns with polysaccharide vaccines are the means to control meningitis epidemics in sub-Saharan Africa. Facing global vaccine shortage, the use of reduced doses, which have been shown to be protective by serum bactericidal activity, can save many lives. In this study, we investigated the antibody responses and avidity of IgG antibodies evoked against the serogroup A capsule of Neisseria meningitidis by different doses of an A/C/Y/W135 polysaccharide vaccine. Volunteers in Uganda were vaccinated with 1/10, 1/5 or a full dose (50 μg) and revaccinated with a full dose after 1 year. Specific IgG geometric mean concentrations and geometric mean avidity indices (GMAI) were determined by a modified enzyme-linked immunosorbent assay (ELISA) using thiocyanate as a chaotropic agent. After vaccination with 1/10 or 1/5 doses, the GMAI increased from 1 month to 1 year. One year following the initial dose, the GMAI levels were higher in the arm receiving reduced doses than for the arm receiving a full dose. Following the second full dose, avidity indices equalized at approximately the same level in the three arms. Although there are practical challenges to the use of reduced doses in the field, our findings suggest that reduced doses of polysaccharide vaccine are able to elicit antibodies of as good avidity against serogroup A polysaccharide as a full dose.
    • Factors associated with Condom Use Problems during Vaginal Sex with main and non-main partners

      DʼAnna, L H; Korosteleva, O; Warner, L; Douglas, J; Paul, S; Metcalf, C; McIlvaine, E; Malotte, C K; California State University, Long Beach, Center for Health Care Innovation, and Department of Math and Statistics, LongBeach, CA 90840, USA. laura.d’anna@csulb.edu (2012-09-01)
      Incorrect condom use is a common problem that can undermine their prevention impact. We assessed the prevalence of 2 condom use problems, breakage/slippage and partial use, compared problems by partnership type, and examined associations with respondent, partner, and partnership characteristics.
    • In vivo assessment of drug efficacy against Plasmodium falciparum malaria: duration of follow-up.

      Stepniewska, K; Taylor, W R J; Mayxay, M; Price, R; Smithuis, F; Guthmann, J P; Barnes, K; Myint, H Y; Adjuik, M; Olliaro, P; et al. (2004-11)
      To determine the optimum duration of follow-up for the assessment of drug efficacy against Plasmodium falciparum malaria, 96 trial arms from randomized controlled trials (RCTs) with follow-up of 28 days or longer that were conducted between 1990 and 2003 were analyzed. These trials enrolled 13,772 patients, and participating patients comprised 23% of all patients enrolled in RCTs over the past 40 years; 61 (64%) trial arms were conducted in areas where the rate of malaria transmission was low, and 58 (50%) trial arms were supported by parasite genotyping to distinguish true recrudescences from reinfections. The median overall failure rate reported was 10% (range, 0 to 47%). The widely used day 14 assessment had a sensitivity of between 0 and 37% in identifying treatment failures and had no predictive value. Assessment at day 28 had a sensitivity of 66% overall (28 to 100% in individual trials) but could be used to predict the true failure rate if either parasite genotyping was performed (r(2) = 0.94) or if the entomological inoculation rate was known. In the assessment of drug efficacy against falciparum malaria, 28 days should be the minimum period of follow-up.
    • Randomized trials to optimize treatment of multidrug-resistant tuberculosis

      Mitnick, C D; Castro, K G; Harrington, M; Sacks, L V; Burman, W; Harvard Medical School, Boston, MA, USA; Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, GA, USA; Treatment Action Group, New York, NY, USA; Food and Drug Administration, Rockville, MD, USA; Denver Public Health and University of Colorado Health Sciences Center, Denver, CO, USA (2007-11-06)
    • Treatment options for visceral leishmaniasis: a systematic review of clinical studies done in India, 1980-2004.

      Olliaro, P L; Guerin, P J; Gerstl, S; Haaskjold, A A; Rottingen, J A; Sundar, S; UNICEF/UNDP/World Bank/WHO Special Programme on Research and Training in Tropical Diseases, WHO, Geneva, Switzerland. olliarop@who.int (Elsevier, 2005-12)
      The state of Bihar in India carries the largest share of the world's burden of antimony-resistant visceral leishmaniasis. We analysed clinical studies done in Bihar with different treatments between 1980 and 2004. Overall, 53 studies were included (all but one published), of which 15 were comparative (randomised, quasi-randomised, or non-randomised), 23 dose-finding, and 15 non-comparative. Data from comparative studies were pooled when appropriate for meta-analysis. Overall, these studies enrolled 7263 patients in 123 treatment arms. Adequacy of methods used to do the studies and report on them varied. Unresponsiveness to antimony has developed steadily in the past to such an extent that antimony must now be replaced, despite attempts to stop its progression by increasing dose and duration of therapy. The classic second-line treatments are unsuited: pentamidine is toxic and its efficacy has also declined, and amphotericin B deoxycholate is effective but requires hospitalisation for long periods and toxicity is common. Liposomal amphotericin B is very effective and safe but currently unaffordable because of its high price. Miltefosine-the first oral drug for visceral leishmaniasis-is now registered and marketed in India and is effective, but should be used under supervision to prevent misuse. Paromomycin (or aminosidine) is effective and safe, and although not yet available, a regulatory submission is due soon. To preserve the limited armamentarium of drugs to treat visceral leishmaniasis, drugs should not be deployed unprotected; combinations can make drugs last longer, improve treatment, and reduce costs to households and health systems. India, Bangladesh, and Nepal agreed recently to undertake measures towards the elimination of visceral leishmaniasis. The lessons learnt in Bihar could help inform policy decisions both regionally and elsewhere.