Syphilis partner notification with men who have sex with men: a review and commentary.

BACKGROUND: Eight US cities experienced large outbreaks of syphilis among men having sex with men (MSM), beginning during 2000-2001. Provider-assisted partner notification via disease intervention specialists has traditionally composed a large part of syphilis control efforts. OBJECTIVES: Report current effectiveness of syphilis partner notification for MSM and identify related problems and solutions. RESULTS: One thousand five hundred seventeen MSM diagnosed with syphilis claimed 10,254 sex partners. Many claimed anonymous partners (median = 65%), or provided insufficient locating information (median = 42%). Median cases found per index case were 0.09 (total = 116), although an additional 197 partners had been previously treated. Principal impediments to partner notification fell into 3 areas: (1) diagnosis outside health department settings delayed interviews, (2) partners were often anonymous, and (3) mistrust among MSM, public health professionals, and health care providers in private settings. CONCLUSIONS: Characteristics of the current outbreaks among MSM make traditional partner notification more difficult than in the past. Some modifications, complements, and even alternatives to partner notification are either planned or in operation.

Identification of hemoglobin degradation products in Plasmodium falciparum.

Malaria parasites break down human hemoglobin to its constituent amino acids by cysteine and aspartic proteinases. However, no one has previously been able to identify hemoglobin cleavage products in intact parasites. When isolated parasites were subjected to non-denaturing polyacrylamide gels electrophoresis, a unique protein band was found which contains heme and reacts with anti-human hemoglobin antibodies. This protein does not appear to represent oxidized or glycosylated hemoglobin, and is present in isolated parasites but not in the cytosol of infected or uninfected erythrocytes. When this band was eluted and subjected to SDS polyacrylamide gel electrophoresis, three bands were seen on Western blots. The proteins in these bands contain proteins with the N-terminal sequences of alpha- and beta-globin chains but molecular masses of only 13.2-13.4 kDa. These data suggest that hemoglobin alpha- and beta-chains are initially cleaved within the parasite phagolysosome to release peptides of 15-17 and 23-25 amino acids from the C-termini of alpha- and beta-globin chains, respectively. Production of the hemoglobin breakdown products was inhibited by E-64, a cysteine proteinase inhibitor, suggesting the involvement of a cysteine proteinase in an early step of hemoglobin degradation.

Host cell invasion by trypanosomes requires lysosomes and microtubule/kinesin-mediated transport.

Invasion of mammalian cells by the protozoan parasite Trypanosoma cruzi occurs by an actin-independent mechanism distinct from phagocytosis. Clusters of host lysosomes are observed at the site of parasite attachment, and lysosomal markers are detected in the vacuolar membrane at early stages of the entry process. These observations led to the hypothesis that the trypanosomes recruit host lysosomes to their attachment site, and that lysosomal fusion serves as a source of membrane to form the parasitophorous vacuole. Here we directly demonstrate directional migration of lysosomes to the parasite entry site, using time-lapse video-enhanced microscopy of L6E9 myoblasts exposed to T. cruzi trypomastigotes. BSA-gold-loaded lysosomes moved towards the cell periphery, in the direction of the parasite attachment site, but only when their original position was less than 11-12 microns from the invasion site. Lysosomes more distant from the invasion area exhibited only the short multi-directional saltatory movements previously described for lysosomes, regardless of their proximity to the cell margins. Specific depletion of peripheral lysosomes was obtained by microinjection of NRK cells with antibodies against the cytoplasmic domain of lgp 120, a treatment that aggregated lysosomes in the perinuclear area and inhibited T. cruzi entry. The microtubule-binding drugs nocodazole, colchicine, vinblastine, and taxol also inhibited invasion, in both NRK and L6E9 cells. Furthermore, microinjection of antibodies to the heavy chain of kinesin blocked the acidification-induced, microtubule-dependent redistribution of lysosomes to the host cell periphery, and reduced trypomastigote entry. Our results therefore demonstrate that during T. cruzi invasion of host cells lysosomes are mobilized from the immediately surrounding area, and that availability of lysosomes at the cell periphery and microtubule/kinesin-mediated transport are requirements for parasite entry.