The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide

Summary: Immune regulation by parasites is a global concept that includes suppression, diversion, and conversion of the host immune response to the benefit of the pathogen. While many microparasites escape immune attack by antigenic variation or sequestration in specialized niches, helminths appear to thrive in exposed extracellular locations, such as the lymphatics, bloodstream, or gastrointestinal tract. We review here the multiple layers of immunoregulation that have now been discovered in helminth infection and discuss both the cellular and the molecular interactions involved. Key events among the host cell population are dominance of the T-helper 2 cell (Th2) phenotype and the selective loss of effector activity, against a background of regulatory T cells, alternatively activated macrophages, and Th2-inducing dendritic cells. Increasingly, there is evidence of important effects on other innate cell types, particularly mast cells and eosinophils. The sum effect of these changes to host reactivity is to create an anti-inflammatory environment, which is most favorable to parasite survival. We hypothesize therefore that parasites have evolved specific molecular strategies to induce this conducive landscape, and we review the foremost candidate immunomodulators released by helminths, including cytokine homologs, protease inhibitors, and an intriguing set of novel products implicated in immune suppression.

Helminth parasites – masters of regulation

Hotez et al. argue that achieving success in the global fight against HIV/AIDS, tuberculosis, and malaria may well require a concurrent attack on the neglected tropical diseases.

/pdf/incorporating-a-rapid-impact-package-for-neglected-tropical-1fvfqimigr.pdf

Incorporating a Rapid-Impact Package for Neglected Tropical Diseases with Programs for HIV/AIDS, Tuberculosis, and Malaria

Surviving a given infection requires the generation of a controlled immune response. Failure to establish or restore homeostatic conditions during or following the onset of an infection can lead to tissue damage. Investigation of the immunoregulatory network that arises in response to the infectious process or that is induced by the pathogen itself should provide insight into therapeutic approaches for the control of infection and any subsequent immunopathology. In this Review, I discuss current hypotheses and points of polemic associated with the origin, mode of action and antigen specificity of the various populations of regulatory T cells that arise during infection.

Regulatory T cells and infection: a dangerous necessity

In natural systems, individuals are often co-infected by many species of parasites. However, the significance of interactions between species and the processes that shape within-host parasite communities remain unclear. Studies of parasite community ecology are often descriptive, focusing on patterns of parasite abundance across host populations rather than on the mechanisms that underlie interactions within a host. These within-host interactions are crucial for determining the fitness and transmissibility of co-infecting parasite species. Here, we highlight how techniques from community ecology can be used to restructure the approaches used to study parasite communities. We discuss insights offered by this mechanistic approach that will be crucial for predicting the impact on wildlife and human health of disease control measures, climate change or novel parasite species introductions.

Emphasizing the ecology in parasite community ecology.

The influence of intestinal worm infections on malaria was studied in individuals from Dielmo, Senegal in 1998. Results suggest that, compared with those infected, individuals free of helminths had the same degree of protection against malaria as that provided by sickle-cell trait, the most potent factor of resistance to malaria identified to date.

Increased frequency of malaria attacks in subjects co-infected by intestinal worms and Plasmodium falciparum malaria.

An outbreak of yellow fever (YF) occurred in the central part of Senegal during October 1995. Thirty-one probable cases were detected and 79 cases were confirmed either by IgM ELISA or by virus isolation (30 strains isolated). The case fatality rate was 18.9%. Incidence of the infection was evaluated by a serosurvey in the area. Males 10-29 years old belonging to the Peul ethnic group were more affected. Moreover, 28 YF virus strains were isolated from mosquitoes and larvae pools and vertical transmission of YF virus by Aedes aegypti was also demonstrated for the first time in the field. This outbreak occurred after the major amplification of the wild cycle of YF virus in 1993 in West Africa. This epidemic represented a typical example of intermediate transmission of YF: both humans and wild vertebrates are involved in the virus cycle through wild mosquitoes with semidomestic habits, mainly Ae. furcifer, Ae. luteocephalus, and domestic vector Ae. aegypti. It was controlled by a prompt immunization campaign. The impact of inclusion of YF vaccine in the Expanded Program of Immunization, which has been conducted in Senegal for eight years, is discussed.

/pdf/re-emergence-of-yellow-fever-in-senegal-in-1995-43zhn2cfwa.pdf

Re-emergence of yellow fever in senegal in 1995

Between January and April 1998, a meningitis outbreak due to serogroup A meningococcus took place in Senegal. The outbreak began in Gandiaye, 165 km to the east of Dakar, and progressed towards the towns of Gossas, Niakkhar, Guinguineo, Fatik, Foundiougne, Dioffior, Sokone, Kaolack, and Nioro. At the same time, the outbreak reached regions of Kaffrine, Koungheul, and Tambacounda in the east of Senegal. A total of 1,350 cases and 200 deaths were reported. The WHO Collaborating Center in Marseilles received 24 strains for analysis. All were serogroup A Neisseria meningitidis, type 4 and subtype P1.9. Multilocus enzyme electrophoresis, performed by Institut Pasteur Paris, showed that the strains belonged to clone III-1. DNA restriction fragments generated by endonuclease BglII and analyzed by pulsed-field gel electrophoresis showed 24 indistinguishable fingerprint patterns similar to those of meningococcus strains isolated from African outbreaks since 1988. Three strains were studied by multilocus sequence typing (MLST) with seven loci. The comparison between sequences and existing alleles on the MLST website (http://mlst.zoo.ox.ac.uk) allowed us to assign these strains to sequence type 5 (ST5), as their sequences were identical to the consensus at seven loci. All 24 strains were susceptible to penicillin, amoxicillin, chloramphenicol, and rifampin. Subgroup III is finishing its spread towards west of the meningitis belt of Africa. To our knowledge, this is the first time subgroup III, and more precisely ST5, strains are reported as being responsible for a meningitis outbreak in Senegal.

The 1998 Senegal epidemic of meningitis was due to the clonal expansion of A:4:P1.9, clone III-1, sequence type 5 Neisseria meningitidis strains.

In Black Africa, the role of hepatitis C virus (HCV) in the onset of chronic hepatic disease is unclear. This is particularly true in Senegal where the prevalence of HCV is moderate. To gain insight into this question, a case-control study including 73 patients and 73 controls was carried out at Principal Hospital in Dakar in 1995. The patients included in this study presented chronic hepatitis in 2 cases cirrhosis in 25 and hepatocellular carcinoma in 46. Patients and controls underwent serologic testing for HCV (ELISA screening test followed by 3rd generation ELISA test in case of positive results and confirmation by immunoblot) with determination of HCV serotype using the immunoenzymatic method. Testing also included research for infection by hepatitis B virus and for anti-delta antibodies. Anti-HCV antibodies were detected in two patients (3 p. 100) and serology was suspicious in two others. Serotype 2 was detected in one of these patients. No positive results were recorded in controls. Fifty-four patients (74 p. 100) and 15 controls (21 p. 100) presented the HBs antigen including 13 patients (24 p. 100) and I control (7 p. 100) with anti-delta antibodies. This study shows that HCV currently plays a minor role in the onset of hepatic disease in hospitalized patients in Senegal. It also confirms the predominant role of hepatitis B and complicating effect of the delta hepatitis virus. These findings are compared with reported data for Black African countries. The impact of HCV appears to be lower in Senegal than in central Africa.

Georges Raphenon

Papers

Increased frequency of malaria attacks in subjects co-infected by intestinal worms and Plasmodium falciparum malaria.

Re-emergence of yellow fever in senegal in 1995

The 1998 Senegal epidemic of meningitis was due to the clonal expansion of A:4:P1.9, clone III-1, sequence type 5 Neisseria meningitidis strains.

[Hepatitis C virus and chronic hepatopathies in Dakar: case-control study].

Prevalence of antibodies to hepatitis C among recently treated leprosy patients in Senegal parallels those in normal populations.