No abstract

No abstract

No abstract

Onchocerciasis (river blindness) is a serious health problem and a severe obstacle to social and economic development, especially in Africa. A complementary DNA fragment coding for an Onchocerca volvulus antigen (OV-16) was cloned and expressed in the plasmid vector pCG808fx. Immune responses to this O. volvulus-specific recombinant antigen were detectable in patients with documented onchocerciasis; the antibody response was also detectable at 3 months and at more than 1 year before infection could otherwise be detected in humans and in chimpanzees experimentally infected with O. volvulus third-stage larvae.

In the first phase III efficacy trial of the malaria vaccine SPf66 in Africa, MOIs in SPf66- and placebo-vaccinated children were analyzed by polymerase chain reaction-restriction fragment length polymorphism of the Plasmodium falciparum merozoite surface antigen 2 (MSA2). MOIs were significantly reduced in asymptomatic vaccine recipients compared with those in asymptomatic placebo recipients; however, no differences were observed among symptomatic children in the vaccine and control groups. These results show that immunization with SPf66 modulates the course of naturally occurring infections, as reflected by reduced MOIs. In placebo recipients, however, there was a significant negative correlation between numbers of infecting genotypes, as identified by MSA2, and morbidity. Asymptomatic placebo recipients had an average of 5 concurrent infections, whereas children with clinical cases had an average of 3.4 infections. These data provide further evidence that premunition from concurrent infections is important in immunity against clinical malaria. No such effect of multiple infections was found in the vaccinated group.

This study examined the development and persistence of immunity in humans presenting defined states of Onchocerca volvulus infection, i.e. in exposed endemic control individuals without microfilaridermia and clinical disease, in patients with patent or post‐patent onchocerciasis, and in patients concurrently infected with Mansonella perstans. Onchocerca volvulus antigen (OvAg)‐specific cellular reactivity was significantly diminished in microfilariae (mf)‐positive patients, while the highest reactivity was measured in exposed but mf‐negative endemic controls, those being free of any clinical signs of onchocercal disease. In patients who became post‐patent, responses to OvAg were significantly augmented, but did not approach entirely the magnitude observed in endemic controls. In onchocerciasis patients with concurrent mansonelliasis, cellular unresponsiveness to OvAg persisted, even when mf of O. volvulus were eliminated permanently by repeated ivermectin therapy. Cells from mf‐positive onchocerciasis patients produced significantly less interferon‐γ (IFN‐γ) (P<0·01) and interleukin‐5 (IL‐5) (P<0·05) in response to OvAg than those taken from endemic controls or post‐patent individuals in whom IFN‐γ and IL‐5 production was similarly high. In contrast, both OvAg‐driven as well as spontaneous IL‐10 secretion was higher in mf‐positive patients than in endemic controls or post‐patent cases. In all individuals examined, serological recognition of OvAg by immunoglobulins was dominated by IgG4; in mf‐positive patients OvAg of 205 000–12 000 molecular weight (MW) were strongly bound. In post‐patent individuals, and similarly in endemic controls, OvAg recognition by IgG4 varied from intense (with numerous antigens being recognized) to weak or absent antigen binding. Significantly elevated OvAg‐specific IgG isotypes were measured in mf‐positive onchocerciasis patients in comparison with endemic controls or post‐patent individuals (with the exception of IgG3). IgG1, IgG2 and IgE were higher, but IgG4 was lower in endemic controls compared with post‐patent onchocerciasis patients. The ratios of IgG4/IgG1 differed (P<0·001) between endemic controls and mf‐positive or post‐patent onchocerciasis patients, with IgG4/IgG1 ratios of R<3·0 being characteristic for endemic controls and post‐patent O. volvulus infection. In conclusion, this cross‐sectional immunoepidemiological investigation showed that distinct states of O. volvulus infection correlate with a particular cellular and humoral immune response. The mf‐free condition appeared to be associated with a vigorous parasite‐specific cellular reactivity and a particular cytokine production profile, while concurrent M. perstans infection depressed OvAg‐specific cellular responsiveness. Antibody responses, in all likelihood, reflected the intensity and state of infection, and not the degree of acquired immunity protective against parasite aggregation.

No abstract

Field studies of malaria in endemic areas frequently. use the presence or levels of parasitaemia, together with the measurement of fever, as the primary criteria Rlth which to identify cases. However, since malaria cases do not always present with measurable fever, and since asymptomatic parasitaemia occurs, additional episode markers might be useful epidemiological tools. We have measured the C-reactive protein and haptoglobin levels in paediatric patients presenting to a village health post in the Kilombero District in Tanzania and in convalescent sera from the same patients, in order to evaluate these acute-phase reactants as alternative markers of Plasmodium falciparum episodes. Among afebrile patients, C-reactive protein levels were highly correlated with parasite density. High C-reactive protein levels are therefore probably indicative of recent clinical malaria cpisodcs in currently afebrile individuals with high parasite densities. An appropriate case definition for malaria in epidemiological studies in endemic areas might therefore be hyperparasitaemia accompanied by either, or both, measurable fever and raised C-reactive protein levels. This would give less biased estimates of the overall burden of malaria morbidity than does a definition which requires measurable fever. Levels of haptoglobin were highly negatively correlated with parasitaemia, but did not appear to be useful episode markers because this correlation was probably not related to acute morbidity. However, haproglobin can be useful to assess at community level The impact of interventions on parasitaemia.