Antibody responses in Plasmodium falciparum malaria and their relation to protection against the disease

Protective immunity against Plasmodium falciparum may be obtained after repeated exposure to infection. Several studies indicate that immunity against the blood stages of the P. Falciparum infection is mainly antibody mediated. Protective antibodies may act either on their own, mediate antibody-dependent phagocytosis and/or cell-mediated neutralization of parasites. This thesis describes several aspects of humoral immune responses to P. falciparum infection in individuals of different age groups, different genetic background and with different degrees of malaria exposure. Several target antigens for antibody-mediated inhibition of parasite growth or invasion have been identified. One such antigen is Pf332, which appears on the surface of parasitized erythrocytes at late trophozoite and schizont stage. This surface exposure makes the antigen a possible target for opsonizing antibodies. We optimized an in vitro assay for studying cellmediated parasite neutralization in the presence of Pf332-reactive antibodies. Our data demonstrate that, Pf332 specific antibodies are able to inhibit parasite growth on their own and in cooperation with human monocytes. The P. falciparum parasites have evolved several mechanisms to evade the host neutralizing immune responses. In this thesis, we show that freshly isolated P. falciparum parasites from children living in a malaria endemic area of Burkina Faso were less sensitive for growth inhibition in vitro by autologous immunoglobulins (Ig) compared with heterologous ones. Analyses of two consecutive isolates taken 14 days apart, with regard to genotypes and sensitivity to growth inhibition in vitro, did not give any clear-cut indications on possible mechanisms leading to a reduced inhibitory activity in autologous parasite/antibody combinations. The frequent presence of persisting parasite clones in asymptomatic children indicates that the parasite possesses as yet undefined mechanisms to evade neutralizing immune responses. Transmission reducing measures such insecticide treated nets (ITNs) have been shown to be effective in reducing morbidity and mortality from malaria. However, concerns have been raised that ITNs usage could affect the acquisition of malaria immunity. We studied the effect of the use of insecticide treated curtains (ITC) on anti-malarial immune responses of children living in villages with ITC since birth. The use of ITC did neither affect the levels of parasite neutralizing immune responses nor the multiplicity of infection. These results indicate that the use of ITC does not interfere with the acquisition of anti-malarial immunity in children living in a malaria hyperendemic area. There is substantial evidence that the African Fulani tribe is markedly less susceptible to malaria infection compared to other sympatrically living ethnic tribes. We investigated the isotypic humoral responses against P. falciparum asexual blood stages in different ethnic groups living in sympatry in two countries exhibiting different malaria transmission intensities, Burkina Faso and Mali. We observed higher levels of the total malaria-specific-IgG and its cytophilic subclasses in individuals of the Fulani tribe as compared to non-Fulani individuals. Fulani individuals also showed higher levels of antibodies to measles antigen, indicating that the intertribal differences are not specific for malaria and might reflect a generally activated immune system in the Fulani.

Police Interviews with Victims and Suspects of Violent and Sexual Crimes : Interviewee's experiences and interview outcomes

The police interview is one of the most important investigative tools that law enforcement has close at hand, and police interview methods have changed during the twentieth century. A good police interview is conducted in the frame of the law, is governed by the interview goal, and is influenced by facilitating factors that may affect the elicited report. The present doctoral dissertation focuses on police interviews in cases of very serious crimes of violence and sexual offences. Results reveal crime victims’ and perpetrators’ experiences of being interviewed and police officers’ attitudes towards conducting interviews related to traumatizing crimes. Study 1 revealed that when police officers interviewed murderers and sexual offenders, the interviewees perceived attitudes characterized by either dominance or humanity. Police interviews marked by dominance and suspects’ responses of anxiety were mainly associated with a higher proportion of denials, whereas an approach marked by humanity, and responses of being respected were significantly associated with admissions. In line with Study 1, the victims of rape and aggravated assault in Study 2 also revealed the experience of two police interview styles, where an interviewing style marked by dominance and responses of anxiety was significantly associated with crime victims’ omissions of information. Moreover, a humanitarian interviewing style, and crime victims’ feelings of being respected and co-operative, was significantly related to crime victims providing all information from painful events. Special squad police officers’ attitudes towards interviewing crime victims, in Study 3, also showed a humanitarian approach and two dominant approaches, one affective and the other refusing. The attitude towards interviewing suspects of crimes in focus revealed humanitarian and dominant interviewing attitudes, and an approach marked by kindness. The present thesis shows that, during their entire career, an overwhelming majority of the special squad police officers have experienced stressful events during patrol as well as investigative duty. Results show that symptoms from stressful event exposures and coping mechanisms are associated with negative attitudes towards interviewing suspects and supportive attitudes towards crime victim interviews. Thus, experiences from stressful exposures may automatically activate ego-defensive functions that automatically generate dominant attitudes. Moreover, it is important to offer police officers who have been exposed to stressful events the opportunity to work through their experiences, for example, through debriefing procedures. After debriefings, police officers are better prepared to meet crime victims and suspects and, through conscious closed-loop processes, to conduct police interviews without awaking ego-defensive functions.