Genomic alterations and gene expression in primary diffuse large B-cell lymphomas of immune-privileged sites: the importance of apoptosis and immunomodulatory pathways.

Primary diffuse large B-cell lymphomas of different immune-privileged sites (IP-DLBCLs) share many clinical and biological features, such as a relatively poor prognosis, preferential dissemination to other immune-privileged sites, and deletion of the HLA region, which suggests that IP-DLBCL represents a separate entity. To further investigate the nature of IP-DLBCL, we investigated site-specific genomic aberrations in 16 testicular, nine central nervous system (CNS), and 15 nodal DLBCLs using array CGH. We also determined minimal common regions of gain and loss. Using robust algorithms including multiple testing procedures and the ACE-it script, which is specifically designed for this task, the array CGH data were combined with gene expression data to explore pathways deregulated by chromosomal aberrations. Loss of 6p21.32-p25.3, including the HLA genes, was associated with both types of IP-DLBCL, whereas gain of 2p16.1-p25.3 was associated with nodal DLBCL. Gain of 12q15-q21.1 and 12q24.32-q24.33 was associated with CNS DLBCL and gain of 19q13.12-q13.43 with testicular DLBCL. Analysis of candidate genes in site-specific regions and minimal common regions revealed two major groups of genes: one involved in the immune response, including regulation of HLA expression, and the other involved in apoptosis, including the p53 pathway. Many of these genes were also involved in homozygous deletions or high-level gains. The presence of both shared and site-specific aberrations in CNS and testicular DLBCLs underlines the concept of IP-DLBCL but also indicates that IP-DLBCLs of the CNS and testis do not form a single entity. The observed aberrations emphasize the importance of the deregulation of anti-tumour immune response and apoptosis pathways.

The practices of spray operators in the Mpumalanga Malaria Control Programme using insecticides for residual indoor spraying

Pesticide poisoning poses a health risk to individuals throughout the world. In Mpumalanga Province spray teams apply local insecticides to indoor surfaces of households just prior to the rainy season to control malaria. Workers are exposed to pesticides during this process. This cross sectional study compared prescribed safe handling and deltamethrin application practices of Mpumalanga malaria spray operators versus actual practices in the field. Most (91) of the spray operators were included in the study. A tick list and interview was utilized to observe field practices and enquire about reasons for non-compliance. Only 28 of operators complied with all prescribed safe handling practices. Gloves; face shields and masks were not utilized as recommended and contributed to the highest levels of non-compliance. Compliance was found to be dependent on gender; age; years of experience; education level and employment status. The low compliance rate necessitates further investigation of the malaria programme occupational safety management system. All stakeholders need to be aware of the consequences of pesticide poisoning and to collaborate in efforts to work towards prevention

Primary testicular diffuse large B-cell lymphomas have activated B-cell-like subtype characteristics.

Diffuse large B-cell lymphomas (DLBCLs) constitute a heterogeneous group of lymphomas in which germinal centre B-cell-like and activated B-cell-like subtypes can be discerned based on pathology, clinical presentation, and gene expression patterns. Testicular DLBCLs form an immune-privileged site-related subgroup of DLBCLs with an unfavourable prognosis. In the present study, cDNA microarray analysis, immunohistochemistry for CD10, Bcl6 and MUM1, and somatic hypermutation analysis of the immunoglobulin heavy chain gene rearrangements were used to determine the subtype of primary testicular DLBCL. Immunohistochemistry revealed 14/22 testicular DLBCLs with an activated B-cell-like immunophenotype and 8/22 with an ambiguous immunophenotype co-expressing CD10 and high levels of MUM1. cDNA microarray analysis of these 22 and four additional cases showed a uniform activated B-cell-like gene expression pattern for both immunophenotypes. Somatic hypermutation analysis of immunoglobulin heavy chain genes showed a very high mutation load in seven cases tested, but intraclonal heterogeneity was found at low level in only one of these cases. It is concluded that primary testicular DLBCLs have uniform activated B-cell-like subtype characteristics despite a number of cases showing an ambiguous immunophenotype.

Insecticide resistance in malaria vector mosquitoes in a gold mining town in Ghana and implications for malaria control.

Malaria control programmes in Africa, for the most part, address only treatment of the disease and supply of insecticide treated bed nets. The impact of these restricted programmes has been limited and new approaches are being advocated, including integrated vector management strategies and partnerships with industry. Mosquito surveys were carried out for AngloGold/Ashanti in preparation for their implementation of an integrated malaria control programme at the Obuasi gold mine in Ghana. Malaria vectors that were collected inside houses were identified to species and molecular forms by PCR, and tested for insecticide resistance using standard WHO bioassays and molecular target site insensitivity (kdr) assays. Species were identified as An. funestus s.s. and An. gambiae S and M forms. The An. gambiae S form samples showed resistance to DDT, pyrethroids and carbamates while An. funestus was resistant to DDT and carbamates. The An. gambiae M form occurred in very low numbers and could not be assessed reliably for resistance. The standard PCR assay for detection of the kdr mutation in An. gambiae S form showed little association with pyrethroid resistance. Subsequent sequencing of the II56 domain containing the kdr mutation from nine surviving mosquitoes showed that eight were homozygous resistant and one heterozygous. This correlated with the bioassay results and with previous studies on West African An. gambiae, but raised concerns about the reliability of the PCR assay for detection of the kdr mutation. As a result of these investigations AngloGold/Ashanti are implementing, in addition to treatment and case management, a vector control programme that includes insecticide resistance management by alternation of various classes of insecticides for house spraying, supply of ITNs, screening of houses and environmental management where appropriate, i.e. integrated vector management.

Cloning and characterization of cDNA clones encoding membrane-bound and potentially secreted major histocompatibility class I receptors from walleye (Stizostedion vitreum).

Major histocompatibility (MH) gene polymorphism has been used to type populations of humans, mice, and fish. Walleye ( Stizostedion vitreum) comprise an economically important fishery in Lake Erie, but whether those in the western basin form a single population or separate shoal- and river-breeding populations is not known. To develop MH gene markers for use in defining their population structure, we constructed a head kidney cDNA library from which five full-length class I heavy-chain clones were isolated and sequenced. Although they came in roughly three sizes, 1300, 1400, and over 2000 bp, the clones all exhibited a high degree of sequence similarity to each other and to known teleost MH class I cDNAs in the area encoding the extracellular domains, but showed dramatic differences in their transmembrane and cytoplasmic domains. One clone had an AG repeat that eliminated the hydrophobicity of the transmembrane domain, indicating that it may encode a secreted class I receptor. The other four clones encode three distinctly different cytoplasmic domains. The two clones that encode the same cytoplasmic domain resemble those of the known teleost MH class I sequences the most. Southern blotting indicated that there were four copies of the gene present in the walleye genome. Northern blotting showed that class I MH genes are expressed in most tissues and mRNAs of all three size classes can be detected. A preliminary survey of the polymorphism of these genes indicates that they will provide useful markers for differentiating fish stocks.

Community knowledge and perceptions about malaria and practices influencing malaria control in Mpumalanga Province, South Africa.

OBJECTIVE: To assess community knowledge and perceptions about malaria and its control in a rural setting. DESIGN: Descriptive cross-sectional survey. SETTING: Tonga district with a population of 116,418, seasonal malaria with an annual incidence of 3,200 cases. SUBJECTS: Female heads of 299 randomly selected households. METHODOLOGY: A total of 299 households were selected from a random sample of 30 clusters. Community knowledge and perceptions about malaria and its control were assessed by interviews with the female head of each of the 299 selected households. RESULTS: Respondents ranked malaria as the third most serious health problem facing the community after TB and AIDS. Seventy-two per cent (214/299) of respondents reported that they knew what malaria disease was and of these, 92.1% (197/214) mentioned mosquito bites as the cause of malaria. The respondents' understanding of the causal role of mosquitoes in malaria was significantly related to their knowledge about disease symptoms (P < 0.001). Reported community compliance with the malaria control programme (MCP) was satisfactory; 86.6% (259/299) of respondents reported that their homes had been sprayed during the past 2 years but 10.0% (30/299) did not know why homes were sprayed. Hospitals or clinics were the facilities where respondents most commonly sought treatment for fever; 66.9% (200/299) reported that they would seek treatment immediately after the onset of high fever. Specific practices such as replastering or washing of inside walls compromised the effectiveness of the MCP. Personal preventive measures were sometimes used against malaria (50.8%, 152/299) and use was positively associated with education level (P = 0.001). Respondents expressed their desire for more information about malaria and their willingness to contribute to the control of malaria in their community. CONCLUSION: The survey collected information which was directly relevant to the development of health education messages to increase community awareness of the problem of malaria, to emphasise the importance of early diagnosis and prompt treatment of malaria, to improve community understanding of the function of indoor residual spraying, and to enlighten the population of the role of mosquitoes in malaria transmission and the availability and benefits of personal protection measures against mosquito bites.

Using a geographical information system to plan a malaria control programme in South Africa.

INTRODUCTION: Sustainable control of malaria in sub-Saharan Africa is jeopardized by dwindling public health resources resulting from competing health priorities that include an overwhelming acquired immunodeficiency syndrome (AIDS) epidemic. In Mpumalanga province, South Africa, rational planning has historically been hampered by a case surveillance system for malaria that only provided estimates of risk at the magisterial district level (a subdivision of a province). METHODS: To better map control programme activities to their geographical location, the malaria notification system was overhauled and a geographical information system implemented. The introduction of a simplified notification form used only for malaria and a carefully monitored notification system provided the good quality data necessary to support an effective geographical information system. RESULTS: The geographical information system displays data on malaria cases at a village or town level and has proved valuable in stratifying malaria risk within those magisterial districts at highest risk, Barberton and Nkomazi. The conspicuous west-to-east gradient, in which the risk rises sharply towards the Mozambican border (relative risk = 4.12, 95% confidence interval = 3.88-4.46 when the malaria risk within 5 km of the border was compared with the remaining areas in these two districts), allowed development of a targeted approach to control. DISCUSSION: The geographical information system for malaria was enormously valuable in enabling malaria risk at town and village level to be shown. Matching malaria control measures to specific strata of endemic malaria has provided the opportunity for more efficient malaria control in Mpumalanga province.