Tanzania Malaria Indicator Surveys 2001 - 2008:\ud Morbidity Indicators and Coverage of Major\ud Malaria Prevention and Control Interventions

Background\ud \ud Malaria continues to be a major public health problem in Africa. In Tanzania alone, thereare an estimated 17 to 20 million malaria cases per year resulting in approximately100,000 deaths. The main strategies to control malaria are vector control through insecticide treated nets (ITNs) and idoor residual spraying (IRS), intermittent preventive treatment during pregnancy (IPTp) and early diagnosis and prompt and effective treatment of cases. In 2001, the first Malaria Mid-Term Strategic Plan (MMTSP) was launched in Tanzania followed by the second MMTSP implemented in 2008. In order to evaluate the MMTSP, the NMCP conducted 4 cross-sectional community-based surveys in the years 2001, 2003, 2005 and 2008, as well as one survey collecting only malaria biomarkers in 2006. The findings of the latest survey are presented and analyzed in the present work.\ud \ud Methods\ud The NMCP 2008 malaria indicator survey was carried out in 21 malaria sentinel districts, one per region, in Mainland Tanzania. Demographic data of all household members and information on mosquito net availability and use was collected, as well as data on use of IPTp and prompt and effective treatment of fever in children. Further, malaria prevalence and haemoglobin levels were tested in children under the age of five years and in currently pregnant women. In the analysis, logistic regressions with the outcome variables net use, prevalence of malaria and anaemia, and linear regressions with the outcome haemoglobin level were conducted, using location, altitude, distance to health facility, sex and age group as explanatories.\ud \ud Data found in this work was compared with both, the Tanzania HIV/AIDS and Malaria Indicator Survey (THMIS) and the Tanzania National Insecticide Treated Nets Programme (NATNETS) survey (both conducted in 2008). Principle findings 8377 households were interviewed with a total population of 40,135. 65% of the households owned at least one mosquito net and 40% owned at least one ITN. Household net ownership was associated with location, altitude and distance to health facility. 42% of the population slept under a net the night before the survey and 27% under an ITN.\ud \ud Location, distance to health facility, sex and age group were significant determinants for net use. Among children under the age of five years, net use was found to be 49% for any net and 33% for ITN, while among pregnant women it was 47% for any net and 31% for ITN. Overall, household net ownership and personal net use increased over the survey years.\ud \ud Malaria and anaemia prevalence among children was 16.1% and 5.6%, respectively. Malaria prevalence was associated with location, altitude, age group and use of ITN, while anaemia prevalence was associated with altitude and age group. Both, prevalence of anaemia and malaria among children under five decreased between 2006 and 2008. 26% of the children reported to have had a fever during the past two weeks. 15% of these children received the first line antimalarial drug within 24 hours from onset. 76% of the women who had delivered during the two years prior to the survey used IPTp and 44% took at least two doses of SP as IPTp.\ud \ud Discussion\ud It was shown that increasing coverage of malaria prevention and control interventions is negatively correlated with malaria and anaemia prevalences, hence lower prevalences for both conditions. The results of the NMCP survey were similar to those of the THMIS and the NATNETS survey and were as well externally confirmed by other studies.\ud \u

In vitro-Untersuchungen von Hämatoporphyrin-Platin(II)-Komplexen - eine neue Klasse von selektiven Photosensibilisatoren mit intrinsischer Zytotoxizität

Als neuer Ansatz zur Behandlung von Karzinomen sollen bei Porphyrin-Platin(II)-Komplexen der zytostatische Effekt des Cisplatins mit der photodynamischen Aktivität des Hämatoporphyrins in einer Substanz kombiniert werden. 4 Hämatoporphyrin-Platin(II)-Komplexe wurden hinsichtlich Dunkeltoxizität, Phototoxizität, zelluläre Aufnahme, intrazelluläre Lokalisation und Verhalten in 3-D-Zellaggregaten untersucht. Dazu wurden die J82-Zelllinie, ein Modell eines gering differenzierten invasiven Urothelkarzinoms, und die UROtsa-Zelllinie, normale urotheliale Zellen, verwendet. Im Chemosensitivitätstest zeigte der wasserlösliche Porphyrin-Platin(II)-Komplex, Diammin{7,12-bis-[1-(polyethylenglykol-750-monomethylether-1-yl)ethyl]-3,8,13,17-tetramethyl-por-phy-rin-2,18-dipropionato}platin(II), einen synergistischen Wirkeffekt im Vergleich zu den Referenzverbindungen Cisplatin, Hämatoporphyrin und einer Mischung aus beiden Verbindungen. Akkumulations-Experimente mit den Monolayer-Kulturen und den Sphäroiden zeigten, dass die Konzentration des wasserlöslichen Porphyrin-Platin(II)-Komplexes in den J82-Tumorzellen etwa 1.5-fach höher ist als in den UROtsa-Zellen. Im Vergleich zu Cisplatin ist die DNA der J82- und UROtsa-Zellen beim Porphyrin-Platin(II)-Komplex stärker platiniert, jedoch besteht kein signifikanter Unterschied zwischen den beiden Zelllinien. Trotz der relativ hohen Molmasse war die Penetration des Porphyrin-Platin(II)-Komplexes nicht auf die äußeren Zelllagen der Sphäroide beschränkt. Der wasserlösliche Porphyrin-Platin(II)-Komplex ist an Zellmembran wie auch an Plasmamembranen, unter anderem an Lysosomen, Mitochondrien und dem Golgi-Apparat, gebunden. Somit ist der Komplex an zelluläre Strukturen assoziiert, die essentiell für die Effektivität der photodynamischen Therapie sind. Zusammenfassend: Porphyrin-Platin(II)-Komplexe sind vielversprechende Kandidaten für eine neue Klasse von selektiven Photosensibilisatoren mit intrinsischer Zytotoxizität

Preparation of novel, water-soluble porphyrin platinum amine compounds with high tumor selectivity and their use for the treatment of benign and malignant tumor diseases

The invention relates to the prepn. of novel, water-sol. porphyrin platinum compds. of the tetraarylporphyrin platinum type or of the hematoporphyrin platinum type in which a platinum diamine is bonded to pendant arm/arms of the porphyrin. with high tumor selectivity and their use for the treatment of benign and malignant tumor diseases. These compds. have high tumor selectivity and are proposed for use in the treatment of benign and malignant tumor diseases. In particular, the compds. are suitable for photodynamic antitumor therapy. Thus, the tetraarylporphyrin platinum complex (I) and the hematoporphyrin platinum complex (II) and related complexes were prepd. and cytotoxic/phototoxic antiproliferative activity against model bladder cancer cell lines TCC-SUP and J82 measured

Hematoporphyrin-derived soluble porphyrin-platinum conjugates with combined cytotoxic and phototoxic antitumor activity

To combine the cytotoxic activity of cisplatin and the phototoxicicity of hematoporphyrin derivatives in the same molecule, hematoporphyrin was derivatized at the two secondary alcohol positions by etherification with oligo- and poly(ethylene glycol) units. The two carboxylic acid groups of the propionate side chains were used to bind platinum fragments. The antiproliferative activity of 35 platinum complexes (0.5, 1, and 5 microM) differing in solubility and type of the platinum fragment and the corresponding porphyrin ligands were studied in tests with TCC-SUP and J82 transitional bladder cancer cells in the dark and after irradiation (lambda = 600-730 nm, 24 J/cm(2)). The most active compounds were found among the porphyrin-platinum conjugates bearing the diammine and (RR/SS)-trans-1,2-diaminocyclohexane ligand. These porphyrin-platinum conjugates, especially the water-soluble species, such as diammine(7,12-bis[1-(poly(ethylene glycol)-750-monomethyl ether-1-yl)ethyl]-3,8,13,17-tetramethylporphyrin-2,18-dipropionato)platinum(II), are promising candidates for the development of a novel type of photosensitizers with intrinsic cytotoxicity, which due to the porphyrin constituent may selectively enrich in tumor tissues

Soluble tetraarylporphyrin-platinum conjugates as cytotoxic and phototoxic antitumor agents

A series of asymmetric tetraarylporphyrins was synthesized from pyrrole, para-substituted oligo- or poly(ethylene glycol) monomethyl ether benzaldehyde and from 4-hydroxybenzaldehyde etherified with diethyl bromomalonate according to the Lindsey method. After hydrolysis of the tetraarylporphyrin esters, the resulting carboxylic acid groups were used to bind platinum fragments. In comparison to analogous hematoporphyrin-platinum conjugates, the title compounds are characterized by a 30 nm bathochromic shift of their absorption bands. The antiproliferative activity of 18 platinum complexes (1, 5, and 10 microM) differing in solubility, type of the platinum fragment, and the corresponding tetraarylporphyrin ligands were studied on TCC-SUP transitional bladder cancer cells in the dark and after irradiation (lambda = 600-730 nm; 24 J/cm(2)). The most active compounds were among the tetraarylporphyrin-platinum conjugates bearing the diammine and (RR/SS)-trans-1,2-diaminocyclohexane ligands

Combined chemotherapeutic and photodynamic treatment on human bladder cells by hematoporphyrin-platinum(II) conjugates

Four porphyrin-platinum complexes, conceived as a new approach in cancer therapy by combining the cytostatic activity of cisplatin or oxaliplatin and the photodynamic effect of hematoporphyrin in the same molecule, were studied in detail with respect to solubility and stability in cell culture medium as well as in terms of cytotoxicity and phototoxicity against J82 bladder cancer cells and UROtsa, normal urothelial cells. This study demonstrated that the most active and promising compound among the porphyrin-platinum conjugates investigated was the water-soluble porphyrin-platinum complex 4 (diammine[7,12-bis[1-(polyethyleneglycol-750-monomethylether-1-yl)ethyl]-3,8,13,17-tetramethylporphyrin-2,18-dipropionato]platinum(II)) which exhibited a synergistic antiproliferative effect compared to cisplatin and hematoporphyrin alone or a combination of the drugs

Distribution and subcellular localization of a water-soluble hematoporphyrin-platinum(II) complex in human bladder cancer cells

The water-soluble porphyrin-platinum complex diammine[7,12-bis[1-(polyethyleneglycol-750-monomethylether-1-yl)ethyl]-3,8,13,17-tetramethylporphyrin-2,18-dipropionato]platinum(II) (PEG-HPPt) was studied with respect to cellular accumulation, subcellular localization, behavior in 3D-cell aggregates and degree of DNA platination on the low-differentiated J82 cells, a model of invasive bladder cancer, and UROtsa, a normal urothelial cell line. Accumulation studies with 2D and spheroid cell cultures revealed that the concentration of PEG-HPPt was 1.7-times higher in J82 cancer cells than in UROtsa cells. Despite its high molecular weight, penetration of PEG-HPPt was not restricted to the peripheral cells of the spheroids. Fluorescence microscopic analysis showed that PEG-HPPt was localized in essential cellular targets of photodynamic therapy. DNA platination in J82 and UROtsa cells was higher by PEG-HPPt than by cisplatin, whereas there was no significant difference between the two cell lines

Carboplatin derivatives with superior antitumor activity compared to the parent compound

A series of new carboplatin derivs. was synthesized by introducing fluoro, chloro, bromo and hydroxy substituents into the cyclobutane ring. The carboxylic acid groups were used for the complexation with platinum(II) fragments bearing two ammonia and (RR/SS)-trans-1,2-diaminocyclohexane ligands, resp., as non-leaving groups. The antiproliferative activity of the new carboplatin analogs differing in the cyclobutanedicarboxylato ligands and the type of platinum fragment were studied in tests with J82 bladder cancer cells and SK-OV-3 as well as cisplatin-resistant NIH:OVCAR-3 ovarian cancer cells. The most active compds. were the 3-fluoro, 3-chloro and 3,3-difluoro derivs. of carboplatin. NMR spectroscopy showed that cis-diammine(3-chloro-1,1-cyclobutanedicarboxylato)platinum(II) was hydrolyzed much faster than carboplatin explaining its higher cytostatic activity