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Four of the most disabling human diseases are syphilis, malaria, schizophrenia, and manic-depressive illness. The history of the development of treatments for these seemingly unrelated disorders intersects at several points. Treatment of tertiary cerebral syphilis (general paresis) by inducing fever with malaria led to a Nobel Prize. Although attempts to synthesize quinine, a plant product effective against malaria, failed, these efforts encouraged industrial organic chemists to synthesize many useful substances, including dyes, antibiotics, and antihistamines. The aniline-derived dye methylene blue was a member of a new class of polycyclic chemicals, the phenothiazines. Efforts to modify phenothiazines to find an antimalarial agent also failed but led to novel antiemetic-sedative antihistamines, including promethazine, promazine, and eventually chlorpromazine--the first effective treatment for schizophrenia and mania. Chlorpromazine has antipsychotic and antimanic properties, and it revolutionized the therapeutics of psychotic illnesses.
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PMID:Neurosyphilis, malaria, and the discovery of antipsychotic agents. 1880 5

Red Lapacho (Tabebuia impetiginosa, syn. Tabebuia avellanedae), a canopy tree indigenous to the Amazonian rainforest and other parts of South America, has been acclaimed to be one of the "miraculous" cures for cancer and tumours. For the first time, during the 1960s, it attracted considerable attention in Brazil and Argentina as a 'wonder drug'. Traditionally, the botanical drug is widely used in local and traditional phytomedicine, usually ingested as a decoction prepared from the inner bark of the tree to treat numerous conditions like bacterial and fungal infections, fever, syphilis, malaria, trypanosomiasis, as well as stomach and bladder disorders. As early as 1873, biomedical uses of Red Lapacho ("Pau D'Arco") were reported. In 1967 after reports in the Brazilian press it came back to the light of clinicians (and the public in general). The news magazine O'Cruzeiro started reporting "miraculous" cures in cancer patients in a hospital. Natural sciences interest in the plant also began in the 1960s when the United States National Cancer Institute (NCI) systematically began researching plant extracts all over the world looking for active compounds against cancer and looked at Tabebuia impetiginosa in considerable detail. Two main bioactive components have been isolated from Tabebuia impetiginosa: lapachol and beta-lapachone. beta-Lapachone is considered to be the main anti-tumour compound, and pro-apoptotic effects were observed in vitro. Some mechanistic studies on this compound's molecular effects have been conducted. The other main constituents isolated from Red Lapacho are also reviewed briefly. The drug appears to be generally safe and one of the most important interactions of Tabebuia impetiginosa has been associated with interference in the biological cycle of Vitamin K in the body. The botanical (drug) material available on the international markets seems to be of varying quality and composition, making a specific assessment of the products' therapeutic claims problematic. This also highlights the need for appropriate analytical techniques, which are reviewed as well. The bioscientific evidence for products derived from Tabebuia impetiginosa is insufficient and one of the core challenges of future research will be--based on the recognition of the drug's widespread use--to establish appropriate quality control procedures. Further research into the clinical effects and the pharmacology of chemically characterized extracts is also warranted.
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PMID:Red Lapacho (Tabebuia impetiginosa)--a global ethnopharmacological commodity? 1899 1

Low birth weight (LBW) is a risk factor for infant mortality, morbidity, growth retardation, poor cognitive development, and chronic diseases. Maternal exposure to diseases such as malaria, HIV, and syphilis has been shown to have a significant impact on birth weight (BW). This study was aimed at determining whether there was a difference in rates of LBW in areas of varying malaria transmission intensity in Korogwe, Tanzania. Retrospective data for one year (June 2004-May 2005) in three maternal and child health (MCH) clinics in the district were analysed. Villages were stratified into three strata: lowlands-semi urban (average altitude of 320m), lowlands-rural (below 600m) and highlands (> or =600m). There was a significant decreasing trend of rate of LBW from rural lowlands to highlands (chi2trend = 7.335, P=0.007). Adjusting for covariates, women in parity-two were at reduced risk of delivering LBW babies compared to first parity women (OR=0.44, 95% CI 0.19-0.98, P=0.045). Similarly, the risk of LBW was higher in women who had delayed MCH gestational booking and in women who conceived during high malaria transmission seasons. There was high degree of preference of digits ending with 0/5 in reporting BW in the studied MCHs. In conclusion, a rate of LWB was high in rural lowlands where malaria is also endemic, and was associated with high malaria transmission seasons.
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PMID:Risk factors for low birth-weight in areas with varying malaria transmission in Korogwe, Tanzania: implications for malaria control. 1902 38

A number of infectious diseases should be considered for inclusion as part of clinical preconception care. Those infections strongly recommended for health promotion messages and risk assessment or for the initiation of interventions include Chlamydia infection, syphilis, and HIV. For selected populations, the inclusion of interventions for tuberculosis, gonorrheal infection, and herpes simplex virus are recommended. No clear evidence exists for the specific inclusion in preconception care of hepatitis C, toxoplasmosis, cytomegalovirus, listeriosis, malaria, periodontal disease, and bacterial vaginosis (in those with a previous preterm birth). Some infections that have important consequences during pregnancy, such as bacterial vaginosis (in those with no history of preterm birth), asymptomatic bacteriuria, parvovirus, and group B streptococcus infection, most likely would not be improved through intervention in the preconception time frame.
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PMID:The clinical content of preconception care: infectious diseases in preconception care. 1953 94

Studying the remains of mummies obtained by archaeological research may provide key information concerning historical pathocoenosis. Paleopathology makes it possible to recognise, characterise and connect different features involved in human pathocoenosis, such as epidemiology, in a historical perspective, and cultural development, via the introduction of new livestock farming techniques and agriculture in general. Several distinct pathologies may produce direct and indirect changes in the skeleton of affected individuals. Therefore bone remains represent very important sources of information to study such diseases. Changes related to trauma and nutrition deficiency as well as secondary signs, induced by tuberculosis, brucellosis, leprosy, syphilis, malaria, periostitis and aspecific osteomyelitis, persist in bones. In addition, other diseases may cause indirect alterations and subsequent secondary bone in the skeleton via different mechanisms. A secondary bone dimorphism may be induced by poliomyelitis. Aspecific lesions may arise in a skeletal bone and then cause secondary alterations in near-bone segments. Reviewing studies of paleopathologic research found in the literature, we emphasize the relationship between the appearance of major infectious diseases and the development of human activities; whereas it is clear that the introduction of livestock farming had a key role in the pathocoenosis of distinct infections such as tuberculosis, brucellosis and leprosy, some doubts and uncertainty remain in relation to the origin of others with epidemiologically important pathologies, such as syphilis.
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PMID:[Contribution of paleopathology to defining the pathocoenosis of infectious diseases (Part one)]. 1915 92

Infection may cause stillbirth by several mechanisms, including direct infection, placental damage, and severe maternal illness. Various organisms have been associated with stillbirth, including many bacteria, viruses, and protozoa. In developed countries, between 10% and 25% of stillbirths may be caused by an infection, whereas in developing countries, which have much higher stillbirth rates, the contribution of infection is much greater. In developed countries, ascending bacterial infection, both before and after membrane rupture, with organisms such as Escherichia coli, group B streptococci, and Ureaplasma urealyticum is usually the most common infectious cause of stillbirth. However, in areas where syphilis is prevalent, up to half of all stillbirths may be caused by this infection alone. Malaria may be an important cause of stillbirth in women infected for the first time in pregnancy. The two most important viral causes of stillbirth are parvovirus and Coxsackie virus, although a number of other viral infections appear to be causal. Toxoplasma gondii, Listeria monocytogenes, and the organisms that cause leptospirosis, Q fever, and Lyme disease have all been implicated as etiologic for stillbirth. In certain developing countries, the stillbirth rate is high and the infection-related component so great that achieving a substantial reduction in stillbirth should be possible by reducing maternal infections. However, because infection-related stillbirth is uncommon in developed countries, and because those that do occur are caused by a wide variety of organisms, reducing this etiologic component of stillbirth much further will be difficult.
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PMID:Infection and stillbirth. 1928 57

Corneal transplantation safety is widely dependent on clinical donor selection. Donor-to-host transmission of rabies and Creutzfeldt-Jakob disease is well established, and it is lethal for the recipient. Taking into consideration this latter figure, contraindications to ocular tissue transplantation include not only rabies, contact with rabies virus, spongiform encephalitis, family history of spongiform encephalitis, recipients of human pituitary-derived hormones before 1987, surgery using dura mater and brain/spinal surgery before 1992, but also CNS diseases of unknown etiology or those with unknown risk of transmission. It has been established that hepatitis B virus and herpes simplex virus can be transmitted by corneal transplantation, and both diseases are contraindications to transplantation. HIV infection, syphilis, hepatitis C, hepatitis A, tuberculosis, HTLV-1 and -2 infection, active leprosy, active typhoid, smallpox and active malaria are also contraindications to ocular tissue transplantation even if no evidence of donor-to-recipient transmission has been demonstrated. A history of corneal refractive surgery in the donor eye, ocular inflammation, retinoblastoma, and malignant tumors of the anterior segment are contraindications to keratoplasty.
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PMID:Donor selection, retrieval and preparation of donor tissue. Donor selection. 1949 34

In the studies of complement fixation described in this paper, the antigens were prepared from (a) normal monkey red cells, (b) parasitized red cells of monkeys dying with Plasmodium knowlesi infection, (c) the spleens of monkeys dying with Plasmodium knowlesi infection; the sera came from (a) normal human beings, (b) patients with syphilis, (c) patients with paresis who were receiving malaria therapy with Plasmodium knowlesi, Plasmodium vivax, or Plasmodium falciparum, and (d) patients with malaria alone. The malarial antigens gave negative complement fixation reactions with 70 to 80 per cent of the luetic and normal sera and weak or doubtful reactions with the remaining 20 to 30 per cent. With the exception of one antigen prepared from spleen, there was no evidence that the malarial antigens were more reactive with Wassermann-positive than with Wassermann-negative sera. Some human sera give weak complement fixation with antigens prepared from normal monkey erythrocytes, and the percentage of these positive reactions is slightly higher with malarial sera than with normal or luetic sera. The most sensitive and specific malarial antigen was prepared from dried parasitized red cells by extraction with saline, freezing, and thawing. This P. knowlesi antigen gives strong complement fixation with malarial sera from human beings infected with P. knowlesi, P. vivax, or P. falciparum. The titer of complement-fixing antibodies reaches a maximum about 1 month after the beginning of the acute infection. At this time all of the P. knowlesi sera tested were positive. After 4 months the reaction diminishes rapidly in titer but may remain positive for 12 months or longer. With P. knowlesi infections in man, the complement fixation reaction remains positive for some time after the infection has apparently disappeared as judged by daily smears and inoculation of monkeys with the blood. The complement fixation reaction in malaria is group-specific rather than species-specific. Sera from patients infected with P. vivax or P. falciparum react in the same way with the P. knowlesi antigen as the homologous sera. Absorption of malarial human sera with normal monkey erythrocytes does not remove the immune bodies which fix complement with malarial antigens.
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PMID:COMPLEMENT FIXATION IN HUMAN MALARIA WITH AN ANTIGEN PREPARED FROM THE MONKEY PARASITE PLASMODIUM KNOWLESI. 1987 Aug 53

1. Spirochetes of relapsing fever have been separated from the blood of heavily infected mice and rats by hemolysing with saponin, followed by repeated washing of the spirochetal suspension with physiological saline. 2. Spirochetes obtained in this manner appear to have broad antigenic specificity. Antigens of this type fixed complement in the presence of serum obtained from man or animals infected with one or other of the recognized strains or "species" of relapsing fever spirochetes. Macroscopic agglutination of the antigens likewise was observed with sera from the same sources. 3. Positive serological reactions were not observed with convalescent sera obtained following infection with other diseases, for example, typhus fever, malaria, Rocky Mountain spotted fever, Weil's disease, syphilis, and typhoid fever. Hyperimmune sera prepared against other pathogens also failed to react with the relapsing fever antigens. 4. No apparent change in the antigen occurred following storage in the ice box for as long as 4 months. 5. The results indicate that treatment of the spirochetes of relapsing fever with saponin yields a relatively stable antigenic preparation which may prove useful in the serological diagnosis of this disease.
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PMID:THE SEROLOGICAL DIAGNOSIS OF RELAPSING FEVER. 1987 48

INTRODUCTION: Implementing Intermittent Preventive Treatment for malaria in Pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) through antenatal care (ANC) clinics is recommended for malaria endemic countries. Vast biomedical literature on malaria prevention focuses more on the epidemiological and cost-effectiveness analyses of the randomised controlled trials carried out in selected geographical settings. Such studies fail to elucidate the economic, psychosocial, managerial, organization and other contextual systemic factors influencing the operational effectiveness, compliance and coverage of the recommended interventions. OBJECTIVE: To review literature on policy advances, achievements, constraints and challenges to malaria IPTp implementation, emphasising on its operational feasibility in the context of health-care financing, provision and uptake, resource constraints and psychosocial factors in Africa. RESULTS: The importance of IPTp in preventing unnecessary anaemia, morbidity and mortality in pregnancy and improving childbirth outcomes is highly acknowledged, although the following factors appear to be the main constraints to IPTp service delivery and uptake: cost of accessing ANC; myths and other discriminatory socio-cultural values on pregnancy; target users, perceptions and attitudes towards SP, malaria, and quality of ANC; supply and cost of SP at health facilities; understaffing and demoralised staff; ambiguity and impracticability of user-fee exemption policy guidelines on essential ANC services; implementing IPTp, bednets, HIV and syphilis screening programmes in the same clinic settings; and reports on increasing parasite resistant to SP. However, the noted increase in the coverage of the delivery of IPTp doses in several countries justify that IPTp implementation is possible and better than not. CONCLUSION: IPTp for malaria is implemented in constrained conditions in Africa. This is a challenge for higher coverage of at least two doses and attainment of the Abuja targets. Yet, there are opportunities for addressing the existing challenges, and one of the useful options is the evaluation of the acceptability and viability of the existing intervention guidelines.
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PMID:Implementing Intermittent Preventive Treatment for Malaria in Pregnancy: Review of Prospects, Achievements, Challenges and Agenda for Research. 1994 8


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