A short history of dapsone, or an alternative model of drug development.

From 1936 until 1996, the drug dapsone treated a diverse array of diseases, including tuberculosis, leprosy, malaria, and AIDS-related pneumonia. This article explores how dapsone transformed from a cure for one disease into a treatment for a totally different malady. This process of reinvention in the clinic represents an alternative model of drug development that the historical literature, focused on success in the laboratory, has largely ignored. The core of the paper discusses the reinvention of dapsone as an antimalarial in the Vietnam War through trials led by Robert J. T. Joy, a physician and military officer. As a case study, it offers a fresh perspective on the clinic-as-laboratory approach that other scholars have addressed in a civilian context. Viewing the randomized clinical trial (RCT) through a military prism will demonstrate how a combat environment combined with the regimentation of the armed forces affected the standard methodology of the RCT.

A short history of dapsone, or an alternative model of drug development.

From 1936 until 1996, the drug dapsone treated a diverse array of diseases, including tuberculosis, leprosy, malaria, and AIDS-related pneumonia. This article explores how dapsone transformed from a cure for one disease into a treatment for a totally different malady. This process of reinvention in the clinic represents an alternative model of drug development that the historical literature, focused on success in the laboratory, has largely ignored. The core of the paper discusses the reinvention of dapsone as an antimalarial in the Vietnam War through trials led by Robert J. T. Joy, a physician and military officer. As a case study, it offers a fresh perspective on the clinic-as-laboratory approach that other scholars have addressed in a civilian context. Viewing the randomized clinical trial (RCT) through a military prism will demonstrate how a combat environment combined with the regimentation of the armed forces affected the standard methodology of the RCT.

[Pneumocystis carinii today--40 years later]. / Pneumocystis carinii dnes--po 40 letech.

Forty years ago Czech scientists, J. Vanek and O. Jírovec, diagnosed Pneumocystis carinii as the agent of interstitial plasmocytic pneumonia in weak infants. At present it is the most frequent pulmonary pathogenic organism in patients suffering from AIDS. In the submitted paper the author summarizes experience and recent findings on the aetiopathogenesis, pathology, clinical picture, diagnosis, treatment and prevention of pneumocystis pneumonia.

[The discovery of Pneumocystis pneumonia and Czechoslovak pediatrics]. / Objev pneumocystové pneumonie a cs. pediatrie.

The author reviews the problem of pneumocystic pneumonia from the paediatric aspect. Assessment of the cause of interstitial plasmacellular pneumonia is in the author's opinion one of the greatest discoveries of our medicine and parasitology in this century. Pneumocystic pneumonia is in recent years of special importance in particular in treatment of impaired immunity.

Retrospective study of Pneumocystis pneumonia over half a century in mainland China.

A retrospective study was performed on case reports of Pneumocystis pneumonia (PCP) from 1959 to 2009 in mainland China. The epidemiological characteristics of PCP over half a century were investigated over two time spans. The first was from 1959, when the first incidence of PCP was reported, to 1984, before the emergence of AIDS in mainland China. The second was from 1985, when the first AIDS case was reported in mainland China, to the end of 2009. A total of 2351 PCP cases were reported during these two time spans, covering a 51-year period. Only seven PCP cases were reported during the first time span. Six were diagnosed by autopsy, accordingly without treatment, whilst the other was diagnosed by open lung biopsy in a living patient who eventually recovered following treatment with sulfadiazine and pyrimethamine. The other 2344 PCP cases were reported during the second time span (1985-2009) from 21 provinces, four municipalities and three autonomous regions. Among the 2344 PCP cases, 70.22 % (1646/2344) were identified together with human immunodeficiency virus (HIV) infection or were in AIDS patients. The remaining 698 non-HIV-infected patients had undergone organ transplantation, had other underlying diseases such as malignancy or hypoimmunity, or had undetermined diagnosis. The results of statistical analysis indicated that AIDS was the most common underlying disease of PCP for patients <1 year and >14 years. For patients aged between 1 and 14 years, haematological malignancy was the most common underlying disease. The trend of the underlying diseases changed with time, showing that the number of PCP patients afflicted by HIV/AIDS increased dramatically, reaching almost threefold during the most recent 5 years compared with the level of the previous 10 years. The number of patients undergoing organ transplantation or with other underlying diseases rose constantly, but the number of malignancies tended to decline from 1995-2004 to 2005-2009. During the second time span (1995-2009), most of the patients (97.61 %) were diagnosed alive and only 56 cases (2.39 %) were identified by autopsy. The mortality of PCP patients treated with anti-Pneumocystis drugs was 14.61 % for those with HIV/AIDS and 15.84 % for those without HIV/AIDS. For the PCP patients without anti-Pneumocystis treatment, all (100 %) of the HIV/AIDS-associated PCP patients died, whilst 13.79 % (4/29) of non-HIV-infected PCP patients survived. These data from epidemiological investigation of PCP in China over a period of half a century may provide useful information for prevention and the development of treatment of PCP.

Plagues in the ICU: a brief history of community-acquired epidemic and endemic transmissible infections leading to intensive care admission.

The ability to diagnose and treat infectious diseases and handle infectious disease outbreaks continues to improve. For the most part, the major plagues of antiquity remain historical footnotes, yet, despite many advances, there is clear evidence that major pandemic illness is always just one outbreak away. In addition to the HIV pandemic, the smaller epidemic outbreaks of Legionnaire's disease, hantavirus pulmonary syndrome, and severe acute respiratory syndrome, among many others, points out the potential risk associated with a lack of preplanning and preparedness. Although pandemic influenza is at the top of the list when discussing possible future major infectious disease outbreaks, the truth is that the identity of the next major pandemic pathogen cannot be predicted with any accuracy. We can only hope that general preparedness and the lessons learned from previous outbreaks suffice.

What caused the epidemic of Pneumocystis pneumonia in European premature infants in the mid-20th century?

An epidemic of interstitial pneumonia principally involving premature infants occurred in Germany and nearby European countries between the 1920s and 1960s. Fatalities were due to Pneumocystis. Because the principal defenses against Pneumocystis are T cells, an acquired T-cell deficiency was postulated. A number of potential causes including malnutrition were considered. All were implausible except for a retrovirus that was benign in adults but virulent in premature infants. Furthermore, we suspect that the virus was imported into Germany from former German African colonies. Premature infants were vulnerable because of the developmental status of their T cells. Given the practices in that part of Europe at that time, the virus was most likely transmitted by contaminated blood transfusions and subsequent contamination of reusable needles and syringes used in injections. Although the epidemic ended 4 decades ago, a search for the postulated retrovirus can be conducted if tissues from affected infants are available.

Pneumocystis carinii: a historical perspective.

The emergence of Pneumocystis carinii pneumonia is traced from its origins as an obscure pulmonary pathogen to its place as a prominent cause of lung infection in patients who have acquired immune deficiency syndrome. Improvements in diagnosis and treatment have resulted in better care of patients with this infection. In addition, basic immunologic and molecular investigations have improved our understanding of the nature of this organism and continue to provide important questions for further research. This is a US government work. There are no restrictions on its use.

Pneumocystis carinii as the cause of human disease: historical perspective and magnitude of the problem: introductory remarks.

The history of the discovery of Pneumocystis carinii as the cause of interstitial plasma cell pneumonia of infants and of opportunistic infection with this parasite in the lungs of immuno-suppressed or severely debilitated adults and children is summarized with an extensive bibliography of the world literature through 1959. The problem of incriminating a nearly ubiquitous saprophyte as the cause of a disease and of elucidating the factors responsible for its causing pathogenesis in certain individuals is reviewed with special reference to slow and latent virus infections. Although formerly there has been much discussion of other possible etiologies of the respiratory syndromes in premature and debilitated infants and in children and adults who are immunodeficient or immunosuppressed in whose lungs the parasite is found, there seems no longer to be any room for doubt that P. carinii is itself the cause of these respiratory disease. The need of determining the genetic constitutions and the specific immunologic deficiencies that render some persons victims to this usually innocuous saprophyte is compelling, and the in vitro cultivation of the organism may aid considerably in unraveling these problems.

[Pneumocystis carinii infections]. / Infections à Pneumocystis carinii.

In children, Pneumocystis carinii pneumonias occur mainly in cases of congenital or acquired immunodeficiencies. Definitive diagnosis rests on the visualization of the parasites, ideally by broncho-alveolar lavage. If the lavage is negative and the patient deteriorates, an open lung biopsy is the next best diagnostic method. Serological methods are unreliable. Treatment with trimethoprim-sulfamethoxazole (TMP) should be instituted as early as possible: a serum level of TMP between 5 and 10 micrograms/ml should be attained. If no improvement occurs after three days, pentamidine should be substituted. Systematic chemoprophylaxis should be given to all high-risk patients.