The pharmacokinetics and pharmacodynamics of atovaquone and proguanil for the treatment of uncomplicated falciparum malaria in third-trimester pregnant women.

OBJECTIVE: To investigate the pharmacokinetics, safety and efficacy of the recommended 3-day treatment regimen of Malarone in third-trimester pregnant women with acute uncomplicated falciparum malaria. METHODS: Twenty-six pregnant women in their third trimester (gestational age: 24-34 weeks) with acute uncomplicated Plasmodium falciparum malaria who fulfilled the enrollment criteria were recruited from the antenatal clinics of Mae Sot Hospital, Tak Province, Thailand, (n = 8) and the Tropical Diseases Research Centre, Ndola, Zambia (n = 18). Patients were treated with four Malarone tablets (GlaxoSmithKline: each tablet contains 250 mg atovaquone and 100 mg proguanil) once daily for 3 consecutive days. Blood samples were taken for pharmacokinetic investigations of atovaquone, proguanil, and cycloguanil up to 288 h (day 14) after the last dose. Urine samples were collected for the evaluation of proguanil and cycloguanil 0-8, 8-16, 16-24 and 24-48 h after the last dose. Efficacy assessments included the clinical and parasitological evaluation of mothers and newborns. Adverse events were evaluated at each visit to the antenatal clinics. RESULTS: Malarone appeared to be effective and well tolerated when used for the treatment of falciparum malaria in pregnant women. All patients showed prompt clinical improvement and the disappearance of parasitaemia after treatment. There were no serious adverse effects or unexpected adverse effects and no stillbirths or spontaneous abortions. The plasma concentration-time profiles of atovaquone and proguanil in most cases were best characterised by the two-compartment open model with zero-order input with/without absorption lag time and first-order elimination. There were no significant differences in any of the pharmacokinetic parameters of atovaquone, proguanil or cycloguanil between patients from Thailand and Zambia. For atovaquone, a Cmax of 1.33-8.33 microg/ml was reached at 2.0-9.3 h after the last dose on day 2. V/F, CL/F and t(1/2beta) were 6.9-39.5 l/kg, 83-384 ml/h/kg, and 57.8-130.8 h, respectively. The Cmax and t(max) values for proguanil versus cycloguanil were 383-918 versus 0-129 ng/ml and 3.3-8.6 versus 3-12 h, respectively. V/F, CL/F, and t(1/2beta) values for proguanil were 10.7-34.0 l/kg, 431-1,662 ml/h/kg and 11.2-30.3 h. The CL(R-CG), t(1/2z), (CG), proguanil/cycloguanil metabolic ratios, AUC ratios for proguanil to cycloguanil (AUC(PG/CG)) were 107.2-1,001 ml/h/kg, 5-95 ml/h/kg, 7.8-20.7 h, 5-57, and 4.7-20.2, respectively. CONCLUSION: The pharmacokinetics of atovaquone and cycloguanil appeared to be influenced by the pregnancy status, resulting in an decrease in the Cmax and AUC of approximately twofold.

Outbreak of Legionnaires' disease associated with a display whirlpool spa.

BACKGROUND: Recognized outbreaks of Legionnaires' disease (LD) are rare; when they occur, they provide opportunities to understand the epidemiology of the illness and improve prevention strategies. We investigated a population-based outbreak. METHODS: After the confirmation of LD in October 1996 in five people in neighbouring towns in southwest Virginia, active surveillance for additional cases was undertaken. A case-control study was conducted to identify exposures associated with illness, followed by a cohort study among employees of the facility at which the source of the outbreak was located in order to assess unrecognized exposure and illness. Samples of likely sources of LD in the facility were cultured for LEGIONELLA: RESULTS: In all, 23 laboratory-confirmed cases of LD were eventually identified. Of the 15 cases in the case-control study, 14 (93%) reported visiting a home-improvement store, compared with 12 (27%) of 45 controls (matched odds ratio [MOR] = 23.3; 95% CI : 3-182). Among home-improvement centre patrons, 10 (77%) of 13 cases questioned recalled either visiting or walking by a display whirlpool spa, compared with 3 (25%) of 12 controls (MOR = 5.5; 95% CI : 0.7-256.0). Two cases' sputum isolates were an exact match, by monoclonal antibody subtyping and arbitrarily primed polymerase chain reaction, to a whirlpool spa filter isolate from the store. Employees reporting more exposure to the display spas were more likely to report symptoms of LD or to have an elevated titre. CONCLUSIONS: This investigation shows that LD can be transmitted from a whirlpool spa used for display only, and highlights the need for minimizing the risk of transmission of LD from all water-filled spas. Key messages This paper describes an investigation of a population-based outbreak of Legionnaires' disease (LD). A case-control study first identified a home-improvement store as the likely source of the outbreak. An environmental investigation later confirmed that finding, as two cases' sputum isolates were an exact match, by monoclonal antibody subtyping and arbitrarily primed polymerase chain reaction, to a whirlpool spa filter isolate from the store. The spa was intended and used for display only.

Congenital syphilis after treatment of maternal syphilis with a penicillin regimen exceeding CDC guidelines.

BACKGROUND: Although congenital syphilis usually occurs as a result of a failure to detect and treat syphilis in pregnant women, failures of the currently recommended regimen to prevent congenital syphilis have been reported. CASE: This report describes an infant with congenital syphilis despite maternal treatment with a regimen exceeding current CDC guidelines. CONCLUSION: Regardless of the regimen used to treat syphilis during pregnancy, clinicians should recognize the possibility of occasional treatment failures and the importance of adequate follow-up of infants at risk for congenital syphilis.

Physical and sexual abuse and associated mental disorders among alcoholic inpatients.

OBJECTIVE: The purpose of this study was to investigate the adult psychiatric correlates of childhood abuse among alcoholic inpatients. METHODS: The 802 patients, who included 321 women, were admitted to one of five New York State alcohol treatment inpatient centers. Each patient was interviewed, and sexual and physical abuse history, DSM-III diagnosis, and other characteristics were recorded. RESULTS: The overall prevalence of reported childhood abuse was 59% for women and 30% for men. Family history of alcoholism was associated with higher levels of physical and sexual abuse. Gender differences in types of childhood abuse (i.e., sexual abuse only, physical abuse only, dual abuse) were evident; 49% of the women and 12% of the men reported sexual abuse (with or without physical abuse), 33% of the women and 24% of the men reported physical abuse (with or without sexual abuse), and 23% of the women and 5% of the men reported dual abuse. Abuse status, and especially dual abuse, was associated with higher rates of antisocial personality disorder and suicide attempts among women and men, with generalized anxiety disorder among women, and with major depression among men. CONCLUSIONS: The findings highlight the long-term associations between sexual and physical abuse and adult coexisting mental disorders among alcoholic inpatients. Addressing unresolved intrapsychic trauma associated with childhood abuse may increase the efficacy of treatment outcomes and reduce relapse rates among alcoholics.

Sporotrichosis following a rodent bite. A case report.

A ten year old boy developed lymphocutaneous sporotrichosis following a wild rodent bite. The infection was successfully treated with potassium iodide. Sporotrichosis in humans has followed bites, pecks and stings inflicted by a variety of animals, birds and insects. Many species of animals are susceptible to infection by Sporothrix schenkii, but transmission from infected animals to man is uncommon.

Efficacy of SIV/deltaB670 glycoprotein-enriched and glycoprotein-depleted subunit vaccines in protecting against infection and disease in rhesus monkeys.

Immunization with an inactivated whole-virus vaccine is highly effective in preventing lentivirus infection. The viral protein(s) essential to the induction of protective responses, however, have not been identified. To define the role of virion components in the induction of protective immunity, we evaluated the efficacy of glycoprotein-enriched and glycoprotein-depleted simian immunodeficiency virus (SIV) subunit vaccines prepared by lentil-lectin affinity chromatography of gradient-purified virions using the immunization and challenge regimen previously found successful with an inactivated whole-virus vaccine. Infection was determined by successful recovery of virus, the induction of SIV-specific antibody responses, and infection of naive recipients by inoculation with lymph-node-derived lymphocytes from the vaccinates. Immunization with the glycoprotein-enriched preparation prevented infection in two out of four monkeys, whereas the glycoprotein-depleted vaccine failed to prevent infection in all four vaccinates tested. However, the glycoprotein-depleted vaccine appeared to moderate the progression of SIV-induced disease compared with non-immunized infected control monkeys inoculated with the same challenge dose. These data suggest that subunit vaccines containing sufficient quantities of viral glycoproteins can protect against SIV infection, whereas subunit vaccines composed predominantly of viral core proteins cannot. The development of effective vaccines against HIV infection should include studies on the optimum presentation of the viral envelope glycoproteins to produce long-term broadly protective immune responses.

A cluster of meningococcal disease on a school bus following epidemic influenza.

An outbreak of meningococcal disease among children on a school bus offered the opportunity to study a proposed association between this infection and preceding influenza infection. Five students who rode the bus became ill with invasive group C meningococcus. Transmission was limited to the bus; there was no evidence for school transmission. All five students reported influenza-like symptoms within several weeks before the development of meningococcal disease. School absenteeism, principally due to upper respiratory tract illness, was higher during the 3 weeks before the outbreak of meningococcal disease than during any period in the preceding 3 1/2 years, suggesting an unusually severe outbreak of respiratory illness. A case-control study comparing students with and without influenza symptoms revealed that the outbreak of respiratory disease was due to B/Ann Arbor/1/86 influenza (geometric mean titers, 86 for 80 patients and 33 for 47 controls [P = .0007]). These data add to the evidence suggesting that influenza respiratory infection predisposes to meningococcal disease.

Fatal occupational electrical injuries in Virginia.

Work-related electrical injuries and fatalities in Virginia were reviewed for the period 1977 to 1985. Of 196 workers electrocuted (0.9/100,000/year), 65% (127) died between May and September. Death rates were highest for male workers in utility companies (10.0/100,000), mining (5.9/100,000), and construction industries (3.9/100,000), but these high risk groups accounted for only 50% of the deaths. Most accidental electrocutions resulted from power line contact (53%) and machine or tool usage or repair (22%). Only 1.5% (2/101) of the workers who died within 6 hours of injury and had blood alcohol concentration tested were legally intoxicated. All workers need safety education on active measures to prevent hazardous electrical exposures, not just those at high risk for electrical injury. Every work-related electrical injury represents a sentinel health event--an opportunity for preventive intervention in the workplace.

AIDS and tuberculosis.

The diagnostic and therapeutic implications of human immunodeficiency virus (HIV) infection and tuberculosis in South Africa, where tuberculosis remains a major health problem, are reviewed. Mycobacterium tuberculosis is a high-grade pathogen and is able to establish infection early in immunodeficiency. With HIV infection showing significant entry into the heterosexual population in the RSA, an increasing number of cases with both infections can be expected to occur. The radiological appearance in combined infection is variable, ranging from a formal cavitatory picture to the more common finding of diffuse pulmonary infiltration. Intrathoracic adenopathy is a more specific sign of tuberculosis in HIV infection, since it is not associated with persistent generalised lymphadenopathy and pulmonary opportunistic infections, such as Pneumocystis carinii pneumonia. Intercurrent pneumonic infections and other pulmonary manifestations of HIV disease render the interpretation of new infiltrates on chest radiography problematical. Tuberculin skin testing remains useful in HIV infection and should be performed in all HIV-infected patients. The value of tuberculosis serology still remains questionable. Standard antituberculosis drug regimens are effective, but maintenance treatment must be continued for life and should include isoniazid and rifampicin. BCG vaccination is recommended routinely at birth in infants with HIV infection and for asymptomatic HIV-infected individuals who have not previously been immunised.

State epidemiology programs and state epidemiologists: results of a national survey.

In 1983, the State Epidemiologists in 46 States completed a survey questionnaire describing the professional qualifications, training, and experience of State health department epidemiologists and the scope of participation by the State Epidemiologists and their staffs in public health programs. The survey identified 224 State health department epidemiologists (estimated U.S. ratio 1.1 per million population). A State health department epidemiologist was most often male (80 percent), frequently (57 percent) was a physician, had an average age of 41 years, and had worked as an epidemiologist for 9 years. Participation in public health programs (either by supervising or providing consultation) by the State Epidemiologists and their staffs focused mainly on general epidemiology and communicable disease programs; fewer than half had participated in programs relating to the health of women and children, chronic diseases, injuries, or in other programs directed towards preventing premature mortality. Recently, the State Epidemiologists have been trying to broaden their activities into these areas; however, the demands created by the acquired immunodeficiency syndrome (AIDS) will mostly likely slow this process. Based on the overall findings and collective experience, it was concluded that State health departments have too few epidemiologists to address the wide variety of important public health problems facing our communities. It was proposed that each State health department have at least four epidemiologists (including one or more physician epidemiologists) and at least one master's level biostatistician and that the epidemiologists-per-population ratio not be less than 1 per million.

Ontario walk-in clinics: a preliminary descriptive study.

Little has been reported about Canadian walk-in clinics. The authors identified and surveyed 34 Ontario walk-in clinics in a preliminary descriptive study. A walk-in clinic was operationally defined as "a clinic that is separate from a hospital, has extended hours, and normally accepts patients without an appointment or a referral." Results showed that most Ontario walk-in clinics are not identifiable by name, have increased in number dramatically in the past two years, have laboratory, X-ray, and electrocardiographic facilities, and have varied practice patterns. Implications for rising health care costs and changing views on family practice were noted and suggestions made for future research.

Walk-in Clinics and Primary Care: Review of the Literature.

Walk-in clinics have proliferated rapidly in many areas of Canada and the United States. Patients who attend these clinics have illnesses that are similar to those seen in family physicians' offices, yet walk-in patients perceive their symptoms to be more urgent and present at a much earlier stage of their illness than patients who attend their family doctor. Research has not yet proven that the opening of walk-in facilities lowers the demand for traditional primary care services; therefore the cost-effectiveness of walk-in clinics needs further evaluation.

Pulmonary non-tuberculous mycobacterial disease.

We confirmed 3 and identified 7 possible cases of pulmonary non-tuberculous mycobacterial disease. The clinical and radiological features were indistinguishable from those of tuberculosis, although a few thin-walled cavities may have been more suggestive of non-tuberculous disease. Previously described predisposing factors were identified in our patients and included previous fibrocavitating disease, chronic airflow obstruction and bronchiectasis. However, 5 patients had no pre-existing lung disease. The difficulties in treating these patients are discussed and in view of the chronic indolent course, prolonged aggressive polypharmacy is usually not indicated. It is recommended that at least two consecutive sputum specimens be sent for culture and drug resistance testing whenever the disease is suspected. This will help differentiate colonisation from infection and rationalise management.

Comparison of lead dislodgment and pocket infection rates after pacemaker implantation in the operating room versus the catheterization laboratory.

To assess and compare the rates of lead dislodgment and pocket infection in patients having procedures performed in the operating room versus those performed in the cardiac catheterization laboratory, we reviewed the records of 85 adult patients who underwent 88 procedures, all performed by one surgical team and having complete follow-ups at our institution from October 8, 1979, through November 7, 1986. Forty-five patients underwent 46 procedures in the operating room, and 40 patients underwent 42 procedures in the cardiac catheterization laboratory. There was one instance of ventricular lead dislodgment noted among the 48 leads implanted in the operating room and one instance of ventricular lead dislodgment among the 58 leads implanted in the cardiac catheterization laboratory. No instances of atrial lead dislodgment were noted. No instances of pocket infection were noted among the 46 procedures performed in the operating room or in the 42 procedures performed in the cardiac catheterization laboratory. We conclude that pacemaker implantation can be performed with equivalent safety and effectiveness in the cardiac catheterization laboratory and in the operating room.

The clinical manifestations of Rhodesian trypanosomiasis: an account of cases contracted in the Okavango swamps of Botswana.

Over 100 years ago, David Livingstone reported the presence of tsetse flies in the Okavango swamps in northern Botswana. They have persisted in the region and recently have been responsible for many cases of Rhodesian sleeping sickness caused by Trypanosoma rhodesiense in visitors to the area. The clinical manifestations in illustrative cases of this disease are described. One patient who refused treatment died five months after being infected. One patient died of encephalopathy complicating treatment with Melarsoprol (Mel B) and one died in a hemorrhagic state associated with a heavy parasitemia early in his illness. Most patients treated early respond well to treatment with specific drugs, usually Suramin, and are cured. In those with involvement of the central nervous system the treatment required is more hazardous, but usually is effective in curing the patient.