This report updates and combines earlier versions of guidelines for the prevention and treatment of opportunistic infections (OIs) in HIV-infected adults (i.e., persons aged >/=18 years) and adolescents (i.e., persons aged 13--17 years), last published in 2002 and 2004, respectively. It has been prepared by the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by clinicians and other health-care providers, HIV-infected patients, and policy makers in the United States. These guidelines address several OIs that occur in the United States and five OIs that might be acquired during international travel. Topic areas covered for each OI include epidemiology, clinical manifestations, diagnosis, prevention of exposure; prevention of disease by chemoprophylaxis and vaccination; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment; management of treatment failure; prevention of disease recurrence; discontinuation of secondary prophylaxis after immune reconstitution; and special considerations during pregnancy. These guidelines were developed by a panel of specialists from the United States government and academic institutions. For each OI, a small group of specialists with content-matter expertise reviewed the literature for new information since the guidelines were last published; they then proposed revised recommendations at a meeting held at NIH in June 2007. After these presentations and discussion, the revised guidelines were further reviewed by the co-editors; by the Office of AIDS Research, NIH; by specialists at CDC; and by HIVMA of IDSA before final approval and publication. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments. Major changes in the guidelines include 1) greater emphasis on the importance of antiretroviral therapy for the prevention and treatment of OIs, especially those OIs for which no specific therapy exists; 2) information regarding the diagnosis and management of immune reconstitution inflammatory syndromes; 3) information regarding the use of interferon-gamma release assays for the diagnosis of latent Mycobacterium tuberculosis (TB) infection; 4) updated information concerning drug interactions that affect the use of rifamycin drugs for prevention and treatment of TB; 5) the addition of a section on hepatitis B virus infection; and 6) the addition of malaria to the list of OIs that might be acquired during international travel. This report includes eleven tables pertinent to the prevention and treatment of OIs, a figure that pertains to the diagnois of tuberculosis, a figure that describes immunization recommendations, and an appendix that summarizes recommendations for prevention of exposure to opportunistic pathogens.

Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.

Many drugs and environmental chemicals are capable of evoking some degree of liver injury. The liver represents a primary target for adverse drug reactions due to its central role in biotransformation and excretion of foreign compounds, its portal location within the circulation exposing it to a wide variety of substances, and its anatomic and physiologic structure. Drug-induced liver injury (DILI) remains the single most common adverse indication leading to drug candidate failure or withdrawal from the market. However, the absolute incidence of DILI is low, and this presents a challenge to mechanistic studies. DILI remains unpredictable making prevention very difficult. In this chapter, we focus on the current understanding of DILI. We begin with an overview regarding the significance and epidemiology of DILI and then examine the clinical presentation and susceptibility factors related to DILI. This is followed by a review of the current literature regarding the proposed pathogenesis of DILI, which involves the participation of a drug, or most often a reactive metabolite of the drug, that either directly affects cellular function or elicits an immune response. It is our hope that this chapter will shed light on the major problems associated with DILI in regards to the pharmaceutical industry, drug regulatory agencies, physicians and pharmacists, and patients.

Drug-induced liver injury.

Acute and chronic hepatitis B virus (HBV) infection is a leading cause of liver disease worldwide. It is estimated that approximately 350 million people worldwide have chronic HBV infection and that 1 million persons die each year from HBV-related chronic liver disease. In the past decade, significant progress in the understanding of the molecular virology and pathogenesis of HBV infection has been made. In addition, effective treatment modalities have been developed for persons with chronic infection. Worldwide, prevention of HBV transmission has become a high priority. In 1992, the Global Advisory Group to the World Health Organization recommended that all countries integrate hepatitis B vaccine into national immunization programs by 1997. Currently, 80 countries have done so and several others are planning to. Many countries have reported dramatic reductions in the prevalence of chronic HBV infection among children born since the hepatitis B vaccine was introduced into infant immunization schedules. Recent reports from Taiwan indicate a reduction in the incidence of liver cancer among children as a result of widespread hepatitis B vaccination programs.

/pdf/update-on-diagnosis-management-and-prevention-of-hepatitis-b-50322jlj9u.pdf

Update on Diagnosis, Management, and Prevention of Hepatitis B Virus Infection

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.23588

Drug‐induced autoimmune hepatitis: Clinical characteristics and prognosis

Hepatitis A virus (HAV) is spread by faecal-oral contact or ingestion of contaminated food or water. Lifelong immunity is conferred by infection or vaccination, so anti-HAV seroprevalence studies can be used to indicate which populations are susceptible to infection. Seroprevalence rates are highly correlated with socioeconomic status and access to clean water and sanitation. Increasing household income, education, water quality and quantity, sanitation, and hygiene leads to decreases in HAV prevalence. Japan, Australia, New Zealand, Canada, the United States, and most European nations have low anti-HAV rates. Although anti-HAV rates remain high in most Latin American, Asian, and Middle Eastern nations, average seroprevalence rates are declining. Surveys from Africa generally indicate no significant decline in anti-HAV rates. Because the severity of illness increases with age, populations with a high proportion of susceptible adults should consider targeted vaccination programmes.

Declining hepatitis A seroprevalence: a global review and analysis.

The increased spread of drug resistant malaria highlights the need for alternatives for treatment and chemoprophylaxis. The combination of atovaquone and proguanil hydrochloride (Malarone, GlaxoSmithKline, NC) has shown high efficacy against Plasmodium falciparum with only mild side effects and has been registered for use in several countries, including Denmark, Germany, Sweden, the United Kingdom, and the United States.1 Treatment failures have been attributed to suboptimal dosage, reinfections, or to a point mutation in the cytochrome b gene. 1 2 Bioavailability of atovaquone depends on the concomitant intake of a fatty diet, yet drug concentrations were not analysed in these reports. We provide evidence of resistance in two patients treated with atovaquone and proguanil hydrochloride for P falciparum infection.

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Details of three patients treated with atovaquone and proguanil hydrochloride (Malarone; GlaxoSmithKline) for Plasmodium …

https://www.bmj.com/content/bmj/326/7390/628.full.pdf

Evidence of Plasmodium falciparum malaria resistant to atovaquone and proguanil hydrochloride: case reports

A total of 500 individuals from five different regions of Ethiopia were studied. Demographic and clinical data were recorded and serologic tests were carried out to detect antigen and antibody markers of hepatitis B virus, hepatitis A virus, and the delta agent. Data on the economic status, number of rooms per household, number of persons per household, type of water supply, and mode of excreta disposal revealed that the majority of the population surveyed lived with economic hardship, overcrowding and poor hygiene. Only 36 persons gave a past history of jaundice. The mean carrier rate of hepatitis B surface antigen (HBsAg) was 6.2%, the mean overall hepatitis B virus marker prevalence was 42%, and in those over 14 years of age it was 76%. Among those who were positive for HBsAg, there was a tendency for hepatitis B e antigen (HBeAg) to decrease and the corresponding antibody (anti-HBe) to increase with advancing age. No woman more than 15 years of age had demonstrable hepatitis B e antigen in serum. Antibody to hepatitis A virus was detected in 84%. Three positive individuals were found to have antibody to the delta agent.

Hepatitis a, b, and delta infection in ethiopia: a serologic survey with demographic data

Forty-six patients with histologically verified chronic active hepatitis (CAH) were divided into three groups according to whether the CAH was virus-induced, drug-induced, or cryptogenic. The frequency of the HL-A antigens 1 and 8 was increased in the cryptogenic group while the other groups did not differ significantly from healthy controls. Autoantibodies were often found in high titres in the drug-induced and cryptogenic groups but were infrequent in the virus-induced group.

https://www.bmj.com/content/bmj/4/5988/77.full.pdf

Trigger factors and HL-A antigens in chronic active hepatitis.

This two-year controlled study was conducted to define the mode of transmission of hepatitis B infection in Ethiopia. Twenty-five of 500 (5%) expectant mothers were identified as HbsAg positive (Group A). A control group of 29 mothers negative for HBsAg (Group B) was randomly selected. These 54 mothers and their families (husbands, infants and the infants' older siblings) were followed for two years with determinations of serological markers of ongoing or past hepatitis B virus infection at 6, 12 and 24 months. Social and clinical data as well as possible factors contributing to the spread of HBV (ie tattoos, circumcision, etc.) were compiled from questionnaires. Twenty-one of the 25 (84%) HBsAg positive mothers had anti-HBe and none had HBeAg. One case of vertical hepatitis B virus transmission was seen while horizontal transmission during the study period occurred in two infants and in two older siblings. Potential risk factors for non-perinatal transmission were highly prevalent in both groups and may represent the main route of transmitting the infection, while, as shown in the present study, the vertical transmission of HBV infection only plays a minor role in the maintenance of the high infection rate in Ethiopia. Vaccinating all babies soon after birth would, therefore, be an effective means of eradicating or reducing the hepatitis B virus infection and its sequelae.

Transmission of Hepatitis B Virus Infection in Ethiopia with Emphasis on the Importance of Vertical Transmission

The case records of 64 patients with 65 episodes of infectious gonarthritis during 1979-88 were reviewed regarding epidemiological, clinical and laboratory data of possible relevance to the course and outcome of the disease. Long-term healing results were evaluated by means of a new scoring system 2-11 years after the acute disease in 46 patients. The infection was acquired by inoculation in 37% and by the hematogenous route in 55%. The major risk factors were trauma to the joint and arthrosis. Staphylococcus aureus was the causative agent in 58% and Streptococci in 15%. Treatment consisted of suction irrigation (86%) or intermittent aspiration (5%) combined with systemic antibiotic treatment. At follow-up, the pain and ache scores of the arthritic joint had decreased by 21% and 16% respectively, compared with the scores of the contralateral control joints. Anatomy and motility were reduced by 9% and 8% respectively. Age 5 days was associated with increased loss of motility. We estimate that 79% of the patients had excellent or good long-term results following treatment of infectious arthritis of the knee. Evaluation of healing after infectious gonarthritis by use of a scoring system is quite feasible and allows comparison of different treatment regimes with improved accuracy.

Johan Lindberg

Papers

Evidence of Plasmodium falciparum malaria resistant to atovaquone and proguanil hydrochloride: case reports

Hepatitis a, b, and delta infection in ethiopia: a serologic survey with demographic data

Trigger factors and HL-A antigens in chronic active hepatitis.

Transmission of Hepatitis B Virus Infection in Ethiopia with Emphasis on the Importance of Vertical Transmission

Septic Arthritis of the Knee: A 10-Year Review and Long-term Follow-up using a New Scoring System