Supporting new vaccine introduction decisions: lessons learned from the Hib Initiative experience.

The introduction of Haemophilus influenzae type b (Hib) vaccine in developing countries has suffered from a long delay. Between 2005 and 2009, a surge in Hib vaccine adoption took place, particularly among GAVI-eligible countries. Several factors contributed to the increase in Hib vaccine adoption, including support provided by the Hib Initiative, a project funded by the GAVI Alliance in 2005 to accelerate evidence-informed decisions for use of Hib vaccine. This paper reviews the strategy adopted by the Hib Initiative and the lessons learned in the process, which provide a useful model to accelerate uptake of other new vaccines.

Establishment of public health security in Saudi Arabia for the 2009 Hajj in response to pandemic influenza A H1N1.

Mass gatherings of people challenge public health capacities at host locations and the visitors' places of origin. Hajj--the yearly pilgrimage by Muslims to Saudi Arabia--is one of the largest, most culturally and geographically diverse mass gatherings in the world. With the 2009 pandemic influenza A H1N1 and upcoming Hajj, the Saudi Arabian Ministry of Health (MoH) convened a preparedness consultation in June, 2009. Consultants from global public health agencies met in their official capacities with their Saudi Arabian counterparts. The MoH aimed to pool and share public health knowledge about mass gatherings, and review the country's preparedness plans, focusing on the prevention and control of pandemic influenza. This process resulted in several practical recommendations, many to be put into practice before the start of Hajj and the rest during Hajj. These preparedness plans should ensure the optimum provision of health services for pilgrims to Saudi Arabia, and minimum disease transmission on their return home. Review of the implementation of these recommendations and their effect will not only inform future mass gatherings in Saudi Arabia, but will also strengthen preparedness efforts in other settings.

Candidemia in pediatric outpatients receiving home total parenteral nutrition.

This is a cohort study of pediatric outpatients receiving total parenteral nutrition (TPN) and follow-up care in a Tennessee hospital between January and June 1999. The study was conducted following an increase in the incidence of candidemia. Of 13 children receiving home TPN, five had candidemia; three were due to Candida parapsilosis. Case patients were more likely to have an underlying hematologic disease (P = 0.02) as well as previous history of fungemia (P = 0.02). Two case patients had successive candidemia episodes 3 months apart; karyotypes and RAPD profiles of each patient's successive C. parapsilosis isolates were similar. Candida spp. were frequently detected in hand cultures from cohort members (four of 10) and family member caregivers (nine of 11); C parapsilosis was isolated from five caregivers. Our findings underscore the challenges of maintaining stringent infection control practices in the home health care setting and suggest the need for more intensive follow-up and coordination of home TPN therapy among pediatric patients.

Blastomycosis in Missouri: epidemiology and risk factors for endemic disease.

Between 1992 and 1999, 93 cases of blastomycosis, including 25 laboratory confirmed cases, were identified in Missouri (annual incidence, 0.2/100,000 population). Mississippi County in southeastern Missouri had the highest incidence (12/100,000) with a much higher rate among blacks than whites in this county (43.21/100,000). The mortality rate, 44% was also higher among blacks. To determine risk factors for endemic blastomycosis, a case-control study was conducted among southeastern Missouri residents. Independent risk factors for blastomycosis were black race and a prior history of pneumonia. No environmental exposures or socioeconomic factors were significantly associated with increased risk. The increased risk among blacks may possibly be related to genetic factors, but further studies are needed to clarify this. However, heightened awareness of the disease and a better understanding of the risk factors are important and may lead to earlier diagnosis and start of treatment, possibly improving outcome.

Population-based surveillance and a case-control study of risk factors for endemic lymphocutaneous sporotrichosis in Peru.

Population-based surveillance and a case-control study were conducted in Abancay, Peru, to estimate the burden of disease and to determine risk factors for sporadic lymphocutaneous sporotrichosis (LS). Laboratory records from local hospitals were reviewed for the years of 1997 and 1998, and prospective surveillance was conducted for the period of September 1998 through September 1999. A case-control study was conducted with 2 matched control subjects per case patient. The mean annual incidence was 98 cases per 100,000 persons. Children had an incidence 3 times higher than that for adults and were more likely to have LS lesions on the face and neck. Identified risk factors included owning a cat, playing in crop fields, having a dirt floor in the house, working mainly outdoors, and having a ceiling made of raw wood or conditions associated with a lower socioeconomic status. Decreased environmental exposure, such wearing protective clothing during construction activities for adults or limiting contact with cats and soil for children, and improvements in living spaces may decrease the incidence of LS.

Secular trend of hospital-acquired candidemia among intensive care unit patients in the United States during 1989-1999.

We describe the annual incidence of primary bloodstream infection (BSI) associated with Candida albicans and common non-albicans species of Candida among patients in intensive care units that participated in the National Nosocomial Infections Surveillance system from 1 January 1989 through 31 December 1999. During the study period, there was a significant decrease in the incidence of C. albicans BSI (P<.001) and a significant increase in the incidence of Candida glabrata BSI (P=.05).

Trends in antifungal drug susceptibility of Cryptococcus neoformans isolates in the United States: 1992 to 1994 and 1996 to 1998.

The antifungal drug susceptibilities of two collections of Cryptococcus neoformans isolates obtained through active laboratory-based surveillance from 1992 to 1994 (368 isolates) and 1996 to 1998 (364 isolates) were determined. The MICs of fluconazole, itraconazole, and flucytosine were determined by the National Committee for Clinical Laboratory Standards broth microdilution method; amphotericin B MICs were determined by the E-test. Our results showed that the MIC ranges, the MICs at which 50% of isolates are inhibited (MIC(50)s), and the MIC(90)s of these four antifungal agents did not change from 1992 to 1998. In addition, very small numbers of isolates showed elevated MICs suggestive of in vitro resistance. The MICs of amphotericin B were elevated (>or=2 microg/ml) for 2 isolates, and the MICs of flucytosine were elevated (>or=32 microg/ml) for 14 isolates. Among the azoles, the fluconazole MIC was elevated (>or=64 microg/ml) for 8 isolates and the itraconazole MIC (>or=1 microg/ml) was elevated for 45 isolates. Analysis of 172 serial isolates from 71 patients showed little change in the fluconazole MIC over time. For isolates from 58 patients (82% of serial cases) there was either no change or a twofold change in the fluconazole MIC. In contrast, for isolates from seven patients (12% of serial cases) the increase in the MIC was at least fourfold. For isolates from another patient there was a 32-fold decrease in the fluconazole MIC over a 1-month period. We conclude that in vitro resistance to antifungal agents remains uncommon in C. neoformans and has not significantly changed with time during the past decade.

Counterpoint: invasive aspergillosis and the environment--rethinking our approach to prevention.

Preventive measures are important in the control of invasive aspergillosis (IA) because diagnosis is difficult and the outcome of treatment is poor. If effective strategies are to be devised, it will be essential to have a clearer understanding of the sources and routes of transmission of Aspergillus species. Nosocomial outbreaks of IA highlight the fact that Aspergillus spores are common in the hospital environment. However, in general, such outbreaks are uncommon. Most cases of IA are sporadic in nature, and many of them are now being acquired outside of the hospital setting. Housing patients in high-energy particulate air-filtered hospital rooms helps prevent IA, but it is feasible and cost-effective only for the highest-risk groups and for limited periods. Control measures, which are designed to protect patients from exposure to spores outside the hospital, are even more difficult. Nevertheless, now that high-risk patients are spending more time outside of the hospital, the cost benefits of antifungal prophylaxis and other preventive measures require careful evaluation.

Trends in mortality due to invasive mycotic diseases in the United States, 1980-1997.

To determine national trends in mortality due to invasive mycoses, we analyzed National Center for Health Statistics multiple-cause-of-death record tapes for the years 1980 through 1997, with use of their specific codes in the International Classification of Diseases, Ninth Revision (ICD-9 codes 112.4-118 and 136.3). In the United States, of deaths in which an infectious disease was the underlying cause, those due to mycoses increased from the tenth most common in 1980 to the seventh most common in 1997. From 1980 through 1997, the annual number of deaths in which an invasive mycosis was listed on the death certificate (multiple-cause [MC] mortality) increased from 1557 to 6534. In addition, rates of MC mortality for the different mycoses varied markedly according to human immunodeficiency virus (HIV) status but were consistently higher among males, blacks, and persons > or =65 years of age. These data highlight the public health importance of mycotic diseases and emphasize the need for continuing surveillance.

The epidemiology of histoplasmosis: a review.

Histoplasmosis is the most common endemic mycosis in the United States and has recently emerged as an important opportunistic infection among human immunodeficiency virus (HIV)-infected persons living in areas where it is endemic. In this article, we describe the epidemiologic and ecologic features of histoplasmosis, highlighting the implications for prevention. Surveillance and education of the public and health care providers are needed to determine the disease burden of histoplasmosis. Development of better diagnostic tests for detection of disease in humans and of the organism in the environment will help in designing better prevention strategies.

Adenovirus type 3 viremia in an adult with toxic shock-like syndrome.

Surveillance by the Unexplained Deaths and Critical Illnesses Project (UNEX) uncovered a novel presentation of adenovirus type 3 infection that satisfied the criteria for toxic shock-like syndrome in a 28-year-old immunocompetent man. Adenovirus may be a cause of toxic shock syndrome; surveillance systems such as UNEX may uncover additional causes of this and other clinically defined infectious syndromes.

Gastrointestinal basidiobolomycosis in Arizona: clinical and epidemiological characteristics and review of the literature.

Gastrointestinal basidiobolomycosis (GIB) is an unusual fungal infection that is rarely reported in the medical literature. From April 1994 through May 1999, 7 cases of GIB occurred in Arizona, 4 from December 1998 through May 1999. We reviewed the clinical characteristics of the patients and conducted a case-control study to generate hypotheses about potential risk factors. All patients had histopathologic signs characteristic of basidiobolomycosis. Five patients were male (median age, 52 years; range, 37--59 years) and had a history of diabetes mellitus (in 3 patients), peptic ulcer disease (in 2), or pica (in 1). All patients underwent partial or complete surgical resection of the infected portions of their gastrointestinal tracts, and all received itraconazole postoperatively for a median of 10 months (range, 3--19 months). Potential risk factors included prior ranitidine use and longer residence in Arizona. GIB is a newly emerging infection that causes substantial morbidity and diagnostic confusion. Further studies are needed to better define its risk factors and treatment.

Multicenter case-control study of risk factors for histoplasmosis in human immunodeficiency virus-infected persons.

We conducted a multicenter case-control study to identify risk factors for histoplasmosis among persons with acquired immunodeficiency syndrome (AIDS) and to evaluate predictors of a poor outcome (defined as death or admission to the intensive care unit). Patients with histoplasmosis were each matched by age, sex, and CD4 lymphocyte count to 3 controls. From 1996 through 1999, 92 case patients and 252 controls were enrolled. Of the case patients, 81 (89%) were men, 50 (55%) were black, 78 (85%) had a CD4 lymphocyte count of <100 cells/microL, 80 (87%) were hospitalized, and 11 (12%) died. Multivariable analysis found that receipt of antiretroviral therapy and of triazole drugs were independently associated with a decreased risk of histoplasmosis. Chronic medical conditions and a history of infections with herpes simplex virus were associated with poor outcome. Triazoles should be considered for chemoprophylaxis for persons with AIDS, especially those who take part in high-risk activities that involve frequent exposure to soil, who have CD4 lymphocyte counts of <100 cells/microL, and who live in areas where histoplasmosis is endemic.

Risk factors for severe pulmonary and disseminated coccidioidomycosis: Kern County, California, 1995-1996.

Surveillance for coccidioidomycosis (CM) and a case-control study for risk factors among adults were conducted in Kern County, California. From January 1995 through December 1996, 905 cases of CM were identified, for an annual incidence of 86 cases per 100,000 population. A total of 380 adults were enrolled in the case-control study: 77 had severe pulmonary disease, 33 had disseminated disease, and 270 control patients had mild disease. Independent risk factors for severe pulmonary disease included diabetes, recent history of cigarette smoking, income of < $15,000 per year, and older age. Oral antifungal therapy before hospitalization was associated with a reduced risk of CM pneumonia. Risk factors for disseminated disease were black race, income of < $15,000 per year, and pregnancy. Early treatment of CM with oral antifungal agents may prevent severe pulmonary disease in groups considered to be at high risk, such as elderly individuals, persons with diabetes, and smokers. Persons at risk for severe CM may benefit from vaccination once an effective CM vaccine is available.

A large-scale North American study of fungal isolates from nails: the frequency of onychomycosis, fungal distribution, and antifungal susceptibility patterns.

BACKGROUND: Onychomycosis, a fungal infection of the nail bed, is responsible for up to 50% of nail disorders. Although several surveys have been conducted in different parts of the world, there have been no multicenter epidemiologic surveys of onychomycosis in North America. OBJECTIVE: A 12-center study was undertaken to (1) determine the frequency of onychomycosis, (2) identify organisms recovered from the nails, and (3) determine the antifungal susceptibility of isolates. METHODS: A total of 1832 subjects participated in this study and completed a comprehensive questionnaire, and nail clippings were collected for potassium hydroxide examination and culturing. RESULTS: The frequency of onychomycosis, as defined by the presence of septate hyphae on direct microscopy and/or the recovery of a dermatophyte, was found to be 13.8%. In general, the dermatophyte isolates were susceptible to the antifungals tested. CONCLUSION: Because of the limited number of large-scale studies, the baseline incidence is not firmly established. However, the higher frequency of onychomycosis in this study may confirm the suspected increase in incidence of disease in North America.

Coccidioidomycosis in human immunodeficiency virus-infected persons in Arizona, 1994-1997: incidence, risk factors, and prevention.

From 1 January 1995 through 31 June 1997, 153 cases of coccidioidomycosis in human immunodeficiency virus (HIV)-infected persons were identified in Arizona (incidence, 41/1000 persons living with AIDS). A case-control study was conducted to evaluate risk factors for coccidioidomycosis in HIV-infected persons. A case was defined as laboratory-confirmed, incident coccidioidomycosis in a person infected with HIV for > or =3 months, and each case patient had 3 control patients matched by county, age group, sex, HIV/AIDS status, and CD4 lymphocyte count. Multivariable analysis identified black race and a history of oropharyngeal or esophageal candidiasis to be associated with increased risk of coccidioidomycosis; protease inhibitor therapy was associated with a reduced risk. In persons with previous history of oropharyngeal or esophageal candidiasis, having received an azole drug was associated with a reduced risk (odds ratio, 0.4; 95% confidence interval, 0.2-0.9; P=.04). Physicians may need to consider azole chemoprophylaxis for HIV-infected persons who live in areas of endemicity, have CD4 cell counts <200/microL, are black, or have a history of thrush.

Risk factors for acute symptomatic coccidioidomycosis among elderly persons in Arizona, 1996-1997.

Because of the increase in incidence of coccidioidomycosis among the elderly in Arizona between 1990 and 1996, a case-control study was conducted to look at risk factors for disease among these persons. Cases (n=89) were persons aged > or =60 years with laboratory-confirmed coccidioidomycosis; 2 control groups were selected, the first by use of random-digit dialing (geographic controls, n=91) and the second by use of lists of persons with negative serologic coccidioidomycosis tests (laboratory-negative controls, n=58). Elderly persons with coccidioidomycosis had spent significantly less time in Arizona than did persons in either control group and were more likely than geographic controls to have congestive heart failure or cancer, to have smoked, or to have taken corticosteroids. Elderly persons who recently have moved to Arizona or who have chronic illnesses and their physicians need to be aware of their higher risk for coccidioidomycosis in order to improve their chances of early diagnosis and treatment. These persons may benefit from vaccination, once an effective vaccine for coccidioidomycosis is developed.

Candida dubliniensis fungemia: the first four cases in North America.

We report the first four North American cases of Candida dubliniensis fungemia, including the first isolation of this organism from the bloodstream of an HIV-infected person. All isolates were susceptible in vitro to commonly used antifungal drugs. This report demonstrates that C. dubliniensis can cause bloodstream infection; however, the incidence of disease is not known.

Epidemiology: surveillance of fungal infections.

Surveillance for fungal diseases is essential to improve our understanding of their epidemiology and to enable research and prevention efforts to be prioritized. In order to conduct better surveillance for fungal diseases, it is important to develop more accurate and timely diagnostic tests, to follow rigorous epidemiological methods and to have adequate support from public health agencies and the pharmaceutical industry. Investigations of nosocomial and community outbreaks of fungal infection have also resulted in a better understanding of the sources and routes of transmission of these diseases, and of the risk factors for infection. This has led to more effective prevention and control strategies. In addition, outbreak investigations have offered excellent opportunities to develop new molecular sub-typing methods, and to evaluate and validate older ones. For example, results obtained from a global epidemiological study of the genomic structure of Cryptococcus neoformans have led to a better understanding of the epidemiology of cryptococcosis. Similarly, a study of variations in the genotype of Trichophyton rubrum has found that patients may become infected with multiple strains, which has important implications for study design when looking at the epidemiology of dermatophyte infections.