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1.  Primary prophylaxis for cryptococcal meningitis and impact on mortality in HIV: a systematic review and meta-analysis 
Future virology  2013;8(9):10.2217/fvl.13.71.
To determine the role of primary antifungal prophylaxis in the prevention of cryptococcal meningitis and all-cause mortality in advanced HIV infection
Materials & methods
This was a systematic review and meta-analysis of randomized trials and observational studies. Google Scholar™, PubMed and Embase databases were searched for relevant studies. Quality was assessed using different criteria, depending on study type. Publication bias was assessed and subgroup and sensitivity analyses were performed. When the results of the meta-analysis were homogeneous, the fixed-effects model was used; when the results of the meta-analysis were heterogenous, the random effects model was used.
Primary prophylaxis prevented cryptococcal meningitis but did not confer protection against overall mortality, although there was evidence of a reduction in cryptococcal-specific mortality in resource-limited settings.
Primary antifungal prophylaxis should be recommended in patients with advanced HIV infection in resource-limited settings with a high incidence of cryptococcal meningitis.
PMCID: PMC3869998  PMID: 24368930
advanced HIV infection; all-cause mortality; cryptococcal meningitis; fluconazole; itraconazole; prevention of cryptococcal meningitis; primary antifungal prophylaxis; resource-limited settings
2.  Isoniazid, Rifampin, Ethambutol and Pyrazinamide Pharmacokinetics and Treatment Outcomes among a Predominantly HIV-Infected Cohort of Adults with Tuberculosis — Botswana 
We explored the association between anti-tuberculosis drug pharmacokinetics and treatment outcomes among pulmonary tuberculosis (TB) patients in Botswana.
Consenting TB outpatients had blood collected 1, 2, and 6 hours after simultaneous isoniazid, rifampin, ethambutol, and pyrazinamide ingestion. Maximum serum concentrations (Cmax) and areas under the serum concentration-time curve (AUC0-6 h) were determined. Clinical status was monitored throughout treatment.
Of 225 participants, 36 (16%) experienced a poor treatment outcome (treatment failure or death); 155 (69%) were HIV-infected. Compared with published standards, low isoniazid Cmax occurred in 84 (37%); rifampin in 188 (84%); ethambutol in 87 (39%); and pyrazinamide in 11 (5%) patients. Median rifampin and pyrazinamide levels differed significantly by HIV status and CD4 cell count (HIV-CD4) categories. Only pyrazinamide pharmacokinetics were significantly associated with treatment outcome; low pyrazinamide Cmax was associated with a higher risk of documented poor treatment outcome than normal Cmax (50% vs. 16%; p<0.01). HIV-infected patients with CD4 <200 cells/μL had higher risk of poor treatment outcome (27%) than HIV-uninfected patients (11%) or HIV-infected patients with CD4 ≥ 200 cells/μL (12%); p=0.01. Adjusting for HIV infection and CD4, patients with low pyrazinamide Cmax were thrice more likely to have poor outcomes than patients with normal pyrazinamide Cmax [adjusted risk ratio = 3.38, 95% confidence interval (1.84 – 6.22)].
Lower-than-expected anti-tuberculosis drug Cmax occurred frequently and low pyrazinamide Cmax was associated with poor treatment outcome. Exploring the global prevalence and significance of these findings may suggest modifications in treatment regimens that could improve TB cure rates.
PMCID: PMC3762461  PMID: 19432554
tuberculosis; HIV/AIDS; pharmacokinetics; treatment outcome
3.  Guest Editorial 
Public Health Reports  2008;123(Suppl 1):1-3.
PMCID: PMC2233732  PMID: 18497008
4.  Incidence of herpes simplex virus type 2 in young reproductive age women in Mysore, India 
There are sparse data on herpes simplex virus type 2 (HSV-2) infection in India. HSV-2 is one of the most common sexually transmitted infections and the primary cause of genital ulcer disease worldwide.
The aim of this study is to describe the incidence of HSV-2 infection among young reproductive age women in Mysore, India.
Setting and Design
Between October 2005 and April 2006, 898 women were enrolled into a prospective cohort study in Mysore, India, and followed quarterly for 6 months.
Materials and Methods
An interviewer administered questionnaire was used to collect demographic and social risk factors, and physical examination was conducted for collection of biological specimens to screen for reproductive tract infections at each visit. Serologic testing was conducted for the presence of HSV-2 antibodies using HerpeSelect HSV-2 enzyme-linked immunosorbent assay.
Statistical Analysis Used
Data were analyzed using R. Incidence density rates were calculated using Poisson distributions with person-time of follow-up as denominator. Person-time was calculated as time from enrollment until time of first positive HSV-2 test.
There were 107 women with HSV-2 antibodies leaving 700 women with negative results at enrollment. The analysis included 696 out of which, there were 36 HSV-2 seroconversions during the study period. The study cohort accumulated roughly 348 woman-years of follow-up, yielding an HSV-2 acquisition rate of 10.4 cases/100 woman-years. All detected infections were asymptomatic.
HSV-2 incidence is moderate in this community sample of young reproductive age monogamous women. More research is needed to establish incidence estimates in different Indian settings.
PMCID: PMC3625929  PMID: 21393886
Herpes simplex virus; herpes simplex virus type 2; incidence; India; Women
5.  Simple and inexpensive point-of-care tests improve diagnosis of vaginal infections in resource constrained settings 
Bacterial vaginosis (BV) and Trichomonas vaginalis infection (TV) have been associated with adverse birth outcomes and increased risk for HIV. We compare the performance of simple inexpensive point-of-care (POC) tests to laboratory diagnosis and syndromic management of BV and TV in poor settings.
Between November 2005 and March 2006, 898 sexually active women attending two reproductive health clinics in Mysore, India were recruited into a cohort study investigating the relationship between vaginal flora and HSV-2 infection. Participants were interviewed and screened for reproductive tract infections. Laboratory tests included serology for HSV-2; cultures for TV, Candida sp., and Neisseria gonorrhoeae; Gram stains; and two POC tests: vaginal pH; and Whiff test.
Of the 898 participants, 411 [45.7%, 95% confidence interval (95% CI): 42.4–49.0%] had any laboratory diagnosed vaginal infection. BV was detected in 165 women (19.1%, 95%CI: 16.5–21.9%) using Nugent score. TV was detected in 76 women (8.5%, 95%CI: 6.7–10.4%) using culture. Among the entire study population, POC correctly detected 82% of laboratory diagnosed BV cases, and 83% of laboratory diagnosed TV infections. Among women with complaints of vulval itching, burning, abnormal vaginal discharge, and/or sores (445/898), POC correctly detected 83% (60 of 72 cases) of laboratory diagnosed BV cases vs. 40% (29 of 72 cases) correctly managed using the syndromic approach (P < 0.001). Similarly, POC would have detected 82% (37 of 45 cases) of TV cases vs. 51% (23 of 45 cases) correctly managed using the syndromic approach (P = 0.001).
In the absence of laboratory diagnostics, POC is not only inexpensive and practical, but also significantly more sensitive than the syndromic management approach, resulting in less overtreatment.
PMCID: PMC3625926  PMID: 19392745
bacterial vaginosis; India; point-of-care; vaginal discharge; Trichomonas vaginalis; resource constrained settings
6.  Prevalence of Trichomonas vaginalis infection among young reproductive age women in India: implications for treatment and prevention 
Sexual health  2009;6(4):339-344.
Trichomonas vaginalis infection is the most common curable sexually transmissible infection (STI) worldwide. The present study describes the burden and correlates of T. vaginalis infection among young reproductive age women in Mysore, India.
Between November 2005 and March 2006, sexually active women aged 15–30 years were recruited from low-income peri-urban and rural neighbourhoods of Mysore, India. Participants were interviewed and offered a physical examination and testing for T. vaginalis, bacterial vaginosis, vaginal candidiasis, Neisseria gonorrheoea and herpes simplex virus type-2 antibodies.
Of the 898 participating women, 76 had a T. vaginalis infection (8.5%, 95% confidence interval [95% CI]: 6.7–10.5%). Nearly all (98%) participants were married and most reported their spouse as their main sex partner. The mean age at marriage was 16.9 years (s.d. 2.9 years) and two-thirds of the sample reported having first sexual intercourse before the age of 19 years. Risk factors independently associated with T. vaginalis infection included early age at first intercourse (adjusted odds ratio [OR] 2.09; 95% CI: 1.09–4.00), concurrent bacterial vaginosis (OR 8.21; 95% CI: 4.30–15.66), vaginal candidiasis (OR 2.40; 95% CI: 1.48–3.89) and herpes simplex virus type-2 infection (OR 3.44; 95% CI: 1.97–6.02).
The burden of T. vaginalis infection at 8.5% is relatively high among a community sample of young reproductive aged women. Because this infection increases the risk of HIV transmission and is associated with adverse pregnancy outcomes, there is a need for increased screening and treatment of this easily curable sexually transmissible infection in India.
PMCID: PMC3619426  PMID: 19917204
correlates; epidemiology; sexually transmissible diseases; women
7.  Acceptability of male circumcision among mothers with male children in Mysore, India 
AIDS (London, England)  2008;22(8):983-988.
There is currently little information on the acceptability of male circumcision in India. This study investigated the acceptability of male circumcision among Indian mothers with male children.
A cross-sectional survey was conducted among a convenience sample of 795 women attending a reproductive health clinic in Mysore, India, between January and April 2007.
Of the 1012 invited eligible participants, 795 women agreed to participate (response rate = 78.5%). The majority of women were Hindus (78%), 18% were Muslims, and 4% were Christians. About 26% of respondents had no schooling, 29% had 7 years of schooling, 42% had 8–12 years, and 3% had more than 12 years. After women were informed about the risks and benefits of male circumcision, a majority of women with uncircumcised children (n = 564, 81%) said they would definitely circumcise their children if the procedure were offered in a safe hospital setting, free of charge, and a smaller number (n = 50, 7%) said they would probably consider the procedure. Only seven women (1%) said that they would definitely/probably not consider male circumcision, and 63 (9%) were unsure.
Since male circumcision has been found to decrease risk of HIV infection among men, it is important to determine its acceptability as a potential HIV prevention strategy in India. This study found male circumcision to be highly acceptable among a broad range of mothers with male children in Mysore, India. Further studies of acceptability among fathers and other populations are warranted.
PMCID: PMC3612934  PMID: 18453858
acceptability; circumcision; India; men; women
9.  Epidemiologic Features of Vulvovaginal Candidiasis among Reproductive-Age Women in India 
Background. Vulvovaginal candidiasis is characterized by curd-like vaginal discharge and itching, and is associated with considerable health and economic costs. Materials and Methods. We examined the incidence, prevalence, and risk factors for vulvovaginal candidiasis among a cohort of 898 women in south India. Participants completed three study visits over six months, comprised of a structured interview and a pelvic examination. Results. The positive predictive values for diagnosis of vulvovaginal candidiasis using individual signs or symptoms were low (<19%). We did not find strong evidence for associations between sociodemographic characteristics and the prevalence of vulvovaginal candidiasis. Women clinically diagnosed with bacterial vaginosis had a higher prevalence of vulvovaginal candidiasis (Prevalence 12%, 95% CI 8.2, 15.8) compared to women assessed to be negative for bacterial vaginosis (Prevalence 6.5%, 95% 5.3, 7.6); however, differences in the prevalence of vulvovaginal candidiasis were not observed by the presence or absence of laboratory-confirmed bacterial vaginosis. Conclusions. For correct diagnosis of vulvovaginal candidiasis, laboratory confirmation of infection with Candida is necessary as well as assessment of whether the discharge has been caused by bacterial vaginosis. Studies are needed of women infected with Candida yeast species to determine the risk factors for yeast's overgrowth.
PMCID: PMC3478712  PMID: 23118494
10.  Bacterial Vaginosis and Risk for Trichomonas Vaginalis Infection: A Longitudinal Analysis 
Sexually transmitted diseases  2011;38(9):882-886.
Bacterial vaginosis (BV) and Trichomonas vaginalis (TV), have been estimated to affect one-quarter to one-third of sexually active women worldwide, and are often found concurrently. Few studies have examined this relationship longitudinally to better understand the direction and temporality of this association.
Between 2005 and 2006, a cohort of 853 young, sexually active women was followed in Mysore, India; participants were interviewed and tested for BV and TV at baseline, and at three- and six-month visits. Generalized estimating equations were used to estimate how changes in vaginal flora between consecutive visits – as defined by Nugent diagnostic criteria for BV - were related to the risk of TV infection at the latter visit, adjusted for sociodemographic and behavioral covariates. Treatment was offered to women with TV and/or symptomatic BV.
After adjustment for covariates, participants with abnormal flora at two consecutive visits had nine times higher risk of TV (95% CI 4.1, 20.0) at the latter visit, relative to those with persistently normal flora. An increased risk of TV was also observed for participants whose flora status changed from normal to abnormal (aRR 7.11, 95% CI 2.8, 18.2) and from abnormal to normal (aRR 4.50, 95% CI 1.7, 11.8).
Women experiencing abnormal flora during a three-month span appear to have significantly increased risk of acquiring TV infection. Reproductive-age women in low-resource settings found to have abnormal vaginal flora should be assessed for TV.
PMCID: PMC3156984  PMID: 21844747
Bacterial vaginosis; Trichomonas vaginalis; India; women; longitudinal analysis
11.  Prevalence & correlates of primary infertility among young women in Mysore, India 
Background & objectives:
There are sparse data on the prevalence of primary infertility in India and almost none from Southern India. This study describes the correlates and prevalence of primary infertility among young women in Mysore, India.
The baseline data were collected between November 2005 through March 2006, among 897 sexually active women, aged 15-30 yr, for a study investigating the relationship of bacterial vaginosis and acquisition of herpes simplex virus type-2 (HSV-2) infection. A secondary data analysis of the baseline data was undertaken. Primary infertility was defined as having been married for longer than two years, not using contraception and without a child. Logistic regression was used to examine factors associated with primary infertility.
The mean age of the women was 25.9 yr (range: 16-30 yr) and the prevalence of primary infertility was 12.6 per cent [95% Confidence Interval (CI): 10.5-15.0%]. The main factor associated with primary infertility was HSV-2 seropositivity (adjusted odds ratio: 3.41; CI: 1.86, 6.26).
Interpretation & conclusions:
The estimated prevalence of primary infertility among women in the study was within the range reported by the WHO and similar to other estimates from India. Further research is needed to examine the role of HSV-2 in primary infertility.
PMCID: PMC3237240  PMID: 22089604
HSV-2; India; infertility; reproductive health; sexually transmitted disease
12.  The Impact of Antiretroviral Therapy in a Cohort of HIV Infected Patients Going in and out of the San Francisco County Jail 
PLoS ONE  2009;4(9):e7115.
Jails are an important venue of HIV care and a place for identification, treatment and referral for care. HIV infected inmates in the San Francisco County jail are offered antiretroviral treatment (ART), which many take only while in jail. We evaluated the effect of ART administration in a cohort of jail inmates going in and out of jail over a nine year period.
Methodology/Principal Findings
In this retrospective study, we examined inmates with HIV going in and out of jail. Inmates were categorized by patterns of ART use: continuous ART - ART both in and out of jail, intermittent ART - ART only in jail; never on ART - eligible by national guidelines, but refused ART. CD4 and HIV viral load (VL) were compared over time in these groups. Over a 9 year period, 512 inmates were studied: 388 (76%) on intermittent ART, 79 (15%) on continuous ART and 45(9%) never-on ART. In a linear mixed model analysis, inmates on intermittent ART were 1.43; 95%CI (1.03, 1.99) times and those never on ART were 2.89; 95%CI (1.71, 4.87) times more likely to have higher VL than inmates on continuous ART. Furthermore, Inmates on intermittent ART and never-on ART lost 1.60; 95%CI (1.06, 2.13) and 1.97; 95%CI (0.96, 3.00) more CD4 cells per month, respectively, compared to continuously treated inmates. The continuous ART inmates gained 0.67CD4 cells/month.
Continuous ART therapy in jail inmate's benefits CD4 cell counts and control of VL especially compared to those who never took ART. Although jail inmates on intermittent ART were more likely to lose CD4 cells and experience higher VL over time than those on continuous ART, CD4 cell loss was slower in these inmates as compared to inmates never on ART. Further studies are needed to evaluate whether or not intermittent ART provides some benefit in outcome if continuous ART is not possible or likely.
PMCID: PMC2744925  PMID: 19771176
13.  Effectiveness of the polysaccharide pneumococcal vaccine among HIV-infected persons in Brazil: a case control study 
Polysaccharide pneumococcal vaccine is recommended for use in HIV-infected adults in Brazil but there is uncertainty about its effectiveness in this patient population.
The main objective of this study was to assess the effectiveness of the 23-valent polysaccharide pneumococcal vaccine against invasive pneumococcal infection among HIV-infected adult patients in São Paulo, Brazil.
A case-control study of 79 cases and 242 controls matched on CD4+ cell count and health care setting was conducted. Among HIV-infected adults in São Paulo, Brazil, with and without S. pneumoniae recovered from a normally sterile site; prior receipt of 23 valent polysaccharide pneumococcal vaccine was determined by review of medical records and patient interview.
After adjustment for confounding factors, the point estimate for the effectiveness of 23 valent polysaccharide vaccine among HIV-infected adults against all invasive pneumococcal infection was 18% (95% CI: <0 to 62%).
We were unable to demonstrate a statistically significant protective effect of 23 valent polysaccharide against invasive pneumococcal infection vaccine among HIV-infected adults in Brazil.
While the vaccine is relatively inexpensive and safe, its effectiveness among HIV-infected adults in Brazil is uncertain.
PMCID: PMC2148048  PMID: 17956620
14.  Serial Testing of Health Care Workers for Tuberculosis Using Interferon-γ Assay 
Rationale: Although interferon-γ (IFN-γ) assays are promising alternatives to the tuberculin skin test (TST), their serial testing performance is unknown.
Objective: To compare TST and IFN-γ conversions and reversions in healthcare workers.
Methods: We prospectively followed-up 216 medical and nursing students in India who underwent baseline and repeat testing (after 18 mo) with TST and QuantiFERON-TB Gold In-Tube (QFT). TST conversions were defined as reactions greater than or equal to 10 mm, with increments of 6 or 10 mm over baseline. QFT conversions were defined as baseline IFN-γ less than 0.35 and follow-up IFN-γ greater than or equal to 0.35 or 0.70 IU/ml. QFT reversions were defined as baseline IFN-γ greater than or equal to 0.35 and follow-up IFN-γ less than 0.35 IU/ml.
Results: Of the 216 participants, 48 (22%) were TST-positive, and 38 (18%) were QFT-positive at baseline. Among 147 participants with concordant baseline negative results, TST conversions occurred in 14 (9.5%; 95% confidence interval [CI] = 5.3–15.5) using the 6 mm increment definition, and 6 (4.1%; 95% CI = 1.5–8.7) using the 10 mm increment definition. QFT conversions occurred in 17/147 participants (11.6%; 95% CI = 6.9–17.9) using the definition of IFN-γ greater than or equal to 0.35 IU/ml, and 11/147 participants (7.5%; 95% CI = 3.8–13.0) using IFN-γ greater than or equal to 0.70 IU/ml. Agreement between TST (10 mm increment) and QFT conversions (⩾ 0.70 IU/ml) was 96% (κ = 0.70). QFT reversions occurred in 2/28 participants (7%) with baseline concordant positive results, as compared with 7/10 participants (70%) with baseline discordant results (p < 0.001).
Conclusions: IFN-γ assay shows promise for serial testing, but repeat results need to be interpreted carefully. To meaningfully interpret serial results, the optimal thresholds to distinguish new infections from nonspecific variations must be determined.
PMCID: PMC2648116  PMID: 16690977
health care workers; interferon-γ assay; serial testing; tuberculin skin test; tuberculosis
15.  Evaluation of Diagnostic Accuracy, Feasibility and Client Preference for Rapid Oral Fluid-Based Diagnosis of HIV Infection in Rural India 
PLoS ONE  2007;2(4):e367.
Oral fluid-based rapid tests are promising for improving HIV diagnosis and screening. However, recent reports from the United States of false-positive results with the oral OraQuick® ADVANCE HIV1/2 test have raised concerns about their performance in routine practice. We report a field evaluation of the diagnostic accuracy, client preference, and feasibility for the oral fluid-based OraQuick® Rapid HIV1/2 test in a rural hospital in India.
Methodology/Principal Findings
A cross-sectional, hospital-based study was conducted in 450 consenting participants with suspected HIV infection in rural India. The objectives were to evaluate performance, client preference and feasibility of the OraQuick® Rapid HIV-1/2 tests. Two Oraquick® Rapid HIV1/2 tests (oral fluid and finger stick) were administered in parallel with confirmatory ELISA/Western Blot (reference standard). Pre- and post-test counseling and face to face interviews were conducted to determine client preference. Of the 450 participants, 146 were deemed to be HIV sero-positive using the reference standard (seropositivity rate of 32% (95% confidence interval [CI] 28%, 37%)). The OraQuick test on oral fluid specimens had better performance with a sensitivity of 100% (95% CI 98, 100) and a specificity of 100% (95% CI 99, 100), as compared to the OraQuick test on finger stick specimens with a sensitivity of 100% (95% CI 98, 100), and a specificity of 99.7% (95% CI 98.4, 99.9). The OraQuick oral fluid-based test was preferred by 87% of the participants for first time testing and 60% of the participants for repeat testing.
In a rural Indian hospital setting, the OraQuick® Rapid- HIV1/2 test was found to be highly accurate. The oral fluid-based test performed marginally better than the finger stick test. The oral OraQuick test was highly preferred by participants. In the context of global efforts to scale-up HIV testing, our data suggest that oral fluid-based rapid HIV testing may work well in rural, resource-limited settings.
PMCID: PMC1838923  PMID: 17426815
16.  Tuberculosis among Health-Care Workers in Low- and Middle-Income Countries: A Systematic Review 
PLoS Medicine  2006;3(12):e494.
The risk of transmission of Mycobacterium tuberculosis from patients to health-care workers (HCWs) is a neglected problem in many low- and middle-income countries (LMICs). Most health-care facilities in these countries lack resources to prevent nosocomial transmission of tuberculosis (TB).
Methods and Findings
We conducted a systematic review to summarize the evidence on the incidence and prevalence of latent TB infection (LTBI) and disease among HCWs in LMICs, and to evaluate the impact of various preventive strategies that have been attempted. To identify relevant studies, we searched electronic databases and journals, and contacted experts in the field. We identified 42 articles, consisting of 51 studies, and extracted data on incidence, prevalence, and risk factors for LTBI and disease among HCWs. The prevalence of LTBI among HCWs was, on average, 54% (range 33% to 79%). Estimates of the annual risk of LTBI ranged from 0.5% to 14.3%, and the annual incidence of TB disease in HCWs ranged from 69 to 5,780 per 100,000. The attributable risk for TB disease in HCWs, compared to the risk in the general population, ranged from 25 to 5,361 per 100,000 per year. A higher risk of acquiring TB disease was associated with certain work locations (inpatient TB facility, laboratory, internal medicine, and emergency facilities) and occupational categories (radiology technicians, patient attendants, nurses, ward attendants, paramedics, and clinical officers).
In summary, our review demonstrates that TB is a significant occupational problem among HCWs in LMICs. Available evidence reinforces the need to design and implement simple, effective, and affordable TB infection-control programs in health-care facilities in these countries.
A systematic review demonstrates that tuberculosis is an important occupational problem among health care workers in low and middle-income countries.
Editors' Summary
One third of the world's population is infected with Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB). In many people, the bug causes no health problems—it remains latent. But about 10% of infected people develop active, potentially fatal TB, often in their lungs. People with active pulmonary TB readily spread the infection to other people, including health-care workers (HCWs), in small airborne droplets produced when they cough or sneeze. In high-income countries such as the US, guidelines are in place to minimize the transmission of TB in health-care facilities. Administrative controls (for example, standard treatment plans for people with suspected or confirmed TB) aim to reduce the exposure of HCWs to people with TB. Environmental controls (for example, the use of special isolation rooms) aim to prevent the spread and to reduce the concentration of infectious droplets in the air. Finally, respiratory-protection controls (for example, personal respirators for nursing staff) aim to reduce the risk of infection when exposure to M. tuberculosis is unavoidably high. Together, these three layers of control have reduced the incidence of TB in HCWs (the number who catch TB annually) in high-income countries.
Why Was This Study Done?
But what about low- and middle-income countries (LMICs) where more than 90% of the world's cases of TB occur? Here, there is little money available to implement even low-cost strategies to reduce TB transmission in health-care facilities—so how important an occupational disease is TB in HCWs in these countries? In this study, the researchers have systematically reviewed published papers to find out the incidence and prevalence (how many people in a population have a specific disease) of active TB and latent TB infections (LTBIs) in HCWs in LMICs. They have also investigated whether any of the preventative strategies used in high-income countries have been shown to reduce the TB burden in HCWs in poorer countries.
What Did the Researchers Do and Find?
To identify studies on TB transmission to HCWs in LMICs, the researchers searched electronic databases and journals, and also contacted experts on TB transmission. They then extracted and analyzed the relevant data on TB incidence, prevalence, risk factors, and control measures. Averaged-out over the 51 identified studies, 54% of HCWs had LTBI. In most of the studies, increasing age and duration of employment in health-care facilities, indicating a longer cumulative exposure to infection, was associated with a higher prevalence of LTBI. The same trend was seen in a subgroup of medical and nursing students. After accounting for the incidence of TB in the relevant general population, the excess incidence of TB in the different studies that was attributable to being a HCW ranged from 25 to 5,361 cases per 100, 000 people per year. In addition, a higher risk of acquiring TB was associated with working in specific locations (for example, inpatient TB facilities or diagnostic laboratories) and with specific occupations, including nurses and radiology attendants; most of the health-care facilities examined in the published studies had no specific TB infection-control programs in place.
What Do These Findings Mean?
As with all systematic reviews, the accuracy of these findings may be limited by some aspects of the original studies, such as how the incidence of LTBI was measured. In addition, the possibility that the researchers missed some relevant published studies, or that only studies where there was a high incidence of TB in HCWs were published, may also affect the findings of this study. Nevertheless, they suggest that TB is an important occupational disease in HCWs in LMICs and that the HCWs most at risk of TB are those exposed to the most patients with TB. Reduction of that risk should be a high priority because occupational TB leads to the loss of essential, skilled HCWs. Unfortunately, there are few data available to indicate how this should be done. Thus, the researchers conclude, well-designed field studies are urgently needed to evaluate whether the TB-control measures that have reduced TB transmission to HCWs in high-income countries will work and be affordable in LMICs.
Additional Information.
Please access these Web sites via the online version of this summary at
• US National Institute of Allergy and Infectious Diseases patient fact sheet on tuberculosis
• US Centers for Disease Control and Prevention information for patients and professionals on tuberculosis
• MedlinePlus encyclopedia entry on tuberculosis
• NHS Direct Online, from the UK National Health Service, patient information on tuberculosis
• US National Institute for Occupational Health and Safety, information about tuberculosis for health-care workers
• American Lung Association information on tuberculosis and health-care workers
PMCID: PMC1716189  PMID: 17194191
17.  Alex Langmuir and CDC 
Emerging Infectious Diseases  2006;12(10):1160-1.
PMCID: PMC3293460  PMID: 17176594
CDC; Alex Langmuir; Joe Mountin
18.  SARS and Common Viral Infections 
Emerging Infectious Diseases  2004;10(6):1143-1146.
In California, molecular testing was useful in decreasing suspicion for severe acute respiratory syndrome (SARS), by detecting common respiratory pathogens (influenza A/B, human metapneumovirus, picornavirus, Mycoplasma pneumoniae, Chlamydia spp., parainfluenza virus, respiratory syncytial virus, and adenovirus) in 23 (45%) of 51 patients with suspected SARS and 9 (47%) of 19 patients with probable SARS.
PMCID: PMC3323182  PMID: 15207072
severe acute respiratory syndrome; SARS; polymerase chain reaction; molecular testing
19.  Antibiotic Resistance Patterns of Bacterial Isolates from Blood in San Francisco County, California, 1996-1999 
Emerging Infectious Diseases  2002;8(2):195-201.
Countywide antibiotic resistance patterns may provide additional information from that obtained from national sampling or individual hospitals. We reviewed susceptibility patterns of selected bacterial strains isolated from blood in San Francisco County from January 1996 to March 1999. We found substantial hospital-to-hospital variability in proportional resistance to antibiotics in multiple organisms. This variability was not correlated with hospital indices such as number of intensive care unit or total beds, annual admissions, or average length of stay. We also found a significant increase in methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and proportional resistance to multiple antipseudomonal antibiotics. We describe the utility, difficulties, and limitations of countywide surveillance.
PMCID: PMC2732439  PMID: 11897073
antibiotic resistance; MRSA; VRE; bacteremia; county surveillance
20.  Trends in Antifungal Drug Susceptibility of Cryptococcus neoformans Isolates in the United States: 1992 to 1994 and 1996 to 1998 
Antimicrobial Agents and Chemotherapy  2001;45(11):3065-3069.
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 (MIC50s), and the MIC90s 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 (≥2 μg/ml) for 2 isolates, and the MICs of flucytosine were elevated (≥32 μg/ml) for 14 isolates. Among the azoles, the fluconazole MIC was elevated (≥64 μg/ml) for 8 isolates and the itraconazole MIC (≥1 μg/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.
PMCID: PMC90783  PMID: 11600357

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