Field Evaluation of Two Rapid Diagnostic Tests for Neisseria meningitidis Serogroup A during the 2006 Outbreak in Niger

The Pastorex^® (BioRad) rapid agglutination test is one of the main rapid diagnostic tests (RDTs) for meningococcal disease currently in use in the “meningitis belt”. Earlier evaluations, performed after heating and centrifugation of cerebrospinal fluid (CSF) samples, under good laboratory conditions, showed high sensitivity and specificity. However, during an epidemic, the test may be used without prior sample preparation. Recently a new, easy-to-use dipstick RDT for meningococcal disease detection on CSF was developed by the Centre de Recherche Médicale et Sanitaire in Niger and the Pasteur Institute in France. We estimate diagnostic accuracy in the field during the 2006 outbreak of Neisseria meningitidis serogroup A in Maradi, Niger, for the dipstick RDT and Pastorex^® on unprepared CSF, (a) by comparing each test''s sensitivity and specificity with previously reported values; and (b) by comparing results for each test on paired samples, using McNemar''s test. We also (c) estimate diagnostic accuracy of the dipstick RDT on diluted whole blood. We tested unprepared CSF and diluted whole blood from 126 patients with suspected meningococcal disease presenting at four health posts. (a) Pastorex^® sensitivity (69%; 95%CI 57–79) was significantly lower than found previously for prepared CSF samples [87% (81–91); or 88% (85–91)], as was specificity [81% (95%CI 68–91) vs 93% (90–95); or 93% (87–96)]. Sensitivity of the dipstick RDT [89% (95%CI 80–95)] was similar to previously reported values for ideal laboratory conditions [89% (84–93) and 94% (90–96)]. Specificity, at 62% (95%CI 48–75), was significantly lower than found previously [94% (92–96) and 97% (94–99)]. (b) McNemar''s test for the dipstick RDT vs Pastorex^® was statistically significant (p<0.001). (c) The dipstick RDT did not perform satisfactorily on diluted whole blood (sensitivity 73%; specificity 57%).Sensitivity and specificity of Pastorex^® without prior CSF preparation were poorer than previously reported results from prepared samples; therefore we caution against using this test during an epidemic if sample preparation is not possible. For the dipstick RDT, sensitivity was similar to, while specificity was not as high as previously reported during a more stable context. Further studies are needed to evaluate its field performance, especially for different populations and other serogroups.     

Design,Development and Evaluation of rK28-Based Point-of-Care Tests for Improving Rapid Diagnosis of Visceral Leishmaniasis

Background

Visceral leishmaniasis (VL) is diagnosed by microscopic confirmation of the parasite in bone marrow, spleen or lymph node aspirates. These procedures are unsuitable for rapid diagnosis of VL in field settings. The development of rK39-based rapid diagnostic tests (RDT) revolutionized diagnosis of VL by offering high sensitivity and specificity in detecting disease in the Indian subcontinent; however, these tests have been less reliable in the African subcontinent (sensitivity range of 75–85%, specificity of 70–92%). We have addressed limitations of the rK39 with a new synthetic polyprotein, rK28, followed by development and evaluation of two new rK28-based RDT prototype platforms.

Methodology/Principal Findings

Evaluation of 62 VL-confirmed sera from Sudan provided sensitivities of 96.8% and 93.6% (95% CI = K28: 88.83–99.61%; K39: 84.30–98.21%) and specificities of 96.2% and 92.4% (95% CI = K28: 90.53–98.95%; K39: 85.54–96.65%) for rK28 and rK39, respectively. Of greater interest was the observation that individual VL sera with low rK39 reactivity often had much higher rK28 reactivity. This characteristic of the fusion protein was exploited in the development of rK28 rapid tests, which may prove to be crucial in detecting VL among patients with low rK39 antibody levels. Evaluation of two prototype lateral flow-based rK28 rapid tests on 53 VL patients in Sudan and 73 VL patients in Bangladesh provided promisingly high sensitivities (95.9% [95% CI = 88.46–99.1 in Sudan and 98.1% [95% CI = 89.93–99.95%] in Bangladesh) compared to the rK39 RDT (sensitivities of 86.3% [95% CI = 76.25–93.23%] in Sudan and 88.7% [95% CI = 76.97–95.73%] in Bangladesh).

Conclusions/Significance

Our study compares the diagnostic accuracy of rK39 and rK28 in detecting active VL cases and our findings indicate that rK28 polyprotein has great potential as a serodiagnostic tool. A new rK28-based RDT will prove to be a valuable asset in simplifying VL disease confirmation at the point-of-care.     

Access to Water Source,Latrine Facilities and Other Risk Factors of Active Trachoma in Ankober,Ethiopia

Objective

This study aims to determine the prevalence and correlates of active trachoma in Ankober, Ethiopia.

Methods

A cross-sectional community-based study was conducted during July 2007. A total of 507 children (ages 1–9 years), from 232 households were included in the study. All children were examined for trachoma by ophthalmic nurses using the WHO simplified clinical grading system. Interviews and observations were used to assess risk factors. Logistic regression procedures were used to determine associations between potential risk factors and signs of active trachoma.

Results

Overall, the prevalence of active trachoma was found to be 53.9% (95%CI 49.6%–58.2%). Presence of fly-eye (fly contact with the eyelid margin during eye examination) (Odds Ratio (OR) = 4.03 95% CI 1.40–11.59), absence of facial cleanliness (OR = 7.59; 95%CI 4.60–12.52), an illiterate mother (OR = 5.88; 95%CI 2.10–15.95), lack of access to piped water (OR = 2.19; 95%CI 1.14–6.08), and lack of access to latrine facilities (OR = 4.36; 95%CI 1.49–12.74) were statistically significantly associated with increased risk of active trachoma.

Conclusion

Active trachoma among children 1–9 years of age in Ankober is highly prevalent and significantly associated with a number of risk factors including access to water and latrine facilities. Trachoma prevention programs that include improved access to water and sanitation, active fly control, and hygiene education are recommended to lower the burden of trachoma in Ankober, Ethiopia.     

Malnutrition and Mortality Patterns among Internally Displaced and Non-Displaced Population Living in a Camp,a Village or a Town in Eastern Chad

Background

Certain population groups have been rendered vulnerable in Chad because of displacement of more than 200,000 people over the last three years as a result of mass violence against civilians in the east of the country. The objective of the study was to assess mortality and nutritional patterns among displaced and non-displaced population living in camps, villages and a town in the Ouddaï and Salamat regions of Chad.

Methodology

Between May and October 2007, two stage, 30-cluster household surveys were conducted among 43,900 internally displaced persons (IDPs) living in camps in Ouaddai region (n = 898 households), among 19,400 non-displaced persons (NDPs) living in 42 villages in Ouaddai region (n = 900 households) and among 17,000 NDPs living in a small town in Salamat region (n = 901 households). Data collection included anthropometric measurements, measles vaccination rates and retrospective mortality. Crude mortality rate (CMR), mortality rate among children younger than 5 years (U5MR), causes of death and the prevalence of wasting (weight-for-height z score <−2) among children aged 6 to 59 months were the main outcome measures.

Conclusions

The CMR among the 4902 IDPs in Gozbeida camps, 4477 NDPs living in a village and 4073 NDPs living in a town surveyed was 1.8 (95% CI, 1.2–2.8), 0.3 (95% CI, 0.2–0.4), 0.3 (95% CI, 0.2–0.5) per 10,000 per day, respectively. The U5MR in a camp (n = 904), a village (n = 956) and a town (n = 901) was 4.1 (95% CI, 2.1–7.7), 0.5 (95% CI, 0.3–0.9) and 0.7 (95% CI, 0.4–1.4) per 10,000 per day, respectively. Diarrhoea was reported to be the main cause of death. Acute malnutrition rates (according to the WHO definition) among 904 IDP children, 956 NDPs children living in a village, 901 NDP children living in a town aged 6 to 59 months were 20.6% (95% CI, 17.9%–23.3%), 16.4% (95% CI, 14.0%–18.8%) and 10.1% (95% CI, 8.1%–12.2%) respectively. The study found a high mortality rate among IDPs and an elevated prevalence of wasting not only in IDP camps but also in villages located in the same region. The town-dweller population remains at risk of malnutrition. Appropriate contingency plans need to be made to ensure acceptable living standards for these populations.     

Men Who Have Sex with Men (MSM) and Factors Associated with Not Using a Condom at Last Sexual Intercourse with a Man and with a Woman in Senegal

Background

Men who have sex with other men (MSM) are a vulnerable population in Africa that has been insufficiently explored. Given the high rate of bisexuality among MSM (73% in the past year), it is important to understand their risk-taking behaviors regarding both men and women.

Methodology/Principal Findings

A socio-behavioral survey was carried out in 2007 among 501 MSM recruited using the snowball sampling method. We explore in this article why a condom was not used during last sexual intercourse with a man and with a woman, taking into account the respondent''s characteristics, type of relationship and the context of the sexual act. In the survey, 489 men reported that they had had sexual intercourse at least once with another man during the previous year, and 358 with a man and with a woman. The main risk factors for not using a condom at last sexual intercourse with another man were having sex in a public place (aOR = 6.26 [95%CI: 2.71–14.46]), non-participation in an MSM prevention program (aOR = 3.47 [95%CI: 2.12–5.69]), a 19 years old or younger partner (aOR = 2.6 [95%CI: 1.23–4.53]), being 24 years or younger (aOR = 2.07 [95%CI: 1.20–3.58]) or being 35 years or over (aOR = 3.08 [95%CI:1.11–8.53]) and being unemployed (aOR = 0.36 [95%CI: 0.10–1.25]). The last sexual intercourse with the respondent''s wife was hardly ever protected (2%). With women, the other factors were a 15 years or younger partner (aOR = 6.45 [95%CI: 2.56–16.28]), being educated (primary: aOR = 0.45 [95%CI: 0.21–0.95], secondary or higher: aOR = 0.26 [95%CI: 0.11–0.62]), being a student (aOR = 2.20 [95%CI: 1.07–4.54]) or unemployed (aOR = 3.72 [95%CI: 1.31–10.61]) and having participated in a MSM prevention program (aOR = 0.57 [95%CI: 0.34–0.93]).

Conclusion

Having participated in a prevention program specifically targeting MSM constitutes a major prevention factor. However, these programs targeting MSM must address their heterosexual practices and the specific risks involved.     

Non-invasive cytology brush PCR diagnostic testing in mucosal leishmaniasis: superior performance to conventional biopsy with histopathology

Background

Traditional methods of diagnosing mucosal leishmaniasis (ML), such as biopsy with histopathology, are insensitive and require collection of an invasive diagnostic specimen.

Methods

We compared standard invasive procedures including biopsy histopathology, biopsy PCR, and leishmanin skin test (LST) to a novel, non-invasive, cytology-brush based PCR for the diagnosis of ML in Lima, Peru. Consensus reference standard was 2/4 tests positive, and outcome measures were sensitivity and specificity. Leishmania species identification was performed by PCR-based assays of positive specimens.

Results

Twenty-eight patients were enrolled, 23 of whom fulfilled criteria for a diagnosis of ML. Sensitivity and specificity of biopsy with histopathology were 21.7% [95% CI 4.9–38.5%] and 100%; 69.6% [95% CI 50.8–88.4%] and 100% for LST; 95.7% [95% CI 87.4–100%] and 100% for biopsy PCR; and 95.7% [95% CI 87.4–100%] and 90% [95% CI 71.4–100%] for cytology brush PCR using both Cervisoft® and Histobrush® cervical cytology brushes. Represented species identified by PCR-RFLP included: L. (V). braziliensis (n = 4), and L. (V). peruviana (n = 3).

Conclusions

Use of commercial grade cytology brush PCR for diagnosis of ML is sensitive, rapid, well tolerated, and carries none of the risks of invasive diagnostic procedures such as biopsy. Further optimization is required for adequate species identification. Further evaluation of this method in field and other settings is warranted.     

Prostatitis,Sexually Transmitted Diseases,and Prostate Cancer: The California Men's Health Study

Background

Prostatitis and sexually transmitted diseases (STDs) have been positively associated with prostate cancer in previous case-control studies. However, results from recent prospective studies have been inconclusive.

Methodogy/Principal Findings

We investigated the association between prostatitis, STDs, and prostate cancer among African American, Asian American, Latino, and White participants of the California Men''s Health Study. Our analysis included 68,675 men, who completed a detailed baseline questionnaire in 2002–2003. We identified 1,658 incident prostate cancer cases during the follow-up period to June 30, 2006. Cox proportional hazards models were used to estimate relative risks and 95% confidence intervals. Overall, men having a history of prostatitis had an increased risk of prostate cancer than men with no history (RR = 1.30; 95% CI: 1.10–1.54). Longer duration of prostatitis symptoms was also associated with an increased risk of prostate cancer (P trend = 0.003). In addition, among men screened for prostate cancer (1 or 2 PSA tests), a non-significant positive association was observed between prostatitis and prostate cancer (RR = 1.10; 95% CI: 0.75–1.63). STDs were not associated with overall prostate cancer risk. In racial/ethnic stratified analysis, Latinos reporting any STDs had an increased risk of disease than those with no STDs (RR = 1.43; 95% CI: 1.07–1.91). Interestingly, foreign-born Latinos displayed a larger risk associated with STDs (RR = 1.87; 95% CI: 1.16–3.02) than U.S. born Latinos (RR = 1.15; 95% CI: 0.76–3.02).

Conclusion

In summary, results from this prospective study suggest that prostatitis and STDs may be involved in prostate cancer susceptibility. While we cannot rule out the possible influence of incidental detection, future studies are warranted to further investigate the role of infectious agents related to prostatitis and STDs in prostate cancer development.     

Antibody-Based Detection Tests for the Diagnosis of Helicobacter pylori Infection in Children: A Meta-Analysis

Background

Numerous serologic tests are available for the diagnosis of H. pylori infection in children. Common designs of antibody-based detection tests are ELISA and Western Blot (WB). For developing countries with limited laboratory resources and access, ELISA would be the preferred method because of its simplicity, lower cost and speed. Although in adults ELISA has proven to be highly accurate in diagnosing H. pylori infection; in children, it has shown variable accuracy.

Methods/Findings

We conducted a systematic review and meta-analysis to assess the accuracy of antibody-based detection tests for the diagnosis of H. pylori infection in children. Selection criteria included participation of at least 30 children and the use of a gold standard for H. pylori diagnosis. In a comprehensive search we identified 68 studies. Subgroup analyses were carried out by technique, immunoglobulin class, and source of test (commercial and in-house). The results demonstrated: 1) WB tests showed high overall performance, sensitivity 91.3% (95% CI, 88.9–93.3), specificity 89% (95% CI, 85.7–91.9), LR+ 8.2 (95% CI, 5.1–13.3), LR− 0.06 (95% CI, 0.02–0.16), DOR 158.8 (95% CI, 57.8–435.8); 2) ELISA-IgG assays showed low sensitivity 79.2% (95% CI, 77.3–81.0) and high specificity (92.4%, 95% CI, 91.6–93.3); 3) ELISA commercial tests varied widely in performance (test for heterogeneity p<0.0001); and 4) In-house ELISA with whole-cell antigen tests showed the highest overall performance: sensitivity 94% (95% CI, 90.2–96.7), specificity 96.4% (95% CI, 94.2–97.9), LR+ 19.9 (95% CI, 7.9–49.8), LR− 0.08 (95% CI, 0.04–0.15) DOR 292.8 (95% CI, 101.8–841.7).

Conclusions/Significance

WB test and in-house ELISA with whole-cell antigen tests are the most reliable tests for the diagnosis of H. pylori infection in children. Antigens obtained from local strains of the community could partially explain the good overall accuracy of the in-house ELISA. Because of its cost and technical demands, in-house ELISA might be more suitable for use in developing countries.     

Treatment of Cryptococcal Meningitis in KwaZulu-Natal,South Africa

Background

Cryptococcal meningitis (CM) remains a leading cause of death for HIV-infected individuals in sub-Saharan Africa. Improved treatment strategies are needed if individuals are to benefit from the increasing availability of antiretroviral therapy. We investigated the factors associated with mortality in routine care in KwaZulu-Natal, South Africa.

Methodology/Principal Findings

A prospective year long, single-center, consecutive case series of individuals diagnosed with cryptococcal meningitis 190 patients were diagnosed with culture positive cryptococcal meningitis, of whom 186 were included in the study. 52/186 (28.0%) patients died within 14 days of diagnosis and 60/186 (32.3%) had died by day 28. In multivariable cox regression analysis, focal neurology (aHR 11 95%C.I. 3.08–39.3, P<0.001), diastolic blood pressure <60 mmHg (aHR 2.37 95%C.I. 1.11–5.04, P = 0.025), concurrent treatment for tuberculosis (aHR 2.11 95%C.I. 1.02–4.35, P = 0.044) and use of fluconazole monotherapy (aHR 3.69 95% C.I. 1.74–7.85, P<0.001) were associated with increased mortality at 14 and 28 days.

Conclusions

Even in a setting where amphotericin B is available, mortality from cryptococcal meningitis in this setting is high, particularly in the immediate period after diagnosis. This highlights the still unmet need not only for earlier diagnosis of HIV and timely access to treatment of opportunistic infections, but for better treatment strategies of cryptococcal meningitis.     

Effectiveness of Multidrug Antiretroviral Regimens to Prevent Mother-to-Child Transmission of HIV-1 in Routine Public Health Services in Cameroon

Background

Multidrug antiretroviral (ARV) regimens including HAART and short-course dual antiretroviral (sc-dARV) regimens were introduced in 2004 to improve Prevention of Mother-to-Child Transmission (PMTCT) in Cameroon. We assessed the effectiveness of these regimens from 6–10 weeks and 12 months of age, respectively.

Methodology/Findings

We conducted a retrospective cohort study covering the period from October 2004 to March 2008 in a reference hospital in Cameroon. HIV-positive pregnant women with CD4 ≤350 cells/mm³ received first-line HAART [regimen 1] while the others received ARV prophylaxis including sc-dARV or single dose nevirapine (sd-NVP). Sc-dARV included at least two drugs according to different gestational ages: zidovudine (ZDV) from 28–32 weeks plus sd-NVP [regimen 2], ZDV and lamuvidine (3TC) from 33–36 weeks plus sd-NVP [regimen 3]. When gestational age was ≥37 weeks, women received sd-NVP during labour [regimen 4]. Infants received sd-NVP plus ZDV and 3TC for 7 days or 30 days. Early diagnosis (6–10 weeks) was done, using b-DNA and subsequently RT-PCR. We determined early MTCT rate and associated risk factors using logistic regression. The 12-month HIV-free survival was assessed using Cox regression. Among 418 mothers, 335 (80%) received multidrug ARV regimens (1, 2, and 3) and MTCT rate with multidrug regimens was 6.6% [95%CI: 4.3–9.6] at 6 weeks, without any significant difference between regimens. Duration of mother''s ARV regimen <4 weeks [OR = 4.7, 95%CI: 1.3–17.6], mother''s CD4 <350 cells/mm³ [OR = 6.4, 95%CI: 1.8–22.5] and low birth weight [OR = 4.0, 95%CI: 1.4–11.3] were associated with early MTCT. By 12 months, mixed feeding [HR = 8.7, 95%CI: 3.6–20.6], prematurity [HR = 2.3, 95%CI: 1.2–4.3] and low birth weight were associated with children''s risk of progressing to infection or death.

Conclusions

Multidrug ARV regimens for PMTCT are feasible and effective in routine reference hospital. Early initiation of ARV during pregnancy and proper obstetrical care are essential to improve PMTCT.     

Diagnostic Accuracy of the Leishmania OligoC-TesT and NASBA-Oligochromatography for Diagnosis of Leishmaniasis in Sudan

Background

The Leishmania OligoC-TesT and NASBA-Oligochromatography (OC) were recently developed for simplified and standardised molecular detection of Leishmania parasites in clinical specimens. We here present the phase II evaluation of both tests for diagnosis of visceral leishmaniasis (VL), cutaneous leishmaniasis (CL) and post kala-azar dermal leishmaniasis (PKDL) in Sudan.

Methodology

The diagnostic accuracy of the tests was evaluated on 90 confirmed and 90 suspected VL cases, 7 confirmed and 8 suspected CL cases, 2 confirmed PKDL cases and 50 healthy endemic controls from Gedarif state and Khartoum state in Sudan.

Principal Findings

The OligoC-TesT as well as the NASBA-OC showed a sensitivity of 96.8% (95% CI: 83.8%–99.4%) on lymph node aspirates and of 96.2% (95% CI: 89.4%–98.7%) on blood from the confirmed VL cases. The sensitivity on bone marrow was 96.9% (95% CI: 89.3%–99.1%) and 95.3% (95% CI: 87.1%–98.4%) for the OligoC-TesT and NASBA-OC, respectively. All confirmed CL and PKDL cases were positive with both tests. On the suspected VL cases, we observed a positive OligoC-TesT and NASBA-OC result in 37.1% (95% CI: 23.2%–53.7%) and 34.3% (95% CI: 20.8%–50.9%) on lymph, in 72.7% (95% CI: 55.8%–84.9%) and 63.6% (95% CI: 46.6%–77.8%) on bone marrow and in 76.9% (95% CI: 49.7%–91.8%) and 69.2% (95% CI: 42.4%–87.3%) on blood. Seven out of 8 CL suspected cases were positive with both tests. The specificity on the healthy endemic controls was 90% (95% CI: 78.6%–95.7%) for the OligoC-TesT and 100% (95% CI: 92.9%–100.0%) for the NASBA-OC test.

Conclusions

Both tests showed high sensitivity on lymph, blood and tissue scrapings for diagnosis of VL, CL and PKDL in Sudan, but the specificity for clinical VL was significantly higher with NASBA-OC.     

T. cruzi OligoC-TesT: A Simplified and Standardized Polymerase Chain Reaction Format for Diagnosis of Chagas Disease

Background

PCR has evolved into one of the most promising tools for T. cruzi detection in the diagnosis and control of Chagas disease. However, general use of the technique is hampered by its complexity and the lack of standardization.

Methodology

We here present the development and phase I evaluation of the T. cruzi OligoC-TesT, a simple and standardized dipstick format for detection of PCR amplified T. cruzi DNA. The specificity and sensitivity of the assay were evaluated on blood samples from 60 Chagas non-endemic and 48 endemic control persons and on biological samples from 33 patients, 7 reservoir animals, and 14 vectors collected in Chile.

Principal Findings

The lower detection limits of the T. cruzi OligoC-TesT were 1 pg and 1 to 10 fg of DNA from T. cruzi lineage I and II, respectively. The test showed a specificity of 100% (95% confidence interval [CI]: 96.6%–100%) on the control samples and a sensitivity of 93.9% (95% CI: 80.4%–98.3%), 100% (95% CI: 64.6%–100%), and 100% (95% CI: 78.5%–100%) on the human, rodent, and vector samples, respectively.

Conclusions

The T. cruzi OligoC-TesT showed high sensitivity and specificity on a diverse panel of biological samples. The new tool is an important step towards simplified and standardized molecular diagnosis of Chagas disease.     

Does Simplicity Compromise Accuracy in ACS Risk Prediction? A Retrospective Analysis of the TIMI and GRACE Risk Scores

Background

The Thrombolysis in Myocardial Infarction (TIMI) risk scores for Unstable Angina/Non-ST–elevation myocardial infarction (UA/NSTEMI) and ST-elevation myocardial infarction (STEMI) and the Global Registry of Acute Coronary Events (GRACE) risk scores for in-hospital and 6-month mortality are established tools for assessing risk in Acute Coronary Syndrome (ACS) patients. The objective of our study was to compare the discriminative abilities of the TIMI and GRACE risk scores in a broad-spectrum, unselected ACS population and to assess the relative contributions of model simplicity and model composition to any observed differences between the two scoring systems.

Methodology/Principal Findings

ACS patients admitted to the University of Michigan between 1999 and 2005 were divided into UA/NSTEMI (n = 2753) and STEMI (n = 698) subpopulations. The predictive abilities of the TIMI and GRACE scores for in-hospital and 6-month mortality were assessed by calibration and discrimination. There were 137 in-hospital deaths (4%), and among the survivors, 234 (7.4%) died by 6 months post-discharge. In the UA/NSTEMI population, the GRACE risk scores demonstrated better discrimination than the TIMI UA/NSTEMI score for in-hospital (C = 0.85, 95% CI: 0.81–0.89, versus 0.54, 95% CI: 0.48–0.60; p<0.01) and 6-month (C = 0.79, 95% CI: 0.76–0.83, versus 0.56, 95% CI: 0.52–0.60; p<0.01) mortality. Among STEMI patients, the GRACE and TIMI STEMI scores demonstrated comparably excellent discrimination for in-hospital (C = 0.84, 95% CI: 0.78–0.90 versus 0.83, 95% CI: 0.78–0.89; p = 0.83) and 6-month (C = 0.72, 95% CI: 0.63–0.81, versus 0.71, 95% CI: 0.64–0.79; p = 0.79) mortality. An analysis of refitted multivariate models demonstrated a marked improvement in the discriminative power of the TIMI UA/NSTEMI model with the incorporation of heart failure and hemodynamic variables. Study limitations included unaccounted for confounders inherent to observational, single institution studies with moderate sample sizes.

Conclusions/Significance

The GRACE scores provided superior discrimination as compared with the TIMI UA/NSTEMI score in predicting in-hospital and 6-month mortality in UA/NSTEMI patients, although the GRACE and TIMI STEMI scores performed equally well in STEMI patients. The observed discriminative deficit of the TIMI UA/NSTEMI score likely results from the omission of key risk factors rather than from the relative simplicity of the scoring system.     

Impact of Community-Based Maternal Health Workers on Coverage of Essential Maternal Health Interventions among Internally Displaced Communities in Eastern Burma: The MOM Project

Background

Access to essential maternal and reproductive health care is poor throughout Burma, but is particularly lacking among internally displaced communities in the eastern border regions. In such settings, innovative strategies for accessing vulnerable populations and delivering basic public health interventions are urgently needed.

Methods

Four ethnic health organizations from the Shan, Mon, Karen, and Karenni regions collaborated on a pilot project between 2005 and 2008 to examine the feasibility of an innovative three-tiered network of community-based providers for delivery of maternal health interventions in the complex emergency setting of eastern Burma. Two-stage cluster-sampling surveys among ever-married women of reproductive age (15–45 y) conducted before and after program implementation enabled evaluation of changes in coverage of essential antenatal care interventions, attendance at birth by those trained to manage complications, postnatal care, and family planning services.

Results

Among 2,889 and 2,442 women of reproductive age in 2006 and 2008, respectively, population characteristics (age, marital status, ethnic distribution, literacy) were similar. Compared to baseline, women whose most recent pregnancy occurred during the implementation period were substantially more likely to receive antenatal care (71.8% versus 39.3%, prevalence rate ratio [PRR] = 1.83 [95% confidence interval (CI) 1.64–2.04]) and specific interventions such as urine testing (42.4% versus 15.7%, PRR = 2.69 [95% CI 2.69–3.54]), malaria screening (55.9% versus 21.9%, PRR = 2.88 [95% CI 2.15–3.85]), and deworming (58.2% versus 4.1%, PRR = 14.18 [95% CI 10.76–18.71]. Postnatal care visits within 7 d doubled. Use of modern methods to avoid pregnancy increased from 23.9% to 45.0% (PRR = 1.88 [95% CI 1.63–2.17]), and unmet need for contraception was reduced from 61.7% to 40.5%, a relative reduction of 35% (95% CI 28%–40%). Attendance at birth by those trained to deliver elements of emergency obstetric care increased almost 10-fold, from 5.1% to 48.7% (PRR = 9.55 [95% CI 7.21–12.64]).

Conclusions

Coverage of maternal health interventions and higher-level care at birth was substantially higher during the project period. The MOM Project''s focus on task-shifting, capacity building, and empowerment at the community level might serve as a model approach for similarly constrained settings. Please see later in the article for the Editors'' Summary     

Prevalence,Clinical Staging and Risk for Blood-Borne Transmission of Chagas Disease among Latin American Migrants in Geneva,Switzerland

Background

Migration of Latin Americans to the USA, Canada and Europe has modified Chagas disease distribution, but data on imported cases and on risks of local transmission remain scarce. We assessed the prevalence and risk factors for Chagas disease, staged the disease and evaluated attitudes towards blood transfusion and organ transplant among Latin American migrants in Geneva, Switzerland.

Methodology/Principal Findings

This cross-sectional study included all consecutive Latin American migrants seeking medical care at a primary care facility or attending two Latino churches. After completing a questionnaire, they were screened for Chagas disease with two serological tests (Biomérieux ELISA cruzi; Biokit Bioelisa Chagas). Infected subjects underwent a complete medical work-up. Predictive factors for infection were assessed by univariate and multivariate logistic regression analysis.1012 persons (females: 83%; mean age: 37.2 [SD 11.3] years, Bolivians: 48% [n = 485]) were recruited. 96% had no residency permit. Chagas disease was diagnosed with two positive serological tests in 130 patients (12.8%; 95%CI 10.8%–14.9%), including 127 Bolivians (26.2%; 95%CI 22.3%–30.1%). All patients were in the chronic phase, including 11.3% with cardiac and 0.8% with digestive complications. Predictive factors for infection were Bolivian origin (OR 33.2; 95%CI 7.5–147.5), reported maternal infection with T. cruzi (OR 6.9; 95%CI 1.9–24.3), and age older than 35 years (OR 6.7; 95%CI 2.4–18.8). While 22 (16.9%) infected subjects had already donated blood, 24 (18.5%) and 34 (26.2%) considered donating blood and organs outside Latin America, respectively.

Conclusions

Chagas disease is highly prevalent among Bolivian migrants in Switzerland. Chronic cardiac and digestive complications were substantial. Screening of individuals at risk should be implemented in nonendemic countries and must include undocumented migrants.     

Morbid Obesity as a Risk Factor for Hospitalization and Death Due to 2009 Pandemic Influenza A(H1N1) Disease

Background

Severe illness due to 2009 pandemic A(H1N1) infection has been reported among persons who are obese or morbidly obese. We assessed whether obesity is a risk factor for hospitalization and death due to 2009 pandemic influenza A(H1N1), independent of chronic medical conditions considered by the Advisory Committee on Immunization Practices (ACIP) to increase the risk of influenza-related complications.

Methodology/Principal Findings

We used a case-cohort design to compare cases of hospitalizations and deaths from 2009 pandemic A(H1N1) influenza occurring between April–July, 2009, with a cohort of the U.S. population estimated from the 2003–2006 National Health and Nutrition Examination Survey (NHANES); pregnant women and children <2 years old were excluded. For hospitalizations, we defined categories of relative weight by body mass index (BMI, kg/m²); for deaths, obesity or morbid obesity was recorded on medical charts, and death certificates. Odds ratio (OR) of being in each BMI category was determined; normal weight was the reference category. Overall, 361 hospitalizations and 233 deaths included information to determine BMI category and presence of ACIP-recognized medical conditions. Among ≥20 year olds, hospitalization was associated with being morbidly obese (BMI≥40) for individuals with ACIP-recognized chronic conditions (OR = 4.9, 95% CI 2.4–9.9) and without ACIP-recognized chronic conditions (OR = 4.7, 95%CI 1.3–17.2). Among 2–19 year olds, hospitalization was associated with being underweight (BMI≤5^th percentile) among those with (OR = 12.5, 95%CI 3.4–45.5) and without (OR = 5.5, 95%CI 1.3–22.5) ACIP-recognized chronic conditions. Death was not associated with BMI category among individuals 2–19 years old. Among individuals aged ≥20 years without ACIP-recognized chronic medical conditions death was associated with obesity (OR = 3.1, 95%CI: 1.5–6.6) and morbid obesity (OR = 7.6, 95%CI 2.1–27.9).

Conclusions/Significance

Our findings support observations that morbid obesity may be associated with hospitalization and possibly death due to 2009 pandemic H1N1 infection. These complications could be prevented by early antiviral therapy and vaccination.     

Clinical and Financial Outcomes Due to Methicillin Resistant Staphylococcus aureus Surgical Site Infection: A Multi-Center Matched Outcomes Study

Background

The clinical and financial outcomes of SSIs directly attributable to MRSA and methicillin-resistance are largely uncharacterized. Previously published data have provided conflicting conclusions.

Methodology

We conducted a multi-center matched outcomes study of 659 surgical patients. Patients with SSI due to MRSA were compared with two groups: matched uninfected control patients and patients with SSI due to MSSA. Four outcomes were analyzed for the 90-day period following diagnosis of the SSI: mortality, readmission, duration of hospitalization, and hospital charges. Attributable outcomes were determined by logistic and linear regression.

Principal Findings

In total, 150 patients with SSI due to MRSA were compared to 231 uninfected controls and 128 patients with SSI due to MSSA. SSI due to MRSA was independently predictive of readmission within 90 days (OR = 35.0, 95% CI 17.3–70.7), death within 90 days (OR = 7.27, 95% CI 2.83–18.7), and led to 23 days (95% CI 19.7–26.3) of additional hospitalization and $61,681 (95% 23,352–100,011) of additional charges compared with uninfected controls. Methicillin-resistance was not independently associated with increased mortality (OR = 1.72, 95% CI 0.70–4.20) nor likelihood of readmission (OR = 0.43, 95% CI 0.21–0.89) but was associated with 5.5 days (95% CI 1.97–9.11) of additional hospitalization and $24,113 (95% 4,521–43,704) of additional charges.

Conclusions/Significance

The attributable impact of S. aureus and methicillin-resistance on outcomes of surgical patients is substantial. Preventing a single case of SSI due to MRSA can save hospitals as much as $60,000.     

Differences in Reporting of Violence and Deliberate Self Harm Related Injuries to Health and Police Authorities,Rawalpindi, Pakistan

Background

The aim of study was to assess differences in reporting of violence and deliberate self harm (DSH) related injuries to police and emergency department (ED) in an urban town of Pakistan.

Methods/Principal Findings

Study setting was Rawalpindi city of 1.6 million inhabitants. Incidences of violence and DSH related injuries and deaths were estimated from record linkage of police and ED data. These were then compared to reported figures in both datasets. All persons reporting violence and DSH related injury to the police station, the public hospital''s ED, or both in Rawalpindi city from July 1, 2007 to June 30, 2008 were included. In Rawalpindi city, 1 016 intentional injury victims reported to police whereas 3 012 reported to ED. Comparing violence related fatality estimates (N = 56, 95% CI: 46–64), police reported 75.0% and ED reported 42.8% of them. Comparing violence related injury estimates (N = 7 990, 95% CI: 7 322–8 565), police reported 12.1% and ED reported 33.2% of them. Comparing DSH related fatality estimates (N = 17, 95% CI: 4–30), police reported 17.7% and ED reported 47.1% of them. Comparing DSH related injury estimates (N = 809, 95% CI: 101–1 516), police reported 0.5% and ED reported 39.9% of them.

Conclusion

In Rawalpindi city, police records were more likely to be complete for violence related deaths as compared to injuries due to same mechanism. As compared to ED, police reported DSH related injuries and deaths far less than those due to other types of violence.     

The Diagnostic and Prognostic Accuracy of Five Markers of Serious Bacterial Infection in Malawian Children with Signs of Severe Infection

Background

Early recognition and prompt and appropriate antibiotic treatment can significantly reduce mortality from serious bacterial infections (SBI). The aim of this study was to evaluate the utility of five markers of infection: C-reactive protein (CRP), procalcitonin (PCT), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), CD163 and high mobility group box-1 (HMGB1), as markers of SBI in severely ill Malawian children.

Methodology and Principal Findings

Children presenting with a signs of meningitis (n = 282) or pneumonia (n = 95), were prospectively recruited. Plasma samples were taken on admission for CRP, PCT, sTREM-1 CD163 and HMGB1 and the performance characteristics of each test to diagnose SBI and to predict mortality were determined. Of 377 children, 279 (74%) had SBI and 83 (22%) died. Plasma CRP, PCT, CD163 and HMGB1 and were higher in HIV-infected children than in HIV-uninfected children (p<0.01). In HIV-infected children, CRP and PCT were higher in children with SBI compared to those with no detectable bacterial infection (p<0.0005), and PCT and CD163 were higher in non-survivors (p = 0.001, p = 0.05 respectively). In HIV-uninfected children, CRP and PCT were also higher in children with SBI compared to those with no detectable bacterial infection (p<0.0005), and CD163 was higher in non-survivors (p = 0.05). The best predictors of SBI were CRP and PCT, and areas under the curve (AUCs) were 0.81 (95% CI 0.73–0.89) and 0.86 (95% CI 0.79–0.92) respectively. The best marker for predicting death was PCT, AUC 0.61 (95% CI 0.50–0.71).

Conclusions

Admission PCT and CRP are useful markers of invasive bacterial infection in severely ill African children. The study of these markers using rapid tests in a less selected cohort would be important in this setting.     

Diagnostic Performance of an Aspergillus-Specific Nested PCR Assay in Cerebrospinal Fluid Samples of Immunocompromised Patients for Detection of Central Nervous System Aspergillosis

Central nervous system (CNS) invasive aspergillosis (IA) is a fatal complication in immunocompromised patients. Confirming the diagnosis is rarely accomplished as invasive procedures are impaired by neutropenia and low platelet count. Cerebrospinal fluid (CSF) cultures or galactomannan (GM) regularly yield negative results thus suggesting the need for improving diagnostic procedures. Therefore the performance of an established Aspergillus-specific nested polymerase chain reaction assay (PCR) in CSF samples of immunocompromised patients with suspicion of CNS IA was evaluated. We identified 113 CSF samples from 55 immunocompromised patients for whom CNS aspergillosis was suspected. Of these patients 8/55 were identified as having proven/probable CNS IA while the remaining 47 patients were classified as having either possible (n = 22) or no CNS IA (n = 25). PCR positivity in CSF was observed for 8/8 proven/probable, in 4/22 possible CNS IA patients and in 2/25 NoIA patients yielding sensitivity and specificity values of 1.0 (95% CI 0.68–1) and 0.93 (95% CI 0.77–0.98) and a positive likelihood ratio of 14 and negative likelihood ratio of 0.0, respectively, thus resulting in a diagnostic odds ratio of ∞. The retrospective analysis of CSF samples from patients with suspected CNS IA yielded a high sensitivity of the nested PCR assay. PCR testing of CSF samples is recommended for patients for whom CNS IA is suspected, especially for those whose clinical condition does not allow invasive procedures as a positive PCR result makes the presence of CNS IA in that patient population highly likely.