Cardiovascular risk factor reduction by community health workers in rural India: A cluster randomized trial.

BACKGROUND: There is a need to identify and test low-cost approaches for cardiovascular disease (CVD) risk reduction that can enable health systems to achieve such a strategy. OBJECTIVE: Community health workers (CHWs) are an integral part of health-care delivery system in lower income countries. Our aim was to assess impact of CHW based interventions in reducing CVD risk factors in rural households in India. METHODS: We performed an open-label cluster-randomized trial in 28 villages in 3 states of India with the household as a unit of randomization. Households with individuals at intermediate to high CVD risk were randomized to intervention and control groups. In the intervention group, trained CHWs delivered risk-reduction advice and monitored risk factors during 6 household visits over 12 months. Households in the non-intervention group received usual care. Primary outcomes were a reduction in systolic BP (SBP) and adherence to prescribed BP lowering drugs. RESULTS: We randomized 2312 households (3261 participants at intermediate or high risk) to intervention (1172 households) and control (1140 households). At baseline prevalence of tobacco use (48.5%) and hypertension (34.7%) were high. At 12 months, there was significant decline in SBP (mmHg) from baseline in both groups- controls 130.3 ±â€¯21 to 128.3 ±â€¯15; intervention 130.3 ±â€¯21 to 127.6 ±â€¯15 (P < .01 for before and after comparison) but there was no difference between the 2 groups at 12 months (P = .18). Adherence to antihypertensive drugs was greater in intervention vs control households (74.9% vs 61.4%, P = .001). CONCLUSION: A 12-month CHW-led intervention at household level improved adherence to prescribed drugs, but did not impact SBP. To be more impactful, a more comprehensive solution that addresses escalation and access to useful therapies is needed.

Predictors of Mortality in Hospitalized Patients With Pesticide Poisoning.

Background Organophosphorus poisoning (OPP) is a prevalent mortality rate that varies from 2% to 25% method of suicides worldwide. ICUs commonly employ various scoring systems such as the Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II), and International Programme on Chemical Safety (IPCS) Poison Severity Score (PSS) tools for risk stratification for mortality prediction scores and prognosis. This study aims to compare the predictive validity of these systems in hospitalized patients suffering from pesticide poisoning in a teaching hospital located in central India. Methods A prospective study design was utilized to gather relevant variables for calculating the GCS, APACHE II, SAPS II, and IPCS scales in patients affected by pesticide poisoning. Data on the administered doses of atropine and pralidoxime (PAM) were also recorded. Results We have identified several independent predictors of mortality among patients suffering from pesticide poisoning. The GCS (P=0.001), tracheostomy (P=0.001), APACHE II score (P=0.01), and SAPS II score (P=0.001) were all found to be significant indicators of mortality. Interestingly, the GCS demonstrated comparable predictive ability for mortality when compared to the APACHE II (0.82 (95% confidence interval (CI) 0.70 to 0.94)) and SAPS II (0.83 (95% CI 0.72 to 0.94)) scores, with no statistically significant difference (P=0.75) observed. Among the variables used in the IPCS PSS (GCS, heart rate, systolic blood pressure (BP), intubation, and pupil size), only GCS (P=0.05), and intubation (P=0.01) exhibited a significant association with mortality. Conclusions Our study determined that the GCS score, SAPS II, IPCS PSS, and APACHE II exhibited equal efficacy in predicting mortality. Notably, the GCS offered an added advantage due to its simplicity and minimal time requirements compared to the other scales.

Impact of round-the-clock, rapid oral fluid HIV testing of women in labor in rural India.

BACKGROUND: Testing pregnant women for HIV at the time of labor and delivery is the last opportunity for prevention of mother-to-child HIV transmission (PMTCT) measures, particularly in settings where women do not receive adequate antenatal care. However, HIV testing and counseling of pregnant women in labor is a challenge, especially in resource-constrained settings. In India, many rural women present for delivery without any prior antenatal care. Those who do get antenatal care are not always tested for HIV, because of deficiencies in the provision of HIV testing and counseling services. In this context, we investigated the impact of introducing round-the-clock, rapid, point-of-care HIV testing and counseling in a busy labor ward at a tertiary care hospital in rural India. METHODS AND FINDINGS: After they provided written informed consent, women admitted to the labor ward of a rural teaching hospital in India were offered two rapid tests on oral fluid and finger-stick specimens (OraQuick Rapid HIV-1/HIV-2 tests, OraSure Technologies). Simultaneously, venous blood was drawn for conventional HIV ELISA testing. Western blot tests were performed for confirmatory testing if women were positive by both rapid tests and dual ELISA, or where test results were discordant. Round-the-clock (24 h, 7 d/wk) abbreviated prepartum and extended postpartum counseling sessions were offered as part of the testing strategy. HIV-positive women were administered PMTCT interventions. Of 1,252 eligible women (age range 18 y to 38 y) approached for consent over a 9 mo period in 2006, 1,222 (98%) accepted HIV testing in the labor ward. Of these, 1,003 (82%) women presented with either no reports or incomplete reports of prior HIV testing results at the time of admission to the labor ward. Of 1,222 women, 15 were diagnosed as HIV-positive (on the basis of two rapid tests, dual ELISA and Western blot), yielding a seroprevalence of 1.23% (95% confidence interval [CI] 0.61%-1.8%). Of the 15 HIV test-positive women, four (27%) had presented with reported HIV status, and 11 (73%) new cases of HIV infection were detected due to rapid testing in the labor room. Thus, 11 HIV-positive women received PMTCT interventions on account of round-the-clock rapid HIV testing and counseling in the labor room. While both OraQuick tests (oral and finger-stick) were 100% specific, one false-negative result was documented (with both oral fluid and finger-stick specimens). Of the 15 HIV-infected women who delivered, 13 infants were HIV seronegative at birth and at 1 and 4 mo after delivery; two HIV-positive infants died within a month of delivery. CONCLUSIONS: In a busy rural labor ward setting in India, we demonstrated that it is feasible to introduce a program of round-the-clock rapid HIV testing, including prepartum and extended postpartum counseling sessions. Our data suggest that the availability of round-the-clock rapid HIV testing resulted in successful documentation of HIV serostatus in a large proportion (82%) of rural women who were unaware of their HIV status when admitted to the labor room. In addition, 11 (73%) of a total of 15 HIV-positive women received PMTCT interventions because of round-the-clock rapid testing in the labor ward. These findings are relevant for PMTCT programs in developing countries.

Nonmalarial acute undifferentiated fever in a rural hospital in central India: diagnostic uncertainty and overtreatment with antimalarial agents.

Nonmalarial acute undifferentiated fever (NMAUF) refers to a febrile illness with no indication of an organ-specific disease after diagnosis of malaria has been excluded. In developing countries, the empirical treatment of NMAUFs with antimalarial drugs continues even in the era of highly specific rapid diagnostic tests (RDTs) for malaria. We carried out a retrospective review of patients with fever admitted to a rural teaching hospital in central India. We categorized patients with NMAUF into different clinical syndromes and determined their demographic profile, inhospital course, and the pattern of antimalarial use. The study sample included 1,197 adult patients who were investigated for malaria; 1,053 (88%) of them had NMAUF, and use of further diagnostics in this group was limited. Despite one or more negative tests for malaria, many patients (39.9%, 95% CI 37.0-43.3) received antimalarial drugs. These results suggest a need for guidelines and training to improve empirical treatment of NMAUF.

Can aspirin help?

Using a combination of aspirin, anti-tuberculosis drugs and steroids may help to reduce the number of strokes and deaths in patients with tuberculous meningitis.

Accuracy and reliability of physical signs in the diagnosis of pleural effusion.

Although pleural effusion is a common disorder among patients presenting with respiratory symptoms, there is limited evidence on the accuracy and reliability of symptoms and signs for the diagnosis of pleural effusion. In our study, conducted at a rural hospital in India, two physicians, blind to history and chest radiograph findings, and to each other's results, independently evaluated 278 patients (196 men), aged 12 and older, admitted with respiratory symptoms. We did a blind and independent comparison of physical signs (asymmetric chest expansion, vocal fremitus, percussion note, breath sounds, crackles, vocal resonance and auscultatory percussion) with the reference standard (chest radiograph). We measured diagnostic accuracy by computing sensitivity, specificity, and likelihood ratios (LRs), and inter-observer reliability by using kappa (kappa) statistic. We performed multivariate analysis to identify the clinical signs that independently predict pleural effusion. The prevalence of pleural effusion was 21% (57/278). The LRs of positive signs ranged from 1.48 to 8.14 and their 95% confidence intervals (CIs) excluded 1. Except for pleural rub, the LRs for negative signs ranged between 0.13 and 0.71. The interobserver agreement was excellent for chest expansion, vocal fremitus, percussion and breath sounds (kappa 0.84-0.89) and good for vocal resonance, crackles and auscultatory percussion (kappa 0.68-0.78). The independent predictors of pleural effusion were asymmetric chest expansion (odds ratio [OR] 5.22, 95% CI 2.06-13.23), and dull percussion note (OR 12.80, 95% CI 4.23-38.70). For the final multivariate model, the area under receiver operating characteristic curve (ROC curve) was 0.88. In conclusion, our data suggest that physical signs may be helpful to rule out but not rule in pleural effusion.

A commercial line probe assay for the rapid detection of rifampicin resistance in Mycobacterium tuberculosis: a systematic review and meta-analysis.

BACKGROUND: Mycobacterium tuberculosis is a leading cause of death worldwide. In multi-drug resistant tuberculosis (MDR-TB) infectiousness is frequently prolonged, jeopardizing efforts to control TB. The conventional tuberculosis drug susceptibility tests are sensitive and specific, but they are not rapid. The INNO-LiPA Rif. TB (LiPA) is a commercial line probe assay designed to rapidly detect rifampicin resistance, a marker of MDR-TB. Although LiPA has shown promising results, its overall accuracy has not been systematically evaluated. METHODS: We did a systematic review and meta-analysis to evaluate the accuracy of LiPA for the detection of rifampicin-resistant tuberculosis among culture isolates and clinical specimens. We searched Medline, Embase, Web of Science, BIOSIS, and Google Scholar, and contacted authors, experts and the manufacturer. Fifteen studies met our inclusion criteria. Of these, 11 studies used culture isolates, one used clinical specimens, and three used both. We used a summary receiver operating characteristic (SROC) curve and Q* index to perform meta-analysis and summarize diagnostic accuracy. RESULTS: Twelve of 14 studies that applied LiPA to isolates had sensitivity greater than 95%, and 12 of 14 had specificity of 100%. The four studies that applied LiPA directly to clinical specimens had 100% specificity, and sensitivity that ranged between 80% and 100%. The SROC curve had an area of 0.99 and Q* of 0.97. CONCLUSION: LiPA is a highly sensitive and specific test for the detection of rifampicin resistance in culture isolates. The test appears to have relatively lower sensitivity when used directly on clinical specimens. More evidence is needed before LiPA can be used to detect MDR-TB among populations at risk in clinical practice.

Bacteriophage- based tests for the detection of Mycobacterium tuberculosis in clinical specimens: a systematic review and meta- analysis.

BACKGROUND: Sputum microscopy, the most important conventional test for tuberculosis, is specific in settings with high burden of tuberculosis and low prevalence of non tuberculous mycobacteria. However, the test lacks sensitivity. Although bacteriophage-based tests for tuberculosis have shown promising results, their overall accuracy has not been systematically evaluated. METHODS: We did a systematic review and meta-analysis of published studies to evaluate the accuracy of phage-based tests for the direct detection of M. tuberculosis in clinical specimens. To identify studies, we searched Medline, EMBASE, Web of science and BIOSIS, and contacted authors, experts and test manufacturers. Thirteen studies, all based on phage amplification method, met our inclusion criteria. Overall accuracy was evaluated using forest plots, summary receiver operating (SROC) curves, and subgroup analyses. RESULTS: The data suggest that phage-based assays have high specificity (range 0.83 to 1.00), but modest and variable sensitivity (range 0.21 to 0.88). The sensitivity ranged between 0.29 and 0.87 among smear-positive, and 0.13 to 0.78 among smear-negative specimens. The specificity ranged between 0.60 and 0.88 among smear-positive and 0.89 to 0.99 among smear-negative specimens. SROC analyses suggest that overall accuracy of phage-based assays is slightly higher than smear microscopy in direct head-to-head comparisons. CONCLUSION: Phage-based assays have high specificity but lower and variable sensitivity. Their performance characteristics are similar to sputum microscopy. Phage assays cannot replace conventional diagnostic tests such as microscopy and culture at this time. Further research is required to identify methods that can enhance the sensitivity of phage-based assays without compromising the high specificity.

Mycobacterium tuberculosis infection in health care workers in rural India: comparison of a whole-blood interferon gamma assay with tuberculin skin testing.

CONTEXT: Mycobacterium tuberculosis infection in health care workers has not been adequately studied in developing countries using newer diagnostic tests. OBJECTIVES: To estimate latent tuberculosis infection prevalence in health care workers using the tuberculin skin test (TST) and a whole-blood interferon gamma (IFN-gamma) assay; to determine agreement between the tests; and to compare their correlation with risk factors. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional comparison study of 726 health care workers aged 18 to 61 years (median age, 22 years) with no history of active tuberculosis conducted from January to May 2004, at a rural medical school in India. A total of 493 (68%) of the health care workers had direct contact with patients with tuberculosis and 514 (71%) had BCG vaccine scars. INTERVENTIONS: Tuberculin skin testing was performed using 1-TU dose of purified protein derivative RT23, and the IFN-gamma assay was performed by measuring IFN-gamma response to early secreted antigenic target 6, culture filtrate protein 10, and a portion of tuberculosis antigen TB7.7. MAIN OUTCOME MEASURES: Agreement between TST and the IFN-gamma assay, and comparison of the tests with respect to their association with risk factors. RESULTS: A large proportion of the health care workers were latently infected; 360 (50%) were positive by either TST or IFN-gamma assay, and 226 (31%) were positive by both tests. The prevalence estimates of TST and IFN-gamma assay positivity were comparable (41%; 95% confidence interval [CI], 38%-45% and 40%; 95% CI, 37%-43%, respectively). Agreement between the tests was high (81.4%; kappa = 0.61; 95% CI, 0.56-0.67). Increasing age and years in the health profession were significant risk factors for both IFN-gamma assay and TST positivity. BCG vaccination had little impact on TST and IFN-gamma assay results. CONCLUSIONS: Our study showed high latent tuberculosis infection prevalence in Indian health care workers, high agreement between TST and IFN-gamma assay, and similar association between positive test results and risk factors. Although TST and IFN-gamma assay appear comparable in this population, they have different performance and operational characteristics; therefore, the decision to select one test over the other will depend on the population, purpose of testing, and resource availability.

Accuracy of physical signs for detecting meningitis: a hospital-based diagnostic accuracy study.

OBJECTIVES: To evaluate accuracy of physical signs for detecting meningitis. PATIENTS AND METHODS: We enrolled patients aged 12 years or more, admitted with acute encephalitis syndrome (fever, headache, altered mental status, vomiting, seizures, neurodeficit) to a rural teaching hospital. The design was a double-blind, cross-sectional analysis of consecutive patients, independently comparing signs of meningeal inflammation (nuchal rigidity, head jolt accentuation of headache, Kernig's sign and Brudzinski's sign) elicited by internal medicine residents against an established reference standard (cerebrospinal fluid white cell count >5 white cells/µL). Diagnostic accuracy was measured by computing sensitivity, specificity and likelihood ratios (LRs) and their 95% confidence interval (CI) values. RESULTS: Of 190 patients (119 men, 71 women; ages 13-81 years; mean 38(SD 18) years) CSF analysis identified meningitis in 99 (52%; 95% CI 44, 59%) patients. No physical sign of meningeal irritation could accurately distinguish those with and without meningitis: nuchal rigidity (LR+ 1.33 (0.89, 1.98) and LR- 0.86 (0.70, 1.06)), head jolt accentuation of headache (LR+ 5.52 (0.67, 44.9) and LR- 0.95(0.89, 1.00)), Kernig's sign (LR+ 1.84 (0.77, 4.35) and LR- 0.93(0.84, 1.03)) and Brudzinski's sign (LR+ 1.69 (0.65, 4.37) and LR- 0.95 (0.87, 1.04)). CONCLUSION: Physical signs of meningeal inflammation do not help clinicians rule in or rule out meningitis accurately. Patients suspected to have meningitis should undergo a lumbar puncture regardless of the presence or absence of physical signs.

Hirayama disease.

A 17-year-old male, who gave up his favorite sport cricket and started playing football, presented with one-year history of slowly progressive atrophic weakness of forearms and hands. Neurological examination showed weak and wasted arms, forearms and hand but no evidence of pyramidal tract, spinothalmic tract and posterior column lesions. Plain cervical spine radiographs showed no abnormal findings. Cervical magnetic resonance imaging (MRI) showed asymmetric cord atrophy; images obtained with neck flexed showed the anterior shifting of the posterior wall of the lower cervical dural sac resulting in cord compression. These findings suggest Hirayama disease, a kind of cervical myelopathy related to the flexion movements of the neck.

Accuracy and reliability of pallor for detecting anaemia: a hospital-based diagnostic accuracy study.

BACKGROUND: Anaemia is a common disorder. Most health providers in resource poor settings rely on physical signs to diagnose anaemia. We aimed to determine the diagnostic accuracy of pallor for anaemia by using haemoglobin as the reference standard. METHODOLOGY/PRINCIPAL FINDINGS: In May 2007, we enrolled consecutive patients over 12 years of age, able to consent and willing to participate and who had a haemoglobin measurement taken within a day of assessment of clinical pallor from outpatient and medicine inpatient department of a teaching hospital. We did a blind and independent comparison of physical signs (examination of conjunctivae, tongue, palms and nailbed for pallor) and the reference standard (haemoglobin estimation by an electronic cell counter). Diagnostic accuracy was measured by calculating likelihood ratio values and 95% confidence intervals (CI) at different haemoglobin thresholds and area under the receiver operating characteristic curve. Two observers examined a subset of patients (n = 128) to determine the inter-observer agreement, calculated by kappa statistics. We studied 390 patients (mean age 40.1 [SD 17.08] years); of whom 48% were women. The haemoglobin was <7 g/dL in 8% (95% confidence interval, 5, 10) patients; <9 g/dL in 21% (17, 26) patients and <12 g/dL in 64% (60, 70) patients. Among patients with haemoglobin <7 g/dL, presence of severe tongue pallor yielded a LR of 9.87 (2.81, 34.6) and its absence yielded a LR of 0. The tongue pallor outperformed other pallor sites and was also the best discriminator of anaemia at haemoglobin thresholds of 7 g/dL and 9 g/dL (area under the receiver operating characteristic curves (ROC area = 0.84 [0.77, 0.90] and 0.71[0.64, 0.76]) respectively. The agreement between the two observers for detection of anaemia was poor (kappa values = 0.07 for conjunctival pallor and 0.20 for tongue pallor). CONCLUSIONS/SIGNIFICANCE: Clinical assessment of pallor can rule out and modestly rule in severe anaemia.

T-cell assays for tuberculosis infection: deriving cut-offs for conversions using reproducibility data.

BACKGROUND: Although interferon-gamma release assays (IGRA) are promising alternatives to the tuberculin skin test, interpretation of repeated testing results is hampered by lack of evidence on optimal cut-offs for conversions and reversions. A logical start is to determine the within-person variability of T-cell responses during serial testing. METHODOLOGY/PRINCIPAL FINDINGS: We performed a pilot study in India, to evaluate the short-term reproducibility of QuantiFERON-TB Gold In Tube assay (QFT) among 14 healthcare workers (HCWs) who underwent 4 serial QFT tests on day 0, 3, 9 and 12. QFT ELISA was repeated twice on the same sets of specimens. We assessed two types of reproducibility: 1) test-retest reproducibility (between-test variability), and 2) within-person reproducibility over time. Test-retest reproducibility: with dichotomous test results, extremely high concordance was noticed between two tests performed on the same sets of specimens: of the 56 samples, the test and re-test results agreed for all but 2 individuals (kappa = 0.94). Discordance was noted in subjects who had IFN-gamma values around the cut-off point, with both increases and decreases noted. With continuous IFN-gamma results, re-test results tended to produce higher estimates of IFN-gamma than the original test. Within-person reproducibility: when continuous IFN-gamma data were analyzed, the within-person reproducibility was moderate to high. While persons with negative QFT results generally stayed negative, positive results tended to vary over time. Our data showed that increases of more than 16% in the IFN-gamma levels are statistically improbable in the short-term. CONCLUSIONS: Conservatively assuming that long-term variability might be at least twice higher than short-term, we hypothesize that a QFT conversion requires two conditions to be met: 1) change from negative to positive result, and 2) at least 30% increase in the baseline IFN-gamma response. Larger studies are needed to confirm our preliminary findings, and determine the conversion thresholds for IGRAs.

Prevalence of abnormal radiological findings in health care workers with latent tuberculosis infection and correlations with T cell immune response.

BACKGROUND: More than half of all health care workers (HCWs) in high TB-incidence, low and middle income countries are latently infected with tuberculosis (TB). We determined radiological lesions in a cohort of HCWs with latent TB infection (LTBI) in India, and determined their association with demographic, occupational and T-cell immune response variables. METHODOLOGY: We obtained chest radiographs of HCWs who had undergone tuberculin skin test (TST) and QuantiFERON-TB Gold In Tube (QFT), an interferon-gamma release assay, in a previous cross-sectional study, and were diagnosed to have LTBI because they were positive by either TST or QFT, but had no evidence of clinical disease. Two observers independently interpreted these radiographs using a standardized data form and any discordance between them resolved by a third observer. The radiological diagnostic categories (normal, suggestive of inactive TB, and suggestive of active TB) were compared with results of TST, QFT assay, demographic, and occupational covariates. RESULTS: A total of 330 HCWs with positive TST or QFT underwent standard chest radiography. Of these 330, 113 radiographs (34.2%) were finally classified as normal, 206 (62.4%) had lesions suggestive of inactive TB, and 11 (3.4%) had features suggestive of active TB. The mean TST indurations and interferon-gamma levels in the HCWs in these three categories were not significantly different. None of the demographic or occupational covariates was associated with prevalence of inactive TB lesions on chest radiography. CONCLUSION/SIGNIFICANCE: In a high TB incidence setting, nearly two-thirds of HCWs with latent TB infection had abnormal radiographic findings, and these findings had no clear correlation with T cell immune responses. Further studies are needed to verify these findings and to identify the causes and prognosis of radiologic abnormalities in health care workers.