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1.  Correlation between dipstick urinalysis and urine sediment microscopy in detecting haematuria among children with sickle cell anaemia in steady state in Ilorin, Nigeria 
Introduction
Haematuria is one of the clinical manifestations of sickle cell nephropathy. Although dipstick urinalysis detects haemoglobin and by extension haematuria; it does not confirm haematuria. Urine sediment microscopy confirms haematuria and constitutes a non-invasive “renal biopsy”. The need to correlate dipstick urinalysis and urine sediment microscopy findings becomes important because of the cheapness, quickness and simplicity of the former procedure.
Methods
Dipstick urinalysis and urine sediment microscopy were carried (both on first contact and a month after) among consecutive steady state sickle cell anaemia children attending sickle cell clinic at the University of Ilorin Teaching Hospital between October 2004 and July 2005.
Results
A total of 75 sickle cell anemia children aged between 1-17 years met the inclusion criteria. Haematuria was found in 12 children (16.0%) and persistent haematuria in 10 children 13.3%. Age and gender did not have significant relationship with haematuria both at first contact (p values 0.087 and 0.654 respectively) and at follow-up (p values 0.075 and 0.630 respectively). Eumorphic haematuria was confirmed in all the children with persistent haematuria with Pearson correlation +0.623 and significant p value of 0.000.
Conclusion
The study has revealed a direct significant correlation for haematuria detected on dipstick urinalysis and at urine sediment microscopy. It may therefore be inferred that dipstick urinalysis is an easy and readily available tool for the screening of haematuria among children with sickle cell anaemia and should therefore be done routinely at the sickle cell clinics.
doi:10.11604/pamj.2013.15.135.1854
PMCID: PMC3852513  PMID: 24319525
Sickle cell nephropathy; children; haematuria; dipstick urinalysis; urine sediment microscopy
2.  Dipstick haematuria and bladder cancer in men over 60: results of a community study. 
BMJ : British Medical Journal  1989;299(6706):1010-1012.
OBJECTIVE--To investigate the prevalence and relevance of dipstick haematuria in a group of men in the community. DESIGN--Prospective study of elderly men invited to attend a health centre for urine screening as part of a health check. SETTING--An inner city health centre in Leeds. SUBJECTS--578 Of 855 men aged 60-85 responding to an invitation to participate. INTERVENTIONS--The subjects had their urine tested with a dipstick (Multistix) for the presence of blood and then tested their urine once a week for the next 10 weeks. Those with one or more positive test results were offered full urological investigation. MAIN OUTCOME MEASURE--The prevalence of urological disease in those subjects with dipstick haematuria. RESULTS--78 Men (13%) had dipstick haematuria on a single test and a further 54 (9%) had evidence of dipstick haematuria when testing their urine once a week during a subsequent 10 week period. Investigation of 87 men disclosed urological disease in 45, including four with a bladder tumour and seven with epithelial dysplasia. CONCLUSION--Dipstick haematuria is a common incidental finding in men over 60 and is associated with appreciable urological disease. The introduction of less invasive methods of investigation, particularly flexible cystoscopy and ultrasonography, has made investigation of these patients simple and safe and makes screening for bladder cancer in the community more feasible.
PMCID: PMC1837876  PMID: 2511941
3.  Patients with new onset haematuria: assessing the discriminant value of clinical information in relation to urological malignancies. 
BACKGROUND: There is little information available to assist general practitioners (GPs) in deciding which patients with haematuria are likely to have a malignancy. AIM: To derive discriminant functions for specific items or clusters of clinical history information in relation to the categorisation of patients presenting to the 'open access' haematuria clinic in Hull. DESIGN OF STUDY: Recruitment of patients via an 'open-access' haematuria clinic. SETTING: A consecutive series of 363 patients aged between 18 and 80 years who attended the clinic. METHOD: Between February 1999 and October 1999 clinical history information derived from the participating patients was compared with the patients' diagnoses. Diagnoses were established by a combination of cystoscopy and radiological assessments and rechecked against the patient records and the hospital patient administration system two to three months later. RESULTS: A number of individual variables seemed to be particularly helpful in discriminating malignancies. However, when indicants were combined using regression shrinkage techniques, only the following variables were preserved: age, sex, type of haematuria, number of episodes of haematuria, hesitancy, poor urinary stream, smoking history, and history of urinary tract infections. CONCLUSION: It is possible to generate helpful discriminant information to assist GPs in making more appropriate decisions in a difficult area of clinical practice. However, it remains a matter of judgement as to how representative the study population is likely to be compared with all haematuria patients encountered in primary care. We have reasonable confidence in the general applicability of the rules for macroscopic haematuria: however, it seems likely that the prediction rules outlined for microscopic haematuria have their greatest relevance once a patient has been referred by a GP. In developing the work further and testing out the discriminators identified in this study, we propose that a primary care-based project now needs to be undertaken focusing on microscopic haematuria with a particular emphasis on addressing selection biases. In addition, there is a more general need to assess the reliability of all the suggested items of clinical discriminant information.
PMCID: PMC1314268  PMID: 11942444
4.  A prospective study of renal disease in patients with early rheumatoid arthritis 
Annals of the Rheumatic Diseases  2001;60(4):327-331.
OBJECTIVES—This prospective study was designed to clarify the frequency, causes, and clinical course of renal disease in patients with early rheumatoid arthritis (RA).
METHODS—235 patients (185 women, mean age 49.4 years) with early RA of less than one year's duration were enrolled and assessed monthly. Proteinuria was defined as a positive dipstick result and microscopic haematuria was defined as the presence of ⩾5 red blood cells per high power field. Urinary abnormalities lasting three months or longer were defined as persistent abnormalities.
RESULTS—At entry, 40 patients exhibited haematuria, two had a raised serum creatinine concentration, and none had proteinuria. During the observation period (average 42 months), persistent haematuria was found in 43, persistent proteinuria in 17, and a raised serum creatinine concentration in 14 patients. Persistent proteinuria was caused by drugs in 14 of 17 patients and disappeared in most cases. Risk factors for drug induced proteinuria included a raised C reactive protein and erythrocyte sedimentation rate and age over 50 at entry. Drugs resulted in a raised serum creatinine concentration in eight of 14 patients. The incidence of haematuria at entry did not differ among patients who had been treated with non-steroidal anti-inflammatory drugs, disease modifying antirheumatic drugs, or no drugs. In some patients with isolated haematuria, the haematuria appeared when the activity of RA was high and resolved when it was low.
CONCLUSIONS—This study suggests that a raised serum creatinine concentration or persistent proteinuria in patients with early RA is predominantly drug related whereas, in contrast, isolated haematuria is more directly associated with the activity of the disease process.


doi:10.1136/ard.60.4.327
PMCID: PMC1753620  PMID: 11247860
5.  A study of microscopical and chemical tests for the rapid diagnosis of urinary tract infections in general practice. 
Aids to the rapid diagnosis of urinary tract infection were assessed by the examination of 325 consecutive urine samples taken in the normal course of work in a general practice. Of these samples 103 produced a pure growth of at least 10(5) organisms per ml. The appearance and smell of each sample was noted and it was then tested by simple low-power microscopy of a drop of urine and by a dipstick which measured leucocyte esterase and nitrite, together with protein, blood and pH. In addition, pus cell counts per mm3 were performed on 272 of the samples using a cytometer chamber. This method is too time-consuming for routine use in the surgery. Neither a cloudy appearance nor haematuria were sufficiently specific to be of much use in the diagnosis of urinary tract infection. In the prediction of a 'positive' culture the sensitivity and specificity of the other tests were as follows: drop method microscopy 95% and 76%, respectively; cytometer count 95% and 81%; leucocyte-esterase estimation 89% and 68%; and nitrite 57% and 96%. These figures may underestimate the true values of the tests in the diagnosis of urinary tract infection because infection may be present in some cases producing growths of less than 10(5) organisms per ml. It is concluded that the most useful aid to the diagnosis of urinary tract infection is low-power microscopy of a drop of urine.
PMCID: PMC1371381  PMID: 2271260
6.  Importance of occult haematuria found at screening. 
A retrospective study of the results of dipstick testing and microscopical examination of urine from 10 050 men undergoing health screening showed a prevalence of occult haematuria of 2.5%. Those patients with occult haematuria who were resident in the United Kingdom and registered with a general practitioner were identified and a questionnaire sent to their general practitioners asking what further investigations had been performed. The response rate was 92% (152/165 inquiries). Fifty nine general practitioners (39%) had not instigated any investigations. Among the 76 patients who underwent some further investigations abnormalities were found in 21 (28%); and among those fully investigated by examination of midstream urine, intravenous urography, and cystoscopy abnormalities were found in 12(50%). These included bladder neoplasms (two; one in a patient aged 37), epithelial dysplasia (one), staghorn calculi (one), and chronic reflux nephropathy (one). It is proposed that occult haematuria should be fully investigated regardless of the age of the patient.
PMCID: PMC1339660  PMID: 3081223
7.  Haematuria. 
Postgraduate Medical Journal  1997;73(857):129-136.
Many serious and potentially treatable diseases of the urinary tract may have haematuria as their only manifestation. However, asymptomatic microscopic haematuria detected by dipstick testing may be seen in up to 16% of screening populations. The great majority of such cases will have no sinister underlying cause, particularly in those under 40 years of age, and so the schedule of further investigations, some of which may be invasive, time-consuming and expensive, needs to be rationalised. In addition, the increasing popularity of 'fast track' clinics for the investigation of haematuria enhances the need for a clear strategy of investigation. Analysis of the epidemiology of asymptomatic haematuria and its causes combined with a consideration of the risk-benefit profile of the available investigations, makes it possible to set out an algorithm for the initial management of this common finding. Careful clinical assessment and basic laboratory tests for renal function, analysis of the urinary sediment and cytological examination of the urine are followed by ultrasound and plain radiography of the urinary tract. Flexible cystoscopy under local anaesthetic is central to the algorithm in patients of all ages. The importance of a nephrological opinion and consideration of renal biopsy, especially in younger patients with other evidence of glomerular disease, is stressed. The role of intravenous urography in excluding pathology of the upper urinary tract, especially in patients over the age of 40, is also considered.
Images
PMCID: PMC2431247  PMID: 9135826
8.  Renal screening in children after exposure to low dose melamine in Hong Kong: cross sectional study 
Objective To investigate the renal outcomes of children after exposure to low dose melamine in Hong Kong.
Design Cross sectional study.
Setting Special assessment centres, Hong Kong.
Participants 3170 children (1422 girls and 1748 boys) aged 12 years or less referred from territory-wide primary care clinics after daily consumption for one month or more of milk products tainted with melamine.
Main outcome measures Presence of renal stones and haematuria.
Results One child had a confirmed renal stone, seven were suspected of having melamine related renal deposits, and 208 (6.6%) were positive for blood in urine by reagent strip. A proportion of these children were followed up at the special assessment centre, but only 7.4% of those positive for blood on reagent strip were confirmed by microscopy, suggesting an overall estimated prevalence of less than 1% for microscopic haematuria.
Conclusions No severe adverse renal outcomes, such as acute renal failure or urinary tract obstruction, were detected in children after exposure to low dose melamine. Our results were similar to territory-wide findings in Hong Kong. Even including the seven children with suspected renal deposits, the prevalence of suspected melamine related abnormalities on ultrasonography was only 0.2%. None of these children required specific treatment. The prevalence of microscopic haematuria was probably overestimated by the reagent strip. These data suggest that large scale and urgent screening programmes may not be informative or cost effective for populations who have been exposed to low dose melamine.
doi:10.1136/bmj.a2991
PMCID: PMC2612581  PMID: 19097976
9.  The value of urinary red cell shape in the diagnosis of glomerular and post-glomerular haematuria. A meta-analysis. 
Postgraduate Medical Journal  1992;68(802):648-654.
The proportion of dysmorphic red cells (DRC) in the urinary sediment and their mean corpuscular volume (MCV) have been claimed to discriminate between glomerular and postglomerular sources of haematuria. To determine the diagnostic value of urinary DRC and MCV, we searched the literature and critically reviewed 21 published studies using a predetermined set of criteria for evaluation. All studies originated from referral centres. Interobserver variability in identifying urinary DRC was reported in four studies and found to be unacceptably large in one. Although reproducible over different samples of the same individual, urinary MCV was unreliable in cases of low-grade haematuria because of interfering debris. Weighted averages and 95% confidence limits of the sensitivity and specificity of the DRC proportion for glomerular disease were 0.88 (0.86-0.90) and 0.95 (0.93-0.97), respectively; those of a low MCV were 1.00 (0.98-1.00) for sensitivity and 0.87 (0.80-0.91) for specificity. Sensitivity and specificity values derived from in-patients were slightly higher than those in referred outpatients. No studies of urinary DRC or MCV in patients with incidentally detected microhaematuria in the primary care setting were found. We conclude that at present the diagnostic value of urinary DRC and MCV is limited. In referral centres, that is, in patients with a high probability of postglomerular haematuria, the test cannot rule out urological lesions, because its specificity for glomerular disease may be as low as 0.80. In the primary care setting, that is, in unselected patients with incidentally detected low-grade haematuria, the accuracy of the test has not been studied but may be even lower. The use of urinary DRC or MCV as an indicator of the source of haematuria is in need of further experimental development and confirmation.
PMCID: PMC2399558  PMID: 1448406
10.  New Rapid Diagnostic Tests for Neisseria meningitidis Serogroups A, W135, C, and Y 
PLoS Medicine  2006;3(9):e337.
Background
Outbreaks of meningococcal meningitis (meningitis caused by Neisseria meningitidis) are a major public health concern in the African “meningitis belt,” which includes 21 countries from Senegal to Ethiopia. Of the several species that can cause meningitis, N. meningitidis is the most important cause of epidemics in this region. In choosing the appropriate vaccine, accurate N. meningitidis serogroup determination is key. To this end, we developed and evaluated two duplex rapid diagnostic tests (RDTs) for detecting N. meningitidis polysaccharide (PS) antigens of several important serogroups.
Methods and Findings
Mouse monoclonal IgG antibodies against N. meningitidis PS A, W135/Y, Y, and C were used to develop two immunochromatography duplex RDTs, RDT1 (to detect serogroups A and W135/Y) and RDT2 (to detect serogroups C and Y). Standards for Reporting of Diagnostic Accuracy criteria were used to determine diagnostic accuracy of RDTs on reference strains and cerebrospinal fluid (CSF) samples using culture and PCR, respectively, as reference tests. The cutoffs were 105 cfu/ml for reference strains and 1 ng/ml for PS. Sensitivities and specificities were 100% for reference strains, and 93.8%–100% for CSF serogroups A, W135, and Y in CSF. For CSF serogroup A, the positive and negative likelihood ratios (± 95% confidence intervals [CIs]) were 31.867 (16.1–63.1) and 0.065 (0.04–0.104), respectively, and the diagnostic odds ratio (± 95% CI) was 492.9 (207.2–1,172.5). For CSF serogroups W135 and Y, the positive likelihood ratio was 159.6 (51.7–493.3) Both RDTs were equally reliable at 25 °C and 45 °C.
Conclusions
These RDTs are important new bedside diagnostic tools for surveillance of meningococcus serogroups A and W135, the two serogroups that are responsible for major epidemics in Africa.
There are several strains ofNeisseria meningitidis that can cause seasonal outbreaks of meningitis in Africa. Treatment of patients and containment of the epidemic through vaccination depends on which strain is responsible. The new dipstick tests described here are accurate and suitable for storage and use in resource-poor settings.
Editors' Summary
Background
Bacterial meningitis, a potentially deadly infection of tissues that line the brain and spinal cord, affects over 1 million people each year. Patients with bacterial meningitis usually have fever, headache, and stiff neck, and may become unconscious and die if the disease is not treated within hours. Most cases of bacterial meningitis occur in Africa, particularly in the arid savannah region south of the Sahara known as the Sahel, where epidemic outbreaks of meningitis occur periodically. This region, also called the “meningitis belt,” extends from Senegal and adjacent coastal countries in West Africa across the continent to Ethiopia. Although most outbreaks tend to occur in the dry season, they differ in frequency in different areas of the meningitis belt, and may involve any of several kinds of bacteria. One of the major causes of epidemic meningitis is Neisseria meningitidis, a meningococcus bacterium that exists in several different groups. Group A has been a common cause of epidemic meningitis in Africa, and some outbreaks were due to group C. More recently, group W135 has emerged as an epidemic strain. In addition to prompt diagnosis and treatment of individual cases, effective public health strategies for controlling meningococcal meningitis include rapid identification of outbreaks and determination of the type of bacteria involved, followed by mass vaccination of people in the surrounding area without delay. Vaccines are chosen on the basis of the responsible meningococcal serogroup: either the inexpensive bivalent vaccine A/C or the expensive, less readily available trivalent vaccine A/C/W135. Before the advent of W135 as an epidemic clone, bivalent vaccine was applied in the meningitis belt without identification of the serogroup. With the appearance of the W135 strain in 2003, however, the determination of serogroup before vaccination is important to select an effective vaccine and avoid misspending of limited funds.
Why Was This Study Done?
Because there are few laboratories in the affected countries and epidemiological surveillance systems are inadequate, it is difficult for health authorities to mount a rapid and effective vaccination campaign in response to an outbreak. In addition, because the two main bacteria (meningococcus and pneumococcus) that cause meningitis require different antibiotic treatments, it is important for doctors to find out quickly which bacteria is causing an individual case. The authors of this study wanted to develop a rapid and easy test that can tell whether meningococcus is the cause of a particular case of meningitis, and if so, which group of meningococcus is involved. As most outbreaks in the meningitis belt occur in rural areas that are distant from well-equipped medical laboratories, it was necessary to develop a test that can be carried out at the patient's bedside by nurses, does not require refrigeration or laboratory equipment, and is highly accurate in distinguishing among the different groups of meningococcus.
What Did the Researchers Do and Find?
The researchers have developed a rapid test to determine whether a patient's meningitis is caused by one of the four most common groups of meningococcus circulating in Africa. The test is done on the patient's spinal fluid, which is obtained by a lumbar puncture (spinal tap) as part of the usual evaluation of a patient thought to have meningitis. The test uses two paper strips, also called dipsticks (one for groups A and W135/Y, and the other for groups C and Y), that can be placed in two separate tubes of the patient's spinal fluid. After several minutes, the appearance of red lines on the dipsticks shows whether one of the four groups of meningococcus is present. The dipsticks can be produced in large quantities and relatively cheaply. The researchers showed that the test dipsticks are stable for weeks in hot weather, and are therefore practical for bedside use in resource-poor settings. They examined the test on stored spinal fluid from patients in Niger and found that the dipstick test was able to identify the correct group of meningococcus more than 95% of the time for the three groups represented in these specimens (the results were compared to a standard DNA test or culture that are highly accurate for identifying the type of bacteria present but much more complicated and expensive).
What Do These Findings Mean?
The new dipstick test for meningococcal meningitis represents a major advance for health-care workers in remote locations affected by meningitis epidemics. This test can be stored without refrigeration and used at bedside in the hot temperatures typical of the African savannah during the meningitis season. The dipsticks are easier to use than currently available test kits, give more rapid results, and are more accurate in telling the difference between group Y and the increasingly important group W135. Further research is needed to determine whether the test can be used with other clinical specimens (such as blood or urine), and whether the test is dependable for detecting group C meningococcus, which is common in Europe but rare in Africa. Nonetheless, the dipstick test promises to be an important tool for guiding individual treatment decisions as well as public health actions, including vaccine selection, against the perennial threat of epidemic meningitis.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030337.
World Health Organization fact sheet on meningococcal meningitis
PATH Meningitis Vaccine Project
US Centers for Disease Control and Prevention page on meningococcal disease
doi:10.1371/journal.pmed.0030337
PMCID: PMC1563501  PMID: 16953658
11.  The haematuria clinic--referral patterns in Northern Ireland. 
The Ulster Medical Journal  1998;67(1):25-28.
One hundred consecutive patients with haematuria were seen over a three month period at the haematuria clinic, Belfast City Hospital. 14% of patients were found to have transitional cell carcinoma of the urinary bladder; all of these presented with frank haematuria and were over 50 years of age. No malignancy was detected in the microscopic haematuria group. 14% of patients with macroscopic haematuria held back for longer than one month before seeking advice from their general practitioner. 23% with macroscopic and 30% with microscopic haematuria had their symptoms noted by the general practitioner for more than a month before they were referred for investigation. The waiting time for initial investigation at the haematuria clinic took longer than six weeks in 52% with macroscopic and 39% with microscopic haematuria. Our study has identified a high-risk group who need immediate referral and investigation. The importance of patient education, rapid referral by general practitioners and also the need to increase the capacity of the haematuria clinic are emphasized.
PMCID: PMC2448693  PMID: 9652195
12.  Phase contrast microscopic examination of urinary erythrocytes to localise source of bleeding: an overlooked technique? 
Journal of Clinical Pathology  1993;46(7):642-645.
AIMS--To localise the source of bleeding in the urinary tract in patients presenting with haematuria. METHODS--Urine samples were obtained from 109 patients with symptoms referable to the urinary tract. The sample was examined for the presence of red blood cells by phase contrast microscopy (PCM) and the proportion of dysmorphic and isomorphic red blood cells was determined. If more than 20% of the red blood cells were dysmorphic a glomerular origin for the site of bleeding was suspected; if less than 20% of the red blood cells were isomorphic a non-glomerular origin was suspected. Phase contrast microscopy and clinical findings were correlated. RESULTS--The correct bleeding site was shown in 27 of 30 (90%) patients with glomerulopathy and in all 17 patients with bleeding from the lower urinary tract, indicating that this method of analysis has a sensitivity of 90% and specificity of 100% for detecting the glomerular source of bleeding. CONCLUSIONS--The examination of urine for dysmorphic and isomorphic red blood cells by phase contrast microscopy is strongly recommended in routine clinical practice for the detection of glomerular and non-glomerular lesions. This technique may avoid unnecessary investigations for the diagnosis of the site of bleeding in patients with haematuria.
Images
PMCID: PMC501394  PMID: 8157752
13.  Urinary red-cell morphology during exercise. 
Midstream urine samples were examined by phase-contrast microscopy before and immediately after 48 subjects participated in a long-distance run. Minor abnormalities were found in six samples before exercise. Eighteen subjects developed proteinuria and five haematuria on dipstick testing after exercise. Forty-four subjects had increased urinary red-cell counts after exercise; of these, 33 had counts above the normal range (800/ml). In all subjects urinary red cells were dysmorphic both before and after exercise, indicating a glomerular source. Ten subjects developed red-cell casts and 42 showed an increase in hyaline and hyaline-granular casts after exercise. There were modest increases in urinary white-cell counts in 35 subjects but little change in urine pH or osmolality with exercise. This study confirms that urinary red-cell counts commonly increase appreciably after exercise. The dysmorphic appearance of the red cells together with the presence of red-cell casts indicates a glomerular source for this common form of exercise haematuria.
Images
PMCID: PMC1500573  PMID: 6814599
14.  Can urine dipstick testing for urinary tract infection at point of care reduce laboratory workload? 
Journal of Clinical Pathology  2005;58(9):951-954.
Aim: The University Hospitals of Leicester NHS Trust microbiology laboratory receives 150 000 urine samples each year, approximately 80% of which prove to be culture negative. The aim of this study was to reduce the proportion of culture negative urines arriving in the laboratory, by producing local evidence based guidelines for the use of urine dipstick testing at point of care within the trust’s three acute hospitals.
Methods: One thousand and seventy six unborated urine samples were dipstick tested at the point of care using an automatic strip reader. Quantitative results for the four infection associated markers—leucocyte esterase, nitrite, blood, and protein—were compared with the results of conventional laboratory microscopy and culture.
Results: The performance of different marker combinations was calculated against the routine laboratory methods. One hundred and seventy five (16.3%) samples were negative for all four markers. Of these dipstick negative samples, only three (1.7% of all true positives) were positive by culture. The absence of all four infection associated markers was found to have a greater than 98% negative predictive value and a sensitivity and specificity of 98.3% and 19.2%, respectively.
Conclusions: A urinary dipstick testing algorithm for infection associated markers was derived for use in hospital patients to screen out negative urines. Two years after distributing the algorithm and promoting access to reagent strips and strip readers, a reduction in the urine workload has been seen against an otherwise increasing laboratory specimen load.
doi:10.1136/jcp.2004.025429
PMCID: PMC1770822  PMID: 16126876
algorithm; infection associated markers; urinary tract infection; urine dipstick testing; workload
15.  Management of macroscopic haematuria in the emergency department 
Emergency Medicine Journal : EMJ  2007;24(6):385-390.
Macroscopic haematuria is a commonly seen condition in the emergency department (ED), which has a variety of causes. However, most importantly, macroscopic haematuria has a high diagnostic yield for urological malignancy. 30% of patients presenting with painless haematuria are found to have a malignancy. The majority of these patients can be managed in the outpatient setting. This review of current literature suggests a management pathway that can be used in the ED. A literature search was done using Medline, PubMed and Google. In men aged >60 years, the positive predictive value of macroscopic haematuria for urological malignancy is 22.1%, and in women of the same age it is 8.3%. In terms of the need for follow‐up investigation, a single episode of haematuria is equally important as recurrent episodes. Baseline investigation in the ED includes full blood count, urea and electrolyte levels, midstream urine dipstick, β human chorionic gonadotrophin, and formal microscopy, culture and sensitivities. Treatment of macroscopic haematuria aims at RESP—Resuscitation, Ensuring, Safe and Prompt. Indications for admission include clot retention, cardiovascular instability, uncontrolled pain, sepsis, acute renal failure, coagulopathy, severe comorbidity, heavy haematuria or social restrictions. Discharged patients should drink plenty of clear fluids and return for further medical attention if the following occur: clot retention, worsening haematuria despite adequate fluid intake, uncontrolled pain or fever, or inability to cope at home. Follow‐up by a urological team should be promptly arranged, ideally within the 2‐week cancer referral target.
doi:10.1136/emj.2006.042457
PMCID: PMC2658267  PMID: 17513531
16.  Low quality of routine microscopy for malaria at different levels of the health system in Dar es Salaam 
Malaria Journal  2011;10:332.
Background
Laboratory capacity to confirm malaria cases in Tanzania is low and presumptive treatment of malaria is being practiced widely. In malaria endemic areas WHO now recommends systematic laboratory testing when suspecting malaria. Currently, the use of Rapid Diagnostic Tests (RDTs) is recommended for the diagnosis of malaria in lower level peripheral facilities, but not in health centres and hospitals. In this study, the following parameters were evaluated: (1) the quality of routine microscopy, and (2) the effects of RDT implementation on the positivity rate of malaria test results at three levels of the health system in Dar es Salaam, Tanzania.
Methods
During a baseline cross-sectional survey, routine blood slides were randomly picked from 12 urban public health facilities in Dar es Salaam, Tanzania. Sensitivity and specificity of routine slides were assessed against expert microscopy. In March 2007, following training of health workers, RDTs were introduced in nine public health facilities (three hospitals, three health centres and three dispensaries) in a near-to-programmatic way, while three control health facilities continued using microscopy. The monthly malaria positivity rates (PR) recorded in health statistics registers were collected before (routine microscopy) and after (routine RDTs) the intervention in all facilities.
Results
At baseline, 53% of blood slides were reported as positive by the routine laboratories, whereas only 2% were positive by expert microscopy. Sensitivity of routine microscopy was 71.4% and specificity was 47.3%. Positive and negative predictive values were 2.8% and 98.7%, respectively. Median parasitaemia was only three parasites per 200 white blood cells (WBC) by routine microscopy compared to 1226 parasites per 200 WBC by expert microscopy. Before RDT implementation, the mean test positivity rates using routine microscopy were 43% in hospitals, 62% in health centres and 58% in dispensaries. After RDT implementation, mean positivity rates using routine RDTs were 6%, 7% and 8%, respectively. The sensitivity and specificity of RDTs using expert microscopy as reference were 97.0% and 96.8%. The positivity rate of routine microscopy remained the same in the three control facilities: 71% before versus 72% after. Two cross-sectional health facility surveys confirmed that the parasite rate in febrile patients was low in Dar es Salaam during both the rainy season (13.6%) and the dry season (3.3%).
Conclusions
The quality of routine microscopy was poor in all health facilities, regardless of their level. Over-diagnosis was massive, with many false positive results reported as very low parasitaemia (1 to 5 parasites per 200 WBC). RDTs should replace microscopy as first-line diagnostic tool for malaria in all settings, especially in hospitals where the potential for saving lives is greatest.
doi:10.1186/1475-2875-10-332
PMCID: PMC3217957  PMID: 22047131
17.  Significance of microhaematuria in young adults. 
The medical records of 1000 asymptomatic male air force personnel were examined retrospectively for the results of 15 yearly examinations of urinary sediment. The study covered the period 1968-82, beginning with the subjects aged 18-33 years. The cumulative incidence of two to four or more red blood cells per high power field found at one or more examinations was 38.7% after an average of 12.2 yearly examinations per person. In 161 subjects two to four or more red blood cells per high power field were found at two or more yearly examinations within a five year period. Intravenous pyelography in 58 cases disclosed asymptomatic nephrolithiasis in six. Cystoscopy performed in 11 cases identified one patient with urethritis, one with a vesical calculus, and one with transitional cell carcinoma of the bladder. Two years before diagnosis the patient with carcinoma had had a single transient finding of 10-12 red blood cells per high power field which was not investigated further. Cystoscopy was performed after an episode of macroscopic haematuria. Renal biopsy in one subject with recurrent microhaematuria and trace proteinuria disclosed focal glomerulonephritis. None of the remaining subjects with microhaematuria developed hypertension or proteinuria, and at the end of the study period all were active and free of urinary symptoms. The observed cumulative incidence of urological neoplasms at 15 years (0.1%) was consistent with that expected in Israeli men aged 18-40 (0.09%). Hence microhaematuria detected during a screening examination probably should not be regarded as a specific sign of a significant lesion and does not of itself warrant urological investigation in adults aged 40 or less.
PMCID: PMC1444134  PMID: 6418299
18.  Danish general practitioners' estimation of urinary albumin concentration in the detection of proteinuria and microalbuminuria. 
BACKGROUND. Microalbuminuria may predict proteinuria and increased mortality in non-insulin dependent diabetic patients. Early detection of microalbuminuria may therefore be essential. AIM. The primary objective of this study was to describe the association between the presence of albuminuria in diabetic patients as detected by general practitioners using conventional reagent strip dipstick tests for albumin, and the urinary albumin concentration as measured in a hospital laboratory. METHOD. A total of 675 newly diagnosed diabetic patients aged 40 years or over were included in the Danish study, diabetes care in general practice. Data for urinary albumin concentration from a morning urine sample and the results of three consecutive dipstick tests for albumin were collected for 417 patients. RESULTS. When defining elevated urinary albumin concentration as 200 mg l-1 or more (proteinuria) the finding of at least one positive test out of the three dipstick tests for albumin had a diagnostic sensitivity of 73% and a specificity of 89%. When the microalbuminuric range (15.0 to 199.9 mg l-1) was added to the definition of renal involvement, the sensitivity of the dipstick test became as low as 28% with a specificity of 96%. CONCLUSION. It is essential for general practitioners to be able to identify proteinuric patients. To achieve this by means of the conventional dipstick test, general practice procedures need to be improved. As it is becoming increasingly well-documented that microalbuminuric non-insulin dependent diabetic patients may benefit from pharmacological treatment of even slight arterial hypertension and heart failure, it seems reasonable to suggest that the use of dipsticks for albumin in general practice be replaced by laboratory quantitative determination of urinary albumin concentration in a morning urine sample.
PMCID: PMC1239138  PMID: 7702885
19.  Detection of Parasite-Specific DNA in Urine Sediment Obtained by Filtration Differentiates between Single and Mixed Infections of Schistosoma mansoni and S. haematobium from Endemic Areas in Ghana 
PLoS ONE  2014;9(3):e91144.
Differential diagnosis of Schistosoma mansoni and S. haematobium, which often occur sympatrically in Africa, requires both urine and stool and the procedures are low in sensitivity. The standard diagnostic tests, such as Kato-Katz (KK) for S. mansoni eggs and presence of haematuria for S. haematobium both lack sensitivity, produce false-negative results and show reduced accuracy with decreasing intensity of infection. The need for a single diagnostic test with high sensitivity and specificity for both parasites is important as many African countries are implementing Mass Drug Administration (MDA) following recommendations of the World Health Organization (WHO). Eighty-six samples of urine sediment obtained by filtration were collected from a group of 5–23 years old people from an endemic area of southern Ghana. DNA was extracted from the urine sediment on filter paper from which a species-specific repeat fragment was amplified by polymerase chain reaction (PCR) with specific primers for S. mansoni and for S. haematobium. Additionally, all participants were tested by KK (stool) and dipstick for haematuria. Diagnostic parameters for all three tests were analyzed statistically. Amplification of species-specific DNA by PCR showed much higher sensitivity (99%–100%) and specificity (100%) compared to KK and haematuria (sensitivity: 76% and 30% respectively) for both schistosome species. The same pattern was observed when the data were stratified for age group and sex specific analysis. In addition PCR amplification detected DNA from 11 individuals infected with both parasites who were negative by KK and haematuria. This approach of detecting parasite specific DNA from either or both species in a single urine specimen is a practical advantage that avoids the need for two specimens and is more effective than standard tests including those based on serology. This promises to improve the effectiveness of surveillance of MDA control programs of schistosomiasis.
doi:10.1371/journal.pone.0091144
PMCID: PMC3954594  PMID: 24632992
20.  Ultrasonography compared with intravenous urography in the investigation of adults with haematuria. 
BMJ : British Medical Journal  1990;301(6760):1074-1076.
OBJECTIVE--To compare ultrasonography with intravenous urography in the investigation of adults with haematuria. DESIGN--Prospective study entailing the examination of all patients with both investigations concurrently. The investigations were performed independently on routine lists by different duty radiologists. Each was aware of the details of the request form but not of the findings of the other investigation. SETTING--Radiology department of a teaching hospital. PATIENTS--155 Consecutive adult patients (aged 18-93) referred from general practitioners and hospital outpatient clinics with a history of haematuria. FOLLOW UP--When results of both examinations proved normal no clinical or radiological follow up was sought. All abnormal findings of either investigation were correlated with results of subsequent imaging studies or operative findings. RESULTS--81 Patients (52%) had normal findings on urography and ultrasonography. Overall, the findings of ultrasonography concurred with those of urography in 144 cases (93%). Among the discrepant findings of the two investigations ultrasonography missed two ureteric calculi; one was in a non-dilated ureter, and in the other case ultrasonography detected the secondary ureteric dilatation. Ultrasound examination alone detected four bladder tumours not visible on urography with sizes ranging from 5 to 21 mm, representing one fifth of the 20 cystoscopically proved bladder tumours detected in the series. Ultrasonography detected all the 22 neoplastic lesions discovered in the study (20 bladder, two renal). Ultrasonography clarified the nature of renal masses evident in three urograms (simple cysts). CONCLUSIONS--Ultrasonography is a safe and accurate method of investigating the urinary tract in adults with haematuria. When combined with a single plain abdominal radiograph it proved to be superior to urography as the primary imaging study in this series. Ultrasonography should certainly be preferred to urography if cystoscopy is not planned. No urothelial tumours of the upper urinary tract were found in the series, reflecting their rarity. For those patients in whom ultrasonography and plain radiography have shown no abnormality and in whom cystoscopic appearances are normal urography would be advisable to exclude urothelial tumours of the upper urinary tract.
PMCID: PMC1664237  PMID: 2249070
21.  Renal function in men with lower urinary tract symptoms at first presentation to urology out-patient department. 
AIM: Current national guidelines state that it is mandatory to perform an estimation of renal function in all males with lower urinary tract symptoms (LUTS). As national audit evidence suggests this is not general practice, we have carried out a study to assess the value of routine testing of renal function in this group. PATIENTS AND METHODS: Serum creatinine or urea was measured in 213 consecutive men presenting to the urology out-patient department with lower urinary tract symptoms. Risk factors for renal dysfunction such as large post-void residual volume, proteinuria, microscopic haematuria, diabetes mellitus and cardiovascular disease were noted. RESULTS: Twelve of 213 patients had abnormal results. One 90-year-old had a raised serum urea but was found to have a normal creatinine level. Ten of the remaining 11 patients would have had their renal dysfunction predicted by history, examination or bedside tests. CONCLUSIONS: Routine measurement of creatinine or urea in men presenting with LUTS with no other risk factors could be considered purely a health screening test. It is suggested that it should no longer be considered as mandatory, in this situation, but used only if specifically indicated. A urine flow rate would be a more useful test in reaching a diagnosis and planning treatment.
doi:10.1308/003588404323043319
PMCID: PMC1964183  PMID: 15140303
22.  Sensitivities and specificities of diagnostic tests and infection prevalence of Schistosoma haematobium estimated from data on adults in villages northwest of Accra in Ghana 
Substantial uncertainties surround the sensitivities and specificities of diagnostic techniques for urinary schistosomiasis. We used Latent Class (LC) modeling to address this problem. In this study 220 adults in three villages northwest of Accra in Ghana were examined using five Schistosoma haematobium diagnostic measures: microscopic examination of urine for detection of S. haematobium eggs, dipsticks for detection of haematuria, tests for circulating antigens, serological antibody tests and ultrasound scans of the urinary system. Testing of the LC model indicated non-invariance of the performance of the diagnostic tests across different age groups while measurement invariance held for males and females and for the three villages. We therefore recommend the use of LC models for comparison between, and the identification of, the most accurate schistosomiasis diagnostic tests. Furthermore, microscopy and haematuria dipsticks were indicated through these models as the most appropriate techniques for detection of S. haematobium infection.
PMCID: PMC2726788  PMID: 19270295
23.  Community-based study on CKD subjects and the associated risk factors 
Nephrology Dialysis Transplantation  2009;24(7):2117-2123.
Background. The study was performed to investigate the prevalence, awareness and the risk factors of chronic kidney disease (CKD) in the community population in Shanghai, China.
Methods. A total of 2596 residents were randomly recruited from the community population in Shanghai, China. All were screened for albuminuria, haematuria, morning spot urine albumin-to-creatinine ratio and renal function. Serum creatinine, uric acid, cholesterol, triglyceride and haemoglobin were assessed. A simplified MDRD equation was used to estimate the glomerular filtration rate (eGFR). All studied subjects were screened by kidney ultrasound. Haematuria, if present in the morning spot urine dipstick test, was confirmed by microscopy. The associations among the demographic characteristics, health characteristics and indicators of kidney damage were examined.
Results. Two thousand five hundred and fifty-four residents (n = 2554), after giving informed consent and with complete data, were entered into this study. Albuminuria and haematuria were detected in 6.3% and 1.2% of all the studied subjects, respectively, whereas decreased kidney function was found in 5.8% of all studied subjects. Approximately 11.8% of subjects had at least one indicator of kidney damage. The rate of awareness of CKD was 8.2%. The logistic regression model showed that age, central obesity, hypertension, diabetes, anaemia, hyperuricaemia and nephrolithiasis each contributed to the development of CKD.
Conclusion. This is the first Shanghai community-based epidemiological study data on Chinese CKD patients. The prevalence of CKD in the community population in Shanghai is 11.8%, and the rate of awareness of CKD is 8.2%. All the factors including age, central obesity, hypertension, diabetes, anaemia, hyperuricaemia and nephrolithiasis are positively correlated with the development of CKD in our studied subjects.
doi:10.1093/ndt/gfn767
PMCID: PMC2698090  PMID: 19193736
awareness; chronic kidney disease; epidemiology; prevalence; risk factors
24.  Automated Detection of Infectious Disease Outbreaks in Hospitals: A Retrospective Cohort Study 
PLoS Medicine  2010;7(2):e1000238.
Susan Huang and colleagues describe an automated statistical software, WHONET-SaTScan, its application in a hospital, and the potential it has to identify hospital infection clusters that had escaped routine detection.
Background
Detection of outbreaks of hospital-acquired infections is often based on simple rules, such as the occurrence of three new cases of a single pathogen in two weeks on the same ward. These rules typically focus on only a few pathogens, and they do not account for the pathogens' underlying prevalence, the normal random variation in rates, and clusters that may occur beyond a single ward, such as those associated with specialty services. Ideally, outbreak detection programs should evaluate many pathogens, using a wide array of data sources.
Methods and Findings
We applied a space-time permutation scan statistic to microbiology data from patients admitted to a 750-bed academic medical center in 2002–2006, using WHONET-SaTScan laboratory information software from the World Health Organization (WHO) Collaborating Centre for Surveillance of Antimicrobial Resistance. We evaluated patients' first isolates for each potential pathogenic species. In order to evaluate hospital-associated infections, only pathogens first isolated >2 d after admission were included. Clusters were sought daily across the entire hospital, as well as in hospital wards, specialty services, and using similar antimicrobial susceptibility profiles. We assessed clusters that had a likelihood of occurring by chance less than once per year. For methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE), WHONET-SaTScan–generated clusters were compared to those previously identified by the Infection Control program, which were based on a rule-based criterion of three occurrences in two weeks in the same ward. Two hospital epidemiologists independently classified each cluster's importance. From 2002 to 2006, WHONET-SaTScan found 59 clusters involving 2–27 patients (median 4). Clusters were identified by antimicrobial resistance profile (41%), wards (29%), service (13%), and hospital-wide assessments (17%). WHONET-SaTScan rapidly detected the two previously known gram-negative pathogen clusters. Compared to rule-based thresholds, WHONET-SaTScan considered only one of 73 previously designated MRSA clusters and 0 of 87 VRE clusters as episodes statistically unlikely to have occurred by chance. WHONET-SaTScan identified six MRSA and four VRE clusters that were previously unknown. Epidemiologists considered more than 95% of the 59 detected clusters to merit consideration, with 27% warranting active investigation or intervention.
Conclusions
Automated statistical software identified hospital clusters that had escaped routine detection. It also classified many previously identified clusters as events likely to occur because of normal random fluctuations. This automated method has the potential to provide valuable real-time guidance both by identifying otherwise unrecognized outbreaks and by preventing the unnecessary implementation of resource-intensive infection control measures that interfere with regular patient care.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Admission to a hospital is often a life-saving necessity—individuals injured in a road accident, for example, may need immediate medical and surgical attention if they are to survive. Unfortunately, many patients acquire infections, some of which are life-threatening, during their stay in a hospital. The World Health Organization has estimated that, globally, 8.7% of hospital patients develop hospital-acquired infections (infections that are identified more than two days after admission to hospital). In the US alone, 2 million people develop a hospital-acquired infection every year, often an infection of a surgical wound, or a urinary tract or lung infection. Infections are common among hospital patients because increasing age or underlying illnesses can reduce immunity to infection and because many medical and surgical procedures bypass the body's natural protective barriers. In addition, poor infection control practices can facilitate the transmission of bacteria—including meticillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE)—and other infectious agents (pathogens) between patients.
Why Was This Study Done?
Sometimes, the number of cases of hospital-acquired infections increases unexpectedly or a new infection emerges. Such clusters account for relatively few health care–associated infections, but, because they may arise from the transmission of a pathogen within a hospital, they need to be rapidly identified and measures implemented (for example, isolation of affected patients) to stop transmission if an outbreak is confirmed. Currently, the detection of clusters of hospital-acquired infections is based on simple rules, such as the occurrence of three new cases of a single pathogen in two weeks on the same ward. This rule-based approach relies on the human eye to detect infection clusters within microbiology data (information collected on the pathogens isolated from patients), it focuses on a few pathogens, and it does not consider the random variation in infection rates or the possibility that clusters might be associated with shared facilities rather than with individual wards. In this study, the researchers test whether an automated statistical system can detect outbreaks of hospital-acquired infections quickly and accurately.
What Did the Researchers Do and Find?
The researchers combined two software packages used to track diseases in populations to create the WHONET-SaTScan cluster detection tool. They then compared the clusters of hospital-acquired infection identified by the new tool in microbiology data from a 750-bed US academic medical center with those generated by the hospital's infection control program, which was largely based on the simple rule described above. WHONET-SaTScan found 59 clusters of infection that occurred between 2002 and 2006, about three-quarters of which were identified by characteristics other than a ward-based location. Nearly half the cluster alerts were generated on the basis of shared antibiotic susceptibility patterns. Although WHONET-SaTScan identified all the clusters previously identified by the hospital's infection control program, it classified most of these clusters as likely to be the result of normal random variations in infection rates rather than the result of “true” outbreaks. By contrast, the hospital's infection control department only identified three of the 59 statistically significant clusters identified by WHONET-SaTScan. Furthermore, the new tool identified six previously unknown MRSA outbreaks and four previously unknown VRE outbreaks. Finally, two hospital epidemiologists (scientists who study diseases in populations) classified 95% of the clusters detected by WHONET-SaTScan as worthy of consideration by the hospital infection control team and a quarter of the clusters as warranting active investigation or intervention.
What Do These Findings Mean?
These findings suggest that automated statistical software should be able to detect clusters of hospital-acquired infections that would escape detection using routine rule-based systems. Importantly, they also suggest that an automated system would be able to discount a large number of supposed outbreaks identified by rule-based systems. These findings need to be confirmed in other settings and in prospective studies in which the outcomes of clusters detected with WHONET-SaTScan are carefully analyzed. For now, however, these findings suggest that automated statistical tools could provide hospital infection control experts with valuable real-time guidance by identifying outbreaks that would be missed by routine detection methods and by preventing the implementation of intensive and costly infection control measures in situations where they are unnecessary.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000238.
The World Health Organization's Prevention of Hospital-Acquired Infections, A Practical Guide contains detailed information on all aspects of hospital-acquired infections
MedlinePlus provides links to information on infection control in hospitals (in English and Spanish)
The US Centers for Disease Control and Prevention also provides information on infectious diseases in health care settings (in English and Spanish)
The WHONET/Baclink software and the SatScan software, the two components of WHONET-SaTScan are both available on the internet (the WHONET-SaTScan cluster detection tool is freely available as part of the version of WHONET/BacLink released June 2009)
doi:10.1371/journal.pmed.1000238
PMCID: PMC2826381  PMID: 20186274
25.  Impact of Xpert MTB/RIF for TB Diagnosis in a Primary Care Clinic with High TB and HIV Prevalence in South Africa: A Pragmatic Randomised Trial 
PLoS Medicine  2014;11(11):e1001760.
Helen Cox and colleagues investigate the impact Xpert MTB/RIF for diagnosing patients with presumptive tuberculosis in a large primary care clinic in Khayelitsha, Cape Town.
Please see later in the article for the Editors' Summary
Background
Xpert MTB/RIF is approved for use in tuberculosis (TB) and rifampicin-resistance diagnosis. However, data are limited on the impact of Xpert under routine conditions in settings with high TB burden.
Methods and Findings
A pragmatic prospective cluster-randomised trial of Xpert for all individuals with presumptive (symptomatic) TB compared to the routine diagnostic algorithm of sputum microscopy and limited use of culture was conducted in a large TB/HIV primary care clinic. The primary outcome was the proportion of bacteriologically confirmed TB cases not initiating TB treatment by 3 mo after presentation. Secondary outcomes included time to TB treatment and mortality. Unblinded randomisation occurred on a weekly basis. Xpert and smear microscopy were performed on site. Analysis was both by intention to treat (ITT) and per protocol.
Between 7 September 2010 and 28 October 2011, 1,985 participants were assigned to the Xpert (n = 982) and routine (n = 1,003) diagnostic algorithms (ITT analysis); 882 received Xpert and 1,063 routine (per protocol analysis). 13% (32/257) of individuals with bacteriologically confirmed TB (smear, culture, or Xpert) did not initiate treatment by 3 mo after presentation in the Xpert arm, compared to 25% (41/167) in the routine arm (ITT analysis, risk ratio 0.51, 95% CI 0.33–0.77, p = 0.0052).
The yield of bacteriologically confirmed TB cases among patients with presumptive TB was 17% (167/1,003) with routine diagnosis and 26% (257/982) with Xpert diagnosis (ITT analysis, risk ratio 1.57, 95% CI 1.32–1.87, p<0.001). This difference in diagnosis rates resulted in a higher rate of treatment initiation in the Xpert arm: 23% (229/1,003) and 28% (277/982) in the routine and Xpert arms, respectively (ITT analysis, risk ratio 1.24, 95% CI 1.06–1.44, p = 0.013). Time to treatment initiation was improved overall (ITT analysis, hazard ratio 0.76, 95% CI 0.63–0.92, p = 0.005) and among HIV-infected participants (ITT analysis, hazard ratio 0.67, 95% CI 0.53–0.85, p = 0.001). There was no difference in 6-mo mortality with Xpert versus routine diagnosis. Study limitations included incorrect intervention allocation for a high proportion of participants and that the study was conducted in a single clinic.
Conclusions
These data suggest that in this routine primary care setting, use of Xpert to diagnose TB increased the number of individuals with bacteriologically confirmed TB who were treated by 3 mo and reduced time to treatment initiation, particularly among HIV-infected participants.
Trial registration
Pan African Clinical Trials Registry PACTR201010000255244
Please see later in the article for the Editors' Summary
Editors' Summary
Background
In 2012, about 8.6 million people developed active tuberculosis (TB)—a contagious mycobacterial disease that usually affects the lungs—and at least 1.3 million people died from the disease. Most of these deaths were in low- and middle-income countries, and a fifth were in HIV-positive individuals, who are particularly susceptible to TB. Mycobacterium tuberculosis, the bacterium that causes TB, is spread in airborne droplets when people with active disease cough or sneeze. The characteristic symptoms of TB include a cough, weight loss, and night sweats. Diagnostic tests for TB include microscopic examination of sputum (mucus coughed up from the lungs), growth (culture) of M. tuberculosis from sputum, and molecular tests (for example, the automated Xpert MTB/RIF test) that rapidly and accurately detect M. tuberculosis in sputum and determine its antibiotic resistance. TB can be cured by taking several antibiotics daily for at least six months, although the emergence of multidrug-resistant TB is making the disease harder to treat.
Why Was This Study Done?
To improve TB control, active disease needs to be diagnosed and treated quickly. However, sputum microscopy, the mainstay of TB diagnosis in many high-burden settings, fails to identify up to half of infected people, and mycobacterial culture (the “gold standard” of TB diagnosis) is slow and often unavailable in resource-limited settings. In late 2010, the World Health Organization recommended the routine use of the Xpert MTB/RIF test (Xpert) for TB diagnosis, and several low- and middle-income countries are now scaling up access to Xpert in their national TB control programs. But although Xpert performs well in ideal conditions, little is known about the impact of its implementation in routine (real-life) settings. In this pragmatic cluster-randomized trial, the researchers assess the health impacts of Xpert in a large TB/HIV primary health care clinic in South Africa, an upper-middle-income country that began to scale up access to Xpert for individuals showing symptoms of TB (individuals with presumptive TB) in 2011. A pragmatic trial asks whether an intervention works under real-life conditions; a cluster-randomized trial randomly assigns groups of people to receive alternative interventions and compares outcomes in the differently treated “clusters.”
What Did the Researchers Do and Find?
The researchers assigned everyone with presumptive TB attending a TB/HIV primary health care clinic in Cape Town to receive either Xpert for TB diagnosis or routine sputum microscopy and limited culture. Specifically, Xpert was requested on the routine laboratory request forms for individuals attending the clinic during randomly designated Xpert weeks but not during randomly designated routine testing weeks. During the 51-week trial, 982 individuals were assigned to the Xpert arm, and 1,003 were assigned to the routine testing arm, but because clinic staff sometimes failed to request Xpert during Xpert weeks, only 882 participants in the Xpert arm received the intervention. In an “intention to treat” analysis (an analysis that considers the outcomes of all the participants in a trial whether or not they received their assigned intervention), 13% of bacteriologically confirmed TB cases in the Xpert arm did not initiate TB treatment by three months after enrollment (the trial's primary outcome) compared to 25% in the routine testing arm. The proportion of participants with microbiologically confirmed TB and the proportion initiating TB treatment were higher in the Xpert arm than in the routine testing arm. Finally, the time to treatment initiation was lower in the Xpert arm than in the routine testing arm, particularly among HIV-infected participants.
What Do These Findings Mean?
These findings show that, in this primary health care setting, the provision of Xpert for TB diagnosis in individuals with presumptive TB provided benefits over testing that relied primarily on sputum microscopy. Notably, these benefits were seen even though a substantial proportion of individuals assigned to the Xpert intervention did not actually receive an Xpert test. The pragmatic nature of this trial, which aimed to minimize clinic disruption, and other aspects of the trial design may limit the accuracy and generalizability of these findings. Moreover, further studies are needed to discover whether the use of Xpert in real-life settings reduces the burden of TB illness and death over the long term. Nevertheless, these findings suggest that the implementation of Xpert has the potential to improve the outcomes of TB control programs and may also improve outcomes for individuals.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001760.
The World Health Organization provides information (in several languages) on all aspects of tuberculosis, including general information on tuberculosis diagnostics and specific information on the roll-out of the Xpert MTB/RIF test; further information about the World Health Organization's endorsement of Xpert MTB/RIF is included in a Strategic and Technical Advisory Group for Tuberculosis report; the “Global Tuberculosis Report 2013” provides information about tuberculosis around the world, including in South Africa
The Stop TB Partnership is working towards tuberculosis elimination and provides patient stories about tuberculosis (in English and Spanish); the Tuberculosis Vaccine Initiative (a not-for-profit organization) also provides personal stories about tuberculosis
The US Centers for Disease Control and Prevention has information about tuberculosis and its diagnosis (in English and Spanish)
The US National Institute of Allergy and Infectious Diseases also has detailed information on all aspects of tuberculosis
The South African National Tuberculosis Management Guidelines 2014 are available
The Foundation for Innovative New Diagnostics, a not-for-profit organization that helps to develop and introduce new diagnostic tests for tuberculosis, malaria, and neglected tropical diseases, has detailed information about the Xpert MTB/RIF test
More information about TB, HIV, and drug-resistant TB treatment in Khayelitsha, Cape Town, South Africa are provided by Médecins sans Frontières, South Africa
doi:10.1371/journal.pmed.1001760
PMCID: PMC4244039  PMID: 25423041

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