Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis: a diagnostic evaluation study.

OBJECTIVES: The diagnosis of extrapulmonary tuberculosis (EPTB) is often made on clinical suspicion alone, resulting in both under- and overdiagnosis and relatively poor outcomes. In this study, we evaluated the clinical utility of the Xpert MTB/RIF on routinely collected extrapulmonary specimens in Ethiopia. METHODS: This study was carried out at Jimma University Specialized Hospital, Southwest Ethiopia. Extrapulmonary specimens were collected from 572 patients clinically suspected of suffering from EPTB. All specimens were tested for TB by smear microscopy, culture, and Xpert MTB/RIF. The diagnostic accuracy of Xpert MTB/RIF was calculated and compared to a composite reference standard (CRS), comprising clinical and laboratory results. RESULTS: In total, 572 extrapulmonary specimens (279 lymph node, 159 pleural, 80 peritoneal, 45 cerebrospinal, and nine pericardial fluids) were tested. The pooled sensitivity and specificity of Xpert MTB/RIF were calculated to be 75% (95% CI 70-80) and 98% (95% CI 97-100) respectively when compared to the CRS. The highest sensitivity was documented for lymph node specimens (90%; 95% CI 86-94), moderate sensitivity for cerebrospinal fluid (53%; 95% CI 28-79), while the sensitivity was lowest for pleural (30%; 95% CI 17-44) and peritoneal (32%; 95% CI 12-51) fluids. Xpert MTB/RIF in addition detected rifampicin resistance in 13 patients, in perfect agreement with results from the line probe assay. CONCLUSIONS: Xpert MTB/RIF may be used as initial diagnostic tool for testing of lymph node specimens from patients suspected of having TB lymphadenitis. The added value of Xpert MTB/RIF to diagnose pleural or peritoneal TB is limited by its poor sensitivity.

HIV testing for key populations in Europe: A decade of technological innovation and patient empowerment complement the role of health care professionals.

OBJECTIVES: With persisting high numbers of new HIV diagnoses in Europe, HIV testing remains an important aspect of HIV prevention. The traditional centralized and medicalized HIV testing approach has been complemented with newly developed and evaluated non-traditional approaches. Two important factors guided this process: technological innovation and empowerment of the patient. METHODS: We present a matrix to develop an HIV testing approach, and elaborate on three commonly used ones: community based testing, self-testing, and self-sampling. Despite non-traditional HIV testing approaches, barriers for testing remain. A potential disadvantage for users is the risk for false-reactive test results. As users receive an orientation test result, a reactive result should be confirmed. Another issue is the window phase, which is longer for some orientation tests compared to a traditional, laboratory-based test. RESULTS: Future implementation of non-traditional HIV testing approaches will depend on legal frameworks throughout Europe. Community testing centers may additionally improve empowerment of key populations by expanding their portfolio to testing and treatment for sexually transmitted infections. Community engagement and ownership may imply a shrinking role for health care providers, but they remain crucial actors for personalized information, counselling and referral to specialized HIV-care for many people. CONCLUSIONS: A highly effective HIV testing strategy to reduce undiagnosed people living with HIV in Europe is needed. Any approach, chosen according to the principles outlined in this paper, should reach the right people, diagnose them in the most accurate way, and optimize linkage to care.

Syphilis reinfections pose problems for syphilis diagnosis in Antwerp, Belgium - 1992 to 2012.

Persons with multiple syphilis reinfections may play an important role in syphilis transmission. We analysed all syphilis tests carried out for people attending the HIV/sexually transmitted infection (STI) clinic at the Institute of Tropical Medicine, Antwerp, Belgium, from 1992 to 2012 to evaluate the extent to which syphilis reinfections were contributing to the syphilis epidemic in Antwerp. We then characterised the features of the syphilis infections in individuals with five or more episodes of syphilis. A total of 729 syphilis episodes were diagnosed in 454 persons. The majority of syphilis episodes occurred in people who had more than one episode of syphilis (445/729; 61%). A total of 10 individuals had five or more episodes of syphilis diagnosed over this period. All were men who have sex with men, HIV positive and on antiretroviral therapy. They had a total of 52 episodes of syphilis diagnosed and treated. In 38/42 of the episodes of repeat syphilis in these 10 individuals, they presented without any signs or symptoms of syphilis. Given that the majority of cases of incident syphilis in our clinic were persons with reinfections and that they frequently presented without signs of symptoms of syphilis, there is a strong case for frequent and repeated screening in all persons with a diagnosis of syphilis.

Incidence of HCV and sexually transmitted diseases among hiv positive msm in antwerp, belgium, 2001-2011.

Recurrent Sexually Transmitted Infections (STIs) are an indication of unsafe sexual practices and may be associated with HCV-infection among HIV-positive men who have sex with men. In a retrospective study we analysed the laboratory data of 99 HIV-positive MSM who acquired HCV during the observation period (cases) and 176 HIV-positive MSM who remained HCV negative during the observation period (controls), all followed at the HIV/STI-clinic in Antwerp, Belgium. All laboratory confirmed STI-episodes were recorded since the date of first consultation at our clinic, until the date of HCV-diagnosis of the cases. The HCV incidence varied between 0.24 (2001) and 1.36 (2011) new cases per hundred person-years, with a peak of 2.93 new cases per hundred person-years in 2009. The number of STI-episodes per person-year follow-up was significantly higher for the cases as compared to the controls for syphilis, non-LGV and LGV Chlamydia infections (p < 0.005). When considering the incidence of STIs that occurred 1 year prior to HCV conversion, all laboratory confirmed STIs remained more frequent among cases, but only the difference in syphilis incidence was statistically significant (p < 0.01). Recurrent STIs among HIV positive MSM should be considered as a behavioural and biological risk factor for acquiring HCV and should lead to intensified screening for HCV and counselling of the patient.

Sexually transmitted infections: what's new?

Since the beginning of the third millennium the incidence of Sexually Transmitted Infections (STIs) is rising in Europe and in Belgium, and this after a steady decline in the second half of last century. It concerns new or lesser known diseases such as Hepatitis C and Lymphogranuloma venereum (LGV) and 'old' diseases such as gonorrhoea and syphilis, occurring in specific risk groups. In this article we give an update of the diagnostic means and therapeutic challenges that are of interest for the clinician. Besides these (re)-emerging diseases we touch on Human Papillomavirus (HPV) and Herpes Simplex (HSV). This selection of diseases is based on the daily experience of the clinicians working in the STI clinic of the Institute of Tropical Medicine in Antwerp. Data and clinical guidelines are derived from the Scientific Institute of Public Health in Brussels, the European and American Centers for Disease Control and Prevention, and the Guidelines of the Flemish Agency for Care and Health. New evolutions in diagnostics, prevention and treatment options make it necessary to regularly update the knowledge of this group of diseases, especially when they are complicated by HIV co-infection. As the incidence of neither HIV nor STIs seem to decrease in Belgium and Europe, it remains necessary to stay aware of the state-of-the-art management.

Voluntary outreach counselling and testing for HIV and STI among men who have sex with men in Antwerp.

BACKGROUND: High risk settings for transmission of HIV and sexually transmitted infections (STI) offer an opportunity for screening of difficult to reach risk groups. METHODS: Free, anonymous counselling and testing for HIV, syphilis, Chlamydia and hepatitis B/C were offered to visitors in two selected gay venues in Antwerp, by a multidisciplinary team. Participants completed an anonymous questionnaire. The STI-test results were communicated by cell phone using standardised text messages. RESULTS: In total, 137 MSM were tested. Facilitators of risky sexual behaviour (alcohol and drug use) were reported by 34 and 21%, respectively. Four men (3%) were newly diagnosed with HIV; 25 men (18%) had an active, transmittable STI. Infected MSM were significantly less often registered with a fixed general practitioner (GP). CONCLUSIONS: Outreach testing in gay venues is a suitable method to detect MSM at risk for HIV/STI. Although the outreach approach is very labour intensive, it shows a high yield of new STI-diagnoses that are not detected in the regular health system.

Uptake of provider-initiated counselling and testing among tuberculosis suspects, Ethiopia.

SETTING: Twenty-seven health centres in Addis Ababa, Ethiopia. OBJECTIVE: To assess the uptake of human immunodeficiency virus (HIV) testing among tuberculosis (TB) suspects in Addis Ababa, and to determine reasons for non-acceptance of the test. DESIGN: From February to March 2009, new TB suspects identified in 27 health centres in Addis Ababa were offered HIV testing. Patients were interviewed by trained nurses using a pretested questionnaire. RESULT: Of the 506 TB suspects, 59% were tested for HIV and accepted the test result. Individuals with knowledge about HIV counselling and testing procedures were 2.5 times more likely to be tested than individuals with poor knowledge. TB suspects who had previously been tested for HIV were twice as likely to accept HIV testing and to receive the result of the test (OR = 2.0, 95%CI 1.4-2.9). Government employees (OR = 2.8, 95%CI 1.2-6.3) and merchants (OR = 2.7, 95%CI 1.2-5.7) were more likely to be tested for HIV as compared to jobless individuals. CONCLUSION: The TB control programme in Ethiopia should increase its educational efforts among all TB suspects, but especially among jobless individuals, to increase the uptake of HIV testing.

Hepatitis C virus infection in HIV-infected men who have sex with men: sustained rising incidence in Antwerp, Belgium, 2001-2009.

During the last decade, outbreaks of acute hepatitis C virus (HCV) infection have been reported among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) in several European countries. To study this emerging infection in MSM in Antwerp, Belgium, we reviewed all cases of newly acquired HCV infection in HIV-positive MSM followed from 2001 to 2009 at the HIV/sexually transmitted infection (STI)reference clinic of the Institute of Tropical Medicine in Antwerp. Newly acquired HCV infection was considered as certain or probable according to local definitions. During the study period, 69 episodes of newly acquired HCV infection (40 certain and 29 probable) were diagnosed in 67 HIV-infected MSM. In only 10 episodes (14%) were the patients symptomatic. The annual incidence of HCV infection in our population of HIV-infected MSM rose steadily from 0.2% in 2001 to 1.51% in 2008, and then peaked to 2.9% in 2009. For 60 episodes (87%), another STI (mainly syphilis and lymphogranuloma venereum) had been diagnosed within the six months before the diagnosis of HCV infection. All but one patient with available genotyping (n=54) were found to be infected with the difficult to-treat HCV genotypes 1 or 4. Our results therefore demonstrate the rising incidence of HCV infection in HIV-positive MSM in Antwerp, since 2001, which reached an alarming level in 2009. Targeted awareness campaigns and routine screening are urgently needed to limit further HCV spread and its expected long-term consequences.

Drug-resistant TB and HIV in resource-limited settings: what TB/HIV programmes can learn from each other.

Although management of drug resistance in tuberculosis (TB) and HIV in poor settings is in its infancy, lessons learned from TB may be relevant to HIV and vice versa. The experience with HIV has shown that rapid scale-up and lower drug pricing are achievable goals. The current prerequisites for obtaining drugs to treat multidrug-resistant TB (MDR-TB) may be too stringent given the immediacy of the MDR-TB problem. We call for a more rapid roll-out of treatment for MDR-TB with fewer administrative encumbrances and a greater sense of urgency in national TB control programmes. On the other hand, antiretroviral roll-out programmes should learn from the genesis of the MDR-TB problem; laboratory monitoring should be enhanced and compliance optimized to avoid the acquisition of additional drug resistance in HIV.

Predominance of a single genotype of Mycobacterium tuberculosis in regions of Southern Africa.

SETTING: Zimbabwe and Zambia. OBJECTIVE: To determine the genetic diversity of Mycobacterium tuberculosis strains isolated from tuberculosis (TB) patients in Zimbabwe and Zambia. DESIGN: M. tuberculosis isolates cultured from TB patients presenting at referral hospitals in Zimbabwe and health care clinics in Zambia were characterised by IS6110 genotyping and/or spoligotyping using internationally standardised methods. Genotypic data were compared to those from Cape Town and the SpolDB3.0 database. RESULTS: A predominant group of strains could be identified among 116/246 (47.2%) Zimbabwean isolates by their characteristic IS6110-banding pattern and unique spoligotype signature, where spacers 21-24, 27-30 and 33-36 were deleted. Comparison with strains from Cape Town showed that they were closely related to a family of strains present in 2.3% of Cape Town patients. Comparison of the spoligotypes with those obtained from 114 isolates from Zambia showed that 74 (65%) of these isolates had the same spoligotype signature. Spoligotypes in the SpolDB3.0 database showed that this group of strains was rarely isolated in other parts of the world, but was commonly isolated in Southern Africa. CONCLUSION: A predominant group of strains infecting approximately half of the patients in the study are major contributors to the TB epidemic in this region. We have designated this group of strains the Southern Africa 1 (SAF1) family.

Accuracy of routine diagnosis of pulmonary tuberculosis in an area of high HIV prevalence.

SETTING: Gweru Provincial Hospital, Zimbabwe. OBJECTIVES: To evaluate the accuracy of the diagnosis of pulmonary tuberculosis (PTB) in routine circumstances. DESIGN: Prospective cohort study of routinely diagnosed PTB patients between September 2000 and September 2001. RESULTS: Of 300 patients started on treatment, 161 (53.7%) were positive on direct microscopy. Of the 139 sputum-negative patients, 51 (36.7%) were positive after concentration of specimens, an additional 30 (21.6%) were positive on culture only and 58 (19.3% of the total) were negative for all laboratory investigations. There was no difference in sex, human immunodeficiency virus (HIV) serostatus or treatment outcome between the culture-positive and culture-negative presumed PTB patients. Sputum-negative patients had an increased risk of dying during treatment (RR 2.39, P = 0.015). CONCLUSIONS: The laboratory findings reveal that PTB could be confirmed in more than 80% of patients put on treatment in this setting. The treatment outcomes of the remainder did not differ from those in patients with microbiologically confirmed PTB. In a high HIV-prevalent area, clinicians rightly consider the results of the sputum microscopy test as only one element in the decision making process to put a patient on TB treatment.

A comparison of direct microscopy, the concentration method and the Mycobacteria Growth Indicator Tube for the examination of sputum for acid-fast bacilli.

SETTING: In countries with high human immunodeficiency virus prevalence, laboratory diagnosis of pulmonary tuberculosis with the standard Ziehl-Neelsen (ZN) technique is characterised by low sensitivity. OBJECTIVE: To compare test characteristics of direct microscopy, the concentration method and the Mycobacteria Growth Indicator Tube (MGIT). DESIGN: Three hundred specimens from patients diagnosed with pulmonary tuberculosis were tested for the presence of mycobacteria. Specimens were stained with ZN, decontaminated by adding 4% NaOH, concentrated by centrifuging and processed in MGIT broth. The gold standard was defined as a positive MGIT culture or a positive acid-fast bacilli smear of material obtained from a negative culture after 42 days. RESULTS: A total of 44 (14.7%) specimens were contaminated. Of 256 valid specimens, 234 (91.4%) were positive according to the gold standard definition. Decontamination and concentration of the sample increased the sensitivity of direct microscopy from 67.5% to 87.1%. Specificity remained unchanged (95.5%). The overall median time to detection of MGIT culture-positive specimens was 5 days, ranging from 4 (direct smear-positive specimens) to 12 days (concentration smear-negative specimens). CONCLUSION: The concentration method substantially increases the sensitivity of direct microscopy without much extra input. The MGIT culture technique has considerable advantages, but its relatively high contamination rate and its high cost make it a less recommendable option for widespread use in routine district laboratories.

Rate of caesarean section as a process indicator of safe-motherhood programmes: the case of Kenya.

The study assessed the value of currently-available data on the rates of caesarean section as an indicator of safe-motherhood programmes. Data, collected through the routine health information system of the Ministry of Health, Kenya, were used for analyzing the available process indicators. The methodology of this study illustrates both usefulness and limitations of readily-available healthcare information. The rate of hospital-based caesarean section was 6.3% of all births (range 0.3-37%), whereas the rate of population-based caesarean section was 0.95% (range 0.1%-4%). The rate of population-based caesarean section indicates a significant unmet need for obstetric care in the rural areas and may be a useful tool for monitoring progress on safe-motherhood initiatives in poor settings. Rates of population-based caesarean section are low in Kenya, especially in the rural areas. The rate of caesarean section may be a valuable process indicator for identifying the gaps in obstetric care and may be used for advocating improvements for healthcare to the relevant authorities.

Caesarean section rate as a process indicator of safe motherhood programmes: the case of Midlands Province.

OBJECTIVE: To evaluate the Safe Motherhood Programme of Midlands Province by means of process indicators, in particular Caesarean Section Rates (CSR), in comparison with the commonly used outcome indicator Maternal Mortality Ratio (MMR). DESIGN: A cross sectional descriptive study. SETTING: Midlands Province, Zimbabwe. MAIN OUTCOME MEASURES: Process indicators of the Safe Motherhood Programme of Midlands Province, and Maternal Mortality Ratio as an outcome indicator for the nation and the province. RESULTS: For Midlands province, a population based CSR of 3.1% was calculated for 1999, which is well below the internationally recommended 5%. The figures for the eight districts ranged considerably from 0.18 to 7.1%. The provincial institutional CSR for the same year was 8.7% (range: 0.53 to 34.5) with a significantly higher rate in private institutions (24%) as compared to government run hospitals (8%), (Chi-square 398.26, p << 0.05). The Ante Natal Care (ANC) coverage ranged from 43.9 to 75.4% with a provincial average of 62.8%. The provincial institutional delivery coverage figure was 55% (range: 49.9 to 63.6%). These findings differed from the figures obtained in the Demographic and Health Survey for the same year: ANC and institutional delivery coverages for the Midlands province were 95.2% and 73% respectively. The availability of obstetric services was well above the minimum acceptable level as defined by the World Health Organisation (WHO) guidelines. CONCLUSION: MMR is not a very useful indicator to monitor progress in Safe Motherhood Programmes. The figures are unreliable, difficult to obtain if population based, and they show a wide range, even within one given year. Process indicators, especially CSR are easily accessible and give insight in the degree of unmet obstetric need and in referral patterns within one district and the province.

Trends in caesarean section rates at a maternity hospital in Mumbai, India.

The steady rise in caesarean section rates is an emerging area of concern in mother-child healthcare and a matter of international attention, since the trend is no longer confined to western industrialized countries. Crude and caesarean section-related perinatal mortality and case-fatality rates may well serve as public-health indicators. Monitoring time-trends in caesarean section rates has been considered a useful approach in the recognition of this rapidly-changing health policy and in estimating the magnitude of this problem. The study examined the observed time-trends in caesarean section rates in relation to perinatal mortality rates and maternal case-fatality rates in a hospital setting in Mumbai, India, using 1957-1998 data on retrospective cohort. Both overall rates and those specific to type of delivery were assessed. During 1957-1998, the caesarean section rates in the Nowrosjee Wadia Maternity Hospital (NWMH) increased from 1.9% to 16%, with the most significant rise over the past decade. The perinatal mortality rate showed a significant reduction from 69 per 1,000 in 1957 to 36 per 1,000 in 1992 and remained steady in the 1990s despite the higher caesarean section rates. The caesarean section rate in the NWMH rose by almost 10-fold during 1957-1998. No improvement in perinatal outcome was observed beyond a caesarean section rate of 10%, but the perinatal mortality rate in caesarean births increased significantly due to a more liberal use of caesarean sections in preterm deliveries and those that yielded low-birth-weight babies.

Effect of a syphilis control programme on pregnancy outcome in Nairobi, Kenya.

OBJECTIVES: To assess the impact of a syphilis control programme of pregnant women on pregnancy outcome in Kenya. METHOD: Women who came to deliver to Pumwani Maternity Hospital (PMH) between April 1997 and March 1998 were tested for syphilis. Reactive rapid plasma reagin (RPR) tests were titrated and confirmed with treponema haemagglutination test (TPHA). Equal numbers of RPR and TPHA negative women were enrolled. Antenatal syphilis screening and treatment history were examined from the antenatal cards. RESULTS: Of 22,466 women giving birth, 12,414 (55%) were tested for syphilis. Out of these, 377 (3%) were RPR reactive of whom 296 were confirmed by TPHA. Syphilis sero-reactive women had a more risky sexual behaviour and coexistent HIV antibody positivity; 26% were HIV seropositive compared with 11% among syphilis negative mothers. The incidence of adverse obstetric outcome defined as low birth weight and stillbirth, was 9.5%. Syphilis seropositive women had a higher risk for adverse obstetric outcome (OR 4.1, 95% CI 2.4-7.2). Antenatal treatment of RPR reactive women significantly improved pregnancy outcome but the risk of adverse outcome remained 2.5-fold higher than the risk observed in uninfected mothers. CONCLUSIONS: These data confirm the adverse effect of syphilis on pregnancy outcome. This study also shows the efficacy of antenatal testing and prompt treatment of RPR reactive mothers on pregnancy outcome.