Human leptospirosis trends, the Netherlands, 1925-2008.

To increase knowledge of leptospirosis in the Netherlands and identify changing trends of this disease over time, we analyzed historical passive surveillance reports for an 84-year period (1925-2008). We found that 2,553 mainly severe leptospirosis cases were diagnosed (average annual incidence rate 0.25 cases/100,000 population). The overall case-fatality rate for patients with reported leptospirosis was 6.5% but decreased over the period, probably because of improved treatment. Ninety percent of reported leptospirosis cases were in male patients. Most autochthonous leptospirosis infections were associated with recreational exposures, but 15.5% of the cases were attributed to accidents that resulted in injury and to concomitant water contact. Since the end of the 1950s, the proportion of imported infections gradually increased, reaching 53.1% of the total during 2005-2008. Most (80.1%) imported infections were associated with sporting and adventurous vacation activities.

Systematic review and meta-analysis: rapid diagnostic tests versus placental histology, microscopy and PCR for malaria in pregnant women.

BACKGROUND: During pregnancy, malaria infection with Plasmodium falciparum or Plasmodium vivax is related to adverse maternal health and poor birth outcomes. Diagnosis of malaria, during pregnancy, is complicated by the absence or low parasite densities in peripheral blood. Diagnostic methods, other than microscopy, are needed for detection of placental malaria. Therefore, the diagnostic accuracy of rapid diagnostic tests (RDTs), detecting antigen, and molecular techniques (PCR), detecting DNA, for the diagnosis of Plasmodium infections in pregnancy was systematically reviewed. METHODS: MEDLINE, EMBASE and Web of Science were searched for studies assessing the diagnostic accuracy of RDTs, PCR, microscopy of peripheral and placental blood and placental histology for the detection of malaria infection (all species) in pregnant women. RESULTS: The results of 49 studies were analysed in metandi (Stata), of which the majority described P. falciparum infections. Although both placental and peripheral blood microscopy cannot reliably replace histology as a reference standard for placental P. falciparum infection, many studies compared RDTs and PCR to these tests. The proportion of microscopy positives in placental blood (sensitivity) detected by peripheral blood microscopy, RDTs and PCR are respectively 72% [95% CI 62-80], 81% [95% CI 55-93] and 94% [95% CI 86-98]. The proportion of placental blood microscopy negative women that were negative in peripheral blood microscopy, RDTs and PCR (specificity) are 98% [95% CI 95-99], 94% [95% CI 76-99] and 77% [95% CI 71-82]. Based on the current data, it was not possible to determine if the false positives in RDTs and PCR are caused by sequestered parasites in the placenta that are not detected by placental microscopy. CONCLUSION: The findings suggest that RDTs and PCR may have good performance characteristics to serve as alternatives for the diagnosis of malaria in pregnancy, besides any other limitations and practical considerations concerning the use of these tests. Nevertheless, more studies with placental histology as reference test are urgently required to reliably determine the accuracy of RDTs and PCR for the diagnosis of placental malaria. P. vivax-infections have been neglected in diagnostic test accuracy studies of malaria in pregnancy.

Costs of relaparotomy on-demand versus planned relaparotomy in patients with severe peritonitis: an economic evaluation within a randomized controlled trial.

INTRODUCTION: Results of the first randomized trial comparing on-demand versus planned-relaparotomy strategy in patients with severe peritonitis (RELAP trial) indicated no clear differences in primary outcomes. We now report the full economic evaluation for this trial, including detailed methods, nonmedical costs, further differentiated cost calculations, and robustness of different assumptions in sensitivity analyses. METHODS: An economic evaluation was conducted from a societal perspective alongside a randomized controlled trial in 229 patients with severe secondary peritonitis and an acute physiology and chronic health evaluation (APACHE)-II score >or=11 from two academic and five regional teaching hospitals in the Netherlands. After the index laparotomy, patients were randomly allocated to an on-demand or a planned-relaparotomy strategy. Primary resource-utilization data were used to estimate mean total costs per patient during the index admission and after discharge until 1 year after the index operation. Overall differences in costs between the on-demand relaparotomy strategy and the planned strategy, as well as relative differences across several clinical subgroups, were evaluated. RESULTS: Costs were substantially lower in the on-demand group (mean, 65,768 euro versus 83,450 euro per patient in the planned group; mean absolute difference, 17,682 euro; 95% CI, 5,062 euro to e29,004 euro). Relative differences in mean total costs per patient (approximately 21%) were robust to various alternative assumptions. Planned relaparotomy consistently generated more costs across the whole range of different courses of disease (quick recovery and few resources used on one end of the spectrum; slow recovery and many resources used on the other end). This difference in costs between the two surgical strategies also did not vary significantly across several clinical subgroups. CONCLUSIONS: The reduction in societal costs renders the on-demand strategy a more-efficient relaparotomy strategy in patients with severe peritonitis. These differences were found across the full range of healthcare resources as well as across patients with different courses of disease. TRIAL REGISTRATION: ISRCTN51729393.

Diagnosing vasovagal syncope based on quantitative history-taking: validation of the Calgary Syncope Symptom Score.

AIMS: It can be difficult to distinguish vasovagal syncope, the most common cause of transient loss of consciousness (T-LOC), from other causes of syncope by history taking. The Calgary Syncope Symptom Score (Calgary Score) is a tool developed for this purpose. We studied its performance in a series of patients presenting with T-LOC. METHODS AND RESULTS: We calculated the Calgary Score for 380 patients presenting with T-LOC to a number of departments of our university hospital. Diagnoses of vasovagal syncope based on the Calgary Score were then compared with the final diagnosis, obtained after additional testing and 2 years of follow-up. The sensitivity of the Calgary Score was 87% (95% CI: 82-91%), at a specificity of 32% (95% CI: 24-40%). Most items of the Calgary Score were less discriminative in our study group than in the original population. Incorrectly labelling patients with syncope as vasovagal was most common in patients with psychogenic pseudosyncope (specificity 21%) but also occurred in patients with cardiac syncope (specificity 32%). CONCLUSION: The sensitivity of the Calgary Score was comparable with the one in the original study, but its specificity was much lower, limiting its value in patients presenting with T-LOC in a general hospital setting.

High diagnostic yield and accuracy of history, physical examination, and ECG in patients with transient loss of consciousness in FAST: the Fainting Assessment study.

BACKGROUND: Transient loss of consciousness (TLOC) is a common clinical problem. OBJECTIVE: The aim of this study was to assess the yield and accuracy of the initial evaluation, consisting of standardized history, physical examination, and ECG performed by attending physicians in patients with TLOC. METHODS AND RESULTS: Five hundred and three adult patients (mean age 53 +/- 19; 56% male) presenting with TLOC to the Academic Medical Center Amsterdam between February 2000 and May 2002 were included in this study. After initial evaluation, the physician made a certain, a highly likely (>80% certain), or no initial diagnosis. Initially undiagnosed patients received additional cardiological testing, additional history taking, and autonomic function tests. After 2 years of follow-up, an expert committee determined the final diagnoses. Two-year follow-up was obtained in 99% of the patients. The yield of certain diagnoses after the initial evaluation was 24%, increasing to 63% after including the highly likely diagnoses. The diagnostic accuracy of the initial certain diagnoses was 93% (95% CI 87-97%), decreasing to 88% (95% CI 84-91%) after inclusion of the initial highly likely diagnoses. CONCLUSION: Attending physicians can make a diagnosis based on initial evaluation in 63% of patients with TLOC, with an overall diagnostic accuracy of 88%. The use of additional testing, beyond history, physical examination, and ECG can be avoided in many patients with TLOC.

Factors associated with posttraumatic stress symptoms in a prospective cohort of patients after abdominal sepsis: a nomogram.

OBJECTIVE: To determine to what extent patients who have survived abdominal sepsis suffer from symptoms of posttraumatic stress disorder (PTSD) and depression, and to identify potential risk factors for PTSD symptoms. DESIGN AND SETTING: PTSD and depression symptoms were measured using the Impact of Events Scale-Revised (IES-R), the Post-Traumatic Symptom Scale 10 (PTSS-10) and the Beck Depression Inventory II (BDI-II). PATIENTS AND PARTICIPANTS: A total of 135 peritonitis patients were eligible for this study, of whom 107 (80%) patients completed the questionnaire. The median APACHE-II score was 14 (range 12-16), and 89% were admitted to the ICU. MEASUREMENTS AND RESULTS: The proportion of patients with "moderate" PTSD symptom scores was 28% (95% CI 20-37), whilst 10% (95% CI 6-17) of patients had "high" PTSD symptom scores. Only 5% (95% CI 2-12) of the patients expressed severe depression symptoms. Factors associated with increased PTSD symptoms in a multivariate ordinal regression model were younger age (0.74 per 10 years older, p=0.082), length of ICU stay (OR=1.4 per doubling of duration, p=0.003) and having some (OR=4.9, p=0.06) or many (OR=55.5, p<0.001) traumatic memories of the ICU or hospital stay. CONCLUSION: As many as 38% of patients after abdominal sepsis report elevated levels of PTSD symptoms on at least one of the questionnaires. Our nomogram may assist in identifying patients at increased risk for developing symptoms of PTSD.

Quality of life within one year following presentation after transient loss of consciousness.

The purpose of this study was to examine (1) changes in quality of life (QoL) within 1 year after presentation with transient loss of consciousness (TLOC) and (2) which factors are predictive of these changes. This study was part of the Fainting Assessment Study (FAST), which assessed diagnostic strategies in patients with TLOC. Adult patients presenting to Academic Medical Center, Amsterdam, The Netherlands, with TLOC were included in the study. QoL was assessed with the generic Short Form 36 and the disease-specific Syncope Functional Status Questionnaire at presentation and 1 year of follow-up. Of 468 included patients, 82% completed questionnaires at presentation and 72% after 1-year follow-up. QoL improved on 7 of 8 subscales of the Short Form 36 and on all summary scales of the Syncope Functional Status Questionnaire. Older age, recurrence, higher level of co-morbidity, and a neurologic or psychogenic diagnosis were predictive of poorer QoL. In conclusion, QoL in patients with TLOC improves significantly over time. Physicians should particularly pay attention to patients who are older, have recurrent episodes, a neurologic or psychogenic diagnosis, and a higher level of co-morbidity because these patients are vulnerable to a relatively poorer QoL.

Continuous event recorders did not affect anxiety or quality of life in patients with palpitations.

OBJECTIVES: Palpitations can generate feelings of anxiety and decrease quality of life (QoL) due to fear of a cardiac abnormality. Continuous event recorders (CERs) have proven to be successful in diagnosing causes of palpitations but may affect patient QoL and anxiety. The aim is to determine anxiety and health-related (HR)-QoL and evaluate the burden of carrying a CER in general practice populations. STUDY DESIGN AND SETTING: Patients (n=244) participated in a randomized trial. One group (n=127) carried a CER during 4 weeks. One hundred and seventeen patients formed the usual care (UC) group. State-Trait Anxiety Inventory (STAI) and the Short Form-36 (SF-36) were administered at study inclusion, after 1, 6 months. RESULTS: At baseline, patients reported greater anxiety and lower QoL than healthy populations. The CER group had three times more cardiac diagnoses than the UC group. No differences were found between CER group and UC group at 6 weeks. At 6 months, the UC group showed QoL improvement and less anxiety compared to the CER group. Type of diagnosis had influence, but did not fully explain these differences. CONCLUSION: A CER does not negatively influence anxiety or QoL. Better outcomes in the UC group might be attributed to less cardiac diagnosis and more emphasis on psychological well-being.

Reliability, validity and responsiveness of the syncope functional status questionnaire.

BACKGROUND: Patients with transient loss of consciousness (TLOC) have poor health-related quality of life (HR-QoL). OBJECTIVE: To test the reliability, validity, and responsiveness of the disease-specific Syncope Functional Status HR-QoL Questionnaire (SFSQ), which yields two summary scales--impairment score (IS) and fear-worry score (FWS). DESIGN: Cohort-study. PARTICIPANTS: 503 adult patients presenting with TLOC. MEASUREMENTS: HR-QoL was assessed using the SFSQ and the Short Form-36 (SF-36) after presentation and 1 year later. To test reliability, score distributions, internal consistency, and test-retest reliability were assessed. To assess validity, scores on the SFSQ and the SF-36 were compared. Clinical validity was tested using known-group comparison. Responsiveness was assessed by comparing changes in SFSQ scores with changes in health status and clinical condition. RESULTS: Response rate was 82% at baseline and 72% at 1-year follow-up. For all scales the full range of scores was seen. Score distributions were asymmetrical. Internal consistency was high (alpha = 0.88 for IS, 0.92 for FWS). Test-retest reliability was moderate to good for individual items and high for summary scales (inter-class correlation = 0.78 for both IS and FWS). Correlations between SFSQ scores and the SF-36 were modest. The SFSQ did not discriminate between patients differing in age and gender but did discriminate between patients differing in number of episodes and comorbid conditions. Changes in SFSQ scores were related to changes in health status and the presence of recurrences but did not vary by TLOC diagnosis. CONCLUSION: The SFSQ is an adequately reliable, valid, and responsive measure to assess HR-QoL in patients with TLOC.

Long-term prevalence of post-traumatic stress disorder symptoms in patients after secondary peritonitis.

INTRODUCTION: The aim of this study was to determine the long-term prevalence of post-traumatic stress disorder (PTSD) symptomology in patients following secondary peritonitis and to determine whether the prevalence of PTSD-related symptoms differed between patients admitted to the intensive care unit (ICU) and patients admitted only to the surgical ward. METHOD: A retrospective cohort of consecutive patients treated for secondary peritonitis was sent a postal survey containing a self-report questionnaire, namely the Post-traumatic Stress Syndrome 10-question inventory (PTSS-10). From a database of 278 patients undergoing surgery for secondary peritonitis between 1994 and 2000, 131 patients were long-term survivors (follow-up period at least four years) and were eligible for inclusion in our study, conducted at a tertiary referral hospital in Amsterdam, The Netherlands. RESULTS: The response rate was 86%, yielding a cohort of 100 patients; 61% of these patients had been admitted to the ICU. PTSD-related symptoms were found in 24% (95% confidence interval 17% to 33%) of patients when a PTSS-10 score of 35 was chosen as the cutoff, whereas the prevalence of PTSD symptomology when borderline patients scoring 27 points or more were included was 38% (95% confidence interval 29% to 48%). In a multivariate analyses controlling for age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, number of relaparotomies and length of hospital stay, the likelihood of ICU-admitted patients having PTSD symptomology was 4.3 times higher (95% confidence interval 1.11 to 16.5) than patients not admitted to the ICU, using a PTSS-10 score cutoff of 35 or greater. Older patients and males were less likely to report PTSD symptoms. CONCLUSION: Nearly a quarter of patients receiving surgical treatment for secondary peritonitis developed PTSD symptoms. Patients admitted to the ICU were at significantly greater risk for having PTSD symptoms after adjusting for baseline differences, in particular age.

Health related quality of life six months following surgical treatment for secondary peritonitis--using the EQ-5D questionnaire.

BACKGROUND: To compare health related quality of life (HR-QoL) in patients surgically treated for secondary peritonitis to that of a healthy population. And to prospectively identify factors associated with poorer (lower) HR-QoL. DESIGN: A prospective cohort of secondary peritonitis patients was mailed the EQ-5D and EQ-VAS 6-months following initial laparotomy. SETTING: Multicenter study in two academic and seven regional teaching hospitals. PATIENTS: 130 of the 155 eligible patients (84%) responded to the HR-QoL questionnaires. RESULTS: HR-QoL was significantly worse on all dimensions in peritonitis patients than in a healthy reference population. Peritonitis characteristics at initial presentation were not associated with HR-QoL at six months. A more complicated course of the disease leading to longer hospitalization times and patients with an enterostomy had a negative impact on the mobility (p = 0.02), self-care (p < 0.001) and daily activities: (p = 0.01). In a multivariate analysis for the EQ-VAS every doubling of hospital stay decreases the EQ-VAS by 3.8 points (p = 0.015). Morbidity during the six-month follow-up was not found to be predictive for the EQ-5D or EQ-VAS. CONCLUSION: Six months following initial surgery, patients with secondary peritonitis report more problems in HR-QoL than a healthy reference population. Unfavorable disease characteristics at initial presentation were not predictive for poorer HR-QoL, but a more complicated course of the disease was most predictive of HR-QoL at 6 months.

Comparison of on-demand vs planned relaparotomy strategy in patients with severe peritonitis: a randomized trial.

CONTEXT: In patients with severe secondary peritonitis, there are 2 surgical treatment strategies following an initial emergency laparotomy: planned relaparotomy and relaparotomy only when the patient's condition demands it ("on-demand"). The on-demand strategy may reduce mortality, morbidity, health care utilization, and costs. However, randomized trials have not been performed. OBJECTIVE: To compare patient outcome, health care utilization, and costs of on-demand and planned relaparotomy. DESIGN, SETTING, AND PATIENTS: Randomized, nonblinded clinical trial at 2 academic and 5 regional teaching hospitals in the Netherlands from November 2001 through February 2005. Patients had severe secondary peritonitis and an Acute Physiology and Chronic Health Evaluation (APACHE-II) score of 11 or greater. INTERVENTION: Random allocation to on-demand or planned relaparotomy strategy. MAIN OUTCOME MEASURES: The primary end point was death and/or peritonitis-related morbidity within a 12-month follow-up period. Secondary end points included health care utilization and costs. RESULTS: A total of 232 patients (116 on-demand and 116 planned) were randomized. One patient in the on-demand group was excluded due to an operative diagnosis of pancreatitis and 3 in each group withdrew or were lost to follow-up. There was no significant difference in primary end point (57% on-demand [n = 64] vs 65% planned [n = 73]; P = .25) or in mortality alone (29% on-demand [n = 32] vs 36% planned [n = 41]; P = .22) or morbidity alone (40% on-demand [n = 32] vs 44% planned [n = 32]; P = .58). A total of 42% of the on-demand patients had a relaparotomy vs 94% of the planned relaparotomy group. A total of 31% of first relaparotomies were negative in the on-demand group vs 66% in the planned group (P <.001). Patients in the on-demand group had shorter median intensive care unit stays (7 vs 11 days; P = .001) and shorter median hospital stays (27 vs 35 days; P = .008). Direct medical costs per patient were reduced by 23% using the on-demand strategy. CONCLUSION: Patients in the on-demand relaparotomy group did not have a significantly lower rate of death or major peritonitis-related morbidity compared with the planned relaparotomy group but did have a substantial reduction in relaparotomies, health care utilization, and medical costs. TRIAL REGISTRATION: http://isrctn.org Identifier: ISRCTN51729393.

Clinical factors associated with quality of life in patients with transient loss of consciousness.

INTRODUCTION: Transient loss of consciousness (TLOC) is common and can be lethal. Although the patients with the most prevalent causes of TLOC have a benign prognosis, morbidity is considerable. Aim of this article, therefore, was to compare the generic quality of life (QoL) of patients presenting with TLOC with that of the general population, to compare the disease-specific QoL with that of an American referral sample, and to examine which sociodemographic and clinical factors are associated with QoL in these patients. METHODS: This study was part of the fainting assessment study (FAST), which assessed diagnostic strategies for adult patients presenting with TLOC to the Academic Medical Center Amsterdam, between February 2000 and May 2002. The generic short form-36 (SF-36) health survey and the disease-specific syncope functional status questionnaire (SFSQ) were used to assess QoL. RESULTS: Of 468 included patients, 82% completed the questionnaires. Patients with TLOC scored poorer on all scales of the SF-36 than the Dutch population, with effect sizes ranging from 0.43 to 1.11 (>0.5 = moderate effect; >0.8 = large effect). The SFSQ indicated mean impairment in 33% of the listed activities (such as driving). Female gender, higher level of comorbidity, shorter duration of complaints, having had more than one syncopal episode, and the presence of presyncopal episodes were associated with poorer QoL. CONCLUSION: TLOC seriously affects QoL, especially in patients with a recent onset of clinical symptoms and those suffering from both syncopal and presyncopal episodes.

Operating Characteristics of a Tuberculosis Screening Tool for People Living with HIV in Out-Patient HIV Care and Treatment Services, Rwanda.

BACKGROUND: The World Health Organization (WHO) 2010 guidelines for intensified tuberculosis (TB) case finding (ICF) among people living with HIV (PLHIV) includes a recommendation that PLHIV receive routine TB screening. Since 2005, the Rwandan Ministry of Health has been using a five-question screening tool. Our study objective was to assess the operating characteristics of the tool designed to identify PLHIV with presumptive TB as measured against a composite reference standard, including bacteriologically confirmed TB. METHODS: In a cross-sectional study, the TB screening tool was routinely administered at enrolment in outpatient HIV care and treatment services at seven public health facilities. From March to September 2011, study enrollees were examined for TB disease irrespective of TB screening outcome. The examination consisted of a chest radiograph (CXR), three sputum smears (SS), sputum culture (SC) and polymerase chain reaction line-probe assay (Hain test). PLHIV were classified as having "laboratory-confirmed TB" with positive results on SS for acid-fast bacilli, SC on Lowenstein-Jensen medium, or a Hain test. RESULTS: Overall, 1,767 patients were enrolled and screened of which; 1,017 (57.6%) were female, median age was 33 (IQR, 27-41), and median CD4+ cell count was 385 (IQR, 229-563) cells/mm3. Of the patients screened, 138 (7.8%) were diagnosed with TB of which; 125 (90.5%) were laboratory-confirmed pulmonary TB. Of 404 (22.9%) patients who screened positive and 1,363 (77.1%) who screened negative, 79 (19.5%) and 59 (4.3%), respectively, were diagnosed with TB. For laboratory-confirmed TB, the tool had a sensitivity of 54.4% (95% CI 45.3-63.3), specificity of 79.5% (95% CI 77.5-81.5), PPV of 16.8% and NPV of 95.8%. CONCLUSION: TB prevalence among PLHIV newly enrolling into HIV care and treatment was 65 times greater than the overall population prevalence. However, the performance of the tool was poorer than the predicted performance of the WHO recommended TB screening questions.

HIV surveillance in Rwanda: readiness assessment to transition from antenatal care-based to prevention of mother-to-child transmission program-based HIV surveillance.

BACKGROUND: In 2013, the World Health Organization (WHO) recommended that for efficiency and ethical considerations, transitioning from antenatal clinic-based surveillance to prevention of mother-to-child transmission (PMTCT)-based routine data should be investigated. An assessment of the readiness for this transition was carried out in Rwanda in 2011 and 2013. METHODS: This assessment applied the WHO recommended method. Individual HIV rapid testing at site was compared to antenatal surveillance results at all existing 30 sites, involving 13 292 women. In addition, PMTCT HIV testing quality assurance and PMTCT routine data quality were assessed at 27 out of the 30 sites. RESULTS: All sentinel sites provided PMTCT services and had a high uptake of HIV testing (more than 90%). At all sites, PMTCT data were recorded in longitudinal and standardized antenatal clinic registers. Twenty-six out of 27 sites had HIV result completeness above 90%. A positive percentage agreement of 97.5% and negative percentage agreement of 99.9% were observed between routine PMTCT and sero-surveillance HIV test results. Of 27 sites, 25 scored more than 80% in all phases of HIV testing quality assurance. CONCLUSIONS: According to WHO standards, Rwanda antenatal care HIV sero-surveillance is ready to transition to PMTCT-based sero-surveillance.

Long-term effectiveness of combination antiretroviral therapy and prevalence of HIV drug resistance in HIV-1-infected children and adolescents in Rwanda.

OBJECTIVE: To determine the long-term outcomes of treatment and prevalence of genotypic drug resistance in children and adolescents on combination antiretroviral therapy. METHODS: A cross-sectional study (September 2009 to October 2010) in which clinical, immunologic and virologic outcomes were assessed at a single-study visit and through patient records in a cohort of HIV-infected children and adolescents. Risk factors for clinical and immunologic responses and virologic outcome were evaluated using logistic regression, and the accuracy of clinical and immunologic criteria in identifying virologic failure was assessed. RESULTS: Four hundred twenty-four patients were enrolled with a median age of 10.8 years (range: 1.7-18.8) and a median duration on combination antiretroviral therapy of 3.4 years (range: 1.0-8.1). Thirty-three percent were stunted and 17% underweight. Eighty-four percent (95% confidence interval: 79-87) of children >5 years had CD4 ≥350 cells/mm and in 74% (95% confidence interval: 62-84) of younger children CD4% was ≥25. CD4 values and age at combination antiretroviral therapy initiation were independently associated with CD4 outcomes; 124 (29%) had HIV-1 RNA ≥1000 copies/mL, with no significant predictors. Sensitivity for weight-for-age and height-for-age and CD4 cells (<350/mm) remained under 50% (15-42%); CD4 cells showed the best specificity, ranging from 91% to 97%. Of 52 samples tested, ≥1 mutations were observed in 91% (nucleoside reverse transcriptase inhibitors) and 95% (non-nucleoside reverse transcriptase inhibitors); 1 to 2 thymidine analogue-associated mutations were detected in 16 (31%) and ≥3 thymidine analogue-associated mutations in 7 (13%). CONCLUSION: Nearly 1 in 3 children showed virologic failure, and >10% of the subgroup of children with treatment failure in whom genotyping was performed demonstrated multiple HIV drug resistance mutations. Neither clinical condition nor CD4 cells were good indicators for treatment failure.

Safety and effectiveness of combination antiretroviral therapy during the first year of treatment in HIV-1 infected Rwandan children: a prospective study.

BACKGROUND: With increased availability of paediatric combination antiretroviral therapy (cART) in resource limited settings, cART outcomes and factors associated with outcomes should be assessed. METHODS: HIV-infected children <15 years of age, initiating cART in Kigali, Rwanda, were followed for 18 months. Prospective clinical and laboratory assessments included weight-for-age (WAZ) and height-for-age (HAZ) z-scores, complete blood cell count, liver transaminases, creatinine and lipid profiles, CD4 T-cell count/percent, and plasma HIV-1 RNA concentration. Clinical success was defined as WAZ and WAZ >-2, immunological success as CD4 cells ≥500/mm3 and ≥25% for respectively children over 5 years and under 5 years, and virological success as a plasma HIV-1 RNA concentration <40 copies/mL. RESULTS: Between March 2008 and December 2009, 123 HIV-infected children were included. The median (interquartile (IQR) age at cART initiation was 7.4 (3.2, 11.5) years; 40% were <5 years and 54% were female. Mean (95% confidence interval (95%CI)) HAZ and WAZ at baseline were -2.01 (-2.23, -1.80) and -1.73 (-1.95, -1.50) respectively and rose to -1.75 (-1.98, -1.51) and -1.17 (-1.38, -0.96) after 12 months of cART. The median (IQR) CD4 T-cell values for children <5 and ≥5 years of age were 20% (13, 28) and 337 (236, 484) cells/mm3 respectively, and increased to 36% (28, 41) and 620 (375, 880) cells/mm3. After 12 months of cART, 24% of children had a detectable viral load, including 16% with virological failure (HIV-RNA>1000 c/mL). Older age at cART initiation, poor adherence, and exposure to antiretrovirals around birth were associated with virological failure. A third (33%) of children had side effects (by self-report or clinical assessment), but only 9% experienced a severe side effect requiring a cART regimen change. CONCLUSIONS: cART in Rwandan HIV-infected children was successful but success might be improved further by initiating cART as early as possible, optimizing adherence and optimizing management of side effects.

"Let's talk about sex": a qualitative study of Rwandan adolescents' views on sex and HIV.

OBJECTIVE: This qualitative study explored the views and experiences of adolescents with perinatally acquired HIV in Kigali, Rwanda, regarding sex, love, marriage, children and hope for the future. DESIGN: The study enrolled 42 adolescents who had received combination antiretroviral therapy for at least 12 months, and a selection of their primary caregivers. Study methods included 3 multiple day workshops consisting of role-playing and focus group discussions (FGDs) with adolescents, 8 in-depth interviews with adolescents, and one FGD with caregivers. RESULTS: The adolescents reported experiencing similar sexual needs and dilemmas as most other adolescents, but with an added layer of complexity due to fears related to HIV transmission and/or rejection by partners. They desired more advice from their parents/caregivers on these topics. Although they struggled with aspects of sex, love, marriage and having children, most agreed that they would find love, be married and have children in the future. The two most discussed HIV-related anxieties were how and when to disclose to a (potential) sex/marriage partner and whether to have children. However, most adolescents felt that they had a right to love and be loved, and were aware of prevention-of-mother-to-child-transmission (PMTCT) options in Rwanda. Adolescents generally spoke about their future role in society in a positive manner. CONCLUSION: Strengthening the life skills of HIV-positive adolescents, especially around HIV disclosure and reduction of HIV transmission, as well as the support skills of parents/caregivers, may not only reduce onward HIV transmission but also improve quality of life by reducing anxiety.

Hepatitis B virus prevalence and vaccine response in HIV-infected children and adolescents on combination antiretroviral therapy in Kigali, Rwanda.

OBJECTIVE: The aim of this study was to determine the prevalence of hepatitis B virus (HBV) infection in a cohort of HIV-infected Rwandan children and adolescents on combination antiretroviral therapy (cART), and the success rate of HBV vaccination in those children found to be HBV negative. METHODS: HIV-infected children and adolescents (age 8-17 years) receiving cART with CD4 T-cells count ≥200 cells/mm and/or ≥15% and without prior HBV vaccination (by history, vaccination cards and clinic records) underwent serologic testing for past (negative HBV surface antigen [HBsAg] with positive antibody to HBV core antigen [cAb] and to HBsAg [anti-HBs]) or active HBV infection (positive HBsAg). Children with any positive HBV serologic tests were excluded from further vaccination; all others completed 3 HBV immunizations with 10 µg of ENGERIX-B. Anti-HBs titer was measured 4-6 weeks after the last immunization. RESULTS: Of 88 children, 6 (7%) children had active HBV infection and 8 (9%) had past HBV infection. The median (interquartile range) age, CD4 T-cell count and cART duration were 12.3 (10.1-13.9) years, 626 (503 to 942) cells/mm and 1.9 (1.5-2.7) years, respectively. Seventeen children had detectable plasma HIV-1 RNA. Seventy-3 children completed 3 immunizations with median (interquartile range) postimmunization anti-HBs concentration of 151 mIU/mL (1.03-650). Overall, 52 children (71%, 95% confidence interval: 61-82) developed a protective anti-HBs response. HIV-1 RNA and CD4 T-cell count were independent predictors of a protective anti-HBs response. Protective anti-HBs response was achieved in 82% of children with undetectable HIV-1 RNA and 77% with CD4 T cells ≥350/mm. CONCLUSIONS: The substantial HBV prevalence in this cohort suggests that HIV-infected Rwandan children should be screened for HBV before cART initiation. HIV viral suppression and CD4 T cells ≥350/mm favored the likelihood of a protective response after HBV vaccination.

Prospective evaluation of three rapid diagnostic tests for diagnosis of human leptospirosis.

BACKGROUND: Diagnosis of leptospirosis by the microscopic agglutination test (MAT) or by culture is confined to specialized laboratories. Although ELISA techniques are more common, they still require laboratory facilities. Rapid Diagnostic Tests (RDTs) can be used for easy point-of-care diagnosis. This study aims to evaluate the diagnostic performance of the RDTs LeptoTek Dri Dot, LeptoTek Lateral Flow, and Leptocheck-WB, prospectively. METHODOLOGY: During 2001 to 2012, one or two of the RDTs at the same time have been applied prior to routine diagnostics (MAT, ELISA and culture) on serum specimens from participants sent in for leptospirosis diagnosis. The case definition was based on MAT, ELISA and culture results. Participants not fulfilling the case definition were considered not to have leptospirosis. The diagnostic accuracy was determined based on the 1(st) submitted sample and paired samples, either in an overall analysis or stratified according to days post onset of illness. RESULTS: The overall sensitivity and specificity for the LeptoTek Dri Dot was 75% respectively 96%, for the LeptoTek Lateral Flow 78% respectively 95%, and for the Leptocheck-WB 78% respectively 98%. Based on the 1(st) submitted sample the sensitivity was low (51% for LeptoTek Dri Dot, 69% for LeptoTek Lateral Flow, and 55% for Leptocheck-WB), but substantially increased when the results of paired samples were combined, although accompanied by a lower specificity (82% respectively 91% for LeptoTek Dri Dot, 86% respectively 84% for LeptoTek Lateral Flow, and 80% respectively 93% for Leptocheck-WB). CONCLUSIONS: All three tests present antibody tests contributing to the diagnosis of leptospirosis, thus supporting clinical suspicion and contributing to awareness. Since the overall sensitivity of the tested RDTs did not exceed 80%, one should be cautious to rely only on an RDT result, and confirmation by reference tests is strongly recommended.