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Kayigamba F.R.,INTERACT | Bakker M.I.,Royal Tropical Institute | Mugisha V.,University of Kigali | de Naeyer L.,INTERACT | And 6 more authors.
PLoS ONE | Year: 2013

Background:Adherence to treatment and sputum smear conversion after 2 months of treatment are thought to be important for successful outcome of tuberculosis (TB) treatment.Methods:Retrospective cohort study of new adult TB patients diagnosed in the first quarter of 2007 at 48 clinics in Rwanda. Data were abstracted from TB registers and individual treatment charts. Logistic regression analysis was done to examine associations between baseline demographic and clinical factors and three outcomes adherence, sputum smear conversion at two months, and death.Results:Out of 725 eligible patients the treatment chart was retrieved for 581 (80%). Fifty-six (10%) of these patients took <90% of doses (defined as poor adherence). Baseline demographic characteristics were not associated with adherence to TB treatment, but adherence was lower among HIV patients not taking antiretroviral therapy (ART); p = 0.03). Sputum smear results around 2 months after start of treatment were available for 220 of 311 initially sputum-smear-positive pulmonary TB (PTB+) patients (71%); 175 (80%) had achieved sputum smear conversion. In multivariable analysis, baseline sputum smear grade (odds ratio [OR] = 2.7, 95% Confidence interval [CI] 1.1-6.6 comparing smear 3+ against 1+) and HIV infection (OR 3.0, 95%CI 1.3-6.7) were independent predictors for non-conversion at 2 months. Sixty-nine of 574 patients (12%) with known TB treatment outcomes had died. Besides other known determinants, poor adherence had an independent, strong effect on mortality (OR 3.4, 95%CI 1.4-7.8).Conclusion:HIV infection is an important independent predictor of failure of sputum smear conversion at 2 months among PTB+ patients. Poor adherence to TB treatment is an important independent determinant of mortality. © 2013 Kayigamba et al.


Borgdorff H.,Amsterdam Institute For Global Health and Development AIGHD | Tsivtsivadze E.,TNO | Verhelst R.,Ghent University | Marzorati M.,Ghent University | And 4 more authors.
ISME Journal | Year: 2014

Cervicovaginal microbiota not dominated by lactobacilli may facilitate transmission of HIV and other sexually transmitted infections (STIs), as well as miscarriages, preterm births and sepsis in pregnant women. However, little is known about the exact nature of the microbiological changes that cause these adverse outcomes. In this study, cervical samples of 174 Rwandan female sex workers were analyzed cross-sectionally using a phylogenetic microarray. Furthermore, HIV-1 RNA concentrations were measured in cervicovaginal lavages of 58 HIV-positive women among them. We identified six microbiome clusters, representing a gradient from low semi-quantitative abundance and diversity dominated by Lactobacillus crispatus (cluster R-I, with R denoting 'Rwanda') and L. iners (R-II) to intermediate (R-V) and high abundance and diversity (R-III, R-IV and R-VI) dominated by a mixture of anaerobes, including Gardnerella, Atopobium and Prevotella species. Women in cluster R-I were less likely to have HIV (P=0.03), herpes simplex virus type 2 (HSV-2; P<0.01), and high-risk human papillomavirus (HPV; P<0.01) and had no bacterial STIs (P=0.15). Statistically significant trends in prevalence of viral STIs were found from low prevalence in cluster R-I, to higher prevalence in clusters R-II and R-V, and highest prevalence in clusters R-III/R-IV/R-VI. Furthermore, only 10% of HIV-positive women in clusters R-I/R-II, compared with 40% in cluster R-V, and 42% in clusters R-III/R-IV/R-VI had detectable cervicovaginal HIV-1 RNA (P trend =0.03). We conclude that L. crispatus-dominated, and to a lesser extent L. iners-dominated, cervicovaginal microbiota are associated with a lower prevalence of HIV/STIs and a lower likelihood of genital HIV-1 RNA shedding.


Bos J.C.,University of Amsterdam | Bos J.C.,Amsterdam Institute for Global Health and Development AIGHD | Smalbraak L.,University of Amsterdam | Macome A.C.,Hospital Central da Beira HCB | And 4 more authors.
International Health | Year: 2013

Background: In sub-Saharan African countries, the high proportion of smear-negative pulmonary TB (SNTB) and extrapulmonary TB (EPTB) contributes to a delay in TB diagnosis and treatment. We evaluated the TB diagnostic process of adult patients with presumptive TB in a referral hospital in Mozambique according to the 2007 WHO recommendations for the diagnosis and treatment of SNTB and EPTB in HIV-prevalent resource-poor settings. Methods: This was a retrospective, cross-sectional study using medical records of patients admitted in June-July 2009. Results: Overall, 514 patient recordswere screened, providing 234 presumptive TB patients. Therewere 70 deaths (29.9%). The evaluation of danger signs was never complete. HIV status was known for 175/234 patients (74.8%), 140 (80.0%) of whom were HIV-positive. A sputum smear microscopy (SSM) result was obtained for 59/234 patients (25.2%). SSM results were positive in 8/59 patients (13.6%). Chest radiography was done in 150/234 patients (64.1%) and 103 (68.7%) were abnormal. A total of 66 patients (28.2%) received TB treatment. Conclusions: The TB diagnostic process in this Mozambican hospital remained largely incomplete according to WHO recommendations and few patients with presumptive TB were identified as TB patients. Deficiencies as described should prompt reconsideration of WHO guideline content and feasibility. © The Author 2013. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved.


Van De Wijgert J.H.H.M.,University of Liverpool | Van De Wijgert J.H.H.M.,Amsterdam Institute for Global Health and Development AIGHD | Verwijs M.C.,Amsterdam Institute for Global Health and Development AIGHD | Verwijs M.C.,University Utrecht | And 2 more authors.
AIDS | Year: 2013

Objective: A 2012 WHO consultation concluded that combined oral contraception (COC) does not increase HIV acquisition in women, but the evidence for depot medroxyprogesterone acetate (DMPA) is conflicting. We evaluated the effect of COC and DMPA use on the vaginal microbiome because current evidence suggests that any deviation from a 'healthy' vaginal microbiome increases women's susceptibility to HIV. Methods: We conducted a systematic review and reanalysed the Hormonal Contraception and HIV Acquisition (HC-HIV) study. Vaginal microbiome outcomes included bacterial vaginosis by Nugent scoring, vaginal candidiasis by culture or KOH wet mount and microbiome compositions as characterized by molecular techniques. Results: Our review of 36 eligible studies found that COC and DMPA use reduce bacterial vaginosis by 10-20 and 18-30%, respectively. The HC-HIV data showed that COC and DMPA use also reduce intermediate microbiota (Nugent score of 4-6) by 11% each. In contrast, COC use (but not DMPA use) may increase vaginal candidiasis. Molecular vaginal microbiome studies (n=4) confirm that high oestrogen levels favour a vaginal microbiome composition dominated by 'healthy' Lactobacillus species; the effects of progesterone are less clear and not well studied. Conclusion: DMPA use does not increase HIV risk by increasing bacterial vaginosis or vaginal candidiasis. COC use may predispose for vaginal candidiasis, but is not believed to be associated with increased HIV acquisition. However, the potential role of Candida species, and vaginal microbiome imbalances other than bacterial vaginosis or Candida species, in HIV transmission cannot yet be ruled out. Further in-depth molecular studies are needed. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Aitken S.C.,University Utrecht | Bronze M.,University of Witwatersrand | Wallis C.L.,Lancet Laboratories | Stuyver L.,Janssen Diagnostics BVBA | And 8 more authors.
Journal of Clinical Microbiology | Year: 2013

In resource-limited settings (RLS), reverse transcriptase (RT) inhibitors form the backbone of first-line treatment regimens. We have developed a simplified HIV-1 drug resistance genotyping assay targeting the region of RT harboring all major RT inhibitor resistance mutation positions, thus providing all relevant susceptibility data for first-line failures, coupled with minimal cost and labor. The assay comprises a one-step RT-PCR amplification reaction, followed by sequencing using one forward and one reverse primer, generating double-stranded coverage of RT amino acids (aa) 41 to 238. The assay was optimized for all major HIV-1 groupMsubtypes in plasma and dried blood spot (DBS) samples using a panel of reference viruses for HIV-1 subtypes A to D, F to H, and circulating recombinant form 01-AE (CRF01-AE) and applied to 212 clinical plasma samples and 25 DBS samples from HIV-1-infected individuals from Africa and Europe. The assay was subsequently transferred to Uganda and applied locally on clinical plasma samples. All major HIV-1 subtypes could be detected with an analytical sensitivity of 5.00E+3 RNA copies/ml for plasma and DBS. Application of the assay on 212 clinical samples from African subjects comprising subtypes A to D, F to H (rare), CRF01-AE, and CRF02-AG at a viral load (VL) range of 6.71E+2 to 1.00E+7 (median, 1.48E+5) RNA copies/ml was 94.8% (n = 201) successful. Application on clinical samples in Uganda demonstrated a comparable success rate. Genotyping of clinical DBS samples, all subtype C with a VL range of 1.02E+3 to 4.49E+5 (median, 1.42E+4) RNA copies/ml, was 84.0% successful. The described assay greatly reduces hands-on time and the costs required for genotyping and is ideal for use in RLS, as demonstrated in a reference laboratory in Uganda and its successful application on DBS samples. Copyright © 2013, American Society for Microbiology. All Rights Reserved.


Aitken S.C.,University Utrecht | Kliphuis A.,PharmAccess International | Bronze M.,University of Witwatersrand | Wallis C.L.,Lancet Laboratories | And 9 more authors.
Journal of Clinical Microbiology | Year: 2013

Virological failure (VF) has been identified as the earliest, most predictive determinant of HIV-1 antiretroviral treatment (ART) failure. Due to the high cost and complexity of virological monitoring, VF assays are rarely performed in resource-limited settings (RLS). Rather, ART failure is determined by clinical monitoring and to a large extent immunological monitoring. This paper describes the development and evaluation of a low-cost, dried blood spot (DBS)-compatible qualitative assay to determine VF, in accordance with current WHO guideline recommendations for therapy switching in RLS. The assay described here is an internally controlled qualitative real-time PCR targeting the conserved long terminal repeat domain of HIV-1. This assay was applied to HIV-1 subtypes A to H and further evaluated on HIV-1 clinical plasma samples from South Africa (n = 191) and Tanzania (n = 42). Field evaluation was performed in Uganda using local clinical plasma samples (n = 176). Furthermore, assay performance was evaluated for DBS. This assay is able to identify VF for all major HIV-1 group M subtypes with equal specificity and has a lower detection limit of 1.00E+03 copies/ml for plasma samples and 5.00E+03 copies/ml for DBS. Comparative testing yielded accurate VF determination for therapy switching in 89% to 96% of samples compared to gold standards. The assay is robust and flexible, allowing for "open platform" applications and producing results comparable to those of commercial assays. Assay design enables application in laboratories that can accommodate real-time PCR equipment, allowing decentralization of testing to some extent. Compatibility with DBS extends access of sampling and thus access to this test to remote settings. Copyright © 2013, American Society for Microbiology. All Rights Reserved.


Aitken S.C.,University Utrecht | Aitken S.C.,University of Witwatersrand | Kliphuis A.,University Utrecht | Wallis C.L.,University of Witwatersrand | And 8 more authors.
Journal of Clinical Virology | Year: 2012

Background: High cost and varying sensitivity for non-B HIV-1 subtypes limits application of current commercial kits for HIV-1 drug resistance genotyping of all major HIV-1 group-M subtypes. Objectives: Our research aimed to develop and validate an assay specific for all major HIV-1 group-M subtypes for use as an alternative to commercial assays for HIV-1 protease (PR) and reverse transcriptase (RT) drug resistance genotyping. Study design: A nested RT-PCR encompassing the entire PR and RT up to amino acid 321 of HIV-1 was designed to detect HIV-1 group-M subtypes. Primers compatible with group-M subtypes were defined and analytical sensitivity of the assay evaluated using a panel of reference viruses for subtypes A-H and CRF01_AE. The assay was subsequently evaluated on 246 plasma samples from HIV-1 infected individuals harboring various group-M subtypes and viral loads (VLs). Results: All major group-M HIV-1 subtypes were detected with an overall analytical sensitivity of 1.00E+03 RNA copies/ml. Application of the genotyping assay on 246 primarily African clinical samples comprising subtypes A (n= 52; 21.7%), B (n= 12; 5.0%), C (n= 127; 52.9%), D (n= 25; 10.4%), CRF01_AE (n= 10; 4.2%), and CRF02_AG (n= 10; 4.2%), and unassigned variants (n= 10; 4.2%), VL range 4.32E+02-8.63E+06 (median 2.66E+04) RNA copies/ml, was ∼98% successful. Conclusions: A group-M subtype-independent genotyping assay for detection of HIV-1 drug resistance was developed. The described assay can serve as an alternative to commercial assays for HIV-1 drug resistance genotyping in routine diagnostics, and for surveillance and monitoring of drug resistance in resource-limited settings (RLS). © 2012 Elsevier B.V.


Van't Hoog A.H.,Amsterdam Institute for Global Health and Development AIGHD | Van't Hoog A.H.,University of Amsterdam | Cobelens F.,Amsterdam Institute for Global Health and Development AIGHD | Cobelens F.,University of Amsterdam | And 5 more authors.
PLoS ONE | Year: 2013

Background: High costs are a limitation to scaling up the Xpert MTB/RIF assay (Xpert) for the diagnosis of tuberculosis in resource-constrained settings. A triaging strategy in which a sensitive but not necessarily highly specific rapid test is used to select patients for Xpert may result in a more affordable diagnostic algorithm. To inform the selection and development of particular diagnostics as a triage test we explored combinations of sensitivity, specificity and cost at which a hypothetical triage test will improve affordability of the Xpert assay. Methods: In a decision analytical model parameterized for Uganda, India and South Africa, we compared a diagnostic algorithm in which a cohort of patients with presumptive TB received Xpert to a triage algorithm whereby only those with a positive triage test were tested by Xpert. Findings: A triage test with sensitivity equal to Xpert, 75% specificity, and costs of US$5 per patient tested reduced total diagnostic costs by 42% in the Uganda setting, and by 34% and 39% respectively in the India and South Africa settings. When exploring triage algorithms with lower sensitivity, the use of an example triage test with 95% sensitivity relative to Xpert, 75% specificity and test costs $5 resulted in similar cost reduction, and was cost-effective by the WHO willingness-to-pay threshold compared to Xpert for all in Uganda, but not in India and South Africa. The gain in affordability of the examined triage algorithms increased with decreasing prevalence of tuberculosis among the cohort. Conclusions: A triage test strategy could potentially improve the affordability of Xpert for TB diagnosis, particularly in low-income countries and with enhanced case-finding. Tests and markers with lower accuracy than desired of a diagnostic test may fall within the ranges of sensitivity, specificity and cost required for triage tests and be developed as such. © 2013 Van't Hoog et al.


Laan J.J.,Huisartsenpraktijk Buitenhof | Van De Vijver S.,AMC | Van De Vijver S.,Amsterdam Institute for Global Health and Development AIGHD
Nederlands Tijdschrift voor Geneeskunde | Year: 2015

A 29 year old man presented with a painless soft mass that was hanging on a string of skin on his upper leg. Physical examination revealed a 5 cm broad, elastic, stalked skin toned mass. On microscopic examination the diagnosis fibrolipoma was objectified..


PubMed | University of Amsterdam, Amsterdam Institute for Global Health and Development AIGHD, University of Ghana, VU University Amsterdam and 2 more.
Type: Journal Article | Journal: PloS one | Year: 2015

Quality care in health facilities is critical for a sustainable health insurance system because of its influence on clients decisions to participate in health insurance and utilize health services. Exploration of the different dimensions of healthcare quality and their associations will help determine more effective quality improvement interventions and health insurance sustainability strategies, especially in resource constrained countries in Africa where universal access to good quality care remains a challenge.To examine the differences in perceptions of clients and health staff on quality healthcare and determine if these perceptions are associated with technical quality proxies in health facilities. Implications of the findings for a sustainable National Health Insurance Scheme (NHIS) in Ghana are also discussed.This is a cross-sectional study in two southern regions in Ghana involving 64 primary health facilities: 1,903 households and 324 health staff. Data collection lasted from March to June, 2012. A Wilcoxon-Mann-Whitney test was performed to determine differences in client and health staff perceptions of quality healthcare. Spearmans rank correlation test was used to ascertain associations between perceived and technical quality care proxies in health facilities, and ordered logistic regression employed to predict the determinants of client and staff-perceived quality healthcare.Negative association was found between technical quality and client-perceived quality care (coef. = -0.0991, p<0.0001). Significant staff-client perception differences were found in all healthcare quality proxies, suggesting some level of unbalanced commitment to quality improvement and potential information asymmetry between clients and service providers. Overall, the findings suggest that increased efforts towards technical quality care alone will not necessarily translate into better client-perceived quality care and willingness to utilize health services in NHIS-accredited health facilities.There is the need to intensify client education and balanced commitment to technical and perceived quality improvement efforts. This will help enhance client confidence in Ghanas healthcare system, stimulate active participation in the national health insurance, increase healthcare utilization and ultimately improve public health outcomes.

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