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Liu J.,University of Virginia | Gratz J.,Kilimanjaro Clinical Research Institute | Amour C.,Haydom Lutheran Hospital | Kibiki G.,Kilimanjaro Clinical Research Institute | And 8 more authors.
Journal of Clinical Microbiology | Year: 2013

The TaqMan Array Card (TAC) system is a 384-well singleplex real-time PCR format that has been used to detect multiple infection targets. Here we developed an enteric TaqMan Array Card to detect 19 enteropathogens, including viruses (adenovirus, astrovirus, norovirus GII, rotavirus, and sapovirus), bacteria (Campylobacter jejuni/C. coli, Clostridium difficile, Salmonella, Vibrio cholerae, diarrheagenic Escherichia coli strains including enteroaggregative E. coli [EAEC], enterotoxigenic E. coli [ETEC], enteropathogenic E. coli [EPEC], and Shiga-toxigenic E. coli [STEC]), Shigella/enteroinvasive E. coli (EIEC), protozoa (Cryptosporidium, Giardia lamblia, and Entamoeba histolytica), and helminths (Ascaris lumbricoides and Trichuris trichiura), as well as two extrinsic controls to monitor extraction and amplification efficiency (the bacteriophage MS2 and phocine herpesvirus). Primers and probes were newly designed or adapted from published sources and spotted onto microfluidic cards. Fecal samples were spiked with extrinsic controls, andDNAand RNAwere extracted using the QiaAmp StoolDNAminikit and the QuickGeneRNATissue kit, respectively, and then mixed with Ag- Path-ID One Step real-time reverse transcription-PCR (RT-PCR) reagents and loaded into cards. PCR efficiencies were between 90% and 105%, with linearities of 0.988 to 1. The limit of detection of the assays in the TAC was within a 10-fold difference from the cognate assays performed on plates. Precision testing demonstrated a coefficient of variation of below5%within a run and 14% between runs. Accuracy was evaluated for 109 selected clinical specimens and revealed an average sensitivity and specificity of 85% and 77%, respectively, compared with conventional methods (including microscopy, culture, and immunoassay) and 98% and 96%, respectively, compared with our laboratory-developed PCR-Luminex assays. This TAC allows fast, accurate, and quantitative detection of a broad spectrum of enteropathogens and is well suited for surveillance or clinical purposes. Copyright © 2013, American Society for Microbiology.


Lyimo R.A.,Kilimanjaro Clinical Research Institute | De Bruin M.,Wageningen University | Van Den Boogaard J.,Radboud University Nijmegen | Hospers H.J.,Maastricht University | And 2 more authors.
BMC Public Health | Year: 2012

Background: To design effective, tailored interventions to support antiretroviral therapy (ART) adherence, a thorough understanding of the barriers and facilitators of ART adherence is required. Factors at the individual and interpersonal level, ART treatment characteristics and health care factors have been proposed as important adherence determinants. Methods. To identify the most relevant determinants of adherence in northern Tanzania, in-depth interviews were carried out with 61 treatment-experienced patients from four different clinics. The interviews were ad-verbatim transcribed and recurrent themes were coded. Results: Coding results showed that the majority of patients had basic understanding of adherence, but also revealed misconceptions about taking medication after alcohol use. Adherence motivating beliefs were the perception of improved health and the desire to live like others, as well as the desire to be a good parent. A de-motivating belief was that stopping ART after being prayed for was an act of faith. Facilitators of adherence were support from friends and family, and assistance of home based care (HBC) providers. Important barriers to ART adherence were the use of alcohol, unavailability of food, stigma and disclosure concerns, and the clinics dispensing too few pills. Strategies recommended by the patients to improve adherence included better Care and Treatment Centre (CTC) services, recruitment of patients to become Home Based Care (HBC) providers, and addressing the problem of stigma through education. Conclusion: This study underscores the importance of designing tailored, patient-centered adherence interventions to address challenges at the patient, family, community and health care level. © 2012 Lyimo et al.; licensee BioMed Central Ltd.


Mbwele B.,Kilimanjaro Clinical Research Institute | Reddy E.,Duke University | Reyburn H.,London School of Hygiene and Tropical Medicine
BMC Pediatrics | Year: 2012

Background: While child mortality is declining in Africa there has been no evidence of a comparable reduction in neonatal mortality. The quality of inpatient neonatal care is likely a contributing factor but data from resource limited settings are few. The objective of this study was to assess the quality of neonatal care in the district hospitals of the Kilimanjaro region of Tanzania.Methods: Clinical records were reviewed for ill or premature neonates admitted to 13 inpatient health facilities in the Kilimanjaro region; staffing and equipment levels were also assessed. Results: Among the 82 neonates reviewed, key health information was missing from a substantial proportion of records: on maternal antenatal cards, blood group was recorded for 52 (63.4%) mothers, Rhesus (Rh) factor for 39 (47.6%), VDRL for 59 (71.9%) and HIV status for 77 (93.1%). From neonatal clinical records, heart rate was recorded for3 (3.7%) neonates, respiratory rate in 14, (17.1%) and temperature in 33 (40.2%). None of 13 facilities had a functioning premature unit despite calculated gestational age <36 weeks in 45.6% of evaluated neonates. Intravenous fluids and oxygen were available in 9 out of 13 of facilities, while antibiotics and essential basic equipment were available in more than two thirds. Medication dosing errors were common; under-dosage for ampicillin, gentamicin and cloxacillin was found in 44.0%, 37.9% and 50% of cases, respectively, while over-dosage was found in 20.0%, 24.2% and 19.9%, respectively. Physician or assistant physician staffing levels by the WHO indicator levels (WISN) were generally low.Conclusion: Key aspects of neonatal care were found to be poorly documented or incorrectly implemented in this appraisal of neonatal care in Kilimanjaro. Efforts towards quality assurance and enhanced motivation of staff may improve outcomes for this vulnerable group. © 2012 Mbwele et al.; licensee BioMed Central Ltd.


Rugemalila J.,Kilimanjaro Christian Medical University College | Maro V.P.,Kilimanjaro Christian Medical University College | Kapanda G.,Kilimanjaro Christian Medical University College | Ndaro A.J.,Kilimanjaro Clinical Research Institute | Jarvis J.N.,London School of Hygiene and Tropical Medicine
Tropical Medicine and International Health | Year: 2013

Objectives: Cryptococcal antigen (CRAG) screening at antiretroviral therapy (ART) initiation and pre-emptive antifungal treatment for those testing positive could prevent many cases of cryptococcal meningitis (CM). To investigate whether CRAG screening would be feasible in Tanzania, we conducted a cross-sectional study measuring CRAG prevalence in ART clinic patients and comparing the novel lateral flow assay (LFA) with the cryptococcal latex agglutination (LA) test. Methods: Consecutive HIV-infected outpatients with CD4 counts <200 cells/μL, who were ART naive or had been on ART for <6 months, were screened for CRAG using the LA and LFA kits. For further assay validation, HIV-infected inpatients with suspected cryptococcal disease were also tested using the LA and LFA kits. Results: Cryptococcal antigen was detected in seven of 218 ART clinic attendees (3%). Six patients (5%) with CD4 cell counts ≤100 cells/μL (n = 124) were CRAG-positive. Agreement between the LA and LFA test in the 218 outpatients was 100%. Another 101 inpatients were tested for CRAG, of whom 56 (55%) were CRAG-positive on both the LA and LFA tests. One patient was positive using the LFA test but negative on the LA test. The overall agreement between the two assays was 99.7%, kappa coefficient 0.99 (standard error 0.06, P < 0.001). Conclusions: Five percentage of ART clinic patients with CD4 cell counts ≤100 cells/μL in northern Tanzania had asymptomatic cryptococcal antigenaemia, suggesting that CRAG screening would be worthwhile in the Tanzanian ART programme. The LFA is a reliable, cheap and practical alternative to LA for detection of CRAG. © 2013 John Wiley & Sons Ltd.


Dima A.L.,University of Amsterdam | Stutterheim S.E.,Open Box | Lyimo R.,Kilimanjaro Clinical Research Institute | De Bruin M.,University of Amsterdam | De Bruin M.,Aberdeen Group
Social Science and Medicine | Year: 2014

Disclosure of HIV status has been the focus of three decades of research, which have revealed its complex relations to many behaviors involved in HIV prevention and treatment, and exposed its central role in managing the HIV epidemic. The causes and consequences of disclosure acts have recently been the subject of several theoretical models. Although it is acknowledged that individual disclosure events are part of a broader process of disclosing one's HIV status to an increasing number of people, this process has received less theoretical attention. In quantitative studies of disclosure, researchers have often implicitly assumed that disclosure is a single unidimensional process appropriately measured via the total number of one's disclosure acts. However, there is also evidence that disclosure may have different causes and consequences depending on the types of actors involved (e.g. family members, friends) and on the presence or absence of the discloser's intention, suggesting that the unidimensionality assumption may not hold. We quantitatively examined the dimensionality of voluntary and involuntary disclosure to different categories of actors, using data collected via structured interviews in the spring of 2010 from 158 people living with HIV in Kilimanjaro, Tanzania. For voluntary disclosure, nonparametric item response analyses identified two multi-category clusters, family and community, and two single-category dimensions, partner and children. Involuntary disclosure consisted of several single- or two-category dimensions. Correlation analyses between the resulting disclosure dimensions and stigma and social support revealed distinct relationships for each disclosure dimension. Our results suggest that treating disclosure as a unidimensional construct is a simplification of disclosure processes that may lead to incorrect conclusions about disclosure correlates. We therefore recommend examining disclosure acts jointly to identify sample-specific dimensions before examining causes and consequences of disclosure. We propose a methodology for investigating disclosure processes, and recommend its adoption in future disclosure studies. © 2014 Elsevier Ltd.


Mbugi E.V.,Muhimbili University of Health and Allied Sciences | Chilongola J.O.,Kilimanjaro Clinical Research Institute
World Allergy Organization Journal | Year: 2010

In Africa, the burden of some diseases has been a problem for centuries. The spectrum of African diseases includes allergies, infections, nutritional deficiencies, and natural disasters. Efforts made by scientists to search for possible means of disease control have been outstanding; however, in some infections, solutions are still out of reach. In disease control programs, it might be worthwhile to pay attention to the most striking diseases than merely follow a holistic approach. This short review tackles the problems of allergy and allergens in Africa as compared with other disease burdens that may suggest the need for a more balanced approach based on priority. Copyright © 2010 by World Allergy Organization.


Lyimo R.A.,Kilimanjaro Clinical Research Institute | Stutterheim S.E.,Open University | Hospers H.J.,MaastrichtUniversity | De Glee T.,Wageningen University | And 2 more authors.
AIDS Patient Care and STDs | Year: 2014

This study examines a proposed theoretical model examining the interrelationships between stigma, disclosure, coping, and medication adherence among 158 HIV-infected patients on antiretroviral therapy (ART) in northern Tanzania. Perceived and self-stigma, voluntary and involuntary disclosure, positive and negative coping, and demographics were assessed by trained interviewers, and self-reported adherence was collected during 5 months follow-up. Data were examined using correlation and regression analyses. The analyses showed that perceived stigma is primarily related to involuntary disclosure, whereas self-stigma is related to voluntary disclosure. Religious coping positively relates to acceptance, whereas perceived stigma explains higher levels of denial of HIV status. Lastly, adherence was negatively affected by alcohol use, self-stigma, and denial. We conclude that adherence is predominantly predicted by negative rather than positive coping mechanisms. Therefore, substituting maladaptive coping mechanisms like denial and alcohol use with a more adaptive coping style may be an important strategy to improve long-term ART adherence and well-being of patients. Moreover, this study showed that it is useful to examine both involuntary and voluntary disclosure when studying its relation with stigma. © 2014, Mary Ann Liebert, Inc.


Van den Boogaard J.,Radboud University Nijmegen | Van den Boogaard J.,Kilimanjaro Clinical Research Institute | Boeree M.J.,Radboud University Nijmegen | Kibiki G.S.,Kilimanjaro Clinical Research Institute | Aarnoutse R.E.,Radboud University Nijmegen
Tropical Medicine and International Health | Year: 2011

Non-adherence to tuberculosis (TB) treatment is a major challenge to global TB control because it increases the risk of treatment failure, relapse and the emergence of drug-resistant TB. Although the problem is widely acknowledged, there is still no clarity about the exact impact of different levels and patterns of non-adherence on treatment outcome. This hampers the provision of adequate advice to patients and clinicians, and it challenges the development and evaluation of adherence-promoting interventions. In this article, we explain why we are still in the dark with respect to predicting how different types of non-adherence to TB treatment affect treatment outcome. We show that we lack uniformity in how we define and measure non-adherence, that we have no easily accessible treatment success indicators, and that the relationship between treatment adherence and outcome is influenced by a number of pathogenic, immunological and pharmacological factors that are only partly understood. We conclude that an integral 'bench and bedside approach' that incorporates experimental studies with in vitro models and animals, as well as observational studies in patients with TB, is needed to help us get out of the dark regarding the adherence-response relationship in TB treatment. © 2011 Blackwell Publishing Ltd.


Tostmann A.,Radboud University Nijmegen | Mtabho C.M.,Kilimanjaro Clinical Research Institute | Semvua H.H.,Kilimanjaro Clinical Research Institute | Van Den Boogaard J.,Radboud University Nijmegen | And 4 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2013

East Africa has a high tuberculosis (TB) incidence and mortality, yet there are very limited data on exposure to TB drugs in patients from this region. We therefore determined the pharmacokinetic characteristics of first-line TB drugs in Tanzanian patients using intensive pharmacokinetic sampling. In 20 adult TB patients, plasma concentrations were determined just before and at 1, 2, 3, 4, 6, 8, 10, and 24 h after observed drug intake with food to estimate the areas under the curve from 0 to 24 h (AUC0-24) and peak plasma concentrations (Cmax) of isoniazid, rifampin, pyrazinamide, and ethambutol. Acetylator status for isoniazid was assessed phenotypically using the isoniazid elimination half-life and the acetylisoniazid/isoniazid metabolic ratio at 3 h postdose. The geometric mean AUC0-24s were as follows: isoniazid, 11.0 h · mg/liter; rifampin, 39.9 h · mg/liter; pyrazinamide, 344 h · mg/liter; and ethambutol, 20.2 h · mg/liter. The Cmax was below the reference range for isoniazid in 10/19 patients and for rifampin in 7/20 patients. In none of the patients were the Cmaxs for pyrazinamide and ethambutol below the reference range. Elimination half-life and metabolic ratio of isoniazid gave discordant phenotyping results in only 2/19 patients. A substantial proportion of patients had an isoniazid and/or rifampin Cmax below the reference range. Intake of TB drugs with food may partly explain these low drug levels, but such a drug intake reflects common practice. The finding of low TB drug concentrations is concerning because low concentrations have been associated with worse treatment outcome in several other studies. Copyright © 2013, American Society for Microbiology.


van den Boogaard J.,Radboud University Nijmegen | Lyimo R.A.,Kilimanjaro Clinical Research Institute | Boeree M.J.,Radboud University Nijmegen | Kibiki G.S.,Kilimanjaro Clinical Research Institute | Aarnoutse R.E.,Radboud University Nijmegen
Bulletin of the World Health Organization | Year: 2011

Objective: To assess adherence to community-based directly observed treatment (DOT) among Tanzanian tuberculosis patients using the Medication Event Monitoring System (MEMS) and to validate alternative adherence measures for resource-limited settings using MEMS as a gold standard. Methods: This was a longitudinal pilot study of 50 patients recruited consecutively from one rural hospital, one urban hospital and two urban health centres. Treatment adherence was monitored with MEMS and the validity of the following adherence measures was assessed: isoniazid urine test, urine colour test, Morisky scale, Brief Medication Questionnaire, adapted AIDS Clinical Trials Group (ACTG) adherence questionnaire, pill counts and medication refill visits. Findings: The mean adherence rate in the study population was 96.3% (standard deviation, SD: 7.7). Adherence was less than 100% in 70% of the patients, less than 95% in 21% of them, and less than 80% in 2%. The ACTG adherence questionnaire and urine colour test had the highest sensitivities but lowest specificities. The Morisky scale and refill visits had the highest specificities but lowest sensitivities. Pill counts and refill visits combined, used in routine practice, yielded moderate sensitivity and specificity, but sensitivity improved when the ACTG adherence questionnaire was added. Conclusion: Patients on community-based DOT showed good adherence in this study. The combination of pill counts, refill visits and the ACTG adherence questionnaire could be used to monitor adherence in settings where MEMS is not affordable. The findings with regard to adherence and to the validity of simple adherence measures should be confirmed in larger populations with wider variability in adherence rates.

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