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Antiretroviral treatment in the private sector in Namibia
Antiretroviral treatment (ART) has been available in the private sector in Namibia since 1998. National guidelines were developed by the Ministry of Health and clinicians of the public and private sector in 2003 and launched at the start of the public sector ART programme by the Ministry of Health. The Namibian HIV Clinicians Society was established around this period to promote adherence to the national guidelines and to provide comprehensive training for health professionals. To monitor adherence to national ART guidelines, in 2003, the Society requested access to anonymized data on ART dispensing from the medical insurance industry. Dispensing data from all Namibian medical insurance companies were obtained. ART regimens were categorized as recommended (non-nucleoside reverse transcriptase inhibitor-based and boosted protease inhibitor [PI]-based), not recommended (non-boosted PI-based or stavudine/didanosine-containing regimens), ineffective (dual therapy) and second line or salvage regimens. This analysis was repeated in 2004, 2005 and 2008. In 2003, only 2306 adult private patients received ART, of which only 1527 (66%) were recommended regimens. In 2008, 7010 private patients received ART, of which 6372 (91%) were recommended regimens. The private sector covered about 15% of the total number of 46,732 reported ART patients reported in the year 2008. Many of these private patients might not have accessed ART in the public sector
High prevalence of primary multidrug resistant tuberculosis in persons with no known risk factors
INTRODUCTION: In high multidrug resistant (MDR) tuberculosis (TB) prevalence areas, drug susceptibility testing (DST) at diagnosis is recommended for patients with risk factors for MDR. However, this approach might miss a substantial proportion of MDR-TB in the general population. We studied primary MDR in patients considered to be at low risk of MDR-TB in Lima, Peru. METHODS: We enrolled new sputum smear-positive TB patients who did not report any MDR-TB risk factor: known exposure to a TB patient whose treatment failed or who died or who was known to have MDR-TB; immunosuppressive co-morbidities, ex prison inmates; prison and health care workers; and alcohol or drug abuse. A structured questionnaire was applied to all enrolled participants to confirm the absence of these factors and thus minimize underreporting. Sputum from all participants was cultured on Lowenstein-Jensen media and DST for first line drugs was performed using the 7H10 agar method. RESULTS: Of 875 participants with complete data, 23.2% (203) had risk factors for MDR-TB elicited after enrolment. Among the group with no reported risk factors who had a positive culture, we found a 6.3% (95%CI 4.4-8.3) (37/584) rate of MDR-TB. In this group no epidemiological characteristics were associated with MDR-TB. Thus, in this group, multidrug resistance occurred in patients with no identifiable risk factors. CONCLUSIONS: We found a high rate of primary MDR-TB in a general population with no identifiable risk factors for MDR-TB. This suggests that in a high endemic area targeting patients for MDR-TB based on the presence of risk factors is an insufficient intervention
Visceral leishmaniasis in the Indian subcontinent: modelling epidemiology and control
BACKGROUND: In the Indian subcontinent, about 200 million people are at risk of developing visceral leishmaniasis (VL). In 2005, the governments of India, Nepal and Bangladesh started the first regional VL elimination program with the aim to reduce the annual incidence to less than 1 per 10,000 by 2015. A mathematical model was developed to support this elimination program with basic quantifications of transmission, disease and intervention parameters. This model was used to predict the effects of different intervention strategies. METHODS AND FINDINGS: Parameters on the natural history of Leishmania infection were estimated based on a literature review and expert opinion or drawn from a community intervention trial (the KALANET project). The transmission dynamic of Leishmania donovani is rather slow, mainly due to its long incubation period and the potentially long persistence of parasites in infected humans. Cellular immunity as measured by the Leishmanin skin test (LST) lasts on average for roughly one year, and re-infection occurs in intervals of about two years, with variation not specified. The model suggests that transmission of L. donovani is predominantly maintained by asymptomatically infected hosts. Only patients with symptomatic disease were eligible for treatment; thus, in contrast to vector control, the treatment of cases had almost no effect on the overall intensity of transmission. CONCLUSIONS: Treatment of Kala-azar is necessary on the level of the individual patient but may have little effect on transmission of parasites. In contrast, vector control or exposure prophylaxis has the potential to efficiently reduce transmission of parasites. Based on these findings, control of VL should pay more attention to vector-related interventions. Cases of PKDL may appear after years and may initiate a new outbreak of disease; interventions should therefore be long enough, combined with an active case detection and include effective treatment
Whole genome sequencing of multiple Leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance
Visceral leishmaniasis is a potentially fatal disease endemic to large parts of Asia and Africa, primarily caused by the protozoan parasite Leishmania donovani. Here, we report a high-quality reference genome sequence for a strain of L. donovani from Nepal, and use this sequence to study variation in a set of 16 related clinical lines, isolated from visceral leishmaniasis patients from the same region, which also differ in their response to in vitro drug susceptibility. We show that whole-genome sequence data reveals genetic structure within these lines not shown by multilocus typing, and suggests that drug resistance has emerged multiple times in this closely related set of lines. Sequence comparisons with other Leishmania species and analysis of single-nucleotide diversity within our sample showed evidence of selection acting in a range of surface- and transport-related genes, including genes associated with drug resistance. Against a background of relative genetic homogeneity, we found extensive variation in chromosome copy number between our lines. Other forms of structural variation were significantly associated with drug resistance, notably including gene dosage and the copy number of an experimentally verified circular episome present in all lines and described here for the first time. This study provides a basis for more powerful molecular profiling of visceral leishmaniasis, providing additional power to track the drug resistance and epidemiology of an important human pathogen
Mortality and immunovirological outcomes on antiretroviral therapy in HIV-1 and HIV-2-infected individuals in the Gambia
OBJECTIVES: This study's objective was to assess outcomes in HIV-1 and HIV-2 infected antiretroviral therapy (ART)-naive patients starting ART in the Gambia, West Africa. DESIGN: A cohort design was used to estimate survival in ART patients and determine whether survival and time to virologic failure varied across patient subgroups. METHODS: Mortality, virologic failures and CD4(+) cell recovery were assessed in a clinical cohort of patients from the Genito-Urinary Medicine (GUM) clinic of the MRC Laboratories in the Gambia. Kaplan-Meier estimates of survival were determined for mortality and virologic failure. A Cox proportional hazards model was used to identify baseline demographic, clinical, immunologic and virologic factors associated with increased risk of death. RESULTS: The overall Kaplan-Meier estimate of survival to 36 months was 73.4% (66.5, 80.3). Survival was marginally higher in HIV-2-infected patients compared to HIV-1-infected patients; it was significantly higher in patients with a baseline CD4(+) lymphocyte cell count of greater than 50 cells/mul compared to those with a baseline CD4(+) count of less than 50 cells/mul. CD4(+) cell recovery was faster in HIV-1-infected individuals compared to HIV-2-infected patients up to 24 months, although this did not result higher mortality in the latter group. No differences in virologic failure were observed by HIV type. CONCLUSION: HIV-1 and HIV-2-infected patients receiving ART in a clinical setting in the Gambia had good survival to 36 months. HIV-2-infected patients did as well as HIV-1-infected patients in terms of long-term immunological and virological responses and overall survival
Post-kala-azar dermal Leishmaniasis in Nepal: a retrospective cohort study (2000-2010)
INTRODUCTION: Post-kala-azar dermal leishmaniasis (PKDL) is a cutaneous complication appearing after treatment of visceral leishmaniasis, and PKDL patients are considered infectious to sand flies and may therefore play a role in the transmission of VL. We estimated the risk and risk factors of PKDL in patients with past VL treatment in south-eastern Nepal. METHODS: Between February and May 2010 we traced all patients who had received VL treatment during 2000-2009 in five high-endemic districts and screened them for PKDL-like skin lesions. Suspected cases were referred to a tertiary care hospital for confirmation by parasitology (slit skin smear (SSS)) and/or histopathology. We calculated the risk of PKDL using Kaplan-Meier survival curves and exact logistic regression for risk factors. RESULTS: Out of 680 past-treated VL patients, 37(5.4%) presented active skin lesions suspect of PKDL during the survey. Thirty-three of them underwent dermatological assessment, and 16 (2.4%) were ascertained as probable (2) or confirmed (14) PKDL. Survival analysis showed a 1.4% risk of PKDL within 2 years of VL treatment. All 16 had been previously treated with sodium stibogluconate (SSG) for their VL. In 5, treatment had not been completed (</=21 injections). Skin lesions developed after a median time interval of 23 months [interquartile range (IQR) 16-40]. We found a higher PKDL rate (29.4%) in those inadequately treated compared to those who received a full SSG course (2.0%). In the logistic regression model, unsupervised treatment [odds ratio (OR) = 8.58, 95% CI 1.21-374.77], and inadequate SSG treatment for VL in the past (OR = 11.68, 95% CI 2.71-45.47) were significantly associated with PKDL. CONCLUSION: The occurrence of PKDL after VL treatment in Nepal is low compared to neighboring countries. Supervised and adequate treatment of VL seems essential to reduce the risk of PKDL development and active surveillance for PKDL is needed
Disease control programs contribution to health system strengthening: good practices and new approaches for scale-up. A study by the Federal Ministry of Health, Ethiopia and the Institute of Tropical Medicine, Antwerp
Surveillance of antibiotic resistance in developing countries, constraints and realities
A realist evaluation of the management of a well-performing regional hospital in Ghana
BACKGROUND: Realist evaluation offers an interesting approach to evaluation of interventions in complex settings, but has been little applied in health care. We report on a realist case study of a well performing hospital in Ghana and show how such a realist evaluation design can help to overcome the limited external validity of a traditional case study. METHODS: We developed a realist evaluation framework for hypothesis formulation, data collection, data analysis and synthesis of the findings. Focusing on the role of human resource management in hospital performance, we formulated our hypothesis around the high commitment management concept. Mixed methods were used in data collection, including individual and group interviews, observations and document reviews. RESULTS: We found that the human resource management approach (the actual intervention) included induction of new staff, training and personal development, good communication and information sharing, and decentralised decisionmaking. We identified 3 additional practices: ensuring optimal physical working conditions, access to top managers and managers' involvement on the workfloor. Teamwork, recognition and trust emerged as key elements of the organisational climate. Interviewees reported high levels of organisational commitment. The analysis unearthed perceived organisational support and reciprocity as underlying mechanisms that link the management practices with commitment. Methodologically, we found that realist evaluation can be fruitfully used to develop detailed case studies that analyse how management interventions work and in which conditions. Analysing the links between intervention, mechanism and outcome increases the explaining power, while identification of essential context elements improves the usefulness of the findings for decision-makers in other settings (external validity). We also identified a number of practical difficulties and priorities for further methodological development. CONCLUSION: This case suggests that a well-balanced HRM bundle can stimulate organisational commitment of health workers. Such practices can be implemented even with narrow decision spaces. Realist evaluation provides an appropriate approach to increase the usefulness of case studies to managers and policymakers
A CATT negative result after treatment for human African trypanosomiasis is no indication for cure
Background: cure after treatment for human African trypanosomiasis (HAT) is assessed by examination of the cerebrospinal fluid every 6 months, for a total period of 2 years. So far, no markers for cure or treatment failure have been identified in blood. Trypanosome-specific antibodies are detectable in blood by the Card Agglutination Test for Trypanosomiasis (CATT). We studied the value of a normalising, negative post-treatment CATT result in treated Trypanosoma brucei (T.b.) gambiense sleeping sickness patients as a marker of cure.
Methodology/Principal Findings: the CATT/T.b. gambiense was performed on serum of a cohort of 360 T.b. gambiense patients, consisting of 242 primary and 118 retreatment cases. The CATT results during 2 years of post-treatment follow-up were studied in function of cure or treatment failure. At inclusion, sensitivity of CATT was 98% (234/238) in primary cases and only 78% (91/117) in retreatment cases. After treatment, the CATT titre decreased both in cured patients and in patients experiencing treatment failure.
Conclusions/Significance: though CATT is a good test to detect HAT in primary cases, a normalising or negative CATT result after treatment for HAT does not indicate cure, therefore CATT cannot be used to monitor treatment outcome