Outcomes of patients with Kaposi's sarcoma who start antiretroviral therapy under routine programme conditions in Malawi.

AIDS-associated Kaposi's sarcoma (KS) is the most common AIDS-related malignancy in sub-Saharan Africa, with a generally unfavourable prognosis. We report on six-month and 12-month cohort treatment outcomes of human immunodeficiency virus (HIV)-positive KS patients and HIV-positive non-KS patients treated with antiretroviral therapy (ART) in public sector facilities in Malawi. Data were collected from standardized antiretroviral (ARV) patient master cards and ARV patient registers. Between July and September 2005, 7905 patients started ART-488 (6%) with a diagnosis of KS and 7417 with a non-KS diagnosis. Between January and March 2005, 4580 patients started ART-326 (7%) with a diagnosis of KS and 4254 with a non-KS diagnosis. At six-months and 12-months, significantly fewer KS patients were alive and significantly more had died or defaulted compared to non-KS patients. HIV-positive KS patients on ART in Malawi have worse outcomes than other patients on ART. Methods designed to improve these outcomes must be found

A National Survey of Teachers on Antiretroviral Therapy in Malawi: Access, Retention in Therapy and Survival

BACKGROUND: HIV/AIDS is having a devastating effect on the education sector in sub-Saharan Africa. A national survey was conducted in all public sector and private sector facilities in Malawi providing antiretroviral therapy (ART) to determine the uptake of ART by teachers and their outcomes while on treatment. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort study was carried out based on patient follow-up records from ART Registers and treatment master cards in all 138 ART clinics in Malawi; observations were censored on September 30(th) 2006. By this date, Malawi's 102 public sector and 36 private sector ART clinics had registered a total of 72,328 patients for treatment. Of these, 2,643 (3.7%) were teachers. Adjusting for double-registration caused by clinic transfers, it is estimated that 2,380 individual teachers had ever accessed ART. There were 15% of teachers starting ART in WHO clinical stage 1 or 2 with a CD4-lymphocyte count of <or=250/mm(3) and 85% starting in stage 3 or 4. By 30(th) September 2006, 1,850 teachers were alive on ART (3.5% of all teachers in Malawi). The probability of being alive on ART at 6-months, 12-months, 18-months and 24-months after treatment initiation was 84%, 79%, 75% and 73% respectively. Retention in treatment was better for women (adjusted HR = 1.8) and in those starting ART in WHO Clinical Stage 1 and 2 (adjusted HR = 1.8). CONCLUSION/SIGNIFICANCE: Rapid scale up of ART has allowed 2,380 HIV-positive teachers to access life-prolonging treatment. There is evidence that this intervention can help to mitigate some of the shortages of teaching personnel in resource-poor countries affected by a generalised HIV epidemic

Malawi’s contribution to “3 by 5”: achievements and challenges

PROBLEM: Many resource-poor countries have started scaling up antiretroviral therapy (ART). While reports from individual clinics point to successful implementation, there is limited information about progress in government institutions at a national level. APPROACH: Malawi started national ART scale-up in 2004 using a structured approach. There is a focus on one generic, fixed-dose combination treatment with stavudine, lamivudine and nevirapine. Treatment is delivered free of charge to eligible patients with HIV and there is a standardized system for recruiting patients, monthly follow-up, registration, monitoring and reporting of cases and outcomes. All treatment sites receive quarterly supervision and evaluation. LOCAL SETTING: In January 2004, there were nine public sector facilities delivering ART to an estimated 4 000 patients. By December 2005, there were 60 public sector facilities providing free ART to 37,840 patients using national standardized systems. Analysis of quarterly cohort treatment outcomes at 12 months showed 80% of patients were alive, 10% dead, 9% lost to follow-up and 1% had stopped treatment. LESSONS LEARNED: Achievements were the result of clear national ART guidelines, implementing partners working together, an intensive training schedule focused on clinical officers and nurses, a structured system of accrediting facilities for ART delivery, quarterly supervision and monitoring, and no stock-outs of antiretroviral drugs. The main challenges are to increase the numbers of children, pregnant women and patients with tuberculosis being started on ART, and to avert high early mortality and losses to follow-up. The capacity of the health sector to cope with escalating case loads and to scale up prevention alongside treatment will determine the future success of ART delivery in Malawi

A national survey of the impact of rapid scale-up of antiretroviral therapy on health-care workers in Malawi: effects on human resources and survival

OBJECTIVE: To assess the human resources impact of Malawis rapidly growing antiretroviral therapy (ART) programme and balance this against the survival benefit of health-care workers who have accessed ART themselves. METHODS: We conducted a national cross-sectional survey of the human resource allocation in all public-sector health facilities providing ART in mid-2006. We also undertook a survival analysis of health-care workers who had accessed ART in public and private facilities by 30 June 2006, using data from the national ART monitoring and evaluation system. FINDINGS: By 30 June 2006, 59 581 patients had accessed ART from 95 public and 28 private facilities. The public sites provided ART services on 2.4 days per week on average, requiring 7% of the clinician workforce, 3% of the nursing workforce and 24% of the ward clerk workforce available at the facilities. We identified 1024 health-care workers in the national ART-patient cohort (2% of all ART patients). The probabilities for survival on ART at 6 months, 12 months and 18 months were 85%, 81% and 78%, respectively. An estimated 250 health-care workers lives were saved 12 months after ART initiation. Their combined work-time of more than 1000 staff-days per week was equivalent to the human resources required to provide ART at the national level. CONCLUSION: A large number of ART patients in Malawi are managed by a small proportion of the health-care workforce. Many health-care workers have accessed ART with good treatment outcomes. Currently, staffing required for ART balances against health-care workers lives saved through treatment, although this may change in the future

NOD2 genetic variants and sarcoidosis-associated uveitis☆

Purpose Identifying genetic risk factors for developing sarcoidosis-associated uveitis could provide insights into its pathogenesis which is poorly understood. We determine if variants in NOD2 confer an increased risk of developing uveitis in adults with sarcoidosis. Methods: In this genetic case-control study, 51 total subjects were enrolled: 39 patients diagnosed with sarcoid-related uveitis and 12 patients with systemic sarcoidosis without ocular involvement as controls. Sanger sequencing of the eleven exons of the NOD2 gene was performed on DNA obtained from whole blood. Sanger sequencing data were aligned against the NOD2 NCBI-RefSeq reference sequence to identify novel mutations in uveitis patients. For common variants, allele frequencies in cases versus controls were compared using the chi-square test. Results: There were no significant differences in NOD2 common variant allele frequencies between sarcoidosis patients with and without uveitis, and none of the pathogenic NOD2 mutations associated with Blau syndrome were found in this cohort. However, four rare, non-synonymous variants were identified in four patients with ocular sarcoidosis and none of the controls. Variants rs149071116, rs35285618, and 16:g.50745164T > C have never been previously reported to be associated with any disease and may be pathogenic. The fourth variant, rs2066845, is associated with Crohn’s disease and psoriatic arthritis. Conclusions: Despite the phenotypic overlap between sarcoidosis and Blau syndrome, none of the established pathogenic NOD2 variants were present in adults with sarcoidosis. However, four novel, rare, non-synonymous variants were identified in four cases with ocular sarcoidosis. Further investigation is needed to explore the potential clinical significance of these polymorphisms

NOD2 genetic variants and sarcoidosis-associated uveitis

Purpose: Identifying genetic risk factors for developing sarcoidosis-associated uveitis could provide insights into its pathogenesis which is poorly understood. We determine if variants in NOD2 confer an increased risk of developing uveitis in adults with sarcoidosis. Methods: In this genetic case-control study, 51 total subjects were enrolled: 39 patients diagnosed with sarcoid-related uveitis and 12 patients with systemic sarcoidosis without ocular involvement as controls. Sanger sequencing of the eleven exons of the NOD2 gene was performed on DNA obtained from whole blood. Sanger sequencing data were aligned against the NOD2 NCBI-RefSeq reference sequence to identify novel mutations in uveitis patients. For common variants, allele frequencies in cases versus controls were compared using the chi-square test. Results: There were no significant differences in NOD2 common variant allele frequencies between sarcoidosis patients with and without uveitis, and none of the pathogenic NOD2 mutations associated with Blau syndrome were found in this cohort. However, four rare, non-synonymous variants were identified in four patients with ocular sarcoidosis and none of the controls. Variants rs149071116, rs35285618, and 16:g.50745164T > C have never been previously reported to be associated with any disease and may be pathogenic. The fourth variant, rs2066845, is associated with Crohn’s disease and psoriatic arthritis. Conclusions: Despite the phenotypic overlap between sarcoidosis and Blau syndrome, none of the established pathogenic NOD2 variants were present in adults with sarcoidosis. However, four novel, rare, non-synonymous variants were identified in four cases with ocular sarcoidosis. Further investigation is needed to explore the potential clinical significance of these polymorphisms

A national survey of the impact of rapid scale-up of antiretroviral therapy on health-care workers in Malawi: effects on human resources and survival

OBJECTIVE: To assess the human resources impact of Malawi’s rapidly growing antiretroviral therapy (ART) programme and balance this against the survival benefit of health-care workers who have accessed ART themselves. METHODS: We conducted a national cross-sectional survey of the human resource allocation in all public-sector health facilities providing ART in mid-2006. We also undertook a survival analysis of health-care workers who had accessed ART in public and private facilities by 30 June 2006, using data from the national ART monitoring and evaluation system. FINDINGS: By 30 June 2006, 59 581 patients had accessed ART from 95 public and 28 private facilities. The public sites provided ART services on 2.4 days per week on average, requiring 7% of the clinician workforce, 3% of the nursing workforce and 24% of the ward clerk workforce available at the facilities. We identified 1024 health-care workers in the national ART-patient cohort (2% of all ART patients). The probabilities for survival on ART at 6 months, 12 months and 18 months were 85%, 81% and 78%, respectively. An estimated 250 health-care workers’ lives were saved 12 months after ART initiation. Their combined work-time of more than 1000 staff-days per week was equivalent to the human resources required to provide ART at the national level. CONCLUSION: A large number of ART patients in Malawi are managed by a small proportion of the health-care workforce. Many health-care workers have accessed ART with good treatment outcomes. Currently, staffing required for ART balances against health-care workers’ lives saved through treatment, although this may change in the future

Assessing the quality of data aggregated by antiretroviral treatment clinics in Malawi

PROBLEM: As national antiretroviral treatment (ART) programmes scale-up, it is essential that information is complete, timely and accurate for site monitoring and national planning. The accuracy and completeness of reports independently compiled by ART facilities, however, is often not known. APPROACH: This study assessed the quality of quarterly aggregate summary data for April to June 2006 compiled and reported by ART facilities ("site report") as compared to the "gold standard" facility summary data compiled independently by the Ministry of Health supervision team ("supervision report"). Completeness and accuracy of key case registration and outcome variables were compared. Data were considered inaccurate if variables from the site reports were missing or differed by more than 5% from the supervision reports. Additionally, we compared the national summaries obtained from the two data sources. LOCAL SETTING: Monitoring and evaluation of Malawi's national ART programme is based on WHO's recommended tools for ART monitoring. It includes one master card for each ART patient and one patient register at each ART facility. Each quarter, sites complete cumulative cohort analyses and teams from the Ministry of Health conduct supervisory visits to all public sector ART sites to ensure the quality of reported data. RELEVANT CHANGES: Most sites had complete case registration and outcome data; however many sites did not report accurate data for several critical data fields, including reason for starting, outcome and regimen. The national summary using the site reports resulted in a 12% undercount in the national total number of persons on first-line treatment. Several facility-level characteristics were associated with data quality. LESSONS LEARNED: While many sites are able to generate complete data summaries, the accuracy of facility reports is not yet adequate for national monitoring. The Ministry of Health and its partners should continue to identify and support interventions such as supportive supervision to build sites' capacity to maintain and compile quality data to ensure that accurate information is available for site monitoring and national planning

Malawi's contribution to "3 by 5": achievements and challenges

PROBLEM: Many resource-poor countries have started scaling up antiretroviral therapy (ART). While reports from individual clinics point to successful implementation, there is limited information about progress in government institutions at a national level. APPROACH: Malawi started national ART scale-up in 2004 using a structured approach. There is a focus on one generic, fixed-dose combination treatment with stavudine, lamivudine and nevirapine. Treatment is delivered free of charge to eligible patients with HIV and there is a standardized system for recruiting patients, monthly follow-up, registration, monitoring and reporting of cases and outcomes. All treatment sites receive quarterly supervision and evaluation. LOCAL SETTING: In January 2004, there were nine public sector facilities delivering ART to an estimated 4 000 patients. By December 2005, there were 60 public sector facilities providing free ART to 37 840 patients using national standardized systems. Analysis of quarterly cohort treatment outcomes at 12 months showed 80% of patients were alive, 10% dead, 9% lost to follow-up and 1% had stopped treatment. LESSONS LEARNED: Achievements were the result of clear national ART guidelines, implementing partners working together, an intensive training schedule focused on clinical officers and nurses, a structured system of accrediting facilities for ART delivery, quarterly supervision and monitoring, and no stock-outs of antiretroviral drugs. The main challenges are to increase the numbers of children, pregnant women and patients with tuberculosis being started on ART, and to avert high early mortality and losses to follow-up. The capacity of the health sector to cope with escalating case loads and to scale up prevention alongside treatment will determine the future success of ART delivery in Malawi