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The Global Fund's principal recipients ... or neglected partners
Abstract
The Global Fund to fight AIDS Tuberculosis and Malaria recently released a progress report for its first 30 months. The Fund has made pledges of US$5.4 million through 2008 and has committed $3.1 billion to almost 300 2-year programmes in nearly 130 countries over four rounds of grants and is on schedule to disburse nearly $1 billion to over 200 programmes by the end of 2004. However the Fund must ensure the quick efficient and effective use of these resources to stem the suffering caused by the three diseases. The Fund’s second significant achievement has been “the pioneering of a number of innovative structures to ensure country ownership speedy and light-handed oversight and performance-based funding...[of] Country Coordinating Mechanisms (CCMs) a variety of recipient structures Local Fund Agents and monitoring and evaluations systems.” Unfortunately the linchpin organisations in this management the principal recipients are being neglected and undervalued by the Fund secretariat the CCMs UN agencies and donors. Principal recipients must be supported if the Fund is to be highly successful. (excerpt)
... The PRs' importance in the Global Fund's operations cannot be overemphasized. However, there are concerns over how well informed the Global Fund is on PRs, for instance, what constitutes an effective environment for sound implementation [3], and what support PRs need to improve their performance [4]. Partly in response to such concerns, the Global Fund recently adjusted its governance structure, allocating more staff towards grant management, and adopted a 'New Funding Model' [5]. ...
... The survey found that most PRs were somewhat unhappy with grant negotiation and signing processes, recommending that the processes be simplified, and that the Fund put more effort in explaining changes. The Fund has in the past been criticized for blaming PRs for poor grant performance without providing them with adequate guidance and support [4]. However, this is an area that the new funding model is designed to address, with the Fund introducing structures to support continuous dialogue between itself and recipients, and across in-country actors. ...
Principal Recipients (PRs) receive money from the Global Fund to fight AIDS, Tuberculosis and Malaria (Global Fund) to manage and implement programs. However, little research has gone into understanding their opinions and experiences. This survey set out to describe these, thereby providing a baseline against which changes in PR opinions and experiences can be assessed as the recently introduced new funding model is rolled out.Methodology: An internet based questionnaire was administered to 315 PRs. A total of 115 responded from 69 countries in Africa, Asia, Eastern Europe and Latin America. The study was conducted between September and December 2012.
Three quarters of PRs thought the progress update and disbursement request (PU/DR) system was a useful method of reporting grant progress. However, most felt that the grant negotiation processes were complicated, and that the grant rating system did not reflect performance.While nearly all PRs were happy with the work being done by sub-Recipients (92%) and Fund Portfolio Managers (86%), fewer were happy with the Office of the Inspector General (OIG). Non-government PRs were generally less happy with the OIG's work compared to government PRs.Most PRs thought the Global Fund's Voluntary Pooled Procurement system made procurement easier. However, only 29% said the system should be made compulsory.When asked which aspects of the Global Fund's operations needed improvement, most PRs said that the Fund should re-define and clarify the roles of different actors, minimize staff turnover at its Secretariat, and shorten the grant application and approval processes. All these are currently being addressed, either directly or indirectly, under a new funding model. Vigorous assessments should nonetheless follow the roll-out of the new model to ensure the areas that are most likely to affect PR performance realize sustained improvement.
Opinions and experiences with the Global Fund were varied, with PRs having good communication with Fund Portfolio Managers and sub-Recipients, but being unhappy with the grant negotiation and grant rating systems. Recommendations included simplifying grant processes, finding performance assessment methods that look beyond numbers, and employing Local Fund Agents who understand public health aspects of programs.
... These organizations have been criticized as slow bureaucracies of middlemen (an after thought of the Global Fund when compared to the CCMs and the review committees) and lacking in appropriate support. In some cases new or young principle funds have collapsed under the pressure to distribute (Hruska, 2004). Other concerns include criticism of a limited vision due to the short funding periods of two to five years, and a lack of consideration to donors and NGOs. ...
The United States' Presidential Emergency Plan for HIV/AIDS Relief (PEPFAR) continues to draw concern from the international community, which argues that PEPFAR is undermining the Global Fund to Fight HIV/AIDS, Tuberculosis, and Malaria. While PEPFAR offers some clear advantages, the handpicking of benefactors remains questionable. Also, its loyalty to faith-based groups denies populations' access to proven birth control methods. In Uganda, PEPFAR has substantially reduced the highly successful ABC program (Abstinence, Be faithful, use Condoms) to the A and B components. This ignores prevailing sexual behaviours by assuming that sex is a choice. The Global Fund is not criticism free but weak proportional funding from donor countries, specifically the United States, is its largest burden. Thus, while PEPFAR campaigns as a vigilant warrior in the fight against HIV/AIDS, it is at best a duplication of existing multilateral pursuits and at worst, a serious hindrance to the global fight against the pandemic. RÉSUMÉ – Le Plan d'Urgence Présidentiel de Lutte contre le VIH/SIDA (PEPFAR) des Etats-Unis attire encore des inquietudes de la part de la communauté internationale, qui soutient que le PEPFAR ébranle le Fonds Global pour combattre le VIH/SIDA, la tuberculose et le paludisme. Alors que le PEPFAR offer quelques avantages précis, la selection des beneficiaries demeure discutable. De plus, sa loyauté aux groupes confessionnels prive les populations de l'accès à des methods de contraceptions qui ont fait leurs preuves. En Ouganda, le PEPFAR a diminué de façon considerable le programme ABC (Abstinence, Be faithful, use Condoms/abstinene, Sois fidèle, utilize des condoms), qui réussissait très bien, aux composantes A et B seulement. Ceci ignore les comportements sexuels actuels en supposant que le sexe est un choix. Le Fonds Global n'est pas sans reproche, mais le faible financement proportionnel des pays donateurs, en particulier les Etats-Unis, est son fardeau le plus lourd. Ainsi, alors que le PEPFAR milite en tant que vaillant guerrier dans le combat contre le VIH/SIDA, c'est au mieux, un duplicat des poursuites multilatérales déjà existantes et au pire, c'est un obstacle de taille au combat global contre la pandémie.
Because survival rates among childhood cancer patients are increasing, assessing the risk of second and subsequent malignant neoplasms (SMNs) is ever more important. Using the Childhood Cancer Survivor Study cohort, we identified the risk of SMNS:
A retrospective cohort of 13 581 children diagnosed with common cancers before age 21 years and surviving at least 5 years was constructed with the use of data from patients treated at 25 U.S. and Canadian institutions. SMNs were ascertained through self-administered questionnaires and verified by pathology reports. Information on therapeutic exposures was abstracted from medical records. The risk of SMN was evaluated by standardized incidence ratios (SIRs) and excess absolute risk. Poisson multiple regression models were used to assess the impact of host and therapy factors on the risk of developing SMNS: All statistical tests were two-sided.
In 298 individuals, 314 SMNs were identified (SIR = 6.38; 95% confidence interval [CI] = 5.69 to 7.13). The largest observed excess SMNs were bone and breast cancers (SIR = 19.14 [95% CI = 12.72 to 27.67] and SIR = 16.18 [95% CI = 12.35 to 20.83], respectively). A statistically significant excess of SMNs followed all childhood cancers. In multivariate regression models adjusted for therapeutic radiation exposure, SMNs of any type were independently associated with female sex (P<.001), childhood cancer at a younger age (P for trend <.001), childhood Hodgkin's disease or soft-tissue sarcoma (P<.001 and P =.01, respectively), and exposure to alkylating agents (P for trend =.02). Twenty years after the childhood cancer diagnosis, the cumulative estimated SMN incidence was 3.2%. However, only 1.88 excess malignancies occurred per 1000 years of patient follow-up.
Success in treating children with cancer should not be overshadowed by the incidence of SMNS: However, patients and health-care providers must be aware of risk factors for SMNs so that surveillance is focused and early prevention strategies are implemented.
Treatment of pediatric acute lymphoblastic leukemia (ALL) is based on the concept of tailoring the intensity of therapy to a patient's risk of relapse. To determine whether gene expression profiling could enhance risk assignment, we used oligonucleotide microarrays to analyze the pattern of genes expressed in leukemic blasts from 360 pediatric ALL patients. Distinct expression profiles identified each of the prognostically important leukemia subtypes, including T-ALL, E2A-PBX1, BCR-ABL, TEL-AML1, MLL rearrangement, and hyperdiploid >50 chromosomes. In addition, another ALL subgroup was identified based on its unique expression profile. Examination of the genes comprising the expression signatures provided important insights into the biology of these leukemia subgroups. Further, within some genetic subgroups, expression profiles identified those patients that would eventually fail therapy. Thus, the single platform of expression profiling should enhance the accurate risk stratification of pediatric ALL patients.
The survival rates of children treated for cancer have dramatically increased after the development of standardized multiple-modality treatment protocols. As a result, there is a rapidly growing population of pediatric cancer survivors in which the long-term genotoxic effects of chemotherapeutic intervention is unknown. To study the genotoxic effects of antineoplastic treatment in children, we performed a comparative analysis of the changes in the frequency of somatic mutations (Mfs) at the hypoxanthine-guanine phosphoribosyltransferase (HPRT)-reporter gene in children treated for acute lymphocytic leukemia (ALL). We measured HPRT Mfs from 130 peripheral blood samples from 45 children with ALL (13, low risk; 22, standard risk; and 10, high risk) from the time of diagnosis, as well as during and after the completion of therapy. We observed a significant increase in mean HPRT Mfs during each phase of therapy (diagnosis, 1.4 x 10(-6); consolidation, 52.1 x 10(-6); maintenance, 93.2 x 10(-6); and off-therapy, 271.7 x 10(-6)) that were independent of the risk group treatment protocol used. This 200-fold increase in mean somatic Mf remained elevated years after the completion of therapy. We did not observe a significant difference in the genotoxicity of each risk group treatment modality despite differences in the compositional and clinical toxicity associated with these treatment protocols. These findings suggest that combination chemotherapy used to treat children with ALL is quite genotoxic, resulting in an increased somatic mutational load that may result in an elevated risk for the development of multi-factorial diseases, in particular second malignancies.
Etoposide is among the most widely used anti-cancer drugs. Its use, however, has been associated with increased risk of secondary acute myeloid leukemia (AML) which is characterized by chromosomal translocations suggesting involvement of recombination-associated motifs at the breakpoints. A PCR-based assay was developed to quantitate the frequency of two illegitimate V(D)J recombinase-mediated genomic rearrangements-a 20-kb deletion in the hprt gene and the bcl2/IgH translocation (t(14;18)) found in non-Hodgkin's lymphoma. We examined both lymphocyte and non-lymphocyte blood cell DNA of children with acute lymphoblastic leukemia (ALL) for changes in the frequencies of these biomarkers during etoposide therapy to determine the level of illegitimate V(D)J recombination changes during therapy. A low level of t(14;18) was found in the lymphocytes before etoposide treatment, which was significantly reduced during etoposide therapy. In before-etoposide samples, no t(14;18) were found among 7.72x107 non-lymphocytes; during treatment none were found among 1.87x108 non-lymphocytes. Deletions were not found before etoposide treatment in either the lymphocytes (6.67x107) or non-lymphocytes (5.43x107) and were non-significantly elevated during etoposide therapy (1 in 1.4x108 lymphocytes and 1 in 1.39x108 non-lymphocytes). It is interesting to note the one patient with an hprt deletion mutation in non-lymphocytes; V(D)J recombination is not normally found in this cell type, but is the cell type from which AML derives. Several patients had clones of t(14;18)-bearing cells as determined by DNA sequence analysis. These results suggest that this etoposide-based chemotherapy was ineffective in producing genomic rearrangements mediated by illegitimate V(D)J recombination in these patients.
More than 70% of children diagnosed with cancer can now be expected to be long-term survivors. However, the consequences of 'cure' might be considerable for the survivors of cancer: 60-70% of young adults who have survived childhood cancer will develop at least one medical disability as a result of their cancer or, more commonly, as a result of their therapy. Of these, the most devastating is a second cancer.
Individuals respond differently to drugs and sometimes the effects are unpredictable. Differences in DNA that alter the expression or function of proteins that are targeted by drugs can contribute significantly to variation in the responses of individuals. Many of the genes examined in early studies were linked to highly penetrant, single-gene traits, but future advances hinge on the more difficult challenge of elucidating multi-gene determinants of drug response. This intersection of genomics and medicine has the potential to yield a new set of molecular diagnostic tools that can be used to individualize and optimize drug therapy.