RESUMO
BACKGROUND: Although non-Hodgkin lymphoma (NHL) is the 6th most common malignancy in Sub-Saharan Africa (SSA), little is known about its management and outcome. Herein, we examined treatment patterns and survival among NHL patients. METHODS: We obtained a random sample of adult patients diagnosed between 2011 and 2015 from 11 population-based cancer registries in 10 SSA countries. Descriptive statistics for lymphoma-directed therapy (LDT) and degree of concordance with National Comprehensive Cancer Network (NCCN) guidelines were calculated, and survival rates were estimated. FINDINGS: Of 516 patients included in the study, sub-classification was available for 42.1% (121 high-grade and 64 low-grade B-cell lymphoma, 15 T-cell lymphoma and 17 otherwise sub-classified NHL), whilst the remaining 57.9% were unclassified. Any LDT was identified for 195 of all patients (37.8%). NCCN guideline-recommended treatment was initiated in 21 patients. This corresponds to 4.1% of all 516 patients, and to 11.7% of 180 patients with sub-classified B-cell lymphoma and NCCN guidelines available. Deviations from guideline-recommended treatment were initiated in another 49 (9.5% of 516, 27.2% of 180). By registry, the proportion of all patients receiving guideline-concordant LDT ranged from 30.8% in Namibia to 0% in Maputo and Bamako. Concordance with treatment recommendations was not assessable in 75.1% of patients (records not traced (43.2%), traced but no sub-classification identified (27.8%), traced but no guidelines available (4.1%)). By registry, diagnostic work-up was in part importantly limited, thus impeding guideline evaluation significantly. Overall 1-year survival was 61.2% (95%CI 55.3%-67.1%). Poor ECOG performance status, advanced stage, less than 5 cycles and absence of chemo (immuno-) therapy were associated with unfavorable survival, while HIV status, age, and gender did not impact survival. In diffuse large B-cell lymphoma, initiation of guideline-concordant treatment was associated with favorable survival. INTERPRETATION: This study shows that a majority of NHL patients in SSA are untreated or undertreated, resulting in unfavorable survival. Investments in enhanced diagnostic services, provision of chemo(immuno-)therapy and supportive care will likely improve outcomes in the region.
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Linfoma Difuso de Grandes Células B , Linfoma de Células T Periférico , Linfoma de Células T , Humanos , Adulto , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The burden of colorectal cancer (CRC) is increasing in Sub-Saharan Africa (SSA). However, little is known about CRC treatment and survival in the region. METHODS: A random sample of 653 patients with CRC diagnosed from 2011 to 2015 was obtained from 11 population-based cancer registries in SSA. Information on clinical characteristics, treatment, and/or vital status was obtained from medical records in treating hospitals for 356 (54%) of the patients ("traced cohort"). Concordance of CRC treatment with NCCN Harmonized Guidelines for SSA was assessed. A Cox proportional hazards model was used to examine the association between survival and human development index (HDI). RESULTS: Of the 356 traced patients with CRC, 51.7% were male, 52.8% were from countries with a low HDI, 55.1% had colon cancer, and 73.6% were diagnosed with nonmetastatic (M0) disease. Among the patients with M0 disease, however, only 3.1% received guideline-concordant treatment, 20.6% received treatment with minor deviations, 31.7% received treatment with major deviations, and 35.1% received no treatment. The risk of death in patients who received no cancer-directed therapy was 3.49 (95% CI, 1.83-6.66) times higher than in patients who received standard treatment or treatment with minor deviations. Similarly, the risk of death in patients from countries with a low HDI was 1.67 (95% CI, 1.07-2.62) times higher than in those from countries with a medium HDI. Overall survival at 1 and 3 years was 70.9% (95% CI, 65.5%-76.3%) and 45.3% (95% CI, 38.9%-51.7%), respectively. CONCLUSIONS: Fewer than 1 in 20 patients diagnosed with potentially curable CRC received standard of care in SSA, reinforcing the need to improve healthcare infrastructure, including the oncology and surgical workforce.
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Neoplasias do Colo , Projetos de Pesquisa , Humanos , Masculino , Feminino , Seguimentos , Instalações de Saúde , África Subsaariana/epidemiologiaRESUMO
There are limited population-based survival data for colorectal cancer (CRC) in sub-Saharan Africa. Here, 1707 persons diagnosed with CRC from 2005 to 2015 were randomly selected from 13 population-based cancer registries operating in 11 countries in sub-Saharan Africa. Vital status was ascertained from medical charts or through next of kin. 1-, 3- and 5-year overall and relative survival rates for all registries and for each registry were calculated using the Kaplan-Meier estimator. Multivariable analysis was used to examine the associations of 5-year relative survival with age at diagnosis, stage and country-level Human Development Index (HDI). Observed survival for 1448 patients with CRC across all registries combined was 72.0% (95% CI 69.5-74.4%) at 1 year, 50.4% (95% CI 47.6-53.2%) at 3 years and 43.5% (95% CI 40.6-46.3%) at 5 years. We estimate that relative survival at 5 years in these registry populations is 48.2%. Factors associated with poorer survival included living in a country with lower HDI, late stage at diagnosis and younger or older age at diagnosis (<50 or ≥70 years). For example, the risk of death was 1.6 (95% CI 1.2-2.1) times higher for patients residing in medium-HDI and 2.7 (95% CI 2.2-3.4) times higher for patients residing in low-HDI compared to those residing in high-HDI countries. Survival for CRC remains low in sub-Saharan African countries, though estimates vary considerably by HDI. Strengthening health systems to ensure access to prevention, early diagnosis and appropriate treatment is critical in improving outcomes of CRC in the region.
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Neoplasias Colorretais/mortalidade , Sistema de Registros/estatística & dados numéricos , África Subsaariana/epidemiologia , Fatores Etários , Idoso , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de SobrevidaRESUMO
BACKGROUND: Although prostate cancer (PCa) is the most commonly diagnosed cancer in men of sub-Saharan Africa (SSA), little is known about its management and survival. The objective of the current study was to describe the presentation, patterns of diagnosis, treatment, and survival of patients with PCa in 10 countries of SSA. METHODS: In this observational registry study with data collection from 2010 to 2018, the authors drew a random sample of 738 patients with PCa who were registered in 11 population-based cancer registries. They described proportions of patients receiving recommended care and presented survival estimates. Multivariable Cox regression was used to calculate hazard ratios comparing the survival of patients with and without cancer-directed therapies (CDTs). RESULTS: The study included 693 patients, and tumor characteristics and treatment information were available for 365 patients, 37.3% of whom had metastatic disease. Only 11.2% had a complete diagnostic workup for risk stratification. Among the nonmetastatic patients, 17.5% received curative-intent therapy, and 27.5% received no CDT. Among the metastatic patients, 59.6% received androgen deprivation therapy. The 3- and 5-year age-standardized relative survival for 491 patients with survival time information was 58.8% (95% confidence interval [CI], 48.5%-67.7%) and 56.9% (95% CI, 39.8%-70.9%), respectively. In a multivariable analysis, survival was considerably poorer among patients without CDT versus those with therapy. CONCLUSIONS: This study shows that a large proportion of patients with PCa in SSA are not staged or are insufficiently staged and undertreated, and this results in unfavorable survival. These findings reemphasize the need for improving diagnostic workup and access to care in SSA in order to mitigate the heavy burden of the disease in the region.
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Antagonistas de Androgênios , Neoplasias da Próstata , África Subsaariana/epidemiologia , Humanos , Masculino , Modelos de Riscos Proporcionais , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/terapia , Sistema de RegistrosRESUMO
OBJECTIVES: To estimate observed and relative survival of prostate cancer patients in sub-Saharan Africa (SSA) and to examine the influence of age, stage at diagnosis and the Human Development Index (HDI). PATIENTS AND METHODS: In this comparative registry study, we selected a random sample of 1752 incident cases of malign prostatic neoplasm from 12 population-based cancer registries from 10 SSA countries, registered between 2005 and 2015. We analyzed the data using Kaplan-Meier and Ederer II methods to obtain outcome estimates and flexible Poisson regression modeling to calculate the excess hazards of death RESULTS: For the 1406 patients included in the survival analyses, 763 deaths occurred during 3614 person-years of observation. Of patients with known stage, 45.2% had stage IV disease, 31.2% stage III and only 23.6% stage I and II. The 1 and 5-year relative survival for the entire cohort was 78.0% (75.4-80.7) and 60.0% (55.7-64.6), while varying between the registries. Late presentation was associated with increased excess hazards and a 0.1 increase in the HDI was associated with a 20% lower excess hazard of death, while for age at diagnosis no association was found. CONCLUSIONS: We found poor survival of SSA prostatic tumor patients, as well as high proportions of late stage presentation, which are associated with inferior outcome. This calls for investment in health-care systems and action regarding projects to raise awareness among the population to achieve earlier diagnosis and improve survival.
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Neoplasias da Próstata , África Subsaariana , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Sistema de RegistrosRESUMO
Cervical cancer is the leading cause of cancer death in African women. We sought to estimate population-based survival and evaluate excess hazards for mortality in African women with cervical cancer, examining the effects of country-level Human Development Index (HDI), age and stage at diagnosis. We selected a random sample of 2760 incident cervical cancer cases, diagnosed in 2005 to 2015 from 13 population-based cancer registries in 11 countries (Benin, Cote d'Ivoire, Ethiopia, Kenya, Mauritius, Mozambique, Namibia, Seychelles, South Africa, Uganda and Zimbabwe) through the African Cancer Registry Network. Of these, 2735 were included for survival analyses. The 1-, 3- and 5-year observed and relative survival were estimated by registry, stage and country-level HDI. We used flexible Poisson regression models to estimate the excess hazards for death adjusting for age, stage and HDI. Among patients with known stage, 65.8% were diagnosed with Stage III-IV disease. The 5-year relative survival for Stage I-II cervical cancer in high HDI registry areas was 67.5% (42.1-83.6) while it was much lower (42.2% [30.6-53.2]) for low HDI registry areas. Independent predictors of mortality were Stage III-IV disease, medium to low country-level HDI and age >65 years at cervical cancer diagnosis. The average relative survival from cervix cancer in the 11 countries was 69.8%, 44.5% and 33.1% at 1, 3 and 5 years, respectively. Factors contributing to the HDI (such as education and a country's financial resources) are critical for cervical cancer control in SSA and there is need to strengthen health systems with timely and appropriate prevention and treatment programmes.
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Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Adulto , África Subsaariana/epidemiologia , Idoso , Escolaridade , Feminino , Desenvolvimento Humano , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Sistema de Registros , Análise de SobrevidaRESUMO
Breast cancer is the leading cancer diagnosis and second most common cause of cancer deaths in sub-Saharan Africa (SSA). Yet, there are few population-level survival data from Africa and none on the survival differences by stage at diagnosis. Here, we estimate breast cancer survival within SSA by area, stage and country-level human development index (HDI). We obtained data on a random sample of 2,588 breast cancer incident cases, diagnosed in 2008-2015 from 14 population-based cancer registries in 12 countries (Benin, Cote d'Ivoire, Ethiopia, Kenya, Mali, Mauritius, Mozambique, Namibia, Seychelles, South Africa, Uganda and Zimbabwe) through the African Cancer Registry Network. Of these, 2,311 were included for survival analyses. The 1-, 3- and 5-year observed and relative survival (RS) were estimated by registry, stage and country-level HDI. We equally estimated the excess hazards adjusting for potential confounders. Among patients with known stage, 64.9% were diagnosed in late stages, with 18.4% being metastatic at diagnosis. The RS varied by registry, ranging from 21.6%(8.2-39.8) at Year 3 in Bulawayo to 84.5% (70.6-93.5) in Namibia. Patients diagnosed at early stages had a 3-year RS of 78% (71.6-83.3) in contrast to 40.3% (34.9-45.7) at advanced stages (III and IV). The overall RS at Year 1 was 86.1% (84.4-87.6), 65.8% (63.5-68.1) at Year 3 and 59.0% (56.3-61.6) at Year 5. Age at diagnosis was not independently associated with increased mortality risk after adjusting for the effect of stage and country-level HDI. In conclusion, downstaging breast cancer at diagnosis and improving access to quality care could be pivotal in improving breast cancer survival outcomes in Africa.
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Neoplasias da Mama/mortalidade , Fatores Socioeconômicos , África Subsaariana/epidemiologia , Fatores Etários , Mama/patologia , Neoplasias da Mama/patologia , Feminino , Seguimentos , Acessibilidade aos Serviços de Saúde/organização & administração , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Melhoria de Qualidade , Sistema de Registros/estatística & dados numéricos , Medição de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: Cervical cancer is the second most common cancer and the leading cause of cancer death in women in sub-Saharan Africa (SSA). METHODS: Trends in the incidence of cervical cancer are examined for a period of 10-25 years in 10 population-based cancer registries across eight SSA countries (Gambia, Kenya, Malawi, Mauritius, Seychelles, South Africa, Uganda and Zimbabwe). A total of 21,990 cases of cervical cancer were included in the analyses. RESULTS: Incidence rates had increased in all registries for some or all of the periods studied, except for Mauritius with a constant annual 2.5% decline. Eastern Cape and Blantyre (Malawi) registries showed significant increases over time, with the most rapid being in Blantyre (7.9% annually). In Kampala (Uganda), a significant increase was noted (2.2%) until 2006, followed by a non-significant decline. In Eldoret, a decrease (1998-2002) was followed by a significant increase (9.5%) from 2002 to 2016. CONCLUSION: Overall, cervical cancer incidence has been increasing in SSA. The current high-level advocacy to reduce the burden of cervical cancer in SSA needs to be translated into support for prevention (vaccination against human papillomavirus and population-wide screening), with careful monitoring of results through population-based registries.
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Papillomaviridae/patogenicidade , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adulto , Idoso , Feminino , Humanos , Quênia/epidemiologia , Pessoa de Meia-Idade , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus , Sistema de Registros , África do Sul/epidemiologia , Uganda/epidemiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologiaRESUMO
Non-Hodgkin lymphoma (NHL) is the sixth most common cancer in Sub-Saharan Africa (SSA). Comprehensive diagnostics of NHL are essential for effective treatment. Our objective was to assess the frequency of NHL subtypes, disease stage and further diagnostic aspects. Eleven population-based cancer registries in 10 countries participated in our observational study. A random sample of 516 patients was included. Histological confirmation of NHL was available for 76.2% and cytological confirmation for another 17.3%. NHL subclassification was determined in 42.1%. Of these, diffuse large B cell lymphoma, chronic lymphocytic leukaemia and Burkitt lymphoma were the most common subtypes identified (48.8%, 18.4% and 6.0%, respectively). We traced 293 patients, for whom recorded data were amended using clinical records. For these, information on stage, human immunodeficiency virus (HIV) status and Eastern Cooperative Oncology Group Performance Status (ECOG PS) was available for 60.8%, 52.6% and 45.1%, respectively. Stage at diagnosis was advanced for 130 of 178 (73.0%) patients, HIV status was positive for 97 of 154 (63.0%) and ECOG PS was ≥2 for 81 of 132 (61.4%). Knowledge about NHL subclassification and baseline clinical characteristics is crucial for guideline-recommended treatment. Hence, regionally adapted investments in pathological capacity, as well as standardised clinical diagnostics, will significantly improve the therapeutic precision for NHL in SSA.
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Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/epidemiologia , Adolescente , Adulto , África Subsaariana , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
Fueled by HIV, sub-Saharan Africa has the highest incidence of Kaposi's sarcoma (KS) in the world. Despite this, KS diagnosis in the region is based mostly on clinical grounds. Where biopsy is available, it has traditionally been excisional and performed by surgeons, resulting in multiple appointments, follow-up visits for suture removal, and substantial costs. We hypothesized that a simpler approach - skin punch biopsy - would make histologic diagnosis more accessible. To address this, we provided training and equipment for skin punch biopsy of suspected KS to three HIV clinics in East Africa. The procedure consisted of local anesthesia followed by a disposable cylindrical punch blade to obtain specimens. Hemostasis is facilitated by Gelfoam®. Patients removed the dressing after 4 days. From 2007 to 2013, 2,799 biopsies were performed. Although originally targeted to be used by physicians, biopsies were performed predominantly by nurses (62%), followed by physicians (15%), clinical officers (12%) and technicians (11%). There were no reports of recurrent bleeding or infection. After minimal training and provision of inexpensive equipment (USD 3.06 per biopsy), HIV clinics in East Africa can integrate same-day skin punch biopsy for suspected KS. Task shifting from physician to non-physician greatly increases access. Skin punch biopsy should be part of any HIV clinic's essential procedures. This example of task shifting may also be applicable to the diagnosis of other cancers (e.g., breast) in resource-limited settings.
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Biópsia/métodos , Pessoal de Saúde/estatística & dados numéricos , Saúde Pública/métodos , Sarcoma de Kaposi/diagnóstico , Análise e Desempenho de Tarefas , Adulto , África Subsaariana/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Punções , Sarcoma de Kaposi/epidemiologia , Sarcoma de Kaposi/patologia , PeleRESUMO
OBJECTIVE: Kenya, like many resource-constrained countries, has a single mycobacterial laboratory, centrally located in Nairobi, with capacity for drug-susceptibility testing (DST) - the gold standard in diagnosing drug-resistant tuberculosis. We describe and evaluate a novel operational design that attempts to overcome diagnostic delivery barriers. METHODS: Review of the public DST programme identified several barriers limiting access: lack of programme awareness amongst physicians, limited supplies, unreliable transport and no specimen tracking methods. Staff visited 19 clinic sites in western Kenya and trained healthcare providers in regard to the novel diagnostics model. Provincial laboratory registries were reviewed to assess utilization of DST services prior to and after programme modification. RESULTS: Onsite training consisted of the inclusion criteria for re-treatment patients - the high-priority group for DST. Additionally, infrastructural support established a stable supply chain. An existing transport system was adapted to deliver sputum specimens. Task shifting created an accession and tracking system of specimens. During the 24 months post-implementation, the number of re-treatment specimens from the catchment area increased from 9.1 to 23.5 specimens per month. In comparing annual data pre- and post-implementation, the proportion of re-treatment cases receiving DST increased from 24.7% (n = 403) to 32.5% (n = 574) (P < 0.001), and the number of multidrug-resistant (MDR) TB cases increased from 5 to 10 cases. CONCLUSION: The delivery model significantly increased the proportion of re-treatment cases receiving DST. Barriers to accessing the national MDR-TB surveillance programme can be overcome through an operational model based on pragmatic use of existing services from multiple partners.
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Atenção à Saúde/normas , Resistência a Medicamentos , Acessibilidade aos Serviços de Saúde , Laboratórios/organização & administração , Mycobacterium tuberculosis , Avaliação de Programas e Projetos de Saúde , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Antituberculosos/uso terapêutico , Conscientização , Competência Clínica , Comportamento Cooperativo , Equipamentos e Provisões/provisão & distribuição , Pessoal de Saúde/educação , Humanos , Quênia/epidemiologia , Laboratórios/normas , Modelos Organizacionais , Seleção de Pacientes , Manejo de Espécimes , Escarro , Meios de Transporte , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologiaRESUMO
BACKGROUND: The monitoring of patients with human immunodeficiency virus (HIV) infection who are treated with antiretroviral medications in resource-limited settings is typically performed by use of clinical and immunological criteria. The early identification of first-line antiretroviral treatment failure is critical to prevent morbidity, mortality, and drug resistance. Misclassification of failure may result in premature switching to second-line therapy. METHODS: Adult patients in western Kenya had their viral loads (VLs) determined if they had adhered to first-line therapy for >6 months and were suspected of experiencing immunological failure (ie, their CD4 cell count decreased by 25% in 6 months). Misclassification of treatment failure was defined as a 25% decrease in CD4 cell count with a VL of <400 copies/mL. Logistic and tree regressions examined relationships between VL and 4 variables: CD4 T cell count (hereafter CD4 cell count), percentage of T cells expressing CD4 (hereafter CD4 cell percentage), percentage decrease in the CD4 T cell count (hereafter CD4 cell count percent decrease), and percentage decrease in the percentage of T cells expressing CD4 (hereafter CD4% percent decrease). RESULTS: There were 149 patients who were treated for 23 months; they were identified as having a 25% decrease in CD4 cell count (from 375 to 216 cells/microL) and a CD4% percent decrease (from 19% to 15%); of these 149 patients, 86 (58%) were misclassified as having experienced treatment failure. Of 42 patients who had a 50% decrease in CD4 cell count, 18 (43%) were misclassified. In multivariate logistic regression, misclassification odds were associated with a higher CD4 cell count, a shorter duration of therapy, and a smaller CD4% percent decrease. By combining these variables, we may be able to improve our ability to predict treatment failure. CONCLUSIONS: Immunological monitoring as a sole indicator of virological failure would lead to a premature switch to valuable second-line regimens for 58% of patients who experience a 25% decrease in CD4 cell count and for 43% patients who experience a 50% decrease in CD4 cell count, and therefore this type of monitoring should be reevaluated. Selective virological monitoring and the addition of indicators like trends CD4% percent decrease and duration of therapy may systematically improve the identification of treatment failure. VL testing is now mandatory for patients suspected of experiencing first-line treatment failure within the Academic Model Providing Access to Healthcare (AMPATH) in western Kenya, and should be considered in all resource-limited settings.
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Fármacos Anti-HIV/uso terapêutico , Erros de Diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , HIV/efeitos dos fármacos , Monitorização Imunológica/métodos , Adolescente , Adulto , Idoso , Contagem de Linfócito CD4 , Relação CD4-CD8 , Feminino , Infecções por HIV/virologia , Humanos , Quênia , Masculino , Pessoa de Meia-Idade , Falha de Tratamento , Carga Viral , Adulto JovemRESUMO
OBJECTIVE: Characterize failure and resistance above and below guidelines-recommended 1000âcopies/ml virologic threshold, upon second-line failure. DESIGN: Cross-sectional study. METHODS: Kenyan adults on lopinavir/ritonavir-based second-line were enrolled at AMPATH (Academic Model Providing Access to Healthcare). Charts were reviewed for demographic/clinical characteristics and CD4/viral load were obtained. Participants with detectable viral load had a second visit and pol genotyping was attempted in both visits. Accumulated resistance was defined as mutations in the second, not the first visit. Low-level viremia (LLV) was detectable viral load less than 1000âcopies/ml. Failure and resistance associations were evaluated using logistic and Poisson regression, Fisher Exact and t-tests. RESULTS: Of 394 participants (median age 42, 60% women, median 1.9 years on second-line) 48% had detectable viral load; 21% had viral load more than 1000âcopies/ml, associated with younger age, tuberculosis treatment, shorter time on second-line, lower CD4count/percentage, longer first-line treatment interruption and pregnancy. In 105 sequences from the first visit (35 with LLV), 79% had resistance (57% dual-class, 7% triple-class; 46% with intermediate-to-high-level resistance to ≥1 future drug option). LLV was associated with more overall and NRTI-associated mutations and with predicted resistance to more next-regimen drugs. In 48 second-visit sequences (after median 55 days; IQR 28-33), 40% accumulated resistance and LLV was associated with more mutation accumulation. CONCLUSION: High resistance upon second-line failure exists at levels above and below guideline-recommended virologic-failure threshold, impacting future treatment options. Optimization of care should include increased viral load monitoring, resistance testing and third-line ART access, and consideration of lowering the virologic failure threshold, though this demands further investigation.
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Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Adulto , Contagem de Linfócito CD4 , Estudos Transversais , Feminino , Genótipo , HIV-1/efeitos dos fármacos , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Quênia , Lopinavir/farmacologia , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ritonavir/farmacologia , Ritonavir/uso terapêutico , Análise de Sequência de DNA , Falha de Tratamento , Carga Viral , Viremia/tratamento farmacológico , Viremia/virologia , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genéticaRESUMO
Esophageal squamous cell carcinoma (ESCC) remains the predominant histological subtype of esophageal cancer (EC) in many transitioning countries, with an enigmatic and geographically distinct etiology, and consistently elevated incidence rates in many Eastern and Southern African countries. To gain epidemiological insights into ESCC patterns across the continent, we conducted a systematic review and meta-analysis of male-to-female (M:F) sex ratios of EC age-standardised (world) incidence rates in Africa according to geography, time and age at diagnosis. Data from 197 populations in 36 countries were included in the analysis, based on data from cancer registries included in IARC's Cancer Incidence in Five Continents, Cancer in Africa and Cancer in Sub-Saharan Africa reports, alongside a systematic search of peer-reviewed literature. A consistent male excess in incidence rates overall (1.7; 95% CI: 1.4, 2.0), and in the high-risk Eastern (1.6; 95% CI: 1.4, 1.8) and Southern (1.8; 95% CI: 1.5, 2.0) African regions was observed. Within the latter two regions, there was a male excess evident in 30-39â¯year olds that was not observed in low-risk regions. Despite possible referral biases affecting the interpretability of the M:F ratios in place and time, the high degree of heterogeneity in ESCC incidence implies a large fraction of the disease is preventable, and directs research enquiries to elucidate early-age exposures among young men in Africa.
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Neoplasias Esofágicas/epidemiologia , Sistema de Registros/estatística & dados numéricos , Adulto , África/epidemiologia , Fatores Etários , Idoso , Feminino , Geografia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto JovemRESUMO
INTRODUCTION: Cancer registration is an important activity for informing cancer control activities. Cancer registries in Sub-Saharan Africa have limited resources to effectively operate because of competing priorities. To date, there has not been an assessment of the resources and funding needed to perform all the activities essential for cancer registration in Kenya. Evidence will help registries to quantify and advocate for the funds needed to sustain, enhance, and expand high quality cancer registration in Kenya. METHODS: In this study, we used the Centers for Disease Control and Prevention's (CDC's) International Registry Costing Tool (IntRegCosting Tool) to evaluate the funding, cost, and labor resources used to perform the cancer registry operations in Nairobi County for two annual periods between July 2012 and June 2014. RESULTS: Funding from grants, research studies, and international organizations provided 70% of the registry operations' cost. For both time periods, the most-costly registry activities were related to administration, management, and training, along with data acquisition activities such as data abstraction, entry, and validation. Even among these core registry activities, however, substantial variations existed. CONCLUSIONS: Stable funding for cancer registry operations is necessary to sustain core registry activities in other to deliver high-quality data, which in turn is necessary to foster evidence-based policies to improve cancer outcomes. As stakeholders look into expanding the Nairobi Cancer Registry into a national program, the cost data provided in this study will help justify the funding required for sustaining and expanding registry activities.
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Custos e Análise de Custo , Neoplasias/epidemiologia , Sistema de Registros , Adulto , Idoso , Feminino , Recursos em Saúde , Humanos , Quênia/epidemiologia , Masculino , Pessoa de Meia-Idade , Avaliação das NecessidadesRESUMO
BACKGROUND: HIV-associated Kaposi sarcoma (KS) is one of the most common malignancies in sub-Saharan Africa. The diagnosis is often based on clinical suspicion, without histopathologic confirmation. When biopsies are performed, the accuracy of interpretation by local pathologists is poorly understood. We assessed the accuracy of clinical suspicion and pathologic diagnosis of KS in 2 East African countries. METHODS: At 2 large HIV care sites in Uganda and Kenya, we evaluated consecutive biopsies performed from October 2008 to January 2013 on HIV-infected adults with clinically suspected KS. Biopsies were interpreted by both local African pathologists and a group of US-based dermatopathologists from a high volume medical center. For the purpose of this analysis, the US-based dermatopathologist interpretation was used as the gold standard. Positive predictive value was used to characterize accuracy of local African clinical suspicion of KS, and concordance, sensitivity, and specificity were used to characterize accuracy of local pathologic diagnosis. RESULTS: Among 1106 biopsies, the positive predictive value of clinical suspicion of KS was 77% (95% confidence interval: 74% to 79%). When KS was not histopathologically diagnosed, clinically banal conditions were found in 35%, medically significant disorders which required different therapy in 59% and life-threatening diseases in 6%. Concordance between African pathologists and US-based dermatopathologists was 69% (95% confidence interval: 66% to 72%). Sensitivity and specificity of African pathologic diagnoses were 68% and 89%, respectively. CONCLUSIONS: Among East African HIV-infected patients, we found suboptimal positive predictive value of clinical suspicion of KS and specific, but not sensitive, histopathologic interpretation. The findings call for abandonment of isolated clinical diagnosis of KS in the region and augmentation of local dermatopathologic services.
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Infecções por HIV/complicações , Sarcoma de Kaposi/diagnóstico , Biópsia , Humanos , Quênia/epidemiologia , Sarcoma de Kaposi/epidemiologia , Sarcoma de Kaposi/patologia , Sensibilidade e Especificidade , Uganda/epidemiologiaRESUMO
Background. Human immunodeficiency virus (HIV)-1 drug resistance mutations (DRMs) often accompany treatment failure. Although subtype differences are widely studied, DRM comparisons between subtypes either focus on specific geographic regions or include populations with heterogeneous treatments. Methods. We characterized DRM patterns following first-line failure and their impact on future treatment in a global, multi-subtype reverse-transcriptase sequence dataset. We developed a hierarchical modeling approach to address the high-dimensional challenge of modeling and comparing frequencies of multiple DRMs in varying first-line regimens, durations, and subtypes. Drug resistance mutation co-occurrence was characterized using a novel application of a statistical network model. Results. In 1425 sequences, 202 subtype B, 696 C, 44 G, 351 circulating recombinant forms (CRF)01_AE, 58 CRF02_AG, and 74 from other subtypes mutation frequencies were higher in subtypes C and CRF01_AE compared with B overall. Mutation frequency increased by 9%-20% at reverse transcriptase positions 41, 67, 70, 184, 215, and 219 in subtype C and CRF01_AE vs B. Subtype C and CRF01_AE exhibited higher predicted cross-resistance (+12%-18%) to future therapy options compared with subtype B. Topologies of subtype mutation networks were mostly similar. Conclusions. We find clear differences in DRM outcomes following first-line failure, suggesting subtype-specific ecological or biological factors that determine DRM patterns.
RESUMO
In resource-limited areas, such as sub-Saharan Africa, problems in accurate cancer case ascertainment and enumeration of the at-risk population make it difficult to estimate cancer incidence. We took advantage of a large well-enumerated healthcare system to estimate the incidence of Kaposi sarcoma (KS), a cancer which has become prominent in the HIV era and whose incidence may be changing with the rollout of antiretroviral therapy (ART). To achieve this, we evaluated HIV-infected adults receiving care between 2007 and 2012 at any of three medical centers in Kenya and Uganda that participate in the East Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortium. Through IeDEA, clinicians received training in KS recognition and biopsy equipment. We found that the overall prevalence of KS among 102,945 HIV-infected adults upon clinic enrollment was 1.4%; it declined over time at the largest site. Among 140,552 patients followed for 319,632 person-years, the age-standardized incidence rate was 334/100,000 person-years (95% CI: 314-354/100,000 person-years). Incidence decreased over time and was lower in women, persons on ART, and those with higher CD4 counts. The incidence rate among patients on ART with a CD4 count >350 cells/mm(3) was 32/100,000 person-years (95% CI: 14-70/100,000 person-years). Despite reductions over time coincident with the expansion of ART, KS incidence among HIV-infected adults in East Africa equals or exceeds the most common cancers in resource-replete settings. In resource-limited settings, strategic efforts to improve cancer diagnosis in combination with already well-enumerated at-risk denominators can make healthcare systems attractive platforms for estimating cancer incidence.
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Sarcoma de Kaposi/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Humanos , Incidência , Quênia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Sarcoma de Kaposi/imunologia , Sarcoma de Kaposi/virologia , Distribuição por Sexo , Uganda/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Cancer of esophagus is the 9 th It is aggressive with poor prognosis especially in its late stage. Cancer of esophagus is geographically unevenly distributed with high incidence found within sharply demarcated geographic confines. Earlier reports from this country indicated relatively high proportion of cases in residents of Western and Central provinces with low incidence in the residents of the Rift Valley Province. This does not seem to be in agreement with our findings. Several aetiological factors have been associated with this type of cancer although their definitive mechanistic role is not clear. OBJECTIVE: The main aim of this study was to describe the incidence, clinical epidemiology and histology of esophageal cancer in the North Rift region of Western Kenya, which forms the patients catchment area of Moi Teaching and Referral Hospital, Eldoret. METHODS: This study involved a review of all available pathology reports beginning from January 1994 up to May 2001 from Moi Teaching and Referral Hospital. All reports of esophageal cancer were abstracted and analyzed according to gender, age and ethnical background. All cases were based on histological diagnosis. Statistical analysis was performed using the SPSS software package. RESULTS: Esophageal cancer in this area is the most common cancer in men, yet it is the third common cancer in women. A male to female ratio of 1.5 to 1 was observed. Our finding also contrast with an earlier reported study that indicated that Rift Valley is a low prevalence area for this type of cancer. The mean age of the patients with this cancer was 58.7 years. The ethnic group most afflicted were Nandis and Luhyas. They are the majority tribes in this area. Squamous cell carcinoma accounted for 90% of the cases. CONCLUSIONS: Cancer of the esophagus is the most common malignancy in males and the third common malignancy in females in the catchment area of Moi Teaching and Referral Hospital, Eldoret. There is need to carry out further work to establish the aetiologic factors behind this neoplasm. This study forms a preliminary basis of further investigation to be undertaken to identify genes that are mutated during the carcinogenic development of this cancer. This may lead to identification of molecular biomarkers to be used in future for the early detection of this neoplasm.
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Neoplasias Esofágicas/epidemiologia , Fatores Etários , Neoplasias Esofágicas/patologia , Feminino , Humanos , Incidência , Quênia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores SexuaisRESUMO
INTRODUCTION: Antiretroviral resistance leads to treatment failure and resistance transmission. Resistance data in western Kenya are limited. Collection of non-plasma analytes may provide additional resistance information. METHODS: We assessed HIV diversity using the REGA tool, transmitted resistance by the WHO mutation list and acquired resistance upon first-line failure by the IAS-USA mutation list, at the Academic Model Providing Access to Healthcare (AMPATH), a major treatment programme in western Kenya. Plasma and four non-plasma analytes, dried blood-spots (DBS), dried plasma-spots (DPS), ViveST(TM)-plasma (STP) and ViveST-blood (STB), were compared to identify diversity and evaluate sequence concordance. RESULTS: Among 122 patients, 62 were treatment-naïve and 60 treatment-experienced; 61% were female, median age 35 years, median CD4 182 cells/µL, median viral-load 4.6 log10 copies/mL. One hundred and ninety-six sequences were available for 107/122 (88%) patients, 58/62 (94%) treatment-naïve and 49/60 (82%) treated; 100/122 (82%) plasma, 37/78 (47%) attempted DBS, 16/45 (36%) attempted DPS, 14/44 (32%) attempted STP from fresh plasma and 23/34 (68%) from frozen plasma, and 5/42 (12%) attempted STB. Plasma and DBS genotyping success increased at higher VL and shorter shipment-to-genotyping time. Main subtypes were A (62%), D (15%) and C (6%). Transmitted resistance was found in 1.8% of plasma sequences, and 7% combining analytes. Plasma resistance mutations were identified in 91% of treated patients, 76% NRTI, 91% NNRTI; 76% dual-class; 60% with intermediate-high predicted resistance to future treatment options; with novel mutation co-occurrence patterns. Nearly 88% of plasma mutations were identified in DBS, 89% in DPS and 94% in STP. Of 23 discordant mutations, 92% in plasma and 60% in non-plasma analytes were mixtures. Mean whole-sequence discordance from frozen plasma reference was 1.1% for plasma-DBS, 1.2% plasma-DPS, 2.0% plasma-STP and 2.3% plasma-STB. Of 23 plasma-STP discordances, one mutation was identified in plasma and 22 in STP (p<0.05). Discordance was inversely significantly related to VL for DBS. CONCLUSIONS: In a large treatment programme in western Kenya, we report high HIV-1 subtype diversity; low plasma transmitted resistance, increasing when multiple analytes were combined; and high-acquired resistance with unique mutation patterns. Resistance surveillance may be augmented by using non-plasma analytes for lower-cost genotyping in resource-limited settings.