Helicobacter pylori infection is the major cause of gastritis. Immunologically, H. pylori gastrit... more Helicobacter pylori infection is the major cause of gastritis. Immunologically, H. pylori gastritis is associated with an infiltration of immune cells into gastric mucosa and the upregulation of various cytokines. Here, we analysed the gene expression of IL-1- and IL-17-related cytokines in regard to H. pylori infection in 85 German and 51 Kenyan patients with reflux-related or dyspeptic symptoms, respectively. Degree of gastritis and density of colonization were assessed histologically in accordance with the updated Sydney classification. Gene expression levels of cytokines IL-1β, IL-8, IL-18, IL-33, IL-17A, IL-17F and IL-23 as well as IL-23R were analysed by real-time RT-PCR. In both populations, H. pylori-infected individuals had significant higher inflammatory scores for activity and chronicity than H. pylori-negative subjects (P values between 0.006 and <0.0001). IL-8 mRNA was induced up to 6-fold in H. pylori-infected patients (P < 0.05), while the expression levels of IL-1β, IL-18, IL-23, IL-33 and IL-23R did not differ with respect to the H. pylori status in both groups. Most strikingly, a significant induction of both IL-17A and IL-17F was noted in H. pylori-infected individuals of both ethnic groups. Almost all IL-17F-positive samples revealed co-expression of IL-17A (40/42, 95.2%). Analysing IL-17A and IL-17F transcript levels of these 40 'double-positive' samples, a highly significant positive correlation between both genes was identified (P < 0.001). Taken together, H. pylori infection leads to a strong upregulation of both IL-17A and IL-17F in the gastric mucosa suggesting a regulatory link between both genes.
There has been an increase in breast cancer in Africa with up to 77% of patients diagnosed with a... more There has been an increase in breast cancer in Africa with up to 77% of patients diagnosed with advanced disease. However, there is little data on survival outcomes and prognostic factors affecting survival in patients with metastatic breast cancer (MBC) in Africa. The study objective was to establish the survival of patients with MBC at a single tertiary health facility, the clinical and pathological characteristics affecting survival and describe the treatment modalities used. This was a retrospective descriptive study conducted at
Promoting best practice in the management of a cancer patient is rooted in the application of new... more Promoting best practice in the management of a cancer patient is rooted in the application of new knowledge derived through various sources including population science, laboratory advances, and translational research. Ultimately, the impact of these advances depends on their application at the patient's bedside. A close collaboration between the oncologist and the pathologist is critical in underwriting progress in the management of the cancer patient. Recent advancements have shown that more granular characteristics of the tumor and the microenvironment are defining determinants when it comes to disease course and overall outcome. Whereas, histologic features and basic immunohistochemical characterization were previously adequate to define the tumor and establish treatment recommendation, the growing capability of the pathologist to provide molecular characterization of the tumor and its microenvironment, as well as, the availability of novel therapeutic agents have revolutionized cancer treatment paradigms and improved patient-outcomes and survival. While such capacity and capability appear readily available in most developed high-income countries (HIC), it will take a concerted and collaborative effort of all stakeholders to pave the way in the same stride in the low and middle-income countries (LMIC), which bear a disproportionate burden of human illness and cancers. Patients in the LMIC present with disease at advanced stage and often display characteristics unlike those encountered in the developed world. To keep stride and avoid the disenfranchisement of patients in the LMIC will require greater participation of LMIC patients on the global clinical trial platform, and a more equitable and affordable sharing of diagnostic and therapeutic capabilities between the developed and developing world. Key to the success of this progress and improvement of patient outcomes in the developing world is the close collaboration between the oncologist and the pathologist in this new era of precision and personalized medicine.
place in many LMICs-a point that we agree with given that minimal training is required to perform... more place in many LMICs-a point that we agree with given that minimal training is required to perform the HPV test on the GeneXpert platform. However, it is crucial that any new point-of-care test is easy to perform, sensitive, and specific, and that it is not vulnerable to user error like VIA, which has performed poorly in LMICs (the test is subjective and requires regular refresher training to maintain accuracy). The new HPV test modification reported on the Gene Xpert by Kuhn and colleagues 8 might be able to overcome this. But, before LMICs adopt point-of-care technologies that can surpass fragile health systems and allow for testing in the absence of traditional laboratory settings, multiple implementation studies examining costeffectiveness, feasibility, and acceptability by healthcare workers and by women of HPV screen-and-treat methods are needed. More importantly, it would be useful to understand how HPV test specificity might be affected by immune status, ART use, and age, as these variables might reduce specificity of the test. 10 We declare no competing interests.
Summary Background Pathology and laboratory medicine diagnostics and diagnostic imaging are cruci... more Summary Background Pathology and laboratory medicine diagnostics and diagnostic imaging are crucial to achieving universal health coverage. We analysed Service Provision Assessments (SPAs) from ten low-income and middle-income countries to benchmark diagnostic availability. Methods Diagnostic availabilities were determined for Bangladesh, Haiti, Malawi, Namibia, Nepal, Kenya, Rwanda, Senegal, Tanzania, and Uganda, with multiple timepoints for Haiti, Kenya, Senegal, and Tanzania. A smaller set of diagnostics were included in the analysis for primary care facilities compared with those expected at hospitals, with 16 evaluated in total. Surveys spanned 2004–18, including 8512 surveyed facilities. Country-specific facility types were mapped to basic primary care, advanced primary care, or hospital tiers. We calculated percentages of facilities offering each diagnostic, accounting for facility weights, stratifying by tier, and for some analyses, region. The tier-level estimate of diagnostic availability was defined as the median of all diagnostic-specific availabilities at each tier, and country-level estimates were the median of all diagnostic-specific availabilities of each of the tiers. Associations of country-level diagnostic availability with country income as well as (within-country) region-level availability with region-specific population densities were determined by multivariable linear regression, controlling for appropriate covariates including tier. Findings Median availability of diagnostics was 19·1% in basic primary care facilities, 49·2% in advanced primary care facilities, and 68·4% in hospitals. Availability varied considerably between diagnostics, ranging from 1·2% (ultrasound) to 76·7% (malaria) in primary care (basic and advanced) and from 6·1% (CT scan) to 91·6% (malaria) in hospitals. Availability also varied between countries, from 14·9% (Bangladesh) to 89·6% (Namibia). Availability correlated positively with log(income) at both primary care tiers but not the hospital tier, and positively with region-specific population density at the basic primary care tier only. Interpretation Major gaps in diagnostic availability exist in many low-income and middle-income countries, particularly in primary care facilities. These results can serve as a benchmark to gauge progress towards implementing guidelines such as the WHO Essential Diagnostics List and Priority Medical Devices initiatives. Funding Bill & Melinda Gates Foundation.
Background: The immune landscape of breast cancer in patients from Sub Saharan Africa is understu... more Background: The immune landscape of breast cancer in patients from Sub Saharan Africa is understudied and findings are mainly extrapolated from studies in Caucasians and African Americans. Given the prognostic value of Tumour Infiltrating Lymphocytes (TILs) in breast cancer subtypes, the paucity of specific TIL marker data among BC patients from Africa, and the limited data on TIL spatial heterogeneity, our aim was to describe the distribution of TILs within the intratumoral stroma and the leading/invasive edge stroma, and evaluate their association across BC subtypes with established risk factors in Kenyan women with BC. Methods: Visual quantification of overall TILs within the intratumoral stroma (sTILs) and the stroma at the leading edge/invasive edge of the tumour (LE-TILs) were performed on Haematoxylin and Eosin stained whole slide sections of pathologically confirmed breast cancer based on the guidelines of the International TIL working group. Tissue Microarrays (TMAs) of tumour were also were constructed and stained with immunohistochemistry for CD3, CD4, CD8, CD68, CD20 and Fox P3. The TMA slides were scanned on the Aperio Digital pathology slide scanner, imported into the Aperio, assigned a template, segmented and annotated before analysis using a nuclear algorithm. Linear and logistic regression models were used to assess the associations between risk factors and tumor features with IHC markers and total TILs, after adjusting for other covariates. Results: A total of 226 invasive breast cancer cases were included in the final analysis for TILs and immune cell markers. The mean age at diagnosis of these breast cancer patients was 48.3 years. The distribution of the BC molecular subtypes defined by IHC markers was 56.2%, 16.8%, 9.3%, and 17.7 % (luminal A, luminal B, HER2-enriched, and TN breast cancers, respectively). On the whole we found that LE TIL proportions were higher than sTIL (41.3% versus 15% for TILs ≥30 and 19.3% and 4.4% for TILs ≥50 respectively). After adjusting for other tumor characteristics, we found higher TILs associated with high KI67 and high grade (for both sTIL and LE-TIL), TNBC (for sTIL only), and HER2 status, luminal B subtype, and smaller tumor size (<4 cm) (for LE-TIL only). Both sTILs and LE-TILs were predominantly composed of CD3, CD8 and CD68 with a much smaller contribution of CD4 and CD20. The percent positive cells for Fox3 were markedly lower compared to other IHC markers for both sTILs and LE-TILs. Conclusions: Our findings with regards to enrichment of TILs in more aggressive breast cancers are similar to what has been previously published. The distinct associations between intratumoral stroma and leading edge TIL measures for some factors highlight the importance of spatial TIL evaluations in future studies. Our findings add to the body of knowledge regarding TILs and TIL subtypes in breast cancer, which underscore the need to conduct studies specific to African populations. Citation Format: Shahin Sayed, Xiaohong R Yang, Dhirendra Govender, Breast Health Study group. Tumour infiltrating lymphocytes (TILs) and immune composition in breast cancer patients from Kenya: Spatial distributions and associations with risk factors and tumour characteristics [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-02-13.
Background: Important information about medical laboratory providers is not readily available to ... more Background: Important information about medical laboratory providers is not readily available to all patients, clinicians nor regulators in Kenya. This study was conducted as part of a wider project aiming to improve access to high quality diagnostics by addressing information asymmetries in the Kenyan market for laboratory services. Objectives: The purpose of this study was to: 1) Gather pricing information for 49 common laboratory tests from medical laboratories in Nairobi, Kenya, noting where these prices were publicly available or withheld. 2) Assess patients' knowledge of testing information including: turnaround time, price, and test availability. Method: This was a cross-sectional study where a mystery caller approach was used to survey 49 tests for turnaround time, price, and availability across 13 laboratories selected purposively. The mystery shopper survey was complemented by 251 patient exit interviews at two Kenyan hospitals to understand whether patients seeking laboratory tests in Nairobi had access to such information. All 251 patients were selected by convenience sampling. Results: We noted that 85% of the private laboratories did not disclose test prices and turnaround times to their patients. There was a wide range of prices on several key tests, with private in-facility laboratories charging an average test price of 468% of the average test price in public laboratories across all the 49 tests. We also found that many patients lacked key information regarding the tests they needed: 65% did not know the purpose of the test while 41% did not know the test price at all. Conclusion: Under the current system, patients have limited access to information regarding the key criteria required to make a rational decision. This has a significant impact on the quality, price, and turnaround time (TAT) offered by the medical laboratories that operate in this dysfunctional market.
American Journal of Clinical Pathology, Dec 6, 2018
Objectives: To compare the most common diagnostic/ laboratory tests across five different referra... more Objectives: To compare the most common diagnostic/ laboratory tests across five different referral hospitals by volume and revenue. Methods: The authors obtained data on volumes and reimbursement rates for the most common 25 tests at the five hospitals with which they are affiliated and organized them to be as comparable as possible. Simple descriptive statistics were used to make crosscountry comparisons. Results: There are strong similarities across all five hospitals in the top five tests by both volume and revenue. However, the top five by volume differ from the top five by revenue. Reimbursement rates also follow common patterns, being lowest for the most common biochemical test; intermediate for the most common hematology and microbiology tests, respectively; and highest for the most common pathology test. Conclusions: Most of the most common tests also appear in the new Essential Diagnostics List. This may inform plans for universal health coverage.
We report a case of typical carcinoid of the lung in a 60-year-old human immunodeficiency virus (... more We report a case of typical carcinoid of the lung in a 60-year-old human immunodeficiency virus (HIV)-positive man diagnosed on brush cytology smears. Bronchial carcinoids are rare tumors, accounting for 1% to 2% of all lung tumors. Although the exact incidence in HIV-infected individuals is not known, the paucity of their documentation in the literature indicates that they may be equally rare. Cytological diagnosis on brush smears is rarely documented as the tumor is covered with mucosa and cellular yield is often not good. In this case, bronchial brushings showed distinctive cytological features of typical carcinoid. The awareness of its characteristic cytological features and differential diagnosis is required for an accurate diagnosis. Clinical awareness that non-acquired immunodeficiency syndrome (AIDS)-defining cancers can also occur in HIV-infected individuals in the context of the prolonged survival in the antiretroviral era is equally important. This case emphasizes the clinical importance of a broad differential diagnosis for lung lesions in HIV-positive patients.
At the end of 2019, the first reports of a new respiratory virus appeared in China. The subsequen... more At the end of 2019, the first reports of a new respiratory virus appeared in China. The subsequent COVID-19 pandemic has affected every person, in every country, in the world. One early lesson was the crucial importance of timely accurate diagnosis. A second lesson was the widespread scarcity of such diagnostic capacity and capability
Background and context: In Africa, up to two thirds of breast cancer patients have been reported ... more Background and context: In Africa, up to two thirds of breast cancer patients have been reported to present with an advanced stage of III or IV at diagnosis leading to a disproportionately higher mortality. In Kenya, breast cancer is the most common cancer in females in terms of diagnosis and mortality. Metastatic breast cancer (MBC) patients are an ignored part of the breast cancer community as they are marginalized in many of the breast cancer related initiatives. MBC suffer from clinical depression, anxiety and four out of five of these women do not receive any services, referral or guidance to help them with their emotional distress. Preferred evidence based methods of support desired by women with MBC, include online support. International resources are not always applicable to the local context thus making them unattractive for people from diverse cultures and background, such as those from Africa. Kenya has a high percentage of literate females and highest Internet usage in the area. This provides a unique opportunity in an otherwise limited resource country to reach out to a significant population of MBC patients. The patients voices are a valuable and trustworthy assessment of their actual needs. They have been used frequently in the area of cancer as a first step in designing needs-tailored interventions. We propose to develop a virtual online forum with the aim of providing patients with MBC, and their caregivers an interactive forum for psycho social support, addressing stigmas, seek relevant clinical advice, find links to the nearest healthcare facilities, download helpful information, participate in support group activities and receive links to other important helpful sites that are locally relevant. We also propose that such forum should also reflect the needs of our patients as described by themselves. Aim: Primary aim of this project is developing a virtual online interactive support forum where MBC patients and their caregivers can access information on social, psychological, spiritual, religious and clinical needs. The purpose is to be partly achieved by assessing the patient needs by needs assessment survey and to evaluate the impact of such intervention on patient knowledge and satisfaction with care. Strategy/Tactics: Web site development is the key component of the project. Patients would be asked to fill out the Supportive Care Needs Survey/The Knowledge Assessment Tool. The surveys will take place at four major cancer treatment hospitals in Kenya. Postlaunch promotion and awareness about Web site will be made and, usage data and knowledge tool to be used to assess the impact and acceptability. Web site updated regularly to address issues identified. Program/Policy process: Information gathered would be made part of policy on national cancer strategy, recommendations to factor in identified patient needs in policy. What was learned: Ongoing process.
International Journal of General Medicine, Apr 1, 2022
The first documented case of COVID-19 in Kenya was recorded March of 2020. Co-morbidities includi... more The first documented case of COVID-19 in Kenya was recorded March of 2020. Co-morbidities including hypertension and diabetes have been associated with increased morbidity, hospitalization, and mortality among COVID-19 patients. This retrospective study describes the clinical characteristics, disease severity, and outcomes among the patient population at a tertiary hospital in Kenya. Methods: This was a retrospective descriptive study of COVID-19 patients who were admitted between March 2020 and December 2020 at the Aga Khan University Hospital in Nairobi, Kenya. Data collected include patient demographic and baseline characteristics. Differences between patients who were known to have diabetes and hypertension during admission were compared for statistical significance. Difference between those who survived and those who died were also compared for statistical significance. Results: A total of 913 records of patients were studied with a mean age of 51.2 years (SD = 16.7), 66.5% were male and 80.8% were of African origin. History of diabetes, hypertension, and HIV status were at 27.3%, 33.1%, and 2.3%, respectively. At presentation, 33.1% (302/913) of patients had known hypertension by history, and following admission, this proportion increased to 37.7% (344/ 913). At presentation, 27.3% (249/913) of patients had known diabetes. During hospital stay, 20.8% (190) more patients were found to have diabetes, raising the overall percent to 48.1% (439/913). When comparing diabetes and hypertension at baseline versus at the end of admission, diabetes increased by 20.8% (p < 0.001) and hypertension by 4.6% (p = 0.049). HIV co-infection was 2.3%, and no patient had tuberculosis. Conclusion: This study showed a high incidence of co-morbidities in patients infected with COVID-19. Diabetes was most common, followed by hypertension. All patients admitted with COVID-19 infection should routinely be tested for diabetes with HbA1c and have regular blood pressure monitoring in order to diagnose occult diabetes and hypertension. Adverse outcomes were found in patients with these co-morbidities and should be monitored and treated appropriately.
Breast cancer is the most prevalent neoplasm and the second leading cause of death among females ... more Breast cancer is the most prevalent neoplasm and the second leading cause of death among females in Kenya. Estrogen and its metabolites are known risk factors for breast cancer. Polymorphisms in these genes and breast cancer susceptibility are unique among different populations. This study aimed to determine the probable associations between estrogen-metabolizing gene variations and other risk factors for breast cancer risk in Kenyan women. Buffy coat samples were obtained from patients diagnosed with estrogen receptor-positive breast cancer, benign breast disease, and healthy volunteers. Genotyping of target polymorphisms was conducted using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis. The rs4646903 variant genotype CC was associated with breast cancer in the case-control model (P=0.001); the heterozygous genotype TC (P=0.01) and the luminal B molecular subtype (P=0.02) showed increased odds of late-stage breast cancer. The rs1048943 var...
At the time of original publication, there was an incomplete listing of contributing authors and ... more At the time of original publication, there was an incomplete listing of contributing authors and their institutions. This revision corrects those omissions.
American Journal of Clinical Pathology, Feb 2, 2021
ObjectivesPeripheral T-cell lymphomas (PTCLs) are heterogeneous, clinically aggressive, and rare.... more ObjectivesPeripheral T-cell lymphomas (PTCLs) are heterogeneous, clinically aggressive, and rare. Subtype distribution varies by geographic location; however, data from sub-Saharan Africa (SSA) are lacking. We sought to elucidate clinicopathologic features of PTCL in SSA.MethodsWe reviewed PTCL consultation cases from three SSA countries. PTCL subtype was determined per 2017 World Health Organization classification. Cases with sufficient material were evaluated by polymerase chain reaction for human T-cell leukemia virus type 1 (HTLV-1) and T-cell receptor γ (TCRG) rearrangement.ResultsAmong 32 cases, median age was 45 years and male-to-female ratio was 1.7. Thirty (94%) of 32 cases required additional workup for subclassification. PTCL, not otherwise specified (PTCL-NOS) was the most common subtype (13/32, 41%), followed by PTCL with T-follicular helper phenotype (6/32, 19%) and systemic anaplastic large cell lymphoma (6/32, 19%). Four (16%) of 25 cases were Epstein-Barr virus positive (EBV+) (2/2 extranodal natural killer/T-cell lymphoma, 1/13 PTCL-NOS, and 1/4 angioimmunoblastic T-cell lymphoma with EBV+ immunoblasts). Two (15%) of 13 patients with PTCL-NOS were human immunodeficiency virus positive. No cases with evaluable DNA (0/15) were HTLV-1 positive, and 9 of 10 showed clonal TCRG rearrangements.ConclusionsIn comparison to Western studies, PTCLs from SSA show similar subtype distribution and male predominance but a younger age at diagnosis. Appropriate diagnosis of PTCL requires extensive ancillary testing not readily available in low-income countries, including much of SSA.
Introduction. Data examining mammographic breast density (MBD) among patients in Sub-Saharan Afri... more Introduction. Data examining mammographic breast density (MBD) among patients in Sub-Saharan Africa are sparse. We evaluated how MBD relates to breast cancer characteristics in Kenyan women undergoing diagnostic mammography. Methods. This crosssectional study included women with pathologically confirmed breast cancers (= 123). Pretreatment mammograms of the unaffected breast were assessed to estimate absolute dense area (cm 2), nondense area (cm 2), and percent density (PD). Relationships between density measurements and clinical characteristics were evaluated using analysis of covariance. Results. Median PD and dense area were 24.9% and 85.3 cm 2. Higher PD and dense area were observed in younger women (< 0.01). Higher dense and nondense areas were observed in obese women (-trend < 0.01). Estrogen receptor (ER) positive patients (73%) had higher PD and dense area than ER-negative patients (≤ 0.02). Triple negative breast cancer (TNBC) patients (17%) had lower PD and dense area (≤ 0.01) compared with non-TNBCs. No associations were observed between MBD and tumor size and grade. Conclusions. Our findings show discordant relationships between MBD and molecular tumor subtypes to those previously observed in Western populations. The relatively low breast density observed at diagnosis may have important implications for cancer prevention initiatives in Kenya. Subsequent larger studies are needed to confirm these findings.
Breast cancer awareness and early detection x Kenya x Low-and middle-income countries x Breast ca... more Breast cancer awareness and early detection x Kenya x Low-and middle-income countries x Breast cancer camps x Breast cancer diagnosis
Helicobacter pylori infection is the major cause of gastritis. Immunologically, H. pylori gastrit... more Helicobacter pylori infection is the major cause of gastritis. Immunologically, H. pylori gastritis is associated with an infiltration of immune cells into gastric mucosa and the upregulation of various cytokines. Here, we analysed the gene expression of IL-1- and IL-17-related cytokines in regard to H. pylori infection in 85 German and 51 Kenyan patients with reflux-related or dyspeptic symptoms, respectively. Degree of gastritis and density of colonization were assessed histologically in accordance with the updated Sydney classification. Gene expression levels of cytokines IL-1β, IL-8, IL-18, IL-33, IL-17A, IL-17F and IL-23 as well as IL-23R were analysed by real-time RT-PCR. In both populations, H. pylori-infected individuals had significant higher inflammatory scores for activity and chronicity than H. pylori-negative subjects (P values between 0.006 and &amp;amp;amp;amp;amp;amp;lt;0.0001). IL-8 mRNA was induced up to 6-fold in H. pylori-infected patients (P &amp;amp;amp;amp;amp;amp;lt; 0.05), while the expression levels of IL-1β, IL-18, IL-23, IL-33 and IL-23R did not differ with respect to the H. pylori status in both groups. Most strikingly, a significant induction of both IL-17A and IL-17F was noted in H. pylori-infected individuals of both ethnic groups. Almost all IL-17F-positive samples revealed co-expression of IL-17A (40/42, 95.2%). Analysing IL-17A and IL-17F transcript levels of these 40 &amp;amp;amp;amp;amp;amp;#39;double-positive&amp;amp;amp;amp;amp;amp;#39; samples, a highly significant positive correlation between both genes was identified (P &amp;amp;amp;amp;amp;amp;lt; 0.001). Taken together, H. pylori infection leads to a strong upregulation of both IL-17A and IL-17F in the gastric mucosa suggesting a regulatory link between both genes.
There has been an increase in breast cancer in Africa with up to 77% of patients diagnosed with a... more There has been an increase in breast cancer in Africa with up to 77% of patients diagnosed with advanced disease. However, there is little data on survival outcomes and prognostic factors affecting survival in patients with metastatic breast cancer (MBC) in Africa. The study objective was to establish the survival of patients with MBC at a single tertiary health facility, the clinical and pathological characteristics affecting survival and describe the treatment modalities used. This was a retrospective descriptive study conducted at
Promoting best practice in the management of a cancer patient is rooted in the application of new... more Promoting best practice in the management of a cancer patient is rooted in the application of new knowledge derived through various sources including population science, laboratory advances, and translational research. Ultimately, the impact of these advances depends on their application at the patient's bedside. A close collaboration between the oncologist and the pathologist is critical in underwriting progress in the management of the cancer patient. Recent advancements have shown that more granular characteristics of the tumor and the microenvironment are defining determinants when it comes to disease course and overall outcome. Whereas, histologic features and basic immunohistochemical characterization were previously adequate to define the tumor and establish treatment recommendation, the growing capability of the pathologist to provide molecular characterization of the tumor and its microenvironment, as well as, the availability of novel therapeutic agents have revolutionized cancer treatment paradigms and improved patient-outcomes and survival. While such capacity and capability appear readily available in most developed high-income countries (HIC), it will take a concerted and collaborative effort of all stakeholders to pave the way in the same stride in the low and middle-income countries (LMIC), which bear a disproportionate burden of human illness and cancers. Patients in the LMIC present with disease at advanced stage and often display characteristics unlike those encountered in the developed world. To keep stride and avoid the disenfranchisement of patients in the LMIC will require greater participation of LMIC patients on the global clinical trial platform, and a more equitable and affordable sharing of diagnostic and therapeutic capabilities between the developed and developing world. Key to the success of this progress and improvement of patient outcomes in the developing world is the close collaboration between the oncologist and the pathologist in this new era of precision and personalized medicine.
place in many LMICs-a point that we agree with given that minimal training is required to perform... more place in many LMICs-a point that we agree with given that minimal training is required to perform the HPV test on the GeneXpert platform. However, it is crucial that any new point-of-care test is easy to perform, sensitive, and specific, and that it is not vulnerable to user error like VIA, which has performed poorly in LMICs (the test is subjective and requires regular refresher training to maintain accuracy). The new HPV test modification reported on the Gene Xpert by Kuhn and colleagues 8 might be able to overcome this. But, before LMICs adopt point-of-care technologies that can surpass fragile health systems and allow for testing in the absence of traditional laboratory settings, multiple implementation studies examining costeffectiveness, feasibility, and acceptability by healthcare workers and by women of HPV screen-and-treat methods are needed. More importantly, it would be useful to understand how HPV test specificity might be affected by immune status, ART use, and age, as these variables might reduce specificity of the test. 10 We declare no competing interests.
Summary Background Pathology and laboratory medicine diagnostics and diagnostic imaging are cruci... more Summary Background Pathology and laboratory medicine diagnostics and diagnostic imaging are crucial to achieving universal health coverage. We analysed Service Provision Assessments (SPAs) from ten low-income and middle-income countries to benchmark diagnostic availability. Methods Diagnostic availabilities were determined for Bangladesh, Haiti, Malawi, Namibia, Nepal, Kenya, Rwanda, Senegal, Tanzania, and Uganda, with multiple timepoints for Haiti, Kenya, Senegal, and Tanzania. A smaller set of diagnostics were included in the analysis for primary care facilities compared with those expected at hospitals, with 16 evaluated in total. Surveys spanned 2004–18, including 8512 surveyed facilities. Country-specific facility types were mapped to basic primary care, advanced primary care, or hospital tiers. We calculated percentages of facilities offering each diagnostic, accounting for facility weights, stratifying by tier, and for some analyses, region. The tier-level estimate of diagnostic availability was defined as the median of all diagnostic-specific availabilities at each tier, and country-level estimates were the median of all diagnostic-specific availabilities of each of the tiers. Associations of country-level diagnostic availability with country income as well as (within-country) region-level availability with region-specific population densities were determined by multivariable linear regression, controlling for appropriate covariates including tier. Findings Median availability of diagnostics was 19·1% in basic primary care facilities, 49·2% in advanced primary care facilities, and 68·4% in hospitals. Availability varied considerably between diagnostics, ranging from 1·2% (ultrasound) to 76·7% (malaria) in primary care (basic and advanced) and from 6·1% (CT scan) to 91·6% (malaria) in hospitals. Availability also varied between countries, from 14·9% (Bangladesh) to 89·6% (Namibia). Availability correlated positively with log(income) at both primary care tiers but not the hospital tier, and positively with region-specific population density at the basic primary care tier only. Interpretation Major gaps in diagnostic availability exist in many low-income and middle-income countries, particularly in primary care facilities. These results can serve as a benchmark to gauge progress towards implementing guidelines such as the WHO Essential Diagnostics List and Priority Medical Devices initiatives. Funding Bill & Melinda Gates Foundation.
Background: The immune landscape of breast cancer in patients from Sub Saharan Africa is understu... more Background: The immune landscape of breast cancer in patients from Sub Saharan Africa is understudied and findings are mainly extrapolated from studies in Caucasians and African Americans. Given the prognostic value of Tumour Infiltrating Lymphocytes (TILs) in breast cancer subtypes, the paucity of specific TIL marker data among BC patients from Africa, and the limited data on TIL spatial heterogeneity, our aim was to describe the distribution of TILs within the intratumoral stroma and the leading/invasive edge stroma, and evaluate their association across BC subtypes with established risk factors in Kenyan women with BC. Methods: Visual quantification of overall TILs within the intratumoral stroma (sTILs) and the stroma at the leading edge/invasive edge of the tumour (LE-TILs) were performed on Haematoxylin and Eosin stained whole slide sections of pathologically confirmed breast cancer based on the guidelines of the International TIL working group. Tissue Microarrays (TMAs) of tumour were also were constructed and stained with immunohistochemistry for CD3, CD4, CD8, CD68, CD20 and Fox P3. The TMA slides were scanned on the Aperio Digital pathology slide scanner, imported into the Aperio, assigned a template, segmented and annotated before analysis using a nuclear algorithm. Linear and logistic regression models were used to assess the associations between risk factors and tumor features with IHC markers and total TILs, after adjusting for other covariates. Results: A total of 226 invasive breast cancer cases were included in the final analysis for TILs and immune cell markers. The mean age at diagnosis of these breast cancer patients was 48.3 years. The distribution of the BC molecular subtypes defined by IHC markers was 56.2%, 16.8%, 9.3%, and 17.7 % (luminal A, luminal B, HER2-enriched, and TN breast cancers, respectively). On the whole we found that LE TIL proportions were higher than sTIL (41.3% versus 15% for TILs ≥30 and 19.3% and 4.4% for TILs ≥50 respectively). After adjusting for other tumor characteristics, we found higher TILs associated with high KI67 and high grade (for both sTIL and LE-TIL), TNBC (for sTIL only), and HER2 status, luminal B subtype, and smaller tumor size (&lt;4 cm) (for LE-TIL only). Both sTILs and LE-TILs were predominantly composed of CD3, CD8 and CD68 with a much smaller contribution of CD4 and CD20. The percent positive cells for Fox3 were markedly lower compared to other IHC markers for both sTILs and LE-TILs. Conclusions: Our findings with regards to enrichment of TILs in more aggressive breast cancers are similar to what has been previously published. The distinct associations between intratumoral stroma and leading edge TIL measures for some factors highlight the importance of spatial TIL evaluations in future studies. Our findings add to the body of knowledge regarding TILs and TIL subtypes in breast cancer, which underscore the need to conduct studies specific to African populations. Citation Format: Shahin Sayed, Xiaohong R Yang, Dhirendra Govender, Breast Health Study group. Tumour infiltrating lymphocytes (TILs) and immune composition in breast cancer patients from Kenya: Spatial distributions and associations with risk factors and tumour characteristics [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-02-13.
Background: Important information about medical laboratory providers is not readily available to ... more Background: Important information about medical laboratory providers is not readily available to all patients, clinicians nor regulators in Kenya. This study was conducted as part of a wider project aiming to improve access to high quality diagnostics by addressing information asymmetries in the Kenyan market for laboratory services. Objectives: The purpose of this study was to: 1) Gather pricing information for 49 common laboratory tests from medical laboratories in Nairobi, Kenya, noting where these prices were publicly available or withheld. 2) Assess patients' knowledge of testing information including: turnaround time, price, and test availability. Method: This was a cross-sectional study where a mystery caller approach was used to survey 49 tests for turnaround time, price, and availability across 13 laboratories selected purposively. The mystery shopper survey was complemented by 251 patient exit interviews at two Kenyan hospitals to understand whether patients seeking laboratory tests in Nairobi had access to such information. All 251 patients were selected by convenience sampling. Results: We noted that 85% of the private laboratories did not disclose test prices and turnaround times to their patients. There was a wide range of prices on several key tests, with private in-facility laboratories charging an average test price of 468% of the average test price in public laboratories across all the 49 tests. We also found that many patients lacked key information regarding the tests they needed: 65% did not know the purpose of the test while 41% did not know the test price at all. Conclusion: Under the current system, patients have limited access to information regarding the key criteria required to make a rational decision. This has a significant impact on the quality, price, and turnaround time (TAT) offered by the medical laboratories that operate in this dysfunctional market.
American Journal of Clinical Pathology, Dec 6, 2018
Objectives: To compare the most common diagnostic/ laboratory tests across five different referra... more Objectives: To compare the most common diagnostic/ laboratory tests across five different referral hospitals by volume and revenue. Methods: The authors obtained data on volumes and reimbursement rates for the most common 25 tests at the five hospitals with which they are affiliated and organized them to be as comparable as possible. Simple descriptive statistics were used to make crosscountry comparisons. Results: There are strong similarities across all five hospitals in the top five tests by both volume and revenue. However, the top five by volume differ from the top five by revenue. Reimbursement rates also follow common patterns, being lowest for the most common biochemical test; intermediate for the most common hematology and microbiology tests, respectively; and highest for the most common pathology test. Conclusions: Most of the most common tests also appear in the new Essential Diagnostics List. This may inform plans for universal health coverage.
We report a case of typical carcinoid of the lung in a 60-year-old human immunodeficiency virus (... more We report a case of typical carcinoid of the lung in a 60-year-old human immunodeficiency virus (HIV)-positive man diagnosed on brush cytology smears. Bronchial carcinoids are rare tumors, accounting for 1% to 2% of all lung tumors. Although the exact incidence in HIV-infected individuals is not known, the paucity of their documentation in the literature indicates that they may be equally rare. Cytological diagnosis on brush smears is rarely documented as the tumor is covered with mucosa and cellular yield is often not good. In this case, bronchial brushings showed distinctive cytological features of typical carcinoid. The awareness of its characteristic cytological features and differential diagnosis is required for an accurate diagnosis. Clinical awareness that non-acquired immunodeficiency syndrome (AIDS)-defining cancers can also occur in HIV-infected individuals in the context of the prolonged survival in the antiretroviral era is equally important. This case emphasizes the clinical importance of a broad differential diagnosis for lung lesions in HIV-positive patients.
At the end of 2019, the first reports of a new respiratory virus appeared in China. The subsequen... more At the end of 2019, the first reports of a new respiratory virus appeared in China. The subsequent COVID-19 pandemic has affected every person, in every country, in the world. One early lesson was the crucial importance of timely accurate diagnosis. A second lesson was the widespread scarcity of such diagnostic capacity and capability
Background and context: In Africa, up to two thirds of breast cancer patients have been reported ... more Background and context: In Africa, up to two thirds of breast cancer patients have been reported to present with an advanced stage of III or IV at diagnosis leading to a disproportionately higher mortality. In Kenya, breast cancer is the most common cancer in females in terms of diagnosis and mortality. Metastatic breast cancer (MBC) patients are an ignored part of the breast cancer community as they are marginalized in many of the breast cancer related initiatives. MBC suffer from clinical depression, anxiety and four out of five of these women do not receive any services, referral or guidance to help them with their emotional distress. Preferred evidence based methods of support desired by women with MBC, include online support. International resources are not always applicable to the local context thus making them unattractive for people from diverse cultures and background, such as those from Africa. Kenya has a high percentage of literate females and highest Internet usage in the area. This provides a unique opportunity in an otherwise limited resource country to reach out to a significant population of MBC patients. The patients voices are a valuable and trustworthy assessment of their actual needs. They have been used frequently in the area of cancer as a first step in designing needs-tailored interventions. We propose to develop a virtual online forum with the aim of providing patients with MBC, and their caregivers an interactive forum for psycho social support, addressing stigmas, seek relevant clinical advice, find links to the nearest healthcare facilities, download helpful information, participate in support group activities and receive links to other important helpful sites that are locally relevant. We also propose that such forum should also reflect the needs of our patients as described by themselves. Aim: Primary aim of this project is developing a virtual online interactive support forum where MBC patients and their caregivers can access information on social, psychological, spiritual, religious and clinical needs. The purpose is to be partly achieved by assessing the patient needs by needs assessment survey and to evaluate the impact of such intervention on patient knowledge and satisfaction with care. Strategy/Tactics: Web site development is the key component of the project. Patients would be asked to fill out the Supportive Care Needs Survey/The Knowledge Assessment Tool. The surveys will take place at four major cancer treatment hospitals in Kenya. Postlaunch promotion and awareness about Web site will be made and, usage data and knowledge tool to be used to assess the impact and acceptability. Web site updated regularly to address issues identified. Program/Policy process: Information gathered would be made part of policy on national cancer strategy, recommendations to factor in identified patient needs in policy. What was learned: Ongoing process.
International Journal of General Medicine, Apr 1, 2022
The first documented case of COVID-19 in Kenya was recorded March of 2020. Co-morbidities includi... more The first documented case of COVID-19 in Kenya was recorded March of 2020. Co-morbidities including hypertension and diabetes have been associated with increased morbidity, hospitalization, and mortality among COVID-19 patients. This retrospective study describes the clinical characteristics, disease severity, and outcomes among the patient population at a tertiary hospital in Kenya. Methods: This was a retrospective descriptive study of COVID-19 patients who were admitted between March 2020 and December 2020 at the Aga Khan University Hospital in Nairobi, Kenya. Data collected include patient demographic and baseline characteristics. Differences between patients who were known to have diabetes and hypertension during admission were compared for statistical significance. Difference between those who survived and those who died were also compared for statistical significance. Results: A total of 913 records of patients were studied with a mean age of 51.2 years (SD = 16.7), 66.5% were male and 80.8% were of African origin. History of diabetes, hypertension, and HIV status were at 27.3%, 33.1%, and 2.3%, respectively. At presentation, 33.1% (302/913) of patients had known hypertension by history, and following admission, this proportion increased to 37.7% (344/ 913). At presentation, 27.3% (249/913) of patients had known diabetes. During hospital stay, 20.8% (190) more patients were found to have diabetes, raising the overall percent to 48.1% (439/913). When comparing diabetes and hypertension at baseline versus at the end of admission, diabetes increased by 20.8% (p < 0.001) and hypertension by 4.6% (p = 0.049). HIV co-infection was 2.3%, and no patient had tuberculosis. Conclusion: This study showed a high incidence of co-morbidities in patients infected with COVID-19. Diabetes was most common, followed by hypertension. All patients admitted with COVID-19 infection should routinely be tested for diabetes with HbA1c and have regular blood pressure monitoring in order to diagnose occult diabetes and hypertension. Adverse outcomes were found in patients with these co-morbidities and should be monitored and treated appropriately.
Breast cancer is the most prevalent neoplasm and the second leading cause of death among females ... more Breast cancer is the most prevalent neoplasm and the second leading cause of death among females in Kenya. Estrogen and its metabolites are known risk factors for breast cancer. Polymorphisms in these genes and breast cancer susceptibility are unique among different populations. This study aimed to determine the probable associations between estrogen-metabolizing gene variations and other risk factors for breast cancer risk in Kenyan women. Buffy coat samples were obtained from patients diagnosed with estrogen receptor-positive breast cancer, benign breast disease, and healthy volunteers. Genotyping of target polymorphisms was conducted using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis. The rs4646903 variant genotype CC was associated with breast cancer in the case-control model (P=0.001); the heterozygous genotype TC (P=0.01) and the luminal B molecular subtype (P=0.02) showed increased odds of late-stage breast cancer. The rs1048943 var...
At the time of original publication, there was an incomplete listing of contributing authors and ... more At the time of original publication, there was an incomplete listing of contributing authors and their institutions. This revision corrects those omissions.
American Journal of Clinical Pathology, Feb 2, 2021
ObjectivesPeripheral T-cell lymphomas (PTCLs) are heterogeneous, clinically aggressive, and rare.... more ObjectivesPeripheral T-cell lymphomas (PTCLs) are heterogeneous, clinically aggressive, and rare. Subtype distribution varies by geographic location; however, data from sub-Saharan Africa (SSA) are lacking. We sought to elucidate clinicopathologic features of PTCL in SSA.MethodsWe reviewed PTCL consultation cases from three SSA countries. PTCL subtype was determined per 2017 World Health Organization classification. Cases with sufficient material were evaluated by polymerase chain reaction for human T-cell leukemia virus type 1 (HTLV-1) and T-cell receptor γ (TCRG) rearrangement.ResultsAmong 32 cases, median age was 45 years and male-to-female ratio was 1.7. Thirty (94%) of 32 cases required additional workup for subclassification. PTCL, not otherwise specified (PTCL-NOS) was the most common subtype (13/32, 41%), followed by PTCL with T-follicular helper phenotype (6/32, 19%) and systemic anaplastic large cell lymphoma (6/32, 19%). Four (16%) of 25 cases were Epstein-Barr virus positive (EBV+) (2/2 extranodal natural killer/T-cell lymphoma, 1/13 PTCL-NOS, and 1/4 angioimmunoblastic T-cell lymphoma with EBV+ immunoblasts). Two (15%) of 13 patients with PTCL-NOS were human immunodeficiency virus positive. No cases with evaluable DNA (0/15) were HTLV-1 positive, and 9 of 10 showed clonal TCRG rearrangements.ConclusionsIn comparison to Western studies, PTCLs from SSA show similar subtype distribution and male predominance but a younger age at diagnosis. Appropriate diagnosis of PTCL requires extensive ancillary testing not readily available in low-income countries, including much of SSA.
Introduction. Data examining mammographic breast density (MBD) among patients in Sub-Saharan Afri... more Introduction. Data examining mammographic breast density (MBD) among patients in Sub-Saharan Africa are sparse. We evaluated how MBD relates to breast cancer characteristics in Kenyan women undergoing diagnostic mammography. Methods. This crosssectional study included women with pathologically confirmed breast cancers (= 123). Pretreatment mammograms of the unaffected breast were assessed to estimate absolute dense area (cm 2), nondense area (cm 2), and percent density (PD). Relationships between density measurements and clinical characteristics were evaluated using analysis of covariance. Results. Median PD and dense area were 24.9% and 85.3 cm 2. Higher PD and dense area were observed in younger women (< 0.01). Higher dense and nondense areas were observed in obese women (-trend < 0.01). Estrogen receptor (ER) positive patients (73%) had higher PD and dense area than ER-negative patients (≤ 0.02). Triple negative breast cancer (TNBC) patients (17%) had lower PD and dense area (≤ 0.01) compared with non-TNBCs. No associations were observed between MBD and tumor size and grade. Conclusions. Our findings show discordant relationships between MBD and molecular tumor subtypes to those previously observed in Western populations. The relatively low breast density observed at diagnosis may have important implications for cancer prevention initiatives in Kenya. Subsequent larger studies are needed to confirm these findings.
Breast cancer awareness and early detection x Kenya x Low-and middle-income countries x Breast ca... more Breast cancer awareness and early detection x Kenya x Low-and middle-income countries x Breast cancer camps x Breast cancer diagnosis
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