- Malawi
steve kamiza
University of Malawi, College of Medicine, Pathology, Department Member
Background: Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of death of women in Africa. Management of breast cancer depends on availability of robust clinical and pathologic prognostic and... more
Background: Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of death of women in Africa. Management of breast cancer depends on availability of robust clinical and pathologic prognostic and predictive factors to guide decision making and the choice of treatment options. Objective: We set out to determine the common histological phenotypes of breast cancer in indigenous Malawian women presenting at Queen Elizabeth Central Hospital (QECH). Methods: We analyzed 63 samples of breast cancer Formalinfixed paraffin-embedded (FFPE) tissues and determined the prevalence of breast cancer over the three year period. Histological phenotypes were matched for age, tumor grade and clinical signs at presentation. The pathology files were retrieved from January 2012 through December 2013 and January through December 2015. Sixty-three breast cancer cases were analyzed for our results showed an increase in the prevalence of breast cancer from 2012 to 2015 as follows 2012 (22/99) 22.2%, 2013 (25/66) 37.9% and 2015 (16/48) 33.3%. Data was analyzed using IBM SPSS® version 20.0 for windows. The chi-square statistical test was used and a p-value of equal to or less than 0.05 was used to indicate statistical significance of the results Results: The histological phenotypes were categorized as follows, invasive ductal carcinoma (IDC) 26 (41.3%), lobular carcinoma 17 (27%), Lobular plus ductal 4 (6.3%), medullary carcinoma 5(7.9%) and papillary intra ductal carcinoma 3(4.8%). Rare breast cancers were 1.6% each with the following proportions, clear cell carcinoma1, Paget disease and squamous cell carcinoma of surface origin1, invasive micro papillary carcinoma 1, oncocytic carcinoma1, solitary myeloma 1, malignant mesenchymal tumor 1, nonkeratinizing squamous cell carcinoma of surface origin plus Ductal carcinoma in situ 1(DCIS) and signet ring variety of mucinous carcinoma1. The common histological grade were grade 2, 32 (50.8%), grade 1,22 (34.9%) and grade 3,4 (6.4%), 5 (7.9%) cases could not be graded Conclusion: The commonest histological phenotype of breast cancer was invasive ductal carcinoma (IDC) followed by lobular carcinoma, and grade two was the commonest histological grade followed by grade one. Most affected age groups were below 50 years of age with a peak at 41 to 50 years of age
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blood-tissue barrier disruption in brain and retina of Malawian children with fatal cerebral malaria
Cerebral malaria (CM) is a complication of Plasmodium falciparum malaria, in which progressive brain swelling is associated with sequestration of parasites and impaired barrier function of the cerebral microvascular endothelium. To test... more
Cerebral malaria (CM) is a complication of Plasmodium falciparum malaria, in which progressive brain swelling is associated with sequestration of parasites and impaired barrier function of the cerebral microvascular endothelium. To test the hypothesis that localised release of matrix metallopeptidase 8 (MMP8) within the retina is implicated in microvascular leak in CM, we examined its expression and association with extravascular fibrinogen leak in a case–control study of post‐mortem retinal samples from 13 Malawian children who met the clinical case definition of CM during life. Cases were seven children who were found on post‐mortem examination to have ‘true‐CM’ (parasite sequestration in brain blood vessels), whilst controls were six children who had alternative causes of death (‘faux‐CM’, no parasite sequestration in blood vessels).
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Impact of infection with human immunodeficiency virus-1 (HIV) on the risk of cancer among children in Malawi- preliminary findings
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The Collaborative Wilms Tumour (WT) Africa Project implemented an adapted WT treatment guideline in six centres in sub‐Saharan Africa. The primary objectives were to describe abandonment of treatment, death during treatment, event‐free... more
The Collaborative Wilms Tumour (WT) Africa Project implemented an adapted WT treatment guideline in six centres in sub‐Saharan Africa. The primary objectives were to describe abandonment of treatment, death during treatment, event‐free survival (EFS) and relapse following implementation. An exploratory objective was to compare outcomes with the baseline evaluation, a historical cohort preceding implementation.
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Outcomes among persons with lymphoma in sub-Saharan African (SSA) remain poor, largely due to resource limitations in diagnostics, therapeutics and supportive care. We hypothesized that subclassification of lymphoma specimens from SSA... more
Outcomes among persons with lymphoma in sub-Saharan African (SSA) remain poor, largely due to resource limitations in diagnostics, therapeutics and supportive care. We hypothesized that subclassification of lymphoma specimens from SSA could improve diagnostic accuracy, thereby altering treatment recommendations and identifying cases responsive to less toxic, targeted agents. The Queen Elizabeth Central Hospital (QECH) in Malawi serves as the teaching hospital for the University of Malawi College of Medicine (UOMCOM) in Blantyre,…
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Background Maternal influenza vaccination protects infants against influenza virus infection. Impaired transplacental transfer of influenza antibodies may reduce this protection. Methods We conducted a cross-sectional study of influenza... more
Background Maternal influenza vaccination protects infants against influenza virus infection. Impaired transplacental transfer of influenza antibodies may reduce this protection. Methods We conducted a cross-sectional study of influenza vaccine-naïve pregnant women recruited at delivery from Blantyre (urban, low malaria transmission) and Chikwawa (rural, high malaria transmission) in Southern Malawi. HIV-infected mothers were excluded in Chikwawa. Maternal and cord blood antibodies against circulating influenza strains A/California/7/2009, A/Victoria/361/2011, B/Brisbane/60/2008 and B/Wisconsin/1/2010 were measured by hemagglutination inhibition (HAI). We studied the impact of maternal HIV infection and placental malaria on influenza antibody levels in mother-infant pairs in Blantyre and Chikwawa, respectively. Results We included 454 mother-infant pairs (Blantyre, n=253; Chikwawa, n=201). HIV-infected mothers and their infants had lower seropositivity (HAI titer ≥1:40) against infl...
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Wilms tumor (WT) has a survival rate above 90% in high income countries. Reported survival rates in sub-Saharan Africa are much lower and long-term outcome is not well known as follow-up is challenging. In Blantyre, Malawi, an adapted WT... more
Wilms tumor (WT) has a survival rate above 90% in high income countries. Reported survival rates in sub-Saharan Africa are much lower and long-term outcome is not well known as follow-up is challenging. In Blantyre, Malawi, an adapted WT treatment guideline with preoperative chemotherapy, supportive care, and strategies to enable children and parents to complete treatment was introduced in 2006. Between 2006 and 2011, 73 children with a unilateral WT were treated. Follow-up, including home visits when needed, was done. Median follow-up time is 5 years (range 14-95 months). Two and five-year event free survivals are 46 and 42%. Causes of treatment failure are: 7% (5/73) abandonment of treatment, 15% (11/73) death during treatment and 30% (22/73) disease-related deaths (persistent disease and relapse). Long-term follow-up is challenging but necessary to be able to assess outcome and the true impact of interventions.
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Retinal vessel changes and retinal whitening, distinctive features of malarial retinopathy, can be directly observed during routine eye examination in children with cerebral malaria. We investigated their clinical significance and... more
Retinal vessel changes and retinal whitening, distinctive features of malarial retinopathy, can be directly observed during routine eye examination in children with cerebral malaria. We investigated their clinical significance and underlying mechanisms through linked clinical, clinicopathological and image analysis studies. Orange vessels and severe foveal whitening (clinical examination, n = 817, OR, 95% CI: 2.90, 1.96-4.30; 3.4, 1.8-6.3, both p<0.001), and arteriolar involvement by intravascular filling defects (angiographic image analysis, n = 260, 2.81, 1.17-6.72, p<0.02) were strongly associated with death. Orange vessels had dense sequestration of late stage parasitised red cells (histopathology, n = 29; sensitivity 0.97, specificity 0.89) involving 360° of the lumen circumference, with altered protein expression in blood-retinal barrier cells and marked loss/disruption of pericytes. Retinal whitening was topographically associated with tissue response to hypoxia. Severe...
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More than 20 million babies are born with low birthweight annually. Small newborns have an increased risk for mortality, growth failure, and other adverse outcomes. Numerous antenatal risk factors for small newborn size have been... more
More than 20 million babies are born with low birthweight annually. Small newborns have an increased risk for mortality, growth failure, and other adverse outcomes. Numerous antenatal risk factors for small newborn size have been identified, but individual interventions addressing them have not markedly improved the health outcomes of interest. We tested a hypothesis that in low-income settings, newborn size is influenced jointly by multiple maternal exposures and characterized pathways associating these exposures with newborn size. This was a prospective cohort study of pregnant women and their offspring nested in an intervention trial in rural Malawi. We collected information on maternal and placental characteristics and used regression analyses, structural equation modelling, and random forest models to build pathway maps for direct and indirect associations between these characteristics and newborn weight-for-age Z-score and length-for-age Z-score. We used multiple imputation to...
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Research Interests: Infectious Diseases, HIV, Malawi, Biological Sciences, Stroke, and 15 moreProspective studies, Humans, Vasculitis, Female, Male, Risk factors, Aged, Middle Aged, Adult, Risk Factors, Case Control Studies, Viral Load, immune reconstitution inflammatory syndrome, Medical and Health Sciences, and HIV infections
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Cervical squamous cell carcinoma (SCC) continues to be a significant cause of cancer morbidity and is the third leading cause of cancer-related death in women worldwide. In sub-Saharan Africa, cervical cancer is not only the most common... more
Cervical squamous cell carcinoma (SCC) continues to be a significant cause of cancer morbidity and is the third leading cause of cancer-related death in women worldwide. In sub-Saharan Africa, cervical cancer is not only the most common female cancer but also the leading cause of cancer-related deaths in women. Malawi, in particular, has the highest burden of cervical cancer. With the increasing use of human papillomavirus (HPV) vaccination, documenting the prevalent HPV types in those high-risk populations is necessary to both manage expectations of HPV vaccination and guide future vaccine development. In this study, we performed HPV typing on 474 cervical SCC samples and analyzed the potential impact of HPV vaccination in this population. Ninety-seven percent of tumors were positive for at least one HPV type, and 54% harbored more than one HPV type. HPV 16 was the most common type (82%), followed by HPV 18 (34%), HPV 35 (24%), and HPV 31 (12%). A vaccine against HPV 16 and 18 woul...
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Key Points NHL subclassification is lacking in Malawi due to resource constraints yet is critical for directing therapy. Targeted gene expression profiling facilitates objective assessment and segregation of biologically defined subsets... more
Key Points NHL subclassification is lacking in Malawi due to resource constraints yet is critical for directing therapy. Targeted gene expression profiling facilitates objective assessment and segregation of biologically defined subsets of NHL from Malawi.
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Malaria antibody responses measured at delivery have been associated with protection from maternal anaemia and low birth weight deliveries. Whether malarial antibodies present in the first half of pregnancy may protect from these or other... more
Malaria antibody responses measured at delivery have been associated with protection from maternal anaemia and low birth weight deliveries. Whether malarial antibodies present in the first half of pregnancy may protect from these or other poor birth outcomes is unclear. To determine whether malaria antibodies in the first half of pregnancy predict pregnancy outcomes, antibodies were measured to a range of merozoite antigens and to antigens expressed on the surface of parasitized red blood cells (pRBCs) in plasma samples collected at 14-20 weeks of gestation from Malawian women. The latter antibodies were measured as total IgG to pRBCs, and antibodies promoting opsonic phagocytosis of pRBCs. Associations between antibodies and maternal haemoglobin in late pregnancy or newborn size were investigated, after adjusting for potential covariates. Antibodies to pRBC surface antigens were associated with higher haemoglobin concentration at 36 weeks. Total IgG to pRBCs was associated with 0.4...
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68 Background: Cancer burden is increasing in Malawi, particularly for HIV-associated malignancies. Methods: With support from the National Cancer Institute, the Malawi Cancer Consortium (MCC) was initiated in September 2014. Partners... more
68 Background: Cancer burden is increasing in Malawi, particularly for HIV-associated malignancies. Methods: With support from the National Cancer Institute, the Malawi Cancer Consortium (MCC) was initiated in September 2014. Partners include the UNC Lineberger Comprehensive Cancer Center, Malawi Ministry of Health, University of Malawi College of Medicine, and Lighthouse Trust. Spanning Malawi’s two major cities, Lilongwe and Blantyre, MCC includes three support cores (administration, analysis, mentoring) and three multi-institution research projects: (1) a national HIV-cancer match study to assess cancer incidence in the ART era; (2) a longitudinal cohort to identify clinical and molecular correlates of KS chemotherapy response; and (3) a longitudinal cohort to elucidate lymphoma biology and develop better treatments for HIV-associated lymphoma. Results: For project 1, 65,500 records from the Malawi National Cancer Registry and Malawi HIV cohorts have been abstracted, and initial ...
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The spleen has an important role in the clearance of malaria parasites, and the role of HIV co-infection on this process is yet to be described. Using a combination of histological and molecular methods, we systematically evaluated... more
The spleen has an important role in the clearance of malaria parasites, and the role of HIV co-infection on this process is yet to be described. Using a combination of histological and molecular methods, we systematically evaluated parasite load across multiple organs from HIV-positive and HIV-negative cases of an autopsy study of pediatric comatose children with malaria infection (n=103) in Blantyre, Malawi. Quantification of parasite load across organs was done using histology. A subset of cases was further characterized for parasite localization and stage of development using immunohistochemistry-based labeling of parasite and host cells (5 HIV-positive, 10 HIV-negative), and quantitative RT-PCR (qRT-PCR) of asexual and sexual-specific genes (4 HIV-positive, 5 HIV-negative). The results were compared with clinical information including HIV status. The HIV-positive rate was 21% for the group studied (20 of 95) and HIV-positive patients had a significantly shorter duration of time ...
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During pregnancy, women living in malaria-endemic regions are at increased risk of malaria infection and can harbour chronic placental infections. Intermittent preventive treatment with sulphadoxine-pyrimethamine (SP-IPTp) is administered... more
During pregnancy, women living in malaria-endemic regions are at increased risk of malaria infection and can harbour chronic placental infections. Intermittent preventive treatment with sulphadoxine-pyrimethamine (SP-IPTp) is administered to reduce malaria morbidity. It was hypothesized that the presence of placental malaria infection and SP-IPTp use would increase the risk of peripheral blood gametocytes, the parasite stage that is transmissible to mosquitoes. This would suggest that pregnant women may be important reservoirs of malaria transmission. Light microscopy was used to assess peripheral gametocytaemia in pregnant women enrolled in a longitudinal, observational study in Blantyre, Malawi to determine the association between placental malaria and maternal gametocytaemia. The relationship between SP-IPTp and gametocytaemia was also examined. 2,719 samples from 448 women were analysed and 32 episodes of microscopic gametocytaemia were detected in 27 women. At the time of enrol...
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Respiratory signs are common in African children where malaria is highly endemic, and thus, parsing the role of pulmonary pathology in illness is challenging. We examined the lungs of 100 children from an autopsy series in Blantyre,... more
Respiratory signs are common in African children where malaria is highly endemic, and thus, parsing the role of pulmonary pathology in illness is challenging. We examined the lungs of 100 children from an autopsy series in Blantyre, Malawi, many of whom death was attributed to Plasmodium falciparum malaria. Our aim was to describe the pathologic manifestations of fatal malaria; to understand the role of parasites, pigment, and macrophages; and to catalog comorbidities. From available patients, which included 55 patients with cerebral malaria and 45 controls, we obtained 4 cores of lung tissue for immunohistochemistry and morphological evaluation. We found that, in patients with cerebral malaria, large numbers of malaria parasites were present in pulmonary alveolar capillaries, together with extensive deposits of malaria pigment (hemozoin). The number of pulmonary macrophages in this vascular bed did not differ between patients with cerebral malaria, noncerebral malaria, and nonmalarial diagnoses. Comorbidities found in some cerebral malaria patients included pneumonia, pulmonary edema, hemorrhage, and systemic activation of coagulation. We conclude that the respiratory distress seen in patients with cerebral malaria does not appear to be anatomic in origin but that increasing malaria pigment is strongly associated with cerebral malaria at autopsy.
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Research Interests: Pathology, Stratification, Medicine, Malawi, Humans, and 15 moreChild, Female, Male, Infant, Doxorubicin, Prognosis, Low Income Countries, Nephrectomy, Postoperative care, Combined Modality Therapy, Child preschool, Wilms tumor, Neoplasm staging, Vincristine, and Paediatrics and reproductive medicine
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Research Interests: Developing Countries, Social Support, Treatment Outcome, Comorbidity, Malawi, and 15 moreMalnutrition, Humans, Incidence, Doxorubicin, Survival Rate, Pediatric Hematology Oncology, Disease Management, Nephrectomy, Delayed Diagnosis, Nutritional Support, Combined Modality Therapy, Neoplasm staging, Vincristine, Cardiovascular medicine and haematology, and Diagnostic errors
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Research Interests: Developing Countries, Adolescent, Medicine, Malawi, Humans, and 10 moreChild, Female, Male, Incidence, Registries, Aged, Middle Aged, Adult, Neoplasms, and Child preschool
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33 Background: Enabled by collaboration and political stability, Malawi is a global leader for HIV research and implementation. We undertook this work to identify ways to leverage successes in HIV treatment and research for cancer and... more
33 Background: Enabled by collaboration and political stability, Malawi is a global leader for HIV research and implementation. We undertook this work to identify ways to leverage successes in HIV treatment and research for cancer and noncommunicable diseases (NCDs). Methods: Over more than two decades, investment from the National Institutes of Health (NIH) and other funders has allowed Malawi participation in international HIV networks. As these sought to address HIV-positive cancer, investment occurred to increase pathology, improve cancer registration, scale up cervical cancer screening, and improve nursing and pharmacy skills for chemotherapy administration. This allowed Malawi to participate in multinational clinical trials for HIV-positive Kaposi sarcoma treatment and cervical cancer prevention. Building on this, Malawi was one of six countries in 2014 to receive an NIH U54 consortium award for HIV-positive malignancies and was one of six countries added to the National Cance...
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Research Interests: Microbiology and Mbio
Cerebral malaria (CM) is a major contributor to malaria deaths, but its pathophysiology is not well understood. While sequestration of parasitized erythrocytes is thought to be critical, the roles of inflammation and coagulation are... more
Cerebral malaria (CM) is a major contributor to malaria deaths, but its pathophysiology is not well understood. While sequestration of parasitized erythrocytes is thought to be critical, the roles of inflammation and coagulation are controversial. In a large series of Malawian children hospitalized with CM, HIV coinfection was more prevalent than in pediatric population estimates (15% versus 2%, P < 0.0001, chi-square test), with higher mortality than that seen in HIV-uninfected children (23% versus 17%, P = 0.0178, chi-square test). HIV-infected (HIV(+)) children with autopsy-confirmed CM were older than HIV-uninfected children (median age, 99 months versus 32 months, P = 0.0007, Mann-Whitney U test) and appeared to lack severe immunosuppression. Because HIV infection is associated with dysregulated inflammation and platelet activation, we performed immunohistochemistry analysis for monocytes, platelets, and neutrophils in brain tissue from HIV(+) and HIV-uninfected children wit...
Research Interests: Microbiology and Mbio
To evaluate the feasibility and effectiveness of dried blood spots (DBS) use for viral load (VL) monitoring, describing patient outcomes and programmatic challenges that are relevant for DBS implementation in sub-Saharan Africa. We... more
To evaluate the feasibility and effectiveness of dried blood spots (DBS) use for viral load (VL) monitoring, describing patient outcomes and programmatic challenges that are relevant for DBS implementation in sub-Saharan Africa. We recruited adult antiretroviral therapy (ART) patients from five district hospitals in Malawi. Eligibility reflected anticipated Ministry of Health VL monitoring criteria. Testing was conducted at a central laboratory. Virological failure was defined as >5000 copies/ml. Primary outcomes were program feasibility (timely result availability and patient receipt) and effectiveness (second-line therapy initiation). We enrolled 1,498 participants; 5.9% were failing at baseline. Median time from enrollment to receipt of results was 42 days; 79.6% of participants received results within 3 months. Among participants with confirmed elevated VL, 92.6% initiated second-line therapy; 90.7% were switched within 365 days of VL testing. Nearly one-third (30.8%) of part...
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Children in sub-Saharan Africa continue to suffer from and succumb to cerebral malaria despite efforts to control or eliminate the causative agent, P falciparum. We present a quantitative histopathological assessment of the sequestration... more
Children in sub-Saharan Africa continue to suffer from and succumb to cerebral malaria despite efforts to control or eliminate the causative agent, P falciparum. We present a quantitative histopathological assessment of the sequestration of parasitized erythrocytes in multiple organs sampled from a prospective series of 103 autopsies performed between 1996 and 2010 in Blantyre, Malawi on pediatric cerebral malaria patients and controls. After the brain, sequestration of parasites was most intense in the gastrointestinal tract, both in cerebral malaria and in other parasitemic patients. Within cases of histologically defined cerebral malaria which includes a "sequestration only" phenotype (CM1) and a "sequestration with extravascular pathology" phenotype (CM2), CM1 was associated with large parasite numbers in the spleen and CM2 with intense parasite sequestration in the skin (CM2). A striking histological finding overall is the marked sequestration of parasitized...
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The retinal and brain histopathological findings in children who died from cerebral malaria (CM) have been recently described. Similar changes occur in both structures, but the findings have not been directly compared in the same... more
The retinal and brain histopathological findings in children who died from cerebral malaria (CM) have been recently described. Similar changes occur in both structures, but the findings have not been directly compared in the same patients. In this study, we compared clinical retinal findings and retinal and cerebral histopathological changes in a series of patients in Blantyre, Malawi, who died of CM. The features systematically compared in the same patient were: (1) clinical, gross and microscopic retinal hemorrhages with microscopic cerebral hemorrhages, (2) retinal and cerebral hemorrhage-associated and -unassociated axonal damage, and fibrinogen leakage, and (3) differences in the above features between the pathological categories of CM without microvascular pathology (CM1) and CM with microvascular pathology (CM2) in retina and brain. Forty-seven patients were included: seven CM1, 28 CM2, and 12 controls. In the 35 malaria cases retinal and cerebral pathology correlated in all features except for non-hemorrhage associated fibrinogen leakage. Regarding CM1 and CM2 cases, the only differences were in the proportion of patients with hemorrhage-associated cerebral pathology, and this was expected, based on the definitions of CM1 and CM2. The retina did not show this difference. Non-hemorrhage associated pathology was similar for the two groups. As postulated, histopathological features of hemorrhages, axonal damage and non-hemorrhage associated fibrinogen leakage correlated in the retina and brain of individual patients, although the difference in hemorrhages between the CM1 and CM2 groups was not consistently observed in the retina. These results help to underpin the utility of ophthalmoscopic examination and fundus findings to help in diagnosis and assessment of cerebral malaria patients, but may not help in distinguishing between CM1 and CM2 patients during life.