Charles Dzamalala

Burden of cancer in Malawi; common types, incidence and trends: National population-based cancer registry

BackgroundCancer is a leading cause of morbidity and mortality worldwide with a majority of cases and deaths occurring in developing countries. While cancer of the lung, breast, colorectum, stomach and prostate are the most common types of cancer globally, in east and southern Africa these are less common and comprehensive data to inform policies are lacking.MethodsNationwide cancer registry was conducted between September and October 2010 in Malawi. New cancer cases registered from 2007 to 2010 were identified from hospital and clinic registers of 81 out of 84 health facilities providing cancer diagnosis, treatment or palliative care services. Demographic and cancer data were extracted from registers and case notes using a standard form.ResultsA total of 18,946 new cases of cancer were registered in Malawi from 2007-2010. Of these 55.9% were females, 7.2% were children aged less than 15 years, 76.5% were adults aged 15-59 years and 16.4% were elderly aged 60 years or more. Only 17.9% of the cases had histologically verified diagnosis, 33.2% were diagnosed clinically and 49.6% based on clinical and some investigations. Amongst females, cancer of the cervix was the commonest accounting for 45.4% of all cases followed by Kaposi sarcoma (21.1%), cancer of the oesophagus (8.2%), breast (4.6%) and non-Hodgkin lymphoma (4.1%). In males, Kaposi sarcoma was the most frequent (50.7%) then cancer of oesophagus (16.9%), non-Hodgkin lymphoma (7.8), prostate (4.0%) and urinary bladder (3.7%). Age-standardised incidence rate per 100,000 population for all types of cancer in males increased from 31 in 1999-2002 to 56 in 2007-2010. In females it increased from 29 to 69. Kaposi sarcoma and cancer of the oesophagus, cervical cancer and Kaposi sarcoma were the main causes for the increased incidence in males and females respectively. It was estimated that, annually at least 8,151 new cases of cancer (all types) occur in Malawi.ConclusionsThis study provided data on common types and trends of cancer that could be used to focus prevention, treatment and control interventions in the context of limited resources. The problem of under-reporting and misdiagnosis of cancer cases has been highlighted.

The systemic pathology of cerebral malaria in African children

Pediatric cerebral malaria carries a high mortality rate in sub-Saharan Africa. We present our systematic analysis of the descriptive and quantitative histopathology of all organs sampled from a series of 103 autopsies performed between 1996 and 2010 in Blantyre, Malawi on pediatric cerebral malaria patients and control patients (without coma, or without malaria infection) who were clinically well characterized prior to death. We found brain swelling in all cerebral malaria patients and the majority of controls. The histopathology in patients with sequestration of parasites in the brain demonstrated two patterns: (a) the “classic” appearance (i.e., ring hemorrhages, dense sequestration, and extra-erythrocytic pigment) which was associated with evidence of systemic activation of coagulation and (b) the “sequestration only” appearance associated with shorter duration of illness and higher total burden of parasites in all organs including the spleen. Sequestration of parasites was most intense in the gastrointestinal tract in all parasitemic patients (those with cerebral malarial and those without).

Genetic Analysis of Circulating and Sequestered Populations of Plasmodium falciparum in Fatal Pediatric Malaria

Falciparum malaria is characterized by cytoadherence of host erythrocytes containing mature asexual-stage parasites and the consequent sequestration of these forms in tissue microvasculature. A postmortem study of pediatric malaria provided us with the opportunity to compare the genetic complexity of circulating and sequestered Plasmodium falciparum populations, in patients with fatal cerebral malaria (CM) versus control subjects with incidental P. falciparum parasitemia who died of causes other than malaria. Parasite genotypes identified in peripheral blood collected at the time of admission to the hospital constituted a subset of those detected in the tissues at death. Despite a higher tissue burden of parasitized erythrocytes in patients with CM than in parasitemic control subjects, parasite populations in tissues from patients with CM were less genetically complex, and the genotypes were more homogeneously distributed throughout the body, than in patients with incidental infection. Our findings support the notion that CM is associated with the emergence of a small number of dominant genotypes in an infected individual.

Sampling of Supraorbital Brain Tissue after Death: Improving on the Clinical Diagnosis of Cerebral Malaria

The clinical diagnosis of cerebral malaria in Plasmodium falciparum-endemic regions is strengthened by demonstration of cerebral sequestration at autopsy. Parasitized comatose patients dying of other causes are less likely to have cerebral sequestration but can be difficult to distinguish, on clinical grounds, from patients dying of cerebral malaria. Sequestered parasites in a cytological preparation of a supraorbital brain sample, obtained after death, can be studied by use of standard thin blood-film staining. We show that, when confirmation by autopsy is not possible, this procedure is a reliable surrogate for histological study of tissue and that it can accurately identify patients with or without sequestered parasites in cerebral capillaries.

Informing etiologic research priorities for squamous cell esophageal cancer in Africa: a review of setting-specific exposures to known and putative risk factors

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in most Eastern and Southern African countries, but its etiology has been understudied to date. To inform its research agenda, we undertook a review to identify, of the ESCC risk factors which have been established or strongly suggested worldwide, those with a high prevalence or high exposure levels in any ESCC‐affected African setting and the sources thereof. We found that for almost all ESCC risk factors known to date, including tobacco, alcohol, hot beverage consumption, nitrosamines and both inhaled and ingested PAHs, there is evidence of population groups with raised exposures, the sources of which vary greatly between cultures across the ESCC corridor. Research encompassing these risk factors is warranted and is likely to identify primary prevention strategies.

ABO blood group phenotypes influence parity specific immunity to Plasmodium falciparum malaria in Malawian women

BackgroundBlood group O has been significantly associated with increased placental malaria infection in primiparae and reduced risk of infection in multiparae in the Gambia, an area with markedly seasonal malaria transmission. This study analyses the association between ABO blood group phenotypes in relation to placental malaria pathology and birth outcomes in southern Malawi, an area with perennial malaria transmission.MethodsA cross-sectional study of 647 mother/child pairs delivering in Montfort Hospital, Chikwawa District between February-June 2004 and January-July 2005 was undertaken. Maternal peripheral and cord blood samples were obtained at delivery. Placental tissue was obtained and malaria histology classified as active, past or no malaria infection. Birth anthropometry was recorded. ABO blood group was measured by agglutination.ResultsIn primiparae, blood group O was significantly associated with increased risk of active placental infection (OR 2.18, 95% CI 1.15–4.6, p = 0.02) and an increased foetal-placental weight ratio compared to non-O phenotypes (5.68 versus 5.45, p = 0.03) In multiparae blood group O was significantly associated with less frequent active placental infection (OR 0.59, 95% CI 0.36–0.98, p = 0.04), and a higher newborn ponderal index compared to non-O phenotypes (2.65 versus 2.55, p = 0.007). In multivariate regression parity was independently associated with increased risk of placental malaria (active andpast infection) in primiparae with blood group O (p = 0.034) and reduced risk in multiparae with the same phenotype (p = 0.015).ConclusionParity related susceptibility to placental malaria is associated with the mothers ABO phenotype. This interaction influences foetal and placental growth and could be an important modifying factor for pregnancy outcomes. The biological explanation could relate to sialic acid dependent placental membrane differences which vary with ABO blood group.

Three year cancer incidence in Blantyre, Malawi (2008-2010)

In this paper, we present incidence rates of different cancers calculated for the population of Blantyre, Malawi for the period 2008–2010, using data from the Malawi Cancer Registry. Active methods were used for case finding, with standard checks for accuracy and validity performed in CanReg 4. During this 3‐year period, a total of 3,711 cases were registered comprising 1,643 men (an estimated age‐standardized incidence rate (ASR) of 169.8 per 100,000) and 2,068 women (ASR 238.7 per 105). Kaposi sarcoma (KS) was the most common cancer in men (40.5% of all cancers in men; ASR 54.0 per 105) while cervical cancer was the commonest in women (33.3%; ASR 88.6 per 105). The incidence rates for esophageal cancer remain one of the highest in the world (ASR 30.9 per 100,000 in men, 22.1 per 100,000 in women). Incidence of cancer of the prostate is relatively low in Blantyre (5.1%; ASR 16.4 per 105), compared with elsewhere in Africa. In childhood, the cancer spectrum is dominated by Burkitt lymphoma (32.5% ASR 90.9 per 106) followed by Wilms tumor (11.3%; ASR 35.9 per 106) and pediatric KS (11.0%; ASR 31.1 per 106). The overall percentage of cases with histological verification was 47.5%, a slight improvement from 42.4% in late 1990s also indicating successful case finding outside laboratories.

Esophageal cancer male to female incidence ratios in Africa: A systematic review and meta-analysis of geographic, time and age trends

Highlights • We conducted a review and meta-analysis of esophageal cancer sex ratios in mainland Africa using data from 197 populations in 36 countries.• We observed a consistent male excess in incidence rates overall and in the high-risk Eastern and Southern African regions.• A male excess was evident in 30–39 year olds in high-risk Eastern and Southern African regions.• Our findings suggest that a substantial fraction of the African EC burden could be avoided by targeting gender-specific exposures.

Frequent HIV and Young Age Among Individuals With Diverse Cancers at a National Teaching Hospital in Malawi

Purpose Cancer surveillance provides a critical evidence base to guide cancer control efforts, yet population-based coverage in Africa is sparse. Hospital-based registries may help fill this need by providing local epidemiologic data to guide policy and forecast local health care needs. We report the epidemiology of patients with cancer recorded by a de novo hospital-based cancer registry at Kamuzu Central Hospital, Malawi, the sole provider of comprehensive oncology services for half the country and location of a high-volume pathology laboratory. Methods We conducted active case finding across all hospital departments and the pathology laboratory from June 2014 to March 2016. Patient demographics, tumor characteristics, treatment, and HIV status were collected. We describe epidemiology of the cancer caseload, registry design, and costs associated with registry operations. Results Among 1,446 registered patients, Kaposi sarcoma and cervical cancer were the most common cancers among men and women, respectively. Burkitt lymphoma was most common cancer among children. The current rate of pathology confirmation is 65%, a vast improvement in the diagnostic capacity for cancer through the hospital’s pathology laboratory. Among leading cancer types, an alarming proportion occurred at young ages; 50% of Kaposi sarcoma and 25% of esophageal, breast, and cervical cancers were diagnosed among those younger than 40 years of age. A systematic, cross-sectional assessment of HIV status reveals a prevalence of 58% among adults and 18% among children. Conclusion We report a high caseload among typically young patients and a significant burden of HIV infection among patients with cancer. In low- and middle-income countries with intermittent, sparse, or nonexistent cancer surveillance, hospital-based cancer registries can provide important local epidemiologic data while efforts to expand population-based registration continue.

Leveraging HIV Research and Implementation for Cancer and Noncommunicable Diseases in Malawi

Abstract 33Background: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 Cancer Institute (NCI) ...