Abstract
BackgroundMalaria is associated with Burkitt lymphoma among children in Sub-Saharan Africa. No longitudinal studies have assessed the long-term risk of other lymphoma or cancer overall. Here, we investigated the risk of lymphoid neoplasms and other cancer after malaria.MethodsWe included 4125 patients diagnosed with malaria in Sweden in 1987–2015, identified either through the National Surveillance Database at the Public Health Agency of Sweden, the National Inpatient and Outpatient Register, or by reports from microbiology departments. A comparator cohort (N = 66,997) matched on sex, age and birth region was retrieved from the general population and an additional cohort with all individuals born in Sub-Saharan Africa registered in the Total Population Register in 1987–2015 (N = 171,756). Incident lymphomas and other cancers were identified through linkage with the Swedish Cancer Register. Hazard ratios (HRs) were assessed using Cox regression with attained age as the timescale.ResultsA total of 20 lymphoid neoplasms and 202 non-haematological cancers were identified among malaria patients during a mean follow-up of 13.3 and 13.7 years, respectively. The overall risk of lymphoid neoplasms was not significantly increased (hazard ratio [HR] 1.24, 95% confidence interval [CI] 0.79–1.94), neither did we find any association with all-site non-haematological cancer (HR 0.89, 95% CI 0.77–1.02). However, in the Sub-Saharan Africa cohort, we observed an increased risk of lymphoid neoplasms after malaria diagnosis (HR 2.39, 95% CI 1.06–5.40), but no difference in the risk of other cancer (HR 1.01, 95% CI 0.70–1.45). The association could not be explained by co-infection with HIV or chronic hepatitis B or C, since the risk estimate was largely unchanged after excluding patients with these comorbidities (HR 2.63, 95% CI 1.08–6.42). The risk became more pronounced when restricting analyses to only including non-Hodgkin and Hodgkin lymphomas (HR 3.49, 95% CI 1.42–8.56).ConclusionIndividuals born in malaria-endemic areas and diagnosed with malaria in Sweden had an increased risk of lymphoid neoplasms, especially B cell lymphoma. There was no association with cancer overall nor did single malaria episodes confer an increased risk in travellers.
Highlights
Malaria is associated with Burkitt lymphoma among children in Sub-Saharan Africa
1271 patients with unnotified malaria were identified through malaria International Classification of Disease (ICD) 9/10 codes from the Inpatients Register (N = 841) or Outpatient Register (N = 430)
The majority were diagnosed with lymphoma at > 50 years of age, and no one was diagnosed < 30 years of age (Table 3). In this nationwide population-based cohort study of patients diagnosed with malaria in Sweden, we observed an over two times increased risk of incident lymphoid neoplasms in patients born in Sub-Saharan Africa, but no increased risk for patients with malaria born in Sweden
Summary
Malaria is associated with Burkitt lymphoma among children in Sub-Saharan Africa. No longitudinal studies have assessed the long-term risk of other lymphoma or cancer overall. The acute complications of malaria are well known, but in addition to direct malaria-related morbidity and mortality, there is increasing evidence that malaria has several long-term effects One such consequence is endemic Burkitt lymphoma, the most common cancer in children in Sub-Saharan Africa [2, 3]. One nested-case control study from the UK used longitudinally collected data from primary care records to assess previous malaria exposure [12], but otherwise, there are to our knowledge no publications with longitudinal design assessing the risk of lymphomas or other cancers in adults with previous malaria Such investigations are difficult to manage in endemic areas where reliable health and recording systems often are lacking and the degree of malaria exposure is complicated to determine due to repeated and asymptomatic infections. We have taken advantage of the unique health and population registries in Sweden to study long-term effects of malaria diagnosed in a mixed population of travellers and migrants
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