Frequent malaria infections could cause cancer in children

A study of Burkitt lymphoma by investigators at St Mary’s Hospital Lacor in Gulu District, together with investigators at the National Cancer Institute in the United States (US) and from universities in Kenya, Uganda and Tanzania has revealed that repeated exposure to Plasmodium falciparum, the parasite that causes malaria, could lead to the development of Endemic Burkitt Lymphoma (eBL), especially in children aged five to 11 years.

The research reveals an association between cumulative malaria infections and endemic Burkitt lymphoma (eBL) in the sub-Saharan African countries of Uganda, Tanzania and Kenya. 

Burkitt’s lymphoma is the most common form of paediatric cancer in the region where malaria is endemic.

The study, which was conducted between 2010 and 2016 in children under 15, using a case-control design (where children with the disease are compared to those without), found a strong positive relationship between the cumulative number of P falciparum infections acquired and the risk of developing eBL.

Dr Martin Ogwang, a director At Lacor Hospital, says the hospital has treated between 200 and 300 cases of eBL annually since 2008 and was able to participate in this study because it has the required infrastructure and volume of patients. 

“St Mary’s Hospital Lacor has the necessary facilities and human resources to carry out high impact research and contribute to the wealth of knowledge in the various diseases its patients present with,” Dr Ogwang says.

The study

Researchers analysed data of about 600 children with Burkitt lymphoma from 49 districts in East Africa and P. falciparum infection risk in healthy regions in the area, grouped by age, region and calendar year between 2000 and 2016. The study regions in Northwest and Northcentral Uganda, Western and Nyanza provinces in Kenya as well as Mara, Mwanza and Geita regions in Tanzania, experience the highest malaria infection rates and Burkitt lymphoma occurrences.

In a research paper published in the US Proceedings of the National Academy of Sciences (PNAS), the research revealed that the risk of Burkitt lymphoma increased by 39 percent for each additional 100 P. falciparum infections.  

“Because we wanted to measure malaria exposure over the life course, we had to first create a new measurement to assess cumulative malaria exposure, including asymptomatic infections,” said Kelly Broen, a PhD student in the Department of Epidemiology at Michigan Public Health and lead author of the study.

“Using this cumulative metric, we found that for every 100 estimated P. falciparum malaria infections, the risk of eBL increases by 39 percent. Although 100 P. falciparum malaria infections may seem like an absurdly high number, the number of cumulative infections among 10-year-olds ranged from four to 315,” she adds.

Dr Sam Mbulaiteye, a researcher from the National Cancer Institute, US, says for every 100 additional infections, the risk for Burkitt lymphoma increases by 39 percent.

“This, therefore, means that efforts to decrease the number of infections will likely reduce the risk of Burkitt’s lymphoma,” he says.

Silent malaria

The study also notes that children who develop the cancer are likely to have suffered from silent malaria for many years. 

Dr Jimmy Opigo, a general physician, says individuals and children who have repeated malaria infections over time eventually achieve increased immune control with a resultant decrease in acute symptoms. Without clinical illness, these infections are silent and remain untreated, resulting in chronic carriage that can last longer.

“Silent malaria infections, therefore, refer to the presence of parasites in the person’s blood without showing any symptoms,” says Dr Opigo.

The study, however, emphasises that the risk to eBL is not related to acute malaria but to chronic malaria after several repeated infections.

What is Burkitt Lymphoma?

Burkitt Lymphoma is the most common childhood cancer in the equatorial regions of sub-Saharan Africa where P. falciparum malaria is endemic. It contributes up to 50 to 75 percent of all childhood cancers, according to the study. 

Burkitt’s lymphoma, the commonest type of cancer among children in Uganda, according to Dr Fadhil Geriga, a paediatric oncologist, is a fast-growing tumour associated with impaired immunity and can be fatal if not treated. “It manifests as a swelling in the jaw,” he says, adding, “Most times, it begins in the form of a simple toothache that leads to a persistent swelling.”

Many times, children are brought to hospital when the cancer is advanced and has spread to other parts of the body which is likely to reduce the outcome of treatment. However, if diagnosed early enough, the cancer is curable, Dr Geriga says.

“Burkitt’s Lymphoma is the first ever known cancer to be cured by chemotherapy but only if detected early. However, other interventions such as surgery and radiotherapy may be used, depending on the stage of the cancer,” says Dr Geriga.

Prevention and management 

The research suggests that in areas with high malaria transmission rates, anti-malaria campaigns may have the additional benefit of reducing eBL risk as well. 

“Community advocates for malaria programmes should include Burkitt ’s lymphoma as a target condition which justifies the application of malaria suppression methods such as indoor residual spraying or the use of insecticide treated bed nets,” says Dr Sam Mbulaiteye.

“So, you can reduce the acute risks of malaria as well as the chronic risks of malaria in this case, Burkitt’s Lymphoma,” he adds.

There are inexpensive measures of preventing malaria infections and these include sleeping under a treated mosquito net. The Ministry of Health early this year gave out long-lasting mosquito nets as a strategy to reduce malaria incidents in the country according to Dr Opigo.

Dr Opigo says the ministry will continue with the traditional methods of preventing malaria in the country with the “under the net '' campaign, insecticide spraying and larviciting (spraying on water sources that are potential breeding places for mosquitoes) and will procure chemicals to be used for indoor residual spraying and “this time, the chemical will be made specifically for use indoors and cannot be used in the gardens.”

In the community

Uganda has the integrated community case management strategy where the ministry uses existing structures such as community health workers (village health teams) that routinely check on the recently discharged patients to monitor any co-morbidity that may appear after the treatment.

Uganda also adopted the WHO guidelines for Intermittent preventive treatment in pregnancy (IPTp), which includes a treatment dose of sulfadoxine- pyrimethamine (SP) for HIV negative women at each scheduled antenatal care visit starting at 13 weeks with a minimum of four weeks between the doses  and the recommended minimum of three doses. This control strategy is aimed at reducing the burden of malaria in certain high-risk groups such as pregnant women and children.

With such a big burden of malaria disease, according to the MoH, the government had planned to introduce a vaccine that would help bring the malaria burden down by the end of last year. However, the vaccine is not yet ready. 

Dr Opigo says the malaria vaccine offers about 50 percent personal protection and works in combination with other control mechanisms.

In October 2022, Uganda launched the Seasonal Malaria Chemoprevention (SMC) across five districts in Karamoja region. 

“This highly effective community based intervention to prevent malaria in the most vulnerable regions involves administering monthly courses of anti-malarial medicines to children aged three to 59 months during peak malaria transmissions. Children who once suffered from malaria are usually followed up with a prophylaxis and are said to be doing well,” Opigo says.