Malaria is not the cause of every fever

Meeting of German and African partners in Mbeya, Tansania.

Malaria remains one of the most dangerous infectious diseases worldwide. People in Africa are particularly affected, where at least half a million people died in 2015 alone—almost 90% were children under the age of five. However, not every child that is admitted to hospital with fever suffers from malaria. More precise diagnostics are urgently needed in order to identify other infections. A study conducted by the German Centre for Infection Research has investigated the different causes of high fever in four different African regions since 2014. The study shows that malaria rarely comes alone. At a workshop in Mbeya, Tanzania, the scientists portray a new picture of malaria.

“A major problem in Africa is that diagnostics are often insufficient for targeted treatment,” explains Professor Jürgen May from the Bernhard Nocht Institute for Tropical Medicine (BNITM) in Hamburg.

Since 2012, he has been coordinating the DZIF African Partner Institutions—an infrastructure that was established for the purpose of collaborating with African scientists. A first major project that the scientists jointly initiated is to help precisely with this issue: "We wanted to improve diagnostics on the ground and learn more about the prevalence of malaria,” May explains, describing the ambitious mission being conducted across all four African partner sites. "Frequently, children admitted to hospital with high fever are initially treated for malaria,” he reports. In the study "Fever of unknown origin" the scientists discovered that this is a mistake, because bacterial and viral infections can sometimes cause fever as well; as co-infections, they often make life difficult for the young patients.

Searching for the main cause

“In Ghana, we included 1,200 children under the age of five in the study; they were admitted with high fever to a hospital in the Ashanti region over a period of one year,” reports Benedikt Hogan from the BNITM.

The scientist has been working in tropical disease medicine for several years, and travels from Hamburg to Kumasi several times a year. Besides malaria microscopy, which is currently still standard in Africa, broader diagnostics are also being conducted on the children’s samples—some directly on the ground and other analyses later in Hamburg or at other DZIF collaboration partner sites. The assessments have not been completely finalised as yet, but the researchers already know now: here in Ghana, malaria is still a major cause of high fever. However, additional infections with bacterial pathogens like Salmonella, which usually only cause gastrointestinal infections in our geographical region, and viral pathogens can also occur. This had not been known previously and highlights the importance of more precise diagnostics for more targeted treatment.

In Mbeya, Tanzania, the analyses also showed that malaria is still the main cause of febrile diseases, and accounts for 40 percent of the cases. Furthermore, the broader diagnostics also made visible viruses that were not suspected to exist in the region.

“For the first time in this region, we have detected the virus that causes Rift Valley fever. Additionally, the dreaded Chikungunya virus was also identified,” says Dr Norbert Heinrich from the LMU Munich. The scientist has been working in Munich and Mbeya for nine years.

Besides malaria, the main themes of this collaboration are tuberculosis and HIV. “Our goal in this study is also to restrict treatment with antibiotics,” explains Heinrich. In most cases today, malaria is treated with a combination of antimalarials and antibiotics, even if there are no bacteria present. The scientist is certain that the problem of antibiotic resistance caused by wrong antibiotic use will also become a problem Africa. The scientists are already devising new projects to work on this problem more intensively as well.

The fight against malaria continues

In Burkina Faso the fever study is still ongoing and in Lambaréné, Gabon, final assessments are being conducted. Besides the study results and improvements made on the ground, the project has led to the four partner institutions growing together across all national borders. “Now that we know the spectrum of pathogens involved in febrile disease, our next step will be to develop rapid tests so as to enable more specific treatment of the children and to identify any resistant pathogens involved,” says May.

The enormous clinical sample collection that the scientists have generated over the past years opens up various opportunities for future research. One important project has already been initiated: with the help of the samples and epidemiological data, the scientists intend to develop a simple and quick diagnostic test that is able to differentiate between malaria and bacteraemia, i.e. bacteria in the blood. Such a method can be life-saving in many cases.

"I look forward to longstanding collaborations with the DZIF,” emphasizes Prof Nyanda Elias Ntinginya, Director of the National Institute for Medical Research - Mbeya Medical Research Centre. There is still a lot to be done—be it for malaria, tuberculosis or HIV.

However, besides diagnostics and treatment, the quest for a vaccine also constitutes a major goal for the malaria researchers. Scientists have been researching this for over 100 years; to no avail up to now. Vaccines that had been developed from individual molecules derived from the malaria pathogen have not provided sufficient protection. In 2014, at the German Center for Infection Research, scientists from Tübingen initiated a study with a new live vaccine. 67 healthy adult volunteers who had never had malaria participated in the study. The results of this study have recently been published in Nature.

New laboratory inaugurated

A new laboratory for intensified tuberculosis research was set up in Mbeya. Having fun at the “official” opening are (from the left): Prof Jürgen May, Dr Timo Jäger, Dr Norbert Heinrich, Dr Nyanda Elias Ntinginya and Dr Angelika Luguru.