Hidden Infections Surface as Malaria Wanes in Namibia’s Zambezi Region

In the floodplains of Namibia’s Zambezi Region, where the Kwando, Linyanti and Chobe rivers converge near the borders of Angola, Zambia, Botswana and Zimbabwe, health workers have long treated fever as a synonym for malaria. A new study suggests that assumption deserves scrutiny. Researchers screening more than a thousand patients who presented for malaria testing in 2017 found molecular fingerprints of two other vector-borne pathogens hiding in the same blood samples: Rift Valley fever virus and spotted fever group Rickettsia, the bacteria behind African tick bite fever. The findings, published in BMC Infectious Diseases, offer some of the first direct evidence that residents of this remote corner of southern Africa are being exposed to zoonotic febrile illnesses that clinicians rarely consider and laboratories rarely test for.

The research team, led by Oscar Madzingira of the University of Namibia’s School of Veterinary Medicine together with collaborators at Charité–Universitätsmedizin Berlin, took advantage of an unusual resource. Between January and December 2017, health facilities across eleven catchment areas in the malaria-endemic Zambezi Region had collected dried blood spot samples from 1,094 individuals undergoing malaria screening. Dried blood spots, in which a few drops of capillary blood are blotted onto filter paper and air-dried, are a practical mainstay of surveillance in settings with limited cold-chain infrastructure. Antibodies remain stable in the dried matrix for months, allowing samples gathered years earlier to be eluted and retested for entirely different pathogens.

That is precisely what the team did. Sera reconstituted from the dried blood spots were run through commercial enzyme-linked immunosorbent assays, or ELISAs, designed to detect immunoglobulin G antibodies against four vector-borne agents: Rift Valley fever virus, Crimean-Congo haemorrhagic fever virus, West Nile virus and spotted fever group Rickettsia. Serology of this kind does not diagnose active infection; instead, it reveals whether a person’s immune system has ever mounted a response to a given pathogen, providing a cumulative record of exposure. In a region where febrile patients are routinely tested only for malaria, such retrospective serology is one of the few windows into the wider landscape of undiagnosed fever.

The results were striking in their asymmetry. Rift Valley fever virus antibodies turned up in 40 of the 1,094 participants, an apparent seroprevalence of 3.66 percent, which statistical correction placed at a true prevalence between 3.56 and 3.66 percent, with a 95 percent confidence interval of 2.51 to 4.98 percent. Spotted fever group Rickettsia antibodies appeared in just two samples, a seroprevalence of 0.18 percent. For the other two viruses the answer was a clean zero: no evidence of exposure to Crimean-Congo haemorrhagic fever virus or West Nile virus anywhere in the cohort. Ten individuals carried antibodies to both Rift Valley fever virus and malaria parasites, a reminder that co-exposure in this ecosystem is not merely theoretical.

Rift Valley fever virus is an RNA virus of the genus Phlebovirus that cycles between mosquitoes and livestock, primarily cattle, sheep and goats. In animals it causes devastating abortion storms and high mortality in young ruminants; in humans, who are infected mainly through contact with infected animal tissues or the bites of infected mosquitoes, it usually produces a self-limiting febrile illness but can progress to severe haemorrhagic disease, encephalitis or ocular lesions with permanent vision loss. The Zambezi Region sits within the Kavango Zambezi Transfrontier Conservation Area, a mosaic of livestock herding, subsistence farming and wildlife corridors where humans, animals and mosquitoes intersect closely. A seroprevalence approaching four percent implies that a meaningful share of the population has encountered the virus at some point, most likely during one of the epizootic waves that periodically sweep southern Africa after heavy rainfall and flooding.

Spotted fever group Rickettsia, by contrast, are obligate intracellular bacteria transmitted by ticks. In southern Africa the best-known member is Rickettsia africae, the agent of African tick bite fever, a flu-like illness frequently acquired by travellers on safari but far less documented in local residents. The very low seroprevalence observed here, two positive samples out of more than a thousand, could reflect genuinely rare exposure, cross-reactivity thresholds in the assay, or the technical limitations of testing antibodies eluted from dried blood spots rather than fresh serum. The authors are careful not to over-interpret the figure; its principal value is as evidence that exposure exists at all in a population where rickettsial disease has essentially never been on the diagnostic radar.

To understand who was getting infected, the team turned to binomial Firth penalized logistic regression, a statistical technique suited to sparse outcomes where conventional logistic regression can produce unstable or infinitely large odds ratio estimates. They examined associations between seropositivity and a battery of demographic, behavioural and clinical variables, including age, sex, occupation, animal contact and reported symptoms. The result was a null finding that is itself informative: no predictor reached statistical significance for either pathogen. Exposure to Rift Valley fever virus and spotted fever group Rickettsia in this population appears broadly distributed rather than concentrated in identifiable high-risk groups, which complicates targeted prevention and suggests that transmission pathways, whether mosquito bites, tick bites, or contact with livestock during birthing and slaughter, touch many parts of the community.

The study’s origins lie in an epidemiological transition that Namibia shares with much of sub-Saharan Africa. Sustained control efforts, including insecticide-treated bed nets, indoor residual spraying and effective artemisinin-based therapy, have driven malaria burden downward in many districts. Yet febrile illness has not disappeared at the same rate. When malaria rapid diagnostic tests come back negative, clinicians are frequently left without an actionable answer, because the alternative causes of fever, from leptospirosis and Q fever to arboviruses and rickettsiae, are rarely included in routine testing algorithms. This diagnostic gap, sometimes called the fever of unknown origin problem of the tropics, means that the true contribution of zoonotic vector-borne pathogens to the residual fever burden remains largely invisible to health systems.

The Zambezi Region is an especially sensitive sentinel for this hidden burden. Its position at the heart of the Kavango Zambezi Transfrontier Conservation Area places it at the junction of intense wildlife movement, cross-border human traffic and livestock production, all of which shape pathogen circulation. Climate variability adds another layer of risk: the floods that replenish the region’s floodplain agriculture also create the breeding habitat that drives mosquito population explosions, the same conditions historically associated with Rift Valley fever epizootics. Surveillance that watches only for malaria in such a setting is, in effect, monitoring one instrument in an orchestra of pathogens.

The authors’ prescription is a One Health surveillance framework that integrates human, animal, vector and environmental monitoring, so that signals of viral or rickettsial activity in livestock herds or mosquito populations can trigger earlier human health responses. They also call for strengthening laboratory diagnostic capacity so that febrile patients who test negative for malaria are not simply sent home with an unexplained illness. Neither intervention is trivial in a region with long distances, limited laboratory infrastructure and competing health priorities. But the study demonstrates that the pathogens are already there, circulating quietly among people who came to clinics for a malaria test and left with no idea they carried antibodies to a virus capable of blinding them or a bacterium their doctors had never been trained to suspect. Making the invisible visible, the study argues, is the first step toward preventing the next outbreak before it announces itself.

Subject of Research: Seroprevalence of Rift Valley fever virus and spotted fever group Rickettsia among febrile patients in the Zambezi Region of Namibia

Article Title: Evidence of exposure to Rift Valley fever virus and spotted fever group Rickettsia among patients presented for malaria screening in the Zambezi region, Namibia (2017)

Article References: Madzingira, O., Lucas, L. T., Charamba, V., Hoebes, E., Matomola, O. C., Eloff, L., Munzel, H., Mumbengegwi, D. R., Chitanga, S., & Junglen, S. (2026). Evidence of exposure to Rift Valley fever virus and spotted fever group Rickettsia among patients presented for malaria screening in the Zambezi region, Namibia (2017). BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14513-x

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14513-x

Keywords: Rift Valley fever virus, spotted fever group Rickettsia, seroprevalence, Zambezi Region, Namibia, malaria, zoonosis, One Health, vector-borne disease, ELISA, dried blood spots, BMC Infectious Diseases