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We Found A Correlation Between Thrombocytopenia

Our main finding was that early diagnosis of the Hantavirus infection nephropathia epidemica significantly reduced inappropriate antibiotic use and hospitalization. The majority of the patients first saw their family doctor, indicating that general practitioners are indeed frontline doctors in outbreaks.

This study’s major strength is the large number of included cases. Most diagnosed patients were aged 41 years or older and there was an overall male predominance. Seroprevalence studies have shown equal distribution of antibodies for Puumala virus between sexes [16]. With our retrospective design, we cannot explain these differences. Another design bias is the varying quality of documentation that could misinterpret the frequency of symptoms. Furthermore, laboratory analyses were performed in a heterogenic manner and at different stages of infection, which may have contributed to an underestimation of the frequency of abnormal values.

Our study is, to the best of our knowledge, the first to examine Hantavirus infections in general practice. According to studies conducted in secondary care, oligo- and polyuria (82% vs. 97%) along with fever and fatigue are considered to be the main findings of NE [17]. The general practitioners in our study captured diverse clinical pictures, with lower frequencies of oligo- and polyuria (21% vs. 31%). This could be explained by possibly milder cases in general practice, early examinations with non-fulminant symptomatology, or may simply be a bias from the retrospective study design. Hospitalization was needed for 38% of patients and was significantly lowered when patients were diagnosed correctly at the first visit, reinforcing the value of sharpened diagnostic tools and guidelines.

We found a correlation between thrombocytopenia, high levels of creatinine, and hospitalization, which is probably explained by more clinically affected patients in the hospitalized group. Compared with other Hantavirus infections, NE has a low mortality, but most patients have acute renal impairment. A correct diagnosis is essential when considering reducing or pausing anticoagulants and kidney-dependent drugs, i.e., Metformin, Allopurinol, lithium carbonate, antipsychotics, and non-steroidal anti-inflammatory drugs. The use of antibiotics was significantly lowered when patients were diagnosed correctly at the first visit. Overuse of antibiotics and emergence of resistance have been recognized to be increasing problems [18-21]. A Cochrane review evaluated studies of various interventions to improve antibiotic prescribing [22]. Case definitions, decision aids, and rapid tests can help GPs make a correct diagnosis and consequently reduce prescription of unnecessary antibiotics [23-25]. There was a significantly higher frequency of hospitalization in the beginning of the NE outbreak. It is not likely to be the case that the infection was less aggressive over time; the declining hospitalization rates might be explained by raised consciousness during the ongoing epidemic.

According to our findings, a decision aid for NE is proposed (Figure 4) that includes screening for haematuria, proteinuria, and thrombocytopenia in patients with suspected HFRS. Elevated levels of creatinine can also be a clue to the diagnosis, but are seen later. We encourage doctors to apply these simple tests on patients with diffuse illness in endemic areas. To secure the diagnosis, serology testing is needed, but may be costly and the results can take several days. The point-of-care test (POC) for Hantavirus infection is currently used only in secondary care. Increased clinical recognition of suspected Hantavirus cases and the use of POC could improve the diagnostic accuracy in general practice and consequently lower the use of antibiotics and cut costs for other investigations and hospitalization.

Early diagnosis of Hantavirus infection by family doctors can reduce inappropriate antibiotic use and hospitalization

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Figure 4. Proposed decision aid for early diagnosis of nephropathia epidemica (NE). *Point-of-care test or serological testing at clinical microbiological laboratory.

We have proposed simple diagnostic tools to confirm the diagnosis in subtle cases. Most NE patients have different levels of renal impairment, but creatinine levels usually return to subnormal or normal levels. However, there is growing evidence of long-term effects after Hantavirus infections including hypertension and proteinuria [26-28], indicating that follow-ups could be valuable and that further research is desirable.

This study indicates that, in endemic areas, Hantavirus infections are important in general practice. General practitioners are the first care providers who can discover outbreaks of infections. It is important to detect new or emerging infections and syndromic surveillance has been suggested [29]. Increased awareness among general practitioners and a reporting system from family medicine offices could improve public health.