General characteristics of patients
All the patients were Chinese nationalities, they all infected malaria out of China. All of them were exported labor services for Africa or two Asian countries(Myanmar and Pakistan). All of the were male, with the median age of 42 years(range from 19 to 62 ) old. All of them have a healthy background, since they had passed body examinations for being a exported labour before going abroad(Table 1).
Clinical signs distributions
Fever is the major manifestation of malaria, 99%(149/150) cases had reported fever with difference length of durations(Median=3 days, range from 1 to 30 days). 83% cases had reported shiver while abnormal body temperatures were presenting. 46% (69/150)cases suffered headache, which was the third most common manifestation of malaria cases. 19%(28/150) cases had reported cough, 54%(15/28) of them were productive cough. Other clinical signs including fatigue (44%, 66/150), anorexia(17%, 26/150), and muscular soreness(15%, 22/150).
Medical history distributions of the patients
In the Hospital Information System(HIS), we recorded the detail of the onset and medical history, and history of current illness. Half of them(50%, 75/150) had been infected by plasmodium for more than once, 68% cases were infected by plasmodium for more than twice.
Of note, 17%(25/150) cases had reported misdiagnosed by other medical facilities, since the malaria lack of specific clinical signs, many doctors in non-history-endemic area had no experience for diagnosis.
To investigate if there was any delay for diagnosis for any reason, we recorded the days from onset of fever before came to our hospital(DOF). The DOFs were range from 0.2-30 days(DOFs may include the days before custom entry) with the median of 3 days.
Geographical and pathogens distributions
Excepted one case came back from Myanmar diagnosed with P. vivax infection, three cases came back from Pakistan infected by P. vivax, other cases were from Africa. Most of the cases were infected or co-infected by P. falciparum, the proportions were 74%(111/150) and %4(6/150) respectively. The second most common infection were caused by P. vivax . The infection and co-infection proportion were 16%(24/150) and 3%(4/150) respectively.
Geographically, most of imported cases were from Democratic Republic of the Congo, the proportion is 23%(34/150), 74%(26/34) cases were infected by P. falciparum. The second most cases were from Equatorial Guinea, the proportion was 14%(21/150), 81%(17/21) of them were infected by P. falciparum(Table 2,3). A Sankey diagram was used for describe the relationship between source of countries and pathogens(Figure 1).
Time distribution of cases
We overlapped the variations of cases for the four years in to one chart. We can figured out no significant peaks were found. The decreasing of 2020 were due to the due to the polices of quarantine for Covid-19.
To understand if the samples from our hospital has the seasonality. We used Edwards Test for seasonality11. The χ2 =2.51 p-value= 0.28. This result rejected the significant seasonality of the cases admission time distribution from the point of statistical view (Figure 2).
Laboratory tests of the patients
According to our regulations, all the patients of malaria were undergone emergency medical evaluations regardless the clinical condition and potential prognosis. The assessment included blood routine, blood biochemical tests, plasmodium and RDT13, X-ray or CT scan for lung, and in most cases PCT and CRP examinations.
For the blood routine tests, the decreased PLT counts were observed in most cases, the median of PLT was 84*109/L(range from 10-624 *109/L). Only 3%(5/150) cases recorded higher WBC counts than 10*109/L(median=5.43*109/L, 1.58-17.15 *109/L). However, 22%(33/150) cases were recorded lower WBC than 4*109/L.
Mild liver injured were common for malaria patients. 13%(20/150) cases had the ALT higher than 2*ULN(Upper limits of normal value, 37U/L). The values of ALT were range from 38 U/L with median of 9-199 U/L. Hypoproteinemia were found in 31%(46/150) cases.
The bacterial infections was the major complication of the malaria patients. 20%(30/150) cases were diagnosed with bacterial infections. 97%(29/30) infections were bacterial pneumonia(one case diagnosed with urinary tract infection). The diagnosis were established by CT scans or X-rays, manifestations, and other necessary examination.
The pathogen examination from blood found 5%(8/150) cases had higher infection rate for more than 5%.
Survival analysis for prolonged hospital stays
The median length of stay(LOS) was 7 days, the range from 3-23 days. We used potential related factors to fit into a cox proportional hazard model to investigate the relevant factors and Hazard Ratios(HRs). The results were listed in Table 1. We defined the failure event as the discharge following advices(no patient discharge against advices), so that the HR value was the risk for discharge, that was, a risk factor for prolonged LOS if HR <1.
In this study, pathogen type(dummy variables), bacterial infection, abnormal liver function, thrombocytopenia(<100*109/L), leukocytopenia(<4.0 *109/L), anemia(<120g/L), jaundice(TBIL>20μmol/L), high infection rate(>5%), long DOF(>5 days), misdiagnosis, hypoproteinemia(ALB<35g/L), PCT, and CRP were included in the full model of cox proportional hazard model.
By using stepwise variables selections, bacterial infection and low thrombocytopenia were found to be statistically significant in model. The hazard ratio were 0.58(p-value=0.01, 95%CI=0.38-0.88) and 0.66(p-value=0.02, 95%CI=0.47-0.94) respectively. The results were listed in Table 4. The survival functions were plotted in Figure 3 and Figure 4.
Of note, according to our analysis, being infected by P. falciparum solely was the risk factor of discharge(HR=4.93, 95% CI=1.74-14.00), that was, being infected by P. falciparum solely was the protective factor for prolonged hospital stays. This because of the differences of treatment scheme for pathogens. This was not the major topic of this paper, however, this factor remained in equation to balance the effects of different pathogens.
The results of log-rank test for survivor functions for bacterial infection and hypoproteinemia were statically significant, the χ2 values were 8.0(p-value=0.00) and 8.16(p-value=0.00) respectively.(Figure 3,4).
Treatments and outcomes
The imported cases of malaria had very low mortality which was reported as 0.5%(90/16733)1. In our study, all the patients were fulfilled the discharge criteria, no patient was dead. All the treatments were complied with national recommendation for malaria treatments(WS/T 485-2016)14.