Cold Agglutinin Disease Prevalence and Immunoglobulin M levels in Patients with Splenomegaly from Endemic Areas for Malaria in Rwanda

Background: Inhabitants from malaria endemic zones often present with enlarged spleen, mainly due to hyper reactive malarial splenomegaly (HMS), and it is seen more commonly associated with elevated levels of Immunoglobulin M (IgM). Cold agglutinin disease is an acquired autoimmune hemolytic anemia (AIHA) that is usually due to cold-reacting IgM autoantibodies directed against red cell antigens. The study was conducted in response to the observed high frequency of transfusion dependent anemia in patients with splenomegaly from malaria endemic zones in southern province of Rwanda. The objectives of this study were to determine the prevalence of cold agglutinin disease and to assess the distribution of IgM antibodies among these patients. Methodology: This was a descriptive, cross-sectional study conducted over a period of six months from June 2016 to December 2016. The study enrolled adult population from malaria endemic areas of the southern province of Rwanda with unexplained splenomegaly. Blood samples for testing IgM levels, cold agglutinin, FBC, and markers of hemolysis were collected from peripheral health settings and analyzed at the laboratory of Butare University Teaching Hospital. Results: During the study period, we enrolled 188 participants with enlarged spleen. One hundred twenty-five (66%) were females and 34% were males. The mean (±SD) age of the study participants was 35.6 ± 15.2 years. Out of 188 participants, only 4.8% were found with significantly positive Cold Agglutinin Titer (CAT) (≥1:64) and 84% of participants were found to have elevated serum IgM level. Hemoglobin level, white blood count and platelets count decrease with severity of splenomegaly, while IgM level increases with spleen size. Conclusion: Among patients with splenomegaly from malaria endemic areas, IgM levels correlate with the stages of splenomegaly while cold agglutinin disease plays a small role in the etiology of anemia.

Imported malaria cases in former endemic and non-malaria endemic areas in China:are there differences in case profile and time to response?

Background:China has achieved zero indigenous malaria case report in 2017.However,along with the increasing of international cooperation development,there is an increasing number of imported malaria cases from Chinese nationals returning from malaria-affeaed countries.Previous studies have focused on malaria endemic areas in China.There is thus limited information on non-endemic areas in China,especially on the performance of malaria surveillance and response in health facilities.Methods:A comparative retrospective study was carried out based on routine malaria surveillance data collected from 2013 to 2017.All imported malaria cases reported within the mainland of China were included.Variables used in the comparative analysis between cases in former endemic and former non-endemic areas,included age,gender and occupation,destination of overseas travel,Plasmodium species and patient health outcome.Monthly aggregated data was used to compare seasonal and spatial characteristics.Geographical distribution and spatial-temporal aggregation analyses were conducted.Time to diagnosis and report,method of diagnosis,and level of reporting/diagnosing health facilities were used to assess performance of health facilities.Results:A total of 16733 malaria cases,out of which 90 were fatal,were recorded in 31 provinces.The majority of cases(96.2%)were reported from former malaria endemic areas while 3.8%were reported from former non-malaria endemic areas.Patients in the age class from 19 to 59 years and males made the highest proportion of cases in both areas.There were significant differences between occupational categories in the two areas(P c 0.001).In former endemic areas,the largest proportion of cases was among outdoor workers(80%).Two peaks(June,January)and three peaks(June,September and January)were found in former endemic and former non-endemic areas,respeaively.Time between the onset of symptoms and diagnosis at clinics was significantly different between the two areas at different level of health facilities(P<0.05).Conclusions:All the former non-endemic areas are now reporting imported malaria cases.However,the largest proportion of imported cases is still reported from former endemic areas.Health facilities in former endemic areas outperformed those in former non-endemic areas.Information,treatment,and surveillance must be provided for expatriates while capacity building and continuous training must be implemented at health facilities in China.

Predictors of malaria rapid diagnostic test positivity in a high burden area of Paletwa Township, Chin State in Western Myanmar

Background:Despite major reductions in malaria burden across Myanmar,clusters of the disease continue to persist in specific subregions.This study aimed to assess the predictors of test positivity among people living in Paletwa Township of Chin State,an area of persistently high malaria burden.Methods:Four villages with the highest malaria incidence from Paletwa Town ship were purposively selected.The characteristics of 1045 subjects seeking malaria diagnosis from the four assigned village health volunteers from January to December,2018 were retrospectively analyzed.Their household conditions and surroundings were also recorded using a checklist.Descriptive statistics and logistic regression models were applied to investigate potential associations between individual and household characteristics and malaria diagnosis.Results:In 2017,the Paletwa township presented 20.9%positivity and an annual parasite index of 46.9 cases per 1000 people.Plasmodium falciparum was the predominant species and accounted for more than 80.0%of all infections.Among 1045 people presenting at a clinic with malaria symptoms,31.1% were diagnosed with malaria.Predictors for test positivity included living in a hut[adjusted odds ratios(aOR):2.3,95%confidence intervals(CI ):1.2-4.6],owning farm animals(aOR:1.7,95% CI:1.1-3.6),using non-septic type of toilets(aOR:1.9,95%CI:1.1-8.4),presenting with fever(aOR:1.9,95%CI:1.1-3.0),having a malaria episode within the last year(aOR:2.9,95%CI:1.45.8),traveling outside the village in the previous 14 days (aOR:4.5,95%CI:1.5-13.4),and not using bed nets(aOR:3.4,95%CI:2.3-5.1).There were no statistically significant differences by age or gender in this present analysis.Conclusions:The results from this study,including a high proportion of P.falciparum infections,little difference in age,sex,or occupation,suggest that malaria is a major burden for these study villages.Targeted health education campaigns should be introduced to strengthen synchronous diagnosis-seeking behaviors,tighten treatment adheren ce,receiving a diagnosis after traveling to endemic regi ons,and using bed nets properly.We suggest in creased surveillance,early diagnosis,and treatment efforts to control the disease and then to consider the local elimination.

Epstein-Barr virus-encoded RNAs as a survival predictor in nasopharyngeal carcinoma

Background Epstein-Barr virus （EBV） infection is one of the most important factors of nasopharyngeal carcinoma （NPC）endemic areas.Transcription of EBV-encoded non-polyadenylated RNAs （EBERs） are presented in most of NPC tumors.Exploring EBERs as a prognostic marker for NPC might further be informative about the biology and the progression of the disease.The aim of this study was to analyze the role of EBV latency in the clinical management of nasopharyngeal carcinoma （NPC）,by detecting EBERs.Methods RNA in situ hybridization （ISH） for detecting EBERs was carried out on 908 NPC tumor tissues.Overall survival （OS） curves were analyzed with the Kaplan-Meier method and the Cox proportional-hazards regression models.Results The median follow-up time was 70 months （1-120 months）.Eight hundred and sixteen （89.9％） from a total of 908 consecutive NPC cases were found to be EBV-EBER positive.EBER-ISH staining revealed nuclear localization in NPC cells.In the Kaplan-Meier analysis for OS,high EBER expression levels in NPC patients were statistically significant positive prognostic factors for survival （log-rank,P=0.022）,especially in adults aged 17-40 years （P=0.023） and in those with advanced stage disease （log-rank,P=0.002）.Cox proportional-hazards regression model analysis showed that the EBER expression level was an independent risk factor for OS （hazard ratio 0.724,P=0.005）.Conclusions EBERs were frequently detected in NPC tumor tissues,and high-level EBER expression correlated with good prognosis in NPC patients,especially in adult patients and in those with advanced stage disease.EBER may serve as a potential prognostic predictor in NPC.

Molecular evidence on the presence of Schistosoma japonicum infection in snails along the Yangtze River, 2015–2019

Background: Due to sustained control activities,the prevalence of Schistosoma japonicum infection in humans,livestock and snails has decreased significantly in P.R.China,and the target has shifted from control to elimination according to the Outline of Healthy China 2030 Plan.Applying highly sensitive methods to explore the presence of S.japonicum infection in its intermediate host will benefit to assess the endemicity or verify the transmission interruption of schistosomiasis accurately.The aim of this study was to access the presence of S.japonicum infection by a loop-mediated isothermal amplification(LAMP)method through a 5-year longitudinal study in five lake provinces along the Yangtze River.Methods: Based on previous epidemiological data,about 260 villages with potential transmission risk of schistosomiasis were selected from endemic counties in five lake provinces along the Yangtze River annually from 2015 to 2019.Snail surveys were conducted in selected villages by systematic sampling method and/or environmental sampling method each year.All live snails collected from field were detected by microscopic dissection method,and then about one third of them were detected by LAMP method to assess the presence of S.japonicum infection with a single blind manner.The infection rate and nucleic acid positive rate of schistosomes in snails,as well as the indicators reflecting the snails’distribution were calculated and analyzed.Fisher's exact test was used to examine any change of positive rate of schistosomes in snails over time.Results: The 5-year survey covered 94,241 ha of environment with 33,897 ha of snail habitats detected accumulatively.Totally 145.3 ha new snail habitats and 524.4 ha re-emergent snail habitats were found during 2015–2019.The percentage of frames with snails decreased from 5.93%[45,152/761,492,95%confidence intervals(CI):5.88–5.98%]in 2015 to 5.25%(30,947/589,583,95%CI:5.19–5.31%)in 2019,while the mean density of living snails fluctuated but presented a downward trend generally from 0.20 snails/frame(155,622/761,492,95%CI:0.17–0.37)in 2015 to 0.13 snails/frame(76,144/589,583,95%CI:0.11–0.39)in 2019.A total of 555,393 live snails were collected,none of them was positive by dissection method.Totally 17 pooling snail samples were determined as positives by LAMP method among 8716 pooling samples with 174,822 of living snails,distributed in 12 villages of Hubei,Hunan,Jiangxi and Anhui provinces.The annual average positive rate was 0.41%(95%CI:0.13–0.69%)in 2015,0%in 2016,0.36%(95%CI:0.09–0.63%)in 2017,0.05%(95%CI:0–0.16%)in 2018,0.05%(95%CI:0–0.15%)in 2019,respectively,presenting a downward trend from 2015 to 2019 with statistical significance(χ^(2)=11.64,P<0.05).Conclusions: The results suggest that S.japonicum infection still persisted in nature along the Yangtze River and traditional techniques might underestimate the prevalence of schistosomiasis in its intermediate hosts.Exploring and integrating molecular techniques into national surveillance programme could improve the sensitivity of surveillance system and provide guidance on taking actions against schistosomiasis.