Dengue and Chikungunya Fever among Viral Diseases in Outpatient Febrile Children in Kilosa District Hospital,Tanzania

Introduction

Viral etiologies of fever, including dengue, Chikungunya, influenza, rota and adeno viruses, cause major disease burden in tropical and subtropical countries. The lack of diagnostic facilities in developing countries leads to failure to estimate the true burden of such illnesses, and generally the diseases are underreported. These diseases may have similar symptoms with other causes of acute febrile illnesses including malaria and hence clinical diagnosis without laboratory tests can be difficult. This study aimed to identify viral etiologies as a cause of fever in children and their co-infections with malaria.

Methods

A cross sectional study was conducted for 6 months at Kilosa district hospital, Tanzania. The participants were febrile children aged 2–13 years presented at the outpatient department. Diagnostic tests such as IgM and IgG ELISA, and PCR were used.

Results

A total of 364 patients were enrolled, of these 83(22.8%) had malaria parasites, 76 (20.9%) had presumptive acute dengue infection and among those, 29(38.2%) were confirmed cases. Dengue was more likely to occur in children ≥ 5 years than in <5 years (OR 2.28, 95% CI: 1.35–3.86). Presumptive acute Chikungunya infection was identified in 17(4.7%) of patients. We observed no presenting symptoms that distinguished patients with Chikungunya infection from those with dengue infection or malaria. Co-infections between malaria and Chikungunya, malaria and dengue fever as well as Chikungunya and dengue were detected. Most patients with Chikungunya and dengue infections were treated with antibacterials. Furthermore, our results revealed that 5(5.2%) of patients had influenza virus while 5(12.8%) had rotavirus and 2(5.1%) had adenovirus.

Conclusion

Our results suggest that even though viral diseases are a major public health concern, they are not given due recognition as a cause of fever in febrile patients. Emphasis on laboratory diagnostic tests for proper diagnosis and management of febrile patients is recommended.     

Etiology of Severe Non-malaria Febrile Illness in Northern Tanzania: A Prospective Cohort Study

Introduction

The syndrome of fever is a commonly presenting complaint among persons seeking healthcare in low-resource areas, yet the public health community has not approached fever in a comprehensive manner. In many areas, malaria is over-diagnosed, and patients without malaria have poor outcomes.

Methods and Findings

We prospectively studied a cohort of 870 pediatric and adult febrile admissions to two hospitals in northern Tanzania over the period of one year using conventional standard diagnostic tests to establish fever etiology. Malaria was the clinical diagnosis for 528 (60.7%), but was the actual cause of fever in only 14 (1.6%). By contrast, bacterial, mycobacterial, and fungal bloodstream infections accounted for 85 (9.8%), 14 (1.6%), and 25 (2.9%) febrile admissions, respectively. Acute bacterial zoonoses were identified among 118 (26.2%) of febrile admissions; 16 (13.6%) had brucellosis, 40 (33.9%) leptospirosis, 24 (20.3%) had Q fever, 36 (30.5%) had spotted fever group rickettsioses, and 2 (1.8%) had typhus group rickettsioses. In addition, 55 (7.9%) participants had a confirmed acute arbovirus infection, all due to chikungunya. No patient had a bacterial zoonosis or an arbovirus infection included in the admission differential diagnosis.

Conclusions

Malaria was uncommon and over-diagnosed, whereas invasive infections were underappreciated. Bacterial zoonoses and arbovirus infections were highly prevalent yet overlooked. An integrated approach to the syndrome of fever in resource-limited areas is needed to improve patient outcomes and to rationally target disease control efforts.     

Prevalence of Bacterial Febrile Illnesses in Children in Kilosa District,Tanzania

Introduction

Bacterial etiologies of non-malaria febrile illnesses have significantly become important due to high mortality and morbidity, particularly in children. Despite their importance, there are few reports on the epidemiology of these diseases in Tanzania, and the true burden of such illnesses remains unknown. This study aimed to identify the prevalence of leptospirosis, brucellosis, typhoid fever and urinary tract infections and their rate of co-infections with malaria.

Methods

A cross-sectional study was conducted at Kilosa district hospital in Tanzania for 6 months. Febrile children aged from 2–13 years were recruited from the outpatient department. Patients were screened by serological tests such as IgM and IgG ELISA, and microscopic agglutination test.

Results

A total of 370 patients were enrolled; of these 85 (23.0%) had malaria parasites, 43 (11.6%) had presumptive acute leptospirosis and 26/200 (13%) had confirmed leptospirosis. Presumptive acute brucellosis due to B. abortus was identified among 26 (7.0%) of patients while B. melitensis was detected in 57 (15.4%) of the enrolled patients. Presumptive typhoid fever due to S. Typhi was identified in thirty eight (10.3%) of the participants and 69 (18.6%) had urinary tract infections. Patients presented with similar symptoms; therefore, the identification of these diseases could not be done based on clinical ground alone. Co-infections between malaria and bacterial febrile illnesses were observed in 146 patients (39.5%). Although antibacterials and/or anti-malarials were prescribed in most patients, some patients did not receive the appropriate treatment.

Conclusion

The study has underscored the importance of febrile bacterial diseases including zoonoses such as leptospirosis and brucellosis in febrile children, and thus such illnesses should be considered by clinicians in the differential diagnoses of febrile diseases. However, access to diagnostic tests for discrimination of febrile illnesses is needed. This would allow febrile patients to receive the correct diagnoses and facilitation of accurate and prompt treatment.     

Arthropod borne disease: the leading cause of fever in pregnancy on the Thai-Burmese border

Background

Fever in pregnancy is dangerous for both mother and foetus. In the 1980''s malaria was the leading cause of death in pregnant women in refugee camps on the Thai-Burmese border. Artemisinin combination therapy has significantly reduced the incidence of malaria in the population. The remaining causes of fever in pregnancy are not well documented.

Methodology

Pregnant women attending antenatal care, where weekly screening for malaria is routine, were invited to have a comprehensive clinical and laboratory screen if they had fever. Women were admitted to hospital, treated and followed up weekly until delivery. A convalescent serum was collected on day 21. Delivery outcomes were recorded.

Principal Findings

Febrile episodes (n = 438) occurred in 5.0% (409/8,117) of pregnant women attending antenatal clinics from 7-Jan-2004 to 17-May-2006. The main cause was malaria in 55.5% (227/409). A cohort of 203 (49.6% of 409) women had detailed fever investigations and follow up. Arthropod-borne (malaria, rickettsial infections, and dengue) and zoonotic disease (leptospirosis) accounted for nearly half of all febrile illnesses, 47.3% (96/203). Coinfection was observed in 3.9% (8/203) of women, mostly malaria and rickettsia. Pyelonephritis, 19.7% (40/203), was also a common cause of fever. Once malaria, pyelonephritis and acute respiratory illness are excluded by microscopy and/or clinical findings, one-third of the remaining febrile infections will be caused by rickettsia or leptospirosis. Scrub and murine typhus were associated with poor pregnancy outcomes including stillbirth and low birth weight. One woman died (no positive laboratory tests).

Conclusion/Significance

Malaria remains the leading cause of fever in pregnancy on the Thai-Burmese border. Scrub and murine typhus were also important causes of fever associated with poor pregnancy outcomes. Febrile pregnant women on the Thai-Burmese border who do not have malaria, pyelonephritis or respiratory tract infection should be treated with azithromycin, effective for typhus and leptospirosis.     

Impact of Pregnancy-Associated Malaria on Infant Malaria Infection in Southern Benin

Background

Infants of mothers with placental Plasmodium falciparum infections at delivery are themselves more susceptible to malaria attacks or to infection in early life.

Methodology/ Principal Findings

To assess the impact of either the timing or the number of pregnancy-associated malaria (PAM) infections on the incidence of parasitemia or malaria attacks in infancy, we followed 218 mothers through pregnancy (monthly visits) up to delivery and their infants from birth to 12 months of age (fortnightly visits), collecting detailed clinical and parasitological data. After adjustment on location, mother’s age, birth season, bed net use, and placental malaria, infants born to a mother with PAM during the third trimester of pregnancy had a significantly increased risk of infection (OR [95% CI]: 4.2 [1.6; 10.5], p = 0.003) or of malaria attack (4.6 [1.7; 12.5], p = 0.003). PAM during the first and second trimesters had no such impact. Similarly significant results were found for the effect of the overall number of PAM episodes on the time to first parasitemia and first malaria attack (HR [95% CI]: 2.95 [1.58; 5.50], p = 0.001 and 3.19 [1.59; 6.38], p = 0.001) respectively.

Conclusions/ Significance

This study highlights the importance of protecting newborns by preventing repeated episodes of PAM in their mothers.     

Factors Associated with Hospital Length of Stay among Cancer Patients with Febrile Neutropenia

Purpose

This study sought to evaluate factors associated with hospital length of stay in cancer patients with febrile neutropenia.

Methods

A prospective cohort study was performed at a single tertiary referral hospital in southern Brazil from October 2009 to August 2011. All adult cancer patients with febrile neutropenia admitted to the hematology ward were evaluated. Stepwise random-effects negative binomial regression was performed to identify risk factors for prolonged length of hospital stay.

Results

In total, 307 cases of febrile neutropenia were evaluated. The overall median length of hospital stay was 16 days (interquartile range 18 days). According to multiple negative binomial regression analysis, hematologic neoplasms (P = 0.003), high-dose chemotherapy regimens (P<0.001), duration of neutropenia (P<0.001), and bloodstream infection involving Gram-negative multi-drug-resistant bacteria (P = 0.003) were positively associated with prolonged hospital length of stay in patients with febrile neutropenia. The condition index showed no evidence of multi-collinearity effect among the independent variables.

Conclusions

Hematologic neoplasms, high-dose chemotherapy regimens, prolonged periods of neutropenia, and bloodstream infection with Gram-negative multi-drug-resistant bacteria are predictors of prolonged length hospital of stay among adult cancer patients with febrile neutropenia.     

Acute Uncomplicated Febrile Illness in Children Aged 2-59 months in Zanzibar – Aetiologies,Antibiotic Treatment and Outcome

Background

Despite the fact that a large proportion of children with fever in Africa present at primary health care facilities, few studies have been designed to specifically study the causes of uncomplicated childhood febrile illness at this level of care, especially in areas like Zanzibar that has recently undergone a dramatic change from high to low malaria transmission.

Methods

We prospectively studied the aetiology of febrile illness in 677 children aged 2–59 months with acute uncomplicated fever managed by IMCI (Integrated Management of Childhood Illness) guidelines in Zanzibar, using point-of-care tests, urine culture, blood-PCR, chest X-ray (CXR) of IMCI-pneumonia classified patients, and multiple quantitative (q)PCR investigations of nasopharyngeal (NPH) (all patients) and rectal (GE) swabs (diarrhoea patients). For comparison, we also performed NPH and GE qPCR analyses in 167 healthy community controls. Final fever diagnoses were retrospectively established based on all clinical and laboratory data. Clinical outcome was assessed during a 14-day follow-up. The utility of IMCI for identifying infections presumed to require antibiotics was evaluated.

Findings

NPH-qPCR and GE-qPCR detected ≥1 pathogen in 657/672 (98%) and 153/164 (93%) of patients and 158/166 (95%) and 144/165 (87%) of controls, respectively. Overall, 57% (387/677) had IMCI-pneumonia, but only 12% (42/342) had CXR-confirmed pneumonia. Two patients were positive for Plasmodium falciparum. Respiratory syncytial virus (24.5%), influenza A/B (22.3%), rhinovirus (10.5%) and group-A streptococci (6.4%), CXR-confirmed pneumonia (6.2%), Shigella (4.3%) were the most common viral and bacterial fever diagnoses, respectively. Blood-PCR conducted in a sub-group of patients (n = 83) without defined fever diagnosis was negative for rickettsiae, chikungunya, dengue, Rift Valley fever and West Nile viruses. Antibiotics were prescribed to 500 (74%) patients, but only 152 (22%) had an infection retrospectively considered to require antibiotics. Clinical outcome was generally good. However, two children died. Only 68 (11%) patients remained febrile on day 3 and three of them had verified fever on day 14. An additional 29 (4.5%) children had fever relapse on day 14. Regression analysis determined C-reactive Protein (CRP) as the only independent variable significantly associated with CXR-confirmed pneumonia.

Conclusions

This is the first study on uncomplicated febrile illness in African children that both applied a comprehensive laboratory panel and a healthy control group. A majority of patients had viral respiratory tract infection. Pathogens were frequently detected by qPCR also in asymptomatic children, demonstrating the importance of incorporating controls in fever aetiology studies. The precision of IMCI for identifying infections requiring antibiotics was low.     

Asymptomatic Malaria in Refugees Living in a Non-Endemic South African City

Background

Asymptomatic malaria infection in refugees is both a threat to the lives of the individuals and the public in the host country. Although South Africa has been experiencing an unprecedented influx of refugees since 1994, data on malaria infection among refugees is lacking. Such information is critical since South Africa is among the countries that have planned to eliminate malaria. The objective of this study was to determine prevalence of asymptomatic malaria infection among a refugee population living in a city of KwaZulu-Natal province, South Africa.

Methods and Findings

A survey was conducted on adult refugee participants who attended a faith-based facility offering social services in a city of KwaZulu-Natal province, South Africa. The participants were screened for the presence of malaria using rapid diagnostic tests and microscopy. Demographic data for the participants were obtained using a closed ended questionnaire. Data was obtained for 303 participants consisting of 51.5% females and 47.5% males, ranging from 19 to 64 years old. More than 95% of them originated from sub-Saharan African countries. Two hundred and ninety participants provided a blood sample for screening of malaria. Of these, 3.8% tested positive for rapid diagnostic test and 5.9% for microscopy. The majority of malaria infections were due to Plasmodium falciparum.

Conclusions

The study confirms the presence of asymptomatic malaria infections among a refugee population residing in a city of KwaZulu-Natal province that is not endemic for malaria. The results have important implications for both public health and malaria control in South Africa, particularly since the country has decided to eliminate malaria by 2018. To achieve this goal, South Africa needs to expand research, surveillance and elimination activities to include non-endemic areas, particularly with high refugee populations. We further recommend use of powerful diagnostic tests such as PCR for these interventions.     

Etiology of Severe Febrile Illness in Low- and Middle-Income Countries: A Systematic Review

Background

With apparent declines in malaria worldwide during the last decade and more widespread use of malaria rapid diagnostic tests, healthcare workers in low-resource areas face a growing proportion of febrile patients without malaria. We sought to describe current knowledge and identify information gaps of the etiology severe febrile illness in low-and middle-income countries.

Methods and Findings

We conducted a systematic review of studies conducted in low-and-middle income countries 1980–2013 that prospectively assessed consecutive febrile patients admitted to hospital using rigorous laboratory-based case definitions. We found 45 eligible studies describing 54,578 patients; 9,771 (17.9%) had a positive result for ≥1 pathogen meeting diagnostic criteria. There were no eligible studies identified from Southern and Middle Africa, Eastern Asia, Oceania, Latin American and Caribbean regions, and the European region. The median (range) number of diagnostic tests meeting our confirmed laboratory case definitions was 2 (1 to 11) per study. Of diagnostic tests, 5,052 (10.3%) of 49,143 had confirmed bacterial or fungal bloodstream infection; 709 (3.8%) of 18,142 had bacterial zoonosis; 3,488 (28.5%) of 12,245 had malaria; and 1,804 (17.4%) of 10,389 had a viral infection.

Conclusions

We demonstrate a wide range of pathogens associated with severe febrile illness and highlight the substantial information gaps regarding the geographic distribution and role of common pathogens. High quality severe febrile illness etiology research that is comprehensive with respect to pathogens and geographically representative is needed.     

Prevalence,Types, Risk Factors and Clinical Correlates of Anaemia in Older People in a Rural Ugandan Population

Background

Studies conducted in high income countries have shown that anaemia is a common medical condition among older people, but such data are scarce in Africa. The objectives of this study were to estimate the prevalence, types, risk factors and clinical correlates of anaemia in older people.

Methods

Participants were aged (≥ 50) years recruited from a general population cohort from January 2012 to January 2013. Blood samples were collected for assessing hemoglobin, serum ferritin, serum vitamin B12, serum folate, C-reactive protein, malaria infection and stool samples for assessment of hookworm infection. HIV status was assessed using an algorithm for HIV rapid testing. Questionnaires were used to collect data on sociodemographic characteristics and other risk factors for anaemia.

Results

In total, 1449 people participated (response rate 72.3%). The overall prevalence of anaemia was 20.3 % (95% CI 18.2-22.3%), and this was higher for males (24.1%, 95% CI=20.7-27.7%) than females (17.5%, 95% CI=15.0-20.1%). In males, the prevalence of anaemia increased rapidly with age almost doubling between 50 and 65 years (p-trend<0.001). Unexplained anaemia was responsible for more than half of all cases (59.7%). Anaemia was independently associated with infections including malaria (OR 3.49, 95% CI 1.78-6.82), HIV (OR 2.17, 1.32-3.57) heavy hookworm infection (OR 3.45, 1.73-6.91), low fruit consumption (OR 1.55, 1.05-2.29) and being unmarried (OR 1.37 , 95% CI 1.01-1.89). However, the odds of anaemia were lower among older people with elevated blood pressure (OR 0.47, 95% CI 0.29-0.77).

Conclusion

Anaemia control programmes in Uganda should target older people and should include interventions to treat and control hookworms and educational programs on diets that enhance iron absorption. Clinicians should consider screening older people with HIV or malaria for anaemia. Further studies should be done on unexplained anaemia and serum ferritin levels that predict iron deficiency anaemia in older people.     

Dengue infection in children in Ratchaburi, Thailand: a cohort study. II. Clinical manifestations

Background

Dengue infection is one of the most important mosquito-borne diseases. More data regarding the disease burden and the prevalence of each clinical spectrum among symptomatic infections and the clinical manifestations are needed. This study aims to describe the incidence and clinical manifestations of symptomatic dengue infection in Thai children during 2006 through 2008.

Study Design

This study is a school-based prospective open cohort study with a 9,448 person-year follow-up in children aged 3–14 years. Active surveillance for febrile illnesses was done in the studied subjects. Subjects who had febrile illness were asked to visit the study hospital for clinical and laboratory evaluation, treatment, and serological tests for dengue infection. The clinical data from medical records, diary cards, and data collection forms were collected and analyzed.

Results

Dengue infections were the causes of 12.1% of febrile illnesses attending the hospital, including undifferentiated fever (UF) (49.8%), dengue fever (DF) (39.3%) and dengue hemorrhagic fever (DHF) (10.9%). Headache, anorexia, nausea/vomiting and myalgia were common symptoms occurring in more than half of the patients. The more severe dengue spectrum (i.e., DHF) had higher temperature, higher prevalence of nausea/vomiting, abdominal pain, rash, diarrhea, petechiae, hepatomegaly and lower platelet count. DHF cases also had significantly higher prevalence of anorexia, nausea/vomiting and abdominal pain during day 3–6 and diarrhea during day 4–6 of illness. The absence of nausea/vomiting, abdominal pain, diarrhea, petechiae, hepatomegaly and positive tourniquet test may predict non-DHF.

Conclusion

Among symptomatic dengue infection, UF is most common followed by DF and DHF. Some clinical manifestations may be useful to predict the more severe disease (i.e., DHF). This study presents additional information in the clinical spectra of symptomatic dengue infection.     

Coxiella burnetii Seroprevalence in Small Ruminants in The Gambia

Background

Q fever is a zoonosis caused by Coxiella burnetii, a Gram negative bacterium present worldwide. Small ruminants are considered the main reservoirs for infection of humans. This study aimed to estimate the extent of C. burnetii infection among sheep and goats in part of The Gambia.

Methodology/Principal Findings

This survey was carried out from March to May 2012 at two areas in The Gambia. The first area comprised a cluster of seven rural villages situated 5–15 km west of Farafenni as well as the local abattoir. A second sampling was done at the central abattoir in Abuko (30 km from the capital, Banjul) in the Western Region. Serum samples were obtained from 490 goats and 398 sheep. In addition, 67 milk samples were obtained from lactating dams. Sera were tested with a Q fever ELISA kit. C. burnetii DNA was extracted from milk samples and then detected using a specific quantitative multiplex PCR assay, targeting the IS1111a element. A multivariable mixed logistic regression model was used to examine the relationship between seropositivity and explanatory variables. An overall seroprevalence of 21.6% was found. Goats had a significantly higher seroprevalence than sheep, respectively 24.2% and 18.5%. Seropositive animals were significantly older than seronegative animals. Animals from the villages had a significantly lower seroprevalence than animals from the central abattoir (15.1% versus 29.1%). C. burnetii DNA was detected in 2 out of 67 milk samples, whereas 8 samples gave a doubtful result.

Conclusion/Significance

A substantial C. burnetii seroprevalence in sheep and goats in The Gambia was demonstrated. People living in close proximity to small ruminants are exposed to C. burnetii. Q fever should be considered as a possible cause of acute febrile illness in humans in The Gambia. Future studies should include a simultaneous assessment of veterinary and human serology, and include aetiology of febrile illness in local clinics.     

Euthermic Endocarditis

Background

Most patients with infective endocarditis (IE) manifest fever. Comparison of endocarditis patients with and without fever, and whether the lack of fever in IE is a marker for poorer outcomes, such as demonstrated in other severe infectious diseases, have not been defined.

Methods and Results

Cases from the Mayo Clinic, Rochester, Minnesota, Division of Infectious Diseases IE registry, a single-center database that contains all cases of IE treated at our center. Diagnosis date between 1970 and 2006, which met the modified Duke criteria for definite endocarditis, without fever was included. There were 240 euthermic endocarditis cases included in this analysis, with 282 febrile controls selected by frequency matching on gender and decade of diagnosis. Euthermic patients had a median age of 63.6 years (±16.1) as compared to 59.0 years (±16.4) in the febrile control group (p=0.001). Median (IQR) symptom duration prior to diagnosis was 4.0 (1.0, 12.0) weeks in the euthermic group compared to 3.0 (1.0, 8.0) weeks in the febrile controls (p= 0.006). From unadjusted analyses, survival rates were 87% in euthermic cases versus 83% in febrile controls across 28-day follow-up (p=0.164), and 72% in euthermic group cases versus 69% in febrile controls across 1-year follow-up (p=0.345). Also unadjusted, the 1-year cumulative incidence rate of valve surgery was higher in euthermic cases versus febrile controls (50% vs. 39%, p= 0.004).

Conclusions

Patients with euthermic endocarditis are older, and lack of fever was associated with longer symptom duration and delayed diagnosis prior to IE diagnosis. Despite a higher unadjusted rate of valve surgery in euthermic patients, the result was not significant when adjusting for baseline confounders. Differences in survival rates at both 28-days and 365-days were not statistically significant between the two groups.     

Impact of Schistosoma mansoni on Malaria Transmission in Sub-Saharan Africa

Background

Sub-Saharan Africa harbors the majority of the global burden of malaria and schistosomiasis infections. The co-endemicity of these two tropical diseases has prompted investigation into the mechanisms of coinfection, particularly the competing immunological responses associated with each disease. Epidemiological studies have shown that infection with Schistosoma mansoni is associated with a greater malaria incidence among school-age children.

Methodology

We developed a co-epidemic model of malaria and S. mansoni transmission dynamics which takes into account key epidemiological interaction between the two diseases in terms of elevated malaria incidence among individuals with S. mansoni high egg output. The model was parameterized for S. mansoni high-risk endemic communities, using epidemiological and clinical data of the interaction between S. mansoni and malaria among children in sub-Saharan Africa. We evaluated the potential impact of the S. mansoni–malaria interaction and mass treatment of schistosomiasis on malaria prevalence in co-endemic communities.

Principal Findings

Our results suggest that in the absence of mass drug administration of praziquantel, the interaction between S. mansoni and malaria may reduce the effectiveness of malaria treatment for curtailing malaria transmission, in S. mansoni high-risk endemic communities. However, when malaria treatment is used in combination with praziquantel, mass praziquantel administration may increase the effectiveness of malaria control intervention strategy for reducing malaria prevalence in malaria- S. mansoni co-endemic communities.

Conclusions/Significance

Schistosomiasis treatment and control programmes in regions where S. mansoni and malaria are highly prevalent may have indirect benefits on reducing malaria transmission as a result of disease interactions. In particular, mass praziquantel administration may not only have the direct benefit of reducing schistosomiasis infection, it may also reduce malaria transmission and disease burden.     

Rift Valley Fever Virus Encephalitis Is Associated with an Ineffective Systemic Immune Response and Activated T Cell Infiltration into the CNS in an Immunocompetent Mouse Model

Background

Rift Valley fever virus (RVFV) causes outbreaks of severe disease in livestock and humans throughout Africa and the Arabian Peninsula. In people, RVFV generally causes a self-limiting febrile illness but in a subset of individuals, it progresses to more serious disease. One manifestation is a delayed-onset encephalitis that can be fatal or leave the afflicted with long-term neurologic sequelae. In order to design targeted interventions, the basic pathogenesis of RVFV encephalitis must be better understood.

Methodology/Principal Findings

To characterize the host immune responses and viral kinetics associated with fatal and nonfatal infections, mice were infected with an attenuated RVFV lacking NSs (ΔNSs) that causes lethal disease only when administered intranasally (IN). Following IN infection, C57BL/6 mice developed severe neurologic disease and succumbed 7–9 days post-infection. In contrast, inoculation of ΔNSs virus subcutaneously in the footpad (FP) resulted in a subclinical infection characterized by a robust immune response with rapid antibody production and strong T cell responses. IN-inoculated mice had delayed antibody responses and failed to clear virus from the periphery. Severe neurological signs and obtundation characterized end stage-disease in IN-inoculated mice, and within the CNS, the development of peak virus RNA loads coincided with strong proinflammatory responses and infiltration of activated T cells. Interestingly, depletion of T cells did not significantly alter survival, suggesting that neurologic disease is not a by-product of an aberrant immune response.

Conclusions/Significance

Comparison of fatal (IN-inoculated) and nonfatal (FP-inoculated) ΔNSs RVFV infections in the mouse model highlighted the role of the host immune response in controlling viral replication and therefore determining clinical outcome. There was no evidence to suggest that neurologic disease is immune-mediated in RVFV infection. These results provide important insights for the future design of vaccines and therapeutic options.     

Clinical Manifestations of Non-O1 Vibrio cholerae Infections

Background

Infections caused by non-O1 Vibrio cholera are uncommon. The aim of our study was to investigate the clinical and microbiological characteristics of patients with non-O1 V. cholera infections.

Methods

The clinical charts of all patients with non-O1 V. cholera infections and who were treated in two hospitals in Taiwan were retrospectively reviewed.

Results

From July 2009 to June 2014, a total of 83 patients with non-O1 V. cholera infections were identified based on the databank of the bacteriology laboratories of two hospitals. The overall mean age was 53.3 years, and men comprised 53 (63.9%) of the patients. Liver cirrhosis and diabetes mellitus were the two most common underlying diseases, followed by malignancy. The most common type of infection was acute gastroenteritis (n = 45, 54.2%), followed by biliary tract infection (n = 12, 14.5%) and primary bacteremia (n = 11, 13.3%). Other types of infection, such as peritonitis (n = 5, 6.0%), skin and soft tissue infection (SSTI) (n = 5, 6.0%), urinary tract infection (n = 3, 3.6%) and pneumonia (2, 2.4%), were rare. July and June were the most common months of occurrence of V. cholera infections. The overall in-hospital mortality of 83 patients with V. cholera infections was 7.2%, but it was significantly higher for patients with primary bacteremia, hemorrhage bullae, acute kidney injury, acute respiratory failure, or admission to an ICU. Furthermore, multivariate analysis showed that in-hospital mortality was significantly associated with acute respiratory failure (odds ratio, 60.47; 95% CI, 4.79-763.90, P = 0.002).

Conclusions

Non-O1 V. cholera infections can cause protean disease, especially in patients with risk factors and during warm-weather months. The overall mortality of 83 patients with non-O1 V. cholera infections was only 7.2%; however, this value varied among different types of infection.     

Malaria Infection Has Spatial,Temporal, and Spatiotemporal Heterogeneity in Unstable Malaria Transmission Areas in Northwest Ethiopia

Background

Malaria elimination requires successful nationwide control efforts. Detecting the spatiotemporal distribution and mapping high-risk areas are useful to effectively target pockets of malaria endemic regions for interventions.

Objective

The aim of the study was to identify patterns of malaria distribution by space and time in unstable malaria transmission areas in northwest Ethiopia.

Methods

Data were retrieved from the monthly reports stored in the district malaria offices for the period between 2003 and 2012. Eighteen districts in the highland and fringe malaria areas were included and geo-coded for the purpose of this study. The spatial data were created in ArcGIS10 for each district. The Poisson model was used by applying Kulldorff methods using the SaTScan™ software to analyze the purely temporal, spatial and space-time clusters of malaria at a district levels.

Results

The study revealed that malaria case distribution has spatial, temporal, and spatiotemporal heterogeneity in unstable transmission areas. Most likely spatial malaria clusters were detected at Dera, Fogera, Farta, Libokemkem and Misrak Este districts (LLR =197764.1, p<0.001). Significant spatiotemporal malaria clusters were detected at Dera, Fogera, Farta, Libokemkem and Misrak Este districts (LLR=197764.1, p<0.001) between 2003/1/1 and 2012/12/31. A temporal scan statistics identified two high risk periods from 2009/1/1 to 2010/12/31 (LLR=72490.5, p<0.001) and from 2003/1/1 to 2005/12/31 (LLR=26988.7, p<0.001).

Conclusion

In unstable malaria transmission areas, detecting and considering the spatiotemporal heterogeneity would be useful to strengthen malaria control efforts and ultimately achieve elimination.     

Burden of Complicated Malaria in a Densely Forested Bastar Region of Chhattisgarh State (Central India)

Background

A prospective study on severe and complicated malaria was undertaken in the tribal dominated area of Bastar division, Chhattisgarh (CG), Central India, with an objective to understand the clinical epidemiology of complicated malaria in patients attending at a referral hospital.

Methods

Blood smears, collected from the general medicine and pediatric wards of a government tertiary health care facility located in Jagdalpur, CG, were microscopically examined for malaria parasite from July 2010 to December 2013. The Plasmodium falciparum positive malaria cases who met enrollment criteria and provided written informed consent were enrolled under different malaria categories following WHO guidelines. PCR was performed to reconfirm the presence of P.falciparum mono infection among enrolled cases. Univariate and multivariate logistic regression analysis was done to identify different risk factors using STATA 11.0.

Results

A total of 40,924 cases were screened for malaria. The prevalence of malaria and P.falciparum associated complicated malaria (severe and cerebral both) in the hospital was 6% and 0.81%, respectively. P.falciparum malaria prevalence, severity and associated mortality in this region peaked at the age of>4–5 years and declined with increasing age. P.falciparum malaria was significantly more prevalent in children than adults (P<0.00001). Among adults, males had significantly more P.falciparum malaria than females (P<0.00001). Case fatality rate due to cerebral malaria and severe malaria was, respectively, 32% and 9% among PCR confirmed mono P.falciparum cases. Coma was the only independent predictor of mortality in multivariate regression analysis. Mortality was significantly associated with multi-organ complication score (P = 0.0003).

Conclusion

This study has revealed that the pattern of morbidity and mortality in this part of India is very different from earlier reported studies from India. We find that the peak morbidity and mortality in younger children regardless of seasonality. This suggests that this age group needs special care for control and clinical management.