Toxoplasma gondii: from animals to humans

Dengue viruses (DENV) are by far the most important arboviral pathogens in the tropics around the world, putting at risk of infection nearly a third of the global human population. DENV are members of the genus Flavivirus in the Family Flaviviridae and comprise four antigenically distinct serotypes (DENV-1-4). Although they share almost identical epidemiological features, they are genetically distinct. Phylogenetic analyses have revealed valuable insights into the origins, epidemiology and the forces that shape DENV evolution in nature. In this review, we examine the current status of DENV evolution, including but not limited to rates of evolution, selection pressures, population sizes and evolutionary constraints, and we discuss how these factors influence transmission, pathogenesis and emergence.

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Dengue-Quo tu et quo vadis?

Background 
Dengue virus (DV) infection is one of the most important mosquito-borne diseases in the tropics. Recently, the severe forms, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), have become the leading cause of death among children in Southern Vietnam. Protective and/or pathogenic T cell immunity is supposed to be important in the pathogenesis of DHF and DSS.


Methodology/Principal Findings 
To identify HLA alleles controlling T cell immunity against dengue virus (DV), we performed a hospital-based case control study at Children's Hospital No.2, Ho Chi Minh City (HCMC), and Vinh Long Province Hospital (VL) in Southern Vietnam from 2002 to 2005. A total of 211 and 418 patients with DHF and DSS, respectively, diagnosed according to the World Health Organization (WHO) criteria, were analyzed for their characteristic HLA-A, -B and -DRB1 alleles. Four hundred fifty healthy children (250 from HCMC and 200 from VL) of the same Kinh ethnicity were also analyzed as population background. In HLA class I, frequency of the HLA-A*24 showed increased tendency in both DHF and DSS patients, which reproduced a previous study. The frequency of A*24 with histidine at codon 70 (A*2402/03/10), based on main anchor binding site specificity analysis in DSS and DHF patients, was significantly higher than that in the population background groups (HCMC 02-03 DSS: OR = 1.89, P = 0.008, DHF: OR = 1.75, P = 0.033; VL 02-03 DSS: OR = 1.70, P = 0.03, DHF: OR = 1.46, P = 0.38; VL 04-05 DSS: OR = 2.09, P = 0.0075, DHF: OR = 2.02, P = 0.038). In HLA class II, the HLA-DRB1*0901 frequency was significantly decreased in secondary infection of DSS in VL 04-05 (OR = 0.35, P = 0.0025, Pc = 0.03). Moreover, the frequency of HLA-DRB1*0901 in particular was significantly decreased in DSS when compared with DHF in DEN-2 infection (P = 0.02).


Conclusion 
This study improves our understanding of the risk of HLA-class I for severe outcome of DV infection in the light of peptide anchor binding site and provides novel evidence that HLA-class II may control disease severity (DHF to DSS) in DV infection.

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Protective and enhancing HLA alleles, HLA-DRB1*0901 and HLA-A*24, for severe forms of dengue virus infection, dengue hemorrhagic fever and dengue shock syndrome.

This is the first report of the largest epidemic of dengue hemorrhagic fever (DHF) virus infection (2006) with IgM-confirmed cases from Karachi, Pakistan. Medical records of 172 IgM-positive patients were reviewed retrospectively for demographic, clinical and laboratory data. Patients were categorized into dengue fever (DF) and DHF according to the WHO severity grading scale. The mean+/-SD age of the patients was 25.9+/-12.8 years, 55.8% were males and the hemoconcentration was recorded in a small number of patients [10 (7.0%)]. Male gender [odds ratio (OR)=14.7, P=0.003), positive history of vomiting (OR=4.3, P=0.047), thrombocytopenia at presentation (OR=225.2, P<0.001) and monocytosis (OR=5.8, P=0.030) were independently associated with DHF, but not with DF. Five cases (2.9%) had a fatal outcome, with a male-to-female ratio of 1:4. Three were from a pediatric group (<15 years). Pulmonary hemorrhages, disseminated intravascular coagulation and cerebral edema preceded death in these patients. The results have highlighted significant findings, such as adult susceptibility to DHF, pronounced abdominal symptoms and lack of hemoconcentration at time of presentation in the study population. These findings may play an important role in the case definitions of future studies from this part of the world.

Dengue outbreak in Karachi, Pakistan, 2006: experience at a tertiary care center.

Dengue occurred sporadically in Bangladesh from 1964 until a large epidemic in 2000 established the virus. We trace dengue from the time it was first identified in Bangladesh and identify factors favourable to future dengue haemorrhagic fever epidemics. The epidemic in 2000 was likely due to introduction of a dengue virus strain from a nearby endemic country, probably Thailand. Cessation of dichlorodiphenyltrichloroethane (DDT) spraying, climatic, socio-demographic, and lifestyle factors also contributed to epidemic transmission. The largest number of cases was notified in 2002 and since then reported outbreaks have generally declined, although with increased notifications in alternate years. The apparent decline might be partially due to public awareness with consequent reduction in mosquito breeding and increased prevalence of immunity. However, passive hospital-based surveillance has changed with mandatory serological confirmation now required for case reporting. Further, a large number of cases remain undetected because only patients with severe dengue require hospitalisation. Thus, the reduction in notification numbers may be an artefact of the surveillance system. Indeed, population-based serological survey indicates that dengue transmission continues to be common. In the future, the absence of active interventions, unplanned urbanisation, environmental deterioration, increasing population mobility, and economic factors will heighten dengue risk. Projected increases in temperature and rainfall may exacerbate this.

The emergence of dengue in Bangladesh: epidemiology, challenges and future disease risk.

SUMMARY: During the febrile illness epidemic in Bangladesh in 2002, 58 people died out of the 6,132 affected. Two hundred hospitalized patients were analyzed clinically, serologically and virologically to determine the features of this dengue infection. Among the 10- to 70-year-old age group of the 200 clinically suspected dengue patients, 100 (50%) were confirmed as dengue cases by virus isolation and dengue IgM-capture ELISA. Of the 100 dengue-confirmed cases, the mean age was 29.0 (±12.4). The possible dengue secondary infection rate determined by Flavivirus IgG-indirect ELISA was 78% in 2002. Eight dengue virus strains were isolated, representing the first dengue virus isolation in the country, and all of the strains were dengue virus type-3 (DEN-3). Sequence data for the envelope gene of the DEN-3 Bangladeshi isolates were used in a phylogenetic comparison with DEN-3 from other countries. A phylogenetic analysis revealed that all 8 strains of DEN-3 were clustered within a well-supported independent sub-cluster of genotype II and were closely related to the Thai isolates from the 1990s. Therefore, it is likely that the currently circulating DEN-3 viruses entered Bangladesh from neighboring countries.

Molecular Characterization and Clinical Evaluation of Dengue Outbreak in 2002 in Bangladesh

The latex agglutination test (Toxoreagent) was used to detect the sero-prevalence of Toxoplasma gondii in 302 Bangladeshi women who were under treatment for various gyneco-obstetric problems at the Mymensingh Medical College during January to June 1991. The over-all sero-prevalence rate was 15.89%, of which 6.25% reacted at 1:32, 33.33% at 1:64, 16.67% at 1:128, 22.92% at 1:256, 6.25% at 1:512 and 14.58% at 1:1024. The positivity rate of 18.60% recorded in women between 31 and 40 years was insignificantly (p > 0.05) higher than that of 15.44% in women between 17 and 30 years of age. Over-all 26.49% of infections resulted in abortion, 6.62 in stillbirths and 30.79% in dystocia, of which 20.0%, 30.0% and 7.53% women had positive titers to T. gondii, respectively, whereas 17.43% women with normal live births had also positive titers to T. gondii. The over-all prevalence rate of abortion in association with T. gondii infection was 5.30% which was higher than the rates of stillbirths (1.99%) and perinatal death (0.66%). It is concluded that toxoplasmosis can cause abortion, stillbirths and perinatal death in Bangladeshi women.

Serological diagnosis of Toxoplasma gondii infection in women associated with gyneco-obstetric problems.

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Molecular Characterization and Clinical Evaluation of Dengue Outbreak in 2002 in Bangladesh

Serological diagnosis of Toxoplasma gondii infection in women associated with gyneco-obstetric problems.