Dengue has emerged as an important arboviral disease with significant impact on the disease burden in population residing in tropical countries. Dengue is spread by the bite of Aedes mosquito. The virus seems to have some hepatotoxic effects. Affliction of liver in form of derangements in the liver function tests is common and may include mild elevations in serum bilirubin, elevated transaminases and derangements in serum albumin. Although asymptomatic in most cases, clinical manifestations like jaundice, and acute liver failure (ALF) may occasionally complicate the clinical picture. Indeed, dengue has been implicated as an important cause of ALF in endemic countries. The present review focuses on the hepatic manifestations and the pathogenesis of the liver injury in dengue.

Dengue and its effects on liver.

Objectives To study the trend in the prevalence of anaemia and low BMI among pregnant women from Eastern Maharashtra and evaluate if low BMI and anaemia affect pregnancy outcomes. Design Prospective observational cohort study. Setting Catchment areas of 20 rural primary health centres in four eastern districts of Maharashtra State, India. Participants 72 750 women from the Nagpur site of Maternal and Newborn Health Registry of NIH’s Global Network, enrolled from 2009 to 2016. Main outcome measures Mode of delivery, pregnancy related complications at delivery, stillbirths, neonatal deaths and low birth weight (LBW) in babies. Results Over 90% of the women included in the study were anaemic and over a third were underweight (BMI Conclusion Maternal anaemia is associated with enhanced risk of stillbirth, neonatal deaths and LBW. The risks increased if anaemia and underweight were present simultaneously. Trial registration number NCT01073475.

https://bmjopen.bmj.com/content/bmjopen/8/8/e021623.full.pdf

Maternal anemia and underweight as determinants of pregnancy outcomes: cohort study in eastern rural Maharashtra, India.

Anemia is the most frequent derailment of physiology in the world throughout the life of a woman. It is a serious condition in countries that are industrialized and in countries with poor resources. The main purpose of this manuscript is to give the right concern of anemia in pregnancy. The most common causes of anemia are poor nutrition, iron deficiencies, micronutrients deficiencies including folic acid, vitamin A and vitamin B12, diseases like malaria, hookworm infestation and schistosomiasis, HIV infection and genetically inherited hemoglobinopathies such as thalassemia. Depending on the severity and duration of anemia and the stage of gestation, there could be different adverse effects including low birth weight and preterm delivery. Treatment of mild anemia prevents more severe forms of anemia, strictly associated with increased risk of fetal-maternal mortality and morbidity.

https://journals.sagepub.com/doi/pdf/10.2217/whe.15.35

Iron Deficiency Anemia in Pregnancy

Clinical implications and treatment of dengue.

To study the clinical profile of dengue fever and its outcome in children with application of revised WHO classification and to identify risk factors for severe dengue. This study was a prospective observational study of children diagnosed with dengue from July 2012 through February 2013 at a tertiary care hospital in Bangalore, Karnataka (South India). Eighty one children including 55(67.9 %) boys and 26(32.1 %) girls were diagnosed with dengue. Mean age of presentation was 8 y. Vomiting (60.5 %), pain abdomen (32 %), headache (30.9 %), myalgia (23.5 %) and bleeding manifestations (16 %) were the common presenting complaints. Facial puffiness (63 %), hepatomegaly (51.9 %), ascites (48.1 %), pleural effusion (39.5 %) and petechiae (14.8 %) were noted during examination. Dengue NS1 antigen, IgM, IgG were positive in 66.7 %, 29.6 % and 18.5 % of cases respectively. Investigations showed hemoconcentration in 72.8 %, leucopenia (34.5 %), thrombocytopenia (82.7 %), abnormal liver function test (LFT) (33.3 %). USG abdomen was suggestive of dengue in 66.7 % and gall bladder edema was noted in 53.1 %. Two patients died out of the total 81 patients with mortality rate of 2.5 %. Number of cases classified as Dengue without warning signs (D), Dengue with warning signs (DW) and Severe Dengue (SD) were 48.1 %, 27.2 % and 24.7 % respectively. Children between 5 and 15 y were most affected by dengue fever. Pain abdomen and vomiting were most common presenting symptoms. Ascites, plerural effusion, hepatomegaly, gall bladder wall thickening and abnormal LFT were found significantly high in severe dengue cases.

Clinical profile of dengue among children according to revised WHO classification: analysis of a 2012 outbreak from Southern India.

Background: Anemia has been a very important nutritional disorder in the world. India has reported high prevalence of anemia in pregnancy. Most of the articles have reported an adverse pregnancy outcome related to anemia. Of late, reports are emerging suggesting anemia could be indeed beneficial. Apart from that, there was no consistency in the timing of hemoglobin considered for analysis. Hence, we designed an observational study to look into these aspects. Methods: 1000 mothers admitted for delivery were recruited and their hemoglobin was measured. Hemoglobin in previous trimesters was noted from their antenatal record. We followed up these mothers till delivery and looked into the gestation and birth weight of the babies. Descriptive statistics was used for baseline characteristics. Comparison of means was done using Student’s t-test. Qualitative variables were compared using Fisher’s exact te st. Results: More than 50% of the mothers were anemic at some point of time during their pregnancy and 39% of the mothers were anemic throughout. Mean birth weight of babies born to anemic mothers was marginally lower compared to that of babies born to nonanemic mothers. This difference was statistically significant. There was 6.5% increase in the incidence of low birth weight babies and 11.5% increase in preterm deliveries in mothers who were anemic in their third trimester.

/pdf/maternal-anemia-in-various-trimesters-and-its-effect-on-4xejmwc11n.pdf

Maternal anemia in various trimesters and its effect on newborn weight and maturity: an observational study.

Objective: Hepatic dysfunction is common in dengue infection and the
degree of liver dysfunction in children varies from mild injury with
elevation of transaminases to severe injury with jaundice. This study
was undertaken to assess the spectrum of hepatic involvement in dengue
infection. Methods: 110 children with serologically positive dengue
fever aged between 2 months - 14 years were studied for their hepatic
functions both clinically and biochemically after excluding malaria,
enteric fever, Hepatitis A and Hepatitis B with relevant
investigations. Findings: All cases were grouped into DF (Dengue
fever), DHF (Dengue hemorrhagic fever) and DSS (Dengue shock syndrome)
according to WHO criteria. The spectrum of hepatic manifestations
included hepatomegaly (79%), hepatic tenderness (56%), jaundice (4.5%),
raised levels of aspartate transaminase (AST)(93 %), alanine
transaminase (ALT)(78%), alkaline phosphatase (AP) (57%), prolonged
prothrombin time (PT) (20%), reduced levels of serum albumin (66%) and
abnormal abdomen ultrasound (65%). Conclusion: Hepatic dysfunction was
observed more in DHF and DSS group compared to DF group. About 17.27%
of children had >10 fold increase in the liver enzymes. There was no
correlation between the degree of hepatic enlargement or hepatic
tenderness with the abnormalities of liver functions. Any child with
fever, jaundice and tender hepatomegaly in geographical areas where
dengue is endemic, the diagnosis of dengue infection should be strongly
considered.

/pdf/hepatic-involvement-in-dengue-fever-in-children-57wdcpl7vx.pdf

Hepatic involvement in dengue Fever in children.

To study the course and complications of hepatitis A in children. Seventy eight children diagnosed as acute viral hepatitis A by IgM antiHAV were prospectively studied for involvement of other systems and complications. The mean age of children was 7.85 ± 3.4 y. Jaundice was present in all the patients as this was the inclusion criteria. Fever was present in 82.1 %, hepatomegaly in 98.7 % and splenomegaly in 39.7 %. More than 5 fold rise in Aspartate transaminase (AST) and Alaninetransaminase (ALT), were seen in 62 cases (79.5 %) and 55 cases (70.5 %) respectively. Coagulopathy (Prothrombin time INR > 1.5) was observed in 12 cases (15.4 %) and abnormal APTT in 10 cases (12.8 %). Thrombocytopenia was observed in 5.1 % of children and 8.9 % had more than 2 hematological abnormalities. Ascites was noted in 35 cases (44.9 %), gallbladder wall thickening in 32 cases (41 %) and pleural effusion in 11 cases (14.1 %). Acute renal failure, acute glomerulonephritis and acute pancreatitis were present in 1 case (1.3 %) each. Raised CK-MB values more than 3 times the normal was noted in 5 cases (6.4 %). On follow up, most of the children recovered completely by 2 mo and prolonged cholestasis was observed in 2 of them. In the present study mortality was 1.3 % and it was attributable to fulminant hepatic failure. Eventhough hepatitis A infection is a self-limiting disease, extrahepatic manifestations and mortality are not uncommon. All cases should be followed up till complete recovery and only a strong index of suspicion will enable us to recognize the complications.

Hepatitis A in children- clinical course, complications and laboratory profile.

Objectives: The aim is to identify the etiology of community acquired pneumonia in children with special reference to atypical bacteria and viruses. Materials and Methods: A total of 94 pneumonia children were enrolled in the study. Sixty-seven did not have an etiological diagnosis by conventional culture. These children were subjected to immunofluorescence assay by Pneumoslide IgM. Results: Ninety-four children were evaluated for etiology by conventional culture. Twenty-seven of them had the bacteriological diagnosis. Rest 67 were further analyzed for causative organism using Pneumoslide immunofluorescence test. Among this group, 38 (56.7%) had etiological diagnosis. Atypical bacteria were identified in 23 cases, most common being Mycoplasma pneumoniae and which was more common between 5 months and 2 years of age. Viruses were identified in 19 cases, and the most common virus was Respiratory syncytial virus. Mixed pathogens were identified in five children., M. pneumoniae was the common offending agent. Conclusions: Atypical bacteria and viruses play an important role as etiological agents in pneumonia in children. Pneumoslide IgM is useful for rapid detection of atypical bacteria and viruses.

Etiology of community acquired pneumonia among children in India with special reference to atypical pathogens

Varicella is usually benign exanthematous disease, which primarily affects children. The common complications are bacterial infection of skin eruptions, pneumonia, cerebellar ataxia, hepatitis, thrombocytopenia and arthritis[1]. Autoimmune hemolytic anemia (AIHA) is a rare complication of varicella and only few cases are reported[2–5]. Overall the incidence of AIHA in children is as low as 0.2/100,000 population[3]. We report AIHA due to chickenpox in a child who responded to steroids.

An 11 year old female was brought with fever of one day followed by pleomorphic skin lesions of 8 days and jaundice of 2 days duration. Her urine and stools were normal. She was conscious, temperature was 37.8°C, HR 160/min, RR 32/min, BP of 90/60 mmHg and SpO2 was 90% in room air. On examination, she had severe pallor and jaundice. There were multiple vesicular and scabbed skin lesions of chicken pox all over the body. There was no evidence of bleeding tendencies, bony tenderness or lymphadenopathy. Abdominal examination revealed 3 cm hepatomegaly and 1 cm splenomegaly. The rest of the examination was unremarkable.

Laboratory investigations: Hb 3.8 g/dL RBC count 1.84×106/L, total leucocyte count 12.1×109/L (polymorphs 88%, lymphocytes 10%, eosinophils 2%), platelet count 303 ×109/L and reticulocyte count 0.5%. RBC indices (MCV, MCH, MCHC) were normal. Peripheral smear showed normocytic normochromic anemia with clumping of RBCs. The Direct Coombs test using polyspecific anti-IgG and anti-C3b/C3d Complement antihuman globulin reagent was positive. Cold agglutinins were not detected and indirect Coombs Test was negative. Total serum bilirubin was 15.5mg/dL (direct bilirubin 1.3mg/dL), SGOT 30 U/L, SGPT 44 U/L, Alkaline phosphatase 123 U/L, total protien 8.5g/L, serum albumin 4.2g/L and serum LDH was 1580 U/L [Normal 230-460 U/L]. Renal function tests and blood sugar were within normal limits. Urine examination was negative for blood, bile salts, bile pigments and microscopy was normal. Urinary urobilinogen was not increased. Hemoglobin electrophoresis was normal. In view of severe pallor, jaundice, classical chicken pox lesions, positive Direct Coombs test, indirect hyperbilirubenemia and elevated LDH values, a diagnosis of varicella AIHA was made and three units of packed RBCs transfused. On the third day of admission, her vitals were normal, Hb was 12.2 g/dL, and reticulocyte count 1%. On the fourth day she developed pallor, Hb dropped to 7.8 g/dL and reticulocyte count was 1.5%. Other investigations: Serology for IgM varicella, IgM anti HAV, HbsAg, Anti HCV, Anti HEV, HIV were negative. Paul Bunnell, Widal test and Quantitative Buffy coat smear for malarial parasites were also negative. Antibody to double stranded DNA and sickling test were negative. Blood culture was sterile and urine chromatography was normal. On the fifth day, she developed severe pallor and the jaundice was same. Investigations at that time revealed Hb of 3.9g/dL, reticulocyte count 1%, total bilirubin was 5.04mg/dL, LDH 1008/L and liver enzymes were normal. Her serum iron, serum ferritin and total iron Binding capacity levels were normal. Chest x-ray, Computerised Tomography scan of neck, thorax and abdomen were normal. She was given three packed RBC transfusions and was started on oral prednisolone 2mg/kg/day in view of continuous hemolysis. After 2 days of steroids her Hb was 6g/dL. After 6 days of prednisolone there was no pallor, mildly icteric, Hb was 10 g/dL with reticulocyte count of 3%. After 10 days of prednisolone there was no pallor or jaundice, Hb was 10.5 g/dl and she was discharged on oral prednisolone 2 mg/kg/day for 6 weeks. She was followed up once a week and after 6 weeks her Hb was 10.8g/dL. Her serum bilirubin and LDH were normal. Prednisolone was reduced by 10% of the initial dose and was kept at this dose for 2 weeks before it was tapered further. At the end of prednisolone therapy Hb reached 14.1g/dL. She was followed up for the next 3 months without any problems.

Chickenpox is one of the most common exanthematous diseases of childhood which can give rise to various complications. AIHA is an uncommon complication of chickenpox [1]. AHIA is characterised by increased erythrocyte destruction due to autoantibodies IgG or IgM directed to red cell antigens[6]. The mortality rate in idiopathic AIHA in children is around 10%[7]. In a series of 865 cases of AIHA only one case was due to chicken pox[8]. In a series of 26 AIHA children, none of them was due to chicken pox[9]. However antivaricella antibodies were not detected in this child. Similar observation during the acute phase of varicella was made by Terada et al[2]. Some authors have made a diagnosis of chicken pox AIHA on clinical criteria without assessing antibody levels[3, 6]. In a review of 6 cases of AIHA due to varicella, only 4 were children and all of them developed hemolysis within 2 weeks of the onset of skin eruptions[2]. Our case also presented with hemolysis on 7th day after the onset of skin eruption.

In spite of severe hemolysis in our child, reticulocyte count was low. Similar observation was made by Naithani et al and probably it is due to hemolytic process affecting the reticulocytes also[9]. Even though it is rare in children, cold agglutinins were reported to be positive in some cases of AIHA due to varicella infection[2, 4, 5]. Cold agglutinins were not seen in our patient. The incidence of AIHA associated with coldagglutinin is higher in adults as a complication of chickenpox than in children[2]. Our child received multiple blood transfusions probably because of continuous destruction of transfused RBCs due to the presence of autoantibodies. Varicella AIHA has been managed conservatively or with the addition of steroids[1–3, 5]. We started on prednisolone in view of continuous severe hemolysis requiring multiple blood transfusions. Prednisolone was given in the same dose, duration and tapered as described by Naithani et al[7]. At the end of prednisolone therapy Hb reached 14.1g/dL without any complications. The mechanism of action of steroids is probably down regulation of Fc receptors on phagocytes, reduced IL-2 production, suppression of sequestration of opsonized red cells by splenic macrophages and reduction in the binding affinity of autoantibodies for red cells[7]. Even drugs like azathioprine, cyclosporine A, cyclophosphamide and IVIG have been used alone or in combinations in refractory AIHA., these are not consistently effective[9].

/pdf/autoimmune-hemolytic-anemia-due-to-varicella-infection-1pbjybi8d4.pdf

VG Manjunath

Papers

Maternal anemia in various trimesters and its effect on newborn weight and maturity: an observational study.

Hepatic involvement in dengue Fever in children.

Hepatitis A in children- clinical course, complications and laboratory profile.

Etiology of community acquired pneumonia among children in India with special reference to atypical pathogens

Autoimmune Hemolytic Anemia due to Varicella Infection.