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Indian Journal for

tthhee PPrraaccttiissiinngg DDooccttoorr

Executive Editor

Bashir Gaash, MD, PhD, DCH


Muzaffar Ahmad, MD, FACP, FIMSA

Medical Quiz: Diagnostic dilemma Childhood Infections: Fever in childhood Immunization: Cold chain maintenance
Medical Quiz: Diagnostic dilemma
Childhood Infections: Fever in childhood
Immunization: Cold chain maintenance
Student’s page: B cell development
Endemic Disease: Viral hepatitis
Surgical emergency: Reduction of rectal prolapse
Global threat: Influenza
Drug update: Cefixime in UTI
Pregnancy: Rh incompatibility
Rural surgery: Operating room etiquette
Heart Disease: Rheumatic Fever
Parent/patient education: Febrile child, asthma, osteoarthritis, cervical cancer
Haematology : Diagnosis of anaemia
Foods we take: Tea
A leaf from the history of Medicine: Joseph Lister
Hazardous waste: Healthcare waste – A Consideration
Special supplement: Drug Use in Hepatic Impairment
Vol I
No. 4
(January 2005)

Indian J for Practising Doctor, Vol: 4


(A bimonthly journal for doctors working in peripheries)

Editor-in-Chief Dr Muzaffar Ahmad, MD, FACP, FIMSA Director Health Services, Kashmir.

Executive Editor Dr Bashir Gaash, MD, PhD, DCH. Principal, Regional Institute of Health & Family Welfare, Kashmir.

Editorial Assistance:

Dr Rehana Kausar, MD, Dipl H&FW

Dr Manzoor Kadri, MBBS, PG Dipl HIV/AIDS Dr Rohini Bhan, MBBS, PG Dipl RCH

Dr Farooq Fazilli, MD Dr Rubina Shaheen, MD Dr Shabnam Bashir, MBBS

Managing Editor:

Neelam Bashir, BCA, G.Tech

Editorial correspondence: P. O. Box: 673 (GPO), Srinagar, Kashmir

[Phones: 951954-255042;


Indian J for Practising Doctor, Vol: 4

Contents: • Medical Quiz IVI • Diagnosis of Anaemia: role of CBC & PBF, 7
• Medical Quiz IVI
• Diagnosis of Anaemia: role of CBC & PBF, 7 (Neha Dahiya)
• Torch Test – Need for Use as a Screening Test, 13 (Naveen Thapliyal, Getta Jain, &
Godavari Pandey)
• Torch Test: Test & Inference, 1??8 (S M Kadri)
• Patient
Osteoarthritis 85.
• Influenza – A Reminder, 18 (Bashir Gaash)
• Cold Chain Maintenance, 27 (Rubina Shaheen)
• Operating Room Etiquette, 34 (W.H.O.)
• Pregnancy: Rh Incompatibility, 39 (Rehana Kausar)
• Fever in Children, 43 (Farooq Fazilli)
• Rheumatic Fever, 52 (Shabnam Bashir)
• Foods We Take: Tea (Neelam Bashir)
• Viral Hepatitis, 78. (Rohini Bhan & Arvind Bhan)
• Immunity: B-Lymphocyte Development, 79, (Gazala Shakoor)
• Role of Cefixime in Paedriatic UTI, ?? (Srividya Rao)
• A Leaf From the History Of Medicine: Joseph Lister, 90 (RIHFW)
• Waste From Health care activities, 91 (Muzaffar Ahmad)
• Reduction of Rectal Prolapse, 95 (Shabnam Bashir)
• Special Supplement: Drug use in Hepatic Impairment, 97 (WHO guidelines)

Indian J for Practising Doctor, Vol: 4


The first two issues of the IJPD met an expectedly warm response. The doctors practicing in the field as well as medical students, both, have enthusiastically welcomed the issue. This has encouraged all those involved in the publication of the journal. The journal, as promised, carries articles of direct relevance to the practising doctor. Anaemia is a common nutritional disorder particularly rampant in the developing world. Classification & typing is generally based on the results of complete blood count and peripheral blood smear. These parameters are easy to do and are within the reach of practitioners even in the remote areas of the country. One article has been put to highlight the role of CBC 7 PBF in diagnosis of anemia. Pregnancy is a special occasion, where the mother’s condition directly affects the child. The so-called TORCH infections are generally mild in the mother but can prove disastrous to the ofetus & the neonate. Accordingly the fetus may abort or the neonate may get congenital anomalies, rashes and CNS calcifications. Rh incompatibility between the mother and her foetus is an important cause of mortality among the neonate, and at the same time is so easy to prevent. One article on this not so infrequent condition has also been included. Als. Cold chain maintenance is an area which is so crucial to the potency of vaccines yet is so easily overlooked. We have discussed this important aspect of immunization is detail. Influenza is a tricky infectio: it is one of the oldest scourges of mankind which runs the danger of attaining pandemic proportions every few years. Why despite all efforts to curb its epidemicity influenza virus still continues to baffle mankind has been fully dealt with. Viral hepatitis is a common infection across the world, and new viruses are emerging with passage of time. Some recent information on this hepatotrophic virus has been shared here. Urinary tract infection in children is a common infection. Infants and younger children require aggressive therapy because they are prone to get pyelonephritis with renal scarring. Traditionally, patients of this tender age have been treated intravenously, but cefexime – a 3 rd generation oral cephalosporin - has made treatment very convenient and cheaper. The role of cefexime in the treatment of urinary tract infection is discussed by our collague from Andhra. Fever in children is one of the commonest symptoms, and may sometimes try the wits of any doctor. Management of paedriatic fever is dealt in with reference to use of antipyretics. Foods we use are not only nutritionally important sometimes have benefits which only recently have been explored and documented. Our favourite beverage, tea, has been found to contain antioxidats and ingredients which could prevent atherosclerosis, heart disease and even cancers.

In a series of essays on establishing and maintaining surgical facilities in remote areas, we are carrying an article on surgery room etiquette. A surgical emergency, reduction of rectal prolapse also has been included. A special supplement on drug use in hepatic impairment has been given as the annexure.

January 2005.

(Executive Editor)

Indian J for Practising Doctor, Vol: 4


Neha Dahiya, DNB (Path), is Consultant Pathologist, & Director, K G Lab Services, Coimbatore, Tamil Nadu.

Srividya Rao, MD, DCH, is a paedriatician from Guntur (Andhra Pradesh), currently working with the Ministry of Health, Islamic Repu blic of Iran. She is stationed at Turbat-e- Hyderiya, Khorasan.

Naveen Thapliyal, MD. is Assistant Professor, Pathology, STMFH & Medical College, Haldwani, Uttaranchal.

Geeta Jain, MD, is Assistant Professor, & Godavari Pandey, MD, Resident, Deptt of Obstetrics & Gynaecology, STMF & Medical College, Haldwani, Uttaranchal.

Rehana Kausar, MD: Faculty Member, Regional Institute of Health, Kashmir, is a postgraduate from SK Institute of Medical Sciences, Soura, Srinagar. Before joining RIHFW she has had a stint in the Department of Community Medicine, SK Institute of Medical Sciences, Srinagar.

Manzoor A Kadri: Trainer at the Regional Institute of Health, Kashmir, was a teacher at the Government Medical College, Srinagar (Department of Microbiology) before joining us.

Farooq Fazilli, MD: Faculty Member, Regional Institute of Health, Kashmir, is a postgraduate from the SK Institute of Medical Scinces, Soura, Srinagar. Before joining the RIHFW, the doctor worked in the Department of Community Medicine, SK Institute of Medical Sciences, Srinagar.

Rubina Shaheen, MD: Faculty member, Regional Institute of Health, Kashmir, is a postgraduate in Microbiology. She taught at the SKIMS before her new appointment.

Gazala Shakoor, MD, is a private practitioner working in Srinagar.

Rohini Bhan is a trainer at the Regional Institute of Health, Kashmir.

Shabnam Bashir is a medical graduate from the Government Medical College, Srinagar.

Bashir Gaash; an International Fellow in Tropical Diseases, is a postgraduate in Social & Preventive Medicine and Health Administration, and currently is the Principal, Regional Institute of Health, Kashmir.

Muzaffar Ahmad; MD in general Medicine, has a Fellowship in Emergency Medicine from USA, and currently is the Director Health Services, Kashmir.

Indian J for Practising Doctor, Vol: 4

Diagnostic dilemmas

Medical Quiz: III

A 10-year old boy presented with a history of lethargy and abnormal behaviour at school. He is taking iron tablets for iron-deficiency anaemia, which was diagnosed by his doctor. The boy is the only child in the family; they live in a 3-bedroomed old house. He is withdrawn and does not want to talk. He has been described as a ‘violent child’ by his mother on several occasions in the last 3 months, and has been expelled from a school club because of his behaviour. His best friends had left him because of his argumentative nature. Sometimes he complains of headache, with fuzzy vision. His eyes were checked twice by optometrist for refraction errors without detection of any abnormalities. The child has once threatened to jump out from the window of his room where he passes most of his time. The child has started losing weight. He wakes up at nights shouting and complaining of headache, which requires analgesics. The boy looks withdrawn and makes no eye contact. He hates the school and does not want to go there. All aspects of the systemic examination are normal. All cranial nerves are intact but he does not like to have a light shone into his eyes. A fundus examination shows papilloedema but no other abnormality. His BP is 120/75 mm, heart rate 70, and respiratory rate 20. X-ray abdomen suggested the presence of ureteral stones and a calcified lesion in the bladder. His lab findings showed:


8.7 g/dl






3.57 laks

Blood sugar

4.5 mmol/l

Urine shows

Proteinuria &


After admission, he had a cranial MRI, which turned to be normal. After mid-night he started to have generalized tonic-clonic seizures for 5 minutes, which stopped after rectal administration of diazepam. There were no more seizures and an EEG was carried out which showed no epileptiform activity. His behaviour fluctuated and a decision was made to treat him as having encephalitis. 1) At this juncture which single test should be carried out?

Abdominal ultrasound Urine toxicology Cystoscopy Ferritin level Ammonia level

Barium swallow IVP Lumbar puncture Lead level Mantoux test

2) Which other two investigations should be carried out to reach at the diagnosis? Blood film

Urinary copper level Long-bone x-ray Abdominal CT CSF for HSB-PCR Repeat EEG

3) What is the diagnosis? The patient was treated and after 6 weeks another blood test was taken which showed that he still had the same problem, even though there had been some improvement in his behaviour and he had started to attend the school in the last 2 weeks.

4) What should the management plan be? Admit to hospital until he finishes the course of treatment Refer to the psychiatrist Inform the social services/child protection team/police? Start treatment again with strict supervision by the community care team.

Indian J for Practising Doctor, Vol: 4


Diagnosis of Anaemia:

Role of CBC & Peripheral Blood Smear

Neha Dahiya*

Anaemia is less than normal number of red blood cells, measured as a decrease in the haemoglobin content of the red blood cells. Anaemia leads to a decrease in the oxygen carrying capacity of blood.

(Answers on pg 18)

There are many types of anemia. Primarily they can be classified into


Anemia because of blood loss


Anemia because of impaired red cell


production Anemia due to increased destruction of RBC (haemolytic anaemia)





anaemia are:



Clinical signs / symptoms



Physical Examination


Laboratory investigations

Fig 1: CBC - Parameters considered while establishing & typifying anaemia:

3) Laboratory investigations Fig 1: CBC - Parameters considered while establishing & typifying anaemia : 7

Indian J for Practising Doctor, Vol: 4

Here focus is on the investigations useful in diagnosing and classifying anaemia.

The most basic of all the tests asked for is “CBC” – a Complete Blood Count, which gives information regarding

presence or absence of anaemia and also helps to classify the type of anaemia to

some extent. The CBC has to be seen in conjunction with a peripheral blood

smear examination. The automated CBC encompasses a number of parameters,

which throw light on the aetiology of

anaemia. A CBC on a haematology cell counter with 5 part differential gives at least 24 parameters as seen in Fig 1.

Table 1


Total red blood cell count




Haematocrit / Packed cell volume

Red Blood Cell Indices:



Mean corpuscular volume








haemoglobin conc


Red cell distribution width

The red blood cell indices help in morphological classification of anemia and aid in further investigational studies.

The macrocytic anaemias can be further divided according to MCV:

1) Slight increase in MCV:

[MCV >100 but <105 fl]













- Myxoedema



In all cases the red cell precursors in the marrow are normal in morphology.

2) Moderate increase in the MCV:

[MCV >105 and <110 fl]

- Liver disease

3) Marked increase in the MCV:

[MCV > 110 fl]

- Megaloblastic due to the lack of vitamin B-12 or folic acid.

The red cell distribution width - “RDW”- assesses the variation in volume of red blood cells. This is equivalent to the microscopic assessment of anisocytosis – variation in cell size

Increased RDW indicates the presence of more than one population of red blood cells.

The RDW expressed as CV (coefficient of variation) has been found to be of some value in the distinction between:

1) Iron deficiency anemia (RDW usually increased) and thalassaemia trait (RDW usually normal). 2) Megaloblastic anemia (RDW often increased) and other causes of macrocytosis (RDW usually normal)

Indian J for Practising Doctor, Vol: 4

Table 2:






Normocytic normochromic anaemia

MCV: 76 to 98 fl MCHC: 32 – 36%

Recent Bleeding




On Blood smear:


Normocytosis, Normochromia, Slight Anisocytosis and Poikilocytosis (ie variation in size and shape of RBC respectively)



Macrocytic anaemia With "Megaloblastic" Marrow


> 98 fl

Pernicious anemia

MCHC > 36%


On Blood smear:

Macrocytosis, Anisocytosis, Poikilocytosis (Teardrop)

Macrocytic Without "Megaloblastic" Marrow


> 98 fl

Liver Disease

MCHC > 32 - 36%


On Blood smear:

Macrocytosis, Target Cells


MCV: < 76 fl

Iron deficiency

MCHC: 32 – 36% if sub-classified as




Microcytic Hypochromic Anaemia

MCHC < 30%, if sub-classified as





On Blood Smear:


Microcytosis, Hypochromia, Anisocytosis, Poikilocytosis

Chronic Blood



Vit. B 6 deficiency

Indian J for Practising Doctor, Vol: 4

Indian J for Practising Doctor; Vol I; No. 4






more than one population of red blood cells. The RDW expressed as CV (coefficient of variation) has been found to be of some value in the distinction between:

1) Iron deficiency anemia (RDW usually increased) and thalassaemia trait (RDW usually normal). 2) Megaloblastic anemia (RDW often increased) and other causes of macrocytosis (RDW usually normal)

CBC provides all this information. On peripheral blood smear one can confirm the same findings eg one can see the presence of microcytes (small RBCs) / macrocytes (large RBCs) / schistocytes (fragmented RBC).





examination have a decisive role in diagnosis and classification of anaemia. Another investigation, which is of

importance, is the “Reticulocyte Count”.

Reticulocyte count reflects erythropoietic activity of the bone marrow and corresponds to the finding of polychromasia on a blood film. The normal range is 0.5 to 1.5% of the red cell population studied. Disease states with increased Reticulocyte counts are:

1. Hemolytic Anaemias

2. After acute hemorrhage

3. Pernicious Anaemia or iron deficiency anaemia after treatment

Disease states

reticulocyte counts are:



1. Aplastic Anaemia

2. Iron Deficiency Anaemia before treatment

3. Pernicious anaemia before treatment

Whenever a patient presents with complaints of fatigue, weakness, mild dyspnoea on exertion, simple haemoglobin estimation is done and if found to be decreased the patient is labelled as having anaemia. It is always advisable to do a CBC along with a peripheral smear, and sometimes a bone marrow examination.

It must be remembered that anaemia could be the result of a benign problem as deficiency of dietary iron or could be a feature of an underlying serious disease.We illustrate our point with two examples:

A 25 year female presented with easy fatigability, and low grade fever off and on. Haemoglobin was found to be 8.5 gm/dl and she was labelled as having anaemia, and started on haematinics. This continued for two months without any significant improvement. Finally she was referred to KG Hospital (Dept of Medicine), where the consultant asked for a CBC and peripheral smear. Her Hb was low with normal MCV indicating normocytic anaemia. Her total WBC count was 15,000/μl and platelets were mildly decreased to 98,000/μl. The peripheral blood smear revealed occasional blasts suggestive of leukaemia and the bone marrow confirmed diagnosis of acute myeloid leukaemia. Her anemaia was due to marrow replacement by leukemic blasts.

In another case, a 60 year old male was diagnosed to have anaemia and tuberculous parotitis and was on put on ATT , but there was no response to the treatment. Patient developed swelling of legs with reduced appetite, nausea and vomiting and was found to have renal failure. At this stage, the patient was referred to the neprology

Indian J for Practising Doctor; Vol I; No. 4

department of the hospital. The only positive findings were Hb 7.7gms%, urea and creatinine were 86 mg and 3.2 mg respectively and the ESR was 120mm/hr. Peripheral smear was showing a normocytic normochromic anaemia. No cause for renal failure could be identified. Hence a bone marrow was done. This revealed multiple myeloma. A renal biopsy was done which showed interstitial infiltrate of myeloma cells in the kidney. Again the anemia was due to marrow replacement by myeloma.

These two cases amply illustrate the fact that a low Hb does indicate anaemia, but for a final diagnosis as to the underlying cause of anemia a panel of investigations is needed.

The protocol followed in K. G Hospital, clinics & laboratory, is – CBC, peripheral smear, reticulocyte count and bone marrow aspiration. It helps to arrive at the correct diagnosis as early as possible.

There is a tendency among the practitioners in peripheral areas to be content with Hb estimation for diagnosis of anaemia and to put the patient on iron. Anaemia is a disease of multiple causation and its scientific management requires an exact classification which can be done only after a complete study of blood. Fortunately, simple and economical tests are available for diagnosis, classification and typing of anemia. Hb estimation merely detects the presence and severity of anaemia. However, further tests are required to classify anaemia for appropriate management. In any case of anaemia, therefore, it is not wise to begin treatment without a CBC & PBF. Nutritional anaemias may be from the deficiency a mononutrient (as iron) or a combination of deficiencies ie iron, other minerals, B 12 & folic acid. In the developing world, at least two of them – iron & folic acid – are generally deficient in diet. Pregnancy anaemia is multifactorial, including hypervolemia, need for the feotus, & iron deficiency. It needs to be seen in that context. In case of children, both preschool age & school age, presence of anaemia may be due to nutritional deficiency generally exacerbated by roundworm or hookworm infestation. Unless the child is rid of the underlying infections, he will not be benefited by nutritional supplementation and therapeutic iron. In smaller children, especially with pica, chronic lead poisoning may mimic iron- deficiency anaemia which is refractory to treatment. Very important causes of anaemia as chronic blood loss should always be borne in mind: loss of blood may be gross and evident as in excessive menstrual loss or incipient and overlooked as microscopic haematuria or blood in stools. In older patient, possibility of a malignancy should never be forgotten. Anaemia may also present as a prominent feature of connective tissue disorder or hypothyroidism.

Indian J for Practising Doctor; Vol I; No. 4

Patient Education


Anaemia (Greek, “bloodlessness”) is a blood condition involving an abnormal reduction in the number of red blood cells (erythrocytes) or in their haemoglobin content. Red blood cells are the means by which oxygen is carried to the various parts of the body. People who are anaemic develop symptoms caused by the inadequate delivery of oxygen to their body tissues. The condition is far more common in women and children than in men. Pregnant mothers and preschool children are especially prone to get anaemia. There are three primary causes: (1) reduced production of red blood cells, which may result from deficiency in nutrients or hormones, or from disease or other conditions; (2) excessive destruction of red blood cells, often a hereditary problem; and (3) excessive blood loss, such as that caused by gastrointestinal ulcers, heavy menstrual periods, or overdose of aspirin. The most usual symptoms of anaemia are pallor, shortness of breath, low vitality, dizziness, and digestive disorders.

The most common type of anaemia is iron-deficiency anaemia, which occurs when the body’s need for iron increases, as during certain periods of childhood (during the first 5 years of life; again during adolescence) and in pregnancy, or when there is insufficient iron in the diet. Pernicious anaemia, a chronic ailment that mostly affects people over 40, is a result of vitamin B 12 deficiency. Rather than a diet deficient in the vitamin, this is usually caused by intestinal malabsorption, resulting in decreased B 12 uptake. Sickle-cell anaemia is the result of a hereditary defect in the synthesis of haemoglobin. Aplastic anaemia occurs when there is severe reduction in red blood corpuscles, and when the bone marrow is unable to regenerate them. Ionizing radiation is one possible cause.

Past treatment of the condition has included removal of the spleen, repeated transfusions of blood, and a diet featuring beef or calf’s liver. Transfusions are still used in cases of acute blood loss; iron supplements for iron-deficiency anaemia and injections of vitamin B 12 for pernicious anaemia are often effective. Synthetically manufactured erythropoietin (normally produced by the human kidney) is now used to stimulate the production and growth of red blood cells. Other therapy focuses on curing the underlying causes of the nutritional or hormonal deficiency. There may be deficiency of folic acid (which is derived from green leafy vegetables) which can cause anaemia which can be diagnodsed from examination of blood and blood film. Blood transfusions and, increasingly, bone marrow transplants, are necessary forms of treatment for aplastic anaemia patients.

Balanced diet containing the required amounts of iron, folic acid and B- 12 should be taken by the vulnerable population to prevent development of anaemia.

Indian J for Practising Doctor; Vol I; No. 4



Naveen Thapliyal*, Geeta Jain**, Godavari Pandey***

Definition The ‘TORCH’ test is a group of antibody titre tests, which measures the presence of antibodies against a specific group of infectious diseases and their level of concentration in the blood. TORCH, an acronym for a special group of infections, may be acquired by a woman during pregnancy with disastrous consequences for the infant. All are grouped together because they can cause a cluster of symptomatic birth defects in newborns, collectively called the TORCH syndrome.

"TORCH" group of infections includes







toxoplasmosis. Other infections, such as hepatitis B,

syphilis, and varicella-herpes zoster.


Rubella, the virus that causes German measles


Cytomegalovirus, or CMV,


5. Herpes simplex virus, the cause of genital herpes

TORCH infections can affect any human; children, men, and non-pregnant women may also catch these infections. However, their importance lies in the fact that they can be they can be transmitted to the fetus while it is in the womb. When a mother is exposed during the first 5 months of pregnancy, serious fetal complications may occur. (Table)

* Assistant Professor, Pathology, ** Assistant

Professor, Obstetric & Gynaecology, *** Senior Resident, Obstetric & Gynaecology, Dr.S.T.M. F.H. & Medical College, Haldwani (UTTARANCHAL)

Table: Complications of TORCH Infections During Pregnancy

Miscarriage . Small-for-gestational-age, or SGA. Congenital heart disease (heart defects the child is born with) Cataract (clouding of the lens of the eye), blindness, or significant visual impairment. Hearing impairment, including deafness. Microcephaly (Small head size). Mental retardation or other learning, behavioral, or emotional problems. Low blood counts (anemia). Liver or spleen enlargement. Pneumonia. Skin rash - usually reddish-purple or brown. Involvement of the central nervous system (encephalitis, calcium deposits in the brain tissue, and seizures). Jaundice. In addition to these symptoms, each of the TORCH infections has its own characteristic differentiating symptom cluster in newborns.

Brief Description:


Toxoplasmosis is caused by Toxoplasma gondii, a parasite that the mother can acquire from handling infected cats, drinking un-pasteurized milk, or eating contaminated meat. The infection is carried transplacentally, and may cause infection of the eyes or central nervous system. The organism can invade brain or muscle tissue and form tissue cysts. Contracted early in pregnancy, toxoplasmosis is more likely to cause a miscarriage or serious birth defects However, the later in pregnancy the mother is infected, the higher the

Indian J for Practising Doctor; Vol I; No. 4

probability that the fetus will be infected. The incidence of toxoplasmosis in newborns is 1 in 1,000 live births.

produces symptoms resembling those of infectious mononucleosis. About 1-2.2% of newborns are infected with CMV. Of

retardation (30%). Newborns that acquire

Syphilis Syphilis is caused by a spirochete (spiral- or coil-shaped bacterium), Treponema pallidum. It is transmitted in the adult population by sexual

this group, 10% will have measurable symptoms. The mortality rate for these symptomatic newborns is 20-30%. Surviving infants with CMV may suffer from hearing problems (15%) or mental

intercourse. About 2-5% of children born


during the birth process or shortly

to mothers diagnosed with syphilis will


birth may develop pneumonia,

have the disease at birth. Syphilis was

hepatitis, or various blood disorders.

added to the TORCH panel because of a rapid increase in reported cases since

Herpes simplex virus (HSV):

1990. Syphilis can cause early delivery, miscarriage, or stillbirth. The mortality rate in infants infected with syphilis is about 54%. With widely available

Herpesvirus infections are among the most common viral infections in man. They are spread by oral, as well as genital, contact. Estimatedly, between 1

antibiotic treatment, Syphilis is now

in 1,000 and 1 in 5,000 infants are born

taking a back seat among the sexually-


HSV infections. About 80% of

transmitted infections.


infections are acquired during the

Rubella :

Rubella is a virus that has a seasonal pattern, with epidemics most likely in the spring. Between 0.1-2% of newborns will be infected with rubella. Birth defects are most likely (85%) in infants infected during the first eight weeks of pregnancy. Infants born with rubella may already show signs of heart disease, retarded growth, hearing loss, blood disorders, vision problems, or pneumonia. They may also develop problems later in childhood, including autism, hearing loss, brain syndromes, immune system disorders, or thyroid disease.

Cytomegalovirus (CMV):

Cytomegalovirus belongs to the herpesvirus group of viruses. It can be transmitted through body secretions, as well as by sexual contact; some newborns acquire CMV through the mother's breast milk. In adults, it

birth process itself; the virus enters the

infant through its eyes, skin, mouth, and

upper respiratory tract. Of the infants

born with HSV infection, about 20% will

have localized infections of the eyes,

mouth, or skin and about 50% will

develop disease spread throughout the

body (disseminated) within 9-11 days

after birth. Disseminated herpes infections attack the liver and adrenal glands, as well as other body organs. Without treatment, the mortality rate is 80%. Even with antiviral medication, the mortality rate is still 15-20%, with 40- 55% of the survivors having long-term damage to the central nervous system. It is critical for the doctor to diagnose HSV infection in the newborn as soon as possible, for effective treatment.

Who is a candidate for the test? Any pregnant woman who has bad obestetric history or has been exposed to the above infections is a candidate for screening.

Indian J for Practising Doctor; Vol I; No. 4

How is the test performed? A blood test measuring antibody- titers is used to detect antibodies to any the suspected TORCH organism. An antibody is a special protein made by the immune system that helps fight infections. The body makes specific antibodies in response to specific infections. These antibodies are made in large amounts when an infection occurs. When the initial sample of blood is taken shortly after exposure, the body may not have had enough time to start making antibodies yet. However, a woman can have antibodies to the infection in her blood because of an old infection or from a vaccine. A second sample of blood is usually taken 10 to 21 days later to see if blood antibody levels or titers against the infection are rising. This generally means that a new infection, instead of an


Manzoor Kadri

TORCH is an acronym for a group of infectious diseases that, while infecting the pregnant women, may cause birth defects in their newborns. The test is a screen for the presence of

any of the antibodies to these infections. Confirmation of an active infection may

require more

specific tests.

The following tests make up the TORCH panel:

old one, is present. If an old infection is the cause of antibodies in the blood, the level of antibodies will not rise with the second blood sample, as it does with a new infection. This is important, because old infections usually do not result in harm to the fetus, except in the case of herpes. Only infections that are newly caught during the early part of pregnancy usually put the fetus at risk.

What do the test results mean? A "negative" test means that the woman does not seem to have a new TORCH infection. A positive test means that high or increasing levels of antibodies were detected. This generally means that the mother has caught a new TORCH infection.

TOxoplasmosis is a parasitic infection that can be passed from mother to baby through the placenta during pregnancy. An infection with Toxoplasma gondii can cause eye and central nervous system infections as well as brain and muscle cysts. If acquired during the pregnancy, it may result in a miscarriage or cause birth defects, though this depends on the time during the pregnancy in which the infection was acquired by the mother. Toxoplasmosis is acquired by ingesting the parasite when handling the excrement of infected cats, drinking unpasteurized goat’s milk, and, most commonly, by eating contaminated meat.


German measles. If contracted early in





Indian J for Practising Doctor; Vol I; No. 4

the pregnancy, the infant may develop heart disease, retarded growth, hearing loss, blood disorders, vision problems, or pneumonia. Problems that may develop during childhood include autism, brain problems, immune disorders, or thyroid disease.


viral infection that the mother may have acquired. More than half of all American adults have been infected with CMV at some point in their life and, in most cases, it does not cause severe illness. It may pass to the fetus during the birth process but can also infect newborns through breast milk. Infected infants may have severe problems, such as hearing loss, mental retardation, pneumonia, hepatitis, or blood disorders.




common viral infection. The two most common infections with HSV are “cold sores” affecting the lips and genital herpes. Both of these infections can recur. HSV is most commonly acquired through oral or genital contact. Newborns who contract the virus usually do so during travel through the birth canal of a woman who has a genital HSV infection. The virus may spread throughout the newborn’s body, attacking vital organs. Treatment with specific antiviral medication should begin as soon as possible in the infected newborn. Even if treated, surviving babies may have permanent damage to the central nervous system.

TORCH test is performed to screen for these infectious diseases that can cause birth defects in newborns and illness in adults. The test is indicated when the mother becomes ill while pregnant or if a baby is born with


congenital abnormalities suspected to be caused by an infection with one of the diseases

Blood Collection

The TORCH panel requires a sample of the infant's blood. Samples from infants are usually obtained by the heel-stick procedure when only a small quantity of blood is needed. The baby's foot is wrapped in a warm cloth for five minutes, to make the blood flow more easily. The foot is then wiped with an alcohol swab and a lancet is used to stick the baby's heel on one side. It is important to avoid the centre of the heel, in order to prevent an inflammation of the bone. No special preparation, other than sterile technique, is required. The only complications associated with the test are those resulting from the heel- stick technique itself (ie scarring, infection of the bone, cellulitis, small lumpy calcium deposits) and the possibility of inaccurate test results.


Normal. The normal result denotes normal levels of IgM in the infant's blood. IgM is a specific class of antibodies that seeks out virus particles. In contrast to adults, IgM is the most common type of immunoglobulin in newborn children. It is, therefore, the most useful indicator of the presence of a TORCH infection. Abnormal results. The abnormal (positive) finding would be high levels of IgM antibody. The test can be refined further for antibodies specific to given disease agents. The TORCH screen, however, can produce both false-positive and false-negative findings. Doctors can measure IgM levels in the infant's cerebrospinal fluid, as well as in the blood, if they want to confirm the TORCH results.

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Usual Concerns of the mother If I have a positive antibody test, does that mean I am infected? A positive IgG antibody test is usually a sign of past-exposure to the TORCH agent and is not a marker for current active infection. Detection of IgM antibody is more difficult, and false negative and false positive results may occur. Any positive results should be confirmed with additional specific tests before the diagnosis is considered valid. If the doctor suspects that you or your newborn may have one of these infections, even though the results were negative, other tests for the suspected infection should be done.

To make the diagnosis of an active infection with one of the TORCH agents, more specific confirmatory tests may be required. In a baby, cerebrospinal fluid testing (requiring a lumbar puncture or “spinal tap”) is often used to confirm toxoplasmosis, herpes and rubella; urine may be cultured for cytomegalovirus; and skin lesions may be scraped and cultured for herpes simplex virus. Making the diagnosis of toxoplasmosis in the pregnant woman or the baby may require additional blood samples, which are sent to a reference laboratory that specializes in such tests.


Answers to Medical Quiz: 4

(from page


1) Lead level 2) Blood film; long-bone x-ray 3) Lead poisoning 4) Start treatment again with strict supervision by the community care team.

Chronic lead poisoning can occur after chewing or sucking pain from old windows or doors. Lead from burning batteries, lead shots for fishing, and old water pipes pose a similar risk. Children from southeast Asia may get lead poisoning from using surma or kajal – eye make up prepared from lead. Affected children may have pica or a compulsive eating disorder. Children working as papier mache workers in Kashmir, who have a habit of mending their brushes with lips, run the risk of getting lead poisoning as the base of most paints is lead oxide. Patients are usually anaemic, are usually diagnosed as having iron-deficiency anaemia, but fail to respond to iron-therapy. Shortly, other clinical features are superimposed on anaemia. They have obstipation, abdominal pain, headache, and behavioural problems, along with a deteriorating school performance.

When poisoning is severe, the child can have convulsions, irritability, loss of consciousness, which may lead to coma and death.

The lead level can be measured; the blood film shows hypochromic, microcytic red cells, and basophilic stippling. Gums may show lead lines. The long-bones show lead-lines which affect mainly their ends. Lead flakes which are radiopaque may be seen on abdominal x-ray. Lead poisoning is one of the causes of increased intracranial pressure, and thus papilloedema is common.







affected environment is very helpful.

Chelating agents (D-penicillamine in mild cases; Ethylene-diamine-tetra-acetic acid or EDTA, in severe cases) are used.

Indian J for Practising Doctor; Vol I; No. 4

Influenza: A Reminder

Bashir Gaash

Influenza has been known since antiquity, at least since 437 BC. The two faintly remembered epidemics of history could have been the ‘English Sweat’ of 1485 and 1551. Nevertheless, the first pandemic which brought the deadly virus to the world stage was the ‘Spanish’ or ‘swine’ influenza of 1918.

Influenza outbreaks occur frequently in all parts of the world including the developed ones. In the UK, for example, increased number of cases occur each winter with an annual mortality of 3000-4000.

Influenza, known since 400 BC, is one of the last great uncontrolled ‘plagues’ of mankind. It will continue to strike mankind off and on because of the inherent survival techniques of the virus

The virus: Influenza virus has 3 different strains, A, B & C, which differ in their ribonucleo-protein moieties. The virus produces 11 different proteins - 3 are surface proteins, while internal proteins are needed for varied functions including keeping the virus alive and virulent. The type A virus has a capacity to undergo consistent genetic changes of their nucleic acids, resulting in annual phenotypic modifications and changes in their surface antigens. Alterations in antigenic structure help the virus to dodge the body’s natural and artificially- induced immune defences. Four of the

internal proteins make up the polymerase enzyme system (functionally transcriptase complex) which triggers replication of virus in the infected host cells.

The virus consists of a central core (nucleocapsid) containing internal proteins and the viral RNA. The major structural protein, matrix protein (M1), integral to the nucleocapsid is responsible for virion integrity. Glycoproteins, which are needed for entering the host cell, project as ‘spikes’ through the lipid envelope.






some 90-120 nm in diameter.

Growth & Replication: The replication cycle of the virus begins when it attaches to specific receptors on epithelial cells lining the respiratory passages. These specific receptors are the terminal sialic (neuraminic) acid residues on the oligosaccharide side-chains of the susceptible cells. The virus enters the cell and gets uncoated so that the viral nucleocapsid (containing RNA and enzymes) is released in to the host cell cytoplasm. Once the nucleocapsid reaches the nucleus, the viral RNA and enzymes direct the formation of mRNA for manufacture of progeny RNA. The RNA matures into nucleocapsid followed by assembly and thus formation of new virus which leave the cell and infect other susceptible cells.

Epidemiologic and clinical behaviour:

despite similar morphology, the 3 strains show different epidemiologic and clinical patterns.

Type A is associated with most of the widespread epidemics and is the only one to produce occasional pandemics. Clinically also the infection is severe with an increased predisposition to secondary bacterial infections. The major

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2 surface proteins, Haemaglutinin (HA) and neuraminidase (NA) undergo subtle, minor changes in structure almost

annually, because of point mutations in viral RNA genes coding for them. (This

is because of the absence of a proof-

reading mechanism to correct mistakes

arising during replication of viral nucleic acid). This annual variability of the type

A virus surface protein, the antigenic

drift, is a major reason for their success

to evade human immune system, and

causing frequent outbreaks and epidemics.

Antigenic drift, which is an ongoing process, is greater for the HA antigen, and leads to distinct alterations in the reactivity of the surface proteins every 2-3 years. These mutations can be detected in the laboratory. These antigenic changes are responsible for the reduced capacity of pre-existing antibodies to previously experienced influenza virus. The failure of neutralization by existent antibodies helps in quicker and wider uptake and dissemination of virus in the body.

Type B generally causes milder illness, but spectrum is broader, from common-cold like illness to typical severe influenza. Type B infection is commoner and more symptomatic in children than adults; infection in adults is milder or asymptomatic. The number of

patients requiring hospitalization is 1/4 th of that with the type A. The mutation rate

is lower than that in type A, therefore

antigenic variability is less.

virus is either

asymptomatic or causes only mild, common-cold like mild symptoms (‘the touch of flu’).




Animal Reservoir: Many animals and birds function as hosts to type A viruses which bear genetically similar but antigenetically different versions of surface haemaglutinin and neuraminidase antigens. Wild avian species are primary extra-human reservoirs of type A virus. When humans are infected with these novel viruses, a localized outbreak may herald a global pandemic. This is because the new surface antigens are not recognized by the human immune defence system, thus the virus meets no resistance to spread at all.

Type A is far more dangerous because of the antigenic drift, extra-human reservoir, potential for pandemics, propensity to cause severe illness, and ability to predispose to secondary bacterial pneumonia. The lower mutation rate and lack of mammalian or avian reservoir for the type B makes it a lesser clinical and epidemiologic problem.

Infectivity: The incubation period of type A influenza is 3 days and of type B virus 4 days. Virus replication in the respiratory tract in adults peaks 48 hours after infection. Newly formed ‘progeny’ virions are shed in nasal secretions and saliva from 1-7 days after infection.

Children start shedding the virus earlier,

ie from the first day, and much longer, ie

upto 13 days after infection. The main transmitters of influenza are preschoolers and school-going children.

Antigenic Shift: Emergence, in the type

A virus, of an HA protein that is novel to

the population results in a large epidemic

or pandemic. In the 20 th century 5 such pandemics have occurred. The deadliest

of these, the ‘Spanish (Swine)’ influenza,

lead to 20 million deaths, particularly among young adults. The last occurred in 1977 with reappearance of the HA

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Influenza elicits strong immune response, yet it continues to occur regularly in the population. This virus causes epidemics of ‘flu’ annually and pandemics at frequent intervals. This is because influenza virus is not only a human virus but has a complex relationship that includes replication in several hosts. Thus influenza A virus infects not only humans but also pigs, birds, horses, mink, and some aquatic mammals such as seals and whales.

At least 14 subtypes of haemagglutinin (H) protein are present in viruses that infect birds; 3 of these can infect human. Similarly there are 9 neuraminidase (N) surface antigens. Viruses that cause worldwide infections (pandemics) can be classified according to their H & N types. Each pandemic is characterized by a new combination (from recombination/reassortment):

The 1918 pandemic was H1N1 The 1957 ‘Asian Flu’ was H2N2 The 1968 ‘Hong Kong Flu’ was H1Ni, and the 1977 flu was, again, H1N1.

These dramatic shifts of H & N serotypes result from the exchange of genome segments by mammalian and avian influenza viruses. Although it is presumed that viruses of one species (as birds) are not efficient at infecting another species (humans), there is evidence of direct infection of human beings by an avian strain (H5N1) in 1997. Since no man will have immunity against such a novel virus, large epidemics, even, pandemics can potentially occur. The only consolation is that such alien viruses are incapable of efficient spread in human beings, and the man proves the dead-end host. There is no man-to-man transmission in such viruses.

Pigs provide very good hosts to both human and avian viruses – the lining of their throats contains receptors for both types of viruses. Thus, pigs act as non-selective hosts for mixed infections of both human and avian types, and thus a good medium for reassortment of H & N of different species. This gives rise to new viruses which can lead to reinfection of human population.

Because of the dense human population in southeast Asia, large number of people come in daily contact with domesticated pigs, ducks, fowl, & geese. There is epidemiological evidence that the 1957 and 1968 pandemics originated in China, and that human N & H serotypes are circulating in wild-fowl population. The intermixing of large numbers of human beings, migratory birds, and domesticated swine & birds provide a continually expanding opportunity for recombinations and reassortments of different influenza viruses and thus emergence of newer viruses.

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antigen similar to those of the 1918 and 1933-34 pandemics.

Curiously all these sudden major changes occurred in China. Most of them arose from genetic re-assortment of surface antigens between human and mammalian/avian strains. Generally, one sub-type of type A infects only a particular species, but when cross- species transmission occurs, genetic re- assortment takes place between the transmitted subtype and type A virus in the recipient host. A new virus subtype is formed with surface proteins from either parent subtype. This virus has the capability to infect the 3 rd host, the human being. The 1957 ‘Asian’ influenza virus obtained 2 genes coding for its HA & NA surface proteins and one gene coding for its internal proteins from an avian subtype. The remaining 5 genes were derived from the pre-existing strain in circulation since 1933-34 pandemic.

15 different haemagglutinin (HA) proteins [H1 to H15] and 9 different neuraminidase (NA) proteins [N1 to N9] are found in influenza strains infecting different hosts including man. However, only 3 of the former (H1, H2, & H3) hade been encountered in all type A strains which had caused epidemics among humans till 1997, when the first evidence of direct infection of man from a virus with non-human HA antigen (H5 avian) appeared in Hong Kong. In 1999, H9 avian got transmitted to humans, who proved to be ‘dead-end’ hosts.

Since the pandemic of 1977 (Russian flu), 2 type A viruses have been circulating among humans: H1N1 (Russian) and H3N2 (Hong Kong). During the last 30 years, though avian

viruses have infected human beings, they have not been able to lead to any major outbreaks. This is because these viruses could establish among human beings and thus there was no man-to-man transmission.

Immunity: Infection elicits both humoral and cellular immune response. Antibodies are protective whether systemic (in serum) or local (at various mucosal surfaces as nose and other areas of the respiratory tract). Humoral response could be life-long but for the antigenic drift shown by the virus which leads to waning of protection over time. Virus-specific CMI (through cytolytic T- cells) leads to destruction of virus-laden cells in the respiratory tract and thus helps in recovery from infection. The cell-mediated immunity is more specific, less amenable to antigenic drift, highly effective but does not take effect till 2-3 days after the initial infection, and is short-lived (lasts for only a few weeks).

Protection from the virus is mainly through humoral response; role of the CMI in early stages is minimal. However, cellular responses take over later and play more dominant part in limiting the already established infection and in eliminating the virus. Elimination of infection is accomplished by destruction the virus-laden, infected cells. Regeneration of the destroyed mucosa occurs 7-10 days after the start of infection.

Transmission: Influenza virus is transmitted from person-to-person through droplets (in nasal secretions and saliva during sneezing & coughing) as well as during the normal daily contact among humans. Thus fomites are also important in spread of infection.

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Pathogenesis: The virus may infect whole respiratory tract from nose down to lungs. Droplets are usually <2 mm, land in the lower respiratory tract, attach to the epithelium and initiate infection. Absence or gross deficiency of the type- specific surface antibody (IgA) facilitates establishment of infection. The establishment of infection depends on:

Various non-specific and virus- specific host factors: Susceptibility of the local mucosal columnar cells makes adherence of virus easier. Muco-ciliary mechanisms get rid of large quantity of virus in non- smokers. Antibodies to type B can not protect from type A infection. Similarly, previously acquired antibodies to either type may not afford any protection to subsequent infection.

Viral factors as quantity of virus inhaled: Larger viral dose overwhelms the local defences.

The intrinsic virulence of the virus, which in turn depends on the type and subtype and changes with antigenic drift and shift.

Within 5-6 hours of establishment of infection, progeny viruses are released to enter other susceptible cells. Lytic replication of the virus leads to almost total destruction of the ciliated epithelial cells of the respiratory tract.

Infection in the nasopharynx leads to a loss of ciliated epithelium – an important nonspecific respiratory defence - in nasopharynx and trachea, which paves way for secondary bacterial infection (streptococcal, staphylococcal, H influenza) in the lower respiratory tract. Fatal pneumonia may ensue in the elderly.

Bronchoscopy shows de-ciliated, oedematous, and acutely inflamed bronchi, trachea and larynx. This results in desquamation of cells.

Local defences & recovery:

1) The virus triggers the interferon release very effectively which coincides with onset of symptoms, levels peaking some 24 hours later. Interferon plays an important role in reducing replication of virus and in limiting spread of virus in the respiratory tract. The systemic features of malaise, aching pain in back and joints, and fever are associated with release of various pro-inflammatory cytokines including interferon, interleulkin-6 and tumour necrosis factor-α.

2) Other nonspecific host factors are soluble factors, such as lung surfactants, sialylglycoproteins and alveolar macrophages take up the virus ands thus prevent it from attaching to and invading the susceptible epithelial cells.

3) In the first (primary) infection, locally elicited antibody response is important. IgA is secreted locally; IgG is derived from the transudate spilling into the respiratory tract secretions from the bloodstream as a result of inflammation. Both these prevent the virus from attaching to the epithelium or entering the cell, by blocking the activities of haemagglutinin proteins. In 80% cases, a primary serum IgG response is seen, which again has to reach the respiratory mucosa for neutralizing the virus.

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Immunologic memory of the local IgA which is specific for the haemagglutinin and neuraminidase proteins of virus could ward off all subsequent infections, provided there were no antigenic drift or shift. Same applies to the serum antibody, mainly IgG.


Clinical presentation In temperate areas, infections usually occur in winter with a threat of outbreaks from December till March. However, cases occur throughout the year. In the UK, a weekly incidence of influenza-like illnesses greater than 400/100,000 population is considered to

constitute an infectious rate of epidemic


In adults, influenza is an acute infection. with an incubation period of 2- 3 days. Usual presentation, after an incubation period of 2-3 days, is an abrupt onset of rhinitis, sore-throat, non- productive cough, with fever (38°-40°C), malaise, headache, chills and myalgia. Clinical picture is of pharyngitis and tracheo-bronchitis. Infection is more severe in smokers. Majority of cases are typical; a minority may be asymptomatic (sub-clinical) or present as simple rihinitis and sore throat.

When uncomplicated, the acute episode lasts for 3-7 days, though weakness may last another week.

In children and adolescents, influenza is slightly milder and of a shorter duration. Subclinical and minor infection is commoner in younger children. However, there could be severe

presentations with high fever and febrile


Children may exhibit more lower respiratory tract involvement presenting as croup or pneumonia. There may be extrapulmonary manifestations as vomiting, abdominal pain and myositis.


In some cases influenza may be complicated by:

1) Myositis: This is commoner in type B infection, and in children recovering from the illness but may occur during acute phase with direct viral invasion of muscle. It begins with acute pain and tenderness in gastrocnemius and soleus muscles leading to extremely painful walking. There is a transient elevation of serum creatine phosphokinase. Very rarely heart muscle may be involved with tachy-dysrhythmias, and elevation of cardiac enzymes. Patients may suffer myoglobinuria and renal failure. The majority recover within 3-4 days. 2) Reye’s syndrome: It occurs particularly in paedriatic influenza patients receiving aspirin. There is acute encephalopathy with cerebral oedema, with fatty degeneration of the liver. The cerebrospinal fluid is normal except for its raised pressure. Liver function tests are abnormal. 3) Pneumonia: Involvement of lung occurs usually in those at high-risk of getting influenza as the elderly, and those with COPD and other cardiopulmonary diseases. However, in some pandemics (as the 1957 Asian pandemic) 1/4 th of all healthy persons got it. The virus replicates in the alveolar epithelial cells. The patient becomes overwhelmingly toxaemic and exhibits a rapid respiratory rate, tachycardia, cyanosis, high fever and hypothension. Chest x-ray shows patchy consolidation in two or more lobes; cavitation or pleural effusion implies bacterial super-infection. Pathological picture is shared by many viruses invading lower respiratory tract: thus, there is interstitial pneumonitis with severe hyperaemia and broadening of the alveolar walls together and mononuclear cell infiltration. The patient may die within 1-4 days. Such severe presentation is usual with

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type A infection. The survivors begin improving some 5-15 days after the start of pneumonia. Usually there are no sequelae. 4) Secondary bacterial infections:

Superinfection with pneumococcus, staph areus and H influenza is common. This is probably because the viral neuraminidase-1 induces apoptosis (programmed cell death) in the invaded epithelial cells and leucocytes, which in turn permits bacterial overgrowth. There is already existent colonization with bacteria in cystic fibrosis and occasionally in COPD, excessive smoking and environmental pollution. Mortality is greatly increased with bacterial superinfection.

Diagnosis is mainly clinical and difficult in absence of an outbreak. During an epidemic an adult with a diffuse interstitial pneumonia is likely to be suffering from influenza virus pneumonia.

Influenza in special categories:

1) Pregnancy & influenza: There is no definitive proof of congenital anomalies or haemotoligical malignancies with influenza. However, in a pandemic caused by a novel virus, pregnant women may contract fatal disease in 2 nd or 3 rd trimester. It was observed in both the 1918 and 1957 pandemics.

2) At risk groups: These include the elderly (75 yr or above, the debilitated, persons with COPD (including asthma and bronchitis), diabetrics, ischaemic heart disease, or renal disease, immuno-compromised persons, and residents of closed institutions where attack rate is very high. The majority of at-risk persons have some degree of immune- compromise. For example, the elderly suffering from thymus involution resulting in T-cell insufficiency. Mortality rate among the elderly with one or more risk-factors attributable to influenza among the elderly is 0.8% as compared to 0.02% in those under 65. In obstructive and occupational respiratory diseases, and among smokers, local epithelial defences (mucociliary clearance) are weakened. Influenza exacerbates asthma in children. Congenital disorders (cystic fibrosis), organ transplants, and HIV infection increase risk of death among young adults. In ischaemic heart disease, hypoxia and myocarditis both increase the mortality. HIV impairs T-cell response which in normal individuals helps in getting rid of virus. Elderly diabetics have a 6-fold increased risk of requiring hospitalization for ketoacidosis , with adverse outcome. The increased risk among them is related to their cardiovascular complications and deranged metabolic control. ************

Further reading:

Bender BS, Small PA. Influenza: pathogenesis & host defences. Semin Respir Inf 1992; 7:38-45 Bush RM, Bender CA, Subbarao K. Predicting the evolution of human influenza A. Science 1999;


Couch, RB. Influenza: prospects for control. Amm Intern Med 2000; 133: 992-8 Das P. Flu experts feel countries are unprepared for a future pandemic. Lancet 2001; 357: 1419. De Jong JC, Rimmelzwaan GF, Fouchier RAM. Influenza virus: A master of metamorphosis. J Infect 2000;


Ellis J, Joseph C, Zambon M. Fifty years of influenza surveillance. Commun Dis Public Health 1999; 2: 81-


Nguyen-Van-Tam JS. Epidemiology of influenza. In: Nicholson KG, Webster RG (ed)> Textbook of nfluenza. Oxford: Blackwell, 1998. Olviera EC, Marik PE, Colice G. Influenza Pneumonia: a descriptive study. Chest 2001; 119:1717. Webster RG. Immunity to influenza in the elderly. Vaccine 2000; 18:1686-9 Potter CW. A history of influenza. J Appl Microbiol 2001; 91:572-9 Simonsen L. The global impact of influenza on morbidity and mortality. Vaccine 1999; 17 Suppl 1

Indian J for Practising Doctor; Vol I; No. 4

Patient Education


Influenza is an acute, infectious, contagious disease of the respiratory tract, especially the trachea, colloquially called flu or, less often, grippe. The symptoms of a simple attack include dry cough, sore throat, nasal obstruction and discharge, and burning of the eyes; more complex cases are characterized by chill, sudden onset of fever, headache, aching of muscles and joints, and occasional gastrointestinal symptoms. In uncomplicated cases, symptoms fade and temperature drops to normal in a few days; the risk of death increases if the disease is accompanied or followed by viral or bacterial pneumonia.

Since the 16th century, at least 31 influenza pandemics (very widespread epidemics) have been described. The most destructive epidemic of modern times, that of 1918, is estimated to have caused 40 million deaths.

The three types of causative virus, known as A, B, and C, were isolated in 1933, 1940, and 1950, respectively; the first two are responsible for disease epidemics. In 1941 it was shown that influenza could be controlled by a vaccine containing virus. The problem of immunization is complicated, because the different types are antigenically unrelated and so do not induce cross-immunity. It is also complicated because immunity to a specific virus persists for less than a year and because these viruses exhibit the

unique quality of periodically mutating to negate any immunity people may develop. The problem has been met by creating polyvalent vaccines: vaccine against type B is combined with vaccines against the subtypes of type A as they evolve. This has required a worldwide surveillance system to detect altered virus forms as soon as they arise, so that adequate stocks of vaccine can be prepared in time. Because it would be prohibitively expensive to prepare vaccine for the entire population each time the virus mutated, vaccine was for a long time administered only to those most susceptible to developing pneumonia when they contract influenza.

The different antigenic types of influenza virus appear in cycles; for instance, the variant appearing in the 1978-1979 season was identical to the virus that was widespread during the early 1950s. Some evidence exists that pandemics occurring 60 to 70 years apart are caused by the same form of virus. Based on this theory, public health officials expected in 1976 that the same virus that caused the 1918 pandemic would reappear. When this form of the organism (known colloquially as swine flu) was isolated from army recruits in Fort Dix, New Jersey, United States, vaccine against it was prepared, and mass inoculation was carried out in the United States. No outbreak, however, of that form of influenza occurred.


hydrochloride, which is taken orally, is effective in preventing influenza caused by influenza A virus, and also moderately effective in treating influenza



Indian J for Practising Doctor; Vol I; No. 4

A after symptoms have appeared. Amantadine is used as an adjunct to immunization for high-risk patients, but immunization is still considered the most effective way to combat the disease. Human infection with avian influenza A (H5N1) viruses were identified in Hong Kong in 1997. As of January 1998, a total of 16 cases and three suspected cases of this new type of influenza had been confirmed. Individuals with high levels of exposure to infected poultry or direct exposure to the virus in the laboratory, or health-care workers, are thought to be at most risk.

Since the 1918 pandemic there have been two other pandemics, in 1957

and 1968, each of which also killed millions around the world. Medical experts now believe it is a question of when and not if another flu pandemic causes infection on a global scale and maybe affects millions of people. Potentially the situation is worse now because of the explosion of international travel in recent decades. However, improved communications and the World Health Organization's monitoring work mean that a deadly strain could be isolated more quickly, allowing doctors more time to formulate a vaccination. Finally, antibiotics, while ineffective against viruses, would be crucial for tackling infections that many victims would develop as a result of influenza.

against viruses, would be crucial for tackling infections that many victims would develop as a result

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Cold Chain Maintenance

Rubina Shaheen

A vaccine must have two characteristics, one is safety and other is potency. The potency of a vaccine is maintained by cold chain. The cold chain is a system of storing and transporting the vaccines at recommended temperatures from the point of manufacture to the point of use. The essential elements of the cold chain are:

Personnel to organize and manage vaccine distribution.

Equipment for storage and transport of vaccine.

Transport facilities

Maintenance of equipment and


Why to maintain the cold chain? Maintenance of cold chain system is important because the vaccines lose their potency if exposed to adverse temperatures. The tables below show the sensitivity of different vaccines to heat and freezing.

Monitoring of Cold Chain:

Monitoring of cold chain regularly is important if you expect it to function effectively and efficiently. The things you will need to monitor are:







Storage temperature

Potency tests


Arrange supplies according to demand and utilization so that there is a regular and smooth flow of vaccines. It

will avoid artificial shortages created by accumulation of large balance stocks at places where the programme is not functioning effectively.



Most sensitive

BCG(after reconstitution) OPV Measles Hepatitis B DPT DT

Least sensitive



TT(Tetanus toxoid)


Vaccines that can be frozen without harm











Hepatitis B



Storage temperature:

All vaccines are to be retained at temperatures between +2 to +8 0 C. A break in the cold chain is indicated if temperature rises above +8 0 C or falls below +2 0 C in case of ILR & other refrigerators.

Potency tests Vaccines produced by production unit are tested for potency before these are released in the market. However, there is no guarantee that this vaccine will remain potent till it is administered to the child; that dependents on a competent cold chain. To actually monitor vaccine potency in the field, one has to send a random sample of oral polio vaccines lifted from field to laboratory for testing potency. This activity is, in addition, and independent of production-testing.

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The concentration of live attenuated polio virus shall constitute the parameter to measure potency. The titration is performed on HEp-2 Cincinnati cells with passage level of <350.

Cases where potency of vaccine from field needs to be checked

When you suspect break in the cold chain

To monitor the efficiency of storage in the field.

As a part of evaluation of vaccination e.g.; sero-conversion studies.

Testing facilities are available at the:


Central Research Institute, Kasauli (H.P).

National Institute of Communicable Diseases, Delhi,










S. K. Institute of Medical Sciences Soura, Srinagar, Kashmir.

OPV has been selected as “indicator” of cold chain as this vaccine is more heat-labile than other vaccines and is easier to test.

Collection of OPV sample for potency testing

Select a used or unused vial of OPV. The used vial must have at least 2ml of vaccine.

Affix an adhesive label on the bottom of the vial name of the Primary Health Centre and date of collection.

Ensure that manufacturer’s label is intact.

Place the labeled vial of OPV in a polythene bag and affix second label indicating the name of the Primary Health Centre on the polythene bag.

Roll the polythene bag around the sample and secure it by a rubber band.

Place the polythene bag containing the sample in vaccine carriers containing enough ice packs.

The samples so collected should be rushed to the headquarters in vaccine carrier observing cold chain, known as the reverse cold chain. If delay is anticipated in transmitting the sample for testing, such samples should be kept in a deep freezer/ILR till they are sent to the testing laboratory.







Total number of samples to be collected from the state in a year is prescribed. Roughly the number of samples to be collected is the same as the number of PHCs in the state.

Out of the total number of samples, 30 percent should be from out-reach session PHCs, 15 percent from district headquarters and 5 percent from walk- in coolers.

For samples collected from out-reach sessions and PHCs, care sold be taken not to take more than one sample from one area/ institution in a year.

The team formed to collect samples should plan their visits in advance and also be responsible for maintenance of the reverse cold chain.

The storage point for vaccines should be codified; so that relationship between samples and storage points can be easily established.

Te samples collected should be rushed to headquarters in a vaccine carrier observing cold chain (reverse cold chain.) and kept in the deep freezer until they are sent for testing in the laboratory.

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The VVM status of the sample should be recorded at the time of collection of sample and the time of receipt of vaccine in laboratory.

Cold chain equipments:

There are equipments of different capacity for storage of vaccines at different levels as under:


These are used for bulk storage of OPV, measles vaccines and also to prepare frozen ice-packs at state stores. They maintain a temperature around minus 20°C. They are available in sizes of 16.5 Cu. Mt. and 32 Cu. Mt. These are provided with two identical cooling units and a standby generator sets. Bulk quantities of ice packs are also made and stored in the walk-in-freezers.


These are used for bulk storage of vaccines at State and Regional stores. They maintain a temperature of +2°C to +8°C. They are available in sizes of 16.5 Cu. Mt. and 32 Cu. Mt, and are used for storage of large quantities of vaccines at state and regional level. This is provided with two identical cooling units and standby generator sets with automatic start and stop facilities. They are also provided with temperature recorder and alarm systems. Walk-in-coolers are established at regional levels, which store vaccines for about 4-5 districts. Both, walk-in collers & walk-in-freezers store three months of requirement of vaccines + 25% buffer stock for the districts they cater.

Deep freezers:

Deep freezers supplied under immunization programme have a top opening lid. The cabinet temperature is maintained between -18° to -20°C. This

is used for storing of OPV and measles vaccine and also for freezing ice packs. In case of power failure, it can maintain the cabinet temperature for 18 to 26 hours, if not opened. These are available in two models, having a capacity of 300 litres and 140 litres. The chest freezers are provided with special insulation, which helps in maintaining inside temperature, in case of electricity failure, for much longer time. The 140 litre-chest freezer can store 65000 doses of vaccines. The 300 litre capacity freezer at district headquarters are to supplied for :

Storage of OPV& measles vaccines

Preparations of ice packs.

The 140 litre capacity freezer at PHC headquarters are to be supplied for:






Preparations of ice packs.


The diluents should not be kept in deep freezers. These should be stored at a temperature between +2° to +8°C and should be transported along with the concerned vaccine.

Preparation of Ice Packs:

Fill the ice pack with water up to the mark and close the cap tightly.

Prepare ice-pack by keeping the water-filled container in freezer or in the freezer compartment of refrigerator so that water freezes.

Do not add salt to the water in the ice pack while placing in the freezer, it will lower the temperature to subzero level which is not recommended for DPT, DT, TT and BCG.

Shake it and invert to check that it is not leaking

Place the ice packs on one side in the freezer initially, placing 16-24 packs,

Indian J for Practising Doctor; Vol I; No. 4

and change to another on the next day.

For emergency requirement a PHC should have 50-60 frozen ice packs at a given time.

Ice Lined Refrigerators:

These type of refrigerators are top-opening because they can hold the cold air inside better than a refrigerator with a front-opening. An ILR can keep vaccine safe with as little as 8 hours continuous electricity supply in a 24 hour period. It is available in two sizes

ILR-MK 300 of 300 litre capacity and

ILR-MK 140 of 140 litre capacity.


district headquarters and MK 140 is

supplied to PHC headquarters.





Inside the ILR, there is a lining of water-containers fitted all around the walls and held in place by frame. While the refrigerator is in operation, water in containers freezes and when the electricity supply fails, then the ice lining keeps the inside temperature of the refrigerator at a safe level for vaccines. In such a situation the temperature remains within safe limits in ILR for much longer than in deep freezers.

ILR has got two sections- the top and the bottom. The bottom of the refrigerator is the coldest place. Therefore, DPT, DT TT and BCG vaccines should not be kept directly on the floor of the refrigerator as they can freeze and get damaged. The top section of the ILR maintains the temperature of +2° to +8°C. BCG, DPT, DT, and TT vaccines are kept in this section in the baskets provided with the refrigerator.

Conventional Refrigerators:

This is to be used in case of breakdown of ILR.

Temperature in the ordinary chamber remains between 4 & 10 degrees. In the ice chamber the temperature fluctuates between 0- 4 degrees centigrade. Overall speaking, the temperature in an ordinary refrigerator ranges from +2 to +8°C.

Measles and polio vaccines are kept on the top shelf below the freezer.

Vaccines should not be frozen or thawed repeatedly as this will decrease their potency.

DPT, DT, TT, BCG and diluents are kept in the middle shelf.

Water bottles with coloured water (to serve as buffer in case of electricity failure) are kept at the bottom shelf and door.

Installation of the equipment:

No electric cold chain equipment should be installed without a voltage stabilizer. Before installation, one should get familiar with various features of Automatic Voltage Stabilizer.

Vaccine Transportation Equipments

Cold boxes Cold boxes are mainly used for transportation of large quantities of vaccines. They can also be used to store vaccines for transfer up to five days. These are of two sizes 5 litres and 20 litres with requisite number of ice packs. The 5 litre cold box can transport about 1500 doses of vaccines; the 20 litre boxes have enough space to transport about 6000 doses of vaccines. The ‘hold over time’ is more than 90 hrs for 5 L and six days for 20L cold box. We may store vaccine in cold boxes in case of breakdown of ILR. The vials of DPT, DT and TT vaccines should not be placed in

Indian J for Practising Doctor; Vol I; No. 4

direct contact with frozen ice packs and should be surrounded by OPV vials.

How to keep cold

condition when not in use




Clean and dry after use

Examine inside and outside surface after every use for cracks.

Check that the rubber seal around the lid is not broken; if broken, replace immediately.

Adjust the tension on the latches so that the lid closes tightly



and locks


Vaccine Carriers Vaccine carriers are used for carrying small quantities of vaccines (16- 20 vials) to the sub-centers or villages by health workers. The vaccine carriers are made of insulated material, the quality of which determines the cold-life of the carrier. These are containers with thick walls and lids of material which does not allow heat to pass through it easily.

Fully frozen ice packs are used to keep vaccines cold in the carrier. The vials of DPT, DT and TT vaccines should not be placed in direct contact with the frozen packs. Do not leave the lid open and do not expose the carrier to the sun. Vaccines can be kept in the carrier for 48 hrs.

If more than one vaccine carrier is being carried, keep the whole range of the vaccines required for the day in the carrier so that only one carrier is opened at a time. Keep the vaccine carrier in good condition when not in use.

Storage temperature:

To measure the temperature during storage/transport, different types of thermometers are used.

Dial thermometers Dial thermometers have been provided to record the temperature in the ILRs / Freezers. One dial thermometer should be kept in every unit. A staff member should be made responsible for recording the temperature. The temperature record should be used to monitor and control the temperature and to take follow up action as required.

Alcohol stem thermometers Alcohol thermometers are much sensitive and accurate than dial thermometers. They can record temperatures from -50°C to +50°C and can be used for ILRs and deep freezers.





storage temperature The temperature in the ILR must be monitored twice daily (morning and

evening). This is done in order to:

Be sure that vaccines were not exposed to temperature above +8 0 Celsius.






working properly.

We must be careful and ensure that the temperature in the ILR does not rise above +8°C. Also one must check that the temperature does not fall below -20°C as it damages the T series (tetanus-containing) of vaccines.

Vaccines are damaged by heat whether they are exposed to a lot

Indian J for Practising Doctor; Vol I; No. 4



Storage temperature in 0 C





Over 37




Stable for 3-7 years

Stable for months

Stable for

at least 6






weeks at 45 0 C, loss of potency





after few ours at




to 65 0 C




of vaccines


Safe storage for 18-24 month although with continuous slow decrease of potency

Stable for one year

Stability varies. Some vaccines stable for two weeks.

Stability varies. Some vaccines loss 50% of potency after one week storage.

At 45 0 c about







potency per day, rapid loss in potency at 50 0 C Unstable. 50% loss after 30 minute exposure

BCG vaccine


Stability varies. 20-30% loss of viability after 3 month storage

Stability varies. 20% loss of viability after 3-14 month storage


to 70 0 C Reconstituted BCG vaccine should not be used beyond one working session (5-6 hours). This

BCG vaccine

recommendation has two bases (1) concern over the risk of contamination, as BCG contains no bacteriostatic agents, and (2) concern over the loss of potency.


Stable for two years Retains satisfactory

Retains satisfactory potency for at least one week.








potency after 2-




day exposure


Unstable-50% loss


to 41 0 c; 80% loss in potency after one day exposure. Inactivation within one hour


Unstable-should be used in one working session

Very unstable; titer may be below acceptable level after Very unstable loss of satisfactory titers after 1-3 days


after one hour. 70% loss after 3 hours


OPV Stable for 6-12 months Unstable, 50% loss




after 20 days. Some vaccines may retain satisfactory titers for 1-2 weeks




41 0 c after At


one 50 0 c of











Stable for 1-4 years

Decline of D-antigen content for type 1 after 20 days

Loss of D-antigen for type1 after 20 days in some vaccines but no significant loss after 4 weeks in others



polio vaccine



of heat in a short time or a small

A break in the cold chain is

amount of





indicated if temperature rises


above +8°C or falls below +2°C





in the ILR; and above -18°C in

demands constant vigilance.

the Deep Freezer.

Indian J for Practising Doctor; Vol I; No. 4

Shake test:

The “shake test” is a test to determine if a vaccine was frozen or not at any time. Freezing can damage DPT, DT, tetanus toxoid (T-series of vaccines), typhoid and hepatitis vaccines. We can find out if any of these was frozen or not by performing this test.

Vaccines never frozen

Smooth and cloudy.

It is clear with no sediment

Vaccines frozen

Vaccines frozen contain granules, and sediments are fond settled at the bottom.

Supply of vaccines:

A health administrator’s major responsibility is to provide vaccines to health centres in time. Before making supplies, we must check the following



(session wise)

Utilization during the previous






get this




monitoring report

Find out balance in hand.

Arrange supplies according to demand & utilization.

monthly monitoring report • Find out balance in hand. • Arrange supplies according to demand &

Indian J for Practising Doctor; Vol I; No. 4

Operating Room Etiquette

(Reproduced from “Surgical Care at the District Hospital”, WHO, Geneva, 2003)

{This section is reproduced for the benefit of doctors and paramedics working in the District & sub-district hospitals of India, particularly J & K State]

The operating theatre is a room specifically for use by the anaesthesia and surgical teams and must not be used for other purposes. A treatment room has equipment similar to an operating theatre, but on a smaller scale. Both rooms require:

Dedicated equipment for procedures Equipment top monitor patients, as required for the procedure Drugs and other consumables, such as sutures, for routine and emergency use.

Goods lighting and ventilation

Ensure that procedures are established for the correct use of the operating room and that all staff are trained to follow them:

Keep all doors to the operating room closed, except as needed for passage of equipment, personnel and the patient. Store some sutures and extra instruments in the operating room to decrease the need for people to enter and leave the operating room during a case. Keep to a minimum the number of people allowed to

enter the operating room, especially after an operation has started. Keep the operating room uncluttered and easy to clean. Between cases, clean and disinfect the table and instrument surfaces. At the end of each day, clean the operating room: start at the top and continue to the floor, including all furniture, overhead equipment and lights; use a liquid disinfectant at a dilution recommended by the manufacturer. Sterilize all surgical instruments and supplies after use and store them protected and ready for the next use. Leave the operating room ready for use in case of an emergency.

Sponge & Instrument Counts

It is essential to keep track of the materials being used in the operating room and during any complicated procedure in order to avoid inadvertent disposal or the potentially disastrous loss of sponges and instruments in the wound.

Indian J for Practising Doctor; Vol I; No. 4

It is standard practice to count supplies (instruments, needles, & sponges):

of the instruments included in that tray for future reference.

Before beginning a case

Scrubbing & Gowning

Before final closure

On completing the procedure

Before each operation, all members of the surgical team – that is, those will

Each hospital should develop a







touch the sterile surgical field, surgical

materials are not left behind or lost. Pay

instruments or the wound – should scrub

special attention to small items sponges.


their hands and arms to the elbows. Scrubbing can not completely sterilize

Create and make copies of a standard list of equipment for use as a checklist to check equipment as it is set up for the case and then as counts are completed during the case. Include space for suture material and other consumables added during the case.

When trays are created with the instruments for a specific case, such as a

the skin, but will decrease the bacterial load and risk of wound contamination from the hands.

written procedure for scrubbing that specifies the length and type of scrub to be undertaken. It is usual that the first scrub of the day is longer (minimum 5 minutes) than any subsequent scrub between consecutive clean operations (minimum 3 minutes).

Caesarean section, also make a checklist

subsequent scrub between consecutive clean operations (minimum 3 minutes). Caesarean section, also make a checklist 36

Indian J for Practising Doctor; Vol I; No. 4

When scrubbing:

1. Remove all jewellery and trim the nails

2. Use soap, a brush (on the nails and finger tips) and running water to clean thoroughly around and underneath the nails.

3. Scrub your hands and arms up to elbows

4. After scrubbing, hold up your arms to allow water to drip off your elbows

5. Turn off the tap with your elbow.

After scrubbing your hands:

1. Dry them with a sterile towel and make sure the towel does not become contaminated.

2. Hold your hands and forearms away from your body and higher than your elbows until you put on a sterile gown and sterile gloves.

and forearms away fr om your body and higher than your elbows until you put on
and forearms away fr om your body and higher than your elbows until you put on

Indian J for Practising Doctor; Vol I; No. 4

Surgical gloves prevent transmission of HIV through contact with blood, but there is always the possibility of accidental injury and of a glove being punctured. Promptly change a glove punctured during an operation and rinse your hand with antiseptic or re-scrub if the glove has leaked during the puncture. Patient safety is of primary concern; do not compromise it. Change your gloves only when it is safe for the patient.

Skin Preparation:

The patient should bathe the night before an elective operation. Hair in the operative site should not be removed unless it will interfere with the surgical

procedure. Shaving can damage the skin so clipping is better if hair removal is required; it should be done in the operating room. Just before the operation, wash the operation site and the area surrounding it with soap and water. Prepare the skin with antiseptic solution, starting in the centre and moving to the periphery. This area should be large enough to include the entire incision and adjacent working area, so that you can manoeuvre during the operation without touching the unprepared skin. Chlorhexidine gluconate and iodine are preferable to alcohol and are less irritating to the skin. The solution should remain wet on the skin for at least two minutes.

alcohol and are less irritating to the ski n. The solution should remain wet on the

Indian J for Practising Doctor; Vol I; No. 4

Indian J for Practising Doctor; Vol I; No. 4 Draping: Scrub, gow n and glove before


Scrub, gow n and glove before covering the patient with sterile drapes. Leave uncovered only the operative field and

those areas necessary for the maintenance of anaethesia. Secure the drapes with towel clips at each corner. Draping exposes the area of th e

ve field and provides a sterile

field for the operating staff to work. This

op erati

is designed to maximize surgical exposure and limit potential for

P regnancy in the Rh-

contamination. There are many approaches to draping, some of which depend on the kind of drapes being used. Do not place drapes until you are gowned and gloved, so as to maintain the sterility of drapes. It is important to secure good exposure and a large sterile area. When laying out the drapes, the edges and folds (which hang below the operating table) are considered to be non-sterile.

Indian J for Practising Doctor; Vol I; No. 4

negative woman

Rehana Kausar

Isoimmunization (maternal blood-group immunization), a disease of

genetic predisposition, has been a focus

of concern for obstetricians for centuries.

Fifty years ago, Landsteiner and Weiner first described their classic experiment in which monkey red-cell antiserum was mixed with blood samples from a selected human population. Levine and colleagues subsequently demonstrated that the immune response in an Rh negative woman was the primary cause

of hemolytic disease in the newborn. The

identification of the rhesus antigen and its description in these classic works are

the cornerstone of modern immuno- hematology. The pregnant woman and her caregiver now have the ability to both avoid and treat this historically difficult problem.

The incidence of Rh negativety in Caucasian population is 15% to 16%. In India the incidence is about 5-8%.

Rh system

A) D antig en : The Rh complex consists of three pairs of antigenic determinants

(Dd, Cc, Ee). The presence of D antigen determines that the individual is Rh +ve. The Rh +ve individual will be found to be homozygous for D (i.eDD) approximately 45% of the time. This results from having inherited the D containing set of alleles from both partners. The remainder of Rh +ve individuals will be heterozygous for the

D locus. A homozygous partner (DD) of

a Rh-ve woman will produce only Rh

positive offspring; a heterozygous partner will produce either Rh +ve or Rh -ve offspring. Rh iso-immunization can occur only in that pregnancy in which a Rh+ve foetus resides, and only that foetus or subsequent Rh +ve foetuses will be affected by the maternally produced Rh antibody.







directed against the c and E , and less commonly against e and C are also associated with hemolytic disease of the newborn. These are called atypical antibodies. A number of other red cell antigens that are not part of the Rh antigen complex are capable of stimulating isoimmunization as well. Because of the efficacy with which Rh immune globulin prophylaxis prevents Rh isoimmunization, hemolytic disease caused by these antigens has become relatively more important.

E tiology: Blood group isoimmunization will occur from one of two pathogenic mechanisms: incompatible blood transfusion or foeto-maternal hemorrhage.

Although the risk of Rh atibility depends on the dose, a

in comp

small inoculum of 50-70 ml of Rh +

blood is needed

immunization. The secondary response will require as little as 0.1 ml of red cells.

to produce

A lthough the mother could be theoretically immunized if enough erythrocytes enter the foetal circulation to elicit an immune response, isoimmunization is rare due to the following reasons:

1) V arying rate of occurrence of



us red cell antigens.