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Tropical Doctor, April I976

PREGNANCY

Obstetrics

Sickle cell disease . In pregnancy K. A. Harrison, MD, FRCOG Professor of Obstetrics & Gynaecology, Ahmadu Bello University Hospital, Zaria, Nigeria

TROPICAL DOCTOR,

1976,6,74-80

There are four normal human haemoglobins (Hb); Hb A, Hb A 2, Hb F, and Hb Gower-z. These haemoglobins are each composed of four amino acid chains to each of which is bound an iron porphyrin compound called haem. The normal haemoglobins all have one pair of amino acid chains in common: alpha chain. In Hb A, alpha chains are paired with beta chains, in Hb A 2 with delta chains, in Hb F with gamma chains, and in Hb Gower-z with epsilon chains. The alpha chains contain 141 amino acids and the non alpha chains 146. Hb Gower-z is present in embryonic life and it disappears during the course of intrauterine development. In the newborn, Hb F accounts for 50-7°% of the total haemoglobin and it normally diminishes to less than 2% by early infancy. In the adult with normal haemoglobin, Hb A comprises about 98% of the total haemoglobin and Hb A 2 and Hb F the remaining 2%. In the abnormal haemoglobins, there may be variations in the structure of the alpha, beta, delta, and gamma chains. Most of the common abnormal haemoglobins differ from the normal haemoglobin by substitution of a single amino acid by another or by the suppression of the production of one pair of amino acid chains. Thus in haemoglobin S, valine replaces glutamic acid in the beta chain. In haemoglobin C,

Fig.

I.

The distribution of haemoglobin S.

.More thon 15%

!i!i;10-150Jq ~1·9%

11 ~;~~;~~~al

Fig.

2.

cases

The distribution of haemoglobin C in Africa.

the change is again in the beta chain where lysine replaces glutamic acid. In thalassaemia, the disorder involves the beta or the alpha chain. When the beta chain is affected, its production is reduced but there is no such impairment in alpha chain synthesis. Consequently, during adult life in beta-thalassaemia, Hb A production is reduced whereas Hb A 2 and Hb F are present in increased amounts. Whether they are normal or abnormal, the production of all haemoglobins is controlled by genes transmitted as alleles in a typical Mendelian fashion. DISTRIBUTION OF SICKLE CELt DISEASE

The term "sickle cell disease" refers to individuals who are S homozygotes (Hb SS), SC heterozygotes (Hb SC), and others who are Svbeta-thalassaemia heterozygotes (Hb S-beta-thalassaemia). Hb S has its highest gene frequency in Uganda and other parts of tropical Africa (Fig. 1), and haemoglobin C is most common in Northern Ghana (Fig. 2). However, this pattern of distribution of abnormal haemoglobins along distinct geographical and racial lines is now changing. At first, forced migration of the slave trade Figures 1 and 2, which appeared in Obstetrics and Gynaecology in the Tropics (published by Edward Arnold, London), are reproduced by kind permission of Mr J. B. Lawson.

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in the eighteenth century took haernoglobins Sand C to the Americas and West Indies; more recently, the pattern of modern travel has brought the problems of abnormal haemoglobins to the attention of doctors who practise in the cosmopolitan centres of the world. As for the thalassaemia syndrome, examples of it have been discovered in practically all populations that have been studied, though it was once thought to be confined to the Mediterranean countries. Hb SS, Hb SC, and Hb S-beta-thalassaemia have similar clinical features. Nevertheless, as regards complications during pregnancy, Hb Ssbeta-thalassaernia carries the best prognosis and Hb SS is the most dangerous (Table I). Hb C is of very little clinical significance unless it is combined with Hb S to form Hb Sc. Although the possession of Hb SS is very dangerous, the contribution it makes to maternal and fetal morbidity or mortality is less than that of Hb SC, This is because in Mrica, where intercurrent infections and malnutrition take a heavy toll of life,

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very few Hb SS children survive to reproductive age, although a larger proportion do so in the West Indies and the United States. PATHOLOGY

Under normal conditions, all the haemoglobin within every red cell is in solution. In the deoxygenated state, however, the solubility ofHb S falls to 2% of normal. As the reduced haemoglobin comes out of solution, it forms the characteristic "tactoids" or sickle cells. This is the phenomenon of sickling, aggravated by an increased concentration of Hb S within the red cell, low oxygen tension, low pH, and an increased osmolarity. When sickling occurs, the viscosity of the blood is increased and the blood flow in the microcirculation diminishes. This causes further deoxygenation of the blood and fall in pH, and a vicious cycle is set in motion which ends with intravascular coagulation of the blood, with resultant vascular occlusion and tissue

Table I. Comparison of the frequency of complications in booked patients with normal haemoglobin genotype and others with sickle cell disease in University College Hospital, Ihadan, Nigeria

*All patients in this group had been admitted earlier in pregnancy with severe anaemia. At delivery, however, only 20 % were still moderately anaemic. Apart from the difference in haemoglobin genotype, this control group was similar to the abnormal haemoglobin groups in most respects. )=

Number of pregnancies.

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infarction. This is one of the basic causes of most of hip arthrodesis, and in Hb SS, other reported findings the complications of the disease. include general contraction of the pelvis, android The other effect of sickle cell disease is also related pelvis, straight sacrum, and a reduction of the pelvic to the formation of the tactoids, In their presence, red area at the mid pelvis. Another feature of sickle cell disease is its influence cell survival is shortened and a state of chronic haemolytic anaemia results, although it is only in on reproductive performance. Until recently, pregHb SS that the anaemia is constant throughout life. nancy was relatively rare especially in Hb SS in whom When the degree of anaemia worsens in Hb SS, and the menarche was delayed and subfertility was comwhen anaemia develops in Hb SC and Hb S-beta- mon. Nonetheless, an increasing number of these thalassaemia, three mechanisms are usually responsible patients are becoming pregnant although their obstetric histories still remain poor. Fetal wastage is high for this. The first is referred to as acute sequestration crisis and there is a high incidence of operative deliveries in which a large volume of blood suddenly pools in largely attributable to fetopelvic disproportion caused the spleen and sometimes in the liver. The spleen by the poor maternal stature and pelvic contraction. Thus sickle cell disease creates special problems becomes enormous, and the haemoglobin drops so precipitously that death from hypovolaemic shock and so long as account is taken of them, the diagnosis may follow. Acute sequestration crisis may be pre- can often be suspected even on clinical grounds. A cipitated by hypoxia, acidosis, venous congestion, or high index of suspicion in all cases of severe anaemia infection. Apart from acute sequestration, severe in pregnant Negro women is also needed. Final anaemia also develops from serious folate deficiency diagnosis, however, can only be made on haematolocausing megaloblastic crisis, and from temporary gical features and on family studies. Where there is a high risk of the disease, mass screening by the sickling marrow hypoplasia. test and haemoglobin electrophoresis are of great value at the first visit of the patients to the antenatal DIAGNOSIS In African medical practice, the diagnosis of sickle clinic. Even where haemoglobin electrophoresis cell disease in female adults is often first made during cannot be performed, simple sickling test of all pregnancy. There is no disputing the clinical features women followed by examination of blood films of especially the recurrent attacks of bone pains which those who sickle, would be better than nothing. In affect not only the patients but some other members Hb SS the blood film shows polychromasia, nucleated of their families. Depending on the severity of the red cells and target cells in addition to sickle cell attacks, the skin over the affected bones may feel hot, forms. In Hb SC, because of the presence of haemoand the bones themselves may be very tender. The globin C, target cells often form more than 10% of the attacks often start in childhood and they may recur total cells, but sickle cell forms will not be seen unless two to three times yearly especially in the cold, wet the patient is acutely anaemic. Target cells are also weather. Each attack of painful crisis may last for seen in Hb S-beta-thalassaemia. two to 15 days, and it is not uncommon for some of the attacks to be associated with episodes of haemolysis, MATERNAL COMPLICATIONS during which there is darkening of the urine from Pregnancy in sickle cell disease is characterized by an increased urobilinogen excretion and also jaundice of increase of complications, some of which are potenthe sclera. In a typical painful crisis, there is fever, tially lethal. They include severe anaemia, bacterial moderate leucocytosis, and a drop in haemoglobin infections, painful crisis, bone marrow fat embolism, and acute sequestration. It is therefore no accident concentration. The spleen is often enlarged in childhood, but by that even with good medical care in parts of tropical the time adult age is reached, the spleen often shrinks Africa, maternal and fetal mortality remain at least down and becomes impalpable, except in areas where five times as high as they are among the general malaria is endemic such as in West Africa. In Ibadan, population. In the West Indies and in the United for example, as many as 70% of the pregnant women States, however, the outlook is better. Painful crisis may occur in any organ but it most with Hb SS have splenomegaly. Bones and joints are often involved in sickle cell often affects the bones and joints. The crises are most disease. Particularly in Hb SS, growth may be frequently encountered during the last four weeks of stunted, and there may be evidence of old dactylitis pregnancy, in labour, and in the first week of the in the fingers and in the toes following infarction of puerperium. For reasons which are not yet clear; the phalanges. Some patients may have an abnormal the duration of the pains at these periods is prolonged, gait due to avascular necrosis of the femoral head and and their severity most marked. The appearance of

Tropical Doctor, April I976

systolic hypertension and proteinuria in a bone pain crisis around the end of pregnancy (sometimes called "pseudotoxaemia") is of grave prognostic significance. It is associated with pulmonary bone marrow fat embolism and in the absence of effective treatment, the mortality from it is high. Another effect of pregnancy on sickle cell disease is the marked increase of the incidence and severity of anaemia, at least in tropical Africa. This is not due to any intrinsic change in haemolysis and in patients who are fully protected from malaria, the red cell survival rates are the same whether or not the patients are pregnant. Among some of these patients profound anaemia may be found and it is often associated with folate deficiency (resulting in megaloblastic bone marrow) or with malaria or with acute sequestration crisis. In areas where Plasmodium falciparum is prevalent, the risk from anaemia is usually great. This is largely due to the fact that in pregnancy, the maternal defences against malarial parasitaemia are lowered. Red cell destruction therefore proceeds at an increased pace and so must haemopoiesis if the haemoglobin concentration is to be maintained at a reasonable level. In the end, both the increased haemopoiesis and pregnancy itself further increase the demand for folic acid. If the dietary intake of folate is low and if this is not supplemented, the bone marrow becomes megaloblastic and anaemia rapidly becomes worse. The part played by acute sequestration in worsening anaemia has already been discussed. The increased liability to develop bacterial infections, especially respiratory and urinary tract infections, is part of the natural history of sickle cell disease and in pregnancy these infections are of increased significance for at least two reasons. They are more difficult to control particularly in the puerperium, and the associated fever and acidosis may accelerate sickling. Another feature of bacterial infections in sickle cell disease is that they are most marked when severe anaemia is present with the haemoglobin and haematocrit levels below 7 g/dl and 20% respectively. ANTENATAL CARE

What matters most in the care of these patients is the prevention of severe anaemia, and the early detection of other medical and obstetric complications. In women with sickle cell disease antenatal supervision must begin in the first trimester of pregnancy; they should attend the antenatal clinic once a fortnight until the thirtieth week and thereafter once weekly. Careful search for evidence of crisis, bacterial infections, and trauma is part of the routine examina-

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tion of these patients. At each attendance, the haemoglobin or haematocrit should be estimated, and enlargement of the spleen and liver is looked for. Once a complication is found, treatment in hospital will be required in every case. As far as prevention of anaemia is concerned, the aim is to give appropriate haematinics and antimalarials (where these are indicated) to maintain the haemoglobin concentration at normal levels of 6 to 9 g/dl in Hb SS, and around 10 g/dl or more in both Hb SC disease and Hb S-beta-thalassaemia. For this purpose, all patients require folic acid tablets 5 mg thrice daily from early in pregnancy. Some patients may fail to take their tablets at home. It is wise to give at each visit to the antenatal clinic a single dose of 30 mg of folic acid, which must be seen to be swallowed by the patient. Iron medication is unnecessary except in areas where the dietary intake of iron is low. The need for antimalarial medication assumes an additional importance in the presence of sickle cell disease. Following malarial attacks in these patients, the accompanying fever will increase the incidence of bone pain crisis, while the repeated haemolytic episodes will cause severe anaemia and secondary folate deficiency. Malarial chemoprophylaxis aims to prevent these complications. In West Africa, for example, a useful regimen is to give oral chloroquine 450 mg of base at the first visit to the antenatal clinic, and afterwards pyrimethamine 25 mg once weekly. Unless a severe exacerbation of anaemia occurs there is no need to transfuse the patients as many of them are well adjusted to their low haemoglobin levels. Nevertheless, repeated transfusions to keep the haemoglobin concentration artificially high may have a place in the management of sickle cell disease. Those who advocate such transfusions stress that by keeping the haemoglobin level high, they manage to depress bone marrow activity and suppress the synthesis of Hb S, thereby lowering the risk of both obstetric complications and the incidence of crises. In practice repeated transfusions involve considerable labour and expense, and they do not prevent the incidence of crises. Indeed, they carry the risk of inducing uterine contractions, febrile reactions, and other complications of massive transfusions such as hepatitis, and for these reasons, this form of transfusion ought to be considered inappropriate to this group of pregnant patients. During a crisis it is essential that any underlying medical reason for its onset such as bacterial infection, dehydration, and acidosis must be looked for and treated. Relief of pain is achieved symptomatically by pethidine injections or codeine tablets. Meanwhile an

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appropriate antibiotic, such as tetracycline, is pre- these reasons, extra care is needed during the conduct scribed, and an increase in the intake of oral fluids is of labour. stressed. The haematocrit or haemoglobin concentraSuch patients should be delivered in hospital with tion is estimated frequently, at least twice daily, and good blood transfusion facilities. One litre of comwhenever there is a drop exceeding 4% or 2 gjdl patible donor blood, preferably of haemoglobin type respectively in any za-hour period, the anaemia is A, should be reserved for each patient and the haecorrected by transfusion of packed blood cells. matocrit or haemoglobin level estimated four to sixHeparin is of value in the treatment of bone pain hourly. Antibiotics are prescribed. crisis, the aim being the prevention of bone marrow Vaginal delivery is best but should labour be profat embolism with sudden death. Since this complica- longed for 24 hours, there should be no hesitation in tion apparently occurs in association with pseudo- terminating it if necessary by caesarean section. toxaemia, and with bone pain crisis in the last four Elective caesarean section has no special advantage weeks of pregnancy, in labour, and in the first four unless there are other obstetric indications for it such days of the puerperium, the use of heparin is re- as fetopelvic disproportion. While conducting the stricted to these periods only. Enough heparin is third stage of labour, blood loss must be reduced and administered intravenously in repeated doses to the active management of this stage of labour is premaintain the clotting time at thrice the normal, and ferred. During the birth of the baby, an intravenous the treatment is continued until the painful crisis injection of 0.5 mg of ergometrine is given and as ceases. While heparinization is continuing, labour soon as the uterus is felt to retract after the expulsion may supervene. On such occasions, in order to prevent of the baby, the placenta is delivered by controlled excessive haemorrhage, it will be best to reverse the cord traction. Blood loss exceeding 150 ml is replaced effect of heparin by an injection of protamine sulphate by transfusion of whole blood if the haemoglobin (10 ml of 1% solution) when the second stage of concentration is over 7 gjdl or by packed blood cell labour is imminent or immediately before an operative transfusion whenever the haemoglobin is under 7 g/dl, delivery. Heparinization should recommence two For operative deliveries, the usual types of anaeshours after delivery, and it should be continued for thesia are all suitable, so long as certain basic considerations are observed. Before anaesthesia is four days. Not infrequently, obstetric complications may induced, severe anaemia should be corrected if arise, as for example, pre-eclampsia, antepartum necessary by blood transfusion until the haemoglobin haemorrhage, and fetal malpresentation. However, concentration is 9 gjdl or more. During anaesthesia, the aim is to avoid sickling, during pregnancy and before the onset of labour, these complications are no more frequent than in and this is achieved by the prevention of hypotension those who do not have sickle cell disease. In general, and hypoxia. Blood loss should be adequately resuch cases do quite well if the standard methods of placed and ideally 30-50% of oxygen given throughobstetric management are followed. However, in the out the period of anaesthesia. case oIfual malpresentations, it is wise to avoid corrections by version, because of the small but PUERPERIUM definite risk' of fetal asphyxia associated with the The use of antibiotics and the frequent estimation of haematocrit or haemoglobin which began during manoeuvre. labour should be continued for the first four days of the puerperium. Painful crises require heparinization LABOUR Following good antenatal care, about half of the until the affected organs are no longer tender. As for patients with sickle cell disease will be expected to breast feeding, this should be encouraged and there have uncomplicated labours. In the rest, some will be is no need to inhibit lactation. In Hb SS (but not in the other forms of sickle cell complicated by obstetric problems, and others by having some of the complications peculiar to sickle disease) both laparotomy (caesarean section) and cell disease. The latter are particularly dangerous if episiotomy wounds easily become septic and wound there is a small haemorrhage or if hypoxia is produced dehiscence is found in as many as 50% of the cases. during anaesthesia. Among women with Hb SS, the This may be related to chronic anaemia or it may be incidence of intrapartum pre-eclampsia is nearly four due to tissue hypoxia resulting from sickling and local times as high as it is in the general population, and in vascular occlusion. Whatever the cause, good surgical all cases of sickle cell disease, prolonged labour is technique ought to go a long way in reducing the dangerous because the dehydration and acidosis which high incidence of wound sepsis and dehiscence. accompany it may precipitate painful crises. For Before the closure of the wounds in layers, adequate

Tropical Doctor, April I976 haemostasis must be secured to prevent haematoma, and in the case of episiotomy wounds, they should be repaired without delay as soon as the third stage of labour is completed. FETAL PROGNOSIS

A high abortion rate and an increased perinatal mortality are characteristic of sickle cell disease. In addition, there is an increased danger to the fetus if there is any degree of intrapartum asphyxia such as is encountered in prolonged labour and in preeclampsia. Perhaps, the reason lies in the fact that where there is intrapartum asphyxia, oxygen tension in the choriodecidual space is reduced, sickling of maternal blood in the same space increases, blood flow in the same space diminishes with a resultant drop in the rate of exchange of oxygen across the placenta. Lastly, mothers with sickle cell anaemia, but not those with other forms of sickle cell disease, produce babies who, at birth, weigh on the average 250 g less than babies of other mothers. This lower birth weight has nothing to do with prematurity or with differences in maternal stature, but it is now thought, on good evidence, to be caused by intrauterine growth retardation associated with maternal anaemia. Any severe maternal anaemia may result in intrauterine growth retardation so long as the maternal haemoglobin remains under 10 gjdl and the haematocrit is under 30% throughout pregnancy; this is the case in Hb SS, but not in the other forms of sickle cell disease, in which a higher haemoglobin level is often maintained. THERAPEUTIC PROBLEMS

Certain problems relating to sickle cell disease are still unexplained. Set against the background of tropical Africa, it is still not known why painful crises are most serious towards the end of pregnancy. In the treatment of painful crises, everyone favours symptomatic treatment by analgesics, but others, arguing on theoretical grounds, have sought to prevent painful crises by the use of drugs none of which have stood the test of time. The list includes magnesium salts, alkalis, acetazolamide, chlorpromazine, high doses of urea, cyanate, hormones, and even distilled water injected intravenously. Therapy with urea and cyanate in pregnancy cannot be justified since their effect on the fetus is still not known. Uncertainty still exists about the management of pseudotoxaemia. At present, exchange transfusion is first performed, immediately afterwards the pregnancy is terminated, and two hours later, treatment by intravenous injections of heparin is begun. This regime, while life saving, is not entirely satisfactory. The ease with which haematomata

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are produced when repeated intravenous injections of heparin are given, suggests that the treatment described needs to be improved upon. Perhaps heparin given by subcutaneous injections in doses totalling not more than 2500 units six-hourly will be safer. The controversy about the place of repeated exchange transfusion in the antenatal management of sickle cell disease need not concern us any longer. It has too many disadvantages to be of much use, and these have been discussed earlier. GENETIC COUNSELLING

Outside pregnancy, the use of mass screening for sickle cell trait has been advocated for the purpose of genetic counselling. In this way, it is argued that the number of patients with this disease may eventually be limited. However there are problems about genetic counselling and one of these is chiefly related to the financial support required to implement it. Despite its cost, this can be said about genetic counselling: provided those who request genetic counselling can understand its implications, it may be useful to them. For the vast majority in the African tropics, this approach to the control ofthe Hb S gene is not of high priority. Family planning may be preferable. However, the use of oral contraceptive agents may cause thromboembolism in women with sickle cell disease, and for this reason, other methods of contraception such as intrauterine contraceptive devices may have to be used wherever possible. SICKLE CELL TRAIT AND OTHER HAEMOGLOBINOPATHIES

The interaction of Hb S with Hb A is called sickle cell trait. It is largely innocuous though rarely haematuria from renal papillary necrosis may develop. The hereditary persistence of Hb F in combination with Hb S (Hb SF) is also known, as are Hb CF, and Hb C-thalassaemia. The patients who possess them are entirely asymptomatic. Hb CC is associated with mild anaemia, hepatosplenomegaly, occasional jaundice, and an increased incidence of atonic postpartum haemorrhage, but maternal and fetal prognoses are not impaired. CONCLUSION

In tropical Africa, where the present socio-economic circumstances are poor, obstructed labour, ruptured uterus, haemorrhage, eclampsia, anaemia, and infections are the main causes of maternal death. As far as reproduction is concerned, the expected improvements in environmental hygiene and standard of living are bound to influence maternal mortality and morbidity. While the proportion of women who die from anaemia and other preventable diseases falls,

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an increasing number of men and women with sickle cell disease will be expected to live longer reproductive lives. Unless a more effective means of controlling sickling is found, in future, the problems of sickle cell disease in pregnancy will assume far greater importance than they do at present. SUMMARY

S-homozygotes, SC heterozygotes, and S-betathalassaemia heterozygotes are the haemoglobinopathies which make up sickle cell disease. Although their clinical features are similar, as regards complications during pregnancy, Hb Svbeta-thalassaemia carries the best prognosis and S-homozygote is the most dangerous, the main causes of mortality being severe anaemia, acute sequestration crisis, bacterial infections, painful episodes, and pulmonary' bone marrow fat embolism. Folic acid and antimalarials (where these are indicated) are often successful in preventing severe anaemia. It is best to reserve blood transfusion to replace .moderate loss or to correct gross anaemia quickly when this is considered severe enough to threaten life. Painful crises are particularly common

Tropical Doctor, April I976

towards the end of pregnancy and in treating these episodes, analgesics, antibiotics, and sometimes heparin are used. S-homozygote carries additional hazards. Because of the prevalence of pelvic contraction, fetopelvic disproportion is common and so the incidence of operative deliveries is high. Many fetuses are lost through an increased incidence of abortion and perinatal mortality. In the survivors, there is evidence of intrauterine growth retardation brought about by continuous maternal anaemia throughout pregnancy. REFERENCES

Fullerton, W. T., et al. (1965). In Abnormal Haemoglobins in Africa, C.l.O.M.S. Symposium. Oxford: Blackwell Scientific Publications. Harrison, K. A., and Ibeziako, P. A. (1973). J. Obstet. Gynaec. Brit. Cwlth, 80, 798. Hendrickse, J. P. de V., et al. (1972). J. Obstet, Gynaec. Brit. Cwlth, 79, 396. Hendrickse, J. P. de V., et al. (1972). J. Obstet. Gynaec. Brit. Cwlth, 79, 410. Lawson, J. B. (1967). "Sickle Cell disease in pregnancy". In Obstetrics and Gynaecology in the Tropics and Developing Countries. Lawson, J. E., and Stewart, D. B., editors. London: Edward Arnold. Perkins, R. P. (1971). Amer. J. Obstet. Gynec., 3, 120.

News and Notes THE NEW MENACE OF MENINGITIS

Meningococcal meningitis has been causing increasing concern in recent years due to changing patterns and an apparent rise in incidence in several parts of the world where it was previously not considered to be much of a public health problem. Large epidemics continue to occur in the Sahel region of Africa, and the disease has also risen to epidemic proportions in a few countries of Latin America, the Middle East, Southern' Africa, Europe and Asia. In general, the diseasetends to occur in cycles of high prevalence at several years' interval, especiallyin children; it occurs most frequently in crowded populations, for example in military barracks. Mortality among untreated cases is 40-50%, and strains of bacteria resistant to sulphonamides have reduced the effectiveness of treatment. The need for other means of prevention is evident and considerable progress has been made in developing vaccines. The meningococci that cause cerebrospinal meningitis belong to several different sero-groups, the most important being groups A and C, which have caused most of the outbreaks studied so far. Group B is also prevalent in many countries. Vaccines are available against two of these three

most widespread groups, A and C, and are thought to confer about 90% protection. There is no vaccine against group B. However, the vaccines have limitations: while group A vaccine seems to protect children over three months of age, group C vaccine does not protect children under two years. Combined A and C vaccines are expensive and routine immunization of children is not advisable. The WHO recommends that vaccination should be undertaken only in the presence of epidemics, as in the recent epidemic of group A and C meningococcal meningitis in Brazil, and that in such cases high-risk groups should be protected first. Recent studies suggest that vaccination of part of the population may decrease the transmission of infection in the population as a whole. In view of the limitations of vaccines at present available, including poor response in young, high-risk groups, and because of logistic difficulties and high costs, sulphonamides and chloramphenicol, which have proved effective against meningitis, can be used for treatment. However, they must be used under strict supervision and control. Early application of drugs, as soon as the first signs of illness appear, is of great importance for success in treatment.

Sickle cell disease in pregnancy.

S-Homozygotes, SC heterozygotes, and S-beta-thalassaemia heterozygotes are the haemoglobinopathies which make up sickle cell disease. Although their c...
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