Management of children with prolonged fever of unknown origin and difficulties in the management of fever of unknown origin in children in developing countries.

This is Part II of a 2-part paper on fever of unknown origin (FUO) in children. It examines the aetiology and management of prolonged FUO in children and the difficulties in the management of FUO in children in developing countries. Part I of this paper discussed acute FUO in children and was published in the March 2001 issue of Paediatric Drugs. Prolonged FUO is documented fever of more than 7 to 10 days which has no apparent source and no apparent diagnosis after 1 week of clinical investigations. About 34% of cases of prolonged FUO are caused by infections, with bacterial meningitis and urinary tract infection accounting for about 6.5 and 11.4%, respectively, of cases attributable to infections. Chronic infections, particularly tuberculosis and 'old' disorders such as Kawasaki disease, cat-scratch disease and Epstein-Barr virus infection presenting with 'new' manifestations, collagen-vascular diseases and neoplastic disorders are the other issues of major concern in prolonged FUO. Overall, however, there is a trend towards an increased number of undiagnosed cases. This is due to advancements in diagnostic techniques, such that illnesses which were previously common among the causes of prolonged FUO are now diagnosed earlier, before the presentation becomes that of prolonged FUO. Clinical examination supplemented with laboratory tests to screen for serious bacterial infections should be the mainstay of initial evaluation of children with prolonged FUO. Use of scanning techniques (such as computerised tomography and ultrasound) as additional supplements to this clinical examination may allow for the earlier diagnosis of causes of prolonged FUO in children such as 'occult' abdominal tumours. A common error in management of children with prolonged FUO is the failure to perform a complete history and physical examination; repeated clinical examination and continued observation are of paramount importance in the diagnosis of difficult cases. Major difficulties in the management of FUO in children in developing countries include constraints in the availability and reliability of laboratory tests, cost, misuse of antibiotics and difficulties encountered in the diagnosis of malaria and typhoid fever. Malaria and typhoid fever are major aetiological considerations in both acute and prolonged FUO in children in developing countries. The newer quinolones may hold great promise for the treatment of serious bacterial infections, including meningitis, which are associated with prolonged FUO in developing countries.

Aetiology and management of children with acute fever of unknown origin.

This is part I of a 2-part paper on fever of unknown origin (FUO) in children. FUO is best defined as fever without obvious source on initial clinical examination and then classified into acute (illness of < or =1 week's duration) and prolonged (>7 to 10 days' duration). Aetiologically, there is a marked overlap between acute and prolonged FUO, and infections are major players in both. Age, climate, local epidemiology and host factors are the major aetiological factors that should be considered in the choice of definitive tests. Depending on age, serious bacterial infections (including bacteraemia, meningitis and urinary tract infection) occur in 3 to 20% of cases of acute FUO. Prevention of mortality and sequelae from these infections, particularly bacteraemia and meningitis, is of particular concern in acute FUO. An individualised approach, based on clinical evaluation supplemented with screening and definitive laboratory tests to determine the need for empiric antibiotic therapy and hospitalisation, seems to be the best approach to acute FUO (although this may be less applicable to neonates and infants younger than 90 days, particularly those aged 0 to 7 days). The place of laboratory tests, empiric antibiotic therapy and hospitalisation are important issues that are likely to remain so for some time.

Orbitocephalic metastases from neuroblastoma: report on three cases.

Three unusual cases of Neuroblastoma with metastasis to the skull and orbit are presented. The bizarre clinical features which make diagnosis and subsequent management difficult are highlighted, suggesting the need for a multi-disciplinary approach.

Sickle cell anaemia in Nigeria: a comparison between Benin and Lagos.

The clinical and haematological features of 77 patients of Bini and 107 patients of Yoruba origin with homozygous sickle cell (SS) disease have been compared. The Bini population were generally younger and had a slightly lower incidence of alpha thalassaemia but even after correction for age and alpha thalassaemia status, this group had significantly lower HbA2 and higher HbF and MCV values. Clinically the Bini group had significantly less dactylitis and more acute chest syndrome. The decreased frequency of dactylitis is consistent with the higher HbF level in the Bini population and the mechanism of the other effects are discussed.

Spleen in sickle cell anemia: comparative studies of Nigerian and U.S. patients.

Anecdotal reports have attributed persistent splenomegaly in African sickle cell anemia (SS) patients to the effects of malaria. However, no comparative studies of patients in malarial and nonmalarial regions have been conducted, and few studies of malaria antibody titers have been reported. In the present study, age- and sex-matched Nigerian patients (n = 310), while it was found only in 8% of U.S. patients (n = 100) from Georgia. There was significant linear correlation between spleen size and Hb levels and with serum immunoglobulins in the Nigerian group. However, serum complement levels (C3 and C4) were not affected by spleen size. In both groups, patients with splenomegaly had fewer circulating pitted red cells than their counterparts without splenomegaly. The mean +/- SE of IgG-specific malaria antibody titer among the Nigerian patients without palpable spleens was 9,386 +/- 2,036; 9,334 +/- 2,980 in those with spleens between 1 and 5 cm, 16,201 +/- 4,502 in those with spleens between 6 and 10 cm, and 22,445 +/- 8,456 in those with spleens above 10 cm. Coexistent alpha-thalassemia did not influence the prevalence of splenomegaly among the Nigerian SS patients. This study provides additional evidence that malaria plays a significant role in the persistence of splenomegaly in African patients.

Alpha-hydroxybutyrate dehydrogenase and the diagnosis of painful crisis in sickle cell anaemia.

To assess the value of alpha-hydroxybutyrate dehydrogenase (alpha-HBDH) in the diagnosis of painful crisis (PC) of sickle cell anaemia (SCA), we studied plasma enzyme levels in 55 children with HbSS and 21 control subjects with haemoglobin genotype AA. In 21 children with SCA, mean plasma alpha-HBDH was 373.8 +/- 113.5 micrograms/l during PC and during steady state in 34 children, it was 341.2 +/- 103.4 micrograms/l. These values were significantly higher than that of 128 +/- 19.5 micrograms/l obtained in control subjects. However, the difference between mean plasma alpha-HBDH levels in SCA children in PC and in steady state was 32.6 micrograms/l, t = 1.095; P < 0.2. There was no correlation between alpha-HBDH levels and reticulocyte counts (r = 0.0856; t = 0.4565; 0.7 < P < 0.6). The high levels of alpha-HBDH in patients with SCA is probably due to chronic haemolysis and not marrow infarction. Therefore, alpha-HBDH is of doubtful value in the diagnosis of painful crisis.

Circumcision: its nature and practice among some ethnic groups in southern Nigeria.

A questionnaire survey carried out in five rural communities in mid-southern Nigeria documents the degree and range of male and female circumcision practices among Bini, Esan, Etsako, Ijaw and Ukwuani ethnic groups. Two hundred and eighty adults (154 males and 126 females) reported on themselves and their 1417 children (757 sons and 660 daughters). Circumcision of both sexes remains widely practised, though the timing of the event and extent of surgery show wide variations among, and sometimes, within ethnic groups. The commonest reason for the practice is a strong desire to continue ethnic traditions. Altered sexual urge for women, increased sexual performance for men, protection of baby's health, as well as general reproductive and aesthetic consideration are also important reasons. Traditional surgeons usually perform the operation and few complications were reported to be associated with the procedure in either sex. Female circumcision in this area is not as destructive or mutilating as in some Arabic and East African cultures. Because of the relatively low rate of complications a major campaign against circumcision in these areas does not at present seem warranted.

Amniotic membrane dressing for burns in children. A cheap method of treatment for developing countries.

Ten children aged seven months to eleven years with superficial burns involving (mean) 24% of total body surface were treated with amniotic membrane dressing in a general ward. The result of treatment was compared with that obtained during an earlier (12 months) period using non biological antimicrobial dressing on the same ward. One patient treated with amnion developed pseudomonas wound infection and another required skin grafting. These children spent an average of 31 days in hospital, as compared with 56 days for the control group. It is concluded that amniotic membrane dressing is to be preferred in the treatment of burns in hospitals in poorer countries, because of it's ready availability, ease of preparation and cheapness of storage.

Inhibitor of in vitro neutrophil migration in sera of children with homozygous sickle cell gene during pain crisis.

There is conflicting evidence for a causal relationship between infection and haematological crisis of sickle cell disease. To find out whether changes in leucotaxis occur during pain crisis, in-vitro neutrophil migration was determined in 38 children with Hb SS during steady state and during pain crisis. Migrations of neutrophils of sickle cell patients was 29 +/ 12 microns in steady state and 27.5 +/- 10.5 microns during pain crisis. These rates were comparable to migration of neutrophils of control children with normal haemoglobin of 34 +/- 9.6 microns. However, with addition of autologous serum to the cell suspension, neutrophil migration of patients in pain crisis was significantly retarded (16 +/- 13 microns) as compared to those in steady state (26 +/- 10.2 microns) and control children (28.7 +/- 10 microns). Sera of children in pain crisis also inhibited migration of neutrophils of healthy adults with normal Hb. Pooled normal plasma reversed inhibitory action of pain crisis serum on autologous and homologous neutrophil migration; but pain crisis plasma did not. Chemotactic effect of sera of Hb SS children in steady state or pain crisis and control children on neutrophils of eight adults with normal Hb were similar and comparable to that of pooled normal serum. Thus, children with sickle cell disease develop chemotactic inhibitor(s) in their circulation during pain crisis. They may lead to defective leucotaxis and enhanced susceptibility to infection.

The hematology of bacterial infections in premature infants.

A series of premature infants was studied for the presence of bacterial infection. On the basis of clinical evidence and bacteriological studies, they were divided into three groups in which sepsis was considered to be proven, possible, or unlikely. Band neutrophil counts were elevated most frequently in the "sepsis-proven" group and the elevation occurred usually within 24 hours of onset of signs of disease. Qualitative changes in neutrophils (Döhle bodies, toxic granulation, and vacuolization) were more frequent in the sepsis-proven group and, together with the band count, provided valuable techniques for the diagnosis of bacterial infections. Thrombocytopenia occurred frequently in the sepsis-proven group and seemed to result from increased utilization or destruction of platelets rather than failure of production. In such cases, evidence of intravascular coagulation was minimal and it was concluded that thrombocytopenia had resulted from a direct effect of the bacteria or its products on platelets and/or endothelium.