Primary hepatocellular carcinoma in intertropical Africa: relationship between age and hepatitis B virus etiology.

Clinical observations of patients with primary hepatocellular carcinoma (PHC) at Le Dantec Hospital, Dakar, Senegal, were studied to determine a correlation with hepatitis B virus (HBV) infection. Of the 103 patients with PHC, 80 had an active HBV infection (HBsAg and/or anti-HBc); 23 showed signs of previous HBV infection (anti-HBs and anti-HBc). The two groups were similar in the detection of alpha-fetoprotein (approximately 60%) and in the major clinical findings: hepatomegaly, 76.25% and 86.96%, respectively; and ascites, 57.50% and 47.83%, respectively. Jaundice, however, was three times more frequent (P < 0.01) in the group of patients with signs of active HBV replication. Distribution of HBV markers as a function of age at onset of PHC revealed that the presence of HBsAg was primarily confined to the sera of the younger patients (< 50 yr old). When compared with leprosy patients and blood donors, the younger PHC patients differed in the frequency of detection of HBsAg and anti-HBs. The older people (> 50 yr old) in the three groups (PHC patients, leprosy patients, and blood donors) had identical HBV markers.

A double-blind comparison of the efficacy and safety of ivermectin and diethylcarbamazine in a placebo controlled study of Senegalese patients with onchocerciasis.

Ivermectin (MK-933) has been compared with diethylcarbamazine (DEC) and placebo in a double-blind study in 30 adult male Senegalese patients with Onchocerca volvulus infection. 10 patients were randomly assigned to each treatment group. Ivermectin was administered as a single oral dose of 12 mg and DEC as 50 mg daily for two days and 100 mg twice daily for the following six days, total 1.3 g in eight days. Skin O. volvulus microfilaria densities remained near pre-study values in the placebo patients, but decreased rapidly with both active drugs to mean values about 2% of pretreatment (Day 8) and then increased slowly, reaching in 12 months about 4% of pre-treatment (ivermectin) and 18% (DEC). This difference is statistically significant. Clinical adverse reactions were recorded in four ivermectin, ten DEC and three placebo patients. One ivermectin and six DEC patients received steroid treatment for relief of these reactions. Serious adverse ocular changes were not seen in any patients, possibly because of the steroid therapy in the DEC patients. Adult O. volvulus from onchocercal nodules one and six months after treatment showed no effect of either drug on viability. Intra-uterine developing forms of the microfilariae appeared normal in all three treatment groups at the one month examination but deformed and degenerated forms were evident at six months in the ivermectin group but not in the DEC and placebo patients. Ivermectin as a single oral dose appears to be a safer and more effective microfilaricidal drug in human onchocerciasis than DEC in the standard multi-dose regimen.

[Hepatitis B and primary cancer of the liver in intertropical Africa]. / Hépatite B et cancer primitif du foie en Afrique Intertropicale.

During the past 15 years, a growing body of evidence incriminates hepatitis B virus as the major factor in the etiology of primary liver cancer. Epidemiological studies throughout the world reported a striking correspondence between areas where the frequency of primary liver cancer is high and where HBV infection is hyperendemic. Moreover, primary liver cancer is commonly associated with cirrhosis of the postnecrotic macronodular type. Such data suggested a sequence hepatitis-cirrhosis-PLC. Such sequence was confirmed by extensive serologic testing studies which reported a high frequency of HBV markers in PLC patients compared to matched control groups. Data collected in Senegal, Mali and Burundi on 12,000 individuals stress the importance of HBV infections in these countries, as the high rate of chronic carrier state in patients suffering from liver cirrhosis or primary liver cancer (62-63%) compared to the general population (12-17%). Other HBV markers including anti-HBs, anti-HBc, HBeAg and anti-HBe had no prognostic value in the sequence hepatitis-cirrhosis-PLC. A new HBV seric marker, the HBsAg/IgM complexes, observed in HBsAg positive individuals, is more frequently detected in PLC patients (50%) and cirrhosis (40%) than in healthy HBsAg carriers (14%). These results would indicate that HBsAg carriers are more likely to develop cirrhosis or primary liver cancer when they evidence HBsAg/IgM complexes. In conclusion, the seric markers of evolution towards primary liver cancer are: HBsAg (the highest known risk factor), the presence in such individuals of HBsAg/IgM complexes, and increased values of alphafoetoprotein.

[Anti-BCG titers of healthy and tuberculous Africans. Use of the indirect immunoperoxidase test]. / Titrage d'anticorps anti-BCG chez des africains sains et tuberculeux. Utilisation d'un test indirect à l'immuno-peroxydase.

This study was intended to assess the presence of antibodies to BCG: immunoglobulin G (IgG) and immunoglobulin M (IgM) in three homogenous african populations: 76 tuberculous patients, 55 adult healthy subjects and 46 newborn. We have used an indirect immuno-peroxidase reaction. Tuberculous patients were clearly distinguished from the other two groups by raised IgG titres, associated with severe clinical and radiological features. In the control population, the IgG anti-BCG were also present, but to a lesser degree. The IgM anti-BCG were seen in high titres (greater than 20 in this study) in healthy adults and patients. The two populations differed significantly (p less than 0.001), nevertheless some healthy adults achieved IgM titres comparable with tuberculous patients. This simple test could be an interesting contributory factor in cases of diagnostic difficult and enables a serological assessment of patients having BCG therapy.

[Salmonellosis in Dakar: bacteriological, clinical, epidemiological and therapeutic aspects. Ten years records (author's transl)]. / Salmonelloses à Dakar. Aspects bactériologiques, cliniques épidémiologiques et thérapeutiques. Bilan de 10 Années.

A study on salmonellosis in Senegal has been carried out in Dakar at the University Hospital of Fann from 1966 to 1976. The authors describe the various methods of isolating the germs (mainly hemoculture and coproculture) and the techniques used for bacteriological research (antibiograms, tests on plasmidic resistance). The results of these investigations, which took the whole of 10 years, are presented below, in accordance with their different aspects: - bacteriological: 1 335 strains of Salmonella have been isolated. Significantly, S. typhi is predominant (56,6 p. 100). But 7 serotypes represent 90 p. 100 of the total strains which are now in existence in Dakar; - clinical: the aspects of these diseases vary: typhoïd fever, encephalitis, diarrheic syndrome, especially among infants, and purulent meningitis, which is generally severe; - therapeutic: 880 strains have been tested with 10 antibiotics. Two groups of Salmonella serotypes are opposed: those which are sensitive (S. typhi, S. typhi murium, S. enteritidis, S. paratyphi C), those which have become resistant (S. stanleyville, S. havana, S. ordonez). The most frequent antibiotype of this kind is ASKCTSu. This is a phenomenon of plasmidic resistance, demonstrated by in vitro experiments; - epidemiological: the lysotypes of 86 strains have been determined. Two epidemiological features must be described: either a stable endemic situation with sensitive strains - or epidemics, lasting several years, with resistant serotypes. Different therapeutic schemes can be used: chloramphenicol for typhoid fever, or sometimes cotrimoxazole, or ampicillin for meningitis. In diarrheic syndrome, symptomatic treatment is enough. Then, the authors give their comments on the special characteristics of salmonellosis in Dakar: - the influence of environment on the various clinical aspects of these diseases: very serious cases of meningitis, typhoid fever, which is more severe than in France, and complications when treatment has gone wrong at the beginning; - antibiograms, which are essential, in order to choose the adequate therapeutics; - and the different aspects of epidemillogy, which are linked to the sensitivity of the serotypes to the most active antibiotics. The existence of several resistant serotypes in Senegal is a real danger: plasmidic resistance could be transferred to S. typhi. In such a situation, epidemiological surveillance of salmonellosis is absolutely necessary, and control of enteric diseases, characterized by foecal transmission, must be carried out, with the techniques available in the country.

Treatment of purulent meningitis with a new cephalosporin-Rocephin (Ro 13-9904). Clinical, bacteriological and pharmacological observations in 24 cases.

In 21 of the 24 cases the diagnosis of purulent meningitis was confirmed by culturing the causal agent and/or by immunological diagnosis. The daily dosage of Rocephin ranged between 15 and 200 mg/kg administered in 2 i.m. injections. A cure was achieved in cases of meningococcal meningitis (1 case with sequelae: blindness in one eye), in 5 out of 6 cases of Haemophilus influenzae meningitis (1 case with severe neuropsychiatric sequelae), in 3 out of 9 cases of pneumococcal meningitis and in 2 out of 4 cases of enterobacterial meningitis. The tolerance was generally excellent. Sterilisation of the cerebrospinal fluid (CSF) was achieved in all 20 cases of meningitis confirmed by culture. The MIC levels are lower than the lowest CSF peak for Rocephin found in this study. The unusual pharmacological behavior of Rocephin makes it possible to achieve and to maintain for a long time highly satisfactory concentration levels in the CSF. These properties of Rocephin should lift the long-standing objections to the use of cephalosporins for the treatment of purulent meningitis.

[Incidence of pathogenic Escherichia coli in acute infantile diarrhea in Dakar]. / Incidence des Escherichia coli pathogènes sur les diarrhées aiguës infantiles à Dakar.

We have studied the incidence of enteropathogenic (EPEC), enteroinvasive (EIEC) and enterotoxigenic (ETEC) Escherichia coli associated with infant acute diarrhoeal disease in Dakar during a period of one year. We report 405 strains of Escherichia coli suspected to be the etiologic agent of the diarrhoea and isolated from 405 diarrheic stools of 0-5 years old children. We have isolated 119 pathogenic Escherichia coli with 63 EPEC (15.5%), 3 ETEC (0.7%) and 53 ETEC (13.1%) including 23 strains releasing heat-labile enterotoxin (LT+) and 30 strains releasing heat-stable enterotoxin (ST+). No ST+/LT+ strain was isolated. Escherichia coli with colonization factor antigens were isolated from 62 children. Almost all of them are CFAI+. Only one strain is CFAII+ and another one agglutinates with both CFAI and CFAII antisera. Among these CFA+ strains 5 belong to the EPEC group, 29 are enterotoxigenic (25 ST+ and 4 LT+) and 28 do not belong to any known etiopathologic group. Near 70% of the pathogenic Escherichia coli are from infants less than one year old, with a highest frequency between 7 and 12 months. Prevalence of ETEC is higher during the raining season. The existence of a great number of strains that belong to none of the 3 groups of etiopathologic Escherichia coli emphasis the need to search other factors of pathogenicity.

[The prognosis and treatment of pneumococcal meningitis in Africa. 402 cases (author's transl)]. / Pronostic et traitement des méningites à pneumocoque en Afrique. 402 observations.

Over a period of 5 years (1973--1977), 1083 patients were hospitalised in the Infectious Disease Clinic of the Dakar University Hospital Centre with bacteriologically confirmed purulent meningitis. The pneumococcus was responsible in 462 cases (42.6%). Analysis of 402 records showed that 234 patients (58.2% of cases) died, 123 were completely cured (30.6%) whilst there were neurological sequelae in 45 cases (28% of the survivors). The chief factors in poor prognosis were the existence and depth of changes in conscious level, age over 20 years, a CSF cell count of less than 500 per mm3, a CSF protein level greater than 2 g per 1 and I CSF antigen level over 8 microgram per ml. From a therapeutic standpoint, the percentage mortality was similar with chloramphenicol and with penicillin G, but complete cures were statistically more frequent in the patients treated initially with chloramphenicol.

[Leprosy and hepatitis B]. / Lèpre et hépatite B.

In 1966, B. S. Blumberg, investigating for carriers of the "Australia" antigen which he had discovered two years before, finds that the percentage is significantly more elevated in a group of leprous patients than in controls. In this initial work, realized at Cebu, Philippines, he mentions a higher percentage of this antigen carriers among the lepromatous than among the tuberculoid patients. He explains his findings by a genetic hypothesis and by the fact that lepromatous patients are more often hospitalized than the tuberculoid ones, thus narrowest contacts could favour the antigen transmission. Later, the established relation between Australia antigen and hepatitis B incites the authors to disregard the very deceiving genetic hypothesis and to build up the most important characteristic of lepromatous leprosy--cell immunity--as opposed to the tuberculoid form where cell immunity is normal. Investigation for seric markers of hepatitis B virus in patients with tuberculoid or lepromatous leprosy provides a model for the study on "cell immunity and hepatitis B". The juxtaposition of geographic areas with high prevalence of leprosy patients and of HBs Ag carriers is a supplementary argument for the study of their connection. Up to now, about fifty works have been published on this subject. Most of them investigate detection of HBs Ag and a few of HBe Ag and HBs Ac. This bibliographical study, including a personal study, reviews markers of hepatitis B virus replication in leprosy patients, incidence of hospitalization and age of these patients, as well as the methodology used.