Management of transitional cell carcinoma of the urinary bladder at Kenyatta National Hospital, Nairobi.

OBJECTIVES: To highlight the management of patients with transitional cell carcinoma of the urinary bladder with regards to clinical presentation, treatment and outcome. DESIGN: A retrospective study. SETTING: Kenyatta National Hospital, Nairobi, Kenya. SUBJECTS: Fifty two patients who presented at Kenyatta National Hospital over a ten year period with histologically proven transitional cell carcinoma of the urinary bladder. There were 41 males and 11 females aged 27 to 84 years. The mean age was 57 years. RESULTS: An average of 5.2 patients per year were seen. The male to female ratio was 3.7:1. Most common clinical presentations were haematuria 98%, Lower abdominal pains 71%. The main investigative procedures done in these patients included cystoscopy in 71.2%, ultrasound 46.2%, IVU 32.7% among others. The treatment modalities were based on the stage of the disease and included surgery 48.1%, combination therapy in 23.1%, chemotherapy in 5.8% and radiotherapy in 3.8%. Surgery was the mainstay of treatment, cystectomy was done in 26.9% and cystostomy and resection of tumour 26.9%. Other surgical methods carried out were transurethral resection of bladder tumour(TURBT), cystectomy and bladder augumentation, channel transurethral resection, cystectomy and ileocondult. Nine patients (17.3%) were not given any treatment because either the disease was too advanced and died before any treatment was instituted or were lost to follow up. Mortality and outcome of the disease was difficult to assess due to poor follow up, however 65.4% of the patients were still alive, 17.3% had died and 17.3% were lost to follow up by the end of the study period. CONCLUSION: Haematuria was the most important presenting clinical feature. Poor record keeping may have contributed to the low number of patients enrolled into the study. The TCC in this study was not thoroughly managed. It is suggested that early diagnosis, early surgery and combination of other treatment modalities should improve the outcome. This can only be possible with further training of health personnel, the education of the public and availability of improved diagnostic as well as treatment facilities especially cystoscopes and resectoscopes. There is need for developing proper management protocols for bladder tumours.

Pattern of transitional cell carcinoma of the urinary bladder as seen at Kenyatta National Hospital, Nairobi.

OBJECTIVE: To highlight the pattern of patients with transitional cell carcinoma of the urinary bladder with regards to age, sex, ethnic origin and histopathological classification. DESIGN: A ten year retrospective study. SETTING: Kenyatta National Hospital, Nairobi, Kenya. SUBJECTS: Fifty two patients who presented at Kenyatta National Hospital over the ten year period with histologically proven transitional cell carcinoma of the urinary bladder. There were 41 males and 11 females aged 27 to 84 years. The mean age was 57 years. RESULTS: The peak incidence was in the 60-69 years age group. The male to female ratio was 4:1. The regional (provincial) distribution revealed Central and Eastern had 77%, Rift valley had 6%, Nairobi, North Eastern, Western and Coast provinces had 2% each. In the ethnic distribution; Kikuyus, Kambas and Merus were 77% while others were 17.3%. Transitional cell carcinoma was found in 67% of the patients, 60% had advanced disease. Twenty nine percent were smokers while 25% consumed alcohol. The main occupation was farming in 65%. The most Common clinical presentations were haematuria 98% and lower abdominal pains in 71%. A total of 99,028 patients were admitted to the surgical wards,transitional cell carcinoma patients represented only 0.6%. CONCLUSION: Transitional cell carcinoma is a rare disease. At Kenyatta National Hospital it only represented 0.6% of all surgical admissions during the study period. It accounted for 67% of all bladder tumours an increase in incidence compared to previous studies. It is common in males more than females, with a peak in the seventh decade. Majority of the patients were from central Kenya. Alcohol, smoking and farming were the most important risk factors. Haematuria was the most important presenting clinical feature. Poor record keeping may have contributed to the low number of patients enrolled into the study. There is need for a thorough prospective study to find out the actual prevalence of bladder tumours.

Schistosoma haematobium-induced urinary tract morbidity correlates with increased tumor necrosis factor-alpha and diminished interleukin-10 production.

This study examined the hypothesis that the nature of the host cellular immune response to schistosome ova is a risk factor for urinary tract morbidity in areas in which Schistosoma haematobium is endemic. S. haematobium-infected children and adolescents with bladder pathology assessed by ultrasonography had 54-fold greater tumor necrosis factor (TNF)-alpha production and a 120-fold greater ratio of TNF-alpha to interleukin (IL)-10 release by peripheral blood mononuclear cells in response to egg antigens, in comparison with control children and adolescents matched by age, sex, and infection severity. Mycobacterial antigens also stimulated 7-fold more TNF-alpha among subjects with bladder morbidity than in control subjects, which suggests an innate predisposition to enhanced TNF-alpha production. Levels of egg antigen-induced IL-4 and -5 and interferon-gamma were equivalent in subjects with and without bladder pathology. Thus, children and adolescents predisposed to increased TNF-alpha production to S. haematobium infection are more likely to develop an exaggerated granulomatous response to ova trapped in the bladder wall, with associated urinary tract pathology.

A new transacting factor that modulates hypoxia-induced expression of the erythropoietin gene.

Hypoxia is a strong stimulus for the transcription of a set of genes, including erythropoietin and vascular endothelial growth factor. Here we report on the cloning, functional significance, and expression of a complementary DNA (cDNA) that is involved in hypoxia-mediated expression of these 2 genes. The full-length cDNA encodes a predicted protein of 806 amino acids that contains a leucine zipper motif. This protein, termed HAF for hypoxia-associated factor, binds to a 17-base pair (bp) region of the erythropoietin promoter, which was shown earlier to participate in hypoxia-induced expression of the erythropoietin gene. In Hep3B cells, clones modified to express HAF antisense RNA showed an attenuated response to hypoxia-mediated induction of both erythropoietin and vascular endothelial growth factor transcription. HAF showed sequence-specific interaction with a DNA element in the 5' untranslated region of VEGF gene. The HAF 2.6-kilobase (kb) messenger RNA (mRNA) is expressed in most adult tissues. The highest expression occurs in fetal liver and the least in adult liver. HAF is the murine homolog of Sart-1, a 125-kd human protein expressed in the nuclei of normal and malignant cells. (Blood. 2000;96:491-497)

Frequent umbilical cord-blood and maternal-blood infections with Plasmodium falciparum, P. malariae, and P. ovale in Kenya.

The prevalence of malaria infection in 102 paired maternal-blood and umbilical cord-blood samples was assessed by microscopy and polymerase chain reaction (PCR) in a holoendemic area in Kenya. Plasmodium falciparum single-species infection was detected in maternal peripheral blood (3.4%), whereas microscopy indicated that no Plasmodium species were in cord blood. In contrast, maternal-blood samples showed a PCR prevalence of 48% for P. falciparum, 25% for P. malariae, and 24% for P. ovale, and cord-blood samples showed a PCR prevalence of 32%, 23%, and 21%, respectively. Although mothers with mixed-species infections were more likely to have offspring infected with mixed species, the specific malaria species were discordant in paired maternal- and cord-blood samples. Triple-species infections were observed in 11 cord- and maternal-blood samples at a 5.5-fold greater frequency than expected. These findings indicate that Plasmodium species infections in cord blood are common, occur at lower densities, and may be acquired before parturition.

Long-term suppression of adult bladder morbidity and severe hydronephrosis following selective population chemotherapy for Schistosoma haematobium.

Repeated selective population chemotherapy of school age children reduces infection and morbidity associated with Schistosoma haematobium infection. To examine the long-term effect of this treatment on susceptibility to re-infection and late disease, a cohort of Kenyans (n = 194) were re-examined for infection and urinary tract morbidity 7-13 years after they underwent annual ultrasonography and treatment for an average of 5 years beginning in 1984 as children. Controls were previously untreated age-matched individuals residing in the same or adjacent villages. The overall prevalence and intensity of infection were equivalent between the 2 groups. In contrast, the prevalence of bladder wall pathology was 11-fold lower in previously treated (1.5%) versus untreated subjects (17%). Severe hydronephrosis was completely reversed. These data demonstrate that treatment significantly reduced urinary tract morbidity despite re-infection, and suggest that the important risk factors for urinary tract morbidity in adulthood are cumulative intensity and duration of infection during early adolescence.

Parameters associated with Schistosoma haematobium infection before and after chemotherapy in school children from two villages in the coast province of Kenya.

We evaluated the impact of praziquantel therapy (40 mg/kg body weight) on indicators of infection with Schistosoma haematobium by following a cohort of infected children from schools located 12 km apart in the Coast province of Kenya, at 0, 2, 4, 6, 12 and 18 months after treatment. Within this period, measurements of infection parameters pertaining to egg counts and haematuria (micro-, macro- and history) were evaluated at all time points. The initial prevalence of 100% dropped significantly 8 weeks after treatment with a similar trend in the intensity of infection. Microhaematuria followed the same trend as observed for egg counts while macrohaematuria remained low after treatment. Reinfection following successful therapy differed significantly between schools; in one school the children were reinfected immediately while those in the other remained uninfected despite similar starting prevalences, intensities of infection and cure rates. Transmission between the two areas looked homogeneous before treatment but when both groups were treated, contrasting transmission patterns became evident. In a regression model we evaluated factors that might be associated with reinfection, and after allowing for pretreatment infection level, age and sex, area (school) remained a highly significant predictor.

Helminth- and Bacillus Calmette-Guérin-induced immunity in children sensitized in utero to filariasis and schistosomiasis.

Infants and children are routinely vaccinated with bacillus Calmette-Guérin (BCG) in areas of the world where worm infections are common. Because maternal helminth infection during pregnancy can sensitize the developing fetus, we studied whether this prenatal immunity persists in childhood and modifies the immune response to BCG. Children and newborns living in rural Kenya, where BCG is administered at birth and filariasis and schistosomiasis are endemic, were examined. T cells from 2- to 10-year-old children of mothers without filariasis or schistosomiasis produced 10-fold more IFN-gamma in response to mycobacterial purified protein derivative than children of helminth-infected mothers (p < 0.01). This relationship was restricted to purified protein derivative because maternal infection status did not correlate with filarial Ag-driven IL-2, IFN-gamma, IL-4, or IL-5 responses by children. Prospective studies initiated at birth showed that helminth-specific T cell immunity acquired in utero is maintained until at least 10-14 mo of age in the absence of infection with either Wuchereria bancrofti or Schistosoma haematobium. Purified protein derivative-driven T cell IFN-gamma production evaluated 10-14 mo after BCG vaccination was 26-fold higher for infants who were not sensitized to filariae or schistosomes in utero relative to subjects who experienced prenatal sensitization (p < 0.01). These data indicate that helminth-specific immune responses acquired during gestation persist into childhood and that this prenatal sensitization biases T cell immunity induced by BCG vaccination away from type 1 IFN-gamma responses associated with protection against mycobacterial infection.

B cell sensitization to helminthic infection develops in utero in humans.

Human neonates are generally deficient in their ability to generate humoral immunity. This deficiency is thought to reflect physiologic immaturity of T and B cell function and lack of previous exposure to exogenous Ags. To determine whether neonatal humoral immunity can be modified by maternal helminth infection during pregnancy, we assessed Ig production by cord blood lymphocytes from healthy newborns of mothers living in an area of Kenya where schistosomiasis, bancroftian filariasis, and geohelminth infections are endemic. Twelve of 40 and 17 of 39 cord blood lymphocyte preparations from healthy newborns in Coast Province, Kenya, spontaneously made polyclonal IgE (range, 0.15-21 ng/ml) and IgG (1.6-10.1 ng/ml) in vitro. In vitro IgE synthesis by cord blood lymphocytes (CBL) was, on the average, 10-fold less than that of PBMC of Kenyan mothers (1.1-98 ng/ml) and was undetectable for CBL from newborns delivered in the United States. Schistosome and filarial Ags stimulated a 3- to > 100-fold increase in the production of polyclonal IgE and parasite-specific IgG Abs by lymphocytes from 10 of 40 and 6 of 39 Kenyan newborns, respectively. CBL observed to have helminth Ag-driven B cell responses were more likely to be from newborns of schistosome- or filaria-infected mothers than from uninfected mothers (p < 0.05). These data indicate that the human fetus can be sensitized in utero to produce helminth-specific B cells and that neonatal B cells are intrinsically capable of IgE and IgG production.

A school-based approach to the control of urinary schistosomiasis and intestinal helminth infections in children in Matuga, Kenya: impact of a two-year chemotherapy programme on prevalence and intensity of infections.

A school- and chemotherapy-based urinary schistosomiasis and intestinal helminth infection control programme was conducted in Matuga Division, Kwale District, Coast Province with teachers taking care of diagnosis, treatment and health education. More than 12,000 children in 36 primary schools were included in the 2-year programme. Results for 20 evaluation schools are presented. Children with haematuria were treated with praziquantel (40 mg/kg) once a year. Within 2 years, the prevalence of haematuria in the schools was reduced from 28% (range 8-68%) to 11.4% (range 3-23%). More than 80% of the schoolchildren were infected with one or more intestinal helminths at baseline. After one year with levamisole mass chemotherapy, single dose (2.5 mg/kg) three times a year (once per school term), the prevalence of Ascaris infection was reduced by 83% from 18% to 3%, but there was no change in pretreatment prevalences of hookworm (57%) and Trichuris (56%) infections. In the second year of the programme, albendazole 600 mg once every six months was administered to the children in 10 randomly selected schools. This resulted in 52% and 23% reductions in prevalences of hookworm and Trichuris infections, respectively, in these schools and a reduction in mean intensity of infection of 52.8% and 50.3%, respectively.

In utero exposure to helminth and mycobacterial antigens generates cytokine responses similar to that observed in adults.

Neonates exposed to parasite antigens (Ags) in utero may develop altered fetal immunity that could affect subsequent responses to infection. We hypothesized that cord blood lymphocytes (CBL) from offspring of mothers residing in an area highly endemic for schistosomiasis, filariasis, and tuberculosis in Kenya would either fail to respond or generate a predominantly Th2-associated cytokine response to helminth and mycobacterial antigens (PPD) in vitro compared to maternal PBMC. Kenyan CBL generated helminth Ag-specific IL-5 (range 29-194 pg/ml), IL-10 (121-2,115 pg/ml), and/or IFN-gamma (78 pg/ml-10.6 ng/ml) in 26, 46, and 57% of neonates, respectively (n = 40). PPD induced IFN-gamma in 30% of Kenyan CBL (range 79-1,896 pg/ml), but little or no IL-4 or IL-5. No Ag-specific IL-4, IL-5, or IFN-gamma release was detected by CBL obtained in the United States (n = 11). Ag-driven cytokine production was primarily CD4-dependent. Cytokine responses to helminth and mycobacterial Ags by maternal PBMC mirrored that observed in neonates. CBL from helminth infected and/or PPD-sensitized mothers produced more Ag-specific cytokines compared to CBL from uninfected mothers (P < 0.05). These data demonstrate that the human fetus develops similar patterns of cytokine production observed in adults and indicates that prenatal exposure may not lead to tolerance or altered fetal immunity. .

Men's knowledge, attitudes and practices with regard to family planning.

PIP: While African men are largely apathetic to family planning, they are not necessarily uninterested. Many African men want to participate more actively in deciding how many children they should have and when to have them, but they lack sufficient information to do so. In some cases, many men do not know about contraceptives. Even those who are aware have little access to such services because family planning programs are designed to serve women. In most African countries, family planning services are widely offered in the prenatal units of public hospitals where many African men feel uncomfortable visiting. Studies in parts of Africa have shown that there is a strong link between knowledge and the use of contraceptives and the level of education as well as economic status; the levels of knowledge and use of family planning methods are lower among the relatively less educated. Both print and electronic media are vital reproductive health information dissemination tools. Innovative Communications System (ICS) has operated a men's only family planning clinic at Kencom House, Nairobi, since 1993. Likewise, the Family Planning Association of Kenya is setting up male-only clinics in Nakuru, Kakamega, and Kisumu districts.^ieng