Cerebral amyloid beta protein deposits and other Alzheimer lesions in non-demented elderly east Africans.

There is little knowledge of the existence of Alzheimer disease (AD) or Alzheimer type of dementia in indigenous populations of developing countries. In an effort to evaluate this, we assessed the deposition of amyloid beta (A beta) protein and other lesions associated with AD in brains of elderly East Africans. Brain tissues were examined from 32 subjects, aged 45 to 83 years with no apparent neurological disease, who came to autopsy at two medical Institutions in Nairobi and Dar es Salaam. An age-matched sample from subjects who had died from similar causes in Cleveland was assessed in parallel. Of the 20 samples from Nairobi, 3 (15%) brains exhibited neocortical A beta deposits that varied from numerous diffuse to highly localized compact or neuritic plaques, many of which were also thioflavin S positive. Two of the cases had profound A beta deposition in the prefrontal and temporal cortices and one of these also exhibited moderate to severe cerebral amyloid angiopathy. Similarly, 2 of the 12 samples from Dar es Salaam exhibited diffuse and compact A beta deposits that were also predominantly reactive for the longer A beta 42 species compared to A beta 40. We also noted that A beta plaques were variably immunoreactive for amyloid associated proteins, apolipoprotein E, serum amyloid P and complement C3. Tau protein reactive neurofibrillary tangles (NFT) were also evident in the hippocampus of 4 subjects. By comparison, 4 (20%) of the 20 samples from randomly selected autopsies performed in Cleveland showed A beta deposits within diffuse and compact parenchymal plaques and the vasculature. These observations suggest A beta deposition and some NFT in brains of non-demented East Africans are qualitatively and quantitatively similar to that in age-matched elderly controls from Cleveland. While our small scale study does not document similar prevalence rates of preclinical AD, it suggests that elderly East Africans are unlikely to escape AD as it is known in developed countries.

A histological and immunohistological study of malarial placentas.

Sections of 18 malaria-infected placentas were stained with haematoxylin and eosin, periodic acid and methenamine silver, and immunohistochemically with monoclonal antibodies against human common leukocyte antigen, CLA (CD 45), B cells (CD 20, L 26), T cells (CD 45RO, UCHL-1) and collagen IV. Parasitized erythrocytes accumulated in the maternal villous spaces, with none in the foetal circulation. These were found in association with inflammatory leukocytes and pigments. Fibrinoid necrosis was more prevalent in the heavily infected placentas. Thickening and reduplication of foetal capillary basement membranes, and a decrease in leukocytes, including B and T cells, were seen in the heavily infected placentas. These findings are in keeping with previously reported depression of cellular and humoral immunity in patients with heavy parasitaemia.

Expression of cytokeratin and neuron-specific enolase in small cell carcinomas of the lung.

Using a polyclonal antibody against human epidermal keratins and a monoclonal antibody against cytokeratins characteristic of simple epithelia, and the Avidin-Biotin system of immunohistochemistry, we have demonstrated cytokeratin expression in 46% and in 60% of small cell carcinomas of the lung at autopsy respectively. The latter gave a diffuse stronger reaction product than the polyclonal antibody. The results suggest that there is a cytokeratin rich and a cytokeratin poor type of small cell carcinoma. Neuron-specific enolase immunohistochemistry was positive in 60% of the cases. Coexpression with cytokeratin was seen in ten cases (30%). The expression of cytokeratin and neuron-specific enolase in small cell carcinomas strongly suggests that they are of an epithelial origin, but are capable of neuroendocrine differentiation.

The incidence of squamous and transitional cell carcinomas of the urinary bladder in northern Tanzania in areas of high and low levels of endemic Schistosoma haematobium infection.

Squamous cell carcinoma is the commonest type of bladder malignancy in most areas of northern Tanzania. Of 172 cases of bladder cancer recorded in 9 years, 72% were squamous cell carcinomas. Of these, 46% had Schistosoma haematobium eggs in sections taken from tumour tissue. The geographical distribution of this tumour closely corresponded to the prevalence of S. haematobium infection. The Mt Kilimanjaro area is free of schistosomiasis and virtually lacks squamous cell carcinoma. Although transitional cell carcinoma is rare in all regions of northern Tanzania, the relative frequency of bladder cancer in the Mt Kilimanjaro area was only one-third of that seen in other regions; population-based incidence rates were also very low in this area.

Evaluation of risk factors for Alzheimer's disease in elderly east Africans.

A number of biological risk factors have been implicated for Alzheimer's disease (AD). The investigation of prevalence rates of AD in crosscultural populations has much potential in validating these factors. We previously assessed brain amyloid beta (A beta) protein deposition and other lesions associated with AD as possible markers for preclinical AD in elderly nondemented East Africans. In further analysis, we demonstrate that 17-19% of elderly East African subjects without clinical neurological disease exhibited neocortical A beta deposits and minimal neurofibrillary changes at necropsy that was qualitatively and quantitatively similar to that in an age-matched elderly control sample from Cleveland, OH. A beta deposits varied from numerous diffuse to highly localized neuritic plaques and were predominantly reactive for the longer A beta 42 species. In parallel studies, we evaluated another recently implicated factor in AD, the apolipoprotein E genotype. We found relatively high frequencies of the apolipoprotein E-epsilon 4 allele in elderly nondemented East Africans. The frequencies were comparable to those in other African populations but higher than in subjects from developed countries. Our limited study suggests that elderly East Africans acquire cerebral lesions found in AD subjects but the apolipoprotein E-epsilon 4 allele may not be a highly specific factor for the disease among East Africans.

Expression of estrogen and progesterone receptors in carcinomas of the female breast in Tanzania.

In Africa breast cancer has been reported to occur frequently in young females and to show an aggressive histological and clinical picture, suggesting that this malignancy might have a different biology from this disease in Western females. To investigate this, the present study assessed by immunohistochemistry the expression of estrogen receptors (ER) and progesterone receptors (PgR) in 60 fresh frozen breast cancer tissues from indigenous Tanzanian patients. This prospective study collected tissues from routine patients treated at the Muhimbili Medical Center, Dar es Salaam, Tanzania. These markers have not been previously investigated in indigenous sub-Saharan females with breast cancer. Patients in this study expressed lower frequencies of ER (33%) and PgR (18%) as compared to literature reports including those about African-Americans. Expression of these markers, however, correlated with the demographic, clinical and histological characteristics in a similar way as observed elsewhere. A compounding effect of younger patients' age, advanced disease or late stage at hospital presentation and race in this geographical region could be responsible for the poor expression of hormonal receptors in the majority of patients as observed in this study. A surprising finding was that the proportion of hormonal receptor positive tumors increased with disease duration. In view of the low frequency of expression of hormonal markers, only 26.7% of the patients would be expected to benefit from hormonal therapy based on their expression of the hormone receptors. There is great need to undertake an inter-African study that would evaluate the hormonal status of more African women with breast cancer in different geographical regions of sub-Saharan Africa and document the true picture of their hormonal status. The outcome of these results could be important for treatment strategies for the second most common cancer among African women.

Immunological profile of endemic and epidemic Kaposi's sarcoma patients in Dar-es-Salaam, Tanzania.

Kaposi's sarcoma (KS) presents in four clinicopathological types namely classical/sporadic (CKS), endemic African (EKS), iatrogenic (IKS) and that associated with AIDS (AKS). Recently a putative herpes virus (HHV-8) was described and shown to be present in all four types of KS. The immunological status of patients with EKS has been conflicting. In this study total leucocyte counts, total lymphocyte counts and lymphocyte subsets of patients with EKS and AKS were determined by flow cytometry and compared to those of healthy HIV-1 seronegative controls. Results show that 50% of EKS lesions were of nodular type. Patients with EKS had significantly lower levels of CD4+ T- lymphocytes and CD4:CD8 ratio but significantly higher CD8+ T-lymphocytes compared to controls. Patients with AKS had significantly lower levels of CD4+ T-lymphocytes and also CD4:CD8 ratios but significantly higher percentage of CD8+ T-lymphocytes when compared with EKS patients. These findings indicate that in both forms of KS there is a certain degree of immunological disturbance which is more conspicuous in AKS because of HIV infection and suggests that HIV-1 acts synergistically with the aetiological agent (HHV-8) to cause a more aggressive type of KS.

Characterisation of benign lesions and carcinomas of the female breast in a sub-Saharan African population.

Carcinoma of the breast is the second most frequent tumour in African females. Breast carcinomas in African females appear about a decade earlier and follow a more aggressive clinical course than those in developed countries. To elucidate this difference we investigated 63 biopsied benign lesions of the female breast for their potential to malignant progression. We also performed histologic typing and grading of 184 female breast carcinomas received at the Muhimbili University Hospital in Dar es Salaam, Tanzania. Fibrocystic disease and fibroadenomas were the most frequent lesions. The majority of patients with fibrocystic disease had no proliferative lesion and thus were not at a significantly increased risk of developing breast carcinomas. For fibroadenomas, no indication for precancerous lesions was found. The vast majority of breast carcinomas investigated were invasive. As a striking feature, the majority of those studied (66%) were of the non-special type (NST), displaying a more aggressive behaviour than the remaining tumours of the special type (ST). In the group of ST tumours, cribriform types constituted 41% of the cases which may be a special feature of the carcinomas in African females. Among the NST, the tumours were either of grade II or grade III, whereas in ST, 25% of the cases were of grade I. Since histology observed in this study is comparable to that seen in patients from the Western society, late hospital presentation with advanced tumour stages may be a major reason for differences in clinical behaviour between African and Western females. A genetic factor, however, may be an important contributing factor.

Neuropathology of human immunodeficiency virus 1 infection. Significance of studying in forensic autopsy cases at Dar es Salaam, Tanzania.

OBJECTIVE: In sub-Saharan Africa, only a few studies of neurologic complications of human immunodeficiency virus 1 (HIV-1) infection have been done. The authors studied neuropathology of HIV-1 infection in Tanzania. DESIGN: Forensic autopsy study at Dar es Salaam, Tanzania. SETTING: A joint research project between Dar es Salaam, Tanzania, and Kumamoto, Japan. PATIENTS: Thirty patients with risk factors for HIV-1 infection. MAIN OUTCOME MEASURES: Human immunodeficiency virus 1 infection was evaluated by HIV-1 antibody test on postmortem serum samples. The brains of HIV-1-infected persons were studied histopathologically. RESULTS: Infection with HIV-1 was identified on postmortem serum samples in 10 of 30 forensic autopsy cases. Neuropathologic changes of the brain were observed in 8 of the 10 HIV-1-infected persons; these changes consisted of lymphocytic meningitis, bacterial meningoencephalitis, cryptococcal meningoencephalitis, tuberculous meningitis with brain abscesses, and intracerebral hemorrhage. CONCLUSIONS: Because none of the persons studied was suspected to have had brain diseases before autopsy, the results suggest that brain diseases of HIV-1-infected patients are likely to go unrecognized in Tanzania. In addition, the high incidence of neuropathologic findings in HIV-1-infected persons indicates that HIV-1-related brain diseases are common in Tanzania, as they are in developed countries. Further forensic autopsy study will determine the range and prevalence of brain complications and have immediate impact on the management of HIV-1-infected patients in Tanzania and other developing countries.

Differential rates of carcinoma of cervix uteri among the Chagga and Pares of Kilimanjaro region, Tanzania.

Cervical cancer is the commonest cancer among females in Northern Tanzania. Female Pares showed a higher age specific incidence rate especially in the older age groups (50-65 years) compared to Chagga females. The incidence per year per 100,000 women, corrected to the standard African population was 5.0 in Moshi and 9.6 in Pare, during the study period. Both of these ethnic groups live in a limited geographic region and are culturally similar. The higher rate of cervical cancer among the Pares seems to be due to their increased sexual activity which is usually with several male partners.

Histopathology of malignant tumours of childhood in Tanzania.

OBJECTIVE: To determine the frequency distribution of malignant tumours of childhood aged 0-14 years. DESIGN: A retrospective histopathological review of 541 cases of malignant tumours of childhood. SETTING: Cancer Registry, Department of Histopathology, Muhimbili Medical Centre, Dar es Salaam, Tanzania. RESULTS: Malignant tumours of childhood accounted for 11.5% of all malignant tumours recorded in the cancer registry. Commonest malignant tumours were lymphomas (53%), of which 31.4% were Burkitt's lymphoma (BL), 14.9% Hodgkin's disease (HD), and 6.6% Non-Hodgkin's lymphoma (NHL). Others were retinoblastoma (12.9%), carcinoma (9%), nephroblastoma and soft tissue sarcoma each 6.7% and Kaposi's sarcoma (5.9%). Bone, germ cell and nervous system tumours were rare. CONCLUSION: These findings may act as a basis for which further studies on malignant tumours of childhood in Tanzania could be carried out.

Neurofibromatosis and malignant schwannomas in Tanzania.

In a five-year-period, twenty three cases of peripheral nerve tumours were seen at the pathology department of Muhimbili Medical Centre. Nine of these had von-Recklinghausen's disease (neurofibromatosis). One of these patients developed malignant schwannomas at two different sites simultaneously. Patients with malignant disease in Tanzania as in other sub-Saharan African countries usually get to the large referral hospitals late in the course of their disease. Despite this delay and the advanced nature of their illness, attempts should be made to achieve satisfactory palliative results.

A comparative study of carcinoma of the breast in an African population.

In a retrospective study of female breast cancer recorded by the Tanzania Cancer Registry, a total of 1028 cases were notified between 1974 to 1987. This represented 8.1% of all female cancers. Of these, 8.0% were below thirty years of age. The peak prevalence was found in the 35 to 44 year old age group. Both the peak prevalence and the high proportion of patients under thirty years suggest that the majority of breast cancer in Tanzania and also in other sub-Saharan African countries are younger than in the populations of North America and Europe. An attempt is made to determine whether this difference is real or is a statistical aberration based on population epidemiology or culture. Mastectomy, the treatment that is usually offered has severe psychological trauma to these young patients. Therefore, early detection of the disease with a breast conservation procedure is advocated.

Dermatofibrosarcoma protuberans: a clinicopathological study in an African population.

Dermatofibrosarcoma protuberans (DFSP) is a slow-growing, locally aggressive fibrous tumour which rarely metastasises to regional lymphnode or distant sites. The rarity, age pattern of occurrence and the male to female ratio of the tumour were found to correspond to reports elsewhere. But contrary to other reports, the lower limb and not the trunk was found to be the site of predilection of the tumour in Tanzania. This and the tendency of occurrence of the tumour on the scalp in females rather than at other sites in the head and neck region seem to implicate trauma as a predisposing factor. It is difficult to differentiate between DFSP, keloids and hypertrophi scars on the basis of clinical presentation without biopsy. The treatment of choice of this lesion is wide excision followed by skin grafting. It is emphasised that all hypertrophi scars and keloids should be histologically examined in order to rule out DFSP so that it is correctly treated in order to avoid recurrence.

Expression of oestrogen and progesterone receptors, Ki-67, p53 and BCL-2 proteins, cathepsin D, urokinase plasminogen activator and urokinase plasminogen activator-receptors in carcinomas of the female breast in an African population.

OBJECTIVE: To determine the expression of oestrogen (ER) and progesterone receptor (PgR), Ki-67, p53, bcl-2 proteins and the proteolytic enzymes cathepsin D (CD), urokinase-plasminogen activator (uPA) and its receptor (uPA-R) in primary carcinomas of the breast from indigenous Tanzanian female patients by immunohistochemistry. DESIGN: Prospective cross-sectional study. SETTING: Muhimbili Medical Centre, Dar es Salaam, Tanzania. SUBJECTS: Sixty patients admitted between 1995 and 1997. RESULTS: Markers were found to be expressed as follows: ER (33.3%), PgR (18.3%), p53 (30%), bcl-2 (43.5%) and the median proliferation rate of Ki-67 was 15%. Proportion of tumours positive for ER, PgR and bcl-2 initially decreased to 12 months disease duration, after which it increased. The observed proliferation rate approaches that reported in developed countries. p53 expression did not influence the proliferation rate nor did bcl-2 expression. ER, PgR and bcl-2 were strongly co-expressed. CD was predominantly expressed in stromal macrophages than in cancer cells. CONCLUSION: The low expression of ER and PgR and their strong co-expression with bcl-2 might negatively influence response to hormonal therapy. The influence of bcl-2 on tumour response to anti-cancer therapy in patients with long disease duration requires urgent clarification. Determination of CD in stromal macrophages rather than in cancer cells may have greater prognostic significance in patients of this region.

Breast cancer and conservative surgery in sub Saharan Africa.

This study investigated the profile of breast cancer patients in Tanzania during 1974-87 period. The results were compared with those of African patients in countries south of the Sahara. The maximum number of patients with breast cancer were seen in the sexually active age groups. In Sudan breast cancer was in leading position amongst all female cancers but with a lower proportion of women below 30 years, 6.4% (95% CI 5.3-7.6); x2 = 7.3 (p = 0.006). While in other sub-Saharan countries the disease ranked second to cervical cancer in frequency, but with a high proportion of patients below 30 years of age. This proportion was highest in Nigeria when compared with other African countries studied 14.7% (95% CI 8.9-22.3); x2 = 3.9 (p = 0.04). Mastectomy continues to be the treatment of choice for breast cancer in the sub Saharan countries despite the fact that this procedure is resented. Also that the Halstedian principle which governed the treatment of the disease for a century now has been disputed regarding its usefulness. The biological basis for adopting conservative surgery for breast cancer, the need for early detection and the oncogenesis of the disease are discussed.

Ploidy and proliferation rates in carcinomas of the breast in Tanzania.

Routinely collected, processed and stored breast cancer tissue blocks recovered from the archives of the Pathology laboratory in Dar es Salaam after storage of up to 3 years were analysed by a flow cytometry for DNA ploidy and S-phase fraction. Results showed that archival material stored in humid tropical conditions may be used for flow cytometric analysis. The mean age of the patients was rather low and aneuploidy was much rarer when compared to studies from Western countries, but the figures on S-phase fraction were comparable. The predominant histological type was infiltrating ductal carcinoma. These results seem to indicate that there may be some differences in the biology of breast cancer between Tanzania and other countries. Studies to confirm these preliminary findings are desirable.

Toxoplasma encephalitis in HIV: case report.

In Tanzania, no data are available on the prevalence of brain infection by toxoplasma in HIV-infected patients. A case of a 35-year old man with fulminant toxoplasma encephalitis (TE) is reported for the first time. TE was not suspected clinically in our patient who presented with a one week history of severe headache and treated empirically with antimalarial drugs. TE was diagnosed postmortem histologically by haematoxylin-eosin and immunohistochemical stain with P30 antibody for toxoplasma antigen. The findings in our case support the suggestion that a high index of suspicion for TE should be maintained in HIV-infected patients presenting with focal neurological symptoms. The case highlights the importance of autopsy studies in not only documenting a toxoplasma brain lesion but also in increasing the awareness for its diagnosis in HIV-infected patients in Tanzania and other developing countries.

Cutaneous squamous cell carcinoma in Tanzania.

The Tanzania Cancer Registry at Muhimbili Medical Centre, Dar es Salaam, Tanzania was reviewed for squamous cell carcinoma of the skin in non-albino African subjects. The data was analysed for age, sex, site and predisposing factors. Our results were then compared with studies previously carried out in Tanzania, elsewhere in Africa and also on Blacks in America. Squamous cell carcinoma of the skin was found to be a common malignancy, and the commonest skin cancer. Its peak was in the 40-49 years age group though it could occur in children under five years of age. The most affected site was the lower limb, followed by the head and the neck. The penis in the male and the vulva in the female were the third most affected sites. The scalp and the lip were more affected in females than males. Chronic trauma, chronic ulcers, and scars were the main predisposing risk factors to the lower limb and the scalp, while ultra violet radiation to the head and neck, and smegma of the uncircumcised penis were thought to be predisposing risk factors.

Epidemiology of intestinal and diffuse types of gastric carcinoma in the Mount Kilimanjaro area, Tanzania.

Carcinoma of the stomach is the commonest malignancy in the Mount Kilimanjaro area of Tanzania, with relative frequencies of 16.3 and 15.1% of all malignancies for males and females, respectively; and even considerably higher population based incidences than in other African registries. In this area with high risk for gastric carcinoma the ratio of intestinal to diffuse type (I:D) was significantly higher, 4.1 compared with 2.1 in the other, lower risk, regions of Northern Tanzania. Tumours of intestinal type were more often seen in young patients around Mount Kilimanjaro than in other countries, 6.0% of the patients with an I:D of 3.7 being under 35 years of age. Likewise, the proportion of females with gastric carcinoma was higher in the Mount Kilimanjaro area with an I:D ratio of 3.1, compared with 1.7 in females from the other regions. The high frequency of stomach cancer in the Mount Kilimanjaro area may be due to the influence of volcanic soils.