Situational analysis for diagnosis and treatment of cervical cancer in mainland Tanzania.

OBJECTIVE: To determine factors influencing early diagnosis and treatment of cervical cancer in Tanzania women. DESIGN: A cross-sectional study. SETTING: Forty primary health care facilities, twenty district/regional and four referral (tertiary) hospitals in mainland Tanzania. RESULTS: The most basic equipment for cytology-based cervical cancer were available at all health care facilities. However, screening against cervical cancer was appallingly inadequate at all levels of health care delivery system. Apart from medical doctors at tertiary level, other medical personnel including nurses were poorly or hardly utilised for cervical cancer screening. Treatment facilities for pre-cancerous lesions in most district, regional and even tertiary hospitals were inadequate or non-existent despite being very simple, cheap and yet very effective. There was total lack of organised institutional or national policy guidelines on cervical cancer screening in Tanzania. CONCLUSION: There is an urgent need to introduce systematic screening against cervical cancer and treatment of precursor lesions at all levels of health care delivery system in Tanzania. A national policy guideline should be urgently drawn addressing specifically frequency of screening and at what age to start screening.

Low dose aspirin in prevention of pregnancy-induced hypertension in primigravidae at the Muhimbili Medical Center, Dar es Salaam.

There is evidence that aspirin in low doses favourably influences the course and outcome of pregnancy in women at risk of developing pregnancy-induced hypertension. We conducted a double blind prospective randomized study to investigate the effect of low dose aspirin in preventing pregnancy-induced hypertension. Two hundred and one primigravidae from twenty weeks of pregnancy and above were screened using the roll-over test. Of the 127 women with an increase in blood pressure during the roll-over test, 126 women entered the study and were treated with a daily dose of either aspirin (80 mg) or placebo up to 10 days before the expected date of delivery. Samples of urine were collected for detection of aspirin. The incidence of pregnancy-induced hypertension in the aspirin treated group was significantly lower than in the placebo treated group; 3.17% versus 15.9% with a p value of 0.02. It is concluded that low daily doses of aspirin taken from twenty weeks of pregnancy significantly reduce the incidence of pregnancy-induced hypertension, possibly through the correction of an imbalance in levels of thromboxane and prostacyclin.

Prevalence of transformation zone Chlamydia trachomatis DNA and serum antibodies in Tanzanian gynaecological in-patients.

Chlamydia trachomatis DNA was detected in cervical transformation zone swabs of gynaecological in-patients from Tanzania by two different polymerase chain reactions (PCR), one targetting the endogenous Chlamydia trachomatis plasmid (pCTT1) and the other a chlamydia genus specific rRNA gene. In only 7/131 (5.3%) cervical samples specific amplification products were obtained, in 6 cases with both PCRs, and in one with the plasmid-PCR alone. A 255 nt sequence was determined from the two plasmid-PCR fragments and revealed only one mismatch against the prototype sequence. Antibodies against genus specific chlamydia antigens were detectable by indirect immunofluorescence with titres > or = 1:256 in 29.0% (38/131) of all patients and in 50.0% (11/22) of patients with pelvic inflammatory disease (P = 0.17). No statistically significant association of either chlamydia antibodies or chlamydial DNA with any clinical condition was observable.

Sequence variation in the E7 gene of human papillomavirus type 18 in tumor and non-tumor patients and antibody response to a conserved seroreactive epitope.

We have determined nucleotide sequences of the E7 open reading frame (ORF) of human papillomavirus type 18 (HPV-18) isolates obtained from 18 cervical carcinomas from Tanzanian and German patients and 8 cervical scrapings from Tanzanian non-tumor patients. The HPV-18 prototype sequence was detected in only 3 out of 26 isolates. Silent mutations were found at nt positions 640 and 751, whereas the mutations observed at nt positions 770, 806, 864 and 865 all change the respectively encoded amino acid. The HPV-18 isolates of 3 German carcinomas showed the same mutations (at position 751) as those of 2 established cervical carcinoma cell lines (HeLa and C4-1), whereas different mutations were found in 16/23 African isolates (at positions 640 and 864), to which the isolate of cell line SW756 was similar (changes at positions 640 and 865). Seven out of 15 HPV-18-positive Tanzanian tumor patients (46.7%) reacted in a peptide ELISA against a recently described seroreactive epitope of the HPV-18 E7 ORF (nt positions 704-769). Mutational changes of the E7 ORF were excluded as a possible explanation for the lack of antibody response, because there was no correlation with the serological results. The seroreactive region appears to be well conserved despite geographically varying mutations within the E7 ORF of HPV-18.

Risk factors for HIV infection in gynaecological inpatients in Dar es Salaam, Tanzania, 1988-1990.

A prevalence of 12.8% for anti-HIV-1 and a prevalence of 16.8% for anti-syphilis antibodies was found in 359 gynaecological inpatients admitted in the Department of Gynaecology and Obstetrics, Muhimbili University College of Health Sciences from 1988 to 1990. The highest HIV prevalence (17.3%) was observed in the youngest age group (14-20 years), whereas the highest syphilis prevalence (22.2%) was found in the oldest age group (> 45 years). Infections with HIV and syphilis were both significantly associated with variables related to sexual behaviour, such as marital status, age at first intercourse and number of sexual partners in the past ten years. After adjustment for these common risk variables linked to sexual behaviour, syphilis infection was still associated with a more than twofold higher risk of HIV infection (odds ratio (OR) = 2.60, p = 0.02) and trichomonas vaginalis infection with a nearly threefold higher risk (OR = 2.96, p < 0.001). These data characterize patients at risk for HIV infection among inpatients of a gynaecological department in East Africa, and indicate that effective measures to prevent sexually transmitted disease may reduce HIV transmission.

Human papillomavirus (HPV) infection, HIV infection and cervical cancer in Tanzania, east Africa.

The presence of HPV-DNA was determined in tumor biopsies of cervical-cancer patients and in cervical swabs of non-cancer patients from Tanzania, East Africa, by Southern blot hybridization and/or PCR. HPV types 16 and 18 were detected in 38% and 32%, respectively, of 50 cervical-carcinoma biopsies. A consensus primer PCR capable of detecting a broad spectrum of HPV types revealed the presence of HPV-DNA in 59% of 359 cervical swabs of non-cancer patients. Type-specific PCR showed that types 16 and 18 accounted for 13.2% and 17.5%, respectively, of all HPV infections. Therefore we concluded that HPV 18 is more prevalent in Tanzania than in any other geographical location so far reported. The strongest risk factors for the presence of any HPV-DNA in the 359 female non-cancer patients were young age and HIV infection. The epidemiology of HPV types 16 and 18 was found to differ from that of other HPV types, being associated in univariate analysis with trichomonas vaginalis infection, martial status (single/divorced), age at first intercourse, and young age at menarche. However, young age at menarche accounted for most of the effects of all other, variables in multivariate analysis. Of the non-cancer patients, 12.8% had antibodies against HIV I (no patient being severely symptomatic), and HIV infection was highly correlated with the presence of HPV-DNA, especially types 16 and 18. While HPV-DNA of any type was detectable 1.4-fold more often in HIV-positive patients than in HIV-negative patients, evidence of an infection with HPV types 16 or 18 was found 2.2-fold more often in the HIV-positive patients. The HIV-positive women did not show an increased rate of cervical cytological abnormalities as assessed by PAP staining of a single cervical smear, the overall rate of abnormalities being 2.8%. Furthermore, the age-adjusted prevalence of HIV antibodies was found to be considerably lower in 270 cervical-carcinoma patients (3% HIV-positive) in comparison with non-cancer patients. Thus there was no association observable between the prevalence of HIV infections and the frequency of cervical cytological abnormalities or cervical cancer in the setting of this cross-sectional study.

PIP: Southern blot hybridization and/or PCR was used to examine tumor biopsies of 53 women with cervical or vaginal cancer at Ocean Road Hospital in Dar es Salaam, Tanzania, and the cervical swabs of 359 women with no cancer at the gynecologic clinic at Muhimbili University College of Health Sciences in Dar es Salaam. Tanzanian and German scientists wanted to determine whether an association existed between human papillomavirus (HPV) infections and HIV, and whether the high prevalence of HIV infection was matched by a high prevalence of HPV infections, cervical dysplasias, and cervical cancer in HIV-positive cases. 59% of the noncancerous women had HPV-DNA. Young age and HIV infection were the greatest risk factors for HPV-DNA in these women (p .0001 for age and HPV-16/18; p = .08 for other HPVs; and p = .03 for HIV). 13.2% and 17.5% of all HPV infections were HPV types 16 and 18, respectively. Tanzania had the highest prevalence of HPV 18 ever reported. HPV-16/18 risk factors included: Trichomonas vaginalis infection (odds ratio [OR] = 2.23; p = .04), single status (OR = 2.55; p = .01), 16 years old or less at first intercourse (OR = 2.1; p = .03), and young age at menarche (OR = 6 for or=12 years old; p = .02 and OR = 3.25 for or=13 years old and or=16 years old; p = .05). Yet, the multivariate analysis revealed young age at menarche had the greatest effect (OR = 6.2 for or= 12 years old, p = .03; OR = 3.73 for or=16 years old, p = .08). 12.8% of noncancerous women tested positive for HIV-1, but none of them were obviously symptomatic. These HIV-positive women had a higher OR if they had HPV-16/18 than if they had other HPV types (4.25 vs. 2.02). Further, they did not have more cervical cytological abnormalities than did the HIV-negative women (overall cervical cytological abnormality rate - 2.8%). The HIV-positive rate for cancerous patients was only 3%. In conclusion, no association existed between HIV infection and cervical cytological abnormalities or cervical cancer.

Chlorinated hydrocarbon content of fetal and maternal body tissues and fluids in full term pregnant women: a comparison of Germany versus Tanzania.

Chlorinated hydrocarbons are distributed worldwide and due to their lipophilic properties and chemical stability they accumulate in the foodchain. The concentrations of 19 different chlorinated hydrocarbons (hexachlorohexane (HCH), DDT and various metabolites and nine different polychlorinated phenyl (PCB) congeners were detected in various body tissues and fluids (maternal and fetal serum, adipose tissue, placenta, amniotic fluid) of full term pregnant women from Germany and Tanzania. Great variation of total toxin burden and toxin distribution within the different body compartments was found. This was in part due to local differences of exposure to some of the chlorinated hydrocarbons. Comparing samples from Germany and Tanzania, typical distribution patterns reflected the specific economic situation of the two countries with a high burden of insecticides (DDT and Dieldrin) in the agricultural country and high levels of constituents of industrial products (hexachlorobenzene (HCB) and PCBs) in Germany. Different chlorinated hydrocarbons seem to show different distribution patterns in body tissues, probably due to their chemical structure, the lipid content of the compartment and the overall toxin burden of the individual. A 10 to 100 fold accumulation of chlorinated hydrocarbons was observed in maternal adipose tissue compared with the other compartments. The concentrations of certain toxins in fetal cord serum and placenta were higher than in maternal serum.

Molecular variants of human papillomavirus type 16 from four continents suggest ancient pandemic spread of the virus and its coevolution with humankind.

We have amplified by the polymerase chain reaction, cloned, and sequenced genomic segments of 118 human papillomavirus type 16 (HPV-16) isolates from 76 cervical biopsy, 14 cervical smear, 3 vulval biopsy, 2 penile biopsy, 2 anal biopsy, and 1 vaginal biopsy sample and two cell lines. The specimens were taken from patients in four countries--Singapore, Brazil, Tanzania, and Germany. The sequence of a 364-bp fragment of the long control region of the virus revealed 38 variants, most of which differed by one or several point mutations. Phylogenetic trees were constructed by distance matrix methods and a transformation series approach. The trees based on the long control region were supported by another set based on the complete E5 protein-coding region. Both sets had two main branches. Nearly all of the variants from Tanzania were assigned to one (African) branch, and all of the German and most of the Singaporean variants were assigned to the other (Eurasian) branch. While some German and Singaporean variants were identical, each group also contained variants that formed unique branches. In contrast to the group-internal homogeneity of the Singaporean, German, and Tanzanian variants, the Brazilian variants were clearly divided between the two branches. Exceptions to this were the seven Singaporean isolates with mutational patterns typical of the Tanzanian isolates. The data suggest that HPV-16 evolved separately for a long period in Africa and Eurasia. Representatives of both branches may have been transferred to Brazil via past colonial immigration. The comparable efficiencies of transfer of the African and the Eurasian variants to the New World suggest pandemic spread of HPV-16 in past centuries. Representatives of the African branch were possibly transferred to the Far East along old Arab and Indonesian sailing routes. Our data also support the view that HPV-16 is a well-defined virus type, since the variants show only a maximal genomic divergence of about 5%. The small amount of divergence in any one geographic location and the lack of marked divergence between the Tanzanian and Brazilian African genome variants two centuries after their likely introduction into the New World suggest a very slow rate of viral evolution. The phylogenetic tree therefore probably represents a minimum of several centuries of evolution, if not an age equal to that of the respective human races.

Iron storage after total dose iron dextran (imferon) infusion

Twenty pregnant women who had been given total dose infusion (TDI) of iron dextran at Muhimbili Medical Centre; Dar es Salaam; Tanzania; had their bone marrows examined and red blood cell parameters measured. In 35 per cent of the study group there was no stainable iron in the marrow. The rest showed abnormally increased amounts of marrow iron; and in three of them there was normal in five and increased in the remainder. This increase was probably pregnancy induced

Human papillomavirus type 18 E6 and E7 antibodies in human sera: increased anti-E7 prevalence in cervical cancer patients.

Antibody-reactive regions on the human papillomavirus type 18 (HPV-18) E6 and E7 proteins were identified with rabbit polyclonal anti-fusion protein sera by screening of an fd phage expression library containing subgenomic HPV-18 DNA fragments and by testing of overlapping decapeptides representing the E6 and E7 open reading frames. Peptides comprising the delineated regions (designated E6/1 to E6/4 and E7/1) were synthesized and used in an enzyme-linked immunosorbent assay (ELISA) to detect anti-HPV-18 antibodies in human sera. A total of 232 human serum samples (identical numbers of cervical cancer patients and age-matched controls) collected in Tanzania were tested. Similar prevalences (between 0.8 and 4.3%) of antibodies recognizing the different E6 peptides were found in the sera from tumor patients and controls. With a synthetic 28-mer peptide (designated pepE701) comprising the E7/1 region, a significant difference was found: 10 of 116 tumor serum samples but 0 of 116 control serum samples showed a specific reaction (P less than 0.001). This observation confirms earlier results with HPV-16 E7 fusion proteins (I. Jochmus-Kudielka, A. Schneider, R. Braun, R. Kimmig, U. Koldovsky, K. E. Schneweis, K. Seedorf, and L. Gissmann, J. Natl. Cancer Inst. 81:1698-1704, 1989). A lower prevalence of anti-HPV-18 E7 antibodies was observed when 188 human serum samples collected in Germany from tumor patients and controls were tested (3 of 94 positive in the cancer group; 0 of 94 positive in the control group). The type specificity of anti-HPV-18 E7 antibodies was demonstrated when the HPV type found by Southern hybridization in the cervical cancer biopsies was compared with seroreactivity: 4 of 8 serum samples obtained from HPV-18 DNA-positive but 0 of 16 serum samples from HPV-18 DNA-negative tumor patients reacted in the HPV-18 E7 ELISA. In addition, HPV-18-positive sera failed to react in a peptide ELISA with the homologous HPV-16 E7 region (M. Müller, H. Gausepohl, G. de Martinoff, R. Frank, R. Brasseur, and L. Gissmann, J. Gen. Virol. 71:2709-2717, 1990) and vice versa.

Advanced abdominal pregnancy in Muhimbili Medical Centre, Tanzania.

A prospective study was conducted at Muhimbili Medical Centre (MMC) over a 2-year period on 16 patients with advanced abdominocyesis. The incidence of 1 in 3259 deliveries was higher than that of previous years. Infertility prior to index pregnancy was a significant antecedent factor (P less than 0.001). The most consistent symptom both in early and late pregnancy was abdominal pain. Difficulty in fetal palpation and abnormal lies were the most significant signs. The sensitivity of clinical suspicion was 68%, ultrasound 85% and X-ray diagnosis 93%. Sepsis was the leading maternal complication, especially when the placenta was left in situ. Perinatal mortality was 87.5% and maternal mortality was 6.4%. Abdominal pregnancy remains a diagnostic challenge and certain aspects of fetal mortality are ill-understood. Early diagnosis of abdominal pregnancy can be improved upon by more detailed history taking, a high index of suspicion and meticulous interpretation of sonographic and radiological signs. It is suggested that the placenta be removed except in the rarest trying cases and that pregnancy be terminated on diagnosis.

The use of oral herbal medicine by women attending antenatal clinics in urban and rural Tanga District in Tanzania.

PIP: A prospective study on the use of oral herbal medicine was conducted on 214 pregnant women attending antenatal clinics in urban and rural Tanga district, which is well-known for traditional healers. There is a perception that traditional healers are very respected locally, and should be cooperated with. However herb effects range from therapeutic to dangerous. The overall prevalence rate of use of herbal medicine was 42%. The prevalence in urban and rural areas was 43.3% and 40.2% respectively. The highest use rate was towards the end of the 1st trimester and during labor, for a total of 87.7%. Of the users, 54% did so to relieve pregnancy-associated symptoms, while the rest used it as a consequence of beliefs, possibly superstitious, circumstantial constraints, and combinations of these. Significant differences were found between women delivering at home (55% used herbal medicine) and in a modern health facility (38.8%), P=0.038, between Moslems (44.4%) and Christians (32.2%), P=0.22, and among tribes. It seems that oral herbal medicines are commonly used in pregnancies and childbirth in Tanga, as well as in other areas, Bagamoyo being an example. Fear of the health facility eivironment as being a place for dying is an interesting factor. A form of Koranic medicine known as Kombe, which included the use of Quranic inscriptions, was used widely. It is recommended that immediate and long-term outcomes of herb-tested pregnancies be evaluated. Phytochemical, toxicological, and pharmacological studies are necessary to enable health workers to warn against inappropriate and dangerous usage.^ieng