Risk of seropositivity to multiple oncogenic human papillomavirus types among human immunodeficiency virus-positive and -negative Ugandan women.

To understand the prospects for human papillomavirus (HPV) mass vaccination in the setting of a developing country, we studied the co-occurrence of seropositivity to multiple high-risk (hr) HPV types among HIV-positive and HIV-negative Ugandan women. Our seroepidemiological study was conducted among 2053 women attending antenatal clinics. Sera were analysed for antibodies to eight hrHPV types of the α-7 (18/45) and α-9 (16/31/33/35/52/58) species of HPV by using a multiplex serology assay. Our results show that seropositivity for greater than one hrHPV type was as common (18 %) as for a single type (18 %). HIV-positive women had higher HPV16, HPV18 and HPV45 seroprevalences than HIV-negative women. In multivariate logistic regression analysis, age (>30 years) and level of education (secondary school and above) reduced the risk, whereas parity (>5) and HIV-positivity increased the risk for multiple hrHPV seropositivity. However, in stepwise logistic regression analyses, HIV-status remained the only independent, stand-alone risk factor [odds ratio (OR) 1.7, 95 % confidence interval (CI) 1.0-2.8). On the other hand, the risk of HPV16 or HPV18 seropositive women, as compared to HPV16 or HPV18 seronegative women, for being seropositive to other hrHPV types was not significantly different when they were grouped by HIV-status (ORHPV16/HIV+ 12, 95 % CI 4.5-32 versus ORHPV16/HIV- 22, 95 % CI 15-31 and ORHPV18/HIV+ 58, 95 % CI 14-242 versus ORHPV18/HIV- 45, 95 % CI 31-65). In conclusion, seropositivity to HPV16, HPV18 and to non-vaccine hrHPV types is common in Ugandan women, suggesting that there is little natural cross-protective immunity between the types. HIV-positivity was an independent, stand-alone, albeit moderate risk factor for multiple hrHPV seropositivity. HPV mass vaccination may be the most appropriate method in the fight against cervical cancer in the Ugandan population.

Burkitt's Lymphoma in Africa; a Review of the Epidemiology and Etiology

Burkitt's lymphoma (BL) was first described in Eastern Africa; initially thought to be a sarcoma of the jaw. Shortly it became well known that this was a distinct form of Non Hodgkin's lymphoma.The disease has given insight in all aspects of cancer research and care. Its peculiar epidemiology has led to the discovery of Epstein Barr virus (EBV) and its importance in the cause of several viral illnesses and malignancies.The highest incidence and mortality rates of BL are seen in Eastern Africa. BL affects mainly children; and boys are more susceptible than girls. Evidence for a causal relationship between EBV and BL in the endemic form is fairly strong. Frequency of association between EBV and BL varies between different patient groups and different parts of the world. EBV may play a role in the pathogenesis of BL by deregulation of the oncogene c-MYC by chromosomal translocation.Although several studies suggest an association between malaria and BL; there has never been a conclusive population study in support of a direct role of malaria in causation of BL.The emergence of HIV and a distinct subtype of BL in HIV infected have brought a new dimension to the disease particularly in areas where both HIV and BL are endemic. BL has been reported as a common neoplasmin HIV infected patients; but not in other forms of immuno-depression; and the occurrence of BL seems to be higher amongst HIV positive adults; while the evidence of an association amongst children is still disputed.The role of other possible risk factors such as low socio-economical status; exposure to a plant species common in Africa called Euphorbiaceae; exposure to pesticies and to other infections such as schistosomiasis and arbovirus (an RNA virus trans- mitted by insect vectors) remain to be elucidated

Feasibility study of serial lumbar puncture and acetazolamide combination in the management of elevated cerebrospinal fluid pressure in AIDS patients with cryptococcal meningitis in Uganda.

A feasibility study of serial lumbar puncture and acetazolamide combination in managing raised cerebrospinal fluid pressure was undertaken in 18 patients with AIDS and cryptococcal meningitis in Uganda. There were no adverse events related to the intervention and improvement in minimental status score, performance score, symptoms and a reduction in intracranial opening pressure were observed. This method is therefore feasible in AIDS-associated cryptococcal meningitis in a resource-poor setting given the observed safety and possible effectiveness, a larger study is warranted.

In vitro activities of voriconazole, fluconazole, and itraconazole against 566 clinical isolates of Cryptococcus neoformans from the United States and Africa.

We investigated the in vitro activity of voriconazole compared to those of fluconazole and itraconazole against 566 clinical isolates of Cryptococcus neoformans from Africa (164) and the United States (402). Isolates were obtained from cerebrospinal fluid (362), blood (139), and miscellaneous sites (65). Voriconazole (MIC at which 90% of the isolates are inhibited [MIC90], 0.12 to 0.25 microg/ml) was more active than either itraconazole (MIC90, 0.5 microg/ml) or fluconazole (MIC90, 8.0 to 16 microg/ml) against both African and U. S. isolates. Isolates inhibited by >/=16 microg of fluconazole per ml were almost all (99%) inhibited by

Fluconazole susceptibility testing of Cryptococcus neoformans: comparison of two broth microdilution methods and clinical correlates among isolates from Ugandan AIDS patients.

We compared the yeast nitrogen base (YNB) broth microdilution method with the National Committee for Clinical Laboratory Standards (NCCLS) M27-A microdilution reference method for measuring the in vitro susceptibility of Cryptococcus neoformans isolates to fluconazole. A total of 149 isolates of C. neoformans var. neoformans from Ugandan AIDS patients was tested by both methods. An overall agreement of 88% between the two microdilution methods was observed. All isolates grew well in both RPMI 1640 and YNB media, and MICs could be read after 48 h of incubation by both methods. The range of fluconazole MICs obtained with the YNB method was broader than that obtained with the NCCLS method. The extended range of MICs provided by the YNB method may be of clinical value, as it appears that the clinical outcome may be better among patients infected with strains inhibited by lower concentrations of fluconazole as determined by the YNB method. The YNB method appears to be a viable option for testing C. neoformans against fluconazole.

Single-dose ampicillin/sulbactam versus ceftriaxone as treatment for uncomplicated gonorrhoea in a Ugandan STD clinic population with a high prevalence of PPNG infection.

During the period November 1989 to March 1991 a total of 330 patients (269 males and 61 females) with signs and symptoms of uncomplicated lower genital tract infections with Neisseria gonorrhoeae were treated at a sexually transmitted disease clinic in Kampala, Uganda. Patients were randomized for treatment with either intramuscular ampicillin/sulbactam (1 g ampicillin/0.5 g sulbactam), plus 1 g probenecid orally, or ceftriaxone (250 mg). In those cases where N. gonorrhoeae was isolated and the patients returned for a follow-up visit, 70/74 (95%) of the patients treated with ampicillin/sulbactam and 71/72 (99%) of those treated with ceftriaxone had favourable clinical outcomes. All 24 patients with penicillinase-producing N. gonorrhoeae (PPNG) treated with ampicillin/sulbactam had a favourable clinical outcome compared with 95% (20/21) of those with PPNG treated with ceftriaxone. The infecting pathogen was eradicated in 65/71 (92%) of the evaluable patients treated with ampicillin/sulbactam and in 60/63 (95%) of the ceftriaxone group. Both drug regimens were well tolerated and there were no reports of adverse drug effects. In summary, in a predominantly male group of clinic patients in Kampala, Uganda, ampicillin/sulbactam was as safe and effective as ceftriaxone in treating uncomplicated gonococcal infections of the lower genital tract caused by either PPNG or non-PPNG strains.

The value of a clinical definition for epidemic KS in predicting HIV seropositivity in Africa.

Kaposi's sarcoma (KS) in African adults can present in endemic (non-HIV-related) and epidemic (HIV-related) forms. We evaluated the usefulness of a clinical case definition for epidemic KS in predicting HIV seropositivity. A total of 235 patients with KS presenting to the Uganda Cancer Institute from January 1, 1988 to March 31, 1990 were evaluated with history and physical examination. Symptomatic patients underwent chest radiography and upper gastrointestinal endoscopy. One hundred seventy-four patients (80%) underwent HIV ELISA testing with Western blot confirmation. The clinical case definition had a 91% sensitivity and a 95% specificity in predicting HIV seropositivity. Oral KS was the most sensitive specific site of involvement in predicting HIV seropositivity. The clinical case definition is useful in assessing patients to determine prognosis and likelihood of responding to aggressive therapy.

The value of a clinical definition for epidemic KS in predicting HIV seropositivity in Africa

Kaposi's sarcoma (KS) in African adults can present in endemic (non-HIV-related) and epidemic (HIV-related) forms. We evaluated the usefulness of a clinical case definition for epidemic KS in predicting HIV seropositivity. A total of 235 patients with KS presenting to the Uganda Cancer Institute from January 1; 1988 to March 31; 1990 were evaluated with history and physical examination. Symptomatic patients underwent chest radiography and upper gastrointestinal endoscopy. One hundred seventy-four patients (80pc) underwent HIV ELISA testing with Western blot confirmation. The clinical case definition had a 91pc sensitivity and a 95pc specificity in predicting HIV seropositivity. Oral KS was the most sensitive specific site of involvement in predicting HIV seropositivity. The clinical case definition is useful in assessing patients to determine prognosis and likelihood of responding to aggressive therapy

Treatment of advanced Hodgkin's disease with high dose melphalan and autologous bone marrow transplantation.

Twenty patients with Hodgkin's disease which had relapsed at least once after chemotherapy, were treated with melphalan 140-220 mg/m2 i.v. followed by reinfusion of non-cryopreserved autologous bone marrow. Four patients (20%) remain alive and disease-free 28, 45, 52, and 96 months after treatment respectively. There were no treatment-related deaths. This appears to be the only reported series of patients treated with a single agent in this situation. The results are comparable to those achieved by multi-agent regimens with autologous or allogeneic bone marrow transplantation.

High dose BCNU chemotherapy with autologous bone marrow transplantation and full dose radiotherapy for grade IV astrocytoma.

In a series of 22 patients, high dose BCNU (800-1,000mg m-2) with autologous bone marrow transplantation was given as the first post-surgical treatment for grade IV astrocytoma and followed by full dose radiotherapy. When compared to historical experience and matched to control patients in national studies, there appeared to be a small prolongation of survival but no increase in the proportion of long survivors. Acute myelosuppression was mild but toxicity to lung and liver was substantial and limited further dose escalation. Late bone marrow failure was seen in 4 patients. Pharmacokinetic studies were performed and suggested that the late marrow failure was due to persistence of BCNU at the time of marrow return. Despite the suggestion of a prolongation of survival this approach is not routinely recommended and a randomised trial is probably not justified.

Phase II trial of carboplatin (JM8) in treatment of patients with malignant mesothelioma.

Seventeen patients with malignant mesothelioma were treated in a phase II study with carboplatin, a cisplatin analogue without significant nephrotoxicity or neurotoxicity. The drug was given in a dose of 300-400 mg/m2 by i.v. infusion, repeating at 28-day intervals. One patient achieved a complete clinical and radiological remission of 15 months' duration, and a second patient achieved a partial response of 11 months' duration (overall response rate 12%; overall response rate in previously untreated patients 20%). Four other previously untreated patients achieved symptomatic relief. Treatment was well tolerated without severe side-effects. Carboplatin, like most other cytotoxic drugs, is active only in a small minority of patients with mesothelioma, but its ability to achieve occasional good responses and frequent symptomatic relief, combined with low toxicity, may justify a short therapeutic trial in patients whose tumour is symptomatic.

Amino (hydroxyethoxymethyl) purine: a new well-absorbed prodrug of acyclovir.

Acyclovir is an effective treatment for herpes simplex and herpes zoster infections, but it is somewhat limited by low oral absorption. 2-amino-9-[(2hydroxyethoxy)methyl]-9H-purine (BW A515U), a new prodrug of acyclovir, when evaluated in 10 patients with haematological malignancies, was well tolerated, excellently absorbed, and produced high plasma concentrations of acyclovir which were comparable to those with intravenous acyclovir. The plasma concentrations after oral BW A515U were much higher than those after oral acyclovir.

To Establish Haematological Reference Ranges among Indigenous Normal Ugandans

Methodology: Eligible subjects were HIV-1 negative; with no demonstratable medical or emotional problems. The parameters considered were absolute lymphocyte counts (AL C); absolute CD4 and CD8 (ACD4; ACD8) and CD4/CD8 count ratio (ABSR). The central 95area under the distribution curve (ACD) of the parameters of interest was considered as well as mean distributions between the sexes. Results: 183 subjects; 69(37.7) females and 114 (62.3) males were submitted to the study. The 95range for the combined groupe for ALC was 1452.5 - 4447.5; for ACD4 558.6-2332.8; for ACD8 252.0-1396.1; and for ABSR 0.682 - 4.37. There was a significant difference (p0.5) in mean ALC and mean (ABSR between sexes. Discussion: This p[ilot study was necessitated by the absence of up-to-date haematological and especially immunologic parameters (CD4; CD8) among normal Ugandans. Currently many laboratories and clinicians use North American and European haematologic reference; and also use various manual methods for determination of CD4 and CD8. These ranges which were established with more accurate method of flow cytometry gives a scientists in Uganda (and by implication Central Africa) and calls for a more extensive study to establish more representative and accurate haematological and immunological parameters