Peter Gichangi

Effect of a syphilis control programme on pregnancy outcome in Nairobi Kenya.

Objectives: To assess the impact of a syphilis control programme of pregnant women on pregnancy outcome in Kenya. Method: Women who came to deliver to Pumwani Maternity Hospital (PMH) between April 1997 and March 1998 were tested for syphilis. Reactive rapid plasma reagin (RPR) tests were titrated and confirmed with treponema haemagglutination test (TPHA). Equal numbers of RPR and TPHA negative women were enrolled. Antenatal syphilis screening and treatment history were examined from the antenatal cards. Results: Of 22 466 women giving birth, 12 414 (55%) were tested for syphilis. Out of these, 377 (3%) were RPR reactive of whom 296 were confirmed by TPHA. Syphilis seroreactive women had a more risky sexual behaviour and coexistent HIV antibody positivity; 26% were HIV seropositive compared with 11% among syphilis negative mothers. The incidence of adverse obstetric outcome defined as low birth weight and stillbirth, was 9.5%. Syphilis seropositive women had a higher risk for adverse obstetric outcome (OR 4.1, 95% CI 2.4–7.2). Antenatal treatment of RPR reactive women significantly improved pregnancy outcome but the risk of adverse outcome remained 2.5-fold higher than the risk observed in uninfected mothers. Conclusions: These data confirm the adverse effect of syphilis on pregnancy outcome. This study also shows the efficacy of antenatal testing and prompt treatment of RPR reactive mothers on pregnancy outcome.

Human papillomavirus types in women with invasive cervical carcinoma by HIV status in Kenya

To evaluate the fraction of invasive cervical carcinoma (ICC) that could be prevented in HIV‐infected women by vaccines currently available against human papillomavirus (HPV)16 and 18, we conducted a cross‐sectional study in women with ICC in Nairobi, Kenya. Fifty‐one HIV‐positive women were frequency‐matched by age to 153 HIV‐negative women. Cervical cells were tested for HPV DNA using polymerase chain reaction‐based assays (SPF10‐INNO‐LiPA). Comparisons were adjusted for multiplicity of HPV types. As expected, multiple‐type infections were much more frequent in HIV‐positive (37.2%) than in HIV‐negative (13.7%) women, but the distribution of HPV types was similar. HPV16 was detected in 41.2% versus 43.8% and HPV16 and/or 18 in 64.7% versus 60.1% of HIV‐positive versus HIV‐negative women, respectively. The only differences of borderline statistical significance were an excess of HPV52 (19.6% versus 5.2%) and a lack of HPV45 (7.8% versus 17.0%) in HIV‐positive women compared to HIV‐negative women, respectively. We have been able to assess an unprecedented number of ICCs in HIV‐positive women, but as we did not know the age of HIV acquisition, we cannot exclude that it had occurred too late in life to affect the type of HPV involved in cervical carcinogenesis. However, if our findings were confirmed, they would suggest that the efficacy of current vaccines against HPV16 and 18 to prevent ICC is similar in HIV‐positive and HIV‐negative women, provided vaccination is administered before sexual debut, as recommended.

HIV and cervical cancer in Kenya

Objectives: To determine the effect of the HIV epidemic on invasive cervical cancer in Kenya. Methods: Of the 3902 women who were diagnosed with reproductive tract malignancies at Kenyatta National Hospital (KNH) from 1989 to 1998, 85% had invasive cervical cancer. Age at presentation and severity of cervical cancer were studied for a 9‐year period when national HIV prevalence went from 5% to 5–10%, to 10–15%. Results: There was no significant change in either age at presentation or severity of cervical cancer. Of the 118 (5%) women who were tested for HIV, 36 (31%) were seropositive. These women were 5 years younger at presentation than HIV‐negative women. Conclusions: A two‐ to three‐fold increase in HIV prevalence in Kenya did not seem to have a proportional effect on the incidence of cervical cancer. Yet, HIV‐positive women who presented with cervical cancer were significantly younger than HIV‐negative women.

The effects of HIV-1 Tat protein on cell cycle during cervical carcinogenesis

The role of HPV in the carcinogenesis of intraepithelial and invasive anogenital lesions is currently well established. E6 and E7 oncoproteins of high risk HPV genotypes are known to inactivate p53 and pRb pathways. Several studies have described an increased prevalence and recurrence of both cervical HPV infection and invasive cervical cancer among HIV-1 positive women compared to HIV-1 negative cases. For these reasons, cervical cancer is considered an AIDS-defining neoplasm. Unlike other AIDS-associated neoplasms, the occurrence of cervical cancer is independent of immune suppression. HIV-1 infection in patients with high grade precancerous lesions and cervical cancers results in a therapy refractory and more aggressive disease phenotype, which is not yet well understood at the molecular level. An upregulation of HPV E6 and E7 gene expressions by HIV-1 proteins such as Tat has been documented by some authors. However, the role of HIV-1 in cervical carcinomas is still unclear. It is already known that HIV-1 Tat protein is able to influence cell cycle progression. Altogether, these facts led us to investigate the effects of Tat on the expression of cell cycle regulator genes. After transfection of HeLa cells with Tat, we analyzed the expression of cell cycle regulators from these cells by IHC and Real-time PCR. A significant reduction in the expression of cell cycle inhibitors of transcription and an increase in the levels of proliferation markers were observed. These results suggest that HIV-1 may enhance cervical carcinogenesis by promoting cell cycle progression. We also found that this HIV-1 Tat-induced cell proliferation was not dependent on the E2F family of transcription factors, and therefore postulate that Sp factors may be involved.

Analysis of Factors Contributing to the Low Survival of Cervical Cancer Patients Undergoing Radiotherapy in Kenya.

Background In contrast to the developed nations, invasive cervical cancer (ICC) is the most common womens malignancy in Kenya and many other locations in sub-Saharan Africa. However, studies on survival from this disease in this area of the world are severely restricted by lack of patient follow-up. We now report a prospective cohort study of ICC in Kenyan women analysing factors affecting tumour response and overall survival in patients undergoing radiotherapy. Methods and Findings Between 2008 and 2010, 355 patients with histologically confirmed ICC were recruited at the Departments of Gynaecology and Radiotherapy at Kenyatta National Hospital (KNH). Structured questionnaires were completed recording socio-demographics, tumour response and overall survival following treatment with combinations of external beam radiation (EBRT), brachytherapy and adjuvant chemotherapy. Of the 355 patients, 42% (146) were lost to follow-up while 18% (64) died during the two year period. 80.5% of patients presented with advanced stage IIB disease or above, with only 6.7% of patients receiving optimal combined EBRT, brachytherapy and adjuvant chemotherapy. Kaplan Meier survival curves projected two year survival at <20%. Conclusion Cervical cancer is preventable yet poverty, poor education, lack of cancer awareness coupled with an absence of regular screening programs, late patient presentation, sub-optimal diagnosis and treatments are major factors contributing to the alarmingly low survival rate of cervical cancer patients in Kenya. It is concluded that simple cost-effective changes in clinical practice could be introduced which would have a marked impact on patient survival in this setting.

Antimicrobial prophylaxis in pregnancy : A randomized, placebo-controlled trial with cefetamet-pivoxil in pregnant women with a poor obstetric history

OBJECTIVE This study was undertaken to measure the impact of a single oral dose of cefetamet-pivoxil on pregnancy outcome in a population with substantial rates of low birth weight and high prevalence rates of maternal infections. STUDY DESIGN A total of 320 pregnant women with a poor obstetric history, defined as a history of low birth weight or stillbirth, were randomized to receive a single oral dose of 2 gm of cefetamet-pivoxil or a placebo at a gestational age between 28 and 32 weeks. Patients were assessed at delivery and 1 week post partum for pregnancy outcome, postpartum endometritis, human immunodeficiency virus-1 and gonococcal infections. RESULTS A total of 253 (79%) women gave birth at the maternity hospital, of whom 210 (83%) attended the follow-up clinic. Overall, 18.1% of these pregnant women were human immunodeficiency virus-1 seropositive, whereas 9.5% had antibodies against Treponema pallidum. There was a significant difference between cefetamet-pivoxil- and placebo-treated women in infant birth weight (2927 gm vs 2772 gm, p = 0.03) and low birth weight (< 2500 gm) rates (18.7% vs 32.8%, p = 0.01, odds ratio 2.1, 95% confidence interval 1.2 to 3.8). The stillbirth rate was 2.2% in the cefetamet-pivoxil group and 4.2% in the placebo group (not significant). Postpartum endometritis was found in 17.3% in the intervention arm versus 31.6% in the placebo group (p = 0.03, odds ratio 2.2, 95% confidence interval 1.1 to 7.6). Neisseria gonorrhoeae was isolated from the cervix in 5 of 103 (4.9%) women in the intervention and in 14 of 101 (13.9%) in the placebo group (p = 0.04, odds ratio 3.2, 95% confidence interval 1.1 to 10.5). CONCLUSION A single oral dose of cefetamet-pivoxil administered to pregnant women with a poor obstetric history seemed to improve pregnancy outcome in this population with high rates of maternal infections. Larger studies should be carried out to examine the public health impact, the feasibility, and the overall cost/benefit ratio of this intervention.

Knowledge, attitudes, and practices regarding emergency contraception among nurses and nursing students in two hospitals in Nairobi, Kenya.

A cross-sectional descriptive study on knowledge, attitudes, and practice about emergency contraception (EC) was conducted among nurses and nursing students using a self-administered questionnaire. One-hundred-sixty-seven qualified nurses and 63 nursing students completed the questionnaire. Over 95% listed at least one regular contraceptive method but only 2.6% spontaneously listed EC as a contraceptive method, whereas 48% of the respondents had heard of EC. Significantly more nursing students than qualified nurses were familiar with EC. Knowledge about the types of EC, applications, and side effects was poor and 49% of the respondents considered EC as an abortifacient. Of those familiar with EC, 77% approved its use for rape victims and 21% for adolescents and schoolgirls. Only 3.5% of all respondents had personally used EC in the past, 23% of those familiar with EC intend to use it in the future, whereas 53% intend to provide or promote it. The view that EC was abortifacient negatively influenced the decision to use or provide EC in the future. The present findings suggest that the level of knowledge of EC is poor and more information is needed. These findings indicate the potential to popularize emergency contraception in Kenya among nurses and nursing students.

HIV Infection Alters the Spectrum of HPV Subtypes Found in Cervical Smears and Carcinomas from Kenyan Women

Infection with high risk HPV is implicated in pre-cancerous squamous intraepithelial lesions and their progression to cervical cancer. In the developed countries, infection with HPV 16 and 18 accounts for ~70% of cervical cancers, but it has been established that HPV type prevalence differs according to worldwide geographical location. In sub Saharan Africa infection with HPV is known to be augmented by HIV, which is endemic in this region. It is not yet clear, however, whether this ultimately influences progression to cervical cancer. PapillocheckTM and multiplex PCR were used to determine the range of HPV genotypes found in cervical smears and carcinomas from HIV positive and negative Kenyan women. Smear samples from HIV-positive women had a higher prevalence of: multiple HPV infections; high-risk HPVs 52, 58, 68, potential high risk 53/70, low-risk 44/55 and abnormal cytology compared to HIV-negative women. A low overall prevalence (~8%) of types 16/18 was found in all smear samples tested (n = 224) although this increased in invasive cervical carcinoma tissues to ~80% for HIV-negative and ~46% for HIV-positive women. Furthermore, HPV45 was more common in cervical carcinoma tissues from HIV-positive women. In summary HIV infection appears to alter the spectrum of HPV types found in both cervical smears and invasive cervical carcinomas. It is hypothesised there could be a complex interplay between these viruses which could either positively or negatively influence the rate of progression to cervical cancer.

Partner notification of pregnant women infected with syphilis in Nairobi Kenya.

We examined partner notification among syphilitic pregnant women in Nairobi. At delivery, 377 women were found to be rapid plasma reagin (RPR) reactive. Data were available for 94% of the partners of women who were tested during pregnancy; over 67% of the partners had received syphilis treatment while 23% had not sought treatment mainly because they felt healthy. Six per cent of the women had not informed their partners as they feared blame and/or violence. Adverse pregnancy outcome was related to lack of partner treatment during pregnancy (7% versus 19%, odds ratio (OR) 3.0, 95% confidence interval (CI) 0.9- 10.0). Our data suggest that messages focusing on the health of the unborn child have a positive effect on partner notification and innovative and locally adapted strategies for partner notification need more attention.

Implications of adopting new WHO guidelines for antiretroviral therapy initiation in Ethiopia

OBJECTIVE To assess the implications of implementing the World Health Organization (WHO) 2010 guidelines for antiretroviral therapy (ART) initiation in adults and adolescents with human immunodeficiency virus (HIV) infection, which recommend initiating ART at a CD4+ T lymphocyte (CD4+) threshold of ≤ 350 cells/mm(3) instead of ≤ 200 cells/mm(3), which was the earlier threshold. METHODS Between April and May 2010, CD4+ test results were collected for all HIV-infected patients recorded in the pre-ART and ART registers of 19 high-patient-load health centres in Addis Ababa, Ethiopia, and the regions of Amhara, Oromia, SNNPR (Southern Nations, Nationalities and Peoples Region) and Tigray. At 12 centres patient records were independently reviewed to assess data accuracy. To estimate the total number of patients who would need ART at health centres if Ethiopia adopted the new WHO guidelines, the number of patients needing ART based on current guidelines were added to the number of asymptomatic patients enrolled in pre-ART with a CD4+ count > 200 but ≤ 350 cells/mm(3) FINDINGS Adoption of the new WHO guidelines would increase the total number of patients on ART in the 19 health centres in Ethiopia by about 30%: from 3583 to 4640. CONCLUSION The shift in the CD4+ threshold for ART initiation will substantially increase the demand for ART in Ethiopia. Since under the current systems only 60% of Ethiopias patients in need of ART are receiving the medications, scaling up ART programmes to accommodate the increased demand for drugs will not be possible unless government funding and support increase concurrently.