Rebecca Luckett

Impact of 2-, 4- and 9-valent HPV vaccines on morbidity and mortality from cervical cancer.

ABSTRACT Cervical cancer causes significant morbidity and mortality worldwide. Most cervical cancers are associated with oncogenic human papillomavirus (HPV), and vaccination with any of 3 available HPV vaccines is anticipated to greatly reduce the burden of cervical cancer. This review provides an overview of the burden of HPV, the efficacy and clinical effectiveness of the bivalent (HPV 16, 18), quadrivalent (HPV 6, 11, 16, 18) and 9vHPV (HPV 6, 11, 16, 1831, 33, 45, 52, 58) vaccines in order to assess the anticipated impact on cervical cancer. All three vaccines show high efficacy in prevention of vaccine-specific HPV-type infection and associated high-grade cervical dysplasia in HPV-naïve women. Early clinical effectiveness data for the bivalent and quadrivalent vaccine demonstrate reduced rates of HPV 16 and 18 prevalence in vaccinated cohorts; data evaluating cervical dysplasia and cervical procedures as outcomes will shed further light on the clinical effectiveness of both vaccines. The bivalent vaccine has demonstrated cross-protection to non-vaccine HPV types, including the types in the 9vHPV vaccine. No clinical effectiveness data is yet available for the 9vHPV vaccine. While HPV vaccination has great promise to reduce cervical cancer morbidity and mortality, estimated benefits are largely theoretical at present. Large population-based clinical effectiveness studies will provide long-term immunogenicity and effectiveness, as well as assessment of cervical cancer as an endpoint, particularly as young vaccinated women enter the appropriate age range to initiate screening for cervical cancer. Strengthening screening and treatment programs will likely have the greatest impact in the short-term on cervical cancer morbidity and mortality

Babesiosis in pregnancy.

BACKGROUND: Babesiosis is an emerging infectious disease caused by a tick-borne parasite that infects red blood cells. Pregnancy is a relatively immunocompromised state that can underlie severe manifestations of parasitic disease. CASE: A healthy primiparous patient in the second trimester developed nonspecific symptoms after a tick bite. Evaluation by obstetrics, primary care, and neurology over 4 weeks yielded diagnoses of Lyme disease, upper respiratory infection, migraine, and medication overuse headache. Babesiosis was diagnosed only after she became acutely ill with hemolysis. She was treated with standard antibiotics and had an uncomplicated pregnancy and healthy newborn. CONCLUSION: Diagnosis of babesiosis in pregnancy requires a high index of suspicion to ensure early treatment and optimal pregnancy outcomes.

Hypertensive disease in pregnancy in Botswana: Prevalence and impact on perinatal outcomes

OBJECTIVES Perinatal morbidity in sub-Saharan Africa has been attributed to infection, obstetric emergencies, and preterm birth, but less is known about hypertension in pregnancy. Our objective was to characterize the prevalence of hypertension in pregnancy and the impact of hypertension on perinatal outcomes in sub-Saharan Africa. STUDY DESIGN We performed surveillance of obstetric records at eight of the largest public hospitals in Botswana. Women were included in this analysis if they were HIV-uninfected and had singleton gestations and at least one prenatal blood pressure measurement. MAIN OUTCOME MEASURES We measured stillbirth, preterm birth, small for gestational age, and neonatal death in women with and without hypertension in pregnancy. RESULTS We included 14,170 pregnancies. Hypertension occurred in 3156 (22.2%) women, with 602 (19.1%) defined as severe. Severe hypertension increased risk of stillbirth (RR 4.4; 95% CI 3.2-6.2), preterm birth (RR 2.5; 95% CI 2.2-2.8), small for gestational age (RR 2.7; 95% CI 2.3-3.1) and neonatal death (RR 5.1; 95% CI 2.9-5.6). Non-severe hypertension increased risk of stillbirth (RR 2.0; 95% CI 1.5-2.7), preterm birth (RR 1.2; 95% CI 1.1-1.3), and small for gestational age (RR 1.6; 95% CI 1.4-1.8). Perinatal outcomes were worse in women with hypertension who had spontaneous preterm birth compared to those who underwent iatrogenic preterm delivery. CONCLUSIONS Hypertension in pregnancy is common in Botswana and leads to a large number of adverse outcomes. Improved management of hypertension in pregnancy may improve perinatal morbidity and mortality.

The Role of Laboratory Supervision in Improving the Quality of Malaria Diagnosis: A Pilot Study in Huambo, Angola

In 2006, the Angolan National Malaria Control Program introduced clinical guidelines for malaria case management, which included diagnostic confirmation of malaria before administration of treatment; however, diagnostic practices were inconsistent and of unknown quality. In 2009, a laboratory supervision program was implemented in Huambo Province, with the goal of assessing and improving diagnosis of malaria within the confines of available in-country resources. Supervisions were carried out from 2009 to 2014 using a standardized supervision tool by national laboratory trainers. Data from the first supervision were compared with that from the final supervision. Over the study period, the number and level of training of laboratory technicians increased, and there was a nonstatistically significant trend toward improved laboratory conditions. There was a significant reduction in false-positive microscopy slide reading (P = 0.0133). Laboratory infrastructural capacity to diagnose other communicable diseases, including syphilis, human immunodeficiency virus and hepatitis B virus infections (P = 0.0012, 0.0233 and 0.0026, respectively), also improved significantly. Laboratory supervision for malaria diagnosis found significant areas for improvement, and in combination with concurrent capacity-building activities, it improved the diagnostic capacity for malaria and other diseases. Importantly, this study demonstrates that locally available resources can be used to improve the accuracy of malaria diagnosis.

HPV vaccination and the effects on rates of HPV-related cancers

Globally, human papillomavirus (HPV) infection is one of the most common sexually transmitted infection. HPV is linked to at least five malignancies including vulvar, vaginal, anal penile, oropharyngeal, and cervical cancer. Three HPV vaccines are currently available: bivalent (HPV 16,18), quadrivalent (HPV 6,11,16,18), and nonavalent (6,11,16,18,31,33,45,52,58) targeting between 2 and 7 oncogenic HPV serotypes. This review highlights the currently epidemiologic burden of HPV-related cancers, efficacy of current HPV vaccines, and speculates about the benefits of widespread HPV vaccination. At present, all three vaccines are effective in reducing cervical disease and anogenital dysplasia in industry sponsored clinical trials and in limited study of clinical effectiveness. Models predict elimination of HPV infection with global vaccination rates of 80% and benefits in reducing malignancy at 20% global coverage. Large population-based clinical efficacy studies of these vaccines will be necessary to assess the true impact of vaccination. HPV vaccines provide a promising primary approach to preventing malignancy and barriers to vaccine access must be addressed to meet vaccination goals.

Correction to: Strengthening medical training programmes by focusing on professional transitions: a national bridging programme to prepare medical school graduates for their role as medical interns in Botswana

CorrectionForllowing publication of the original article [1], the first author reported that there was a typographical error in the name of one of his co-authors. The correct spelling is Alemayehu Bedada, not Alemayhu Bedada.

Will HPV vaccination affect cervical cancer morbidity and mortality world-wide?

There is considerable hope that HPV vaccination will dramatically reduce the morbidity and mortality associated with cervical cancer. Theoretically, the quadrivalent and bivalent vaccines could prevent 70% of cervical cancer and the nonavalent vaccine, 90%, however, the reality is not that simple. Cervical cancer is the fourth most commonly diagnosed cancer in women worldwide and the second in women in the developing world. Sub-Saharan Africa, Central America, the Caribbean, and south-central Asia have disproportionately high rates of cervical cancer compared to Europe, Australia, and North America. In 2012, there were 527,600 cases of newly diagnosed cervical cancer and 85% of these cases occurred in the developing world. Similarly, mortality from cervical cancer is disproportionately high in the developing world. Two out of every 3 women diagnosed with cervical cancer in sub-Saharan Africa will die from the disease, whereas only one in 3 will die in North America. But cervical cancer is preventable, diagnosable, and treatable, so why do we see such a dire situation for women in lowand middleincome countries (LMICs)? While effective screening has reduced the incidence of cervical cancer in high-income countries, there is limited availability of and access to these services in LMICs, and where they are available, the quality is variable. Early stage symptoms of cervical cancer are nonspecific, including vaginal discharge, irregular vaginal bleeding, and post-coital bleeding, and do not always prompt a patient to seek care. Thus, screening is essential, and life-saving: precancerous lesions identified through screening are treated to prevent progression to cervical cancer. Once cervical cancer develops, it is still curable if detected and treated in its earliest stages. Curative treatments are limited when patients present at advanced stages of disease. The International Federation of Gynecology and Obstetrics (FIGO) has established clinical staging criteria for cervical cancer. The FIGO stage at diagnosis is inversely related to prognosis. In developed countries, women are more frequently diagnosed at an early stage of disease through screening. Though data on stage at presentation are limited in the developing world, available data from Kenya and Zimbabwe show that over 80% of women in these countries present with advanced stage disease, a point at which curative options are extremely limited. These patients with advanced cervical cancer suffer significant end-stage morbidities, including hemorrhage, obstructive renal failure, leakage of urine or feces through vaginal fistulas caused by tumor invasion, lymphedema of the lower extremities, and severe low back and abdominal pain. Limited availability of treatment services are also a major factor behind the disproportionate morbidity and mortality in developing countries. Treatment for cervical cancer includes surgery, radical surgery, chemotherapy and radiation, either alone or in combination. Surgical options are limited to those with very early stage disease. Treatment beyond straightforward simple surgery requires specialists, equipment and infrastructure that are not available or affordable in many parts of the world, and many women do not even have access to basic radiation therapy services. Palliation of symptoms is also limited in resource-poor settings, exacerbating the impact of the late-stage morbidities that patients manifest. How is the HPV vaccine going to change all of this? Data on the bivalent, quadrivalent and the newest nonavalent vaccine are encouraging in that infection with high risk HPV, the oncogenic precursor to cervical cancer, could theoretically be prevented. However, the projected 70–90% reduction in cervical cancer that is forecasted is based on ideal study conditions, and assumes that all women are vaccinated before they are infected with the covered high risk types, that duration of immunogenicity is life-long, and that there is no change in the proportion of cancers caused by the non-covered vaccine types. What is the reality? As we have seen with screening and treatment programs, even when evidence-based interventions are known, their implementation in real clinical practice is far from perfect. In the case of HPV vaccination, there are several issues to consider: many women are already infected with HPV; vaccine acceptability has limited its uptake; vaccine schedules are rigorous; the duration of protection is unknown; and the vaccines are expensive, making access in LMICs challenging. While the HPV vaccine has great potential to protect the generation of young girls being vaccinated now, those