Typhoid fever.

Typhoid fever is an invasive bacterial disease associated with bloodstream infection that causes a high burden of disease in Africa and Asia. Typhoid primarily affects individuals ranging from infants through to young adults. The causative organism, Salmonella enterica subsp. enterica serovar Typhi is transmitted via the faecal-oral route, crossing the intestinal epithelium and disseminating to systemic and intracellular sites, causing an undifferentiated febrile illness. Blood culture remains the practical reference standard for diagnosis of typhoid fever, where culture testing is available, but novel diagnostic modalities are an important priority under investigation. Since 2017, remarkable progress has been made in defining the global burden of both typhoid fever and antimicrobial resistance; in understanding disease pathogenesis and immunological protection through the use of controlled human infection; and in advancing effective vaccination programmes through strategic multipartner collaboration and targeted clinical trials in multiple high-incidence priority settings. This Primer thus offers a timely update of progress and perspective on future priorities for the global scientific community.

Suspected Exposure to Filoviruses Among People Contacting Wildlife in Southwestern Uganda.

Background: Human and filovirus host interactions remain poorly understood in areas where Ebola hemorrhagic fever outbreaks are likely to occur. In the Bwindi region of Uganda, a hot spot of mammalian biodiversity in Africa, human livelihoods are intimately connected with wildlife, creating potential for exposure to filoviruses. Methods: We tested samples from 331 febrile patients presenting to healthcare facilities near Bwindi Impenetrable Forest, Uganda, by polymerase chain reaction (PCR) analysis and Western blot, using recombinant glycoprotein antigens for Ebola virus (EBOV), Sudan virus (SUDV), Bundibugyo virus (BDBV), and Marburg virus. Behavioral data on contact with wildlife were collected to examine risk factors for filovirus seropositivity. Results: All patients were negative for active filovirus infection, by PCR analysis. However, patients were seroreactive to SUDV (4.7%), EBOV (5.3%), and BDBV (8.9%), indicating previous exposure. Touching duikers was the most significant risk factor associated with EBOV seropositivity, while hunting primates and touching and/or eating cane rats were significant risk factors for SUDV seropositivity. Conclusions: People in southwestern Uganda have suspected previous exposure to filoviruses, particularly those with a history of wildlife contact. Circulation of filoviruses in wild animals and subsequent spillover into humans could be more common than previously reported.

Primary Prevention of Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Guideline.

PURPOSE: To provide resource-stratified (four tiers), evidence-based recommendations on the primary prevention of cervical cancer globally. METHODS: The American Society of Clinical Oncology convened a multidisciplinary, multinational panel of oncology, obstetrics/gynecology, public health, cancer control, epidemiology/biostatistics, health economics, behavioral/implementation science, and patient advocacy experts. The Expert Panel reviewed existing guidelines and conducted a modified ADAPTE process and a formal consensus-based process with additional experts (consensus ratings group) for one round of formal ratings. RESULTS: Existing sets of guidelines from five guideline developers were identified and reviewed; adapted recommendations formed the evidence base. Five systematic reviews, along with cost-effectiveness analyses, provided evidence to inform the formal consensus process, which resulted in agreement of ≥ 75%. RECOMMENDATIONS: In all resource settings, two doses of human papillomavirus vaccine are recommended for girls age 9 to 14 years, with an interval of at least 6 months and possibly up to 12 to 15 months. Individuals with HIV positivity should receive three doses. Maximal and enhanced settings: if girls are age ≥ 15 years and received their first dose before age 15 years, they may complete the series; if no doses were received before age 15 years, three doses should be administered; in both scenarios, vaccination may be through age 26 years. Limited and basic settings: if sufficient resources remain after vaccinating girls age 9 to 14 years, girls who received one dose may receive additional doses between age 15 and 26 years. Maximal, enhanced, and limited settings: if ≥ 50% coverage in the priority female target population, sufficient resources, and cost effectiveness, boys may be vaccinated to prevent other noncervical human papillomavirus-related cancers and diseases. Basic settings: vaccinating boys is not recommended.It is the view of the American Society of Clinical Oncology that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.

Advocacy, communication, and partnerships: Mobilizing for effective, widespread cervical cancer prevention.

Both human papillomavirus (HPV) vaccination and screening/treatment are relatively simple and inexpensive to implement at all resource levels, and cervical cancer screening has been acknowledged as a "best buy" by the WHO. However, coverage with these interventions is low where they are needed most. Failure to launch or expand cervical cancer prevention programs is by and large due to the absence of dedicated funding, along with a lack of recognition of the urgent need to update policies that can hinder access to services. Clear and sustained communication, robust advocacy, and strategic partnerships are needed to inspire national governments and international bodies to action, including identifying and allocating sustainable program resources. There is significant momentum for expanding coverage of HPV vaccination and screening/preventive treatment in low-resource settings as evidenced by new global partnerships espousing this goal, and the participation of groups that previously had not focused on this critical health issue.

Factors influencing the acquisition and correct and consistent use of the top-lit updraft cookstove in Uganda.

This study looked at the effects of select behavior change interventions on the purchase and the correct and consistent use of a locally fabricated top-lit updraft (TLUD) stove in Uganda. Behavior change interventions included training of community sales agents and village health team volunteers on household air pollution and correct use, referral of interested community members to sales agents, community cooking demonstrations, information flyers, and direct sales of TLUDs and processed wood. Qualitative and quantitative research methods shaped interventions and were used to understand attitudes and practices related to TLUD stove acquisition and use. Results showed that TLUDs were appreciated because they use wood efficiently, cook quickly, reduce smoke, and produce charcoal. However, the substantial purchase price barrier, combined with the cost of processed wood, effectively eliminated the cost savings from its significant fuel efficiency. This made it difficult for the TLUD to be a meaningful part of most households' cooking practices.

Feasibility of delivering HPV vaccine to girls aged 10 to 15 years in Uganda.

BACKGROUND: Cervical cancer is a leading cause of mortality among women in Uganda. The availability of the human papillomavirus (HPV) vaccine presents an opportunity to prevent cervical cancer. The Government of Uganda conducted a demonstration project exploring the feasibility of two delivery strategies. OBJECTIVE: To explore the feasibility of two HPV vaccine delivery strategies: 1) a stand-alone school-based strategy that selected girls based on their enrolment in grade 5 (known as the "grade-based" strategy; and 2) an age-based strategy that delivered the HPV vaccine based on the girls' age (10-year-olds). This strategy combined the delivery of the vaccine with the distribution of deworming medication and vitamin A through an existing Child Days Plus program. METHODS: A qualitative study that explored the feasibility of the two delivery strategies from the perspective of health workers, district leaders, and staff of the Uganda National Expanded Programme on Immunization, utilizing in-depth interviews and focus group discussions. RESULTS: Coverage data showed that more girls (88%) were vaccinated using the grade-based strategy and completed all three doses compared to those (73%) vaccinated using the age-based strategy. Health workers and teachers indicated that determining vaccination eligibility was easier by grade than by age and there were minor disruptions to health services and school programs during vaccinations, as reported by health workers and teachers using the grade-based strategy. CONCLUSION: HPV vaccine delivery at schools using grade eligibility was more feasible than selecting girls by age. Lessons learned in Uganda could be relevant for countries considering implementing HPV vaccinations.

Immunogenicity of bivalent HPV vaccine among partially vaccinated young adolescent girls in Uganda.

BACKGROUND: Investigations of vaccine efficacy and immunogenicity for adult females receiving fewer than three doses of human papillomavirus (HPV) vaccine have suggested protection against infection and precancerous lesions. We investigated the immunogenicity of bivalent HPV vaccines among adolescent girls from Uganda who received one, two, or three vaccine doses. METHODS: Young girls vaccinated through a government program in Uganda were invited to participate. HPV16- and HPV18-specific antibodies were measured at ≥24 months after the last vaccine dose using an enzyme linked immunoassay in girls who received one (n=36), two (n=145), or three (n=195) doses. RESULTS: Nearly all subjects (99%) were HPV16 and HPV18 seropositive at the time of blood-draw. Geometric mean antibody levels (GMTs) were: HPV161-dose=230 EU/mL, HPV162-dose=808 EU/mL, and HPV163-dose=1607 EU/mL; HPV181-dose=87 EU/mL, HPV182-dose=270 EU/mL, and HPV183-dose=296 EU/mL. The GMT ratio for 2:3 doses was 0.50 (HPV16) and 0.68 (HPV18) and did not meet the non-inferiority criteria (i.e., lower bound of 97.5% confidence interval of the GMT ratio greater than 0.50). The GMT ratio for 1:3 doses for HPV16 and HPV18 was inferior, but absolute GMTs for one dose were higher than adult women who received one dose (HPV16=124 EU/mL, HPV18=69 EU/mL) where efficacy has been demonstrated. CONCLUSIONS: Even though immunogenicity with less than three doses did not meet a priori non-inferiority thresholds, antibody levels measured ≥24 months after last dose were similar to those of adult women who have been followed for more than eight years for efficacy.

Screen-and-treat approach to cervical cancer prevention using visual inspection with acetic acid and cryotherapy: experiences, perceptions, and beliefs from demonstration projects in Peru, Uganda, and Vietnam.

Cervical cancer is preventable but continues to cause the deaths of more than 270,000 women worldwide each year, most of them in developing countries where programs to detect and treat precancerous lesions are not affordable or available. Studies have demonstrated that screening by visual inspection of the cervix using acetic acid (VIA) is a simple, affordable, and sensitive test that can identify precancerous changes of the cervix so that treatment such as cryotherapy can be provided. Government partners implemented screening and treatment using VIA and cryotherapy at demonstration sites in Peru, Uganda, and Vietnam. Evaluations were conducted in the three countries to explore the barriers and facilitating factors for the use of services and for incorporation of screen-and-treat programs using VIA and cryotherapy into routine services. Results showed that use of VIA and cryotherapy in these settings is a feasible approach to providing cervical cancer prevention services. Activities that can help ensure successful programs include mobilizing and educating communities, organizing services to meet women's schedules and needs, and strengthening systems to track clients for follow-up. Sustainability also depends on having an adequate number of trained providers and reducing staff turnover. Although some challenges were found across all sites, others varied from country to country, suggesting that careful assessments before beginning new secondary prevention programs will optimize the probability of success.

Using formative research to design a behavior change strategy to increase the use of improved cookstoves in peri-urban Kampala, Uganda.

Household air pollution from cooking with biomass fuels negatively impacts maternal and child health and the environment, and contributes to the global burden of disease. In Uganda, nearly 20,000 young children die of household air pollution-related pneumonia every year. Qualitative research was used to identify behavioral determinants related to the acquisition and use of improved cookstoves in peri-urban Uganda. Results were used to design a behavior change strategy for the introduction of a locally-fabricated top-lit updraft gasifier (TLUD) stove in Wakiso district. A theoretical framework--opportunity, ability, and motivation--was used to guide the research and behavior change strategy development. Participants consistently cited financial considerations as the most influential factor related to improved cookstove acquisition and use. In contrast, participants did not prioritize the potential health benefits of improved cookstoves. The theoretical framework, research methodology, and behavior change strategy design process can be useful for program planners and researchers interested in identifying behavioral determinants and designing and evaluating improved cookstove interventions.

Screen-and-treat approach to cervical cancer prevention using visual inspection with acetic acid and cryotherapy: experiences, perceptions, and beliefs from demonstration projects in Peru, Uganda, and Vietnam.

Cervical cancer is preventable but continues to cause the deaths of more than 270,000 women worldwide each year, most of them in developing countries where programs to detect and treat precancerous lesions are not affordable or available. Studies have demonstrated that screening by visual inspection of the cervix using acetic acid (VIA) is a simple, affordable, and sensitive test that can identify precancerous changes of the cervix so that treatment such as cryotherapy can be provided. Government partners implemented screening and treatment using VIA and cryotherapy at demonstration sites in Peru, Uganda, and Vietnam. Evaluations were conducted in the three countries to explore the barriers and facilitating factors for the use of services and for incorporation of screen-and-treat programs using VIA and cryotherapy into routine services. Results showed that use of VIA and cryotherapy in these settings is a feasible approach to providing cervical cancer prevention services. Activities that can help ensure successful programs include mobilizing and educating communities, organizing services to meet women's schedules and needs, and strengthening systems to track clients for follow-up. Sustainability also depends on having an adequate number of trained providers and reducing staff turnover. Although some challenges were found across all sites, others varied from country to country, suggesting that careful assessments before beginning new secondary prevention programs will optimize the probability of success.

Human papillomavirus vaccine delivery strategies that achieved high coverage in low- and middle-income countries.

OBJECTIVE: To assess human papillomavirus (HPV) vaccination coverage after demonstration projects conducted in India, Peru, Uganda and Viet Nam by PATH and national governments and to explore the reasons for vaccine acceptance or refusal. METHODS: Vaccines were delivered through schools or health centres or in combination with other health interventions, and either monthly or through campaigns at fixed time points. Using a two-stage cluster sample design, the authors selected households in demonstration project areas and interviewed over 7000 parents or guardians of adolescent girls to assess coverage and acceptability. They defined full vaccination as the receipt of all three vaccine doses and used an open-ended question to explore acceptability. FINDINGS: Vaccination coverage in school-based programmes was 82.6% (95% confidence interval, CI: 79.3-85.6) in Peru, 88.9% (95% CI: 84.7-92.4) in 2009 in Uganda and 96.1% (95% CI: 93.0-97.8) in 2009 in Viet Nam. In India, a campaign approach achieved 77.2% (95% CI: 72.4-81.6) to 87.8% (95% CI: 84.3-91.3) coverage, whereas monthly delivery achieved 68.4% (95% CI: 63.4-73.4) to 83.3% (95% CI: 79.3-87.3) coverage. More than two thirds of respondents gave as reasons for accepting the HPV vaccine that: (i) it protects against cervical cancer; (ii) it prevents disease, or (iii) vaccines are good. Refusal was more often driven by programmatic considerations (e.g. school absenteeism) than by opposition to the vaccine. CONCLUSION: High coverage with HPV vaccine among young adolescent girls was achieved through various delivery strategies in the developing countries studied. Reinforcing positive motivators for vaccine acceptance is likely to facilitate uptake.

Factors influencing utilization of voluntary counseling and testing service in Kasenyi fishing community in Uganda.

This article reports on part of a study that described models of voluntary counseling and testing (VCT) service delivery and analyzed how a model influenced uptake of VCT services in a Ugandan community. A quantitative, exploratory, and descriptive design was used. Respondents (N = 127, 52% male, 48% female) provided data during structured interviews. Although knowledge about HIV transmission and prevention was high, only 47.2% of respondents had been tested for HIV. Married people were less likely to have been tested than unmarried people. The most common reasons for testing included risky lifestyle, signs and symptoms related to HIV, sex partners' risky lifestyles, and a sex partner's death. The most common barriers to testing were fear of results, belief that it was not necessary, and lack of time. VCT use was low. Sensitization to testing, mobilization of the community, and improving the quality and volume of VCT services are needed.

Health systems and immunization financing for human papillomavirus vaccine introduction in low-resource settings.

This descriptive qualitative study synthesizes health system and immunization financing assessments performed through formative research in India, Peru, Uganda, and Vietnam using a non-probability sample of national and sub-national stakeholders; and recommends appropriate and effective strategies for HPV vaccine delivery in low-resource settings. We conclude that maximum feasibility and acceptability and lowest cost for delivering HPV vaccine can be achieved by implementing through national immunization programs; by partnering with other sectors, such as education and maternal-child health; by strengthening existing human resources and cold chain infrastructures where needed; and finally, by considering schools for reaching the target population.

Safety and immunogenicity of recombinant low-dosage HIV-1 A vaccine candidates vectored by plasmid pTHr DNA or modified vaccinia virus Ankara (MVA) in humans in East Africa.

The safety and immunogenicity of plasmid pTHr DNA, modified vaccinia virus Ankara (MVA) human immunodeficiency virus type 1 (HIV-1) vaccine candidates were evaluated in four Phase I clinical trials in Kenya and Uganda. Both vaccines, expressing HIV-1 subtype A gag p24/p17 and a string of CD8 T-cell epitopes (HIVA), were generally safe and well-tolerated. At the dosage levels and intervals tested, the percentage of vaccine recipients with HIV-1-specific cell-mediated immune responses, assessed by a validated ex vivo interferon gamma (IFN-gamma) ELISPOT assay and Cytokine Flow Cytometry (CFC), did not significantly differ from placebo recipients. These trials demonstrated the feasibility of conducting high-quality Phase 1 trials in Africa.