Evaluation of a phased pneumococcal conjugate vaccine introduction in Mongolia using enhanced pneumonia surveillance and community carriage surveys: a study protocol for a prospective observational study and lessons learned.

BACKGROUND: Streptococcus pneumoniae causes substantial morbidity and mortality among children. The introduction of pneumococcal conjugate vaccines (PCV) has the potential to dramatically reduce disease burden. As with any vaccine, it is important to evaluate PCV impact, to help guide decision-making and resource-allocation. Measuring PCV impact can be complex, particularly to measure impact on one of the most common and significant diseases caused by the pneumococcus, namely pneumonia. Here we outline the protocol developed to evaluate the impact of 13-valent PCV (PCV13) on childhood pneumonia in Mongolia, and a number of lessons learned in implementing the evaluation that may be helpful to other countries seeking to undertake pneumonia surveillance. METHODS: From 2016 PCV13 was introduced in a phased manner into the routine immunisation programme with some catch-up by the Government of Mongolia. We designed an evaluation to measure vaccine impact in children aged 2-59 months with hospitalised radiological pneumonia as a primary outcome, with secondary objectives to measure impact on clinically-defined pneumonia, nasopharyngeal carriage of S. pneumoniae among pneumonia patients and in the community, and severe respiratory infection associated with RSV and/or influenza. We enhanced an existing hospital-based pneumonia surveillance system by incorporating additional study components (nasopharyngeal swabbing using standard methods, C-reactive protein, risk factor assessment) and strengthening clinical practices, such as radiology as well as monitoring and training. We conducted cross-sectional community carriage surveys to provide data on impact on carriage among healthy children. DISCUSSION: Establishing a robust surveillance system is an important component of monitoring the impact of PCV within a country. The enhanced surveillance system in Mongolia will facilitate assessment of PCV13 impact on pneumonia, with radiological confirmed disease as the primary outcome. Key lessons arising from this evaluation have included the importance of establishing a core group of in-country staff to be responsible for surveillance activities and to work closely with this team; to be aware of external factors that could potentially influence disease burden estimates; to be flexible in data collection processes to respond to changing circumstances and lastly to ensure a consistent application of the pneumonia surveillance case definition throughout the study period.

Vaginal ring adherence in sub-Saharan Africa: expulsion, removal, and perfect use.

In sub-Saharan Africa, HIV incidence and prevalence remain disproportionately high among women. Vaginal rings (VRs) have been formulated for the delivery of antiretroviral-based microbicides, and their favorable safety and tolerability profiles reported in clinical studies. Although the concept of drug release through a VR has existed since 1970, and VRs have been marketed since 1992 for contraceptive or hormone replacement purposes, VR use as a microbicide delivery system is a novel application. This is the first study to evaluate VR adherence among African women in the context of its potential use as an HIV prevention method, to examine predictors of adherence, and to describe clinical or contextual reasons for VR removals or nonadherence. This was a randomized trial of the safety and acceptability of a placebo VR worn for 12 weeks in 170 HIV-negative, African women aged 18-35 in four clinic sites in South Africa and Tanzania. The findings suggest that adherence to VR use in the context of HIV prevention trials in these communities should be high, thereby enabling more accurate assessment of an active microbicide safety and efficacy.

High acceptability of a vaginal ring intended as a microbicide delivery method for HIV prevention in African women.

Vaginal rings (VRs) are new methods for continuous delivery of microbicides. This is the first study to quantitatively and qualitatively explore the acceptability of rings in Africa: 157 HIV-negative, sexually active women aged 18-35 used a placebo silicone elastomer ring for 12 weeks. They completed product acceptability questionnaires every 4 weeks. We conducted 6 exit focus group discussions with a subset of 48 women and 19 in-depth interviews with male partners. Retention in the study was high (97 %). Initial insertion at the clinic was successful on first attempt for 81 % of participants. Most women were comfortable using the ring, and very few (≤2 %) could feel it during daily activities or had ring-related physical or emotional problems. In the qualitative interviews many participants reported that they initially had concerns about using the ring. However, only a minority of women actually reported concerns with the ring during the study. The most frequent concern was that the ring would get lost inside the body (20 %), and this was significantly correlated with study site, frequently thinking about the ring and reporting that the ring was not very easy to remove. Qualitative data suggest that informants grew to like the ring because it felt securely placed, was unnoticeable during daily activities, and felt "normal" during sex. The ring appeared to be highly acceptable for women and men. Initial concerns with this novel method suggest a need for enhanced product counseling when VRs are introduced.

Poor sensitivity of field rapid HIV testing: implications for mother-to-child transmission programme.

We validated rapid HIV tests among pregnant women in a clinical setting. Field testing was performed using First Response 1,2,3 or Standard Diagnostic and Pareekshak tests. Results were confirmed by third generation HIV ELISA. Discordant or negative, specimens were confirmed by RNA PCR and a fourth generation ELISA test. Sensitivity and specificity were 94.5% (CI: 85.8-98.2) and 100% for First Response; 87.5% (CI: 46.7-99.3) and 100% (CI: 87.7-100%) for Standard Diagnostic and 90.2% (CI: 81.2-95.4) and 100% (CI: 98-100%) for Pareekshak. These sensitivities were lower than laboratory validation which approached 100%. The low-field sensitivity results have implications for Prevention of Mother-to-Child Transmission services.

Healthcare utilisation patterns for respiratory and gastrointestinal syndromes and meningitis in Msunduzi municipality, Pietermaritzburg, KwaZulu-Natal Province, South Africa, 2013.

BACKGROUND: Public health facilities are used by the majority of South Africans, and healthcare utilisation surveys have been a useful tool to estimate the burden of disease in a given area. OBJECTIVES: To describe care-seeking behaviour in a periurban site with a high prevalence of HIV infection, as well as barriers to seeking appropriate healthcare. METHODS: We conducted a cross-sectional household survey in 22 wards of the Msunduzi municipality in KwaZulu-Natal Province, South Africa, from October to December 2013 using a simple random sample of households selected from a 2011 census enumeration. A primary caregiver/adult decision-maker was interviewed regarding demographic data as well as health status and recent self-reported episodes of selected illnesses and healthcare utilisation. RESULTS: Of the 2 238 eligible premises visited, 1 936 households (87%) with a total of 9 733 members were enrolled in the study. Of these, 635 (7%) reported one or more episodes of infectious illness during the study period. Public health clinics were most frequently consulted for all illnesses (361/635, 57%). Private healthcare (general practitioner, private clinic, private hospital) was sought by 90/635 of individuals (14%), only 13/635 (2%) reported seeking care from traditional healers, religious leaders or volunteers, and 71/635 (11%) did not seek any medical care for acute illnesses. Individuals in the lowest income group were more likely to seek care at public health facilities than those in the highest income group (70% v. 32%). CONCLUSIONS: Public health facility-based surveillance may be representative of disease patterns in this community, although surveillance at household level shows that high-income individuals may be excluded because they were more likely to use private healthcare, and the proportion of individuals who died at home would have been missed by facility-based surveillance. Data obtained in such surveys may be useful for public health planning.

Factors associated with missed and delayed DTP3 vaccination in children aged 12 - 59 months in two communities in South Africa, 2012 - 2013.

BACKGROUND: Although immunisation services are available to all children in South Africa (SA), many children miss or have delays in receiving vaccines. There are limited data on factors associated with missed or delayed vaccination in children in this setting. OBJECTIVES: To assess vaccination coverage and factors associated with missed and delayed diphtheria-tetanus-pertussis vaccine third dose (DTP3) vaccination in children aged 12 - 59 months in two SA communities. METHODS: We used data from household-level healthcare utilisation surveys conducted in Soweto in 2012 and in Pietermaritzburg in 2013. Information on vaccination status was recorded from the Road to Health cards or vaccination history from clinics for children aged <5 years. Factors associated with missed or delayed DTP3 vaccination were assessed using unconditional logistic regression. RESULTS: Of a total of 847 eligible children aged 12 - 59 months, 716 had available vaccination information. Overall DTP3 vaccination coverage was high for both sites: 90.6% in Pietermaritzburg and 93.9% in Soweto. However, 32.6% and 25.2% of DTP3 vaccinations were delayed (received after 18 weeks of age) in Pietermaritzburg and Soweto, respectively. The median delay for DTP3 vaccinations was 4.7 weeks (interquartile range 1.7 - 23.0). Factors associated with delayed DTP3 vaccination included being born in 2010 (adjusted odds ratio (aOR) 3.0, 95% confidence interval (CI) 1.4 - 6.3) or 2011 (aOR 2.7, 95% CI 1.3 - 5.7) compared with being born in 2008, probably due to vaccine shortages; a low level of education of the primary caregiver, with children whose caregivers had completed secondary education having lower odds of delayed vaccination (aOR 0.5, 95% CI 0.3 - 0.9) than children whose caregivers only had primary education; and maternal HIV status, with unknown status (aOR 3.5, 95% CI 1.6 - 7.6) associated with higher odds of delay than positive status. Factors associated with missed DTP3 vaccination (not vaccinated by 12 months of age) included two or more children aged <5 years in a household (aOR 2.4, 95% CI 1.2 - 4.9) compared with one child, and household monthly income <ZAR500 (aOR 3.4, 95% CI 1.1 - 11.4) compared with ≥ZAR2 000. CONCLUSIONS: Despite high overall DTP3 coverage observed in two communities, many vaccinations were delayed. Vulnerable groups identified in this study should be targeted with improved vaccination services to enhance uptake and timeliness of vaccination.

A comparison of women's, providers' and ultrasound assessments of pregnancy duration among termination of pregnancy clients in South Africa.

OBJECTIVE: To compare providers' and women's estimates of duration of pregnancy with ultrasound estimates for determining medical abortion eligibility. DESIGN: Cross-sectional study. SETTING: Public termination of pregnancy (TOP) services in three provinces. SAMPLE: A total of 673 women attending the above services for TOP. METHODS: Women participating in a medical abortion feasibility study in South Africa provided estimates of pregnancy duration and date of last menstrual period (LMP). Each woman also had clinical and ultrasound exams. We compared estimates using the four methods, calculating the proportion of women in the 'caution zone' (< or = 8 weeks gestation by woman or provider estimate and > 8 weeks by ultrasound). MAIN OUTCOME MEASURES: Mean gestational age by each method; difference between provider and LMP estimates and ultrasound estimates; and percentage of women in the 'caution zone'. RESULTS: Women's estimates of pregnancy duration were 19 days fewer than ultrasound estimates (95% CI = -27 to 63). Mean provider- and LMP-based estimates were two (95% CI = -30 to 35) and less than one day(s) (95% CI = -46 to 51) fewer than ultrasound estimates. Comparing provider and ultrasound estimates, 15% of women were in the 'caution zone'; this fell to 12% if estimates of 9 weeks or fewer were considered acceptable. CONCLUSIONS: Provider estimates of gestational age were sufficiently accurate for determining eligibility for medical abortion. LMP-based estimates were also accurate on average, but included more extreme differences from ultrasound estimates. Medical abortion could be provided in TOP facilities without ultrasound or with ultrasound on referral.