Strategies for primary HPV test-based cervical cancer screening programme in resource-limited settings in India: Results from a quasi-experimental pragmatic implementation trial.

BACKGROUND: In order for low and middle income countries (LMIC) to transition to Human Papilloma Virus (HPV) test based cervical cancer screening, a greater understanding of how to implement these evidence based interventions (EBI) among vulnerable populations is needed. This paper documents outcomes of an implementation research on HPV screening among women from tribal, rural, urban slum settings in India. METHODS: A mixed-method, pragmatic, quasi-experimental trial design was used. HPV screening on self-collected cervical samples was offered to women aged 30-60 years. Implementation strategies were 1) Assessment of contextual factors using both qualitative and quantitative methods like key informant interviews (KII), focus group discussions (FGDs), pre-post population sample surveys, capacity assessment of participating departments 2) enhancing provider capacity through training workshops, access to HPV testing facility, colposcopy, thermal ablation/cryotherapy at the primary health care centers 3) community engagement, counselling for self-sampling and triage process by frontline health care workers (HCWs). Outcomes were assessed using the RE-AIM (Reach, Effectiveness, adoption, implementation, maintenance) framework. RESULTS: Screening rate in 8 months' of study was 31.0%, 26.7%, 32.9%, prevalence of oncogenic HPV was 12.1%, 3.1%, 5.5%, compliance to triage was 53.6%, 45.5%, 84.6% in tribal, urban slum, rural sites respectively. Pre-cancer among triage compliant HPV positive women was 13.6% in tribal, 4% in rural and 0% among urban slum women. Unique challenges faced in the tribal setting led to programme adaptations like increasing honoraria of community health workers for late-evening work and recalling HPV positive women for colposcopy by nurses, thermal ablation by gynaecologist at the outreach camp site. CONCLUSIONS: Self-collection of samples combined with HCW led community engagement activities, flexible triage processes and strengthening of health system showed an acceptable screening rate and better compliance to triage, highlighting the importance of identifying the barriers and developing strategies suitable for the setting. TRIAL REGISTRATION: CTRI/2021/09/036130.

Description and outcomes of patients with eclampsia and severe pre-eclampsia in a rural hospital in North-Eastern Bihar: A retrospective study.

Background: Hypertension is one of the most common medical disorders complicating pregnancy. In India, high blood pressure contributes to 7.1% of maternal deaths. This study was carried out to describe the characteristics and pregnancy outcomes of patients presenting with eclampsia or pre-eclampsia to a secondary care hospital in rural India. Methods: Patients diagnosed with pre-eclampsia or eclampsia between January 2018 and April 2021 were identified and included in the study. Medical records were searched and general patient characteristics, obstetrical history, information about the antenatal period, mode of delivery and outcomes were documented and analysed. Results: Among the 3651 women who delivered in this hospital during this time period, 2.3% (n = 83) presented with eclampsia and 1.9% (n = 71) with pre-eclampsia. More than 50% of the women delivered by lower segment caesarean section among both the eclamptics and pre-eclamptics. The stillbirth rate among those with either pre-eclampsia or eclampsia was 1 per 1000. The number of low birth weight babies born to those presenting with eclampsia (66.7%) was significantly more than those presenting with pre-eclampsia (48.6%). Eclampsia/pre-eclampsia accounted for 21% of all maternal deaths with a case fatality rate of 2.6%. Conclusions: This study identified that in this setting the patients presenting with eclampsia were much higher than those presenting with pre-eclampsia which is in stark contrast to the status even in developing countries. This could be an important finding indicating poorer health-seeking behaviour among the population and will need more studies on various interventions to change this status.

A retrospective study on the microbial spectrum and antibiogram of uropathogens in children in a secondary care hospital in Rural Vellore, South India.

BACKGROUND: Urinary tract infection (UTI) is common among children. Empiric antibiotics have to be started as early as possible or it may lead to an irreversible renal parenchymal damage and renal scarring in children. The objectives were to determine the prevalence and microbial profile of paediatric UTI and to determine the antimicrobial susceptibility pattern. METHODOLOGY: This is a retrospective study which looked at urine cultures of children below 15 years that were sent during the study period. RESULTS: Among the total urine cultures sent only 21.2% showed significant growth of organisms. The most common organism isolated was E. coli (75.5%). E. coli was least sensitive to cefpodoxime and co-trimoxazole, whereas highly sensitive to nitrofurantoin. Of the total children who had significant growth, 46% had ESBL. DISCUSSION: The prevalence of culture-proven UTI among children was found to be 21.2%. The most common organism isolated among the study population was E. coli (75.5%) followed by Enterococcus species (19.0%) and Klebsiella species (14.5%). It was also found that E. coli was least sensitive to cefpodoxime (31.6%) and co-trimoxazole (26.3%), moderately to amoxicillin-clavulanate (52.4%), whereas highly sensitive to nitrofurantoin (82.9%). This was similar with the studies done at other secondary care hospitals, in Oman and Oddanchathram, South India. CONCLUSIONS: With the increasing resistance, cephalosporins should not be used in treating paediatric UTI, whereas nitrofurantoin can be started as an empiric antibiotic, which can later be changed according to the susceptibility pattern.

Feasibility, uptake and real-life challenges of a rural cervical and breast cancer screening program in Vellore, Tamil Nadu, South India.

BACKGROUND: Early detection of breast and cervical cancer by organized screening has been found to reduce mortality rates in trials, but documentation of programme results and challenges is rarely done from non-trial settings. This study reports results of a population-based cancer control programme in a rural block in Vellore, Tamil Nadu, population size (116,085), targeting a population of 18,490 women aged 25-60 years, between November 2014 and March 2018. METHODS: Village-based health education sessions were conducted by social workers, using trained volunteers and health workers to motivate eligible women. Screening was done at a secondary level hospital, by trained general physicians using visual inspection with acetic acid and clinical breast examination, followed by colposcopy, radiological imaging (breast) and biopsy as required. RESULTS: A total of 8 volunteers and 17 health workers motivated women for 93 health education and screening sessions, in 46 out of 82 villages. While 1,890/18,490 (10.2 per cent) were screened for breast cancer, 1,783 (9.6 per cent) were screened for cervical cancer, with a yield of 3.4/1,000 for cervical pre-cancer/cancer. The main challenges were creating time for screening activities in a busy secondary hospital and difficulty in ensuring treatment completion of screen-detected cases. CONCLUSIONS: Population-based cancer screening programs can be offered by secondary hospitals that also run primary care services, to increase screening rates. Clear referral systems need to be established, bearing in mind that social factors, especially poor family support, may pose a threat to treatment, in spite of easy availability of cure.

Outcomes of external cephalic version for antenatal women with breech presentation in a secondary hospital in Vellore, Tamil Nadu - a retrospective review

Objective: Breech presentation is the most common fetal malpresentation at term, with an incidence of 3-4%. External cephalic version (ECV) is a procedure that can be offered to women with breech presentation beyond 36 weeks of gestation to convert it to cephalic presentation, reducing the risks of a vaginal breech delivery and the morbidities associated with caesarean section. Material and Methods: We retrospectively reviewed the records of women who underwent ECV between October 2012 and June 2020 with the objectives of determining the success rate of the procedure, the mode of delivery, the maternal and neonatal outcomes, periprocedural complications and their management. Results: Among the 200 women who underwent the procedure with a 64% success rate (128 women), there were 110 vaginal deliveries (56.7%) including five vaginal breech deliveries, and 84 women (43.2%) underwent caesarean section, which included 24 women who had successful ECV but needed emergency caesarean for other indications. There was no significant difference in the neonatal APGAR scores in those who had a successful ECV and those who did not. Only three women (1.5%) experienced any significant periprocedural complication. Conclusion: These results suggest that ECV improves the possibility of a vaginal delivery with an overall low complication rate, reducing the neonatal risks associated with vaginal breech delivery and the maternal morbidity of a caesarean section. It may thus contribute to reducing the primary caesarean section rate, making it a useful intervention, especially in limited resource settings.

Perceived Stigma Regarding Mental Illnesses among Rural Adults in Vellore, Tamil Nadu, South India.

BACKGROUND: Stigma is an important factor that determines whether individuals seek treatment for mental illnesses. Studies assessing public perceptions regarding mental illnesses are scarce in India. This study documents the stigma perceived by a rural population toward patients with mental illness and their families. MATERIALS AND METHODS: A cross-sectional pilot study was done in five villages, selected by simple random sampling, from a rural block in Vellore, Tamil Nadu. Households in each village were selected by systematic random sampling. From the selected households, 150 subjects aged 18-65 years, without known mental disorders, were chosen by convenience sampling, based on availability. Stigma was assessed using the Devaluation of Consumers Scale (DCS) and Devaluation of Consumer's Families Scale (DCFS). RESULTS: The proportion with high perceptions of stigma associated with mentally ill persons was 63.8%, among the 150 interviewed rural respondents (women: 112, median age: 37 years). The proportion which perceived that there was public stigma toward families of those with mental illnesses was 43.4%. Older respondents (>37 years) had higher perceptions of stigma (odds ratio: 2.07; 95% confidence interval: 1.02-4.20) than others. CONCLUSION: The high perception of stigma associated with persons who are mentally ill as well as their families needs to be kept in mind while planning interventions to decrease the treatment gap for psychiatric morbidity, especially in rural areas.

The Duration of Intestinal Immunity After an Inactivated Poliovirus Vaccine Booster Dose in Children Immunized With Oral Vaccine: A Randomized Controlled Trial.

Background: In 2014, 2 studies showed that inactivated poliovirus vaccine (IPV) boosts intestinal immunity in children previously immunized with oral poliovirus vaccine (OPV). As a result, IPV was introduced in mass campaigns to help achieve polio eradication. Methods: We conducted an open-label, randomized, controlled trial to assess the duration of the boost in intestinal immunity following a dose of IPV given to OPV-immunized children. Nine hundred healthy children in Vellore, India, aged 1-4 years were randomized (1:1:1) to receive IPV at 5 months (arm A), at enrollment (arm B), or no vaccine (arm C). The primary outcome was poliovirus shedding in stool 7 days after bivalent OPV challenge at 11 months. Results: For children in arms A, B, and C, 284 (94.7%), 297 (99.0%), and 296 (98.7%), respectively, were eligible for primary per-protocol analysis. Poliovirus shedding 7 days after challenge was less prevalent in arms A and B compared with C (24.6%, 25.6%, and 36.4%, respectively; risk ratio 0.68 [95% confidence interval: 0.53-0.87] for A versus C, and 0.70 [0.55-0.90] for B versus C). Conclusions: Protection against poliovirus remained elevated 6 and 11 months after an IPV boost, although at a lower level than reported at 1 month. Clinical Trials Registration: CTRI/2014/09/004979.

The effect of azithromycin on the immunogenicity of oral poliovirus vaccine: a double-blind randomised placebo-controlled trial in seronegative Indian infants.

BACKGROUND: Oral poliovirus vaccine is less immunogenic and effective in low-income countries than in high-income countries, similarly to other oral vaccines. The high prevalence of intestinal pathogens and associated environmental enteropathy has been proposed to explain this problem. Because administration of an antibiotic has the potential to resolve environmental enteropathy and clear bacterial pathogens, we aimed to assess whether antibiotics would improve oral poliovirus vaccine immunogenicity. METHODS: We did a double-blind, randomised, placebo-controlled trial of the effect of azithromycin on the immunogenicity of serotype-3 monovalent oral poliovirus vaccine given to healthy infants living in 14 blocks of Vellore district, India. Infants were eligible to participate if they were 6-11 months old, available for the study duration, and lacked serum neutralising antibodies to serotype-3 poliovirus. Infants were randomly assigned (1:1) at enrolment to receive oral 10 mg/kg azithromycin or placebo once daily for 3 days, followed by serotype-3 monovalent oral poliovirus vaccine on day 14. The primary outcome was detection of serum neutralising antibodies to serotype-3 poliovirus at a dilution of one in eight or more on day 35 and was assessed in the per-protocol population (ie, all those who received azithromycin or placebo, oral poliovirus vaccine, and provided a blood sample according to the study protocol). Safety outcomes were assessed in all infants enrolled in the study. The trial is registered with the Clinical Trials Registry India, number CTRI/2014/05/004588. FINDINGS: Between Aug 5, 2014, and March 21, 2015, 754 infants were randomly assigned: 376 to receive azithromycin and 378 to placebo. Of these, 348 (93%) of 376 in the azithromycin group and 357 (94%) of 378 infants in the placebo group completed the study per protocol. In the azithromycin group, 175 (50%) seroconverted to serotype-3 poliovirus compared with 192 (54%) in the placebo group (risk ratio 0·94, 95% CI 0·81-1·08; p=0·366). Azithromycin reduced faecal biomarkers of environmental enteropathy (calprotectin, myeloperoxidase, α1-antitrypsin) and the prevalence of bacterial but not viral or eukaryotic pathogens. Viral pathogens were associated with lower seroconversion. Three serious adverse events were reported (two in the azithromycin group and one in the placebo group), but none was considered related to the study interventions. INTERPRETATION: Azithromycin did not improve the immunogenicity of oral poliovirus vaccine despite reducing biomarkers of environmental enteropathy and the prevalence of pathogenic intestinal bacteria. Viral interference and innate antiviral immune mechanisms might be more important determinants of the immunogenicity of live-virus oral vaccines. FUNDING: Bill & Melinda Gates Foundation.